Serum TNF-α Research Articles

Dietary glycerides of valerate ameliorate diarrhea and impact intestinal physiology and serum biomarkers in weaned piglets infected with enterotoxigenic Escherichia coli F18.

In the commercial swine farm setting, the post-weaning period is a critical window during which piglets are highly susceptible to infection and enterotoxigenic E. coli (ETEC)-associated diarrhea. Short chain fatty acids and their glycerides are compounds which may influence intestinal health; however, valerate is one that has not been well-characterized for its role as a dietary supplement. Therefore, the major objective of this experiment was to investigate two forms of valerate glycerides on diarrhea, intestinal physiology, and systemic immunity of weaned pigs experimentally infected with ETEC F18. Dietary treatments included a control diet and three additional diets supplemented with 0.075% monovalerin, 0.1% monovalerin, or 0.1% trivalerin, respectively. Piglets were weaned (21-24 d of age), individually housed, and experimental diets were fed throught the 28-day trial period. After a seven-day period, all piglets were inoculated on three consecutive days with 1010 CFU ETEC F18/3mL. Growth performance was monitored throughout the trial and daily diarrhea scores were recorded. Rectal swabs were collected for bacterial culture to confirm the presence or absence of β-hemolytic coliforms throughout the trial. Serum samples were collected and analyzed for inflammatory biomarkers on d 0, 3, 6, and 21 post-inoculation (PI) and untargeted metabolomics on d 6 PI. Intestinal mucosa and tissue sections were harvested from pigs sacrificed on d 7 PI for gene expression and histology analysis. All data, except for frequency of diarrhea and metabolomics, were analyzed by ANOVA using the PROC MIXED of SAS. Dietary trivalerin reduced (P < 0.05) the frequency of severe diarrhea over the entire trial period and the frequency of β-hemolytic coliforms on d 7 PI compared with control. The intestinal villus height on d 7 PI in jejunum tissue was increased (P < 0.05) in pigs fed trivalerin. The mRNA expression of TNF-α was decreased (P < 0.05) in the trivalerin group, while that of ZO1 was increased (P < 0.05) compared with control. Throughout the trial, serum TNF-α was reduced in pigs fed trivalerin compared with control. Serum metabolites, adenosine, inosine, and shikimic acid were reduced (P < 0.05) on d 6 PI in all treatment groups compared with control. In conclusion, the present results indicate supplementing dietary valerate glycerides exhibited beneficial impacts on diarrhea, inflammation, and intestinal gene expression of piglets during the post-weaning period.

Follicle-stimulating hormone induces depression-like phenotype by affecting synaptic function.

Depression is one of the most common affective disorders in people's life. Women are susceptibility to depression during puberty, peripartum and menopause transition, when they are suffering from sex hormone fluctuation. A lot of studies have demonstrated the neuroprotective effect of estrogen on depression in women, however, the effect of FSH on depression is unclear. In this study, we investigated the role of FSH on depression in mice. Our study demonstrated that FSH induced depression-like behaviors in mice in a dose-dependent manner. This induction was associated with elevated levels of pro-inflammatory cytokines, including IL-1β, IL-6, and TNF-α in both serum and hippocampal tissues. Additionally, FSH treatment resulted in impaired synaptic plasticity and a reduction in the expression of key synaptic proteins. It is noteworthy that the depression-like behaviors, inflammatory cytokines expression and synaptic plasticity impairment induced by FSH could be alleviated by knocking down the expression of FSH receptor (FSHR) in the hippocampus of the mice. Therefore, our findings reveal that FSH may play an important role in the pathogenesis of depression and targeting FSH may be a potential therapeutic strategy for depression during hormone fluctuation in women.

Contemporaneous Inflammatory, Angiogenic, Fibrogenic, and Angiostatic Cytokine Profiles of the Time-to-Tumor Development by Cancer Cells to Orchestrate Tumor Neovascularization, Progression, and Metastasis.

