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Jul 2020 DOI 10.14302/issn.2379-7835.ijn-20-3448
The aim of this study was to determine the influence of chronic supplementation with grape juice (400ml), in modulating the anthropometric and biochemical parameters. Thirty-nine seniors participated and were evaluated at baseline after 30 days. The chronic consumption of grape juice reduced weight, BMI and waist circumference. Indeed, the consumption modulated biochemical parameters, decreased the total cholesterol levels, Low-density lipoprotein (LDL) cholesterol, Urea and GGT. In addition, the intake of juice improved the performance in the TUG test, and caused more stability in the elderly. The levels of protein oxidation declined and the antioxidant potential significantly increased as well as SOD and the ratio SOD / CAT. In contrast, levels reduced sulfhydryl groups to consumption. In nuclear changes there are a decrease in the frequency of MN and picnosis. In conclusion, grape juice could be an excellent option to improve quality of life in elderly.
Apr 2020 DOI 10.14302/issn.2575-7881.jdrr-20-3267
The phytochemicals are endowed with antioxidant activities because of the presence of plentiful polyphenols and many other phytochemicals. However, some recent reports have suggested that phytochemicals from certain plant species exhibit DNA damaging properties mainly due to presence of alkaloids. In the present study, pBR322, Salmonella typhi DNA, insect DNA and human DNA were treated with hexanolic extract of Argemone mexicana and Thevesia peruviana leaves to assess their DNA damaging abilities. Another set of experiments was carried out using the methanolic extracts of Citrus lemon leaves to assess their DNA protecting abilities from damage of DNA by extracts of A. mexicana and T. peruviana at 150000 ppm for all DNAs used. The results indicated that the leaves extract of A. mexicanaand T. peruviana demonstrated significant DNA damaging potential at higher concentrations. In contrast, the extracts from C. limonat 15000 ppm showed maximum DNA protective properties for all DNAs used.
Mar 2020 DOI 10.14302/issn.2379-7835.ijn-20-3175
Local Nigerian men have been using AuriculariaPolytricha as a treatment for sexual dysfunction without supporting evidence from scientific experiments. This study was to investigate the effect of ethanolic extract of A. Polytricha on testicular DNA expression and some oxidative stress markers using STZ-Induced diabetic rats as a model. The experiment included six groups, Group A (Normal Control, treated with normal saline), Group B (treated with 65mg/kg.bw of STZ), Groups C, D, and E (treated with 250mg/kg.bw, 500mg/kg.bw, 1000mg/kg.bw AP after inducing diabetics), and Group F (treated with 40mg/kg.bw metformin after inducing diabetics). The experiment lasted for 35 days. After termination of the experiment, Fuelgen nuclear reaction was used for DNA demonstration to assess testicular DNA distribution while serum Superoxide Dimutase (SOD), Catalase and Melondialdehyde where evaluated using reagent based antioxidant enzyme assay. Results reveals that SOD and Melondialdehyde activities were remarkably (p<0.05) higher in diabetic control animals when compared with the normal control group. Values in Groups C, D and F that were administered with 250, 500mg/kg.bw A. polytricha and metformin respectively were also significantly (p<0.05) increased when compared with the normal control group. However, diabetic animals placed on 1000mg/kg.bw A. polytrichadid not show any statistical significance in comparison with normal control group but was remarkably (p<0.01) decreased when compared to the diabetic group that received low dose A. polytricha, an indication that the reversal is dose dependent. Catalase concentration in diabetic control animals was remarkably (p<0.05) higher when compared to the normal control but was not significantly (p<0.05) different in groups D (DM+500mg/kg.bw A. polytricha) and E (DM+1000mg/kg.bw A. polytricha) when compared with the normal control group. Diabetic control animals showed reduced magenta colour intensity of DNA and increased clustering and cross linking of DNA strands when compared with the normal control. However the degree of cross link in DNA strands was reduced in the diabetic animals placed on 1000mg/kg.bw A. polytrichawhen compared with the diabetic control group. Reversal in DNA damage and values of serum oxidative stress markers following administration of graded doses of A. polytricha could be attributed to essential phytochemical and therapeutic constituents in A. polytricha like polyphenol and flavonoid which can be found useful in prevention and treatment of diabetes induced testicular dysfunction. In summary, AP can contribute to a reversal in DNA damage and levels of serum oxidative stress markers in treating diabetes-induced testicular dysfunction.
May 2018 DOI 10.14302/issn.2637-6075.jpae-18-2062
Estimates of the genetic diversity of Large Japanese field mouse Apodemusspeciosus populations and identification of their plant food resources were conducted in an industrial green space, where were constructed on reclaimed land and belonged to the Aichi Refinery of Idemitsu Kosan Co., Ltd., in Aichi Prefecture, Japan. A total of six mitochondrial D-loop haplotypes were identified in 50 mice. Habitat condition with the highest number of captured individuals had abundant broad-leaved trees and understory vegetation. A minimum spanning network, which did not form a ring-shaped network, revealed that the hereditary population structure was weak. The low genetic diversity observed in the study area was thus attributed to isolation from other populations once the population in the study area by sea and road, which is more than 30 m wide. In order to identify which plant food resources were utilized by mice captured inside the industrial green space, partial chloroplast rbcL sequences were amplified by PCR from DNA extracted from 43 feces samples. Calculations of sample completeness curve revealed that 25 of the taxa identified in this study comprised approximately 90% of the food plant resources in the study area. Of the 21 plant families identified from the obtained rbcL sequences, members of the Rosaceae (28.0%), Fagaceae (17.2%), Lauraceae (14.2%) and Oleaceae (7.7%) were dominant. To ensure the continued survival of A. speciosuspopulation in this industrial green space would be to preferentially conserve plant species that are used as food resources by this species.
Aug 2017 DOI 10.14302/issn.2638-4469.japb-17-1563
GAGA-binding proteins in plants are encoded by the BARLEY B-RECOMBINANT / BASIC PENTACYSTEINE (BBR/BPC) family, which can be spilt into several groups on the basis of sequence divergence. The proteins of the different groups share an evolutionary conserved BASIC PENTACYSTEINE (BPC) domain at their very C-terminus that is important for DNA binding. Hallmark of this domain are five Cysteines at defined positions and spacing, which are considered to form a zinc-finger like structure that is involved in GAGA-motif recognition. Here, we report the formation of stabile homodimers between Arabidopsis thaliana group I member BPC1 or between group II member BPC6 in SDS-PAGE. Serial mutations of the highly conserved five Cysteines in the BPC domain of Arabidopsis thaliana BPC1 were tested for their capacity to bind to GAGA-motifs by DPI-ELISA. Our results do not support the idea of a direct involvement of these residues in making physical contact with the DNA, e.g. by formation of a zinc-finger structure. Instead, the data implies an indispensable function for the five Cysteines in homodimerization and stabilization of the protein structure by disulfide bonds. Accordingly, protein folding and structure prediction suggests the formation of a scaffold for dimerization that is supported by three intermolecular and one intramolecular S-S bond. The high degree of conservation between the BPC domains from the different groups and from different species denotes that this role for the five Cysteines might be evolutionary retained.
Jul 2017 DOI 10.14302/issn.2639-1716.jn-17-1495
Diets high in unsaturated fatty acids, especially those containing high levels of linoleic acid, e.g., corn oil, enhance mammary gland tumorigenesis in experimental animals. In contrast, diets high in long-chain polyunsaturated fatty acids such as eicosapentaenoic (EPA) and docosahexaenoic (DHA), e.g. menhaden oil, appear to have a suppressive effect on this tumorigenic process. Many mechanisms have been proposed to explain the tumor inhibitory action exerted by menhaden oil and other fish oils, e.g., differences in prostaglandin metabolism, energy efficiency, alterations of the immune system, changes in lipid peroxidation, etc. Fundamental to a mechanistic understanding of this phenomenon, however, is an understanding as to whether or not the tumor inhibitory activities of dietary fish oil is mediated via an inhibition of tumor cell proliferation or mediated via an enhancement of tumor cell loss. Whether the amount of dietary fat or the type of fat effects mammary tumorigenic processes, via an effect on tumor cell proliferation or tumor cell loss, has not been clearly established. In the studies described in this communication, three methods were utilized to study tumor cell proliferation, i.e., H3-thymidine autoradiographic analysis, 5-bromo 2'-deoxyuridine (Brdu) flow cytometric analysis, and proliferative cell nuclear antigen (PCNA) flow cytometric analysis. Two methods were used to study tumor cell loss, i.e., a determination of the I125Urd tumor emission rate and a determination of a cell loss factor from the formulas of Steel and Begg. The tumor examined was the human breast carcinoma cell line MDA- MB231 maintained in athymic nude mouse. No significant difference in cell proliferation between carcinomas of mice fed a high corn oil diet (20% w/w) and a diet high in fish oil (19% menhaden oil, 1% corn oil). In contrast, a significant (p<0.05) increase in the rate of I125Urd emission rate and cell loss factor from the carcinomas in the fish oil fed mice compared to the corn oil fed mice was observed. In summary, the decreased tumor volume in the human breast carcinomas maintained in athymic nude mice fed a fish oil diet as compared to those fed a corn oil diet, appears to be due, at least in part, to an increased rate of carcinoma cell loss rather than a decreased rate of carcinoma cell proliferation.
