Search results for “inflammation”

RETRACTED: A Microglia Initiated Target Therapy in Neuroinflammation for Alzheimer’s Patients

This article has been retracted on 20 March 2025. VIEW THE RETRACTION NOTICE (https://doi.org/10.14302/issn.2998-4211.jalr-25-5855) The research is focused on neuroinflammation a normal physiological process which is known to be associated with neurodegenerative diseases could be the potential targeted therapy via the microglia cells, it starts with defining Alzheimer’s; a neurodegenerative disease which causes deposition of Aβ (amyloid beta) protein in the cerebral cortex as well as NFT (neurofibrillary tangles) in the hippocampus and basal ganglia. The paper then describes process of neuroinflammation, microglia’s role, apolipoprotein E4 gene in relation to Alzheimer’s, which leads to different stem cell research and how pruning microglia as well as targeting microglia receptors in the brain is being used in current research trials, we included multiple meta-analysis showing microglia receptors being targeted currently by emerging drugs like propofol, antibodies CSF1R inhibitor etc, which are currently under trial phase, the research ends with concluding potential diagnostic markers like sirt1 considered to be an anti-aging protein which can be used as therapeutic interventions and Lps effect on Sirt 1. A Microglia initiated target therapy in Neuroinflammation for Alzheimer’s Patients.

Retraction Note: A Microglia Initiated Target Therapy in Neuroinflammation for Alzheimer’s Patients

Acute pneumonia: infection or inflammation in the lung?

This commentary examines pneumonia as infection and inflammatory syndrome, parsing diagnostic criteria and implications for antimicrobial stewardship.

Autoimmune Diseases: Genes, Inflammation And Environment

A concise review of autoimmune disease etiology emphasizes genetic susceptibility, inflammatory pathways, and environmental exposures. It points to systems approaches for risk stratification and prevention with illustrative examples.

Transiently Raised IOP Equivalent to That Experienced During Ocular Surgery Causes Moderate Inflammation but does not Affect Retinal Function or Result in Retinal Ganglion Cell Loss in An Animal Model

Purpose: High intraocular pressure (IOP) is known to result in retinal ganglion cell (RGC) loss, both with chronically raised intraocular pressure (such as with glaucoma) and with acute raises in pressure (due to injury or acute angle closure). Because IOP is often raised during ocular surgery, the purpose of this study was to evaluate the effect of transient moderate IOP on retinal function, RGC survival and the expression of Connexin 43 (Cx43) and glial fibrillary acidic protein (GFAP), ubiquitously expressed central nervous system (CNS) proteins that are known to be elevated during the retinal inflammatory response to injury. Materials and Methods: Wistar rats were exposed to transient IOP at 40 mmHg for 5 or 30 minutes, and 60 mmHg for 5 minutes (via cannulation of the anterior chamber with a saline reservoir raised to a height corresponding to the desired IOP), mimicking potential IOP rises during surgery such as DSAEK and some laser procedures (LASIK and femtosecond laser cataract surgery). Separate groups of animals had IOP maintained at 10 mmHg for 5 or 30 minutes as cannulation controls, or 120 mmHg for 60 minutes as positive controls. Changes in the optic nerve and retina were assessed immunohistochemically for GFAP and Cx43 expression. Retinal function was assessed using electroretinography (ERG) recorded at baseline and 14 days after the IOP rise and compared with RGC counts. Results: Results showed that there was a differential GFAP labelling pattern observed in the anterior optic nerve in the 40 mmHg 30 minute and 60 mmHg 5 minute groups 4 hours after manipulation. Gap junction protein Cx43 was minimally up-regulated in the retina in the short-term. There was, however, minimal long-term effect on retinal function and no RGC loss. Conclusions: n conclusion, elevations of IOP that are short in duration such as those occurring during surgical procedures, do not cause significant changes long-term in retinal function or RGC survival. Key Messages: Cx43 and GFAP are known to be elevated during the retinal inflammatory response to injury. No previous study has explored the effect of moderate and relatively short increases in IOP on the initial inflammatory response. We observed a mild glial inflammatory response in the anterior optic nerve, but only a minimal up-regulation of Cx43. However, transient and moderate IOP rises did not induce long term disruption to RGC function or number as measured by electrophysiology and RGC counts, respectively. This is applicable to clinical practice, as it means the IOP elevations that occur during some surgical procedures are unlikely to be causing long term damage in retinal function or RGC survival.

Diabetic Mouse Delayed Wound Model Following Treatment with the NerveStim™ Neuropathy System

Delayed wound healing in diabetes is characterized by impaired angiogenesis, persistent inflammation, extracellular matrix dysregulation, and peripheral neuropathy. A preclinical study was conducted using a diabetic mouse delayed wound model to evaluate the surrounding tissue of a wound, (its periwound) and its tissue responses following treatment with the NerveStim™ Neuropathy System, a combination topical gel and neuromuscular electrical stimulation platform. Periwound tissue was harvested at Day 14 and analyzed using NanoString gene expression profiling. Treated animals demonstrated visibly increased periwound tissue thickness compared to untreated controls. Differential expression analysis identified 76 significantly upregulated and 17 downregulated genes. Upregulated pathways included angiogenesis (Vegfa, Fgf2, Pdgfb, Nos3), neurotrophic signaling (Ngf, Bdnf, Scn9a, Trpv1), macrophage polarization (Arg1, Mrc1, Il10), and extracellular matrix remodeling (Col1a1, Col3a1, Mmp9, Timp1). Downregulation of select pro-inflammatory mediators (Nos2, Mif) was observed. These coordinated transcriptional changes are consistent with activation of reparative immune, neurovascular, and matrix remodeling pathways in diabetic periwound tissue.

Activation of Transcription Factor EB Protects Against Proinflammatory Insults Through NF-κB Inhibition in Keratinocytes

Keratinocytes are pivotal in mediating cutaneous inflammation. Identifying anti-inflammatory factors within these cells holds promise for developing novel therapeutic strategies to manage skin inflammation. Transcription factor EB (TFEB) has recently emerged as a key regulator linking cellular energy metabolism to inflammatory processes, primarily through its influence on autophagy and NF-κB signaling. However, whether TFEB activation exerts anti-inflammatory effects in keratinocytes remains unclear. In vitro inflammation model was established in HaCat cells by incubation with proinflammatory mediators LPS and IL-1β. Cell viability and TFEB expression and phosphorylation were measured. The effect of TFEB activation by C1 and adenoviral TFEB overexpression on the expression of proinflammatory genes including COX-2, MCP-1 and IL-6 were detected. Also, IκBα protein level were determined. TFEB phosphorylation is increased while TFEB total protein expression is inhibited by treatment with LPS and IL-1β. Pharmacological activation of TFEB by compound C1 and TFEB overexpression suppressed the expression of COX-2, MCP-1 and TNF-α induced by LPS and IL-1β. TFEB overexpression increased basal IκBα expression and restored IκBα level under LPS treatment. TFEB knockdown reduced TFEB expression and lowered basal expression level of COX-2, MCP-1 and TNF-α. Our findings indicate that TFEB activation can mitigate inflammatory gene expression in keratinocytes triggered by LPS and IL-1β. This implicates TFEB as a significant novel modulator of cutaneous inflammation, highlighting its potential as a therapeutic target. Targeting TFEB could thus be a viable strategy for developing new treatments for chronic inflammatory skin conditions.

Conjunctival Resection for Mooren's Ulcer Refractory to Medical Therapy: A Case Report

Purpose To report a rare case of Mooren’s ulcer in a healthy young male without systemic autoimmune disease, and to highlight the effectiveness of conjunctival resection as therapy for cases unresponsive to medical management. Case report A 34-year-old immunocompetent male presented with progressive peripheral corneal ulceration in the left eye. Extensive systemic and infectious evaluations, including rheumatologic, immunologic, and microbiological testing, were unremarkable. Human leukocyte antigen genotyping was DR17(03)-negative and DQ2-positive. Rheumatological evaluation yielded no definitive systemic diagnosis. Despite immunosuppressive therapy with adjuvant medications, the epithelial defect and stromal inflammation persisted. The patient underwent conjunctival resection, resulting in marked reduction in inflammation, rapid re-epithelialization, and structural stabilization of the cornea. Histopathology of excised conjunctiva showed nonspecific inflammation without granulomatous changes, vasculitis, or neoplastic features. During follow-up, patient remained in remission with visual acuity preserved at 6/6 bilaterally and no recurrence. Conclusion Mooren’s ulcer is rare but vision-threatening. Early recognition, comprehensive evaluation, and timely surgical intervention can be vision-saving. This case highlights the role of a multidisciplinary approach and supports conjunctival resection as a useful adjunct in refractory disease. Long-term follow-up is essential.