Cytokines can promote various cancer processes, such as angiogenesis, epithelial to mesenchymal transition (EMT), invasion, and tumor progression, and maintain cancer stem-cell-like (CSCs) cells. The mechanism(s) that continuously promote(s) tumors to progress in the TME still need(s) to be investigated. The data in the present study analyzed the inflammatory, angiogenic, fibrogenic, and angiostatic cytokine profiles in the host serum during tumor development in a mouse model of human pancreatic cancer. Pancreatic MiaPaCa-2-eGFP cancer cells were subcutaneously implanted in RAG2xCγ double mutant mice. Blood samples were collected before cancer cell implantation and every week until the end point of the study. The extracted serum from the blood of each mouse at different time points during tumor development was analyzed using a Bio-Plex microarray analysis and a Bio-Plex 200 system for proinflammatory (IL-1β, IL-10, IFN-γ, and TNF-α) and angiogenic and fibrogenic (IL-15, IL-18, basic FGF, LIF, M-CSF, MIG, MIP-2, PDGF-BB, and VEGF) cytokines. Here, we find that during cancer cell colonization for tumor development, host angiogenic, fibrogenic, and proinflammatory cytokine profiling in the tumor-bearing mice has been shown to significantly reduce host angiostatic and proinflammatory cytokines that restrain tumor development and increase those for tumor growth. The proinflammatory cytokines IL-15, IL-18, and IL-1β profiles reveal a significant host serum increase after day 35 when the tumor began to progress in growth. In contrast, the angiostatic cytokine profiles of TNFα, MIG, M-CSF, IL-10, and IFNγ in the host serum revealed a dramatic and significant decrease after day 5 post-implantation of cancer cells. OP treatment of tumor-bearing mice on day 35 maintained high levels of angiostatic and fibrogenic cytokines. The data suggest an entirely new regulation by cancer cells for tumor development. The findings identify for the first time how pancreatic cancer cells use host cytokine profiling to orchestrate the initiation of tumor development.

Anti-arthritic activity of Trayodashang guggulu, a classical Ayurvedic formulation against complete Freund’s adjuvant-induced rheumatoid arthritis in rats

BackgroundRheumatoid arthritis is a chronic autoimmune disease affecting millions of people across the world. Trayodashang guggulu (TG) is a classical Ayurvedic formulation used for the treating joint diseases since decades in the Indian system of traditional medicine. The aim of the study was to evaluate anti-arthritic activity of TG against complete Freund’s adjuvant-induced arthritis in Wistar rats.MethodsArthritis was induced by single injection of 0.1 ml complete Freund’s adjuvant into the intraplanter surface of left hind paw of Wistar rats. TG was administered orally at the doses of 100, 200, 400 and 800 mg/kg body weight for 14 days. In the preventive dose group, TG was administered at the dose of 100 mg/kg body weight, orally for 28 days. Paw swelling, joint circumference, serum rheumatoid factor, C-reactive protein, serum IL-1β, TNF-α and histopathological parameters were assessed for the evaluation of arthritis. Effects of TG were compared with standard allopathic drug ibuprofen.ResultsTG reversed complete Freund’s adjuvant-induced arthritis in rats when used for 14 and 28 days. Serum rheumatoid factor, C-reactive protein, IL-1β and TNF-α were decreased in rats treated with both standard drug ibuprofen and TG.ConclusionOral administration of TG reduced experimentally induced rheumatoid arthritis in rats by reversing elevated level of serum biochemical markers as well as reducing joint destruction similar to ibuprofen. Results obtained from the study paved the way in exploring more specific mechanisms of action of TG involving in vitro and in silico models.

Effects of 6-week olanzapine treatment on serum IL-2, IL-4, IL-8, IL-10, and TNF-α levels in drug-naive individuals with first-episode schizophrenia

BackgroundSchizophrenia is a complex neuropsychiatric disorder. Growing evidence indicates that the activation of the inflammatory response system with interleukin (IL)-2, IL-4, IL-8, IL-10, and tumor necrosis factor-alpha (TNF-α) plays an important role in the pathogenesis of schizophrenia,. However, clinical data on cytokine levels in patients with schizophrenia treated with antipsychotics are inconsistent or inconclusive. In this study, we have examined inflammatory factors’ alterations and their relationship to changes in clinical symptoms before and after olanzapine treatment of drug-naive patients with first-episode schizophrenia.MethodsWe recruited 142 hospitalized patients with first-episode schizophrenia as a study group; blood samples were collected, and the patients were assessed for clinical symptoms at baseline and after 6 weeks of olanzapine treatment. One hundred individuals with no history of mental illness were also recruited as healthy controls. Blood samples were collected, and the serum levels of IL-2, IL-4, IL-8, IL-10, and TNF-α were determined using an enzyme cycling assay. The severity of clinical symptoms was assessed according to the Positive and Negative Syndrome Scale (PANSS).ResultsIndividuals with schizophrenia had lower IL-8 levels and higher IL-10 levels than healthy controls (P < 0.001). Positive correlations were detected between serum IL-2 and IL-10 concentrations and each subscale of the PANSS (all P < 0.05). Moreover, a negative correlation existed between the serum IL-8 concentration and the PANSS negative score (r = − 0.172, P = 0.040). After 6 weeks of treatment, serum IL-8 levels in the patient group were lower than at baseline (P < 0.001), whereas serum IL-10 and TNF-α levels were higher than at baseline (all P < 0.05). Therefore, serum IL-10 can be determined as an independent risk factor for outcome in patients with first-episode schizophrenia (P = 0.02, OR = 2.327). Furthermore, serum IL-2, IL-10, and TNF-α levels were significantly lower, whereas the serum IL-8 level was significantly higher (P < 0.001) in the healthy control group than in the “response” and “no-response” treatment groups respectively.ConclusionsOur results indicate that serum IL-2, IL-8, IL-10, and TNF-α levels may be involved in the pathophysiological mechanisms of schizophrenia and correlate with the effects of olanzapine.