May 2026 DOI 10.14302/issn.2572-3030.jcgb-26-6307
The development of tumor biomarkers derived from blood, or its components, has become pivotal in advancing early cancer diagnosis. Malignant transformations induce cancer-specific alterations in the transcriptome, proteome, and secretome of tumor cells. Recent studies highlighted similar alterations in peripheral blood mononuclear cells (PBMCs) in cancer patients, which appear to mirror the state of transformation in tumor cells. These findings suggest an intercellular communication–driven mechanism rather than a systemic inflammatory response and, in addition to current ctDNA-based liquid biopsy biomarkers, point to a novel, simple, and highly robust approach for the early detection of cancer. Using this phenomenon to advance PBMC-based biomarker development, it will be essential to achieve 3D in vitro tumor models that reproduce a highly physiological tumor microenvironment (TME). Likewise, more enhanced 3D ex vivo models are required to enable the replication of cell-to-cell and organ-to-organ communication. These systems will guide the self-organization of mixed microenvironments derived from different tissues and enable them to accurately reproduce the molecular connections underlying these alterations. In this study, an innovative new modular 3D co-culturing approach was used to expose PBMCs to lung tumoroids, under physiologically relevant conditions. Changes in DNA fragmentation of PBMCs in the presence of lung cancer were quantified and used as a biomarker. To validate the predictiveness of this biomarker, our results were compared with clinical data from a clinical evaluation study. Similar to the clinical trial observations, PBMCs, when exposed to lung tumoroids, showed a significantly lower level of DNA fragmentation (37%). This modular 3D co-culturing model showed a predictiveness of the clinical data of > 90%, demonstrating its power to monitoring cell-to-cell communication effects and support the development of blood-based biomarkers.
Nov 2025 DOI 10.14302/issn.2326-0793.jpgr-25-5573
Advancements in proteomic and genomic technologies have transformed molecular biology by enabling comprehensive analysis of biological systems at the molecular level. This literature review explores the evolution, methodologies, and practical applications of key proteomic and genomic techniques. In proteomics, tools such as two-dimensional electrophoresis, mass spectrometry, Western blotting, Edman degradation, and functional protein microarrays have facilitated high-throughput protein identification, post-translational modification analysis, and biomarker discovery. Similarly, genomic methodologies like PCR, recombinant DNA technology, gel electrophoresis, and Southern blotting have revolutionized gene detection, manipulation, and expression profiling. The review also highlights the interdisciplinary impact of these technologies across clinical diagnostics, oncology, autoimmune disorders, infectious disease surveillance, cardiovascular research, and personalized nutrition. Integrative approaches combining proteomics and genomics are enabling the discovery of novel therapeutic targets, improving disease classification, and advancing precision medicine. Despite current limitations, such as the absence of amplification techniques for proteins and challenges in data interpretation, ongoing innovations promise to bridge these gaps. This synthesis underscores the pivotal role of molecular techniques in deepening our understanding of human biology and accelerating biomedical advancements for improved healthcare outcomes.
Sep 2024 DOI 10.14302/issn.2690-4721.ijcm-24-5195
The persistence of multidrug-resistant (MDR) Salmonella Typhi (S. Typhi) is a challenge especially in regions where typhoid is endemic. Surveillance of circulating genotypes of MDR S. Typhi is crucial in typhoid acute cases and carriers. This study aimed to investigate genotypic diversity of S. Typhi from symptomatic and asymptomatic children in endemic settings in Nairobi, Kenya. Symptomatic and asymptomatic individuals’ ≤ 16 years were recruited at four health facilities and tested for typhoid through stool cultures. The S. Typhi isolates were subjected to antibiotic susceptibility testing to investigate multidrug resistance. The MDR S. Typhi isolates’ DNA was extracted and illumina sequenced. Raw reads were de novo assembled and analyzed by pathogen-watch. From the 90 sequenced isolates, 60 (67%) were confirmed to be S. Typhi (sequence Type 1 and genotype 4.3.1). Out of the 60 S. Typhi strains; 39 (65%) had plasmids, from these 38 (97%) had IncHI1 plasmids alone. Out of the 60, 59 (98%) S. Typhi isolates had blaTEM-1D. Point mutations conferring reduced susceptibility to quinolones were detected in 42 (70%) of S. Typhi isolates, from these; 14 (33%) had gyrA S83Y , and 28 (67%) gyrB S464F genes, respectively. This study reports 4.3.1 (H58) as the most dominant S. Typhi genotype responsible for spread of MDR phenotypes carried on IncHI1 plasmids. Presence of MDR S. Typhi with resistance genes such as blaTEM-1Dand reduced susceptibility to ciprofloxacin especially among asymptomatic individuals, reiterates the need for use of typhoid conjugate vaccine among vulnerable children as a control and prevention measure against typhoid.
Jul 2024 DOI 10.14302/oap.jc-23-4781
As a first step towards clarifying the basis of the cooperation and conflict seen in chimeric binary mixes of Dictyostelium giganteum, we examined the karyotype of six natural isolates. All six had 5 haploid chromosomes. No meiotic figures were seen. Fluorescence in-situ hybridization was carried out using conserved D. discoideum centromeric DNA sequences as probes. From it, we infer that two chromosomes are sub-metacentric, one is metacentric and two are telocentric.
Mar 2024 DOI 10.14302/issn.2997-2108.jcc-20-3675
Pemphigus vulgaris is an autoimmune-mediated blistering disease. Cervical involvement is rare. A 38 year old nulliparous woman with PV on oral prednisolone and azathioprine was referred to the Gynaecology service for an abnormal cervical cytological smear showing low-grade squamous intraepithelial lesion. She was asymptomatic, 10 pack-year smoker, and reported no abnormal vaginal bleeding. Colposcopy was unsatisfactory with inadequate visualisation of the transformation zone due to severe cervico-vaginitis. A small focus of aceto-white epithelium was seen, surrounded by peeling, friable epithelium. HPV DNA test was negative. Punch biopsy demonstrated metaplastic squamous epithelium with intraepidermal suprabasal blister formation with acantholysis. Well-vascularised dermal papillae lined residual basal cells, giving rise to a tombstone appearance. There was no evidence of CIN/CGIN or invasive malignancy. An ulcer was also seen in the left buccal region. Repeat colposcopy after 6 weeks showed a small ulcerated area at the biopsy site with rolled healing edges, and a separate small ulcer. Cervical smear and colposcopy 6 months later were unremarkable. The incidence of cervical pemphigus vulgaris may be underestimated because women with pemphigus are often managed by Dermatologists without gynaecological input. In many published cases, cervical involvement was only detected after gynaecological examination due to symptoms such as dyspareunia, post-coital bleeding or vaginal discharge. Cervical smears of patients with pemphigus vulgaris typically display acantholysis, which may be misinterpreted as reparative, inflammatory, or neoplastic change. There have been reports of unnecessary hysterectomy due to such misdiagnoses. Review by an experienced cyto-pathologist is required in the event of diagnostic uncertainty.
Sep 2023 DOI 10.14302/issn.2574-4496.jtc-23-4722
Background Patients with distant metastatic Medullary Thyroid Carcinoma (MTC) have an estimated 40% ten-year survival rate. Gain of function mutations in the REarranged during Transfection or RET gene in MTC can result in an aggressive phenotype resistant to traditional therapy. In this case report, we describe the treatment of an MTC patient with a unique RET kinase deletion mutation. Case presentation Since diagnosis, 21 years ago, this patient has had chronically elevated calcitonin levels (>40,000 pg/mL) that was unable to be controlled by conventual therapy and clinical trials. As result of uncontrolled MTC, metastatic disease was found in the spine, liver, and lungs. Circulating tumor DNA (ctDNA) analysis identified a RET 898-901Del mutation, reported as a variant of unknown significance. The treating physician identified that the deletion was in the activation loop of RET kinase and considered that the mutation was constitutively activating RET kinase. The patient was prescribed Pralsetinib, a small molecule inhibitor targeting the ATP binding site of RET. Pralsetinib treatment achieved a durable response and was able to significantly decrease serum calcitonin levels (<200 pg/mL) and tumor size. Conclusion This RET deletion mutation is a pathogenic mutation with comparable enzymatic activity to the more common RET M918T mutation. The case report highlights the versatility of structural biologic approaches to guide therapeutic decisions.
Apr 2023 DOI 10.14302/issn.2576-6694.jbbs-22-4390
Background The genetic material of the genetically modified crop has been altered to develop the necessary insect resistance features by introducing genes from the Bt (Bacillus thuringiensis) bacterium. The objective of this study was to find smuggled GM Bt crops in the Metema farming area and examine its environmental effects. Method An experimental; Completely Randomized Design (CRD) was used to collect crop samples in the study area. The CTAB (Cetyltrimethyl ammonium bromide) technique was used to isolate DNA from all transported samples, and the purity was determined using a Nano Drop spectrophotometer. Conventional PCR with particular primers for different Bt gene events was used to detect the presence of genes. Furthermore, utilizing Bt cotton specific primer sets, the prevalence of GM cotton was measured, and amplified fragments were confirmed using agarose gel electrophoresis. Result The PCR results revealed that 15 (33.3 percent) of the samples were Bt cotton smuggled from Sudan. The PCR assay also revealed the presence of GM maize. Moreover, the effects of GM genes on the environment were studied in diseased samples, and no transgenes were found. Furthermore, domestic and indigenous crops were used to determine horizontal gene transfers of GM genes to other crops, and the transgene was not found in any of the samples analyzed. Conclusion: In the current study, 28 (13.4%) of the 209 (100%) total analyzed samples were GM crops which indicated the presence of unauthorized GM seeds in the study area. Environmental impact studies and horizontal gene transfer data similarly revealed that the Bt gene was not transferred to other crops and had no harmful environmental effects. For a better understanding of the Impact of imported unauthorized GM seeds, more additional detection of GM events should be done by expanding the sampling site and sample types.
