Serum Levels Of Tumor Necrosis Factor-alpha Research Articles

Glycitein prevents reserpine-induced depression and associated comorbidities in mice: modulation of lipid peroxidation and TNF-α levels.

Depression is a debilitating mood disorder affecting millions worldwide and continues to pose a significant global health burden. Due to the multifaceted nature of depression, the current treatment regimens are not up to mark in terms of their multitargeting potential and least side effect profile. Molecules within the isoflavone class demonstrate promising potential in alleviating depression and associated conditions, offering a multifaceted approach to manage mental health concerns. Therefore, the current study was designed to explore the potential of glycitein, an isoflavone in managing reserpine-induced depression and associated comorbidities in mice. Reserpine (0.5mg/kg; i.p.) administration for the first 3days induced depression and associated comorbidities as evidenced by increased immobility time in forced swim test (FST) and tail suspension test (TST), along with reduced locomotor activity in the open field test (OFT) and increased latency to reach the platform in the Morris water maze (MWM) test. Reserpine treatment also upregulated and downregulated the brain thiobarbituric acid reactive substance (TBARS) and glutathione (GSH) levels, respectively. Furthermore, reserpine administration also uplifted the level of TNF-α in the serum samples. Glycitein (3mg/kg and 6mg/kg; p.o.) treatment for 5days prevented the depressive effect of reserpine. It also improved the spatial memory at both dose levels. Moreover, in biochemical analysis, glycitein also reduced the brain TBARS and serum tumor necrosis factor-alpha (TNF-α) levels. Whereas, no significant effect was seen on the brain GSH level. Glycitein (6mg/kg) was found to be more effective than the 3mg/kg dose of glycitein. Overall results delineate that glycitein has the potential to manage depression and impaired memory by inhibiting lipid peroxidation and inflammatory stress.

Integrated microbiome and metabolomics revealed the protective effect of baicalin on alveolar bone inflammatory resorption in aging

BackgroundWith the growing aging population and longer life expectancy, periodontitis and tooth loss have become major health concerns. The gut microbiota, as a key regulator in bone homeostasis, has gathered immense interest. Baicalin, a flavonoid compound extracted from Scutellaria baicalensis Georgi, has shown antioxidant and anti-inflammatory activities. PurposeThis study investigated, for the first time, the protective mechanism of baicalin against alveolar bone inflammatory resorption in aging mice by regulating intestinal flora and metabolites, as well as intestinal barrier function. MethodsA ligature-induced periodontitis model was established in d-galactose (D-gal)-induced aging mice, and baicalin was administered at different dosages for 13 weeks. Body weight was measured weekly. The antioxidant and anti-inflammatory activity of baicalin were evaluated using serum superoxide dismutase (SOD), malonaldehyde (MDA), interleukin-6 (IL-6), and tumor necrosis factor-alpha (TNF-α) levels. The immune capability was assessed by thymus and spleen indices. Histopathological changes were observed in the heart, liver, ileum, and periodontal tissues. Alveolar bone absorption of maxillary second molars was examined, and osteoclasts were counted by tartrate-resistant acid phosphatase (TRAP) staining. Furthermore, fecal samples were analyzed using 16S rRNA sequencing and non-targeted metabolomics to identify differences in intestinal bacterial composition and metabolites. ResultsBaicalin exhibited anti-aging properties, as evidenced by increased SOD activity and decreased levels of MDA, IL-6, and TNF-α in serum compared to the control group. Baicalin also ameliorated alveolar bone loss in the d-gal-induced aging-periodontitis group (p < 0.05). Furthermore, baicalin restored ileal permeability by up-regulating the expression of ZO-1 and occludin in aging-periodontitis groups (p < 0.05). Alpha diversity analysis indicated that baicalin-treated mice harbored a higher diversity of gut microbe. PCoA and ANOSIM results revealed significant dissimilarity between groups. The Firmicutes/Bacteroidetes (F/B) ratio, which decreased in periodontitis mice, was restored by baicalin treatment. Additionally, medium-dosage baicalin promoted the production of beneficial flavonoids, and enriched short-chain fatty acids (SCFAs)-producing bacteria. ConclusionIntestinal homeostasis is a potential avenue for treating age-related alveolar bone loss. Baicalin exerts anti-inflammatory, antioxidant, and osteo-protective properties by regulating the gut microbiota and metabolites.

