Tumor Necrosis Factor-alpha Levels Research Articles

Aqueous babassu extract limits IL-6 and TNF-α expression on indomethacin-induced gastric lesions in rats

In addition to previously been used with therapeutic purposes among traditional population in the northeast of Brazil, the pharmacologic properties of babassu (Orbignya Phalerata) have already been shown in many studies through the last thirty years. The objective of this study was to evaluate the capacity of babassu extract on prevent inflammatory response in Wistar rats’ gastric tissue, exposed to Indomethacin, against positive and negative control. The animals were distributed in three groups of five rats each. Group I received the babassu extract, Group II received omeprazole, as positive control, and Group III received distilled water, as negative control. Those three substances were administrated by intragastric gavage. 24 hours after the ulcer induction, with intragastric indomethacin, blood samples were collected, and total gastrectomy was performed. The gastric samples were rinsed with 0,9% saline, then gastric lavage and gastric tissue were systematic analyzed. The parameter for evaluation were presence or absence of Inflammation, Necrosis, Fibrosis, Reepithelization, Neocapillary and Ulcer extension on histologic analysis of the gastric sample, as well as Interleukin-6 (IL-6) and Tumor necrosis factor alpha (TNF-α) levels in gastric lavage and plasma. The histologic assessment has found significantly higher signals of tissue damage, in number, on distilled water group when compared with Babassu group and Omeprazole. The gastric lavage analysis has also shown significant statistically higher concentrations of IL-6 and TNF-α in gastric lavage(p=0,032) in negative control group than in both Babassu and Omeprazole groups. Finally, this study has found that Aqueous Babassu Extract has the property of prevent gastric damage tissue in rats exposed to indomethacin, such property was found to be equivalent to the Omeprazole property, the establish pharmaceutical treatment for preventing PUD.

Focal or diffuse bladder wall thickness on bladder computed tomography indicates more severe bladder wall inflammation in patients with interstitial cystitis.

The classification of different phenotypes of interstitial cystitis/ bladder pain syndrome (IC/BPS) provides different pathophysiology and associated treatment strategies. Most clinical studies have focused on bladder symptoms and cystoscopic findings. This study analyzed bladder wall thickness (BWT) and compared bladder conditions, urinary biomarkers, and histopathology among patients of IC/BPS with different BWT. A total of 182 patients with cystoscopy-proven IC/BPS underwent abdominal computed tomography (CT) before intervention. The BWT on CT was classified as smooth, focal thickness, and diffuse thickness. Clinical symptoms, urodynamic findings, cystoscopic characteristics, presence of Hunner's lesion, urinary biomarkers, and bladder histopathology were compared among the three subgroups. Among the patients, 85 had smooth, 64 had focal, and 33 had diffuse BWT. There was a significant trend of patients with focal and diffuse BWT being significantly older with higher symptom scores, smaller bladder capacity, higher grade of glomerulations, and incidence of Hunner's IC. Pathological findings revealed that patients with diffused BWT, followed by those with focal thickness, had the greatest uroepithelial cell denudation and plasma cell infiltration. Patients with diffuse BWT has higher rate of inflammatory cell infiltration, nerve bundle hyperplasia, and granulation tissue. The urinary levels of tumor necrosis factor-alpha and oxidative stress biomarkers in IC/BPS patients with different BWT were significantly higher than those in the controls. BWT in CT scans can reflect chronic inflammation of the bladder wall in patients with IC/BPS, which is clinically relevant for the diagnosis and treatment of IC subtypes.

Dynamic assessment of blood inflammation markers in patients during the rehabilitation period after surgical treatment for external genital endometriosis

