Search

Background: New pharmaceutical forms of natural compounds such as curcumin can be an effective intervention to control peritonitis and abdominal adhesion. Objectives: This study investigates the effects of slow-release curcumin-loaded selenium nanoparticles (Cur@S.N) on some inflammatory biomarkers in experimental peritonitis. Methods: After synthesizing selenium nanoparticles (S.N) and (Cur@S.N), experimental peritonitis was surgically induced in 80 adult male rats. The control group received no treatment, whereas the other groups received single intraperitoneal doses of 0.25 mg/kg S.N, 50 mg/kg curcumin, and 0.25+50 mg/kg (Cur@S.N). Blood malondialdehyde (MDA), nitric oxide (NO), interleukin 6 (IL-6), and tumor necrosis factor-alpha (TNFα) were measured on days 3, 7 and 14, and also intra-abdominal adhesion assessment was done. Results: On day 3, NO levels in all treatment groups significantly decreased (P>0.05), while the lowest level was seen on day 14 in the S.N group (P˂0.05). MDA was significantly lower in the S.N and Cur@S.N groups than in the control on days 3, 7 and 14 (P˂0.05). TNF-α levels in S.N and Cur@S.N groups were significantly lower than in the control group on day 3 (P≤0.05). Meanwhile, the S.N group had the lowest level on day 14. IL-6 significantly decreased on days 3 and 7 in the Cur@S.N and curcumin groups compared to the control group (P˂0.05). Conclusion: Cur@S.N group possesses significant anti-inflammatory efficacy by reducing MDA, NO, IL-6 and TNF-α, decreasing peritonitis and intra-abdominal adhesion. [ABSTRACT FROM AUTHOR]

This study aims to investigate the effects of the Galectin‐3 (Gal‐3) inhibitor TD139 on inflammation and the extracellular signal‐regulated kinase (ERK)/c‐Jun N‐terminal kinase (JNK)/p38 pathway in gestational diabetes mellitus (GDM). Human placental tissues were treated with TD139 and TNF‐α, assessing Gal‐3, ERK/JNK/p38 activation, and inflammatory cytokines. GDM was induced in mice via subcutaneous injections of streptozotocin (STZ). After confirming GDM, mice were treated with 15 mg/kg TD139 on GD 10.5 12.5, 14.5, 16.5, and 18.5. Serum inflammatory cytokines were measured on GD 20.5, and post‐delivery placental tissues were analyzed. Data were analyzed using one‐way or two‐way repeated measures ANOVA with post hoc tests. TD139 suppressed TNF‐α‐induced increases in Gal‐3, IL‐1β, IL‐6, MCP‐1, and ERK/JNK/p38 activation in placental tissues. In STZ‐induced GDM mice, TD139 reduced glucose levels, weight loss, and food and water intake. TD139 significantly lowered TNF‐α, IL‐1β, IL‐6, and MCP‐1 in serum and placental tissues and inhibited the ERK/JNK/p38 pathway. TD139 improved pup numbers in GDM mice compared to untreated ones. TD139 reduces inflammation and inhibits the ERK/JNK/p38 pathway in TNF‐α stimulated placental tissues and STZ‐induced GDM mice, suggesting its therapeutic potential for managing GDM‐related placental inflammation and improving pregnancy outcomes. The study used TNF‐α to mimic GDM in placental tissues and an STZ‐induced GDM mouse model, which may not fully represent human GDM complexity. Future research should explore alternative models, and broader signaling pathways, and thoroughly evaluate TD139's safety in pregnancy. [ABSTRACT FROM AUTHOR]

Background: Tumor necrosis factor alpha (TNF-α) produces an inflammatory process and plays a critical role against infection and in the control of viral infection. The present study was conducted to determine the status of serum TNF-α in hospitalized patients with coronavirus disease-2019 (COVID-19). Methods: In this cross-sectional study the serum TNF-α level, sex, and age, were determined in patients with COVID-19. The association between variables was determined using the student t-test, analysis of variance (ANOVA) test, multiple logistic regression analysis, and the statistical package for the Social Sciences (SPSS)- 18 (p < 0.05). Results: A total of 91 (women 41.75%, and men 58.24%) patients with a mean serum TNF-α level of 9.9 picograms per milliliter (pg/mL) were considered. In all (100%) patients, the TNF-α serum level was more than the normal limit (P=0.95). 95.60% of patients suffered severe COVID-19, with a TNF-a serum level of 10.20 pg/mL (P=0.87). Mean TNF-α serum levels in women and men were 11.37 pg/mL and 8.8 pg/mL, respectively (P= 0.17). In the age group of > 70 years (11.30 pg/mL), serum TNF-α concentration was higher than the other age groups (p>0.05). Conclusion: A significant proportion of women and men patients with COVID-19 in the middle and old age had a high concentration of serum TNF-α which may indicate the severity of the disease. Serum TNF-α level is different in women and men of different ages, so it can contribute to treatment strategies. [ABSTRACT FROM AUTHOR]

Background: Preeclampsia, a complex hypertensive disorder unique to pregnancy, significantly impacts maternal and fetal health worldwide, with a prevalence of 2–8%. This condition results from a complex interplay of genetic, environmental, and immunological factors. Aim and objectives: This study aims to investigate the genetic predispositions to preeclampsia, focusing on specific gene polymorphisms among pregnant women at Central Hospital Auchi, Nigeria. Materials and methods: We examined the endothelial nitric oxide synthase (eNOS), vascular endothelial growth factor (VEGF), angiotensin-converting enzyme (ACE), and tumor necrosis factor-alpha (TNF-α) genes in 200 pregnant women, equally divided between preeclamptic patients and normotensive controls. Results: The eNOS G894T polymorphism was significantly associated with preeclampsia, with the T allele nearly doubling the risk. The VEGF C936T polymorphism's T allele also indicated a higher risk. The D allele in the ACE gene's insertion/deletion (I/D) polymorphism significantly increased the risk, as did the A allele in the TNF-α G308A polymorphism. Conclusions: These findings highlight the importance of genetic factors in preeclampsia and suggest that genetic screening could improve risk stratification and early detection. Future research should integrate genetic, epigenetic, and environmental data to understand preeclampsia's multifaceted nature and develop targeted therapies. This study underscores the potential of personalized medicine in managing and reducing the risks associated with preeclampsia. [ABSTRACT FROM AUTHOR]

Objective: To investigate the effects of a drug‐coated balloon (DCB) on inflammatory cytokines in patients with coronary artery calcification (CAC) after interventional therapy. Methods: This study included 58 patients with coronary heart disease who underwent coronary angiography (CAG) from October 2020 to September 2021. Patients were divided into CAC and non‐CAC groups, and a DCB was used to intervene in the target lesions. Ten‐milliliter preoperative and postoperative blood samples were drawn from the coronary lesions in both groups to detect the expression of serum interleukin‐6 (IL‐6), tumor necrosis factor‐alpha (TNF‐α), and intercellular adhesion molecule‐1 (ICAM‐1). All patients were subjected to a 6‐month follow‐up to observe the incidence of major adverse cardiac events (MACEs). Results: No significant differences in baseline clinical data were found between the groups. Serum IL‐6, TNF‐α, and ICAM‐1 expressions in coronary blood samples immediately before DCB were not significantly different from those after DCB in all patients. After DCB, serum TNF‐α expression in the CAC group was significantly lower than that in the non‐CAC group (p < 0.05). In contrast, no significant difference in serum IL‐6 and ICAM‐1 expression was found between the groups. During the 6‐month follow‐up, no significant difference in the incidence of MACE was found between both groups. Conclusions: DCB reduced the expression of inflammatory cytokine TNF‐α in CAC, which may be one of the key mechanisms underlying the treatment of CAC by DCB. [ABSTRACT FROM AUTHOR]