Chronic kidney disease amplifies severe kidney injury and mortality in a mouse model of skin arsenical exposure.

In previously published work, we elucidated the role of cutaneous arsenical exposure in promoting acute kidney injury (AKI) in adult healthy mice. Here, we determine whether pre-existing chronic kidney disease (CKD) increases the severity of AKI. Following exposure to aristolochic acid (AA) (a nephrotoxic phytochemical in humans), mice manifested classical markers of CKD, including robust interstitial fibrosis and loss in kidney function. Skin challenge with phenylarsine oxide (PAO), a surrogate for warfare arsenicals, led to significantly worse kidney injury, as evidenced by tubulointerstitial fibrosis, glomerulosclerosis, a persistent loss of estimated glomerular filtration rate and mortality in AA-induced CKD mice compared to mice without CKD. These PAO-challenged CKD mice exhibited enhanced production of serum/urine NGAL, and a significant rise in serum creatinine along with histological markers of kidney injury, including brush border loss, tubular atrophy, cast formation, glomerular injury, and interstitial inflammatory cell infiltration. Serum cytokines IL-4, IL-6, IFN-γ, IL-12p70, TNF-α, and IL-18 significantly elevated in CKD mice following PAO exposure when compared to animals exposed to PAO alone. Furthermore, we found increased TUNEL-positive tubular cells in the kidneys of CKD mice following PAO exposure, suggesting enhanced PAO-mediated cell death in CKD mice. Mechanistically, we determined that DNA damage-regulated p53 signaling was a major mediator of cellular responses to PAO in CKD mice. In summary, our data demonstrate that CKD significantly increased severity of AKI following exposure to arsenicals and suggest that human populations with preexisting CKD could be highly susceptible to arsenical-mediated kidney injury and associated morbidity and mortality.

Association Between Elevated Serum Histidine Decarboxylase and Tumor Necrosis Factor-Alpha Levels and High Risk in tic Disorder Children

Background: Children with tic disorder (TD) have been reported to exhibit abnormal levels of certain peripheral proteins, but none of these abnormalities have been established as biomarkers for diagnosis. Objectives: The purpose of this study is to evaluate serum histidine decarboxylase (HDC) and tumor necrosis factor-alpha (TNF-α) levels in children with TD, assess their relationship with TD development, and provide reliable biomarkers for prediction and risk management in clinical settings. Methods: In the present study, serum HDC and TNF-α levels from 118 no-comorbid and medication-naive TD patients and 111 age-matched healthy controls were measured using enzyme-linked immunosorbent assay (ELISA) kits. Tic severity was assessed using the Yale Global Tic Severity Scale (YGTSS). Binary logistic regression analysis was used to evaluate the relationship between serum HDC and TNF-α levels and TD development. Results: An increase in serum HDC and TNF-α levels was observed in TD patients compared with controls. Further analysis revealed a significant association between elevated HDC and TNF-α levels and TD development, with a significant ROC curve for HDC and TNF-α as potential risk factors. Conclusions: This study identified a high prevalence of elevated serum HDC and TNF-α levels in children with TDs and provides evidence that elevated blood HDC and TNF-α may be potential risk factors for TD development.

TLR2 and NLRP3 Orchestrate Regulatory Roles in Escherichia coli Infection-Induced Septicemia in Mouse Models

Introduction: Escherichia coli (E. coli) is a significant commensal gram-negative bacterium that can give rise to various diseases. The roles of Toll-like receptor 2 (TLR2) and the NOD-like receptor pyrin domain-containing protein 3 (NLRP3) inflammasome in sepsis induced by E. coli infection remain unclear. Methods: In vivo, we investigated differences in mortality, production of inflammatory mediators, organ damage, neutrophil count, and bacterial load during E. coli infection in C57BL/6J mice, as well as in mice deficient in TLR2 or NLRP3. In vitro, we investigated the impact of E. coli on the activation of TLR2 and NLRP3 in macrophages and the influence of TLR2 and NLRP3 on the activation of inflammatory signaling pathways and the secretion of inflammatory mediators in macrophages induced by E. coli infection. Results: TLR2-deficient (TLR2−/−) and NLRP3-deficient (NLRP3−/−) mice exhibit significantly increased mortality and organ damage after E. coli infection. These mice also show elevated levels of TNF-α and IL-10 in serum and peritoneal lavage fluid. Additionally, TLR2−/− and NLRP3−/− mice display heightened neutrophil recruitment and increased bacterial load in the blood. Furthermore, macrophages from these mice demonstrate a significant reduction in the activation of the MAPK signaling pathway. Conclusion: TLR2 and NLRP3 play crucial roles in modulating inflammatory mediator expression, immune cell recruitment, and bactericidal activity, thereby preventing excessive tissue damage and reducing mortality in E. coli-induced sepsis.