Background. Providing rehabilitation care to women with external genital endometriosis (EGE) after surgical treatment requires an interdisciplinary approach to selecting patient management strategy and biomarkers for objective monitoring of health status.Objective: to determine the feasibility of using inflammatory biomarkers in women undergoing rehabilitation after EGE surgical treatment to assess the quality of care.Material and methods. The study included 40 EGE patients (main group), 40 patients with other gynecological pathologies (comparison group), and 40 nearly healthy women (control group). All participants with gynecological pathologies underwent surgical treatment with subsequent rehabilitation. The severity of the inflammatory process was assessed using the following inflammation biomarkers: serum interleukin-6 (IL-6), tumor necrosis factor alpha (TNF-a), citrullinated histone H3 (CitH3), and the neutrophil to lymphocyte ratio (NLR). The dynamics of changes in biomarker levels were measured before surgery, 1 week and 3 months after it.Results. The assessment of inflammatory biomarker serum concentrations indicated the presence of inflammatory processes in patients of both the main and comparison groups. However, the levels of IL-6, TNF-a, CitH3 and NLR among EGE patients were statistically significantly higher compared to similar parameters in women with other gynecological pathologies. One week after surgery, the main group showed a significant increase in concentrations of IL-6, CitH3 and NLR and a decrease in TNF-a levels compared to baseline values. Three months after surgery, a significant reduction in the severity of the inflammatory process in the main group was observed compared to the values obtained 1 week after surgery. In several cases, the levels of inflammatory biomarkers were statistically significantly lower than baseline values. Notably, the serum concentration of CitH3 decreased to levels observed in nearly healthy women.Conclusion. An inflammatory process was recorded in EGE patients, which can be corrected through surgical intervention. Using serum concentrations of CitH3 as a marker for assessing the quality of surgical treatment for EGE and managing patients during the rehabilitation phase was proved to be viable.

Study of the occurrence of metabolic dysfunction-associated fatty liver disease in obstructive sleep apnea hypopnea syndrome and its risk factors

Objective: To analyze the occurrence of metabolic dysfunction-associated fatty liver disease (MAFLD) and related inflammatory indicators in obstructive sleep apnea hypopnea syndrome (OSAHS) and explore the risk factors of MAFLD. Methods: A cross-sectional study. From January 2022 to October 2024,172 patients with sleep disorders were enrolled in the First Affiliated Hospital of Soochow University,including 38 patients with non-OSAHS,53 patients with mild OSAHS,37 patients with moderate OSAHS,and 44 patients with severe OSAHS. The occurrence of MAFLD was comprehensively judged from three aspects: metabolic dysfunction-associated fatty liver (MAFL),elevated liver enzymes,and liver fibrosis. The situation of MAFLD and the level of related inflammatory markers were compared among the four groups. Binary logistic regression was used to analyze the risk factors for MAFLD in OSAHS. Results: There were significant differences in the prevalence of MAFL,the percentage of elevated liver enzymes,and interleukin-6 and tumor necrosis factor-alpha levels among the four groups (P<0.05). The differences of fibrosis-4 index and C-reactive protein among the four groups were not statistically significant (P>0.05). Binary logistic regression showed that BMI,triglycerides,longest time of sleep apnea and tumor necrosis factor-alpha were the risk factors for MAFL (P<0.05). BMI,glucose,and apnea-hypopnea index were the risk factors for elevated liver enzymes (P<0.05). Conclusions: OSAHS is strongly associated with MAFLD,and the involvement of OSAHS in the occurrence and development of MAFLD may be related to obesity,lipid metabolism disorders,insulin resistance,inflammatory responses,and intermittent hypoxia.

Circulatory age-associated B cells: Their distinct transcriptomic characteristics and clinical significance in drug-naïve patients with rheumatoid arthritis.

Age-associated B cells (ABCs) have been implicated in the pathogenesis of autoimmune diseases. However, the global gene expression and clinical significance of circulatory ABCs in rheumatoid arthritis (RA) remain poorly understood. Here, single-cell RNA sequencing identified nine B cell subsets in peripheral blood of RA patients, including ABCs. Increased phagocytosis and antigen presentation were functionally enriched by the genes expressed differentially in ABCs. Network analysis and in vitro experiments demonstrated SYK as a key regulator defining the myeloid-like phenotypes in ABCs. Flow cytometry showed that the proportion of ABCs correlated with RA activity and serum tumor necrosis factor-alpha level. Notably, ABCs above a cutoff threshold specifically distinguished RA from healthy controls and indicated higher disease activity. This study highlights the myeloid characteristics of circulatory ABCs regulated by SYK in RA. Increased ABCs may reflect disease activity and could serve as a potential biomarker in RA.