Abstract This study aims to investigate the effects of the Galectin‐3 (Gal‐3) inhibitor TD139 on inflammation and the extracellular signal‐regulated kinase (ERK)/c‐Jun N‐terminal kinase (JNK)/p38 pathway in gestational diabetes mellitus (GDM). Human placental tissues were treated with TD139 and TNF‐α, assessing Gal‐3, ERK/JNK/p38 activation, and inflammatory cytokines. GDM was induced in mice via subcutaneous injections of streptozotocin (STZ). After confirming GDM, mice were treated with 15 mg/kg TD139 on GD 10.5 12.5, 14.5, 16.5, and 18.5. Serum inflammatory cytokines were measured on GD 20.5, and post‐delivery placental tissues were analyzed. Data were analyzed using one‐way or two‐way repeated measures ANOVA with post hoc tests. TD139 suppressed TNF‐α‐induced increases in Gal‐3, IL‐1β, IL‐6, MCP‐1, and ERK/JNK/p38 activation in placental tissues. In STZ‐induced GDM mice, TD139 reduced glucose levels, weight loss, and food and water intake. TD139 significantly lowered TNF‐α, IL‐1β, IL‐6, and MCP‐1 in serum and placental tissues and inhibited the ERK/JNK/p38 pathway. TD139 improved pup numbers in GDM mice compared to untreated ones. TD139 reduces inflammation and inhibits the ERK/JNK/p38 pathway in TNF‐α stimulated placental tissues and STZ‐induced GDM mice, suggesting its therapeutic potential for managing GDM‐related placental inflammation and improving pregnancy outcomes. The study used TNF‐α to mimic GDM in placental tissues and an STZ‐induced GDM mouse model, which may not fully represent human GDM complexity. Future research should explore alternative models, and broader signaling pathways, and thoroughly evaluate TD139's safety in pregnancy.

Abstract Background Preeclampsia, a complex hypertensive disorder unique to pregnancy, significantly impacts maternal and fetal health worldwide, with a prevalence of 2–8%. This condition results from a complex interplay of genetic, environmental, and immunological factors. Aim and objectives This study aims to investigate the genetic predispositions to preeclampsia, focusing on specific gene polymorphisms among pregnant women at Central Hospital Auchi, Nigeria. Materials and methods We examined the endothelial nitric oxide synthase (eNOS), vascular endothelial growth factor (VEGF), angiotensin-converting enzyme (ACE), and tumor necrosis factor-alpha (TNF-α) genes in 200 pregnant women, equally divided between preeclamptic patients and normotensive controls. Results The eNOS G894T polymorphism was significantly associated with preeclampsia, with the T allele nearly doubling the risk. The VEGF C936T polymorphism's T allele also indicated a higher risk. The D allele in the ACE gene's insertion/deletion (I/D) polymorphism significantly increased the risk, as did the A allele in the TNF-α G308A polymorphism. Conclusions These findings highlight the importance of genetic factors in preeclampsia and suggest that genetic screening could improve risk stratification and early detection. Future research should integrate genetic, epigenetic, and environmental data to understand preeclampsia's multifaceted nature and develop targeted therapies. This study underscores the potential of personalized medicine in managing and reducing the risks associated with preeclampsia.

Background: Tumor necrosis factor alpha (TNF-α) produces an inflammatory process and plays a critical role against infection and in the control of viral infection. The present study was conducted to determine the status of serum TNF-α in hospitalized patients with coronavirus disease-2019 (COVID-19). Methods: In this cross-sectional study the serum TNF-α level, sex, and age, were determined in patients with COVID-19. The association between variables was determined using the student t-test, analysis of variance (ANOVA) test, multiple logistic regression analysis, and the statistical package for the Social Sciences (SPSS)-18 (p < 0.05). Results: A total of 91 (women 41.75%, and men 58.24%) patients with a mean serum TNF-α level of 9.9 picograms per milliliter (pg/mL) were considered. In all (100%) patients, the TNF-α serum level was more than the normal limit (P=0.95). 95.60% of patients suffered severe COVID-19, with a TNF-a serum level of 10.20 pg/mL (P=0.87). Mean TNF-α serum levels in women and men were 11.37 pg/mL and 8.8 pg/mL, respectively (P= 0.17). In the age group of > 70 years (11.30 pg/mL), serum TNF-α concentration was higher than the other age groups (p>0.05). Conclusion: A significant proportion of women and men patients with COVID-19 in the middle and old age had a high concentration of serum TNF-α which may indicate the severity of the disease. Serum TNF-α level is different in women and men of different ages, so it can contribute to treatment strategies.

The neurotoxicity of 3-Nitropropionic acid (3-NP) is well known. Herein, the prophylactic versus therapeutic effects of quercetin (QCT) were investigated against 3-NP-induced behavioral anomalies and oxidative neural damage. Thirty male mice were assigned into five groups; the negative control group, the QCT group (25 mg/kg/day, p.o. for 21 days), the 3-NP group (17 days), the prophylactic group (QCT administration for 14 consecutive days, and then 3-NP was administrated), the therapeutic group (3-NP was administrated and then QCT for 21 days). At the end of the animal treatment, behavioral studies were assessed. Subsequently, the brain sample tissues were assessed for oxidative stress-related parameters and histological evaluation. Moreover, the potential interaction between 3-NP and tumor necrosis factor-alpha (TNF-α) was evaluated by using a molecular docking study. 3-NP markedly led to neurotoxicity which was indicated by behavioral deficits (motor behavior, depression-like behavior, memory dysfunction, and passive avoidance) and oxidative damage. Blind and targeted molecular docking results showed good interaction between 3-NP and TNF-α. However, the prophylactic effects of QCT were superior to the therapeutic effects for attenuating 3-NP-induced neurobehavioral and oxidative neural changes in experimental mice, which histological changes of the brain's striatum region approved our findings. Taken together, the antioxidant activity of QCT remarkably could attenuate 3-NP-induced neurobehavioral deficits and mitochondrial dysfunctions in mice. [ABSTRACT FROM AUTHOR]

Linguatula serrata is a neglected parasitic zoonosis with less research recorded throughout the globe on the physiological and immunological alteration of dogs infested by these zoonotic parasites. This study aimed to evaluate the effects of L. serrata infestation on the dogs after experimental infestation with the nymphs by determining oxidative stress levels and immunological genes of cellular immunity. Larvae of L. serrata were collected from the infested goat mesenteric lymph nodes by cutting it, and the nymphs were liberated; these nymphs were mixed with saline at 37–40 °C for experimental infestation of dogs and observed infestation to puppies using viable nymphal stages (movable, not traumatized or dead). Blood and sera samples were sampled from the dog after 6 months of infestation. The nasal mucosa and its mucus were collected from the infested dogs as well as negative controls for evaluation of gene expression such as tumor necrosis factor-alpha (TNF-α) and gamma interferon (IFN-γ) activity and interleukin (1β and 6). Infested dogs exhibited lower hemoglobin concentration, packed cell volume (PCV), and total erythrocyte count than non-infested control dogs. Dogs had high AST and ALT levels, leukocytosis with prominent eosinophilia, and low hematological values. The oxidative stress was higher in experimentally infested dogs than control non-infested dogs. The genetic characterization of the nymphal stage of L. serrata was recorded as the first confirmation in Egypt. The four examined genes were expressed regularly against nasopharynx linguatulosis in experimentally infested dogs. This study is the first report on the genetic characterization of L. serrata from goat origin in Egypt. [ABSTRACT FROM AUTHOR]