Investigation into actions of Xiebai and Zengye decoction on cough sensitivity, airway inflammation and gut microbiota in the rat model of post-infectious cough

This work was undertaken to observe therapeutic effect of Xiebai and Zengye (XBZY) decoction on post-infectious cough (PIC) in rats, as well as its effect on gut microbiota and the exploration of the intestinal microecological mechanisms of XBZY decoction in the treatment of PIC. Using a random number table, the rats that were successfully modelled were assigned to the PIC, XBZY group (14.8 g/kg/d), and montelukast sodium treatment (MAS) group (1 mg/kg/d). The cough sensitivity of rats and changes in fecal water content were assessed, and serum interleukin-8 (IL-8) and tumor necrosis factor-alpha (TNF-α) levels were determined by ELISA. The histopathological changes in the bronchus and colon tissues were observed under the microscope after hematoxylin-eosin staining. Short-chain fatty acids (SCFAs) in fecal samples were measured by gas chromatography, and changes in gut microbiota were observed using 16S rRNA sequencing. The PIC rats showed decreased fecal water content, increased cough sensitivity, elevated serum TNF-α and IL-8 levels, and higher bronchitis scores comparing to normal control group. The PIC rats showed reductions in SCFAs and significant changes in the structure of gut microbiota. XBZY decoction intervention led to increased fecal water content in rats, reduced cough sensitivity, decreased serum IL-8 and TNF-α levels, decreased bronchitis scores, and alleviated inflammatory cell infiltration was observed in the colonic mucosa. Additionally, elevated SCFAs levels were observed in the PIC rats. XBZY decoction intervention improved alpha-/beta-diversity, and corrected microbiota imbalance in PIC rats. SCFAs, TNF-α and IL-8, acetic acid was revealed to be positively associated with Allobaculum but inversely correlated with unclassified_f_Oscillospiraceae; propanoic acid was positively associated with Lactobacilli but negatively associated with Romboutsia; butanoic acid exhibited positive correlations with Akkermansia and Lactobacilli, but negative correlations with unclassified_f_Oscillospiraceae, Eubacterium_xylanophilum_group, and Lachnospiraceae_NK4A136_group; Additionally, TNF-α was inversely linked to Allobaculum, while IL-8 was positively related to Romboutsia and Turicibacter. In conclusion, XBZY decoction significantly reduced cough sensitivity and airway inflammation in PIC rats while ameliorating stool dryness and colonic inflammation. The protective effects of XBZY decoction could be linked to modulat gut microbiota in PIC rats, and regulat SCFAs contents in PIC rats, while the regulator mechanisms of XBZY decoction in gut microbiota still requires further in-depth investigation.

Association of Tumor Necrosis Factor-Alpha with Psychopathology in Patients with Schizophrenia.

We investigated the relationship between serum tumor necrosis factor-alpha (TNF-α) levels and psychopathological symptoms, clinical and socio-demographic characteristics and antipsychotic therapy in individuals with schizophrenia. TNF-α levels were measured in 90 patients with schizophrenia and 90 healthy controls matched by age, gender, smoking status, and body mass index. The Positive and Negative Syndrome Scale (PANSS) was used to assess the severity of psychopathology in patients. No significant differences in TNF-α levels were detected between the patients and controls (p=0.736). TNF-α levels were not correlated with total, positive, negative, general, or composite PANSS scores (all p>0.05). A significant negative correlation was observed between TNF-α levels and the PANSS cognitive factor (ρ=-0.222, p=0.035). A hierarchical regression analysis identified the cognitive factor as a significant predictor of the TNF-α level (beta=-0.258, t=-2.257, p=0.027). There were no significant differences in TNF-α levels among patients treated with different types of antipsychotics (p=0.596). TNF-α levels correlated positively with the age of onset (ρ=0.233, p=0.027) and negatively with illness duration (ρ=-0.247, p=0.019) and antipsychotic treatment duration (ρ=-0.256, p=0.015). These results indicate that TNF-α may be involved in cognitive impairment in schizophrenia, and would be a potential clinical-state marker in schizophrenia.

Uric acid is independently associated with interleukin‐1β levels in tear fluid of hyperuricemia and gout patients

To explore pro-inflammatory cytokines status in the tear fluid of patients with hyperuricemia and gout and its association with uric acid level. A total of 58 control subjects, 58 hyperuricemia patients including 40 asymptomatic hyperuricemia and 18 gout participants were recruited in this study. For tear analysis, each patient's tears were collected using capillary action microcaps after stimulation. Tear uric acid levels were measured using chemiluminescence. Tear and serum interleukin-1beta (IL-1β) and tumor necrosis factor-alpha (TNF-α) levels were measured using enzyme-linked immunosorbent assay. The correlation of serum and tear uric acid levels with IL-1β and TNF-α were determined. Tear uric acid levels were significantly higher in hyperuricemia group (98.2 ± 51.5vs. 42.7 ± 24.0 µmol/L, p < .001) than in controls group. IL-1β concentrations were significantly higher in hyperuricemia eyes compared to control eyes (210.2 ± 113.9vs. 142.6 ± 29.8 pg/mL, p < .001). Multiple linear regression analysis showed that tear uric acid levels were independently positively associated with tear IL-1β concentrations (B = 0.192, p < .001). However, no significant correlations were found between serum or tear uric acid and TNF-α level. Moreover, there were no statistically differences of tear IL-1β and TNF-α levels between the asymptomatic hyperuricemia and gout groups. Tear uric acid levels were higher in patients with hyperuricemia and gout than in controls. There was a significant positive correlation between tear uric acid value and tear IL-1β level, implying an interaction between hyperuricemia and ocular inflammation responses.

Correlation Between Serum Tumor Necrosis Factor-Alpha (TNF-α) and Clinical Severity of Tuberculosis: A Hospital-Based Study.