Evaluation of the Anti-Mycobacterial and Anti-Inflammatory Activities of the New Cardiotonic Steroid γ-Benzylidene Digoxin-15 in Macrophage Models of Infection

Cardiotonic steroids modulate various aspects of the inflammatory response. The synthetic cardiotonic steroid γ-benzylidene digoxin 15 (BD-15), a digoxin derivative, has emerged as a promising candidate with potential immunomodulatory effects. However, its biological activity remains largely unexplored. This study investigated the anti-mycobacterial and anti-inflammatory effects of BD-15 in an in vitro macrophage infection model with Mycobacterium spp. Unlike digoxin, which showed significant toxicity at higher concentrations, BD-15 exhibited no cytotoxicity in RAW 264.7 cells (a murine macrophage cell line). Both compounds were evaluated in Mycobacterium smegmatis-infected RAW 264.7 cells, reducing bacterial burden without direct bactericidal activity. Additionally, both modulated pro-inflammatory cytokine levels, notably by decreasing tumor necrosis factor alpha (TNF-α) and interleukin-1 beta (IL-1β) levels. BD-15 specifically reduced NOD-, LRR-, and pyrin-domain-containing protein 3 (NLRP3) inflammasome expression and increased interleukin-10 (IL-10) production. Notably, BD-15 reduced colony-forming unit (CFU) counts in Mycobacterium tuberculosis-infected RAW 264.7 cells. Toxicity assays in HepG2 cells (a human liver cancer cell line) showed that BD-15 had minimal hepatotoxicity compared to digoxin, and both demonstrated negligible acute toxicity in an Artemia salina bioassay. These findings revealed the immunomodulatory effects of cardiotonic steroids in a bacterial infection model and highlighted BD-15 as a safer alternative to digoxin for therapeutic applications.

The impact of dietary fiber on colorectal cancer patients based on machine learning

ObjectiveThis study aimed to evaluate the impact of enteral nutrition with dietary fiber on patients undergoing laparoscopic colorectal cancer (CRC) surgery.MethodsBetween January 2023 and August 2024, 164 CRC patients were randomly assigned to two groups at our hospital. The control group received standard nutritional intervention, while the observation group received enteral nutritional support containing dietary fiber. Both groups were subjected to intervention and continuously observed until the 14th postoperative day. An observational analysis assessed the impact of dietary fiber intake on postoperative nutritional status in CRC patients. The study compared infection stress index, inflammatory factors, nutritional status, intestinal function recovery, and complication incidence between groups. Additionally, four machine learning models—Logistic Regression (LR), Random Forest (RF), Neural Network (NN), and Support Vector Machine (SVM)—were developed based on nutritional and clinical indicators.ResultsIn the observation group, levels of procalcitonin (PCT), beta-endorphin (β-EP), C-reactive protein (CRP), interleukin-1 (IL-1), interleukin-8 (IL-8), and tumor necrosis factor-alpha (TNF-α) were significantly lower compared to the control group (p &amp;lt; 0.01). Conversely, levels of albumin (ALB), hemoglobin (HB), transferrin (TRF), and prealbumin (PAB) in the observation group were significantly higher than those in the control group (p &amp;lt; 0.01). Furthermore, LR, RF, NN, and SVM models can effectively predict the effects of dietary fiber on the immune function and inflammatory response of postoperative CRC patients, with the NN model performing the best. Through the screening of machine learning models, four key predictors for CRC patients were identified: PCT, PAB, ALB, and IL-1.ConclusionPostoperative dietary fiber administration in colorectal cancer enhances immune function, reduces disease-related inflammation, and inhibits tumor proliferation. Machine learning-based CRC prediction models hold clinical value.

Effects of Jianpi therapy for cancer-related fatigue:a meta-analysis of randomized controlled trials