Exploring the Mechanism of Complex Lemon-Angelica Sinensis-Boswellia Essential Oil on Anxiety Disorders with Melasma Through Network Pharmacology and Experimental Validation

The incidence rate of melasma is notably high among patients with anxiety disorders. Aromatherapy primarily influences the physiological and psychological states of individuals through the inhalation or application of essential oils, thereby facilitating the treatment or alleviation of various conditions. This study aims to explore the action mechanism of complex lemon-angelica sinensis -boswellia essential oil (CEO) in treating anxiety disorders with melasma. We investigated the active ingredients, targets, and pathways of CEO in relation to anxiety and melasma using network pharmacology. We employed cell assays and conducted nebulized essential oil inhalation tests on CUMS mice to validate the intervention effects of CEO on anxiety. A total of 28 active components, including neryl acetate, 3-butenylphthalide and octyl acetate, and 26 cross-targets, such as ESR1, CCND1 and PIK3CA, were identified. GO and KEGG pathway analyses indicated that these cross-targets were primarily involved in endocrine regulation, cell proliferation, and apoptosis, specifically through PI3K/Akt signaling pathway and calcium signaling pathway. The experimental results demonstrated that CEO significantly reduced the secretion of NO, TNF-a and IL-6, as well as the mRNA expressions of ESR1, CCND1 and PIK3CA in cells compared to the inflammatory cell model. Furthermore, CEO notably decreased the forced swimming immobility time of mice and the levels of IL-1β, ESR1 and CCND1 in hippocampus when compared to model mice. These findings suggest that CEO may regulate ESR1, CCND1 and PIK3CA through its citral, 3-butylphthalate and neryl acetate, thereby influencing endocrine function, cell proliferation and apoptosis, inhibiting inflammation and anxiety-like behavior in CUMS-induced mice.

Plasma TREM2 Levels, Alcohol Consumption, and Liver Enzymes in Patients with Alcohol use Disorder: A Sex-Dependent Relationship Involving MS4A6A Genetic Polymorphism

Alcohol use disorder (AUD) is the most prevalent substance use disorder. Excessive alcohol consumption leads to a range of health issues. We set out to identify inflammatory markers linked to alcohol consumption, which might ultimately offer novel insight into genetic underpinnings and have implications for alcohol-associated disease. Alcohol consumption and blood-based multi-omics data were collected by The Mayo Clinic Center for Individualized Treatment of Alcohol Dependence study. Plasma samples from patients with AUD were used for proteomics analysis using the OLINK “Explore Inflammation” panel (n=410). Liver enzymes were also measured. A genome-wide association study (GWAS) was performed to explore the relationship between genetic variants and plasma TREM2 levels. Our findings show thatplasma triggering receptor expressed on myeloid cells 2 (TREM2), a key gene associated with neurodegenerative disease, was the most significant signal correlated with alcohol consumption, and has also been associated with liver enzyme levels in patients with AUD. We identified the rs7232 single nucleotide polymorphism (SNP) in MS4A6A as a key genetic variant associated with plasma TREM2 levels, with the minor allele (A) linked to higher TREM2 levels and increased alcohol consumption, particularly in men. Furthermore, MA4A6A is an ethanol-responsive gene in a SNP-dependent manner, and the variant genotype of the rs7232 SNP was associated with lower expression for MA4A6A due to proteasome-mediated protein degradation. In summary, this study provides insight into the relationship between plasma TREM2 levels, alcohol consumption, and liver function in AUD patients, shedding light on genetic factors underlying alcohol-related diseases.

A Cross Sectional Analysis of Frailty and Markers of Frailty in Young People Living with HIV/AIDS

Background Frailty is an ageing-associated state linked to poor prognostic outcomes. Chronic inflammation due to HIV-infection, AIDS-related infections. and the adverse effects of antiretroviral therapy (ART) all contribute to frailty in people living with HIV/AIDS (PLHA). Frailty has been comprehensively studied in populations comprising predominantly of Caucasian PLHA. However, there remains a dearth of such data in Indian populations, especially in younger PLHA. Methodology This cross-sectional study aimed to estimate the prevalence of frailty in PLHA (18 - 50 years) who had been on ART for 24-60 months and identify markers linked to frailty. Frailty was assessed in 152 subjects using the Fried frailty-index. Parameters measured included the mid-upper arm and calf circumferences, pain-severity (using the Brief Pain Inventory), highly-sensitivity C-reactive protein, d-dimer, and interleukin-6. Results The prevalence of frailty and pre-frailty were 6.58% and 23.02%, respectively. Reduced grip strength and self-reported exhaustion were associated with frailty (15.79% and 13.16%, respectively). Low calf-circumference and mid-upper arm circumference were not significantly associated with frailty/pre-frailty. The prevalence of pain was 21.7% and both pain severity and pain interference were significantly associated with frailty/pre-frailty. CD-4 counts at the time of assessment showed an inverse association with frailty. Elevated C-reactive protein (CRP of 0.04 associated with 0.49 probability of frailty (95% CI 0.40 – 0.59), CRP of 0.12 associated with 0.63 probability of frailty (95% CI 0.47 – 0.76)). D-dimer levels were not significantly associated with frailty /pre-frailty. Conclusion In this first-of-its-kind study on frailty in young PLHA (mean age 37 years) from the Indian sub-continent, the prevalence of frailty and pre-frailty was 6.58% and 23.02%, respectively. Multivariate analysis showed a strong association of frailty with pain severity, CD4 count at time of assessment, hs-CRP levels and duration of ART.

The Useful Conclusion in our Experience Regarding the Sacral Injection

Caudal injection is a type of epidural injection that is administered to the lower back to reduce pain and inflammation. The injection contains a steroid medication that is injected into the lower part of the epidural space, which surrounds the nerve roots in the lower back. The procedure is usually performed on an outpatient basis, and most patients experience relief from back pain within a few days. The sacral injection is another name for a caudal epidural injection. It is a type of spinal epidural injection that is administered to the sacral hiatus, which is the opening at the base of the spine near the tailbone. The injection is used to treat nerve pain and inflammation caused by conditions such as spinal canal stenosis, herniated disks, degenerative disk disease, sciatica, or radiculopathy.

Is Vagus Nerve Therapy a Potential Alzheimer's Disease Treatment?

A potential treatment for Alzheimer's disease is vagus nerve therapy, which has been made possible by considerable advances in neuroscience. An essential component of the autonomic nervous system, the vagus nerve regulates memory, inflammation, and cognition. Researchers hope to delay the progression of Alzheimer's disease and improve cognitive function by implanting a vagus nerve stimulator (VNS). Alzheimer's patients have higher heart rate variability, according to an ECG study, which may be advantageous. To completely grasp its mechanics and long-term effectiveness, more research is necessary.

A case of delayed allergy after cyanoacrylate closure of varicose veins, diagnosed by drug-induced lymphocyte stimulation test

Objectives The number of cases of cyanoacrylate closure (CAC) system for varicose veins has been increasing worldwide. However, as this is a new treatment method, the potential adverse effects and other details remain unclear. In particular, the cause of inflammation in embolized veins is still under debate. Methods We performed a drug-induced lymphocyte stimulation test (DLST) on a patient with allergic-like symptoms after CAC.  Results The DLST was strongly positive in this case, and the patient underwent total removal of the CAC-filled vein due to difficulty controlling the symptoms with medication. After that the state was recovered and no medication was continued. Conclusion We encountered a case that a delayed allergy by CA after CAC treatment developed in, eventually leading to the total removal of the CA-filled vein. It was suggested that with doubting allergic-like symptom after CAC, DLST for CA could show not only the diagnosis of the delayed allergy to CA, but also the later treatment policy with stimulation index (S.I.) in the positive cases.

Study of Anti-Inflammatory Effects of Black Cumin (Nigella Sativa) and Honey on Mice (Mus Musculus)

The study was conducted to determine the effect of Nigella sativa (Kalonji) and Honey as an anti-inflammatory agent for humans and animals. The study was carried out on 20 Albino Mice of almost equal size and weight. All the mice were given 5% solution of formalin in a dose of 0.5ml injection in their right hind paw to produce artificial inflammation. The mice were divided into four groups of five animals in each and were randomly allotted to four treatments as Group A (Control) where no Nigella sativa extract and honey were given, Group B where the mice were given only the ethanolic extract of Nigella sativa in the dose of 0.05ml injection as a remedy of inflammation, Group C where the mice were given only the honey orally in a dose of 0.05mg and Group D where mice were given 50% (0.025ml) intraperitoneally of Nigella sativaextract and 50% (0.75mg) of honey as an anti-inflammatory agents. The data was statistically analyzed by the Analysis of Variance (ANOVA) and the results showed that the inflammation was significantly (p<0.05) reduced in mice given treatments compared to untreated control group and among treated groups. The mice given the extract of Nigella sativa (Group B) showed better results (p<0.05) in reducing the inflammation compared to other groups (C and D), Group D where the mice were given 50% (0.025ml) Nigella sativa extract and 50% (0.75mg) honey showed better results (p<0.05) than mice given only honey. Overall, both the extract of Nigellasativa and the honey were almost equally successful in reducing the inflammation in mice which showed that these two agents can successfully be used as anti-inflammatory drugs in humans and animals.