The main aim of this study was to assess the correlation between serum tumor necrosis factor-alpha (TNF-α) levels the and clinical severity of tuberculosis. This was a hospital-based case-control prospective study and was conducted at the Sher-i-Kashmir Institute of Medical Sciences, a tertiary care hospital in the northern part of India, from May 2016 to May 2018. The subjects were recruited in the study considering inclusion and exclusion criteria. All patients with pulmonary tuberculosis as well as patients with extrapulmonary tuberculosis were included as subjects and a clinical severity score based on anemia, weight loss, presence of hypoxia, and radiological features was calculated and compared with TNF-α levels. Age- and sex-matched healthy individuals were recruited as controls. A total of 75 subjects comprising 50 cases and 25 controls were taken for the study. There were 34 (68.0%) patients with elevated TNF-α levels while only 16 (32.0%) patients had normal TNF-α levels. And, TNF-α levels were normal in 21 (84%) control subjects as compared to tuberculosis (TB) patients. Such difference in serum TNF-α levels between cases and controls was statistically significant (p<0.05). The mean serum TNF-α level in TB cases was 1265.63 pg/mL, while the mean serum TNF-α level in controls was 312.06 pg/mL. The difference in serum TNF-α levels between the two groups was statistically significant (p<0.01). We observed a significant increase in serum TNF-α levels with the increase in clinical severity score. Serum TNF-α levels were significantly associated with increased severity of TB.

The Effects of Methotrexate and Biologics on the Symptoms of Depression and Anxiety in Patients with Psoriasis.

In patients with psoriasis, psychiatric co-morbidities accompany quite frequently. We aimed to compare the effects of methotrexate and biologics on psychiatric comorbidities, and also examine the relationship of these symptoms with systemic inflammation parameters. Sixty patients with psoriasis treated with biologics or methotrexate were enrolled. At the baseline and the 24th week of the treatment, the patients filled Beck Anxiety Inventory (BAI), Beck Depression Inventory (BDI), and Dermatology Life Quality Index (DLQI), inflammation was assessed with serum C-reactive protein (CRP) and tumour necrosis factor-alpha (TNF-α) levels. The decrease in BAI and BDI scores at the 24th week was significant in both the groups. When the decrease in BAI and BDI scores of the two groups were compared, no significant differences were found between the groups. The decrease in DLQI scores of the patients who received biologics was significantly superior compared to the patients who received methotrexate (P = 0.007). There was no significant correlation between the change in serum inflammation parameters and the decrease in the BDI/BAI scores. In patients with psoriasis, biologics and methotrexate reduce the symptoms of depression and anxiety. The difference between the two groups was insignificant. Biologics improve the quality of life better than methotrexate. Systemic inflammation parameters do not reflect the changes in these symptoms in such patients.

Pharmacological Mechanism of Pingxiao Formula against Colorectal Cancer.

Colorectal cancer (CRC) is the most common cancer worldwide and develops due to a broad range of causative factors. Pingxiao (PX) formula and Xihuang (XH) formula are two commonly used drugs to treat CRC, especially as an alternative therapy for those patients who could not suffer surgery, chemotherapy, or immunotherapy, namely, elder or advanced CRC patients. However, the pertinent pharmacological mechanisms are still elusive. The investigation was designed to explain the pharmacological mechanisms of the PX formula. A murine model of CRC was established by injecting CT26.WT cells into the caecum of 4-week-old male Balb/c mice, following PX or XH treatment for 30 days. Network pharmacology analysis combined with weighted gene coexpression network analysis (WGCNA) predicted the pharmacological mechanisms and therapeutic value. High-throughput 16S rRNA sequencing determined the alterations in the gut microbiota communities. Western blotting, immunofluorescence, and flow cytometry examined the influence of PX on the tumor microenvironment (TME). Injection of CT26.WT-induced CRC in Balb/c mice was markedly attenuated by PX treatment. Compared with XH administration, PX exhibited a stronger antitumor effect, such as smaller tumor volume, lower interleukin 17 (IL-17), IL-6 and tumor necrosis factor-alpha (TNFα) serum levels, and higher interferon-gamma (IFN-γ) concentration. Network pharmacology analysis demonstrated that both PX and XH targets were enriched in cancers and inflammatory responses. RNA sequencing confirmed that PX treatment induced cancer cell apoptosis and inhibited inflammatory reactions within the tumor. Moreover, the PX formula considerably restored homeostasis of the gut microbiota, which was not observed in the XH group. PX targets, those associated with the survival probability of CRC patients, correlated with macrophage (Mφ) infiltration, which presented an independent risk factor for the CRC outcome. PX treatment promoted the transition of alternatively activated Mφs (M2 Mφs) to classically activated Mφs (M1 Mφs). Moreover, the peritoneal Mφs from the PX group inhibited the migration of CW26.WT cells, as evidenced by the wound healing experiment and transwell assay, which was consistent with the decreased expression of the vascular endothelial growth factor (VEGF). Furthermore, the coculturing system confirmed that PX-treated Mφs suppressed colorectal tumor-derived organoid proliferation. PX formula exhibits a potential antitumor effect against CRC by suppressing the colonization of pathological microorganisms, reshaping Mφ effector functions and hence inhibiting cancer cell proliferation.