PurposeThe Jianpi therapeutic strategy in traditional Chinese medicine aims to enhance the spleen’s digestive function and overall wellness. It has shown promise in improving cancer-related fatigue (CRF). This research systematically evaluates the effectiveness of Jianpi therapy in reducing fatigue in cancer patients through a meta-analytic review.MethodsAn exhaustive search was performed within PubMed, Embase, Web of Science, Cochrane Library, SinoMed, Wanfang Data, China Science and Technology Journal Database, and China National Knowledge Infrastructure (CNKI) for randomized controlled trials concerning the application of Jianpi therapy to address CRF. The search spanned from the commencement of each database’s records to April 1, 2024. The extracted data were subjected to analysis using Stata (Version 15.1), with the selection of either a random-effects or fixed-effects model based on the heterogeneity among studies. Outcome measures were demonstrated with standardized mean differences (SMDs) or mean differences (MDs), and each complemented by a 95% confidence interval (CI). The Cochrane Risk of Bias Assessment Tool 2.0 was utilized to assess the potential biases within the studies.ResultsA comprehensive analysis was performed on 45 eligible studies, all of which were conducted within China and encompassed a total of 3,596 participants. The meta-analysis indicated that Jianpi decoction alone exhibited the most significant improvement in the proportion of CD4 cells (SMD=1.34, 95% CI 0.54 to 2.31, P&amp;lt;0.001) and hemoglobin (MD=7.45, 95% CI 4.18 to 10.72, Z=4.47, P&amp;lt;0.001), while also more significantly reducing Piper Fatigue Scale scores (SMD=-2.05, 95% CI -2.71 to -1.39, P&amp;lt;0.001). The combined therapy, which integrated Jianpi therapy with standard care, demonstrated the greatest advantage in enhancing the proportion of CD3 cells (SMD=1.25, 95% CI 0.46 to 2.04, P&amp;lt;0.001). Furthermore, Jianpi therapy was found to be effective in lowering tumor necrosis factor-alpha levels (MD=-7.79, 95% CI -11.24 to -4.34, P&amp;lt;0.001) and concurrently enhancing interferon-gamma (MD=5.15, 95% CI 3.20 to 7.09, P=0.002), interleukin-2 (MD=8.37, 95% CI 6.14 to 10.59, P&amp;lt;0.001).ConclusionOur research indicates that Jianpi therapy effectively alleviates CRF, reduces inflammation, and strengthens immune function. However, further high-quality, multicenter randomized controlled trials are essential to confirm these findings and strengthen the evidence.Systematic review registrationhttps://www.crd.york.ac.uk/PROSPERO/, identifier CRD42024566739.

SW033291 promotes liver regeneration after acetaminophen-induced liver injury in mice.

Acetaminophen (APAP) is a commonly utilized antipyretic and analgesic drug. Overdose of APAP is a primary contributor to drug-induced liver injury and acute liver failure (ALF). SW033291 has been shown to play a role in tissue regeneration in various diseases; however, its potential to facilitate liver regeneration following APAP-induced hepatic injury remains unexamined. Thus, this study focused on exploring the therapeutic impacts and mechanisms of SW033291 on liver damage by establishing models of APAP-induced acute liver injury in mice. The results showed that treatment with SW033291 reduces serum alanine aminotransferase (ALT) and aspartate aminotransferase (AST) activities, decreases the area of hepatic necrosis, increases glutathione (GSH) levels, and decreases tissue malondialdehyde (MDA) content, as well as the expression levels of tumor necrosis factor-alpha (TNF-α), interleukin-1β (IL-1β), and interleukin-6 (IL-6) in mice with liver injury. It could also promote hepatocyte proliferation and inhibit apoptosis by increasing tissue prostaglandin E2 (PGE2) levels. In conclusion, SW033291 demonstrates the capacity to ameliorate APAP-induced hepatic injury in mice by fostering liver regeneration, attenuating oxidative stress, and modulating inflammatory responses, thereby presenting itself as a promising candidate for the development of therapeutic interventions targeting acute liver failure.

Effects of Dexpanthenol on Corneal Neovascularization and Inflammation on Rat Model.

To evaluate the effect of subconjunctival injection of dexpanthenol on corneal neovascularization and inflammation in rats with induced chemical burns. This experimental study included 40 female albino Wistar rats. Chemical burns were induced in the right eye of all rats on the first day, and the left eye was used as a control. Rats were randomly divided into 5 groups. The no-treatment group (group 1) received no injections. Balanced salt solution injection in the sham group (group 2), dexpanthenol injection in the dexpanthenol group (group 3), bevacizumab injection in the bevacizumab group (group 4), and combined dexpanthenol and bevacizumab injection in the combined group (group 5) were administered subconjunctivally on day 7. The right corneas of all rats were photographed on days 7 and 14 to evaluate corneal neovascularization. The 2 corneal images were compared, and the differences were analyzed. All rats were euthanized, and the corneas were isolated. The levels of tumor necrosis factor-alpha (TNF-α), vascular endothelial growth factor-A, malondialdehyde (MDA), apoptosis, reduced glutathione (GSH), and total oxidant status were measured in rat corneas. Dexpanthenol reduced corneal neovascularization, and the difference was significant compared with the no-treatment and sham groups (P < 0.05). No significant difference in corneal neovascularization was observed between the dexpanthenol and bevacizumab groups. Dexpanthenol had a significant positive effect on vascular endothelial growth factor-A, TNF-α, total oxidant status, MDA, and GSH levels compared with the sham group (P < 0.05). Dexpanthenol may help control corneal neovascularization and inflammation after chemical burns.