This prospective cross-sectional study evaluated the diagnostic and prognostic role of cerebrospinal fluid (CSF) tumor necrosis factor-alpha (TNF-α) in children with cerebral malaria (CM) and its role in the differentiation of CM from non-cerebral severe malaria. CSF TNF-α was measured using a human TNF-α enzyme-linked immunosorbent assay kit of 39 cases of CM and 19 cases of non-cerebral severe malaria. CSF TNF-α levels were significantly higher in CM (p  < 0.001). Based on the receiver operating characteristics curve, a cutoff value of CSF TNF-α was 5.7 pg/ml for diagnosis of CM with sensitivity, specificity, positive predictive value (PPV) and negative predictive value (NPV) of 87.2%, 94.7%, 97.1% and 78.3% respectively. The cutoff value of CSF TNF-α was 13.7 pg/ml for predicting adverse outcomes in CM with sensitivity, specificity, PPV and NPV of 100%, 96.8%, 88.9% and 100%, respectively. However, the cutoff value of CSF TNF-α was 4.96 pg/ml for predicting adverse outcomes in non-cerebral severe malaria with a sensitivity, specificity, PPV and NPV of 100%, 94.1%, 88.9% and 100% respectively. So, CSF TNF-α is an excellent biomarker and can be used as a diagnostic and prognostic tool. More studies are needed to establish CSF TNF-α as a predictor of neurological sequelae. [ABSTRACT FROM AUTHOR]

Non-HLA-directed regulatory autoantibodies (RABs) are known to target Gprotein coupled receptors (GPCRs) and thereby contribute to kidney transplant vasculopathy and failure. However, the detailed underlying signaling mechanisms in human microvascular endothelial cells (HMECs) and immune cells need to be clarified in more detail. In this study, we compared the immune stimulatory effects and concomitant intracellular and extracellular signaling mechanisms of immunoglobulin G (IgG)-fractions from kidney transplant patients with allograft vasculopathy (KTx-IgG), to that from patients without vasculopathy, or matched healthy controls (Con-IgG). We found that KTx-IgG from patients with vasculopathy, but not KTx-IgG from patients without vasculopathy or Con-IgG, elicits HMEC activation and subsequent upregulation and secretion of tumor necrosis factor alpha (TNF-α) from HMECs, which was amplified in the presence of the protease-activated thrombin receptor 1 (PAR1) activator thrombin, but could be omitted by selectively blocking the PAR1 receptor. The amount and activity of the TNF-α secreted by HMECs stimulated with KTx-IgG from patients with vasculopathy was sufficient to induce subsequent THP-1 monocytic cell activation. Furthermore, AP-1/cFOS, was identified as crucial transcription factor complex controlling the KTxIgG-induced endothelial TNF-α synthesis, and mircoRNA-let-7f-5p as a regulatory element in modulating the underlying signaling cascade. In conclusion, exposure of HMECs to KTx-IgG from patients with allograft vasculopathy, but not KTx-IgG from patients without vasculopathy or healthy Con-IgG, triggers signaling through the PAR1-AP-1/c-FOS-miRNA-let7-axis, to control TNF-a gene transcription and TNF-α-induced monocyte activation. These observations offer a greater mechanistic understanding of endothelial cells and subsequent immune cell activation in the clinical setting of transplant vasculopathy that can eventually lead to transplant failure, irrespective of alloantigen-directed responses. [ABSTRACT FROM AUTHOR]

Tetrahydrocurcumin (THC) has been shown to possess anti-angiogenic activities. This study aims to investigate the effects of THC on adipose angiogenesis and expression of angiogenic factors that occurs in 60% high-fat diet-induced obese mice. Male ICR mice were randomly divided into 3 groups: mice fed with a low-fat diet (LFD group); mice fed with very high fat diet (VHFD group), and mice fed with VHFD supplemented with THC (300 mg/kg/day orally) (VHFD+THC treated group) for 6 weeks. Body weight (BW), food intake, fasting blood sugar (FBS), lipid profiles and visceral fats weight (VF) were measured. The microvascular density (MVD), TNF-α, VEGF, MMP-2, and MMP-9 expressions were evaluated. The VHFD group had significantly increased total cholesterol, triglyceride, food intake, BW, VF, VF/BW ratio, adipocyte size and the number of crown-liked structures as compared to LFD group. THC supplementation markedly reduced these parameters and adipocyte hypertrophy and inflammation in white adipose tissues. MVD, TNF-α, VEGF, MMP-2, and MMP-9 were over-expressed in the VHFD group. However, THC supplementation decreased MVD and reduced expression of TNF-α, VEGF, MMP-2, and MMP-9. In conclusion, THC suppressed angiogenesis in adipose tissue by the downregulation of TNF-α, VEGF, MMP-2, and MMP-9. With its effects on lipid metabolism as well as on food consumption, THC could contribute to lower visceral fat and body weight. Overall, our study demonstrated the potential benefit of THC in mitigating obesity and associated metabolic disorders along with elucidated the suppression of adipose angiogenesis as one of its underlying mechanisms.

Diverticular disease (DD) is the most frequent condition in the Western world that affects the colon. Although chronic mild inflammatory processes have recently been proposed as a central factor in DD, limited information is currently available regarding the role of inflammatory cytokines, such as tumor necrosis factor-alpha (TNF-α). Therefore, we conducted a systematic review and meta-analysis aiming to assess the mucosal TNF-α levels in DD. We conducted a systematic literature search using PubMed, Embase, and Scopus to identify observational studies assessing the TNF-α levels in DD. Full-text articles that satisfied our inclusion and exclusion criteria were included, and a quality assessment was performed using the Newcastle–Ottawa Scale (NOS). The principal summary outcome was the mean difference (MD). The results were reported as MD (95% confidence interval (CI)). A total of 12 articles involving 883 subjects were included in the qualitative synthesis, out of which 6 studies were included in our quantitative synthesis. We did not observe statistical significance related to the mucosal TNF-α levels in symptomatic uncomplicated diverticular disease (SUDD) vs. the controls (0.517 (95% CI −1.148–2.182)), and symptomatic vs. asymptomatic DD patients (0.657 (95% CI −0.883–2.196)). However, the TNF-α levels were found to be significantly increased in DD compared to irritable bowel disease (IBS) patients (27.368 (95% CI 23.744–30.992)), and segmental colitis associated with diverticulosis (SCAD) vs. IBS patients (25.303 (95% CI 19.823–30.784)). Between SUDD and the controls, as well as symptomatic and asymptomatic DD, there were no significant differences in the mucosal TNF-α levels. However, the TNF-α levels were considerably higher in DD and SCAD patients than IBS patients. Our findings suggest that TNF-α may play a key role in the pathogenesis of DD in specific subgroups and could potentially be a target for future therapies. [ABSTRACT FROM AUTHOR]

Background: This study explores the association of neutrophil-to-lymphocyte (NLR), monocyte-to-lymphocyte (MLR), and platelet-to-lymphocyte (PLR) ratios with the 3-month treatment response and persistence of tumor necrosis factor-alpha (TNF-α) blockers in patients with ankylosing spondylitis (AS). Methods: This retrospective cohort study investigated 279 AS patients who were newly initiated on TNF-α blockers between April 2004 and October 2019 and 171 sex- and age-matched healthy controls. Response to TNF-α blockers was defined as a reduction in the Bath AS Disease Activity Index of ≥50% or 20 mm, and persistence referred to the time interval from the initiation to discontinuation of TNF-α blockers. Results: Patients with AS had significantly increased NLR, MLR, and PLR ratios as compared to controls. The frequency of non-response at 3 months was 3.7%, and TNF-α blockers' discontinuation occurred in 113 (40.5%) patients during the follow-up period. A high baseline NLR but not high baseline MLR and PLR showed an independently significant association with a higher risk of non-response at 3 months (OR = 12.3, p = 0.025) and non-persistence with TNF-α blockers (HR = 1.66, p = 0.01). Conclusions: NLR may be a potential marker for predicting the clinical response and persistence of TNF-α blockers in AS patients. [ABSTRACT FROM AUTHOR]