Therapeutic Potential of Methanolic Stem Extract of Costus afer on Serum Uric Acid, Tumor Necrosis Factor-alpha (TNF-α), and Interleukin-6 (IL-6) Levels in Monosodium Urate (MSU)-Induced Gouty Arthritis in Wistar Rats

The therapeutic potential of methanolic stem extracts of Costus afer was investigated to evaluate their effects on serum uric acid, TNF-α, and IL-6 levels, which are the key biomarkers associated with inflammatory and metabolic disorders like gouty arthritis. Qualitative and quantitative phytochemical analysis of C. afer indicated the presence of flavonoids, alkaloids, phenol, anthraquinone and glycosides, these bioactive compounds have been implicated for numerous medicinal uses and as such the therapeutic potentials of the extract were investigated by administering varying doses (100 mg/kg, 200 mg/kg, and 400 mg/kg) of the extract to a Wistar rat model with induced gouty arthritis and assessing its impact compared to a control group and an untreated MSU group. The results revealed that the extracts significantly reduced ( serum uric acid levels in a dose-dependent manner, with the high dose achieving a reduction below the control level. Additionally, the extracts effectively decreased ( TNF-α and IL-6 levels, indicating potent anti-inflammatory properties. The high dose exhibited the most substantial reduction in these biomarkers, underscoring the extract’s therapeutic potential. These findings support the traditional use of C. afer and provide scientific validation for its application in managing hyperuricemia and inflammatory conditions.

Metabolic effects of quercetin on inflammatory and autoimmune responses in rheumatoid arthritis are mediated through the inhibition of JAK1/STAT3/HIF-1α signaling

BackgroundRheumatoid arthritis, a chronic autoimmune disease, is characterized by synovial hyperplasia and cartilage erosion. Here, we investigated the potential mechanism of action of quercetin, the main component of flavonoids, in treating rheumatoid arthritis.ObjectTo examine the anti-arthritic effects of quercetin and elucidate the specific mechanisms that differentiate its metabolic effects on autoimmune and inflammatory responses at the synovial cell level.MethodsWe created a collagen-induced arthritis (CIA) model in Wistar rats, which were administered quercetin (50 or 100 mg/kg) continuously for four weeks via stomach perfusion. The arthritis score, histopathological staining, radiological assessment, and serum biochemical parameters were used to study the impact of quercetin on disease improvement. Additionally, immunofluorescence was employed to detect JAK1/STAT3/HIF-1α expression in rat joints. Moreover, the effects of quercetin (20, 40, and 80 µmol/L) on the properties and behavior of synovial fibroblasts were evaluated in an in vitro MH7A cell model using flow cytometry, CCK8, and transwell assays. Further, the mRNA expression levels of inflammatory cytokines IL1β, IL6, IL17, and TNFα were assessed by quantitative real-time PCR. Glucose, lactate, lactate dehydrogenase, pyruvate, pyruvate dehydrogenase, and adenosine triphosphate assay kits were employed to measure the metabolic effects of quercetin on synovial fibroblasts. Finally, immunoblotting was used to examine the impact of quercetin on the JAK1/STAT3/HIF-1α signaling pathway in synovial fibroblasts.ResultsIn vivo experiments confirmed the favorable effects of quercetin in CIA rats, including an improved arthritis score and reduced ankle bone destruction, in addition to a decrease in the pro-inflammatory cytokines IL-1β, IL-6, IL-17, and TNF-α in serum. Immunofluorescence verified that quercetin may ameliorate joint injury in rats with CIA by inhibiting JAK1/STAT3/HIF-1α signaling. Various in vitro experiments demonstrated that quercetin effectively inhibits IL-6-induced proliferation of MH7A cells and reduces their migratory and invasive behavior, while inducing apoptosis and reducing the expression of the pro-inflammatory cytokines IL1β, IL6, IL17, and TNFα at the mRNA level. Quercetin caused inhibition of glucose, lactate, lactate dehydrogenase, pyruvate, and adenosine triphosphate and increased pyruvate dehydrogenase expression in MH7A cells. It was further confirmed that quercetin may inhibit energy metabolism and inflammatory factor secretion in MH7A cells through JAK1/STAT3/HIF-1α signaling.ConclusionsQuercetin’s action on multiple target molecules and pathways makes it a promising treatment for cartilage injury in rheumatoid arthritis. By reducing joint inflammation, improving joint metabolic homeostasis, and decreasing immune system activation energy, quercetin inhibits the JAK1/STAT3/HIF-1α signaling pathway to improve disease status.

Platelet-rich plasma ameliorates cartilage degradation in rat models of osteoarthritis via the OPG/RANKL/RANK system.