Deficiency of Adenosine Deaminase Type 2 (ADA2) DADA2 Masquerade as Lupus

DADA2 (deficiency of adenosine deaminase type 2) is an autoinflammatory autosomal recessive disease resulting from biallelic loss of function mutations in ADA2 gene. Clinical presentation and age of onset vary widely even among related patients, and variability of symptoms and severity manifestations include bone marrow failure, autoinflammation, immunodeficiency and vasculitis. Here, we report a case of young male with adult onset DADA2, who presented with fever, lower limbs skin rash, joint pain, and anemia resembling systemic lupus erythematous (SLE). DADA2 has an extremely variable clinical phenotype. It was described into three categories: inflammatory/vascular, immune dysregulation, and hematologic. However, the data is scant in describing autoimmunity phenotype in DADA2 and further studies are required to investigate the clinical correlation and presence of autoantibodies. We recommend genetic testing in cases with lupus-like disease especially if there is consanguinity between parents and family history of vasculitis.

Pyrexia And Liver Injury After A Second SARS-CoV-2 Vaccination: Macrophage Activation Manifested In Liver

Vaccination against severe acute respiratory syndrome coronavirus 2 (SARS-Co V-2) has contributed to control of the coronavirus disease 2019 (COVID-19). On the other side, vaccination of SARS-CoV-2 could trigger autoimmune or inflammatory diseases. We present a 50-year-old female with well-controlled optic neuromyelitis with prednisolone (PSL) maintained at a dose of 2.5 mg/day. She ran a fever and liver injury was indicated 5 weeks after a second COVID-19 vaccination (BNT162b2 mRNA/Pfizer ). Liver biopsy showed accumulation of macrophages around the central veins, identified using anti-CD68 antibodies. As the treatment, cyclosporine A improved liver injury. COVID- 19 vaccination may have triggered liver inflammation due to cytokine storm via macrophage activation in the liver.

Assessment of the Factors that Contribute for the Cause of Asthma Disease in Ambo Town

Asthma is a chronic disease of airways; that is widely characterized by an increased responsiveness to a large variety of stimuli, airway inflammation and obstruction. It is the most common respiratory disorder disease in developed and developing countries. The study was aimed to assess the factors that contribute for the cause of asthma disease in Ambo town and cross-sectional survey was conducted to gather information from March to April 2022. 30 respondents were selected using purposive sampling technique for interview and data collections. According to the study the more affected age group were 22-32(53%) and the major risk factor for the disease was air pollution (53%). The pollution is due to domestic wastes that are discharged to the environment. Therefore, the government and extension health workers should aware the community about the risk factors of asthma and proper waste disposal mechanisms.

Effect of Extracts of Dialium guineense Stem Bark on Lipid Profile and CCl4- Induced Histological Changes in Liver of Wistar Rats

The present study investigated the effect of aqueous and ethanol extracts of Dialiumguineense stem bark on lipid profile and CCl4- induced histological changes in liver of Wistar rats. Adult male Wistar rats (n = 25) weighing 160 – 180 g (mean weight = 170 ± 10 g) were randomly assigned to five groups (5 rats per group): normal control, CCl4 control, silymarin, aqueous extract and ethanol extract groups. With the exception of normal control, the rats were exposed to CCl4 (single oral dose of 1.0 mL/kg body weight, bwt). Silymarin group rats were administered standard hepatoprotective drug, silymarin, at a dose of 100 mg/kg bwt, while those in the two treatment groups received 1000 mg/kg bwt of aqueous or ethanol extract orally for 28 days. Lipid profile parameters were determined in plasma, while rat liver was subjected to histopathological examination. The results showed that the levels of total cholesterol (TC), triacylglycerol (TG), high-density lipoprotein cholesterol (HDL-C), very-low density lipoprotein cholesterol (VLDL-C), low-density lipoprotein cholesterol (LDL-C) as well as atherogenic index of plasma (AIP) were significantly lower in CCl4 control group than in normal control group, but they were increased by extract treatment (p < 0.05). However, there were no significant differences in atherogenic coefficient (AC) and cardiac risk ratio (CRR) among the groups (p > 0.05). Carbon tetrachloride (CCl4) markedly disrupted the structure of hepatocytes and induced steatosis (intra-hepatocyte fat in-growth and inflammation) which was predominantly microvesicular. However, treatment with aqueous and ethanol extracts of D. guineense stem bark showed marked regeneration of hepatocytes (unremarkable hepatic lobular architecture). The toxic hepatic injury induced by CCl4 was significantly blocked by the plant extracts.

Sub-Xiphoid Abscess and Sinus after Open Heart Surgery

Purpose Is it safe to excise only the external portion of the pacemaker wires? This presentation aims to find out the proper way to manage pacing wires postoperatively. Methods We report 5-cases of sub-xiphoid abscesses and sinuses after valve surgery. Each case presented with a recurrent abscess that opens and drains its contents through a sinus around the lower-most portion of the xiphoid process. The duration between open heart surgery and evolution of these abscesses varied between 18 and 60 months. Valve surgeries were mitral and/or aortic valve replacement. Surgeons usually insert pacemaker wires to control any persistent post-operative arrhythmias that can affect hemodynamic circulation. On the day of discharge, some surgeons (not in our center) usually excise the pacemaker wires. Results The remaining intra-thoracic portions underwent some degree of corrosion that caused a state of chronic inflammation, sinus track formation and abscess evolution. This indicated radiological examination and surgical exploration to extract these foreign bodies. These 5 cases were diagnosed and operated upon between 15th January 2022 and 1st March2022, all at Abo-Khalifa Emergency Hospital-Ismailia, Egypt. Conclusions This confirms the significance of total withdrawal of the external pacemaker wires. Surgeons should not apply tight sutures at the site of insertion of the wires.

Duodenocolic Fistula: A Rare Complication of Gastrointestinal Tuberculosis

Introduction Benign duodenocolic fistula (DCF), also known as a non-malignant fistula between the duodenum and colon, with or without cecum-involvement, is an unusual complication of different gastrointestinal (GI) diseases 12. Case This is a case of a 28-year-old Filipino female who presented with periumbilical pain for five months, with associated anorexia, fever, and weight loss. Biopsy showed chronic granulomatous inflammation with caseation necrosis and Langhan’s type giant cells consistent with tuberculous etiology (Figure 6 and Figure 7). Category I Anti-TB treatment for six months was started and the service planned to repeat both colonoscopy and CT-scan after the initial round of anti-TB treatment. Conclusion Benign duodenocolic fistula in the form of extrapulmonary TB is a rare GI finding that is triggered by inflammatory processes. Proper management in this case was to treat the underlying TB infection which is endemic in the Philippines.

Evaluation of Inflammatory Serum Cytokines after Treatment with the Consciousness Energy Healing Based Proprietary Test Formulation on Combination of Cecal Slurry, LPS and E. Coli Induced Systemic Inflammatory Response Syndrome (SIRS) in Sprague Dawley Rats