Oct 2022 DOI 10.14302/issn.2572-3030.jcgb-22-4284
Upon considering the anticancer effects of larger oligomeric proanthocyanidins and observing various papers reporting the high resolution mass spectroscopy of the oligomeric proanthocyanidins, it is determined that the unusual 13C enrichment in some plant oligomeric proanthocyanidins may be responsible for the anticancer activities of these food products. Such correlation of the 13C in the oligomeric proanthocyanidins also correlate with their scavenging of free-radicals, anti-virial and anti-bacterial properties. Proanthocyanidins in grape seeds are observed to have high enrichment in heavy isotopes of 2H, 13C, 15N and/or 17O. Mass analysis of DNA from human cancer cells are compared to normal human cells and cancer cells show bond specific enrichment of heavy isotopes in nucleotides G, A, T and C. On such basis, this study suggests possible stronger interactions of proanthocyanidins with DNA in cancer verses DNA in normal cells due to heavy isotope bond specific enrichments in both proanthocyanidins and the cancer DNA. Such 13C interactions from oligomeric proanthocyanidins with nucleic acids and proteins involved in replications, transcriptions and translations in cancer cells for interacting and chemically altering anabolism and cell division of the cancer cells are consistent with the author’s mechanism for normal cell to cancer cell transformations via possible replacements of primordial 1H, 12C, 14N, 16O, and 24Mg isotopes by nonprimordial 2H, 13C, 15N, and 17O and 25Mg isotopes in the proteins and nucleic acids. Such is also consistent with the proposed treatment for cancer by the author by use of foods containing proteins, nucleic acids, carbohydrates and/or drug molecules enriched with the nonprimordial isotopes of 2H, 13C, 15N, and 17O and 25Mg.
Aug 2022 DOI 10.14302/issn.2835-2165.jfsh-22-4263
In Pakistan, production of poultry has been evolved as a good alternate of beef and mutton. In this study multiplex PCR approaches were adopted to differentiate and detect avian mycoplasma in a single PCR reaction as a step forward in the economization of PCR detection. From the total of 25 samples, 25 (100%) had a positive Mycoplasma isolation result. The biochemical test yielded the highest number of isolations, with MG accounting for 10/25. Commercial DNA-based PCR kits have been developed as a result of recent advancements in diagnostic techniques for Mycoplasma infections. Tetracyclines, fluoroquinolones, tilmicosin, tylosin, spiramycin Infections should be reduced as much as possible.
Mar 2022 DOI 10.14302/issn.2572-3030.jcgb-22-4121
Introduction Genomic mutations in TP53 gene in association with etiological risk factors have been associated with oral carcinogenesis. Herein, we screened for genomic variants of TP53 predisposing to oral cancers in Senegalese patients. Methodology 88 patients with confirmed diagnostic were recruited after informed consent. Blood samples were collected from each patient to perform DNA extraction, PCR amplification of all coding exons of TP53 followed by Sanger Sequencing of PCR products. Nucleotide sequences were analysed with Genalys software. 94 blood donors with no cancer diagnosis were also recruited as controls for association study between the most common variants identified in patients and predisposition to oral cancers. Results Sequence analysis showed that 52.27% of patients carry at least one mutation in TP53. Eleven genomic variants were identified, 7 variants already reported in databases and 4 new variants. The most recurrent variants in this study already reported as cancer-related variants were Pro72Arg (rs1042522; Arginine frequency estimated at 31.26%) and a 16 bp insertion in intron 3 (rs59758982; allelic frequency estimated at 26.25%). Haplotype analysis between these variants showed a strong linkage disequilibrium (D’ = 0.999, r2 = 0.153 and p-value < 0.05). However, association study did not find any significant association with susceptibility to oral cancer (p-value > 0.05). Conclusion Our study highlighted that despite the absence of association between the two most common cancer-related variants in Senegalese patients diagnosed with oral cancer, their strong LD suggested that they could be transmitted together in a common haplotype which may be implicated in oral carcinogenesis.
Feb 2022
Using samples of small cell lung tumors, a research team led by biologist Dr. Raymond discovered two new ways to induce tumor cell death. By activating ferroptosis, one of two subtypes of tumor cells can be targeted: first, iron-dependent cell death due to oxidative stress, and second, oxidative stress. Therefore, cell death can also be induced in a different way. Both types of cell death must be caused by drugs at the same time to eliminate the majority of the tumor mass. It is currently in clinical trials for cancer treatment. Auranofin, which inhibits the production of protective antioxidants in cancer cells, has been used to treat rheumatoid arthritis for decades. Future clinical trials using this combination therapy will determine the extent to which this targeted treatment option improves the prognosis of small cell lung cancer patients. It is currently in clinical trials for cancer treatment. Lung cancer is the leading cause of cancer death in the United States. Despite evidence of molecular abnormalities in biological specimens, progress in this disease is hampered by the lack of diagnostic markers useful for clinical practice. The majority of patients with lung cancer are still diagnosed at an advanced stage, when prognosis is poor. This article reviews new strategies being studied for the early detection of lung cancer. These strategies involve new methods of imaging (including low-dose computed tomography CT scanning), DNA analysis, and proteomic-based techniques. These strategies have not only improved our understanding of lung cancer but show promise in offering better survival to patients with this deadly disease. Of paramount importance in the search for methods of early detection is the need for the identification of the ideal population to screen, a multidisciplinary approach, and validation of promising techniques.
Oct 2021 DOI 10.14302/issn.2641-5526.jmid-21-3900
In this theoretical discovery of a law of Life, there is MATHEMATICS (Geometry, Bits and Numbers) that UNIFY 3 universes as complementary as ATOMIC MASS, WAVES, and INFORMATION (DNA, RNA and Amino Acids). The discovery of a simple numerical formula for the projection of all the atomic mass of life-sustaining CONHSP bioatoms leads to the emergence of a set of Nested CODES unifying all the biological, genetic and genomic components by unifying them from bioatoms up to 'to whole genomes. In particular, we demonstrate the existence of a digital meta-code common to the three languages of biology that are RNA, DNA and amino acid sequences. Through this meta-code, genomic and proteomic images appear almost analogous and correlated. The analysis of the textures of these images then reveals a binary code as well as an undulatory code whose analysis on the human genome makes it possible to predict the alternating bands constituting the cariotypes of the chromosomes. The application of these codes to perspectives in astrobiology, cancer, and specifically in INFORMATION THEORY with the emergence of binary codes and regions of local stability (voting process), whose fractal nature we demonstrate, is illustrated. PREFACE by Professor Luc Montagnier Addendum by Robert Friedman M.D After the discovery of the DNA double helix structure allowing both the stable storage of genetic information and its transfer through messenger RNA to protein synthesis organelles themselves structured by RNA most abundant in cells, the ribosomal. This wonder of nature exists in ALL living beings from the virus to humans and is based on two codes, the linear sequence of nucleotides and that derived from codons where three nucleotides allow with a certain flexibility - synonymous codons - the choice in the twenty amino acids. But we are missing a third CODE the one governing at multicellular beings from the rotifer to human, the stabilized modulation of gene expression in a nutshell the differentiation of cells from the single cell of the fertilized egg. It is logical to think that this program which begins as soon as fertilization is written in the DNA. We are also prone to associate it with non-coding DNA sequences although they control gene expression. I introduce here the notion developed by Jean-Claude Pérez of mathematical harmony, a higher order present in all living beings and whose existence it finds in genomes, including those of viruses. Thus the natural evolution of variants of the genome of coronavirus Covid 19 tends towards increasingly long Fibonacci series. It remains to determine the Who, the How and the Why of such developments. I will bet with my mathematician colleague that waves and fractals play a role. Luc Montagnier ADDENDUM Jean-claude has given scientists a strong new direction for research. He has identified a unified field of science guided by the Golden Ratio and Fibonacci Sequence. By identifying an overall guiding principle that makes possible fractal-like nesting at all levels of biological manifestation, future researchers can begin with the "whole" instead of the "parts". If we know that complex systems are organized at varying levels by the Golden Ratio and Fibonacci Sequence, we can look for those universal patterns first and then fill in the gaps with small details to complete the picture. It's like having an overall view of a crossword puzzle before beginning to assemble the individual pieces. Without an overarching vision and guiding principle, completing the puzzle is infinitely more difficult. Once scientists and researchers realize and begin using this "SECRET IN HIDDEN IN PLAIN SIGHT," their discoveries will be orders of magnitude more fruitful. Robert Friedman M.D
Mar 2021 DOI 10.14302/issn.2329-9487.jhc-21-3742
Cardiovascular disease is actually a major cause of mortality, illness and hospitalization worldwide. Several risk factors have been identified that are strongly associated with the development of cardiovascular disease. Public prevention strategies have relied predominately on managing environmental factors that contribute to cardiovascular disease, such as obesity, smoking and lack of exercise. The understanding of the role of genetics in cardiovascular disease development has become much more important to link genetics with the onset of disease and response to therapy. This seeks to examine how genes can predispose individuals to cardiovascular disease and how this knowledge might be applied to more comprehensive preventive strategies in the future. In addition, the review explores possibilities for genetics in cardiovascular disease treatment, particularly through the use of identified driver genes and gene therapy. To fully understand the biological implications of these associations, there is a need to relate them to the exquisite, multilayered regulation of protein expression and regulatory elements, mutation, microRNAs and epigenetics. Understanding how the information contained in the DNA relates to the operation of these regulatory layers will allow us not only to better predict the development of cardiovascular disease but also to develop more effective therapies.