Osteoarthritis (OA) is one of the most common degenerative joint diseases in the elderly, which is featured by the degradation of articular cartilage. Recently, platelet-rich plasma (PRP) injection into the affected joint has become one biological therapy for OA treatment. The OPG/RANKL/ RANK signalling has been reported to mediate OA progression. Our study aimed to confirm whether PRP injection retards OA development through the regulation of the OPG/RANKL/RANK system. The OA rat models were induced by medial menisci resection combined with anterior cruciate ligament transection. Four weeks after surgery, OA-induced rats received intra- articular injection with 50 μL PRP once a week for 6 weeks. Rats were euthanised one week after the 6th injection. Rat knee joints were subjected to histopathological examination by haematoxylin- eosin (H&E) and safranin O staining. Osteoprotegerin (OPG), receptor activator of nuclear factor kappa B (RANK), and RANK ligand (RANKL) in the articular cartilage of rats were tested through immunofluorescence staining and western blotting. Serum interleukin-1β (IL-1β) and interleukin-6 (IL-6) levels were measured by enzyme-linked immunosorbent assay (ELISA). Matrix metalloproteinase- 13 (MMP-13), aggrecan, collagen α, IL-1β, IL-6, tumour necrosis factor-alpha (TNF-α), and nuclear factor kappa-B (NF-κB) mRNA and protein expression in rat articular cartilage were examined by real-time quantitative polymerase chain reaction (RT-qPCR) and western blotting, respectively. Intra-articular injections of PRP significantly improved the structural integrity of the articular cartilage and enhanced the synthesis of glycosaminoglycans. PRP reduced MMP-13 protein level but increased aggrecan and collagen α protein levels in articular cartilage of OA rats. OA-induced increase in serum IL-1β, IL-6, and TNF-α concentrations as well as increased MMP-13, and decreased collagen II mRNA levels were reversed by the administration of PRP. OA increased IL-1β, TNF-α, and NF-κB mRNA expression in rat articular cartilage whereas PRP administration ameliorated these changes. Moreover, in the articular tissue of OA-induced rats the increased OPG protein level was further elevated by PRP injections whereas the protein level of RANK did not change. The increase in the protein level of RANKL in OA-induced articular tissue was offset by PRP administration. PRP elevated OPG mRNA expression and the OPG/RANKL mRNA ratio, but reduced RANKL mRNA expression and the RANKL/RANK mRNA ratio in the articular tissue of OA-induced rats. PRP mitigates cartilage degradation and inflammation in experimental knee OA by regulating the OPG/RANKL/RANK signalling system.

Increased serum phenylalanine/tyrosine ratio associated with the psychiatric symptom of anti-NMDAR encephalitis.

Encephalitis associated with antibodies against the N-methyl-D-aspartate receptor (NMDAR) results in a distinctive neuro-psychiatric syndrome. It has been reported that the serum phenylalanine-tyrosine (Phe/Tyr) ratio increases during infection. However, the connection between phenylalanine-tyrosine metabolism and psychiatric symptoms remains unclear. We enrolled 24 individuals with anti-NMDAR encephalitis and 18 individuals with non-inflammatory neurological diseases (OND). Chromatography was used to measure serum levels of phenylalanine and tyrosine. Serum and cerebrospinal fluid (CSF) TNF-α levels were obtained from the clinical database. The modified Rankin Scale (mRS) score and Glasgow Coma Scale (GCS) score were recorded during the acute phase. The area under the curve (AUC) of the receiver operating characteristic curve was used to assess prediction efficacy. In NMDAR patients, levels of serum Phe and the ratio of serum Phe/Tyr were higher compared to OND patients. The serum Phe/Tyr ratio was also elevated in NMDAR patients with psychiatric syndrome. Furthermore, serum Phe and Tyr levels were correlated with inflammatory indexes. The serum Phe/Tyr ratio is elevated in NMDAR patients with psychiatric syndrome and is associated with severity. Therefore, the serum Phe/Tyr ratio may serve as a potential prognostic biomarker.

Lactobacillus rhamnosus ameliorates experimental autoimmune neuritis via modulation of gut microbiota and metabolites

BackgroundGuillain-Barre syndrome (GBS), an autoimmune disease of the peripheral nervous system, is hallmarked by demyelination and immune cellular infiltration. Experimental autoimmune neuritis (EAN), considered a GBS prototype model, has been studied for its potential therapeutic benefits from lactobacilli. This study evaluated the protective role of Lactobacillus rhamnosus GG (GG) for treatment in EAN. T cell ratio, inflammation factors, sciatic nerve pathology, intestinal permeability, and gut inflammation were assessed on day 19 post-immunization to evaluate GG's effect on EAN. Fecal metabolomics and 16s rRNA microbiome analysis were conducted to elucidate its mechanism. ResultsGG dynamically balanced CD4+/CD8+T cell ratio, reduced serum IL-1β and TNF-α expression, improved sciatic nerve demyelination and inflammation, and enhanced neurological scores during peak disease period. Intestinal mucosal damage was evident in EAN rats, with downregulated Occludin and ZO-1 and upregulated IL-1β, TNF-α, and Reg3γ. GG treatment restored intestinal mucosal integrity, upregulated Occludin and ZO-1, and downregulated IL-1, TNF-α, and Reg3γ. GG partially rectified the gut microbiota and metabolite imbalance in EAN rats. ConclusionGG mitigates EAN through immune response modulation and inflammation reduction via the gut microbiota and metabolites.