Is Punica granatum Efficient Against Sepsis? A Comparative Study of Amifostine Versus Pomegranate.

Sepsis is a clinical condition causing tissue damage as a result of infection and an exaggerated immune response. Sepsis causes 11 million deaths annually, a third of which are associated with acute lung injury (ALI). Rapid and effective treatment is crucial to improve survival rates. Punica granatum (pomegranate) is rich in polyphenols and demonstrates strong antioxidant activity, while amifostine acts as a free radical scavenger. This study aimed to investigate the antioxidant and anti-inflammatory effects of P. granatum peel extract (PGPE) and amifostine in sepsis-related ALI. Experimental groups included Control, CLP (cecal ligation and puncture-induced sepsis), Amf (200 mg/kg amifostine, intraperitoneally), and PGPE250, and PGPE500 (250 and 500 mg/kg PGPE via oral gavage, respectively). Thiobarbituric acid reactive substances (TBARS), total thiol (TT), tumor necrosis factor-alpha (TNF-α) levels, and metalloproteinases 2 and 9 (MMP-2 and MMP-9) were assessed in the lung tissue. Biochemical analysis demonstrated that TBARS and TNF-α levels significantly decreased in both the PGPE and amifostine treatment groups compared to the CLP group, while TT levels showed notable improvement. Histopathological evaluation revealed reduced MMP-2 and MMP-9 immunopositivity in the PGPE250 and PGPE500 groups. These findings highlight the lung-protective properties of PGPE, underscoring its potential as a therapeutic agent for sepsis-induced acute lung injury.

Effect of ketosis induced by on delayed-onset muscle soreness, inflammation and redox status: a randomized, open-label, crossover pilot study.

Previous studies show that ketosis caused by the consumption of low-carbohydrate diets improves cognitive functions and that ketogenic diets can be used to treat epilepsy. In vivo and in vitro experiments have shown that ketosis regulates pain, inflammation, and oxidative stress. Thus, we investigated the effects of ketosis induced by a low-carbohydrate diet on muscle soreness, inflammation, and redox status in human subjects. The research method was an open-label, crossover, pilot study. The study included eight men with no exercise habits associated with muscle soreness and consumed a low-carbohydrate and a normal diet for 6 days. Each dietary intake was for 3 days, and the participants performed the isotonic exercise on the fourth day. Before and after the exercise (immediately after, 24 h later, and 48 h later), the subjective value of muscle soreness, interleukin-6 level, tumor necrosis factor-alpha level, total ketone bodies, and redox status biomarkers were measured. The results revealed that the low-carbohydrate-diet group showed no significant difference in the subjective value of muscle soreness, whereas the normal diet group showed a significant increase in the subjective muscle soreness scale after 24 h. There were no significant changes in biomarkers of inflammation and redox status in either group. This result suggests that ketosis caused by consuming a low-carbohydrate diet suppresses delayed-onset muscle soreness. However, the ketosis state did not suppress inflammation or oxidative stress markers.

Toll-like Receptor 4 Polymorphisms (rs4986790, rs4986791) and Serum Tumor Necrosis Factor Alpha levels in Chronic Obstructive Pulmonary Disease and Lung Cancer

Toll-like Receptor 4 Polymorphisms (rs4986790, rs4986791) and Serum Tumor Necrosis Factor Alpha levels in Chronic Obstructive Pulmonary Disease and Lung Cancer

Diffuse large B-cell lymphoma cell-derived exosomal NSUN2 stabilizes PDL1 to promote tumor immune escape and M2 macrophage polarization in a YBX1-dependent manner.