Aug 2020 DOI 10.14302/issn.2691-8862.jvat-20-3513
This paper explores the trends, issues and challenges confronting the successful vaccine development for the novel Coronavirus disease (COVID-19). Right from the commencement of the COVID-19 pandemic, no drugs or vaccine has been developed nor approved for treating those down with COVID-19. This year, the scientific community and the vaccine industry have been asked to respond urgently to SARS-COVID-2 pandemic. Presently numerous vaccine development platforms are under process and DNA- and RNA-based platforms showing great potential followed by recombinant-subunit vaccines. Through explorative research, it was established that companies involved in COVID-19 vaccine development are facing big challenges in the scientific, economic and logistical perspectives. Amongst these challenges are distrust, misinformation, and about understanding the immune system interaction with the vaccine being developed, as well as with the pathogen itself. Adjudged as insurmountable may be too early a conclusion. The race is on and progresses are being made. Proper understanding of trends, metrics and dynamics revolving around COVID-19 vaccine development is crucial in expanding possibilities for positive results from ongoing vaccine research. In this review, we spotlight on the most recent developments in COVID-19 vaccine, including top 10 early candidates that may hit the market in next few months.
May 2020 DOI 10.14302/issn.2575-7881.jdrr-20-3343
Background Anemia of chronic disease is anemia found in certain chronic disease states, is typically marked by the disturbance of iron homeostasis or hypoferremia. Chronic renal failure is currently known as Chronic Kidney Disease (CKD) or Chronic Renal Insufficiency (CRI) implies long-standing, progressive and irreversible renal parenchyma disease resulting in diminished renal function up to 40 to 60%. Often, chronic kidney disease is diagnosed as a result of screening of people known to be at risk of kidney problems, such as those with high blood pressure or diabetes and those with a blood relative with chronic kidney disease. This disease may also be identified when it leads to one of its recognized complications such as cardiovascular disease, anemia, or pericarditis. Methods Sysmex kx21 used to CBC and the Cobase411 used to iron profile. Enzyme-Linked immunoassay (ELISA) was used to determine the level of serum hepcidin. Sample preparation and PCR detection of HAMP DNA Polymorphisms: Restriction digestion of PCR products was done using Fast Digest. (Figure 1). Results Serum hepcidin levels higher in patients with anemia of chronic kidney disease compared with healthy controls mean. The polymorphisms of the hepcidin gene promoter in Sudanese patients with ACKD showed that the hepcidin HAMP AA genotype 70, AG 23, and GG 7 in 100 patients dialysis-dependent and AA 83, AG 17 and GG 0, and the allele A are more frequent in patients affected by ACKD. Significant statistical association observed between the hepcidin level and end-stage kidney disease. Conclusion This study evaluates for the first time the association between anemia of chronic kidney disease and hepcidin genes promoter polymorphisms and show that the hepcidin HAMP AA genotype and the allele A are more frequent in patients affected by ACKD, further investigation is needed, our data support the hypothesis and hepcidin HAMP are important in the pathophysiology of ACKD.
Mar 2020 DOI 10.14302/issn.2691-8862.jvat-20-3275
Coronavirus nanoparticles show a strong peak of Plasmon absorption in ultraviolet–visible zone. A strong interaction exists between the surface of Coronavirus nanoparticles and Bcr–Abl tyrosine–kinase inhibitors (TKI) such as Imatinib (STI571), Nilotinib (AMN107), Dasatinib (BMS–345825), Bosutinib (SKI–606), Ponatinib (AP–24534) and Bafetinib (INNO–406). Bcr–Abl tyrosine–kinase inhibitors (TKI) such as Imatinib (STI571), Nilotinib (AMN107), Dasatinib (BMS–345825), Bosutinib (SKI–606), Ponatinib (AP–24534) and Bafetinib (INNO–406) cause to aggregation of Coronavirus nanoparticles linked to DNA/RNA and hence, lead to widening of peak Plasmon of Coronavirus nanoparticles surface at 550 (nm) and emerging a new peak at higher wavelength. In the current project, this optical characteristic of Coronavirus nanoparticles is used to time investigate of interaction between different Bcr–Abl tyrosine–kinase inhibitors (TKI) such as Imatinib (STI571), Nilotinib (AMN107), Dasatinib (BMS–345825), Bosutinib (SKI–606), Ponatinib (AP–24534) and Bafetinib (INNO–406) and Coronavirus nanoparticles. The results were shown that Bcr–Abl tyrosine–kinase inhibitors (TKI) such as Imatinib (STI571), Nilotinib (AMN107), Dasatinib (BMS–345825), Bosutinib (SKI–606), Ponatinib (AP–24534) and Bafetinib (INNO–406) with shorter chain length interact faster with Coronavirus nanoparticles. Therefore, a simple and fast method for identification of Bcr–Abl tyrosine–kinase inhibitors (TKI) such as Imatinib (STI571), Nilotinib (AMN107), Dasatinib (BMS–345825), Bosutinib (SKI–606), Ponatinib (AP–24534) and Bafetinib (INNO–406) with various chain length using red shift in surficial Plasmon absorption is presented.
Dec 2019 DOI 10.14302/issn.2326-0793.jpgr-19-3114
Background During the last two decades, the polymorphism of Angiotensin-Converting Enzyme (ACE) gene has been extensively studied among different human populations. In humans, several studies have shown the relationship between this polymorphism and the risk of many serious diseases with a heavy burden of health in developing countries. After analyzing the polymorphism in the population, the present study was also concerned with the investigation of an eventual association between hypertension, stroke, cancer prostate and I/D polymorphism of the ACE gene. Materials and Methods Our study population included 163 Baka (pygmy) and 158 Fang (Bantu) from Gabon to evaluate the polymorphism in the country. Concerning the diseases, we included 105 patients and 120 controls for hypertension, 37 patients stroke matched with 50 controls and 97 patients with prostate cancer were recruited. All participants in the study were genotyped for the ACE I/D polymorphism obtained by polymerase chain reaction amplification on genomic DNA. Results Our analysis showed that the ACE D allele DD genotype frequencies were highest of all the data so far in human populations. We obtained a frequency of 0.138 for I allele and 0.862 for D allele among pygmy and the frequencies of 0.313 and 0.687 respectively for the I and D alleles. This difference was significant (p<0.05). In patients, we revealed the predominance of D allele and DD genotype for hypertension (0.27 for I allele and 0.73 for D allele), for stroke (0.15 for I allele and 0.85 for D allele) and 83% of individuals with cancer prostate carry the D allele. D allele and DD genotype are associated with risk to hypertension whereas allele I seem protective at the occurrence of stroke (p<0.05 between healthy and controls). Conclusion We show that the D allele and DD genotype were higher in this population. Also theses two signatures may be associated at genetic risk of hypertension, stroke and prostate cancer in this country deprived of human resources for quality care of many patients.
Aug 2019 DOI 10.14302/issn.2574-4526.jddd-19-2963
Four cases are reported with splanchnic aneurysms of the branches of the main arteries. Three of the cases presented as emergencies. Possible rupture was present in Case 2 and true rupture in Case 4. The etiology of Cases 1 and 2 may have been a floxacin antibiotics, Table 1. This report is the first clinical chronological association of the antibiotics and arterial and aortic pathology. This association was supported by nationwide research by Pasternak, 11. Detailed experimental work done on mice showed connective tissue fragmentation and arterial cell injury. Apparently, the above antibiotic induced mitochondrial DNA damage and dysfunction, 9.
Feb 2019 DOI 10.14302/issn.2689-4602.jes-18-2431
The existing hypotheses on speciation rely on Mendelian genes and mutations in them. However, genome-wide sequencing demonstrates that the Mendelian genes account less than one-tenth of the entire genome DNA. This means that a greater part of the genome has not yet been subject to large-scale evolutionary consideration. This paper deals with the conditional mutations in drosophila, which are mutations of the genes belonging to a special category (ontogenes) controlling the program of individual development. The ontogenes presumably reside in the DNA of intergenic spaces and introns. Conditional mutations display a number of properties absent in the mutations of Mendelian genes. These specific properties allow three key problems in speciation to be solved: (1) the possibility of emergence of new traits as a result of sequential mutagenesis; (2) selection of mutants; and (3) establishment of isolation. We have shown that (1) the mutations in ontogenes are able to form new multigenic regulatory blocks that escape selection during their creation; (2) mutations in ontogenes allow for existence of constantly acting zygotic selection, which is by no means less important for speciation than Darwinian selection; and (3) owing to their conditionally lethal effect, the mutations in ontogenes are able to create biological isolation barrier. This gives the grounds for assuming that the emergence of mutations in ontogenes is a necessary condition for speciation.
Feb 2019 DOI 10.14302/issn.2643-0282.imsj-18-2508
The present study introduce an overview on the cladal structure of Symbiodinium population associated with some species of scleractinean corals and fire coral in the Egyptian Red Sea coast and discuss the possible consequences of recent climate changes on coral reefs. Cladal structure of Symbiodinium populations associated with eight keystone species of scleractinean corals and one species of fire coral that collected along Egyptian Red Sea coast, during 2012-2013, had been resolved based on 18S nrDNA and ITS2 genetic markers. Only Symbiodinium subclades C1 and A1 were identified from all examined species. Symbiodinium C1 was the dominant subclade that associated with 61% of coral samples. Results revealed that the studied pocilloporid corals were associated with Symbiodinium C1 and/or A1 while acroporids were only associated with Symbiodinium C1. The present data also indicated that Symbiodinium C1 occurred at high densities than A1 or A1+C1 combination. Because of the relative thermal susceptibility of clades C and A, the current study addresses that the recent climate changes may derive dramatic changes on community structure of coral reefs at the Red Sea.