Sepsis is a systemic inflammatory response to a confirmed or suspected infection. The transition from sepsis to septic shock causes high rate of mortality. The aim of this experiment was to evaluate the anti-inflammatory potential of the Biofield Energy Treated (Blessed) Proprietary Test Formulation and Biofield Energy Healing (Blessing) Treatment per se to Sprague Dawley rats on Cecal Slurry, LPS, and E. coli-induced systemic inflammatory response syndrome (SIRS) model. In this experiment, various proinflammatory cytokines such as tumor necrosis factor-α (TNF-α), interleukin-1β (IL-1β), IL-6, IL-10, IL-12, 1L-17, and interferon-γ (IFN-γ) were analysed using ELISA. A test formulation was formulated including minerals (magnesium, zinc, calcium, selenium, and iron), vitamins (ascorbic acid, pyridoxine HCl, vitamin E, cyanocobalamin, and cholecalciferol), Panax ginseng extract, β-carotene, and cannabidiol isolate. The constituents of the test formulation were divided into two parts; one section was defined as the untreated test formulation, while the other portion of the test formulation and three group of animals received Biofield Energy Healing Treatment remotely for about 3 minutes by a renowned Biofield Energy Healer Mr. Mahendra Kumar Trivedi. The level of TNF-α was significantly reduced by 40.50%, 85.36% (p≤0.01), 50.66% (p≤0.01), 87.38% (p≤0.01), and 58.63% (p≤0.01) in G5 (Cecal Slurry, LPS, and E. coli + Biofield Energy Treated test formulation), G6 (Cecal Slurry, LPS, and E. coli + Biofield Energy Treatment per se to animals from day -15), G7 (Cecal Slurry, LPS, and E. coli + Biofield Energy Treated test formulation from day -15), G8 (Cecal Slurry, LPS, and E. coli + Biofield Energy Treatment per se + Biofield Energy Treated test formulation from day -15), and G9 (Cecal Slurry, LPS, and E. coli + Biofield Energy Treatment per se animals + untreated test formulation) groups, respectively as compared to the disease control (G2) group. Additionally, the level of IL-1β was decreased by 17.04%, 15.56%, and 12.59% in G6, G8, and G9 groups, respectively as compared to the untreated test formulation (G4) group. The level of IL-6 was significantly (p≤0.001) reduced by 36.18%, 50.24%, 43.25%, 52.69%, and 38.23% in the G5, G6, G7, G8, and G9 groups, respectively as compared to the G2 group. The level of IL-10 was altered by 70.53%, 49.25%, 60.18%, 41.54%, and 58.89% in G5, G6, G7, G8, and G9 groups, respectively as compared to the G2 group. Moreover, the level of IL-12 was decreased by 30.24%, 31.67%, 29.82%, 45.77%, and 50.54% in the G5, G6, G7, G8, and G9 groups, respectively as compared to the G2. The level of IL-17 was reduced by 48.75%, 59.61%, 59.28%, 62.49%, and 58.65% in the G5, G6, G7, G8, and G9 groups, respectively as compared to the G2. IFN-γ expression was reduced by 49.56%, 24.09%, 23.7%, 56.98%, and 44.94% in G5, G6, G7, G8, and G9 groups, respectively than G2. Overall, the data suggested anti-inflammatory potentials of the Biofield Energy Treated test formulation and Biofield Energy Treatment per se along with preventive measure on the animal with respect to various inflammatory conditions that might be beneficial various types of systemic inflammatory disorders specially sepsis, trauma, septic shock or any types of injuries. Therefore, the results showed the significant slowdown the inflammation-related disease progression and its complications in preventive treatment groups viz. G6, G7, G8, and G9.

Protective Role of Quercetin Against Rotenone- Induced Hepato and Nephrotoxicity in Swiss Albino Mice

Rotenone is well known environmental neurotoxin used to induce Parkinson’s disease (PD) model. Numerous studies are investigated its toxicity on the brain but few studies are available that examined its toxicity on the liver and kidney. Therefore, the main aim of the present work was to explore the toxicity of rotenone on the liver and kidney and its protection through quercetin. Administration of rotenone orally at the dose of (5mg/kg b.w daily for 60 days) caused a significant increase in the levels of liver function and renal function biomarkers as compared to controls. A significant increase in the level of lipid peroxidation, nitric oxide, and decrease in the levels of reduced glutathione, reduction in the activities of catalase and superoxide dismutase were observed in the liver and kidney as compared to control. The histopathological and SEM study in rotenone-treated mice showed alteration and signs of inflammation in the liver and kidney. While co-treatment of quercetin orally (30 mg/kg b.w for 60 days) together with rotenone, reversed the above parameters. In conclusion, rotenone significantly damages the liver and kidney, and the administration of quercetin along with rotenone shown a protective role. This study provides a new insight into where rotenone-induced liver and kidney dysfunction could be successfully protected by quercetin.  

Evaluation of Renal and Cardioprotective Potential of the Biofield Energy Treated Proprietary Test Formulation on L-NAME and High Fat Diet-Induced Cardiovascular Disorders in Sprague Dawley Rats

The aim of this study was to evaluate the impact of Biofield Energy Treated/Blessed Proprietary Test Formulation and Biofield Energy Treatment/Blessing per se on kidney biomarkers on L-NAME and high fat diet (HFD)-induced cardiovascular disorders in Sprague Dawley rats. In this experiment, the functional kidney biomarkers such as epinephrine/adrenaline, inducible nitric oxide synthase (iNOS), angiotensin-II, C-reactive protein (CRP), and renin were measured using ELISA assay. A test formulation was formulated including minerals (magnesium, zinc, copper, calcium, selenium, and iron), vitamins (vitamin C, vitamin B6, vitamin B12, vitamin B9, and vitamin D3), cannabidiol (CBD) isolate, Panax ginseng extract, and β-carotene. The components of the test item were divided into two; one section was defined as the untreated test formulation, while the other part and three group of animals received Mr. Mahendra Kumar Trivedi’s Biofield Energy healing/Blessing remotely for about 3 minutes. The results showed that the level of adrenaline was reduced by 31.62%, 19.58%, 34.32%, 37.07%, and 29.87% in the G5 (L-NAME + HFD + the Biofield Energy Treated test formulation), G6 (L-NAME + HFD + Biofield Energy Treatment per se to animals from day -15), G7 (L-NAME + HFD + the Biofield Energy Treated test formulation from day-15), and G8 (L-NAME + HFD + Biofield Energy Treatment per se plus the Biofield Energy Treated test formulation from day-15), and G9 (L-NAME + HFD + Biofield Energy Treatment per se animals plus the untreated test formulation) groups, respectively as compared to the disease control group (G2). Moreover, the level of iNOS was reduced by 56.76%, 49.51%, 61.79%, 57.63%, and 62.44% in the G5, G6, G7, G8, and G9 groups, respectively, as compared to the disease control group (G2). Additionally, the level of angiotensin-II was decreased by 41.09%, 34.92%, 60.65%, 53.28%, and 60.09% in the G5, G6, G7, G8, and G9 groups, respectively, as compared to the G2 group. The level of CRP was decreased by 47.21%, 38.89%, 59.81%, 55.52%, and 64.02% in the G5, G6, G7, G8, and G9 groups, respectively as compared to the G2 group. Besides, the level of renin was decreased by 20.27%, 20.13%, 12.99%, and 25.73% in the G5, G7, G8, and G9 groups, respectively as compared to the G2 group. Overall, the data suggested significance improvement of vital functional kidney biomarkers of the Biofield Energy Treated/Blessed test formulation and Biofield Energy Treatment per se along with preventive measure on the animal with respect to various pathological conditions that might be beneficial various types of cardiovascular disorders. Therefore, the results showed the significant slowdown the inflammation-related cardiovascular disease progression and its complications/symptoms in the preventive Biofield Energy Treatment group per se and/or Biofield Energy Treated/Blessed Test formulation groups (viz. G6, G7, G8, and G9).

Rosemary (Salvia rosmarinus): Health-Promoting Benefits and Food Preservative Properties

Natural food preservatives in the form of herb extracts and spices are increasing in popularity due to their potential to replace synthetic compounds traditionally used as food preservatives. Rosemary (Salvia rosmarinus) is an herb that has been traditionally used as an anti-inflammatory and analgesic agent, and currently is being studied for anti-cancer and hepatoprotective properties. Rosemary also has been reported to be an effective food preservative due to its high anti-oxidant and anti-microbial activities. These properties allow rosemary prevent microbial growth while decreasing food spoilage through oxidation. Rosemary contains several classes of compounds, including diterpenes, polyphenols, and flavonoids, which can differ between extracts depending on the extraction method. In particular, the diterpenes carnosol and carnosic acid are two of the most abundant phytochemicals found in rosemary, and these compounds contribute up to 90% of the anti-oxidant potential of the herb. Additionally, several in vivo studies have shown that rosemary administration has a positive impact on gastrointestinal (GI) health through decreased oxidative stress and inflammation in the GI tract. The objective of this review is to highlight the food preservative potential of rosemary and detail several studies that investigate rosemary to improve in vivo GI health.