In this review article, we aimed to discuss intricate roles of SD in modulating depression in preclinical and clinical studies. Decades of research have shown the inconsistent effects of SD on depression, focusing on SD duration. However, inconsistent role of SD seems to be more complicated, and SD duration cannot be the only one factor. Regarding this issue, we chose some important factors involved in the effects of SD on cognitive functions and mood including brain-derived neurotrophic factor (BDNF), vascular endothelial growth factor (VEGF), serotonin, cortisol, and tumor necrosis factor-alpha (TNF-α). It was concluded that SD has a wide-range of inconsistent effects on BDNF, VEGF, serotonin, and cortisol levels. It was noted that BDNF diurnal rhythm is significantly involved in the modulatory role of SD in depression. Furthermore, the important role of VEGF in blood–brain barrier permeability which is involved in modulating depression was discussed. It was also noted that there is a negative correlation between cortisol and BDNF that modulates depression. Eventually, it was concluded that TNF-α regulates sleep/wake cycle and is involved in the vulnerability to cognitive and behavioral impairments following SD. TNF-α also increases the permeability of the blood–brain barrier which is accompanied by depressive behavior. In sum, it was suggested that future studies should focus on these mechanisms/factors to better investigate the reasons behind intricate roles of SD in modulating depression. [ABSTRACT FROM AUTHOR]

Visceral leishmaniasis is a neglected tropical disease that can be lethal if not treated. The available medicines have severe side effects, such as toxicity and drug resistance. Various investigations are looking into new anti-leishmanial compounds from natural products that have little impact on host cells. Lupeol, a triterpenoid present in the flora of many edible plants, has been shown to have antimicrobial properties. The present study investigated the immunomodulatory effects of lupeol on U937 macrophages infected with Leishmania donovani , focusing on the expression of key cytokines and enzymes involved in the immune response. U937 macrophages were infected with Leishmania donovani amastigotes and treated with varying concentrations of lupeol throughout three days. The expression levels of inducible nitric oxide synthase (iNOS), tumor necrosis factor-alpha (TNF-α), and interleukin-10 (IL-10) were measured using real-time polymerase chain reaction (RT-PCR). A positive simulation of gene expression was estimated using ΔΔCT to assess relative expression. The results demonstrated that lupeol significantly upregulated iNOS and TNF-α expression, especially at higher concentrations, indicating enhanced pro-inflammatory and anti-leishmanial activity. Interestingly, IL-10 expression also increased, suggesting a complex immunomodulatory role of lupeol that involves both pro-inflammatory and anti-inflammatory pathways. Pearson correlation analysis revealed a strong association between iNOS and TNF-α (0.97692), as well as a moderate correlation between iNOS and IL-10 (0.51603). These findings suggest that lupeol may promote a balanced immune response, enhancing the body's ability to combat L. donovani while potentially mitigating excessive inflammation. Lupeol can potentially serve as a novel therapeutic agent against visceral leishmaniasis. [ABSTRACT FROM AUTHOR]

Objective: Worldwide, preeclampsia (PE) is a multifactorial disorder reported in 2--5% of pregnancies, which increases mortality during pregnancy. In general, 10--15% of maternal deaths are directly related to PE and eclampsia. One of the susceptibility genes for PE is tumor necrosis factor-α (TNF-α) expressed by most immune cells. TNF-α is a protein involved in various biological processes, including proliferation and apoptosis, as well as the expression of inflammatory genes. The goal of this study was to investigate the role of TNF-α single nucleotide polymorphism (SNP) -308G/A (rs1800629) and their relationship with TNF-α in PE patients. Materials and methods: The SNP was genotyped in 90 cases and 90 controls. Whole blood was collected from women with PE and normal pregnancy in EDTA containing tubes, and DNA extraction was performed from their blood lymphocytes according to a standard phenol-chloroform procedure. Then, DNA was genotyped by real-time PCR and the polymorphism was detected by TaqMan assay. Serum levels of TNF-α protein were measured by enzyme-linked immunosorbent (ELISA) assay. Results: TNF-α levels in women with PE were significantly higher than in healthy ones (p<0.001). We did not observe any correlation between allelic outbreak (p=0.3) and TNF-α-308G/A polymorphism (p=0.7) with the incidence of PE. Conclusion: Although TNF-α-308G/A gene polymorphism does not appear to affect susceptibility to PE, an increased level of serum TNF-α can be used as a predictor for PE during pregnancy. We recommend that more research be conducted on possible factors related to the incidence of PE. [ABSTRACT FROM AUTHOR]

Objective: Worldwide, preeclampsia (PE) is a multifactorial disorder reported in 2–5% of pregnancies, which increases mortality during pregnancy. In general, 10–15% of maternal deaths are directly related to PE and eclampsia. One of the susceptibility genes for PE is tumor necrosis factor-α (TNF-α) expressed by most immune cells. TNF-α is a protein involved in various biological processes, including proliferation and apoptosis, as well as the expression of inflammatory genes. The goal of this study was to investigate the role of TNF-α single nucleotide polymorphism (SNP) -308G/A (rs1800629) and their relationship with TNF-α in PE patients. Materials and methods: The SNP was genotyped in 90 cases and 90 controls. Whole blood was collected from women with PE and normal pregnancy in EDTA containing tubes, and DNA extraction was performed from their blood lymphocytes according to a standard phenol-chloroform procedure. Then, DNA was genotyped by real-time PCR and the polymorphism was detected by TaqMan assay. Serum levels of TNF-α protein were measured by enzyme-linked immunosorbent (ELISA) assay. Results: TNF-α levels in women with PE were significantly higher than in healthy ones (p

Diverticular disease (DD) is the most frequent condition in the Western world that affects the colon. Although chronic mild inflammatory processes have recently been proposed as a central factor in DD, limited information is currently available regarding the role of inflammatory cytokines, such as tumor necrosis factor-alpha (TNF-α). Therefore, we conducted a systematic review and meta-analysis aiming to assess the mucosal TNF-α levels in DD. We conducted a systematic literature search using PubMed, Embase, and Scopus to identify observational studies assessing the TNF-α levels in DD. Full-text articles that satisfied our inclusion and exclusion criteria were included, and a quality assessment was performed using the Newcastle–Ottawa Scale (NOS). The principal summary outcome was the mean difference (MD). The results were reported as MD (95% confidence interval (CI)). A total of 12 articles involving 883 subjects were included in the qualitative synthesis, out of which 6 studies were included in our quantitative synthesis. We did not observe statistical significance related to the mucosal TNF-α levels in symptomatic uncomplicated diverticular disease (SUDD) vs. the controls (0.517 (95% CI −1.148–2.182)), and symptomatic vs. asymptomatic DD patients (0.657 (95% CI −0.883–2.196)). However, the TNF-α levels were found to be significantly increased in DD compared to irritable bowel disease (IBS) patients (27.368 (95% CI 23.744–30.992)), and segmental colitis associated with diverticulosis (SCAD) vs. IBS patients (25.303 (95% CI 19.823–30.784)). Between SUDD and the controls, as well as symptomatic and asymptomatic DD, there were no significant differences in the mucosal TNF-α levels. However, the TNF-α levels were considerably higher in DD and SCAD patients than IBS patients. Our findings suggest that TNF-α may play a key role in the pathogenesis of DD in specific subgroups and could potentially be a target for future therapies.