Association of Serum Apelin levels with Peripheral Neuropathy in Type-2 Diabetes Mellitus

Objectives: To determine serum levels of Apelin in healthy individuals, type-2 diabetic patients and diabetic peripheral neuropathy patients (DPN) and to find the correlation with serum Apelin levels and serum fasting blood glucose, glycosylated hemoglobin.&#x0D; Study Design: Cross-sectional analytical study.&#x0D; Place and Duration of Study: Physiology Department and Centre for Research in Experimental and Analytical Medicine (CREAM) lab of the Army Medical College/National University of Medical Sciences (NUMS) Rawalpindi Pakistan, from Jan to Dec 2021.&#x0D; Methodology: A total of 90 individuals comprising three Groups having 30 subjects in each were recruited. Group-I included thirty healthy subjects, and Group-II consisted of thirty newly diagnosed patients having T2DM, Group-III consisted of thirty T2DM patients with DPN. We used Michigan Neuropathy Screening Instrument (MNSI) to assess neuropathy. Serum Apelin and tumour necrosis factor-alpha (TNF-alpha) levels were recorded from the blood samples of all subjects by enzyme-linked immunosorbent assay (ELISA) using human serum Apelin and TNF-alpha ELISA kit catalogue no. E2014Hu (bio-assay technology) and E0082Hu (Bio-assay technology), respectively.&#x0D; Results: The mean values of serum Apelin were higher in Group-III compared to Group-II and Group-I, and a statisticallysignificant difference was found (p value=0.001). The serum Apelin levels showed a strong negative correlation with Group-III serum FBG, HbA1c and TNF-alpha with r value -0.728, -0.79, and -0.95, respectively.&#x0D; Conclusion: Serum Apelin has a beneficial role in DPN in T2DM, with reduced TNF-alpha levels as one of the possible mechanisms.Keywords: Apelin, Diabetic peripheral neuropathy, TNF-alpha, Type-2 diabetes mellitus.

Effect of acute omega 3 supplementation reduces serum tumor necrosis factor-alpha (TNF-a) levels, pain intensity, and maintains muscle strength after high-intensity weight training

This study aims to analyze the acute effect of omega 3 supplementation on serum TNF-α levels, pain intensity, and muscle strength after high-intensity weight training. A total of 20 adult males with a BMI of 18.00-24.99 were enrolled in this study. Subjects were divided into 2 groups, namely (K1) with placebo and (K2) with omega 3 supplementation with a dose of 1000 mg (540 mg EPA and 360 mg DHA). The intervention was carried out 24 hours after high-intensity weight training. The data in this study were taken before and after the intervention. Measurement of serum TNF-α levels using a human ELISA kit, measurement of pain intensity using visual analog scale (VAS), measuring muscle strength using a leg dynamometer. The data analysis technique is used if the data is normally distributed, namely Paired t-test and Independent t-test, if the data has not normally distributed the analysis used is the Wilcoxon signed-rank test. Omega 3 supplementation significantly reduced serum TNF-α levels (p-0.035), significantly reduced pain levels (p-0.007), and did not significantly decrease the strength (p-0.100). Omega 3 supplementations can reduce serum TNF-α levels, pain intensity, and omega 3 supplementations can maintain muscle strength after high-intensity weight training as evidenced by the absence of a significant decrease in muscle strength after high-intensity weight training.

A multi-strain probiotic blend reshaped obesity-related gut dysbiosis and improved lipid metabolism in obese children.

Background and aimsObese children are more prone to becoming obese adults, and excess adiposity consequently increases the risk of many complications, such as metabolic syndromes, non-alcoholic fatty liver disease, cardiovascular disease, etc. This study aimed to evaluate the effects of multi-strain probiotics on the gut microbiota and weight control in obese children.MethodsA double-blind, randomized, placebo-controlled trial was carried out on overweight and obese children. Subjects received 12 weeks of treatment with supplementary probiotics that contained three strains: Lactobacillus salivarius AP-32, L. rhamnosus bv-77, and Bifidobacterium animalis CP-9, plus diet and exercise guidance. A total of 82 children were enrolled, and 53 children completed the study.ResultsThe supplementation of multi-strain probiotics resulted in a significant effect demonstrating high-density lipoprotein (HDL) and adiponectin elevation. At the same time, body mass index (BMI) and serum total cholesterol, low-density lipoprotein (LDL), leptin, and tumor necrosis factor-alpha (TNF-α) levels were reduced. Lactobacillus spp. and B. animalis were particularly increased in subjects who received probiotic supplements. The abundance of Lactobacillus spp. was inversely correlated with the ether lipid metabolism pathway, while that of B. animalis was positively correlated with serum adiponectin levels.ConclusionOur results show that obesity-related gut dysbiosis can be reshaped by the supplementation of a multi-strain probiotic to improve lipid metabolism. The regular administration of a multi-strain probiotic supplement may be helpful for weight control and health management in overweight and obese children.