Oral Administration of Lactiplantibacillus plantarum CCFM8661 Alleviates Dichlorvos-Induced Toxicity in Mice

Dichlorvos (DDVP) is an organophosphorus pesticide commonly used in agriculture for pest control, which may enter the organism from the food chain and cause harm. This study aimed to investigate the mitigation effect of Lactiplantibacillus plantarum CCFM8661 (a strain of the bacteria) on DDVP toxicity. Sixty male mice were randomly divided into five groups including control (saline), model (DDVP), low-dose, medium-dose, and high-dose groups, and alleviating effect was evaluated by determining body weight, pesticide residues, oxidative stress, and inflammation, and by histological analysis. The results showed that compared with the model group, body weight and acetylcholinesterase activity, and SOD, CAT, T-AOC, and GSH levels significantly increased, and serum DDVP content, MDA level, IL-1β, and TNF-α significantly decreased after administration of the L. plantarum CCFM8661. The study demonstrated that L. plantarum CCFM8661 exhibited a significant detoxification effect on pesticide toxicity in mice, providing a theoretical basis for the application of probiotics in mitigating pesticide-induced damage.

Antioxidant and immunomodulatory activities of ethanol extracts from Syzygium cumini L. Skeels and Pogostemon cablin Benth

Syzygium cumini and Pogostemon cablin are mostly cultivated in tropical climates for culinary and perfumery purposes, yet their potential medicinal properties remain underreported. The aim of this study was to examine the antioxidant and immunomodulatory activities of ethanol extracts from S. cumini (EESC) and P. cablin (EEPC). Reflux extraction was carried out using 96% ethanol on the collected plant specimens to produce EESC and EEPC. Secondary metabolites of each extract were identified using gas chromatography-mass spectrometry (GC-MS). The extracts were measured for total phenol and flavonoid levels and 2,2-diphenyl-1-picrylhydrazyl (DPPH) scavenging activity. The immunomodulatory activity test was carried out in vivo by assessing several parameters, including the phagocytic index via the carbon clearance method, organ indices, antibody titers, and delayed-type hypersensitivity (DTH) response, using sheep red blood cells (SRBC) as antigens. The extracts were also examined for their anti-inflammatory activity in acute and chronic inflammation models. In the DPPH antioxidant test, EESC and EEPC had IC50 values of 12.33 µg/mL and 182.17 µg/mL, respectively. Both extracts showed immunosuppressant activity, marked by a phagocytic index of &lt;1. EESC yielded lower organ indices for the liver (p=0.025 at 200 mg/kg BW), spleen (p=0.028 at 100 mg/kg BW), and thymus (p=0.032 at 200 mg/kg BW) compared to the control group. For EEPC, lower organ indices were observed in the liver at 100 mg/kg BW (p=0.005) and 200 mg/kg BW (p=0.031). In the primary antibody titer and DTH tests, both EESC and EEPC showed immunosuppressant activity at 200 and 400 mg/kg BW (p&lt;0.05). The extracts suppressed both the innate and adaptive immune systems. Both EEPC (p=0.004) and EESC at 100 mg/kg BW (p=0.03) significantly reduced serum TNF-α levels. In conclusion, EESC and EEPC have the potential as immunosuppressive and anti-inflammatory agents.

Evaluation of the level of tumor necrosis factor-alpha and lactate dehydrogenase in acute lymphoblastic leukemia patients