Jan 2019 DOI 10.14302/issn.2643-0282.imsj-18-2448
Fungal infections increased substantially in the last years, becoming a relevant public health problem. Many of these infections account for high rates of morbidity and mortality. The emergence of resistant fungal clinical isolates have also motivate studies to find new antifungal therapies. Candida albicans is an oportunistic pathogen and affects a great number of immunocompromised patients worldwide. The marine ecosystem has been considered a rich source of bioactive metabolites due to the complexity and originality of its structures. Proteins and peptides from marine organisms have been shown to have antiviral, anti-inflammatory, antimalarial, anticancer, antimicrobial and antifungal properties. Arenicins are antimicrobial peptides isolated from the marine lugworm Arenicola marina with 21 amino acid residues in a β-hairpin structure. Dihydrofolate reductase, exo-b-(1,3)-glucanase and sterol 14α-demethylase are essential C. albincas enzymes that take part in DNA, cell wall and membrane metabolism, respectively. The present study evaluates the interaction of arenicin with important enzymes of C. albicans related to cell wall, ergosterol and DNA metabolism in order to elucidate possible molecular targets. We showed through an in silico approach, that a single compound from a marine worm (A. marina), can bind to three C. albicans essential proteins. The interaction occurs in regions inside the active site or at least near, with amino acid residues evaluated as hot spots. Arenicin is a new promising antifugal drug. The next step is to investigate protein-protein interactions performed by DHFR, EBG and CYP51 and assess whether arenicin is able to disrupt essential interaction or not.
Jan 2019 DOI 10.14302/issn.2639-3166.jar-18-2502
The compound 1,4-dimethylnaphthalene, originally isolated from dormant potatoes, is currently in use as a commercial sprout inhibitor. Growers and processors report a reduction in fungal infections in potatoes treated with DMN resulting in increased yields. To assess the effects of DMN on fungal growth a culture of Fusarium oxysporum was isolated from potato tubers and identified via DNA fingerprinting using the 18ITS ribosomal region. Growth of F. oxysporum was inhibited by 31% after four days of exposure to DMN but overall rate of spore germination was not affected by DMN treatment. The growth of additional fungi, including Alternaria alternata, Aspergillus niger, Epicoccum nigrum, Gnomoniopsis smithogilvyi, Phoma medicaginis, and Pythium ultimum was inhibited by DMN as was suppression of sporulation in A. niger. These results suggest that DMN is fungistatic at the application levels examined.
Nov 2018 DOI 10.14302/issn.2572-3030.jcgb-18-2428
Head and neck cancers (HNCs) are the most prevalent and aggressive type of cancers. Genetic, epigenetic, environmental and viral risk-factors are associated with HNC carcinogenesis. Persistent infection of oncogenic human papillomaviruses (HR-HPVs) represent distinct biological, molecular and epigenetic entities in HNCs. There are three main epigenetic mechanisms that regulate transcription, these are DNA methylation, histone modifications and alteration in non-coding RNA networks, which can dissected to identify innovative and accurate epigenetic biomarkers for diagnosis and prognosis of HNC patients. Due to the lacunae of accurate distinctive biomarkers for the definite diagnosis of HNC, the identification of predictive epigenetic markers is necessary that might modify or increase HNC patient’s survival. In this mini review, we briefly summarize the current knowledge of different epigenetic biomarkers in HNC.
Oct 2018 DOI 10.14302/issn.2379-7835.ijn-18-2419
Folic acid is essential in the body for the production of DNA and also plays various vital functions within the body. This study on folic acid was done to analyze the results of the Trivedi Effect® on its physicochemical and thermal properties with the help of analytical techniques. The method involves dividing the test sample into two parts. The first part was termed as a control sample, and no treatment was given to it; while the second part received the Biofield Energy Treatment remotely by a renowned Biofield Energy Healer, Gopal Nayak and termed as the treated sample. The study revealed that the particle sizes reduced by 7.01% (d10), 6.53% (d50), 8.37% (d90), and 15.99% {D(4,3)}, thus increased the surface area by 1.72%, in the treated sample compared with the control sample. The PXRD data showed changes in the peak intensities and crystallite sizes ranging from -36.81% to 113.41% and -15.79% to 318%, respectively, thus increased in the average crystallite size by 22.55% of the treated sample compared with the control sample. The TGA analysis of the treated sample revealed a 3.94% increase in total weight loss that resulted in the remarkable reduction in the residual amount by 14.99%, in comparison to the untreated sample. The latent heat of fusion (ΔHfusion) and latent heat of decomposition (ΔHdegradation) were significantly altered by -10.33% and 10.46%, respectively in the treated sample compared to the untreated sample. The study denoted that the Biofield Energy Treatment is a novel approach that could be used to develop some polymorph of folic acid and that might improve its solubility, dissolution, and bioavailability in comparison to the control sample. Hence, the treated folic acid in the nutraceutical/pharmaceutical formulations might be useful concerning better drug performance and efficacy.
Sep 2018 DOI 10.14302/issn.2641-9467.jgrc-18-2270
Rice, as one of the most important crops in the world, is facing an ever-accelerating challenge from climate change. Epigenetic modification with its substantially high epimutation rate and the possibility for some epigenetic variation to act as a heritable contributor to crop environmental adaptability may hold great potentials for rapid crop breeding. Epigenetic modification is controlled by epigenetic pathways, and mutations disturbing the epigenetic pathways may lead to significant epigenetic and/or genetic changes. This is especially true for rice, whose genome is rich in epigenetic modifications and transposable elements (TEs) that are generally epigenetically silenced. Here, in this paper, we first reviewed the pathways that establish, maintain and remove rice DNA methylation, which is the most well studied epigenetic marker, as well as the genes that are involved. We then discussed how TEs amplify the phenotypic impact of epigenetic changes that could be a result of epigenetic pathway disturbances. At last, we presented the enormous amount of rice genome data that are publically available, within which great genetic variation in the genes that are involved within the epigenetic pathways is embedded. This genetic variation awaits to be exploited for their potentials in generating a heritable source of variation for rapid environmental adaptation, which may hold tremendous importance for rice breeding in the face of climate change.
Aug 2018 DOI 10.14302/issn.2572-3030.jcgb-18-2183
This paper reviews the state of cancer research in the post-mutation era. It presents cancer as a highly complex disease viewed differently by scientists from various research fields. Histopathologists considered cancer as a disease of cell differentiation, cancer cell biologists overestimated the causal role of accumulated DNA mutations. More recently molecular biologists have focused on driver genes and driver mutations, regulatory gene networks and deregulation of the genomic balance between unicellular and multicellular gene sets (UG/MG balance). From a developmental biological standpoint, there is a clear analogy between the reproductive life cycles of cancer and protists. The key player of both analogous life cycles is the polyploid cyst, the atavistic cyst-like structure aCLS (PGCC). In the analogy to protists, we assume that the first aCLS initiating cancer originates from a mitoticly blocked cell (cell of origin of cancer, protoprecursor) that escapes death entering an atavistic reproductive process of polyploidisation and depolyploidisation; it forms the atavistic cyst-like structure aCLS and numerous daughter cells (microcells). The microcell progeny develops a multi-lined cell lineage containing stem cells as well as somatic and reproductive cells and clones. Subsequent aCLSs are formed sequentially by committed daughter cells or occasionally by stressed somatic cells. Accordingly, cancer initiation occurs by genomic changes leading to the amitotic cell state and reactivation of an atavistic life cycle. In humans, atavistic life cycles and hyperpolyploidisation (n >16) are mostly repressed by stable gene regulatory networks – but not in cancer. The permanent UG/MG gene conflict and robust ancient surveillance mechanisms trigger a cascade of molecular lesions leading to genomic heterogeneity and aberrant cancer cell states.
Aug 2018 DOI 10.14302/issn.2576-6694.jbbs-18-2173
Bioinformatic tools is widely used to manage the enormous genomic and proteomic data involving DNA/protein sequences management, drug designing, homology modelling, motif/domain prediction ,docking, annotation and dynamic simulation etc. Bioinformatics offers a wide range of applications in numerous disciplines such as genomics. Proteomics, comparative genomics, nutrigenomics, microbial genome, biodefense, forensics etc. Thus it offers promising future to accelerate scientific research in biotechnology
Jul 2018 DOI 10.14302/issn.2832-5311.jpcd-18-2150
The apical meristem of the growing point of plants contains proplastids, precursors of chloroplasts. The main attention of investigators was paid to the transformation of proplastids into chloroplasts. The formation of proplastids of the apical meristem of wheat seedlings was investigated in the present work and described for the first time in the scientific literature. Ultrastructural images of apical meristem areas showed that the formation of the proplastide body includes several stages: localization of plastid DNA in the cytoplasmic matrix in close contact with cytoplasmic ribosomes, the formation of membrane vesicles containing plastid DNA, the step-by-step filling of these vesicles with dense contents, and the formation of mature proplastids.
May 2018
Genetics alone cannot thoroughly expound the environmental impact on the molecular complexity of the endocrine system. Epigenetic-induced alteration in gene expression has emerged as a way in which environmental compounds may exert endocrine effects. The environmental compounds that interfere with normal endocrine signaling are one of the largest classes of toxicants we are exposed to, on a daily basis. Epigenetic mechanisms, mainly the methylation of DNA and the modification of histones, lead to differentiated activation and deactivation of genome domains creating phenotype plasticity and divergent endocrine function among populations and individuals, as well. The issues examined in the present review are related to environmental epigenetics, and more precisely, the epigenetic-mediated modulation and relevance of endocrine disrupting chemicals, focusing on three broad aspects: 1) persistence of EDs, 2) their major hormonal effects and 3) the potential of compounds previously considered as endocrine disruptors to induce epigenetic effects. Evidence suggests that environmental exposures notably impact expression of endocrine-related genes and, thus, affect clinical endocrine outcomes.