Red Rice Bran Extract Attenuates Adipogenesis and Inflammation on White Adipose Tissues in High-Fat Diet-Induced Obese Mice.

Red rice bran extract (RRBE) has been reported to have the potential for in vitro metabolic modulation and anti-inflammatory properties. However, little is known about the molecular mechanisms of these potentials in adipose tissue. This study aimed to evaluate the in vivo anti-adipogenic, anti-hypertrophic, and anti-inflammatory activities of RRBE and its major bioactive compounds in mice. After six weeks of consuming either a low-fat diet or a high-fat diet (HFD), 32 mice with initial body weights of 20.76 ± 0.24 g were randomly divided into four groups; the four groups were fed a low-fat diet, a HFD, a HFD plus 0.5 g/kg of RRBE, or a HFD plus 1 g/kg of RRBE, respectively. The 6-week treatment using RRBE reduced HFD-induced adipocyte hypertrophy, lipid accumulation, and inflammation in intra-abdominal epididymal white adipose tissue (p < 0.05) without causing significant changes in body and adipose tissue weight, which reductions were accompanied by the down-regulated expression of adipogenic and lipid metabolism genes, including CCAAT/enhancer-binding protein-alpha, sterol regulatory element-binding protein-1c, and hormone-sensitive lipase (p < 0.05), as well as inflammatory genes, including macrophage marker F4/80, nuclear factor-kappa B p65, monocyte chemoattractant protein-1, tumor necrosis factor-alpha, and inducible nitric oxide synthase (p < 0.05), in adipose tissue. Furthermore, RRBE significantly decreased serum tumor necrosis factor-alpha levels (p < 0.05). Bioactive compound analyses revealed the presence of phenolics, flavonoids, anthocyanins, and proanthocyanidins in these extracts. Collectively, this study demonstrates that RRBE effectively attenuates HFD-induced pathological adipose tissue remodeling by suppressing adipogenesis, lipid dysmetabolism, and inflammation. Therefore, RRBE may emerge as one of the alternative food products to be used against obesity-associated adipose tissue dysfunction.

Serum Tumor Necrosis Factor-Alpha Levels in Acute Leukemia and Its Prognostic Significance.

IntroductionTumor necrosis factor-alpha (TNF-α) is a pleiotropic cytokine that facilitates malignant cells in immune evasion, survival, and treatment resistance by generating a favorable milieu for them. It is shown to be ectopically produced by malignant/leukemic and immune cells in the tumor microenvironment, providing a tumor-supportive environment and playing an important part in the establishment and progression of malignant cells. It is linked to hyperleukocytosis, high blast count, and poor clinical outcomes in acute leukemia (AL). Considering the varied role and different expression patterns of tumor necrosis factor-alpha in acute leukemia and its clinical relevance, the present study was planned to monitor the level of tumor necrosis factor-alpha in patients with acute leukemia and its correlation with disease outcome. The aim of this study was to monitor the level of tumor necrosis factor-alpha in patients with acute leukemia at the time of diagnosis and after induction chemotherapy.Material and methodsThe study included cases classified as acute leukemia based on morphological examination, bone marrow analysis, and flow cytometry. In all patients with acute leukemia (n = 90) and controls (n = 10), the serum tumor necrosis factor-alpha level was measured using a Diaclone Human ELISA kit (Diaclone, Besancon, France) (solid phase sandwich ELISA) at diagnosis and after induction chemotherapy.ResultsTumor necrosis factor-alpha levels were substantially higher in T-acute lymphoblastic leukemia (T-ALL) cases, followed by acute myeloid leukemia (AML) and B-acute lymphoblastic leukemia (B-ALL), at the time of diagnosis, compared to the control. A significant reduction in serum tumor necrosis factor-alpha level was seen in patients with acute leukemia after induction phase chemotherapy (P < 0.05). Tumor necrosis factor-alpha levels were considerably reduced (P < 0.001) in the majority of acute leukemia cases after the induction phase, while high tumor necrosis factor-alpha levels were positively correlated with incomplete remission status in the remaining cases.ConclusionTumor necrosis factor-alpha is involved in the progression of acute leukemia and its relapse. High levels of tumor necrosis factor-alpha are linked to leukocytosis, high blast counts, and worse survival in patients with acute leukemia. Monitoring of tumor necrosis factor-alpha may be helpful in patients with acute leukemia in view of available antitumor necrosis factor-alpha therapy.