Analgesic and Anti-Pyretic Activities of the Root Bark of Rutidea Parviflora (Rubiaceae)

This study aims at investigating the antipyretic activity of different solvent fractions of the root bark of Rutideaparviflora(Rubiaceae). This plant is used ethno-botanically by the people of Ethiope East-West Local Government Area of Delta State, Nigeria to treat various ailments such as inflammation, fever and pain. This necessitated this research to validate its local use, due to the scanty literature and information present about this plant. It has also shown some anti-cancer and anti-inflammatory activity in previous researches. The present study is a randomized control study. Acetic acid induced writhing was employed for analgesic testing. Acetic acid was used to induce writhing in Wistar rats which were divided into fourteen (14) groups. The groups were administered extracts and fractions of the plant (200 mg/kg and 400 mg/kg). The animals were observed for number of writing movements and the percentage writhing was calculated. Baker’s yeast induced pyrexia was employed for the antipyretic testing. The animal groups were administered extracts and fractions of the plant (200 mg/kg and 400 mg/kg), with Paracetamol as the standard drug (100 mg/kg) and Normal saline (control) for both experiments. The body temperature of the rats was measured rectally over a period of five (5) hours. All values of P<0.05 were taken as significant. The organic extract, aqueous extract and various fractions (n-hexane, ethyl-acetate, n-butanol and aqueous) produced significant inhibition of writhing responses and pyrexia in a dose dependent manner and time dependent manner respectively. The aqueous extract at a dose of 400mg/kg showed the greatest reduction in writhing, 91.58% compared to the standard drug (paracetamol) which may suggest that the fraction possesses better efficacy than paracetamol as an analgesic. The observed activities could be attributed to these bioactive compounds: Palmatine, Urs-12-ene-24-oic-3-oxo-methyl ester and Gallic acid contained in R. parviflora.

Evaluation of Vitamin D3 metabolite (25-OH Vit D3), Neurotransmitter (ACh), and the Expression of Proinflammatory Cytokines (IL-6 and TNF-α) in Tissue Homogenate after Administration of Biofield Energy Healing-based Novel Proprietary Test Formulation and Biofield Treatment per se to the Animals in Vitamin D3 Deficiency Diet (VDD)-induced Sprague Dawley Rats

A novel proprietary test formulation was designed which included minerals, vitamins, β-carotene, cannabidiol isolate,and Panax ginseng extract. This present study was evaluated the impact of the Trivedi Effect® on novel proprietary test formulation in male Sprague Dawley rats, fed with vitamin D3 deficiency diet (VDD). The novel test formulation was divided into two parts; one part was defined as untreated test formulation, while the other part was defined as the Biofield Energy Treated sample, which received the Biofield Energy Healing Treatment by renowned Biofield Energy Healer, Mr. Mahendra Kumar Trivedi. The level of 25-OH Vit. D3 was measured in brain homogenate, which was found to be increased by 20.13%, 24.12%, 45.86%, 14.79%, and 29.96% in the G5 group treated with Biofield Treated test formulation, Biofield Energy Treatment per se to the animals (G6), 15 days pre-treatment of Biofield Energy Treated test formulation (G7), Biofield Energy Treatment per se plus Biofield Energy Treated test formulation from day -15 (G8), and untreated test formulation to the Biofield Energy Treated animals (G9) groups respectively, as compared with the disease control (G2) group. Brain acetylcholine (ACh) level was increased by 61.33% in the G7 group as compared with the untreated test formulation (G4) group. The expression of interleukin-6 (IL-6) was significantly reduced by 43.44% (p≤0.01), 30.93%, 21.42%, 45.99% (p≤0.01), and 60.85% (p≤0.01), respectively as compared with the G4. Lung pro-inflammatory cytokine tumor necrosis factor alpha (TNF-α) level was significantly reduced in the G5, G6, G7, and G8 by 24.86%, 32.55% (p≤0.01), 30.12% (p≤0.01), and 42.69% (p≤0.01), respectively, as compared with the G4 group. Altogether, the Biofield Treated test formulation and/or per se treatment to the animals significantly improved the levels of active form of vitamin D3 metabolite (25-OH Vit D3) and neurotransmitter (ACh); consequently significantly lowered the expression of proinflammatory cytokines (IL-6 and TNF-α). Therefore, the energized test formulation or per se treatment could be effectively useful against neuronal damage and inflammation for the management of brain disorders such as Alzheimer’s disease, dementias, brain cancer, epilepsy and other seizure disorders, mental disorders, and Parkinson’s. Thus, the results showed a significant slowdown of disease progression and all other disease-related complications/symptoms in the preventive Biofield Energy Treatment group per se and the Biofield Energy Treated Test formulation groups (viz. G6, G7, G8, and G9) as compared to the disease control group.

Evaluation of Gall Bladder Mucosal Changes in Relation to the Type of Stones in Patients Undergoing Laparoscopic Cholecystectomy: A Retrospective Study of 394 Patients

Background and Aim Gallbladder (GB) cancer is a highly fatal malignancy and approx. 10% new cases are diagnosed every year in India. The GB cancer has poor prognosis due to progressive nature. Understanding of risk factors that lead to GB development is urgently required for better management of the disease. Presence of stones in gall bladder generates varied mucosal reactions, which leads to different types of histopathological changes in mucosa. Here, our aim is to study the correlation between various types of mucosal responses e. g. inflammation, hyperplasia, metaplasia and carcinoma with different characteristics e. g. number and morphology of gallstones both in males and females. Materials and Methods A retrospective study of gallstones was performed on 438 cases of cholecystectomies operated laparoscopically based on the histological changes. Out of 438 cases, 394 (89.95%) were associated with gallstones and the rest 44 (10.05%) belonged to acalculous cholecystitis. The mucosal changes in calculous gall bladder were studied in 394 cases and its correlation with number and types of observed gallstones were evaluated. Tissue sections were taken from the fundus, body, neck and abnormal area of gallbladder for histopathological studies. Results Our study has revealed the higher incidence of inflammatory changes in males, while gall bladder hyperplasia, intestinal metaplasia and cancer cases were found mostly in females. Conclusion Our study showed that changes in the number and morphology of gallstones are directly associated with the mucosal changes in gallbladder e.g. inflammation, hyperplasia, metaplasia and gall bladder carcinoma.

Therapeutic Evaluation of Neemazal® Against Experimental Eimeria Tenella Infection in Broiler Chickens, Jos - Nigeria

Coccidiosis in poultry is caused by protozoan parasites of the Eimeria species, which is responsible for worldwide economic losses. The aim of this study was to evaluated the therapeutic effect of NeemAzal® on Eimeria tenellain broiler Chickens as compared to Amprolium as a standard anticoccidial drug. A total of One Hundred and Sixty (160) broiler chicks were purchased, acclimatized and randomly divided into 4 groups (G1, G2, G3 & G4). G1 non-infected, non-treated (negative control), (G2) infected with 20000 E. tenella oocysts (positive control), (G3) infected and treated with Amprolium (Standard, 7 mg/kg b.w. for 5 days) and (G4) infected and treated with NeemAzal®200 mg/kg b.w. for 5 days). Evaluation was by clinical signs, performance data (weight gain, oocyst shed/gram faeces (OPG) and histopathology of the Caecum, Liver and Kidney. The data showed that birds infected with E. tenellahad an output of 1.3×105±3,333 oocysts per gram faeces on day 5 post inoculation. This output is significantly decreased to 0.37×105±3,111 oocysts in neem-treated birds. Infection with E. tenellainduced marked histopathological alterations in the caecum in the form of inflammation, vacuolation of the epithelium, and destruction of some villi. NeemAzal® decrease body weight loss of infected chickens. Moreover, the number of goblet cells stained with Hematoxylin and Eosin (H&E) within the infected villi was significantly lowered (P≤0.05). The results revealed that chicks of G1 had the best performance data compared to G2, G3& G4. In G3 & G4 there were a remarkable improvement in the data on performance, clinical signs, gross and microscopically caecal lesions compared to G2. Amprolium (G3) was shown to be superior to NeemAzal® (G4) compared to G2. NeemAzal® could be a good alternative for use as a coccidiostat to supplement the expensive anti-coccidiostats in the market.

The Mechanism of Decline of Senescent Skeletal Muscle Satellite Cell Self-Renewal and Regenerative Proliferation: The Role of Heparan Sulfate-FGF-2--FGFR1-p38αMAPK Axis, Sprouty1, miR-1, miR-133 and miR-29a