Apr 2018
The global analysis of 3 human genomes of increasing levels of evolution (neanderthal / sapiens build34 of 2003 / sapiens hg38 of 2013) reveals 2 levels of numerical constraints controlling, structuring and optimizing the DNA sequences of these genomes. A global constraint - which we will call "HGO" for "Human Genome Optimum" - optimizes the genome at its global scale of 3.5 billion base pairs. This same operator when applied to each of the 24 individual chromosomes reveals a hierarchical structure of these 24 chromosomes according to a numerical spectrum of amplitude ½ Phi extending from chromosome 4 to chromosome 19. This first level of comparison reveals a very Great analogy between these 3 genomes. Then we introduce a global analysis method of roughness or fractal texture of the DNA sequences at the level of each chromosome. After having demonstrated that the chromosome4 seems to play a privileged role in the human genome, radically differentiating it from the 23 other chromosomes, we limit the study to the exhaustive analysis of different whole chromosomes4 relative to the 6 primates Homosapiens, Neanderthal, Chimpanzee, Orang-outan, Gorilla and Macaque. There are then remarkable resonances and periods - based on the sequences of Fibonacci and Lucas - totally differentiating the chromosomes 4 of these different primate species: 21 base pairs period for the chimpanzee and the urang-outan, 34 bases pairs period for Man, and 55 base pairs period for the gorilla. Finally, the major result is that the comparative analysis of the respective chromosomes4 of sapiens and neanderthal shows for the first time major differences in long-range fractal structures between the DNA sequences of these two genomes. Thus, while the chromosome4 of sapiens has an obvious resonance of 34 nucleotides, that of Neanderthal seems "torn" between two attractors of fractal textures, one on this same resonance 34, but with a roughness radically different from that of sapiens, While the other resonance is tuned to the number of Lucas 123. Finally, on a more theoretical level, this method reveals properties of "discrete digital standing waves" such as periods, resonances, phase shifts or phase positions. To conclude, we suggest that this chromosome4 could possibly play a role as a "referential" with respect to each of the 23 other chromosomes of the nuclear genome and possibly also with respect to the mitochondrial mtDNA genome.
Dec 2017 DOI 10.14302/issn.2576-6694.jbbs-17-1869
Introduction Bovine papillomavirus (BPV) is the etiological agent of bovine papillomatosis, infectious and neoplastic disease, characterized by the presence of multiple papillomas that can regress spontaneously or to persist and progress to malignancies when in association with environmental cofactors. Although recognized that the BPV can induce DNA damages, the viral role following cancer initiation remains unresolved. Based on this, we stablished cell lines derived from cutaneous papilloma, fibropapilloma and esophageal carcinoma to study the BPV action on epithelial-mesenchymal transition (EMT). Our results showed strong evidences that the virus action can contribute to EMT and, therefore, metastasis. Aim In this study, we analyzed the expression levels of the EMT markers (cytokeratin 10, STAT3 Y705, Oct-3/4 and vimentin) in paraffin-embed samples, using the same tissues that originated the cell lines previous studied, aiming to validate the results observed using cell lines. Material and Methods Expression levels of these markers was analyzed by immunohistochemistry and the collagen composision by Picrosirius red staining. Results We verified an overexpression of these markers in fibroblastoid cells present into the epidermis and ketarinocyte-like cells into the dermis present in dermo-epidermal junction. These data reinforce our previous results using cell cultures, validating both systems (cell culture and paraffin-embed tissues) as useful models to study the natural history of BPV-infected lesions. Conclusion Altogether, the results from these systems indicate that the BPV promote the cancer progression and metastasis through the transdifferentiation of an epithelial to mesenchymal cells (EMT).
Dec 2017 DOI 10.14302/issn.2641-7669.ject-17-1789
We aimed to study the effect of buspirone, an anxiolytic drug and 5-HT1A agonist on liver injury induced by carbon tetrachloride (CCl4) in rats. Rats were orally treated with CCl4 (2.8 mL/kg in olive oil) along with buspirone at 10, 20 or 30 mg/kg once daily starting with CCl4 and for one week thereafter. Aspartate aminotransferase (AST) and alanine aminotransferase (ALT) as well as alkaline phosphatase (ALP) activities were determined in the serum. Markers of oxidative stress: lipid peroxidation (malondialdehyde; MDA), reduced glutathione (GSH), nitric oxide (nitrite/nitrate) levels were measured in the liver. Moreover, paraoxonase 1 activity was determined in the liver and serum. The administration of CCl4 led to significant increases in serum ALT, AST, and ALP activities. Results showed that there were significantly increased hepatic MDA, nitrite and decreased GSH levels. PON1 activity decreased both in the liver and serum, respectively. The immunohistochemical investigations using anti-caspase-3 antibody revealed that CCl4 caused apoptosis to many hepatocytes. DNA studies showed that CCl4 caused hypoploidy in hepatocytes. Rats treated with 20-30 mg/kg buspirone showed significant decrease in serum ALT and AST by 19.5-34.3% and 24.2-31.4%, respectively. Serum ALP decreased by 21.7% after 30 mg/kg buspirone. In the liver, the higher dose of the drug resulted in decreased MDA (by 15.8%), decreased nitric oxide (17.4%) and increased GSH (by 20.1%). Significantly increased serum PON1 activity by 43.9-53.5% was observed after treatment with 20-30 mg/kg buspirone. On histopathologic examination of liver sections, there was mild protective effect for the drug at 30 mg/kg. Sections stained with anti- caspase- 3 confirmed the results obtained from histopathological examination. Moreover, buspirone given at 30 mg/kg resulted in an increase in % of cells containing normal values of DNA. These results indicate that buspirone decreases liver oxidative stress and exerts protective effect against CCl4- toxicity. The study thus indicates more beneficial effects of buspirone as an anxiolytic drug and that the drug could be used safely in patients with liver disease.
Sep 2017 DOI 10.14302/issn.2575-7881.jdrr-17-1749
Though, directed evolution/In vitro evolution has greatly enhanced the applicability of natural biomolecules, there is still a big void in synthetic biology, which could be filled only when we are able to make novel/synthetic functional biomolecules. Terminal deoxyribonucleotidyl transferase (TdT) is the only known DNA polymerase, which can add deoxyribonucleotides without the requirement of a DNA template. Here, we are introducing the concept of Template-Independent Synthesis of Nucleic Acids (TISNA), where we have exploited the property of terminal deoxyribonucleotidyl transferase to add deoxyribonucleotides to the 3’ end of an oligonucleotide for the generation of de novo libraries of ssDNA, dsDNA coding sequences and RNA. We are able to generate libraries that have diversity not only in sequence but also in length in a single library itself. The length of double stranded random gene libraries generated using this approach ranges from 200 base pairs to 10 kilobase pairs. The ability to make random nucleic acid libraries from scratch (independent of any template information) in the laboratory could open up new avenues and holds promise for the pharmaceutical and biotechnological sectors.
Aug 2017 DOI 10.14302/issn.2578-2371.jslr-17-1669
Aims: To describe the clinical, biological and evolutionary features of mono infected patients treated with tenofovir in Togo. Method: It is a descriptive, prospective study. Patients were treated with Tenofovir Disoproxil Fumarate (TDF). The inclusion criteria were: active chronic HBV (HBs Ag-positive for more than 6 months, high aminotransferases, the HBV –DNA ≥ 2000 IU / ml for HBeAg negative or ≥ 20 000 IU / ml for HBeAg positive and significant fibrosis) and absence of HCV, HDV, or co-infection HIV. Results: Among patients with HBV in our department, only 10.68% were treated with TDF. The mean age of patients was 33.01±9.81years. There was male predominance (68%). The circumstances of discovery were mainly during blood donation (65.3%) and a routine checkup (14.7%). Clinical examination was normal in most of cases (86.7%) apart from hepatomegaly (9.3%) and icterus (4%).) The HBeAg was negative in 89.3%; the average DNA was 7.56 ±8.01 log10 IU/ml. Abdominal ultrasonography was performed in all patients and we found hepatomegaly (18.67%), splenomegaly (10.67%), and ascites (5.3%). The assessment of fibrosis and activity had enabled to find a fibrosis higher or equal to 2 in 12 cases (48%) and an activity higher or equal to 2 in 9 cases (36%). The clinical and virologic outcome was marked by an undetectable viral load (HBV-DNA˂10 IU/l) in 89.3% of the patients after 1 year of treatment. Conclusion: TDF had helped to find out an undetectable viral load in in 89.3% of the patients after one year of treatment.
Aug 2017 DOI 10.14302/issn.2575-7881.jdrr-17-1701
Functional nucleic acids are a kind of nucleic acid sequences with special functions, which can specifically bind with the target substances or catalyze the reactions. Many target, including mycotoxins, small RNA, heavy metal ions and DNA segment, can bind to particular selected oligonucleotides, and then realized the detection. The uses of functional nucleic acids to detect the genetically modified organism (GMO) have been pursued using different approaches. Meanwhile, the flanking sequence, which was the most specific target in the GMO detection, was also usually separated with the help of functional nucleic acid. During the detection, the functional nucleic acid provided superior sensitivity, specificity and success rate compared with the traditional methods. In this report, we described different functional nucleic acids used in the GMO detection, they were classified based on their structures, and some of them were developed in our lab. The principle, structural composition, advantage, and the comparisons of the functional nucleic acids were reported. Considering most of the functional nucleic acids are fluorescently-labeled, in order to reduce the cost, more and more functional nucleic acids without labeling are under research.