Traditional Mongolian medicine (HHQG) attenuates CCl4-induced acute liver injury through inhibiting monocyte/macrophage infiltration via the p-P38/p-JNK pathway

Ethnopharmacological relevanceHonghua Qinggan 13 Flavor Pills (HHQG), whose Mongolian name is Guri Gumu-13, is a traditional Mongolian medicine, that was stated in the “Diagnosis and Treatment of Ming Medical Code”. The HHQG has been included in the Mongolian Medicine Division of the Ministry of Health Drug Standards (1998 edition). Based on our clinical expertise, HHQG demonstrated satisfactory therapeutic effects in hepatitis and liver failure. However, the pharmacological effects and potential mechanisms of HHQG have not been investigated. Aim of the studyIn this study, we combined network pharmacology, transcriptomics, and molecular biology to detect the underlying mechanism for the effect of HHQG on acute liver injury in mice. Materials and methodsNetwork pharmacology was used to explore the pathways involved in the protective effect HHQG in acute liver injury. This effect was further verified by injecting carbon tetrachloride (CCl4; 10 mL/kg, i.p.) to induce acute liver injury in mice. Serum markers of liver injury, morphology, histology, and monocyte/macrophage infiltration in the liver tissue were investigated. Transcriptomics further defined the HHQG targets. Transwell analysis was performed to confirm that HHQG inhibited monocyte/macrophage RAW.264.7 infiltration. qPCR and Western blot were performed to explore the mechanism of action of HHQG. ResultsNetwork pharmacology showed that HHQG exerted anti-oxidative and anti-inflammatory effects and promoted metabolic effects against acute liver injury. Pretreatment of mice with HHQG significantly maintained their body weight and decreased serum tumor necrosis factor-alpha (TNF-α) levels induced by CCl4 treatment in vivo. Histopathological examination further confirmed that HHQG protected the liver cells from CCl4-induced damage. Importantly, HHQG significantly inhibited CCl4-induced monocyte/macrophage infiltration. Transcriptomic analysis revealed that HHQG significantly reduced the expression of chemokines and cell adhesion molecules. We determined that HHQG significantly downregulated the expression of the key chemokine (monocyte chemokine protein-1, CCL2) at the gene and protein levels. Further research showed that HHQG inhibited chemokine production in hepatocytes by inhibiting the p-P38 and p-JNK pathways, thereby reducing monocyte/macrophage infiltration. ConclusionsThese combined data showed that HHQG alleviated acute liver injury in mice, and further verified that HHQG exerted protective effects by inhibiting the production of CCL2 and reducing the infiltration of monocyte/macrophage by inhibiting the p-P38 and p-JNK pathways.

Relation of serum level of tumor necrosis factor-alpha to cognitive functions in patients with Parkinson\u2019s disease

BackgroundInflammation is suggested to play a role in the development of non-motor Parkinson’s disease (PD) symptoms. We aimed to investigate the association between serum tumor necrosis factor-alpha (TNF-α) levels and cognition in PD patients. Thirty patients with PD and 30 healthy controls were included. Evaluation and staging of PD were done using Unified PD Rating Scale. Cognitive assessment was done using Addenbrooke’s Cognitive Examination (ACE-III) and trail making B tests. Measurement of serum levels of TNF-α was done.ResultsPatients had significantly worser cognitive scores than controls except for language subclass of ACE score. Mean serum TNF-α level was significantly greater in PD patients as compared to controls. TNF-α serum level was significantly negatively correlated with ACE visuospatial function. Sensitivity and specificity of TNF-α to detect cognitive dysfunction in PD using ACE III and trail making B tests were (73.1, 75%), (57.1, 56.2%), respectively, whereas sensitivity and specificity of TNF-α to detect severity of PD using H&Y staging in PD were 50%.ConclusionPatients with PD frequently have cognitive impairment. Elevated serum TNF-α levels in patients with PD, and association of this cytokine to visuospatial impairment, implicate this pro-inflammatory cytokine in the neurobiology of cognitive impairment in PD.

Tumour Necrosis Factor Alpha Serum Levels and its Gene Polymorphism 850 C/T (rs1799724) as Prognostic Markers of Traumatic Brain Injury Outcome

Introduction: Road traffic accidents have been responsible for the high incidence of head injuries. In a study from India, it was reported that there were 150 Traumatic Brain Injury (TBI) cases per 1,00,000 population, out of which 20 succumbed to death. In the repair process of TBI many chemicals play a role, of which, Tumour Necrosis Factor alpha (TNF-a) is important as TNF-a was shown to possess both neurotoxic and neuroprotective activity. Aim: To evaluate the serum levels of TNF-a and its functional polymorphism in TBI patients and assessing the outcome. Materials and Methods: The prospective cohort observational study was conducted in the Department of Genetics and Molecular Medicine, Kamineni Hospitals, Hyderabad, Telangana, India, from June 2008 to May 2012. It included 126 patients of both sexes with severe and moderate head injuries based on Glasgow Coma Scale (GCS) scores. A 3 mL of plain/Ethylenediaminetetraacetic acid (EDTA) blood sample was drawn from individuals immediately after admission, which was used for serum TNF-a assessment and DNA isolation for TNF-a genotype analysis. The TNF-a levels were measured by Enzyme Linked Immunosorbent Assay (ELISA) using KRISHGEN Biosystems (Catalog No. KB 100-HTNF a) kit. Outcome assessment was done based on Glasgow Outcome Scale (GOS). Statistical analysis was accomplished by Open Epi version 3.01 software. Odd’s Ratio (OR) were used to calculate risk of good/bad outcome with 95% confidence interval and results with a p&lt;0.05 were considered statistically significant. Results: A total of 126 subjects of Indian origin were enrolled in this study. The mean age of the subjects was 36.7±12.97 years. Out of the 126 patients, 46.8% (59) had multiple lesions. The patients with &lt;40 pg/mL (as per the kit specifications) TNF-a levels were 67.50% (85/126), while those with &gt;40 pg/L were 32.50% (41/126). The most common genotype found in the TBI patients was TT with a frequency of 60.3% (76/126), followed by CT with a frequency of 16.6% (21/126) and CC with a frequency of 23% (29/126). When genotype and TNF-a serum levels were studied together, it was seen that low TNF-a level (11-40 pg/mL) was associated with C allele and CC genotype, while those with TT genotype had high TNF-a level (&gt;40 pg/mL) when compared with other genotypes (CC, CT) and this was found to be statistically significant with an OR=3.4064, (95% CI= 1.8426 to 6.2975), p=0.0001. Higher percentage of death and disability was seen in patients with TT genotype while CC genotype showed good recovery at six months with OR=3.6441 (95% CI=1.911 to 6.946), p=0.0001. This suggests that T allele of TNF-a C850T polymorphism has a 3.6 fold higher risk of bad outcome in patients with TBI. Conclusion: The C allele and CC genotype of rs1799724 polymorphism was associated with positive outcome at three to six months. Thus, evaluating TNF-a levels and evaluating the genotype of rs1799724 polymorphism at admission, can be taken as prognostic marker. It can also be used as a target for therapeutic intervention.