Abstract: BACKGROUND: Acute lymphoblastic leukemia (ALL) is an abnormal clonal proliferation of early hemopoietic precursor cells in bone marrow (BM). There are certain cytokines like tumor necrosis factor alpha ( TNF-α) which plays a crucial role in the development and progression of malignant process, and other enzymes like lactate dehydrogenase (LDH) which has prognostic value. OBJECTIVE: The aims of this study were to evaluate the level of serum TNF-α and LDH in ALL patients at diagnosis and post-induction chemotherapy. PATIENTS, MATERIALS, AND METHODS: This was an observational–analytical study, which was done in Ibn-Sina Teaching Hospital in the period between May 2023 and November 2023. It included 22 newly diagnosed patients with ALL. All patients underwent complete blood count, bone marrow examination, flowcytometry, serum TNF-α and LDH at diagnosis and post induction chemotherapy. RESULTS: In 22 patients with ALL, at diagnosis, the means of serum TNF-α (97.89 ± 52.945 ng/l), serum lactate dehydrogenase(1138.94 ± 430.10 IU/l), and percentage of blasts cells in BM (0.742 ± 0.181) in B-ALL. The means of serum TNF-α (165.33 ± 23.437 ng/l), serum lactate dehydrogenase (1633.33 ± 497.426 iu/l), and percentage of blasts cells in BM (0.816 ± 0.125) in T-ALL were statistically higher than those among the controls (s.TNF-a (18.09 ± 6.795 ng/l), s.LDH (142.59 ± 61.626 IU/l), and percentage of blasts cells in BM 0.0 ± 0.0) with P = 0.000 for all parameters mentioned, respectively. After induction phase chemotherapy in B-cell ALL , there were a significant reduction noted for serum TNF-α (29.26 ± 18.648 ng/l) and LDH levels (245.47 ± 154.592 IU/l) and a significant decrease in the percentage of blasts cells (0.07 ± 0.060).also in T-cell ALL there were a significant reduction noted for serum TNF-a (26.00 ± 11.135 ng/l) serum LDH (347.66 ± 160.300 IU/l) and percentage of blasts cells in bone marrow (0.06 ± 0.046). All of the postchemotherapy acute leukemia cases with lower TNF-α levels had complete remission (100%). CONCLUSIONS: There were significant increases in serum TNF-α and LDH in ALL patients at diagnosis; while after induction, there was a significant reduction in their levels. Complete remission from the disease was associated with lower levels of serum TNF-α in newly diagnosed patients.

Adiponectin and Inflammatory Marker Levels in the Elderly Patients with Diabetes, Mild Cognitive Impairment and Depressive Symptoms.

Some studies suggest that low-grade inflammation and adipokines may be involved in mild cognitive impairment (MCI) and depression in subjects with type 2 diabetes; however, the available data concerning the elderly population are limited. Therefore, we conducted novel research to determine the serum adiponectin, hs-CRP and TNF-α levels in elderly diabetic patients with MCI and depressive symptoms and to identify the factors associated with MCI in this group. A total of 178 diabetic patients (mean age 84.4 ± 3.4 years) were screened for MCI and depressive symptoms. Various biochemical and biomarker data were collected. We found that patients with MCI and depressive symptoms demonstrated lower adiponectin levels and high hs-CRP and TNF-α. In this group, adiponectin concentration was negatively correlated with hs-CRP, TNF-α, HbA1c, and GDS-30 scores and positively correlated with MoCA scores. Multivariable analysis found the risk of MCI to be associated with higher TNF-α levels, fewer years of formal education, an increased number of comorbidities, and the presence of CVD. We concluded that low-grade inflammation and the presence of adipokines are associated with MCI and depressive symptoms in elderly diabetics. Further research should evaluate the suitability of Hs-CRP, TNF-α, and adiponectin as diagnostic markers for MCI and potential therapeutic targets.

Evaluation of the effect of pentoxifylline on the prevention of paclitaxel‑induced peripheral neuropathy in breast cancer patients: a randomized controlled study

BackgroundPaclitaxel-induced peripheral neuropathy (PIPN) is one of the most common and debilitating toxicity. Up till now, no treatment or preventive medication is recommended by guidelines. Pentoxifylline has been found to prevent PIPN in animal models. This study aimed to evaluate the tolerability and efficacy of pentoxifylline in preventing PIPN. To our knowledge, this is the first clinical trial to evaluate the potential effect of pentoxifylline on the prevention of PIPN in breast cancer (BC) patients.ResultsA simple-randomized placebo-controlled study was conducted on 60 BC patients receiving weekly paclitaxel and either pentoxifylline 400 mg twice daily (n = 30) or placebo (n = 30) for 12 weeks. Only 55 patients completed the study. The main objective was the evaluation of the effect of pentoxifylline on the incidence of PIPN which revealed no significant difference between the pentoxifylline group (85%) and the placebo group (100%). Secondary objectives included time to develop grade 2 or 3 (TTG 2/3) PIPN, the patient’s quality of life (QOL), serum tumor necrosis factor-α (TNF-α) and malondialdehyde and the tolerability of pentoxifylline. The median TTG 2/3 PIPN was not reached in the pentoxifylline group compared to 77 days (95% confidence interval of 70.91 to 83.07) in the placebo group. However, the difference did not reach significance. The assessment of the impact of PIPN on QOL was performed at baseline and at weeks 4, 8 and 12 using Functional Assessment of Cancer Therapy/Gynecologic Oncology Group-Neurotoxicity (FACT/GOG-NTX) subscale. The magnitude of the worsening in the QOL was significantly lower in the pentoxifylline group than in the placebo group at weeks 4, 8, and 12 (p values = 0.028, 0.003, and 0.018, respectively). Analysis of the serum TNF-α and malondialdehyde revealed no significant differences between the groups. Pentoxifylline was safe, tolerable and did not affect paclitaxel toxicity.ConclusionOral pentoxifylline (400 mg twice daily) did not decrease the incidence of PIPN. However, it improved patients’ QOL significantly.Trial registration Clinical Trials.gov, NCT05189535. Registered 4 October 2021, https://classic.clinicaltrials.gov/ct2/show/NCT05189535.