Diffuse large B-cell lymphoma (DLBCL) is a prevalent and aggressive form of non-Hodgkin's lymphoma with a complex etiology. NOP2/Sun domain 2 (NSUN2) is an RNA methyltransferase that has been linked to the regulation of gene expression in various cancers. However, the function of NSUN2 in DLBCL, specifically its contribution to exosome-driven tumor progression, remains to be thoroughly elucidated. Quantitative real-time polymerase chain reaction was used to analyze the expression of NSUN2 and programmed death ligand 1 variant (PDL1). Western blotting assay was performed to detect the protein levels of NSUN2, PDL1 and Y-box binding protein 1 (YBX1). Cell proliferation was analyzed by cell counting kit-8 and 5-Ethynyl-2'-deoxyuridine assays. Cell apoptosis and CD206-positive cells were quantified by flow cytometry. The levels of tumor necrosis factor-alpha and interferon-γ in cell supernatant were analyzed by enzyme-linked immunosorbent assays. m6A RNA immunoprecipitation and RNA pull-down assays were performed to determine the association between NSUN2 and PDL1. An RNA immunoprecipitation assay was used to analyze the association of YBX1 and PDL1. In vitro findings were validated in a mouse model. NSUN2 was overexpressed in DLBCL tissues and cells. DLBCL cell-derived exosomes facilitated the transfer of NSUN2 to DLBCL cells, which in turn promoted tumor cell proliferation, M2 macrophage polarization, and immune escape and inhibited cell apoptosis. In addition, NSUN2 stabilized PDL1 mRNA through an m5C-dependent mechanism and a YBX1-dependent pathway. Moreover, the suppression of PDL1 significantly mitigated the effects induced by NSUN2 within DLBCL cell-derived exosomes on cellular proliferation, apoptosis, M2 macrophage polarization, and immune evasion. Further, DLBCL cell-derived exosomal NSUN2 promoted tumor growth by regulating PDL1. NSUN2 in DLBCL cell-derived exosomes stabilized PDL1 in a YBX1-dependent manner and thus promoted tumor immune escape and M2 macrophage polarization. These findings highlight the potential of targeting the NSUN2-PDL1 axis as a novel therapeutic strategy for DLBCL.

Roflumilast attenuates doxorubicin and cyclophosphamide combination-induced chemobrain in rats through modulation of NLRP3/ASC/caspase-1/GSDMD axis.

The aim of this study is to investigate the neuroprotective effect of roflumilast, a phosphodiesterase-4 (PDE-4) inhibitor on cognitive impairment induced by doxorubicin (DOX)/cyclophosphamide (CP) combination therapy and to elucidate its modulatory effect on the pyroptosis pathway. Rats were allocated into five groups: a control group, a DOX/CP-intoxicated group, two groups receiving DOX/CP plus low-dose (0.5 mg/kg/day) or high-dose (1 mg/kg/day) roflumilast, and a roflumilast-only group. Behavioral assessments and brain tissue analyses were conducted, including histopathological staining and the measurement of inflammatory and oxidative stress markers. DOX/CP treatment resulted in cognitive impairment, abnormal brain histology. It significantly elevated the levels of tumor necrosis factor-alpha (TNF-α), interleukin-1 beta (IL-1β), and malondialdehyde (MDA). Concurrently, superoxide dismutase (SOD) activity was reduced. Pyroptosis-associated markers, including nucleotide-binding oligomerization domain-like receptor family pyrin domain-containing 3 (NLRP3), apoptosis-associated speck-like protein (ASC), caspase-1, gasdermin-D (GSDMD), and interleukin-18 (IL-18) were upregulated. Apoptotic marker caspase-3 also exhibited increased expression. Conversely, administration of roflumilast (1 mg/kg/day) for four weeks ameliorated these pathological changes. Roflumilast improved cognitive function, reduced oxidative stress, and modulated inflammatory signaling. Additionally, it suppressed pyroptotic and apoptotic pathways within hippocampal tissue. These results suggest that roflumilast exerts neuroprotective effects against chemotherapy-induced cognitive dysfunction and neurodegeneration through inhibition of the NLRP3/caspase-1/GSDMD pyroptosis pathway.