Acute lung injury (ALI), during the progression of infectious shock, leads to systemic inflammatory response syndrome with increased pulmonary capillary membrane permeability due to pulmonary inflammation and uncontrolled inflammatory responses. It may cause fatality in patients. Here, we evaluated the protective effect of breviscapine on ALI in rats with infectious shock. Sprague-Dawley (SD) rats were assigned into Sham, model [lipopolysaccharide (LPS) group], and breviscapine treatment groups (LPS + breviscapine group) and weighed. The lung coefficient, and the wet-to-dry weight ratio (W/D) and moisture content of lung tissues were calculated. The pathological changes of the lung tissues were detected using hematoxylin-eosin (HE) staining, and the protein expressions of interleukin-1 beta (IL-1β), IL-6, and tumor necrosis factor-alpha (TNF-α) were determined by enzyme-linked immunosorbent assay. Western blotting was conducted to measure the protein expressions of toll-like receptor-9 (TLR-9) and nuclear factor-kappa B (NF-κB) (p65). Compared with LPS group, breviscapine significantly lowered the lung coefficient and the W/D and moisture content of lung tissues, relieved the pathological changes of lung tissues, reduced the protein expression levels of IL-1β, IL-6, and TNF-α, weakened the activation of NF-κB (p65) in lung tissues, and repressed the protein expressions of TLR-9 and NF-κB (p65). [ABSTRACT FROM AUTHOR]

The neuroimmune mechanism underlying neuropathic pain has been extensively studied. Tumor necrosis factor-alpha (TNF-α), a key pro-inflammatory cytokine that drives cytokine storm and stimulates a cascade of other cytokines in pain-related pathways, induces and modulates neuropathic pain by facilitating peripheral (primary afferents) and central (spinal cord) sensitization. Functionally, TNF-α controls the balance between cell survival and death by inducing an inflammatory response and two programmed cell death mechanisms (apoptosis and necroptosis). Necroptosis, a novel form of programmed cell death, is receiving increasing attraction and may trigger neuroinflammation to promote neuropathic pain. Chronic pain is often accompanied by adverse pain-associated emotional reactions and cognitive disorders. Overproduction of TNF-α in supraspinal structures such as the anterior cingulate cortex (ACC) and hippocampus plays an important role in pain-associated emotional disorders and memory deficits and also participates in the modulation of pain transduction. At present, studies reporting on the role of the TNF-α–necroptosis pathway in pain-related disorders are lacking. This review indicates the important research prospects of this pathway in pain modulation based on its role in anxiety, depression and memory deficits associated with other neurodegenerative diseases. In addition, we have summarized studies related to the underlying mechanisms of neuropathic pain mediated by TNF-α and discussed the role of the TNF-α–necroptosis pathway in detail, which may represent an avenue for future therapeutic intervention. [ABSTRACT FROM AUTHOR]

Copyright of Baghdad Science Journal is the property of Republic of Iraq Ministry of Higher Education & Scientific Research (MOHESR) and its content may not be copied or emailed to multiple sites or posted to a listserv without the copyright holder's express written permission. However, users may print, download, or email articles for individual use. This abstract may be abridged. No warranty is given about the accuracy of the copy. Users should refer to the original published version of the material for the full abstract. (Copyright applies to all Abstracts.)

Abstract Background In the bone marrow microenvironment (BM), endothelial cells are individual cells that form part of the sinusoidal blood vessels called the “bone marrow endothelial-vascular niche.” They account for less than 2% of the bone marrow cells. They play essential functions by generating growth and inhibitory factors that promote the hematopoietic stem cells (HSCs) regulation. In response to inflammatory stimuli, the BMECs increase in proliferation to maintain the blood vessels’ integrity within the BM. The inflammatory response releases cytokines such as tumor necrosis factor-alpha (TNF-α) that promote vascular endothelial cells’ expansion and upregulation of adhesion molecules (ICAM-1 and VCAM-1, respectively) in the BM. However, the evaluation of mouse BMECs in the bone marrow microenvironment is scared by a lack of mouse bone marrow endothelial cell primary culture Methods Two steps approach for isolation of bone marrow endothelial cells (BMECs) from mice. In brief, the bone marrow cells extracted from the mice long bones were cultured overnight with Dulbecco’s modified Eagle’s medium (DMEM) supplemented with 20% fetal bovine serum (FBS) and antibiotics to separate between marrow-derived adherent and non-adherent cells. The floating cells were discarded, and the adhered section detached with accutase and BMECs selected using CD31 microbeads. The isolated BMECs were cultured in a dish pre-coated with rat-tail collagen type 1 with endothelial cells medium supplement with growth factors. The cells were verified by confocal microscopy for morphology and tube formation by matrigel assay. We validate the cells’ purity by flow cytometry, RT-qPCR, immunofluorescence staining, and immunoblotting by established BMEC markers, PECAM-1, VE-cadherin, vascular endothelial cell growth factor receptor-2 (VEGFR2), CD45, E-selectin, and endothelial selectin adhesion molecule (ESAM). Lastly, we characterize BMEC activation with recombinant TNF-α. Results Our method clearly defined the cells isolated have the characteristics of BMECs with the expression of CD31, VE-cadherin, E-selectin, VEGFR-2, and ESAM. The cells’ response to TNF-α indicates its inflammatory function by increasing proliferation and upregulation of adhesion molecules. Conclusions This study outline a simple new technique of isolating mouse BMEC primary culture and a suitable method to evaluate the function and dysregulation of BMEC in in vitro studies using mouse models.

• Apigenin might regulate the differentially altered protein (DEPs) while reducing inflammation in RA. • TNF-α activates the differential expression of pro-inflammatory cytokines, TTR, and RAGE via NF-kB pathway activation. • Anti-inflammatory effect of apigenin impedes TNF-α mediated dysregulation or expression associated with RA pathogenesis. Rheumatoid arthritis (RA) is a chronic inflammatory disease induced by TNF-α, which increases fibroblast-like synoviocytes inflammation, resulting in cartilage destruction. The current work sought to comprehend the pathophysiological importance of TNF-α stimulation on differential protein expression and their regulation by apigenin using in-vitro and in-vivo models of RA. The human RA synovial fibroblast cells were stimulated with or without TNF-α (10 ng/ml) and treated with 40 μM apigenin. In-silico, in-vitro and in-vivo studies were performed to confirm the pathophysiological significance of apigenin on pro-inflammatory cytokines and on differential expression of TTR and RAGE proteins. TNF-α induced inflammatory response in synoviocytes revealed higher levels of IL-6, IL-1β, and TNF-α cytokines and upregulated differential expression of TTR and RAGE. In-silico results demonstrated that apigenin has a binding affinity towards TNF-α, indicating its potential effect in the inflammatory process. Both in-vitro and in-vivo results obtained by Western Blot analysis suggested that apigenin reduced the level of p65 (p = 0.005), TTR (p = 0.002), and RAGE (p = 0.020). The findings of this study suggested that TNF-α promotes the differential expression of pro-inflammatory cytokines, TTR, and RAGE via NF-kB pathways activation. Anti-inflammatory effect of apigenin impedes TNF-α mediated dysregulation or expression associated with RA pathogenesis. [ABSTRACT FROM AUTHOR]

Background: This study explores the association of neutrophil-to-lymphocyte (NLR), monocyte-to-lymphocyte (MLR), and platelet-to-lymphocyte (PLR) ratios with the 3-month treatment response and persistence of tumor necrosis factor-alpha (TNF-α) blockers in patients with ankylosing spondylitis (AS). Methods: This retrospective cohort study investigated 279 AS patients who were newly initiated on TNF-α blockers between April 2004 and October 2019 and 171 sex- and age-matched healthy controls. Response to TNF-α blockers was defined as a reduction in the Bath AS Disease Activity Index of ≥50% or 20 mm, and persistence referred to the time interval from the initiation to discontinuation of TNF-α blockers. Results: Patients with AS had significantly increased NLR, MLR, and PLR ratios as compared to controls. The frequency of non-response at 3 months was 3.7%, and TNF-α blockers’ discontinuation occurred in 113 (40.5%) patients during the follow-up period. A high baseline NLR but not high baseline MLR and PLR showed an independently significant association with a higher risk of non-response at 3 months (OR = 12.3, p = 0.025) and non-persistence with TNF-α blockers (HR = 1.66, p = 0.01). Conclusions: NLR may be a potential marker for predicting the clinical response and persistence of TNF-α blockers in AS patients.