Relationship of inflammatory mediators and sex-related parameters in Jordanian adult men patients with Covid-19.

Recent epidemiological data suggest that Co - ro navirus disease 2019 (COVID-19) has a gender predisposition, with men being more seriously affected than women. Furthermore, older men accounting for most deaths. Therefore, this study aimed to investigate the serum testosterone, inhibin B, intrleukin-6 (IL-6) and tumor necrosis factor-alpha (TNF-a) levels in different age groups of Jordanian males with SARS-CoV2 infection and to evaluate the correlation of these markers in male patients with COVID-19. This study was performed on 157 selected individuals divided into two groups; COVID-19 patients and healthy controls. The participants of each group were further divided into two subgroups based on the age (20-50 years and 51-80 years age groups). The biochemical tests that were performed in this research are testosterone, inhibin-B, TNF-a, and IL-6. The levels of IL-6 were significantly higher in COVID-19 patients than healthy individuals (7.63 ± 6.30 vs. 5.54 ± 2.10, P=0.006). Similarly, the difference between the levels of TNF-a in the study groups were statistically significant (P=0.001). The mean testosterone levels in COVID-19 patients and healthy controls were 1.53 ± 1.24 and 3.87 ± 1.44, respectively (P<0.001), whereas the mean inhibin B levels in COVID-19 patients (54.29 ± 7.33) were lower than in healthy controls (64.14 ± 37.66) with P = 0.011. TNF-a was significantly and positively correlated with age (r = 0.263, P=0.018) and IL-6 (r = 0.245, P=0.027). Inhibin B had a significant, but negative correlation with TNF-a (r = -0.326, P = 0.003). It can be concluded that most men seeking medical attention with symptomatic COVID-19 had low testosterone and inhibin B levels with increased both IL-6 and TNF-a, which are independent of age conforming the deleterious effects of SARS-CoV-2 infection on testicular function and immune response induction.

One-lung ventilation patients: Clinical context of administration of different doses of dexmedetomidine.

BackgroundOpen and endoscopic thoracic surgeries improve surgical exposure by One-lung ventilation (OLV). The aim of this study was to investigate the effects of different doses of dexmedetomidine on inflammatory response, oxidative stress, cerebral tissue oxygen saturation (SctO2) and intrapulmonary shunt in patients undergoing one-lung ventilation (OLV).MethodsSeventy-five patients undergoing open pulmonary lobectomy in our hospital from January 2016 to December 2017 were enrolled and randomly divided into high-dose dexmedetomidine group (group D1, 1 mg/kg, n=25), low-dose dexmedetomidine group (group D2, 0.5 mg/kg, n=25) and control group (group C, n=25). Then, arterial blood and internal jugular venous blood were taken before anesthesia induction (T0) and at 15 min after twolung ventilation (T1) and 5 min (T2) and 30 min (T3) after OLV for later use. Next, the changes in hemodynamic parameters [mean arterial pressure (MAP), heart rate (HR) and pulse oxygen saturation (SpO2)] of patients were observed in each group. Enzyme-linked immunosorbent assay (ELISA) was carried out to detect serum inflammatory factors such as interleukin-6 (IL-6) and tumor necrosis factor-alpha (TNF-α) and oxidative stress indicators [superoxide dismutase (SOD) and malondialdehyde (MDA)]. The changes in SctO2, arterial partial pressure of oxygen (PaO2) and intrapulmonary shunt Qs/Qt (a measurement of pulmonary shunt: right-to-left shunt fraction) were observed. Additionally, the changes in lung function indicators like lung dynamic compliance (Cdyn) and airway peak pressure (Ppeak) were determined.ResultsThere were no statistically significant differences in the MAP, HR and SpO2 among three groups at each observation time point (P>0.05). At T2 and T3, the levels of serum IL-6, TNF-α and IL-8 were obviously decreased in group D1 and D2 compared with those in group C (P<0.05), and the decreases in group D1 were overtly larger than those in group D2, and the decreases at T3 were markedly greater than those at T2 (P<0.05). In comparison with group C, group D1 and D2 had notably reduced levels of serum reactive oxygen species (ROS) and MDA (P<0.05) and remarkably increased SOD content (P<0.05) at T2 and T3, and the effects were markedly better in group D1 than those in group D2. Besides, they were significantly superior at T3 to those at T2 (P<0.05). The SctO2 in group D1 and D2 was evidently lowered at T2 and T3 compared with that at T0, and the decrease in group D1 was distinctly smaller than that in group D2 (P<0.05). The Qs/Qt was significantly lower in group D1 and D2 than that in group C at T2 and T3 (P<0.05), while the PaO2 content was notably raised (P<0.05), and the decrease and increase were significantly larger in group D1 than those in group D2, and they were obviously greater at T3 to those at T2 (P<0.05). At T0 and T1, no significant differences were detected in the Cdyn, Pplat and Ppeak among three groups. At T2 and T3, the Cdyn was significantly elevated, while the Pplat and Ppeak overtly declined (P<0.05), and group D1 had greater changes in comparison with group D2, and the changes were obviously more evident at T3 to those at T2 (P<0.05).ConclusionsDexmedetomidine effectively ameliorates inflammatory response and oxidative stress, lowers oxygenation, Qs/Qt and the decrease in SctO2 and improves lung function during OLV, with good efficacy.