Jun 2017 DOI 10.14302/issn.2576-9359.jot-17-1603
Single-nucleotide polymorphisms (SNPs) in genes involved in immune responses and in the pharmacokinetics/pharmacodynamics of immunosuppressive drugs influence transplant outcomes of patients receiving the same immunosuppressive therapy. The aim of our preliminary study was to determine the SNPs profiles of ABCB1/MDR-1, UGT1A9, IMPDH2, IL-10 and TNF-α genes associated with acute rejection (AR) events in renal allograft recipients. DNA was extracted from whole blood samples of 220 individuals in 3 experimental groups; Case: 41 kidney transplant patients with AR event(s), Control I: 109 kidney transplant patients without AR event, Control II: 70 healthy blood donors. Acute rejection defined as rapid, unexplained rise in serum creatinine was biopsy-proven. 19 SNPs were analyzed by Sanger Sequencing. Analysis of allele and genotype frequencies and gene-disease association tests were performed. Allele frequencies of healthy persons are in line with ones reported from Europe indicating that the studied population is representative. Statistically significant differences only by the comparison of kidney transplant patients with AR event(s) and healthy individuals are found for rs2032582 and rs1045642 SNPs of ABCB1/MDR1, the latter is also not in Hardy-Weinberg equilibrium in our population. Patients with specific alleles for these SPNs are more prone to have acute rejection events. Certain allele variants of ABCB1/MDR1 by modifying the effectiveness of the drugs may compromise the success of the immunosuppressive therapy and put patients at higher risk to reject the new organ. Therefore screening for these polymorphisms before transplantation would help clinicians to more accurately personalize medications.
Apr 2017 DOI 10.14302/issn.2372-6601.jhor-17-1463
Melanoma is considered to be a very aggressive cancer due to its rapid growth, early and multiple metastases and limited response to standard treatment. Many researchers have hypothesized that the combination of radiation therapy and immunotherapy in the treatment of melanoma primary tumors and metastases improves the efficiency of these methods as compared to their use separately. Therefore, combined therapy is an increasingly popular topic in radiation oncology. Although the mechanism of immune response to ionizing radiation remains unclear, known are the factors involved in the immune response, including NK and CD8(+) T cells. Many studies have demonstrated the importance of inflammatory factors, primarily cytokines, in the response to ionizing radiation. In turn, many cytokines released in an irradiated organ, such as tumor necrosis factor α (TNFα), interleukins IL1 and IL6 and transforming growth factor beta (TGFβ), can induce the production of significant amounts of reactive oxygen species that are associated with the induction of DNA damage in tumor cells. In relation to anticancer immunotherapy, the clinical data obtained to date can encourage future studies combining radiation therapy and the inhibitors of cell division checkpoints in the treatment of advanced melanoma. In a recent study, melanoma cell lines became more sensitive to radiation after BRAF inhibition, which provides a potential synergistic mechanism of BRAF inhibitor (BRAFi) combined with radiation therapy for better effects of treatment. In this article, we present a systematic review of the literature on the use of the combination of radiation therapy and immunotherapy in the treatment of melanoma.
Jan 2017 DOI 10.14302/issn.2572-3030.jcgb-16-1307
Interpreting variants of uncertain significance (VUS) for their effect on protein function, and therefore for the risk of developing cancer, has become a challenge in clinical practice for genetic counselling services. The present work combines structural bioinformatics and systems biology based mathematical modelling approaches with the aim of determining the pathogenicity of the mutation c.5434C->G (p.Pro1812Ala) in the BRCA1 gene (detected in a patient from a high risk family) and also to mechanistically understand the effect of this mutation in DNA damage response, a key process in cancer development. The results obtained showed that this mutation prevents the interaction of BRCA1 with key proteins of the cell cycle, subsequently impairing BRCA1-dependent induction of cell cycle arrest. The comparison of the molecular mechanisms associated with the native BRCA1 protein and the mutated variant function in DNA damage response showed that the latter undergoes a reduction in its ability to modulate pathways that are critical for DNA repair and cell cycle control. Therefore, this variant will not be able to exert its tumor suppressive action. Interestingly, these conclusions can be extrapolated to all mutations that, like c.5434C>G (p.Pro1812Ala) BRCA1, cause loss of BRCT domain activity.
Jan 2017 DOI 10.14302/issn.2575-7881.jdrr-16-1375
We checked our simple screening technique for detection of the known polymorphism of rs769217, and the two acatalasemic mutations in exon 9 of the catalase gene. This fast and inexpensive method yielded better resolution than those of the standard SSCP. We suppose that the method detects the spontaneously formed single stranded DNAs.
Oct 2016 DOI 10.14302/issn.2572-3030.jcgb-16-1190
Background: Gastric cancer (GC) ranks as the fourth most common cancer and the second leading cause of cancer deaths worldwide. Epstein-Barr virus is a well-known oncogenic virus, it is responsible for 10% of gastric carcinomas across the world. The aim of study was to determine the prevalence of EBV associated with GC in Sudanese patients. Method: Fifty Paraffin embedded blocks of gastric biopsy specimens diagnosed as gastric carcinoma were collected from Soba university hospital and Ribat teaching hospital, Khartoum, Sudan. DNA was extracted from the paraffin-embedded tissue, and then Epstein-Barr virus gene was detected by polymerase chain reaction (PCR). Result: Among the gastric biopsy specimens 27 (54.0%) were of male and 23(46.0%) were of female. Eleven EBV positive samples were found in gastric carcinomas (22.0%), 8 (72.7%) were of male and 3(27.2%) were of female. The mean age of the patients was 56 years, the most positive cases were between 50-59 years old, and (10%) of them are alive in Khartoum. Conclusions: There exists an association between EBV and gastric carcinoma in some Sudanese patients.
Jul 2016 DOI 10.14302/issn.2381-862X.jwrh-15-806
Background and Objectives: The prevalence of abnormal cervical cytology in morbidly obese women using ThinPrep® liquid-based Pap Test™ and HPV DNA Test™ is unknown. We aimed to investigate whether women with morbid obesity have a higher frequency of abnormal Pap smears compared with nonobese women, and to explore the rate of Pap smear screening in morbidly obese women. Design and Setting: We conducted a retrospective study over five years in two general government hospitals in Dubai. Patients and Methods: We screened ThinPrep slides and HPV DNA of morbidly obese women and nonobese women. The age, ethnicity, demographic and socioeconomic backgrounds of the two groups were matched. We studied hypertension (HTN), diabetes (DM), infertility, sexually transmitted diseases (STD), connective tissue disease (CTD), immunosuppression and oral contraceptive pills (OCP) as potential risk cofactors. Results: Only 90 (29%) out of 310 morbidly obese women had had Pap tests. They showed more prevalence (P<0.05) of ASC-US, high-risk HPV DNA and LSIL 16 positive (18%) (95% CI: 7.0, and of endometrial AGCs {4 positive (4.5%) (95% CI: 0.3-13.5)} than the nonobese women (n=8175), {279 positive (3%) (95% CI: 3.0-3.8} , and {2 positive (0.024%) (CI:0.01-0.09)}. There were no endocervical AGCs, HSIL or squamous cancer in morbidly obese women. DM, HTN, OCPs, CTD and STD were more common in morbidly obese women having abnormal Pap smears. Conclusions: Low-grade squamous abnormalities, high-risk HPV, and endometrial AGCs are more frequent in morbidly obese women than in nonobese women. Women with morbid obesity have a low rate of cervical screening. This, among other factors, could increase the risk of these women to abnormal cervical cytology. This vulnerable group should benefit from more frequent cervical cytology screening. Appropriate clinical and educational measures should be implemented to encourage compliance to Pap smears. Weight reduction might help.
Jun 2016
Earlier studies reported significant association of obesity, hypertension and Type2 Diabetes Mellitus (T2DM). Genetic and many disease-associated alleles have been identified through GWAS and applied to T2DM and indicated roles of renin-angiotensin system (RAS) in insulin signaling pathway and insulin resistance has been well documented. Angiotensin converting enzyme (ACE) gene catalyzes the conversion of angiotensin I to angiotensin II and also inactive the vasodilatation and hence renin-angiotensin system (RAS) in insulin signaling pathway and insulin resistance has been reported. To best of the knowledge we are reporting for the first time regarding association of ACE gene polymorphism with body composition, physiological and metabolic variables among any endogamous ethnic group (Kurmis) from of West Bengal, Eastern India. To achieve the purpose, total 197 (male 99 and female 98) randomly selected apparently healthy unrelated adult individuals of Kurmi population of Purulia District, West Bengal, India were incorporated in the present study. Anthropometric variables, physiological variables (blood pressure) and metabolic variables (PP blood sugar) have been collected using standard techniques. Extracted genomic DNA was PCR amplified and genotyped to understand ACE gene I/D polymorphism. The result demonstrated significant (p<0.05) sexual dimorphism in PBF. MAP and PP blood sugar found to be in normal range among the Kurmis. ACE gene polymorphism showed no deletion of the Kurmis and hence, only the prevalence of ACE II (insertion-Insertion) genotype has been noticed. The present study vindicated on the basis of body composition in terms of fat patterning, physiological and metabolic variables and ACE gene polymorphism that there is very low or no risk of T2DM among the Kurmis of West Bengal, India.