Neutrophils, the most abundant subset of leukocytes in the blood, play a pivotal role in host response against invading pathogens. However, in respiratory diseases, excessive infiltration and activation of neutrophils can lead to tissue damage. Tanimilast-international non-proprietary name of CHF6001—is a novel inhaled phosphodiesterase 4 (PDE4) inhibitor in advanced clinical development for the treatment of chronic obstructive pulmonary disease (COPD), a chronic inflammatory lung disease where neutrophilic inflammation plays a key pathological role. Human neutrophils from healthy donors were exposed to pro-inflammatory stimuli in the presence or absence of tanimilast and budesonide—a typical inhaled corticosteroid drug-to investigate the modulation of effector functions including adherence to endothelial cells, granule protein exocytosis, release of extracellular DNA traps, cytokine secretion, and cell survival. Tanimilast significantly decreased neutrophil-endothelium adhesion, degranulation, extracellular DNA traps casting, and cytokine secretion. In contrast, it promoted neutrophil survival by decreasing both spontaneous apoptosis and cell death in the presence of pro-survival factors. The present work suggests that tanimilast can alleviate the severe tissue damage caused by massive recruitment and activation of neutrophils in inflammatory diseases such as COPD. [ABSTRACT FROM AUTHOR]

Tuberculous granuloma formation is mediated by hypoxia-inducible factor 1 alpha (HIF-1α), and is essential for establishing latent tuberculosis infection (LTBI) and its progression to active tuberculosis (TB). Here, we investigated whether HIF-1α expression and adjacent mechanisms were associated with latent or active TB infection. Patients with active TB, individuals with LTBI, and healthy controls were recruited, and the expression of cytokine genes IL15, IL18, TNFA, IL6, HIF1A, and A20 in peripheral blood mononuclear cells (PBMCs) and serum vitamin D (25(OH)D3) levels were evaluated. Additionally, nuclear factor kappa B (NF-κB) and tumor necrosis factor-alpha (TNF-α) levels were analyzed in PBMC lysates and culture supernatants, respectively, after HIF-1α blockade with 2-methoxyestradiol. We observed that IL-15 expression was higher in individuals with LTBI than in patients with active TB, while IL-18 and TNF-α expression was similar between LTBI and TB groups. Additionally, serum 25(OH)D3 levels and expression of IL-6, HIF1A, and A20 were higher in patients with active TB than in individuals with LTBI. Moreover, PBMCs from individuals with LTBI showed decreased NF-κB phosphorylation and increased TNF-α production after HIF-1α blockade. Together, these results suggest that under hypoxic conditions, TNF-α production and NF-κB pathway downregulation are associated with the LTBI phenotype. [ABSTRACT FROM AUTHOR]

Neonatal sepsis is a prime cause of neonatal deaths across the globe. Presently, various medical tests and biodevices are available in neonatal care. These diagnosis platforms possess several limitations such as being highly expensive, time-consuming, or requiring skilled professionals for operation. These limitations can be overcome through biosensor development. This work discusses the assembling of an electrochemical sensing platform that is designed to detect the level of tumor necrosis factor-alpha (TNF-α). The sensing platform was moderated with nanomaterials molybdenum disulfide nanosheets (MoS2NSs) and silicon dioxide-modified iron oxide nanoparticles (Fe3O4@SiO2NPs). The integration of nanomaterials helps in accomplishing the improved characteristics of the biosensor in terms of conductivity, selectivity, and sensitivity. Further, the molecularly imprinted polymer (MIP) approach was incorporated for sensing the presence of TNF-α on the surface of the working electrode. The electrochemical response of the electrode was recorded at different conditions. A broad concentration range was selected to optimize the biosensor from 0.01 pM to 100 nM. The sensitivity of the biosensor was higher and it exhibits a lower detection limit (0.01 pM). [ABSTRACT FROM AUTHOR]

Inhibition of Tumor Necrosis Factor-alpha (TNF-alpha) represents a therapeutic approach towards the management or treatment of various inflammatory diseases like rheumatoid arthritis and cancer, but the current treatment regimen against this target in these diseases is the use of antibodies which may trigger an autoimmune response. This suggests a search for small-molecule inhibitors that could selectively inhibit the protein target. In the present study, fifty-five bioactive compounds of plant origin with already reported anti-inflammatory activities were screened for their affinity for TNF-alpha using a molecular docking strategy. We combined results from three different software packages (iGEMDOCK, MOE, & SAMSON) to come up with the best binders of the target. In addition, the resulting binders were subjected to in silico ADMET (Absorption, distribution, metabolism, excretion, and toxicity) and 100 ns molecular dynamics simulation to determine their drug-like properties and atomistic binding mechanisms respectively. Of the fifty-five evaluated bioactive compounds, Rutin, Schisantherin A, and Hesperidin performed well in the three software packages, with considerable ranking therewith. Interestingly, these compounds did not only interact with hotspot residues on TNF-alpha but also apparently balanced well on the knife-edge of pharmacokinetics and toxicity. More importantly, from the RMSD, RMSF, ROG, SASA, and hydrogen bond analysis, it was seen that Rutin, Schisantherin A, & Hesperidin exhibited stability in the active pocket of the protein. These results portend the three compounds as potent inhibitors of TNF-alpha that should be considered for further evaluation and drug development.

Background: As a disease characterized by chronic neutrophilic inflammation, various sputum biomarkers have been investigated in the association with the severity and prognosis of bronchiectasis. However, there is lack of data on the association between sputum interleukin-1beta (IL-1β), interleukin-8 (IL-8) and tumor necrosis factor-alpha (TNF-α) levels at clinical stable state and the clinical, spirometric and blood inflammatory parameters, as well as prognostic scores. The purpose of the study is to assess the association between sputum IL-1β, IL-8 and TNF-α levels at clinical stable state and various clinical and laboratory parameters in bronchiectasis., Methods: A prospective study was conducted in a major regional hospital and tertiary respiratory referral centre in Hong Kong, including 44 Chinese patients with bronchiectasis. The correlation between stable state sputum IL-1β, IL-8 and TNF-α levels with various clinical, laboratory and spirometric parameters in bronchiectasis, as well as FACED [forced expiratory volume in one second (FEV 1 ), age, chronic colonisation by Pseudomonas aeruginosa , radiological extension and dyspnoea]/E-FACED (FACED plus exacerbations) scores were assessed., Results: Baseline sputum IL-1β level was found to have significant moderate positive correlation with baseline blood high sensitivity C-reactive protein (hs-CRP) level with Pearson correlation coefficient (r) of 0.529 (P=0.001). Baseline sputum IL-8 level was found to have significant moderate positive correlation with baseline FACED and E-FACED score with r of 0.574 (P<0.001) and 0.539 (P<0.001) respectively. Baseline sputum TNF-α level was found to have significant moderate positive correlation with baseline FACED score with r of 0.520 (P<0.001)., Conclusions: Sputum IL-1β and, IL-8 and TNF-α levels were shown to have significant correlation with various clinical, laboratory and spirometry parameters in bronchiectasis, as well as more severe disease as measured by FACED and E-FACED scores., Competing Interests: Conflicts of Interest: All authors have completed the ICMJE uniform disclosure form (available at https://jtd.amegroups.com/article/view/10.21037/jtd-24-573/coif). W.C.K. reports that the study was supported by the Hong Kong College of Physicians Young Investigator Research Grant, Hong Kong College of Physicians. The other authors have no conflicts of interest to declare., (2024 Journal of Thoracic Disease. All rights reserved.)