Aging mammalian skeletal muscle satellite cells (MuSCs) undergo a decline of stem cell/progenitor cell proliferative and regenerative capacity, and the development of a physiological milieu characteristic of a state of chronic sterile inflammation. p38αMAPK and ERK1/2 are two major signaling pathways that regulate the age-associated decline of MuSC proliferative capacity. In this review we propose the following mechanism that links the p38αMAPK pathway to the decline of self-renewal and regenerative capacity of aged MuSCs: a) the HS-FGF-2-FGFR1-p38αMAPK-Axis, a tightly linked homeostatic signaling complex, is in synchrony with the autoinhibition of FGFR1; b) autoinhibition contributes to the Axis’ regulation of the homeostasis of P-p38αMAPK activity in juvenile MuSC; c) this combination of protein-protein interactions is characteristic of a juvenile cytoplasmic milieu of beneficial P-p38αMAPK activity and d) includes Sprouty1 inhibition that supports the stimulation of FGF-2 --> miR-29a; e) the miR29a dismantles the basement membrane in preparation for the initiation of replication; f) an age-associated impaired, dysregulated, over-sulfated heparan sulfate ligand (HS)-FGF-2 fails to activate FGFR1 in aged MuSCs; g) this uncouples its regulation of p38αMAPK and ERK1/2 pathways and results in desensitization of FGFR1; h) desensitization of FGFR1 and Sprouty1 interaction in aged MuSC uncouples their regulation of P-p38αMAPK in the aged MuSCs; i) this enables a state of chronic sterile inflammation to promote and sustain an increased level of P-p38αMAPK activity; and, j) the increased activity of P-p38αMAPK in aged MuSC stimulates the production of cell cycle inhibitors, miR-1 and miR-133, thereby attenuating the expression of the cell cycle regulators, SP1 and cyclin D1, resulting in a G1/S arrest; j) the increased level of p38αMAPK activity promotes the apoptosis of the aged activated MuSCs. This mechanism involves the synergistic interactions of HS-FGF2-FGFR-1, Sprouty (spry1), miR-1, miR-133 and miR-29a that unify the extracellular niche and intracellular milieu for the juvenile vs age-associated regulation of proliferative capacity of the MuSC. Our hypothesis unifies these interactions with the role of the extracellular niche and intracellular milieu in the stimulation of juvenile proliferation vs age-associated decline of skeletal muscle satellite cell self-renewal and regenerative proliferation. Word Count = 344

The Elliptical Aggregates – Idiopathic Granulomatous Mastitis

Idiopathic granulomatous mastitis was initially scripted in 1972 by Kessler and Wolloch and is cogitated as an infrequent, benign, chronic inflammatory disorder. It commonly implicates females of reproductive age group, especially women who have breast fed in the preceding five to six years. Idiopathic granulomatous mastitis is commonly discerned in Asia and Mediterranean region although true incidence is undetermined. Diverse ethnicities delineate a diverse disease prevalence. Elimination of adjunctive causes of granulomatous inflammation makes idiopathic granulomatous mastitis a diagnosis of exclusion. As per the natural history, idiopathic granulomatous mastitis is designated as a self limiting disorder 1.

Capsaicin: A Potential Therapy Adjuvant for Intestinal Bowel Disease

Most of the patients with inflammatory bowel disease avoid pepper or spicy food, alleging that this condiment causes anal sensation of burning and accelerates intestinal movements. Capsaicin is the main bioactive component of peppers responsible for the pungent flavor that characterizes red peppers. Capsaicin has been related to several biological effects, including decreased body fat, antianti-inflammatory, anticarcinogenic, antioxidant activites and modulator of intestinal motility. These actions mostly are due to its role as an agonist of the transient receptor potential vanilloid 1 (TRPV1), expressed in the mesenteric nervous system and epithelial cells of the colon. Nonetheless, the anti-inflammatory action of capsaicin is also related to its role in activating the peroxisomal proliferator-activated receptor gamma (PPAR-γ). Topical capsaicin formulations are already used for pain management, but oral administration of capsaicin is rare. Here, we discuss the main actions of capsaicin that could interfere with the symptoms and severity of IBD. Although animal experiments suggest a beneficial effect of capsaicin on colitis, clinical studies exploring the potential analgesic and anti-inflammatory of capsaicin on Crohn or Ulcerative Colitis are scarce. We concluded that there is no evidence that capsaicin aggravates IBD symptoms or severity. On the opposite, experimental studies suggest that capsaicin could reduce intestinal inflammation by a mechanism that could involve not only the TRPV1 receptor but also PPAR γ. However, clinical studies are still scarce, and data regarding capsaicin concentrations, routes of administration, and long-term side-effects need to be better understood before its use.

Cytokines Level (Il8 and Il17) in Pregnant Women with Toxoplasmosis in Khartoum State

Toxoplasmosis is one of the most important zoonotic diseases worldwide caused by Toxoplasma gondii that leads to abortion or hydrocephalus during pregnancy. It’s a comparative cross-sectional one designed to assess immunoglobulins and cytokines in pregnant women. A total of 300 venous blood samples were collected from each pregnant woman and centrifuged to obtain serum. Patient’s information was recorded in a questionnaire previously designed for the purpose of analysis. In addition, 40 uninfected women were enrolled in the study as control group to assess the level of IL8 and IL17 cytokines. The overall seropositive rate of Toxoplasma gondii infection was 22.6%. Within the positive cases of study population, only 16 and 13 showed positive results of IL8, IL17 respectively. The results showed highly significant increase in the mean serum level of IL8 (210.25pg/ml) and IL17 (203.15 pg/ml) when compared to the control group who showed 68.9 pg/ml and 54.8 pg/ml respectively. The serum level of proinflammatory cytokines investigated in this study seems to be increased in patients with serological evidence of Toxoplasma gondii infection. Our study concludes that IL-17 and IL-8 involved in the induction of inflammation and toxoplasmosis disease.

A Triple-Blind, Placebo-Controlled Randomized Trial of the Effect of Bilateral Alternating Somatosensory Stimulation on Reducing Stress-Related Cortisol and Anxiety During and After the Trier Social Stress Test

The aim of this clinical study was to determine the efficacy of bilateral alternating somatosensory stimulation for the management of stress and anxiety during and after the Trier Social Stress Test (TSST), a laboratory procedure for reliably inducing stress in human subjects. For this, a randomized, placebo-controlled, triple-blinded clinical trial of 80 qualified subjects was conducted. Subjects were randomized into two groups, a treatment group (n=40) and a control (placebo) group (n=40). Metrics of emotional stress assessed were a subjective rating of the level of emotional stress and salivary cortisol levels, both obtained at 3 timepoints: before treatment (baseline), immediately following completion of the TSST, and after 20 minutes of rest following completion of the TSST. Results showed that the treatment group had a statistically greater decrease in the subjective rating of stress relative to the control group both immediately following the TSST and 20 minutes after the TSST. Salivary cortisol levels in the treatment group were also lower than the control group at those same time points. These results suggest that bilateral alternating somatosensory stimulation may be effective in reducing subjective levels of stress and anxiety. It also may actively attenuate stress-related cortisol levels, which may reflect a mechanism for reducing cortisol-induced inflammation back to baseline after exposure to stressful situations.

Oregano (Origanium Vulgare) Extract for Food Preservation and Improving Gastrointestinal Health

The Mediterranean diet has long been known to provide a variety of health benefits including cardiovascular protection, cancer prevention, and lowering gastrointestinal inflammation. Oregano (Origanium vulgare) is an herb prominent in the Mediterranean diet, and has been shown to possess several bioactive properties including anti-oxidant, anti-microbial, anti-inflammatory, and analgesic properties. The anti-oxidant and anti-microbial properties of oregano also make it a strong candidate as a natural food preservative. Because of the recent public concern with synthetic food preservatives, natural alternatives are increasingly being evaluated for effective food preservation. Oregano extract (OE) and essential oil (OEO) are two such agents that have shown promise as natural food preservatives. Additionally, oregano is being evaluated for its positive effect on gastrointestinal health, suggesting an additional benefit of food preservation with oregano. This review will describe in vitro studies related to the anti-microbial and anti-oxidant properties of oregano along with food preservation studies with oregano in various model food matrices. The major phytochemical content reported for OE and OEO will also be outlined to highlight the importance of characterizing the extract that is used, since the extraction process can have a significant effect on the phytochemicals therein. Finally, in vivo studies that investigate the gastrointestinal health benefits of oregano, specifically against inflammation, will be addressed to describe the role of oregano on gastrointestinal health.

Developing Cellular & Molecular Biomarkers for Anti-Inflammatory Activities of Probiotic Bacteria in Fermented Foods

We present below a mechanistic cellular and molecular approaches for the development of Anti-Inflammatory biomarkersof Probiotic Bacteria in Fermented Foods. Probiotics are live microorganisms that promote human health by counteracting the noxious toxic gut microflora in human intestine, by modulating of the tight junctions, and by increasing mucin production, enforcing intestinal epithelial cell barrier function, modifying microbial community within the gut intestinal disorders, and improving immune responses associated with chronic inflammation in experimental animal models, collectively enhancing human health. Cytokine secretion by intestinal epithelial cells and macrophages are regulated by probiotics through key signaling pathways such as nuclear factor-κB and mitogen-activated kinases, resulting in alleviation of several disorders such as allergies, diabetes, obesity, heart diseases and cancer. MicroRNAs are small non-coding RNA molecules involved in transcriptional and post-translational regulation of gene expression by inhibiting gene translation. Using in vitro and in vivo approaches in cell lines and mice models to study effects of probiotic conditional media and heat-killed bacterial strains with anti-inflammatory effect to elucidate the mechanisms by which probiotics affect signaling pathways, and by using global cytokine and microRNA gene expression analyses approaches to develop biomarkers for studying different pro- and anti-inflammatory activities, and using statistical approaches to analyse the data, we show that cytokines and miRNAs have an essential role in regulation of cancerous and inflammatory pathways. This mechanistic approach will result in developing specific disease biomarkers for the early diagnosis of certain pathogenic states, as well as evaluating the effect of different dietary components on developed biomarkers in health states that will promote and enhance human health. Comparing the concordance of the in vitro to the in vivo research findings will confirm the correspondence of both approaches to each other. Moreover, this study will have a major public health relevance in elucidating the role of miRNAs and their targets in inflammation, paving the way to diagnosing and treating of pathogenic human disease stages.