Effect of Vitamin D Supplementation on Serum Cytokines Level in Patients with Type 2 Diabetes Mellitus with and Without Foot Infection

Introduction: Diabetic foot infections (DFIs) are a common and serious complication in individuals with diabetes mellitus. Low levels of Vitamin D have been proposed as a risk factor for diabetic foot and may be associated with cytokine dysregulation. This study aimed to evaluate the effect of Vitamin D supplementation on circulating levels of tumor necrosis factor-alpha (TNF-α) and interleukin-6 (IL-6) in Type 2 diabetes mellitus (T2DM) patients with and without foot infections. Methods: T2DM patients with and without foot infections were enrolled as cases and controls. Both groups were supplemented with a total 300,000 IU oral dose of Vitamin D. Serum concentrations of 25 (OH) Vitamin D and cytokines (TNF-α, IL-6) were measured in both groups at baseline and follow-up using radioimmunoassay and enzyme-linked immunosorbent assay, respectively. Results: Serum concentrations of 25 (OH) Vitamin D significantly increased in both groups (cases: P &lt;0.0001; controls: P =0.012). The difference in mean (±standard deviation) levels of circulating serum inflammatory cytokines, TNF-α and IL-6, at baseline and follow-up was not significant in controls but was significant in cases (TNF-α: P =0.0001; IL-6: P =0.0026). Conclusion: Vitamin D supplementation, particularly a high dose (60,000 IU/week) for a short period (5 weeks), significantly reduces inflammatory cytokines TNF-α and IL-6 in patients with DFI, supporting its beneficial role in managing inflammation.

Rutin attenuates complete Freund's adjuvant-induced inflammatory pain in rats.

Rutin is a bioflavonoid compound renowned for its anti-oxidative, anti-inflammatory, and antinociceptive properties. The present study aims to assess its therapeutic efficacy on complete Freund's adjuvant (CFA)induced inflammatory pain. Arthritis was induced in Wistar rats via subcutaneous administration of CFA into the right hind paw. Rutin (15 and 30 mg/kg) and indomethacin (5 mg/kg, orally) were given once daily for three weeks. Parameters observed included alterations in paw swelling perimeter, arthritis scores, and body weight. Additionally, antinociceptive activity was measured through thermal hyperalgesia and cold allodynia responses. The Tumor necrosis factor-alpha (TNF-α) level in the serum was measured. Malondialdehyde (MDA), thiol levels, catalase, and superoxide dismutase (SOD) activities were also evaluated as serum oxidative stress markers. Rutin and indomethacin significantly suppressed alterations in paw edema, pain responses, and arthritis scores and reduced the loss of body weight in contrast to disease-control rats. Furthermore, in contrast to disease control rats, rutin and indomethacin treatment exhibited an anti-inflammatory effect through a marked reduction in TNF-α levels in the serum. Rutin and indomethacin demonstrated a significant increase in catalase and SOD activities, a total thiol level, and a decrease in MDA level compared to the disease-control rats. These results suggest that rutin's antiarthritic effect is mediated by its antinociceptive, anti-oxidant, and anti-inflammatory properties.

Sub-chronic Berberine supplementation in prepubertal male rats relieved pro-inflammatory stressors and enhanced reproductive functional parameters

Berberine (BER) is a potent antioxidant and anti-inflammatory compound with several health benefits. We investigated the impact of sub-chronic BER supplementation on male rat reproductive function from the prepubescence to adulthood. Wistar rat pups (PND 21) were divided into five groups (n = 10 pups/group). The control animals received distilled water (2 mL/kg, p.o), and the treated groups received different doses of BER: 25, 50, 100, and 200 mg/kg body weight, p.o) from PND 28 to PND 68. Using biochemical, histomorphological, and pathology methods, we examined the reproductive function of the treated rats. Compared to the control, prepubertal BER supplementation showed no significant effect on body/organ weight. Graded doses of BER supplementation improved (p < 0.05) reproductive hormone levels (FSH, luteinising, prolactin and testosterone), testicular enzyme activities (alkaline phosphatase, acid phosphatase, lactate dehydrogenase), and sperm functional parameters. Also, BER supplementation increased antioxidant enzyme activities and total thiol levels, decreased (p < 0.05) reactive oxygen and nitrogen species, lipid peroxidation and protein carbonyl, nitric oxide, tumour necrosis factor-alpha (TNF-α) levels, and myeloperoxidase activity in rat’s hypothalamus, epididymis and testes. The histology of examined organs of rats treated with BER was comparable to the control, exhibiting abundant spermatozoa (epididymis and testes) and neuronal cells (hypothalamus). These findings suggest that BER supplementation substantially enhanced male rat reproductive function by lowering oxidative stress-related damage to cellular macromolecules, such as protein carbonylation and lipid peroxidation. Moreover, BER reduced pro-inflammatory stresses in the organs under investigation. We highlight the benefits of BER for supporting reproductive health, with potential therapeutic uses to relieve disorders of reproductive function. Nevertheless, additional research is required to clarify the molecular and functional test biomarkers that require BER to have effects that promote reproductive health.