Dietary Bacteriophage Administration Alleviates Enterotoxigenic Escherichia coli-Induced Diarrhea and Intestinal Impairment through Regulating Intestinal Inflammation and Gut Microbiota in a Newly Weaned Mouse Model

This study aimed to investigate the effects of dietary bacteriophage administration on diarrhea and intestinal impairment induced by enterotoxigenic Escherichia coli (ETEC) in a newly weaned mouse model. Forty-four newly weaned C57BL/6 mice were divided into four treatment groups, where they were provided either the control diet or the bacteriophage-supplemented diet, with or without ETEC infection. The results show that the bacteriophage administration resulted in increased body weight, decreased diarrhea score, and improved jejunal histopathology in ETEC-infected mice. The bacteriophage administration enhanced the intestinal barrier function of the ETEC-infected mice, as indicated by the reduced serum DAO level and the increased expression of Claudin-1, Occludin, and ZO-1 at both the mRNA and protein levels in the jejunum. Also, the bacteriophage administration resulted in a decrease in serum TNF-α and IL-1β levels, a down-regulation of TNF-α and IL-6 mRNA levels in the jejunum, and the inhibition of jejunal TLR-4/NF-κB pathway activation induced by ETEC infection. Moreover, the bacteriophage administration increased the levels of acetic acid, propionic acid, butyric acid, and total short-chain fatty acids in the caecum content. The bacteriophage administration increased the Shannon index, increased the abundance of Bacteroidota and Muribaculaceae, and decreased the abundance of Verrucomicrobiota and Akkermansiaceae in the colon contents of the ETEC-infected mice. Spearman’s correlation analysis indicates that the protective effects of bacteriophage on ETEC-induced intestinal impairment, inflammation, and intestinal barrier function are associated with regulating the abundance of Bacteroidota and Muribaculaceae in the colon contents of mice. Collectively, bacteriophage administration alleviates ETEC-induced diarrhea and intestinal impairment through regulating intestinal inflammation and gut microbiota in newly weaned mice.

Chemerin, TNF − α and the degree of albuminuria in patients with diabetic kidney disease

BackgroundChronic inflammation has been increasingly recognized as an essential pathogenic mechanism for the development and progression of diabetic kidney disease (DKD). Chemerin is an adipokine which has been suggested to be related to inflammation and has been correlated with the development of diabetic complications. We aimed to explore the potential links between chemerin, TNF – α, as a marker of systemic inflammation, and the level of albuminuria in patients with type 2 diabetes mellitus (T2DM). MethodThe study included 84 patients with T2DM and 10 normoalbuminuric non-diabetic controls. Demographic, clinical and laboratory data including chemerin and TNF-α levels were collected. ResultsA total of 84 diabetic patients were enrolled, 32 males (38.1 %), with mean age 57.9 ± 10.7 years. They were divided into 3 groups: A1: 14 with normalbuminuria, A2: 27 with microalbuminuria, and A3: 43 with macroalbuminuria (uACR < 30, 30–300 and > 300 mg/gm respectively). Chemerin and TNF-α levels increased with the progress of albuminuria (control: 21.3 (14.7 –77), A1: 794 (683–925), A2: 1150 (962.9 – 1221.5) and A3: 1466 (1197.5 – 2002.5) ng/ml; p < 0.001) and (control: 77.9 (59 – 96.8), A1: 85.2 (71–116.3), A2: 87.3 (81 – 97.5) and A3: 99 (85.1 – 142.5) pg/ml; p = 0.009) respectively. Among the diabetics, a significant association was evident between serum chemerin and serum TNF-α (r = 0.53; p < 0.001). On linear stepwise regression analysis, chemerin was significantly associated with TNF-α and HbA1c (unstandardized β 10.881 and 272.68 respectively, p < 0.001); and TNF-α was significantly correlated with chemerin, uACR (unstandardized β 0.059 and 0.004 respectively, p < 0.001) and HbA1c (unstandardized β −13.699, p = 0.014). ConclusionOur findings suggest a potential role of chemerin and TNF-α in the development and progression of DKD, and thus support the role of the inflammatory pathway. Larger follow up studies are warranted to further explore the potential links between chemerin, inflammation and DKD.