Effect of Bone Marrow and Adipose Mesenchymal Stem Cells on Rat Intestinal Injury Induced by Methotrexate

Methotrexate (MTX) is an anti-metabolite in cancer chemotherapy and is associated with various toxicities assigned to inflammation and oxidative stress. The present study was undertaken to corroborate the therapeutic effects of bone marrow mesenchymal stem cells (BM-MSCs) and adipose-derived mesenchymal stem cells (AD-MSCs) in MTX-induced intestinal toxicity in experimental animals as compared with dexamethasone (Dex). Rats were divided into five groups: I-Normal control group, II- MTX (14 mg/kg, as a single dose/week for 2 weeks), III & IV- BM-MSCs & AD-MSCs (2 × 106 cells/rat, 1 week after last dose of MTX), respectively, plus V- Dex (0.5 mg/kg/ for 7 days, 1 week after last dose of MTX). MTX induced marked intestinal elevation of interleukin-6, total oxidant, and nitrite/ nitrate, caspase-3 contents and myeloperoxidase activity, along with the reduction of reduced glutathione content and catalase activity. In conclusion, the positive modulation of MTX toxicity could be attributed to the free radical scavenging, anti-inflammatory and antiapoptotic potential of BM-MSC and AD-MSCs which will possibly make them as remarkable hopeful for the treatment of intestinal injury.

Action Mechanisms and Therapeutic Targets of Renal Fibrosis

Renal fibrosis was a chronic and progressive process affecting kidneys in chronic kidney disease (CKD), regardless of cause. Although no effective targeted therapy yet existed to retard renal fibrosis, a number of important recent advances have highlighted the cellular and molecular mechanisms underlying the renal fibrosis. The advances including TGF-β/Smad pathway, oxidative stress and inflammation, hypoxia and gut microbiota-derived from uremic solutes were highlighted that could provide therapeutic targets. New therapeutic targets and strategies that are particularly promising for development of new treatments for patients with CKD were also highlighted.

Minimal Risk Level Derivation for Cadmium: Acute and Intermediate Duration Exposures

The Agency for Toxic Substances and Disease Registry (ATSDR) lists cadmium as one of its priority hazardous substances. The agency conducted a comprehensive literature review of cadmium and used the information to develop a toxicological profile that identified the full range of health effects associated with exposure to cadmium. It included an assessment that identified screening levels, termed health guidance values or minimal risk levels (MRLs), below which adverse health effects are not expected. In this paper, we describe how MRLs for cadmium are derived. For the acute inhalation MRL, the traditional no observed adverse effect level or lowest observed adverse effect level (NOAEL/LOAEL) approach is used; for the oral intermediate MRL, the benchmark dose (BMD) approach is used. MRLs were developed for the most sensitive route-specific end points, other than mortality and cancer that were sufficiently supported and justified by the data. These included an acute duration (1–14 day exposure) inhalation MRL of 0.03 µg Cd/m3 for alveolar histiocytic infiltration and focal inflammation in alveolar septa and an intermediate duration (15–365 day exposure) oral MRL of 0.5 µg Cd/kg/day for decreased bone mineral density

Docosahexaenoic Acid Supplementation is Not Anti- Inflammatory in Adipose Tissue of Healthy Obese Postmenopausal Women

Adipose tissue inflammation is associated with obesity comorbidities. Reducing such inflammation may ameliorate these comorbidities. n-3 fatty acids have been reported to have anti-inflammatory properties in obesity, which may modulate this inflammatory state. In the current study a 1 gram per day oral supplement of the n-3 fatty acid docosahexaenoic acid (DHA) was administered for 12 weeks to 10 grade 12 obese postmenopausal women and markers of adipose tissue and systemic inflammation measured and compared before and after supplementation. DHA administration resulted in approximately a doubling of plasma and red cell phospholipid and adipose tissue DHA content but no change in systemic markers of inflammation, such as circulating C-reactive protein (CRP) or interleukins (IL) 6, 8 and 10 (IL-6, IL-8, IL-10). DHA supplementation did not alter the adipose tissue marker of inflammation crown-like structure density nor did it affect any gene expression pathways, including anti-inflammatory, hypoxic and lipid metabolism pathways. The obese postmenopausal women studied were otherwise healthy, which leads us to suggest that in such women DHA supplementation is not an effective means for reducing adipose tissue or systemic inflammation. Further testing is warranted to determine if n-3 fatty acids may ameliorate inflammation in other, perhaps less healthy, populations of obese individuals.

Frailty and the Immune System

Frailty describes a medical syndrome that confers increased vulnerability to disproportionate changes in health status following minor stressors. With loss of homeostatic reserve in multiple physiological systems, frailty conveys an increased risk of adverse health outcomes. Despite the lack of a clear universal definition, the utilisation of two landmark operational models has allowed a rapid expansion in frailty-centred research. The pathophysiology of frailty is yet to be elucidated in the literature, but a critical role for a heightened inflammatory state is hypothesised. Raised levels of pro-inflammatory cytokines are associated with frailty, with emerging evidence relating their biochemical action with development of the frailty phenotype. Dysregulation of both the innate and adaptive immune system are key components of the frailty syndrome. Remodelling of the T cell compartment and upregulated inflammatory pathways are theorised to propagate the heightened inflammatory state critical in the frailty syndrome. Increased neutrophil counts, in conjunction with ineffective neutrophil migration associated with age, is theorised to produce tissue damage and secondary inflammation conducive of the inflammatory picture in frailty. Beyond the gold standard of the comprehensive geriatric assessment, management of frailty is a fast-evolving area of research. Exercise interventions have shown promising results, improving functional ability and showing beneficial immunomodulation. Vitamin D supplementation, with proposed anti-inflammatory effects, nutritional support and pharmacological treatments all provide promising areas for future therapeutic intervention.

Importance of Neutrophil/Lymphocyte Ratio in Squamous-Cell Carcinoma of the Larynx

Aim: The relation between inflammation and cancer has been known since the 19th century. However, investigations on the pathogenesis and pathophysiology of this relation have begun recently. It was demonstrated that increased neutrophil/lymphocyte ratio is a poor prognostic factor in some malignancies. The present study aimed to determine whether preoperative neutrophil/lymphocyte ratio has a prognostic value in larynx cancer. Method: Preoperative blood analyses of 139 patients, who underwent subtotal or total laryngectomy for larynx cancer between 2003 and 2013 at Marmara University School of Medicine, Department of ENT, were retrospectively evaluated. Neutrophil/lymphocyte ratio (NLR) was calculated dividing absolute neutrophil count by absolute lymphocyte count. Optimal cut-off value for NLR was determined by receiver operating characteristics (ROC) curve analysis. Statistical analyses were done using IBM SPSS statistic 22.0 (IBM SPSS, Turkey) and Med Calc 12.3.0 package programs. Results: The sensitivity of NLR in predicting advanced-stage (Stage 3 and 4) squamous-cell carcinoma of the larynx (LSSC), T4 LSSC and lymph node metastasis at different cut-off values were 66.2%, 83.9% and 73.8%, respectively and the specificity was 76.7%, 66.2% and 65.2%, respectively. Staging according to T classification revealed that NLR significantly increases with tumor stage (p<0.001). Statistically significant relation was determined between lymph node metastasis of tumor and neutrophil/lymphocyte ratio (p=0.003). Comparing overall survival (OS) and disease-free survival (DFS) between the cases with NLR <3.02 and the cases with NLR >3.02, it was demonstrated that OS and DFS are significantly lower in the cases with NLR<3.02 (p: 0.001 vs. p<0.05 for OS and p: 0.013 vs. p<0.05 for DFS) Conclusion: NLR increases with the stage of disease in LSSC. NLR is a simple, cheap, repeatable and valuable parameter that can be obtained from routine analyses, gives information about poor prognosis and survival, and is able to predict T4 LSSC, advanced-stage LSSC (stage 3-4) and lymph node metastasis.