Alogliptin attenuates testicular damage induced by monosodium glutamate in both juvenile and adult male rats by activating autophagy: ROS dependent AMPK/mTOR.

Monosodium glutamate (MSG) is one of the most commonly used food additives, known for its adverse health effects. Alogliptin (ALO) is a highly selective dipeptidyl peptidase-4 inhibitor, but its role in male reproductive function remains debated. The study was designed to evaluate and compare the potential of ALO in mitigating MSG-induced testicular toxicity in juvenile and adult male rats. Juvenile and adult male rats were treated with either MSG or pretreated with ALO before MSG administration. The rats then received ALO and MSG concurrently for 28 days. Testicular tissues were isolated and subjected to histo-biochemical and molecular assessments. Our results demonstrated that ALO reversed MSG-induced testicular injury, as evidenced by the restoration of reproductive hormone balance (increased serum luteinizing hormone and testosterone concentrations), suppression of oxidative stress injury (decreased testicular malondialdehyde, increased superoxide dismutase activity, and minimal 8-hydroxy-2'-deoxyguanosine immunoreactivity), inflammation (reduced testicular tumor necrosis factor-alpha levels), and fibrosis (decreased testicular collagen fiber deposition). Additionally, ALO impeded apoptosis and activated autophagy by decreasing caspase-3 activity, stimulating the AMPK/mTOR pathway, downregulating Bax and SQSTM-1/p62 expression, upregulating Bcl2 and Beclin 1, promoting testicular proliferation (increased number of proliferating cell nuclear antigen-positive cells in the testis), restoring glycogen content in the testis (mild to moderate periodic acid-Schiff reaction), and preserving testicular architecture. MSG induced more severe adverse testicular effects in juvenile rats, while ALO pretreatment was more protective in adult rats. ALO's anti-inflammatory, antioxidant, antiapoptotic, pro-autophagic, antifibrotic, and proliferative actions in the testis suggest its promising potential for combating male reproductive dysfunction.

15-Deoxy-Δ-12,14-Prostaglandin J2 Represses Immune Escape of Lung Adenocarcinoma by Polarizing Macrophages Through Epidermal Growth Factor Receptor/Ras/Raf Pathway.

Lung adenocarcinoma (LUAD) is a widespread and deadly form of cancer. Prostaglandin 15-deoxy-Δ-12,14-prostaglandin J2 (15d-PGJ2) possesses antioxidant, anti-inflammatory, and anticancer properties. However, it is unclear whether this effect on LUAD progression stems from its ability to influence macrophage polarization. By utilizing 3- (4,5-Dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide (MTT), flow cytometry, colony formation, transwell assays, and enzyme linked immunosorbent assay (ELISA), we investigated how 15d-PGJ2 affects A549 cell viability, proliferation, apoptosis, and invasion, as well as levels of interleukin (IL)-4, IL-13, and IL-17. Human monocytic cell line THP-1 was induced into M2 macrophages using phorbol 12-myristate 13-acetate and IL-4/IL-13, followed by treatment with 15d-PGJ2. The study employed flow cytometry to observe the polarization of macrophages, quantitative reverse transcription polymerase chain reaction (qRT-PCR) to identify epidermal growth factor receptor (EGFR) expression, western blot for identifying expression of macrophage marker proteins, and examining EGFR/rat sarcoma (Ras)/rapidly accelerated fibrosarcoma (Raf) activation. In a coculture setup, CD8+ T cells were shown to have a proliferation capacity by carboxifluorescein diacetate succinimidyl ester (CFSE), a killing ability by lactate dehydrogenase, and an analysis of their interferon gamma and tumor necrosis factor alpha levels by ELISA. 15d-PGJ2 reduced invasion capacity and expression of inflammatory cytokines, lowered A549 cell viability in a dose-dependent way, and promoted apoptosis. 15d-PGJ2 facilitated the transition of M2 macrophages to the M1 type, inhibited Ras/Raf pathway activation, reduced EGFR expression in macrophages, and stimulated CD8+ T cells to enhance anti-tumor immunity. 15d-PGJ2 repressed M2 macrophage polarization and LUAD immune evasion by targeting the EGFR/Ras/Raf pathway in macrophages.