Apr 2016 DOI 10.14302/issn.2575-7881.jdrr-15-863
It was, previously, reported that the specific pattern of the compositional features of particular human-mouse orthologs defining in human two clusters, named C2 and C5, are present in different clusters in mouse. Since, thus, these orthologs can harbor a significant number of nucleotide differences a large sample of human-mouse orthologs having in human the C2 and C5 compositional features were collected in order to identify the orthologs that have been conserved or diverged during speciation. From the collection, 945 and 1051 orthologs had in human the C2 and C5 profile, respectively, while in mouse only 77 and 125, respectively, had these profiles. We further analyzed whether or not the frequency-usage of trinucleotides having the same gross composition computed from the reading of all nearest-neighbors of the DNA sequence might convey a layer of biological information in terms of chromosomal topology and function. In human, more than 50% of the C2 and C5 genes were found distributed in six chromosomes and preferentially located in GC-rich bands of chromosomes 11, 16 and 19. It was, also, found that 80% of the entire set of genes of band 19p13.3 had the C2 and C5 profile. The data shown also indicate that the proteins codified by the C5 genes have a bias towards nucleus and cytoplasm and specific post-translational modifications while the proteins codified by the C2 genes are mainly located in the cellular membrane or secreted to the external cellular milieu and particular post-transcriptional modifications
Feb 2016 DOI 10.14302/issn.2374-9431.jbd-15-890
Purpose Signal Transducer and Activator of Transcription 4 (STAT4) is important for signaling by interleukins (IL-12 and IL-23) and type 1 interferons and has been found to have several simple nucleotide polymorphisms (SNPs) associated with human disease. STAT4 SNPs were computationally examined with respect to changes in potential transcriptional factor binding sites (TFBS) and these changes were discussed in relation to human disease. Methods The JASPAR CORE and ConSite databases were instrumental in identifying the TFBS. The Vector NTI Advance 11.5 computer program was employed in locating all theTFBS in theSTAT4 gene from 4 kb upstream of the transcriptional start site to 8.3 kb past the 3’UTR. The JASPAR CORE database was also involved in computing each nucleotide occurrence (%) within the TFBS. Results The STAT4 SNPs in the 70 kb intron between exon 2 and 3 are in linkage disequilibrium and have previously been found to be significantly associated with several vasculitis diseases as well as diabetes. The SNP alleles were found to alter the DNA landscape for potential transcriptional factors (TFs) to attach resulting in changes in TFBS and thereby, alter which transcriptional factors potentially regulate the STAT4 gene. These STAT4 SNPs should be considered as regulatory (r) SNPs. Conclusion The alleles of each rSNP were found to generate unique TFBS resulting in potential changes in TF STAT4 regulation. These regulatory changes were discussed with respect to changes in human health that result in disease.
Feb 2016 DOI 10.14302/issn.2326-0793.jpgr-15-889
Purpose The endothetal Per-Arnt-Sim (PAS) domain protein 1 (EPAS1) gene which encodes hypoxia-inducible-factor-2 alpha (HIF2a) is a transcription factor that is involved in the response to hypoxia. EPAS1 has been found to have four (rs56721780, rs6756667, rs7589621, rs1868092) simple nucleotide polymorphisms (SNPs) associated with human disease.These SNPs were computationally examined with respect to changes in potential transcriptional factor binding sites (TFBS) and these changes were discussed in relation to disease and alterations in high altitude adaptation in humans. Methods The JASPAR CORE and ConSite databases were instrumental in identifying the TFBS. The Vector NTI Advance 11.5 computer program was employed in locating all theTFBS in theEPAS1 gene from 1.6 kb upstream of the transcriptional start site to 539 bps past the 3’UTR. The JASPAR CORE database was also involved in computing each nucleotide occurrence (%) within the TFBS. Results The EPAS1 SNPs in the promoter, intron two and the 3’UTR regions have previously been found to be significantly associated with disease and different levels of high-altitude hypoxia among native Tibetans. The SNP alleles were found to alter the DNA landscape for potential transcriptional factors (TFs) to attach resulting in changes in TFBS and thereby, alter which transcriptional factors potentially regulate the EPAS1 genesuch as for the glucocorticoid and mineralocorticoid nuclear receptor binding sites created by the rs7589621 rSNP EPAS1-G allele. These receptors regulate carbohydrate, protein and fat metabolism. Also the minor rs7589621 rSNP EPAS1-A creates a punitive TFBS for the FOXC TF which is an important regulator of cell viability and resistance to oxidative stress. These EPAS1 SNPs should be considered as regulatory (r) SNPs. Conclusion The alleles of each rSNP were found to generate unique TFBS resulting in potential changes in TF EPAS1 regulation. The punitive changes in TFBS created by the four rSNPs could very well influence the significant cline in allele frequencies seen in Tibetans with increasing altitude or the haplotype association with high altitude polycythemia in male Han Chinese. These regulatory changes were discussed with respect to changes in human health that result in disease and sickness.
Jan 2016 DOI 10.14302/issn.2379-8572.joa-15-814
Background and Objective: The etiological factors for nasal polyps include infection, inflammation or an imbalance of a metabolic pathway. This study was designed to compare serum Helicobacter pyloriantibodies and H. pylori–DNAs between cases of nasal polyp and controls (nasal fracture). Patients and Methods: This case control study was carried out in ENT Department of Rasul Hospital in Tehran (2007-2008), upon nasal polyp tissues in 62 cases and inferior nasal turbinate mucosa in 25 controls. H. pylori–DNAs were searched by qualitative polymerase chain reaction (PCR) and serum specific H. pylori antibodies (ELISA IgG and IgA). Comparative tests were performed for the 2 groups, and P value < 0.05 was considered as statistically significant. Results: The mean age of cases and controls were 37.5 ± 13.7 and 31 ± 11.5 years, respectively. H. pylori–DNA was found in 32.3% (20/62) of the cases and 4% (1/25) of the controls (P value = 0.005). Serum H. pylori antibody (IgA) was found in 14.5% (9/62) of the cases and 4% (1/25) of the controls (P value = 0.27). However, previous immunity (IgG) was higher in 71% of the cases and 32% of the controls (P = 0.001). Conclusion: H. pylori infection may play a key role in the formation of nasal polyps. We recommend the PCR as the best method of searching for H. pylori infection. However, from the data obtained in this investigation it could not be determined whether or not H. pylori play a pathogenic role. Long-term antibiotics treatment in cases with nasal polyp, especially in cases with severe chronic rhinosinusitis where patients do not respond to surgery or steroids, may be useful. More randomized controlled trial (RCT) studies are necessary to validate the role of H. pylori infection in nasal polyp and the effect of antibiotics for eradication of H. pylori infection.
May 2015 DOI 10.14302/issn.2379-7835.ijn-14-603
Epigenetic mechanisms based on DNA methylation, histone modifications and RNA interference have recently showed important association to the development of a wide variety of diseases such as cancer, cardiovascular, metabolic, skin, autoimmune diseases and neurologic disorders. In the context of preventive aspects, the importance of nutrition on epigenetic function has been revealed. Therefore, drastic changes in dietary modifications may contribute to reduced disease risk. For instance, dietary intervention has been showed to affect DNA methylation in Alzheimer’s disease patients. Moreover, maternal high-fat diet can regulate gene expression through promoter histone modifications. Most importantly, RNA interference and particularly micro-RNA mediated regulation of gene expression has been linked to disease development. Remarkably, dietary intake has been demonstrated to significantly affect various miRNAs and their regulation on gene function. In this review, the relationship between epigenetics and disease and development of drugs based on epigenetic targets is presented as well as the influence of dietary intake on epigenetic mechanisms and its effect on disease prevention and therapy will be discussed.
Jan 2015 DOI 10.14302/issn.2379-7835.ijn-14-606
Telomeres are strings of DNA that are not themselves genes but that extend every chromosome beyond its last gene. Terminal telomeres are sacrificed during every mitotic event in human cells (“telomere attrition”), preserving the functional genome despite the “end replication problem.” However, the “telomeric theory of biological aging” suggests that when an individual cell has reproduced itself a sufficient number of times (the “Hayflick limit”), some the its telomeres have become critically shortened (“telomeric crisis”) and cannot completely “cap off” a chromosome, and any further attempts to replicate such a chromosome would produce damaged DNA and a dysfunctional cell (“cellular aging”). As cells enter telomeric crisis, they usually initiate intracellular signaling cascades that arrest DNA replication and mitotic activity, converting biologically active cells into inactive cells (“cellular senescence”). The progressive accumulation of senescent cells impairs the healthy functioning of tissues and produces “biological aging.” Oxidative stress damages telomeres and accelerates telomere attrition and biological aging. Premature biological aging is associated with degenerative diseases and diminished quality of life. Reducing the level of systemic oxidative stress can ease the oxidative drive toward cellular senescence and premature biological aging. Increased intakes of antioxidant-rich foods and specific antioxidant nutrients (such as fruits and vegetables, α -lipoic acid, astaxanthin, eicosapentaenoic acid, docosahexaenoic acid, trans-resveratrol, N-acetylcysteine, methylsulfonylmethane, lutein, vitamin C, vitamin D, vitamin E, and γ-tocotrienol) may decrease cellular and systemic oxidative stress and decelerate biological aging.
Dec 2014 DOI 10.14302/issn.2326-0793.jpgr-14-598
Colorectal cancer is one of the most commonly diagnosed cancers worldwide and its prevalence can be reduced by changes to lifestyle and diet. Fermentation of dietary fibre by the gut microbiota and formation of short chain fatty acids, in particular butyrate, is widely thought to play a role in preventing development of the disease. Despite butyrate’s known pro-apoptotic effects, a subpopulation of cancer cells is able to overcome these anti-neoplastic effects of colonic luminal butyrate to proliferate and establish tumours in vivo. In this study, a time course analysis of HT29 and HT29-BR cells treated with butyrate was conducted and global gene expression analysis was used to identify novel mechanisms associated with butyrate-induced apoptosis and in the acquisition of butyrate resistance. Bioinformatic analysis of the data identified deregulated O-GlcNAcylation activity and disruption to gene transcription by BRD4 as possible factors involved with butyrate-induced apoptosis. EGF signalling was identified as being potentially involved in the acquisition of butyrate resistance. Furthermore, the expression of the minichromosome maintenance protein family was significantly reduced in the HT29-BR cell line reflecting disruptions to the DNA replication process. Together, this may confer a unique survival advantage for cells with acquired butyrate resistance.