Using quantitative MRI to study brain responses to immune challenge with interferon-α

Inflammatory processes in the Central Nervous System (CNS) have been proposed to mediate the association between peripheral inflammation and the development of psychiatric disorders, but we currently lack sensitive measures of CNS inflammation for human studies in vivo. Here we used quantitative MRI (qMRI) to explore the in vivo central response to a peripheral immune challenge in healthy humans, and we assessed whether changes in quantitative relaxometry MRI parameters were associated with changes in peripheral inflammation.Quantitative relaxation times (T1 & T2) and Proton Density (PD) were measured in n ​= ​6 healthy males (mean age ​= ​30.5 ​± ​6.8 years) in two MRI assessments collected before and 24 ​hours after a subcutaneous injection of the proinflammatory cytokine and immune activator, interferon-alpha (IFN-α). Serum levels of immune markers and markers of blood-brain barrier integrity (S100B) were also measured before and after the injection.Region of interest and histogram-based analyses (optimized for the small sample size) showed a statistically significant increase of both T1 (t(5) ​= ​3.78, p ​= 0.013) and PD (t(5) ​= ​2.91, p ​= ​0.033) parameters in the bilateral hippocampus after IFN-α administration. T1 peak values in bilateral hippocampus were positively correlated with serum Tumour Necrosis Factor-alpha levels at 24 ​h after the injection, when this cytokine peaked (Spearman's rho ​= ​0.67, p ​= ​0.018) and negatively correlated with S100B levels (Spearman's rho ​= ​−0.826, p ​= ​0.001).Our data suggest that peripheral administration of IFN-α produces acute changes in brain qMRI which might indicate a brain immune response. This is supported by the association of such changes with low-grade peripheral inflammation.

Potential use of ground brown rice for weanling pigs.

The purpose of the current study was to assess the effects of substituting corn with ground brown rice on growth performance, immune status, and gut microbiota in weanling pigs. Seventy-two weanling pigs (28 d old with 6.78 ± 0.94 kg body weight [BW]) were randomly allotted to two dietary treatments with six pens and six pigs (three barrows and gilts) per pen within a randomized complete block design. The control pigs were fed a typical diet for weanling pigs based on corn and soybean meal diet (control diet: CON), and the other pigs were fed a formulated diet with 100% replacement of corn with ground brown rice for 35d (treatment diet: GBR). Growth performance, immune status, and gut microbiota of weanling pigs were measured. The substitution of corn with GBR did not affect growth performance or diarrhea frequency. Additionally, there were no differences in white blood cell number, hematocrit, cortisol, C-reactive protein, and serum tumor necrosis factor-alpha levels between pigs fed CON or GBR for the first 2 wk after weaning. However, weanling pigs fed GBR had lower (P < 0.05) serum transforming growth factor-beta 1 level than those fed CON. Furthermore, weanling pigs fed GBR had increased (P < 0.05) relative abundance of phylum Firmicutes and genus Lactobacillus and Streptococcus and decreased (P < 0.05) relative abundance of phylum Bacteroidetes and genus Clostridium and Prevotella in the gut microbiota compared with those fed CON. In conclusion, there was no significant difference in growth performance when corn was replaced with ground brown rice in diets for weanling pigs. Furthermore, the substitution of corn with ground brown rice in weaning diet modulated immune status and gut microbiota of pigs by increasing beneficial microbial communities and reducing harmful microbial communities. Overall, ground brown rice-based diet is a potential alternative to corn-based diet without negative effects on growth performance, immune status, and gut microbiota changes of weanling pigs.