Addressing the gastrointestinal health associated with schizophrenia: The argument for a new nutrition-based intervention

The purpose of this paper is to review the literature linking schizophrenia with chronic inflammation and gluten sensitivity. In addition, the paper discusses the need for dietary interventions that may improve multiple health outcomes for patients. Individuals with schizophrenia are at much greater risk for the development of additional autoimmune disorders. Second generation anti-psychotic medications are the most effective treatment for schizophrenia, but there are numerous potential side effects to the medications. More specifically, individuals with schizophrenia who are treated with SGAs are at increased risk for obesity, diabetes, as well as elevated lipids and blood pressure. An effective evidence-based dietary intervention has the potential to improve numerous outcomes for individuals with schizophrenia.

Changes in Gingival Crevicular Fluid Volume and Flow Rate During Orthodontic Treatment

Background: Gingival crevicular fluid (GCF) is regarded as a promising medium for detection of periodontal disease activity. bone loss is a major feature of periodontal disease, although we are unable to determine the time of this bone loss and therefore periodontal disease activity. During orthodontic treatment small forces are applied, resulting in bone remodeling which allows tooth movement. Orthodontic model may be used as a preliminary stage in evaluating gingival crevicular fluid role in bone turnover. Aims: To detect GCF and to monitor it's volume and flow rate following orthodontic activation, and to determine at what stage inflammation and bone resorption reach their maximum. Materials and Methods: GCF samples were collected from 10 adult orthodontic patients (mean age = 22.3 , range 20-24year) on 3,7,10,14,21,28,35 days after activation of orthodontic appliance, from the tooth surface where bone resorption was expected to occur. A total of 330 GCF sample were collected using filter paper strip, the volume measured by weighing. Results: An insignificant increase in GCF volume and flow rate was noted in the tenth day after activation of the orthodontic appliance activation. At 35 days GCF reached its minimum flow rate. There was considerable variation between subjects and between the same subject on different days Conclusion: Increase in GCF volume and flow rate reflects the effect of orthodontic adjustment rather than oral hygiene, as there were no clinical inflammatory changes during the period of orthodontic treatment studied.

Metabolic Acidosis and Cardiovascular Disease in Patients on Peritoneal Dialysis

Backgroud: Metabolic acidosis, a common condition particularly in end stage renal disease patients, results in malnutrition and inflammation. In this study, we focused on the importance of metabolic acidosis on manifestations of cardiovascular disease in patients on peritoneal dialysis. Methods: We studied 20 patients on continuous ambulatory peritoneal dialysis (CAPD), 15 males and 5 females, on mean age 61.6 ±11.3 years old. Metabolic acidosis was determined by serum bicarbonate concentrations less than 22mmol/L, which were measured in gas machine. Dialysis adequacy was defined by total Kt/V/week for urea including peritoneal Kt/V for urea and residual GFR (ml/min/1.73m2). High sensitivity C-reactive protein (hsCRP) was measured using enzyme linked immunoabsorbed assay (ΕLISA). The concentrations of intact-parathormone (i-PTH) and beta2-microglobulin (beta2M) were measured by radioimmunoassays. Arterial stiffness was measured as carotid-femoral pulse wave velocity (c-f PWV) and augmentation index (AIx). We built a Cox regression analysis to predict coronary artery disease (CAD), congestive heart failure (CHF) and peripheral vascular disease (PVD). Results: Serum bicarbonate levels were inversely associated to beta2M, i-PTH and AIx (r=-0.451, p=0.04, r=-0.477, p=0.03 and r=-0.569, p=0.009 respectively). Cox- regression analysis revealed significant association of serum bicarbonate levels and PVD having as confounders traditional and specific for these patients risk factors. Conclusion: Metabolic acidosis may be an independent risk factor for arterial stiffening and peripheral vascular disease manifestation in patients on peritoneal dialysis.

Evaluation of Crest Guideline Validity for Diagnosis of Non-Facial Cellulites

Cellulitis is an acute, spreading pyogenic inflammation of the dermis and subcutaneous tissue, usually complicating a wound, ulcer, or dermatosis. Inappropriate diagnosis of cellulitis is a problem and would need prospective rather than retrospective studies to quantify the extent. There is one national guideline for the management of patients with cellulitis. The aim of this study is to determine the validity of Crest guideline in the patients with non-facial cellulitis. This prospective cohort study was conducted on all Adult patients with cellulites who were admitted at Resole-Akram and Sina emergency department between November 2013 and January 2014. Based on admission duration, the patients were randomly divided into two groups including primary and secondary outcome, <24-hours or >24-hours admission, respectively. Out of 89 admitted patients, 55% were hospitalized over 24 hours and 20% of them had significant systemic symptoms. The most patients (n= 42) had either systemically ill or systemically well or class II followed by classes I (n=28), III (n=18), and IV (n=1). There was significant relevancy between age, fever, PR, infected organ, leukocytosis, diabetes mellitus, IUDA, human bite, and primary outcome. In conclusion, factors associated with admission were age, presence of multiple comorbid conditions, diabetes mellitus, human bite, IUDA, infected organ, leukocytosis and fever. These results showed that the decision in the emergency department was mostly the same as Crest guideline and the prospection of admission and discharge of these patients was almost according to the educations of Crest guideline.

Low Laser Therapy Plus Non-Surgical Periodontal Treatment Reduces Interleukin-1 Beta Serum Levels

Objectives: Periodontal disease is associated to widespread systemic inflammation, and further to both cardiovascular morbidity and mortality. Data from intervention studies demonstrated the beneficial effects of periodontal therapy in reducing vascular diseases. The present study was aimed to explore whether low-level Laser therapy as an adjunct to scaling and root planning reduces serum levels of inflammatory cytokines. Material and Methods: Thirty patients were enrolled. All recruited participants underwent blood sampling and dental inspection for periodontal indexes measurement. Plaque index, gingival index and probing depth were employed as measures of periodontal disease. Afterwards, patients underwent scaling and root planning plus low-level Laser therapy. Inflammatory biomarkers and periodontal indexes were measured before treatment and twenty weeks after treatment. Results: Plaque index, gingival index and probing depth largely improved at the follow-up visit, resulting more than halved from the baseline. Furthermore, a significant reduction of serum interleukin-1 beta has been observed (1.1 SD 2.1 vs 0.5 SD 1.3, P = 0.04), whereas serum interleukin-6 levels remained substantially unchanged. Blood C-reactive protein levels decreased at the follow-up, but not reaching statistical significance. Conclusions: therapy addressed to a local improvement of periodontal disease gives a reduction of systemic inflammation, possibly beneficial for cardiovascular health.

Role of Helicobacter Pylori in Nasal Polyp Formation: A Case-Control Study in Tehran, Iran

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.

Management of Absent Capsular Support with a new Intraocular Lens Design

Purpose: To describe a new intraocular lens that can be implanted in case of rupture of the posterior capsule and lack of capsular support. Methods: This experimental study was carried out on ten Flanders rabbits. The right eye of each rabbit underwent intra capsular lens extraction and two peripheral iridectomies, and the new lens was implanted with an optic rest in the posterior chamber. Additionally, the haptics rest in the angle of the anterior chamber through peripheral iridectomies. Main outcome measures were lens stability inside the eye and complications regarding this technique. Results: Intraocular lenses remained in a stable position with only a mild inflammatory reaction; four eyes developed hyphema that disappeared 10 days after surgery. Conclusion: The new lens design has good intraocular stability when posterior capsular support is absent and only produced minimal inflammation inside the eye.

Kynurenines and Vitamin B6: Link Between Diabetes and Depression.

The increased association between depression and diabetes mellitus is generally acknowledged. Recent studies suggest that depression leads to diabetes.However, the underlying molecular mechanisms for this association remain unclear.Literature and our data indicate that inflammatory and/or stress factors in depression up-regulate tryptophan (TRP) conversion into kynurenine (KYN), a substrate for nicotinamide adenine dinucleotide (NAD) biosynthesis. Deficiency of vitamin B6, a co-factor of the key enzymes of KYN – NAD pathway, shunts KYN metabolism from formation of NAD towards production of xanthurenic (XA) and kynurenic (KYNA) acids. Human and experimental studies reveal that XA, KYNA and their metabolites interfere with production, release and biological activity of insulin. We propose that inflammation- and/or stress-induced up-regulation of TRP – KYN metabolism in combination with vitamin B6 deficiency is one of the mechanisms mediating increased risk of diabetes in depression. Consequently, monitoring formation of diabetogenic KYN derivatives might help to identify subjects-at-risk for the development of diabetes. Pharmacological down-regulation of the TRP – KYN – NAD pathway and maintenance of adequate vitamin B6 status might help to prevent the development of diabetes in depression and other conditions associated with inflammation/stress–induced excessive production of KYN and vitamin B6 deficiency, e.g., obesity, cardiovascular diseases, aging, menopause, pregnancy, and hepatitis C virus infection.