Cinnamon and its bioactive ingredients such as cinnamaldehyde (CA), with broad pharmacological profiles, are important parts of daily diet in many cultures. Moreover, there are plenty motivating patents on efficacy of nutritional phytochemicals as novel anti-inflammatory drugs in patients with inflammatory bowel disease (IBD). This study intended to evaluate the effects of CA on inflammatory biomarkers in acetic acid-induced colitis rats. Colitis was induced in all animals, except in sham group, using acetic acid (4%). Following colitis induction, in 3 groups, CA was administrated orally at 2, 4 and 8 mg/kg/day for 2 days (once a day). Other groups were defined as the control (only treated with acetic acid), sham group (normal saline), and a standard group (Dexamethasone). To evaluate the inflammation sites, macroscopic and microscopic markers were assessed. Tissue concentrations of interleukin (IL)-6 and tumor necrosis factor-alpha (TNF)-α, were assessed by ELISA assay kits, while myeloperoxidase (MPO) was measured spectrophotometrically. The mRNA expression of toll like receptor (TLR)-4 in colon tissue was assessed by Real time-PCR. CA at 4 mg/kg/day and 8 mg/kg/day significantly improved microscopic and macroscopic manifestations of colitis tissues. TNF-α, MPO, and IL-6 levels were significantly lower in CA treated groups at all the concentrations tested (P < 0.001). CA at 4 and 8 mg/kg/day significantly downregulated the mucosal gene expression of TLR-4. CA attenuated experimental colitis by means of colitis symptoms, reduction in inflammation cytokines, decline of neutrophil infiltration, and suppression of TLR-4 expression in acetic acid-induced colitis. CA improved colitis in animal model through suppression of inflammatory parameters and downregulation of TLR-4 mRNA expression. [ABSTRACT FROM AUTHOR]

Triple-negative breast cancer (TNBC) is a heterogeneous subtype of breast cancer. Anti -PD-1/PD-L1 treatment for advanced TNBC is still limited to PD-L1-positive patients. Ataxia telangiectasia mutated (ATM) is a switch molecule for homologous recombination and repair. In this study, we found a significant negative correlation between ATM and PD-L1 in 4 TNBC clinical specimens by single-cell RNA sequencing (scRNA-seq), which was confirmed by immunochemical staining in 86 TNBC specimens. We then established ATM knockdown TNBC stable cell lines to perform in vitro studies and animal experiments, proving the negative regulation of PD-L1 by ATM via suppression of tumor necrosis factor-alpha (TNF-α), which was confirmed by cytokine array analysis of TNBC cell line and analysis of clinical specimens. We further found that ATM inhibits TNF-α via inactivating JNK/c-Jun by scRNA-seq, Western blot and luciferase reporter assays. Finally, we identified a negative correlation between changes in phospho-ATMS1981 and PD-L1 levels in TNBC post- and pre-neoadjuvant therapy. This study reveals a novel mechanism by which ATM negatively regulates PD-L1 by downregulating JNK/c-Jun/TNF-α in TNBC, shedding light on the wide application of immune checkpoint blockade therapy for treating multi-line-resistant TNBC. • A negative correlation between PD-L1and ATM expression in TNBC. • ATM negatively regulated PD-L1 expression through TNF-α. • ATM inhibits TNF-α by inactivating JNK/c-Jun signaling pathway. • ATM as a potential biomarker for diagnosis and prediction of immunotherapy. • The combination of ATM inhibitors and immunotherapy may benefit more patients with TNBC. [ABSTRACT FROM AUTHOR]

The neuroimmune mechanism underlying neuropathic pain has been extensively studied. Tumor necrosis factor-alpha (TNF-α), a key pro-inflammatory cytokine that drives cytokine storm and stimulates a cascade of other cytokines in pain-related pathways, induces and modulates neuropathic pain by facilitating peripheral (primary afferents) and central (spinal cord) sensitization. Functionally, TNF-α controls the balance between cell survival and death by inducing an inflammatory response and two programmed cell death mechanisms (apoptosis and necroptosis). Necroptosis, a novel form of programmed cell death, is receiving increasing attraction and may trigger neuroinflammation to promote neuropathic pain. Chronic pain is often accompanied by adverse pain-associated emotional reactions and cognitive disorders. Overproduction of TNF-α in supraspinal structures such as the anterior cingulate cortex (ACC) and hippocampus plays an important role in pain-associated emotional disorders and memory deficits and also participates in the modulation of pain transduction. At present, studies reporting on the role of the TNF-α–necroptosis pathway in pain-related disorders are lacking. This review indicates the important research prospects of this pathway in pain modulation based on its role in anxiety, depression and memory deficits associated with other neurodegenerative diseases. In addition, we have summarized studies related to the underlying mechanisms of neuropathic pain mediated by TNF-α and discussed the role of the TNF-α–necroptosis pathway in detail, which may represent an avenue for future therapeutic intervention.

Background: In the bone marrow microenvironment (BM), endothelial cells are individual cells that form part of the sinusoidal blood vessels called the "bone marrow endothelial-vascular niche." They account for less than 2% of the bone marrow cells. They play essential functions by generating growth and inhibitory factors that promote the hematopoietic stem cells (HSCs) regulation. In response to inflammatory stimuli, the BMECs increase in proliferation to maintain the blood vessels' integrity within the BM. The inflammatory response releases cytokines such as tumor necrosis factor-alpha (TNF-α) that promote vascular endothelial cells' expansion and upregulation of adhesion molecules (ICAM-1 and VCAM-1, respectively) in the BM. However, the evaluation of mouse BMECs in the bone marrow microenvironment is scared by a lack of mouse bone marrow endothelial cell primary culture Methods: Two steps approach for isolation of bone marrow endothelial cells (BMECs) from mice. In brief, the bone marrow cells extracted from the mice long bones were cultured overnight with Dulbecco's modified Eagle's medium (DMEM) supplemented with 20% fetal bovine serum (FBS) and antibiotics to separate between marrow-derived adherent and non-adherent cells. The floating cells were discarded, and the adhered section detached with accutase and BMECs selected using CD31 microbeads. The isolated BMECs were cultured in a dish pre-coated with rat-tail collagen type 1 with endothelial cells medium supplement with growth factors. The cells were verified by confocal microscopy for morphology and tube formation by matrigel assay. We validate the cells' purity by flow cytometry, RT-qPCR, immunofluorescence staining, and immunoblotting by established BMEC markers, PECAM-1, VE-cadherin, vascular endothelial cell growth factor receptor-2 (VEGFR2), CD45, E-selectin, and endothelial selectin adhesion molecule (ESAM). Lastly, we characterize BMEC activation with recombinant TNF-α. Results: Our method clearly defined the cells isolated have the characteristics of BMECs with the expression of CD31, VE-cadherin, E-selectin, VEGFR-2, and ESAM. The cells' response to TNF-α indicates its inflammatory function by increasing proliferation and upregulation of adhesion molecules. Conclusions: This study outline a simple new technique of isolating mouse BMEC primary culture and a suitable method to evaluate the function and dysregulation of BMEC in in vitro studies using mouse models. [ABSTRACT FROM AUTHOR]

Copyright of Baghdad Science Journal is the property of Republic of Iraq Ministry of Higher Education & Scientific Research (MOHESR) and its content may not be copied or emailed to multiple sites or posted to a listserv without the copyright holder's express written permission. However, users may print, download, or email articles for individual use. This abstract may be abridged. No warranty is given about the accuracy of the copy. Users should refer to the original published version of the material for the full abstract. (Copyright applies to all Abstracts.)

Neutrophils, the most abundant subset of leukocytes in the blood, play a pivotal role in host response against invading pathogens. However, in respiratory diseases, excessive infiltration and activation of neutrophils can lead to tissue damage. Tanimilast-international non-proprietary name of CHF6001—is a novel inhaled phosphodiesterase 4 (PDE4) inhibitor in advanced clinical development for the treatment of chronic obstructive pulmonary disease (COPD), a chronic inflammatory lung disease where neutrophilic inflammation plays a key pathological role. Human neutrophils from healthy donors were exposed to pro-inflammatory stimuli in the presence or absence of tanimilast and budesonide—a typical inhaled corticosteroid drug-to investigate the modulation of effector functions including adherence to endothelial cells, granule protein exocytosis, release of extracellular DNA traps, cytokine secretion, and cell survival. Tanimilast significantly decreased neutrophil-endothelium adhesion, degranulation, extracellular DNA traps casting, and cytokine secretion. In contrast, it promoted neutrophil survival by decreasing both spontaneous apoptosis and cell death in the presence of pro-survival factors. The present work suggests that tanimilast can alleviate the severe tissue damage caused by massive recruitment and activation of neutrophils in inflammatory diseases such as COPD.

Tuberculous granuloma formation is mediated by hypoxia-inducible factor 1 alpha (HIF-1α), and is essential for establishing latent tuberculosis infection (LTBI) and its progression to active tuberculosis (TB). Here, we investigated whether HIF-1α expression and adjacent mechanisms were associated with latent or active TB infection. Patients with active TB, individuals with LTBI, and healthy controls were recruited, and the expression of cytokine genes IL15, IL18, TNFA, IL6, HIF1A, and A20 in peripheral blood mononuclear cells (PBMCs) and serum vitamin D (25(OH)D3) levels were evaluated. Additionally, nuclear factor kappa B (NF-κB) and tumor necrosis factor-alpha (TNF-α) levels were analyzed in PBMC lysates and culture supernatants, respectively, after HIF-1α blockade with 2-methoxyestradiol. We observed that IL-15 expression was higher in individuals with LTBI than in patients with active TB, while IL-18 and TNF-α expression was similar between LTBI and TB groups. Additionally, serum 25(OH)D3 levels and expression of IL-6, HIF1A, and A20 were higher in patients with active TB than in individuals with LTBI. Moreover, PBMCs from individuals with LTBI showed decreased NF-κB phosphorylation and increased TNF-α production after HIF-1α blockade. Together, these results suggest that under hypoxic conditions, TNF-α production and NF-κB pathway downregulation are associated with the LTBI phenotype.

Status epilepticus (SE) is a life‐threatening neurologic disorder that can be as both cause and consequence of neuroinflammation. In addition to previous reports on anti‐inflammatory property of the anti‐migraine medication sumatriptan, we have recently shown its anticonvulsive effects on pentylenetetrazole‐induced seizure in mice. In the present study, we investigated further (i) the effects of sumatriptan in the lithium–pilocarpine SE model in rats, and (ii) the possible involvement of nitric oxide (NO), 5‐hydroxytryptamin 1B/1D (5‐HT1B/1D) receptor, and inflammatory pathways in such effects of sumatriptan. Status epilepticus was induced by lithium chloride (127 mg/kg, i.p) and pilocarpine (60 mg/kg, i.p.) in Wistar rats. While SE induction increased SE scores and mortality rate, sumatriptan (0.001‐1 mg/kg, i.p.) improved it (P < 0.001). Administration of the selective 5‐HT1B/1D antagonist GR‐127935 (0.01 mg/kg, i.p.) reversed the anticonvulsive effects of sumatriptan (0.01 mg/kg, i.p.). Although both tumor necrosis factor‐α (TNF‐α) and NO levels were markedly elevated in the rats' brain tissues post‐SE induction, pre‐treatment with sumatriptan significantly reduced both TNF‐α (P < 0.05) and NO (P < 0.001) levels. Combined GR‐127935 and sumatriptan treatment inhibited these anti‐inflammatory effects of sumatriptan, whereas combined non‐specific NOS (L‐NAME) or selective neuronal NOS (7‐nitroindazole) inhibitors and sumatriptan further reduced NO levels. In conclusion, sumatriptan exerted a protective effect against the clinical manifestations and mortality rate of SE in rats which is possibly through targeting 5‐HT1B/1D receptors, neuroinflammation, and nitrergic transmission. [ABSTRACT FROM AUTHOR]

The aim of this study is to assess the toxicity of some heavy metals and parasitic infection in fishes as well as the immunological status of these fishes infected with different parasites. Between January 2018 and January 2019, 360 Nile tilapia (Oreochromis niloticus) near four farms and in the Nile River in Giza were examined for external and internal parasites. In addition, samples were expressed for two genes using quantitative real-time polymerase chain reaction. Samples were also taken from muscles and water for toxicological analysis of different heavy metals. In the skin, the mean TNF-α levels in the monogenea and mixed protozoan parasites (Trichodina and Myxobolus spp.) were 18.00 ± 0.67 and 13.65 ± 0.54, respectively. In the gills, the mean TNF-α of monogenea, Centrocestus formosanus, and encysted metacercaria (EMC) with monogenea group means was 20.45 ± 0.74, 23.00 ± 0.74, and 25.78 ± 0.74, respectively. In muscles with EMC, the mean TNF-α level was 14.67 ± 0.70. In livers with EMC, the mean TNF-α level was 26.78 ± 0.70. In the skin, the mean IL-1β level in monogenea and protozoan parasites (Trichodina and Myxobolus spp.) was significantly different (25.00 ± 0.69 and 15.00 ± 0.43, respectively). In the gills, the mean IL-1β level of the monogenean group was 21.00 ± 0.79, whereas C. formosanus showed the significantly highest value (27.00 ± 0.74). The mean IL-1β level of EMC with the monogenea group was 24.00 ± 1.54. Results showed that the level of Zn, Pb, Cu, and Cd was the highest in tissues of fish than permissible limits (PLs). Histopathological examination of different examined tissues exhibited serious pathological alterations. Monogenetic trematodes were detected in the examined fish, and their presence was accompanied by hyperplasia and fusion of the secondary gill lamellae. EMC of digenetic trematodes was frequently observed in the gills and in the cartilage rod. In conclusion, the parasite infection can upregulate the immunological cytokines with different levels with different infections. [ABSTRACT FROM AUTHOR]

Insulin resistance in gestational diabetes increases maternal and fetal complications. Tumor necrosis factor-alpha (TNF-α) is an inflammatory factor associated with insulin resistance. The aim of this study was to determine the association between pregnancy serum TNF-α level and postpartum insulin resistance in patients with gestational diabetes mellitus. 50 pregnant women, including 25 cases of gestational diabetes and 25 healthy pregnant women, were evaluated. First, during the third trimester of pregnancy, serum TNF-α level of all cases were measured. Two months after delivery, based on the obtained results from insulin levels and a 2-hour glucose tolerance test, HOMA-IR and HOMA-B were calculated, and the association between serum TNF-α level and insulin resistance was determined. Data were analyzed using independent t-test, Mann-Whitney, and chi-square test in SPSS software. The mean serum level of TNF-α in women with gestational diabetes mellitus was higher than healthy subjects, but there was no significant difference between the two groups. The serum level of insulin, HOMA-IR and HOMA-B indices in women with gestational diabetes mellitus were higher than healthy subjects, with a significant difference in all of the measures between two groups (P=0.0001). There was no significant correlation between TNF-α and HOMA-IR levels in insulin-resistant mothers two months after delivery (r=−0.33). Also, no significant correlation was detected between pregnancy TNF-α levels and HOMA-B index. Despite the higher serum levels of insulin, HOMA-IR, and HOMA-B in the diabetic group, the serum TNF-α level did not show any correlation with insulin resistance after delivery.

Abstract Background Polycystic ovary syndrome (PCOS) is the main cause of female infertility. Interactions among genetic, biochemical, and immunological factors can affect the pathogenesis of PCOS. As a proinflammatory cytokine, tumor necrosis factor-α (TNF-α) plays an important role in this regard. The present study aimed to evaluate the association of the rs361525 gene single-nucleotide polymorphism (SNP) and TNF-α serum levels with the hormonal and biochemical characteristics of PCOS in Iranian individuals. Methods The SNP rs361525 in the TNF-α gene was analyzed by polymerase chain reaction–restriction fragment length polymorphism (PCR-RFLP) in a total of 111 PCOS patients and 105 healthy females. Serum levels of TNF-α, lipid and hormone profiles, and biochemical factors were measured using enzyme-linked immunosorbent assay (ELISA) and calorimetric methods, as appropriate. Results The TNF-α serum level was higher in women with PCOS compared with the control group (p 0.05). Higher levels and significant differences were found for the HOMA factor, luteinizing hormone/follicle-stimulating hormone (LH/FSH), testosterone, and body mass index (BMI) in the PCOS group compared with the control group (p