Tumor Necrotic Factor-alpha Research Articles

In silico and experimental potentials of 6-shogaol and meglumine antimoniate on Leishmania major: multiple synergistic combinations through modulation of biological properties.

Conventional therapeutic agents are no longer adequate against leishmaniasis. This complex condition continues to have a high mortality rate and public health impact. The present study aimed to explore an extensive array of experiments to monitor the biological activities of 6-shogaol, a major component of ginger, and meglumine antimoniate (MA or Glucantime®). The binding affinity of 6-shogaol and inducible nitric oxide synthase (iNOS), a major enzyme catalyzing nitric oxide (NO) from L-arginine was the source for the docking outline. The inhibitory effects of 6-shogaol, MA, and mixture were assessed using colorimetric and macrophage assays. Antioxidant activity was inferred by UV-visible spectrophotometry. Variably expressed genes were measured by quantifiable real-time polymerase chain reaction. Apoptotic and cell cycle profiles were analyzed by flow cytometry. Moreover, a DNA fragmentation assay was performed by electrophoresis and antioxidant metabolites include superoxide dismutase (SOD), catalase (CAT), and also nitric oxide (NO) by enzyme-linked immunosorbent assay. 6-shogaol and MA exhibited multiple synergistic mechanisms of action. These included a remarkable leishmanicidal effect, potent antioxidative activity, a high safety index, upregulation of M1 macrophages/Th1-associated cytokines (including, γ-interferon, interleukin-12p40, tumor necrotizing factor-alpha, and associated iNOS), significant cell division capture at the sub-G0/G1 phase, a high profile of apoptosis through DNA fragmentation of the nuclear components. In addition, the activity of NO was substantially elevated by treated intracellular amastigotes, while SOD and CAT activities were significantly diminished. This study is exclusive because no similar investigation has inclusively been conducted before. These comprehensive mechanistic actions form a logical foundation for additional advanced study.

Suppressing anti-citrullinated protein antibody-induced osteoclastogenesis in rheumatoid arthritis using anti-CD64 and PAD-2 inhibitors.

To evaluate the role of Fcγ receptors (FcγR) and peptidyl arginine deiminase (PAD) in anti-citrullinated protein antibody (ACPA)-induced fibroblast-like synoviocytes (FLSs)-mediated osteoclastogenesis in patients with rheumatoid arthritis (RA). FLSs and peripheral blood mononuclear cells were collected from patients with RA. We stimulated RA-FLS with ACPA (100 ng/ml) with and without anti-cluster of differentiation (CD)32a/CD64 (FcγRIIA/FcγRI) antibody and PAD-2/4 inhibitors. Flow cytometry and enzyme-linked immunosorbent assay were also performed. CD14+ monocytes were cultured with receptor activator of nuclear factor kappa beta (RANKL) and macrophage colony-stimulating factor, and ACPA-stimulated RA-FLSs were added. These cells were cultured for 14 days, and osteoclastogenesis was quantified using tartrate-resistant acid phosphatase (TRAP) staining. ACPA increased RANKL+ and tumour necrotic factor-alpha (TNF-α+) FLS, which decreased dose-dependently by adding 5 and 10 ug/mL anti-CD64 antibody rather than anti-CD32a antibody. In PAD inhibitor experiments, the proportion of RANKL+ and TNF-α+ FLS decreased in 50 μM condition containing PAD-2 inhibitor rather than PAD-4 inhibitor. The co-culture of ACPA-stimulated RA-FLSs and osteoclast precursors increased the TRAP+ multinucleated osteoclast count, which was decreased by anti-CD64 antibody and PAD2 inhibitor. The present study showed that ACPA increased RANKL and pro-inflammatory cytokine expression in RA-FLSs, and ACPA-activated RA-FLSs could augment osteoclastogenesis. These processes were inhibited by treatment with anti-CD64 antibody and PAD-2 inhibitors. These results show that CD64 and PAD-2-induced pathways may be involved in ACPA-induced FLS activation and osteoclastogenesis in patients with RA. Therefore, regulating the CD64 and PAD-2 pathways may improve RA treatment.

Dapagliflozin dampens liver fibrosis induced by common bile duct ligation in rats associated with the augmentation of the hepatic Sirt1/AMPK/PGC1α/FoxO1 axis

Liver fibrosis is considered an epidemic health problem due to different insults that lead to death. Dapagliflozin (DAPA), a sodium-glucose cotransporter-2 (SGLT2) inhibitor, is one of the newer anti-diabetic drugs used to manage type 2 diabetes mellitus (T2DM). DAPA exerted beneficial effects in many human and rat models due to its antioxidant, anti-inflammatory and antifibrotic activities. AimDue to previously reported capabilities related to DAPA, we designed this study to clarify the beneficial role of DAPA in liver fibrosis triggered by common bile duct ligation (CBL) in male rats. MethodsFor 14 or 28 days after CBL procedures, DAPA was administered to the rats orally at a dose of 10 mg/kg once daily. The effects of DAPA were evaluated by assaying liver enzymes, hepatic oxidant/antioxidant parameters, serum levels of tumor necrotic factor alpha (TNF-α), and AMP-activated protein kinase (AMPK). In addition, we measured the hepatic expression of fibrosis regulator-related genes along with evaluating liver histological changes. Key findingsDAPA successfully decreased hepatic enzymes and malondialdehyde levels, increased superoxide dismutase activity, elevated catalase levels, decreased serum levels of TNF-α, elevated serum levels of AMPK, decreased liver hydroxyproline content, upregulated Sirt1/PGC1α/FoxO1 liver gene expressions, down-regulated fibronectin-1 (Fn-1), collagen-1 genes in liver tissues, and improved the damaged liver tissues. Deteriorated biochemical parameters and histological liver insults associated with CBL were more pronounced after 28 days, but DAPA administration for 14 and 28 days showed significant improvement in most parameters and reflected positively in the histological structures of the liver. SignificanceThe significance of this study lies in the observation that DAPA mitigated CBL-induced liver fibrosis in rats, most likely due to its antioxidant, anti-inflammatory, and antifibrotic effects. These results suggest that DAPA's beneficial impact on liver fibrosis might be attributed to its interaction with the Sirt1/AMPK/PGC1α/FoxO1 pathway, indicating a potential mechanistic action for future exploration.

Effect of Mat Pilates Training on Blood Pressure, Inflammatory, and Oxidative Profiles in Hypertensive Elderly.

To determine the effects of mat Pilates training on blood pressure, inflammatory, and antioxidative markers in hypertensive elderly people, 34 hypertensive subjects aged 60-75 years were randomly divided into a control group (CON; n = 17) and a mat Pilates training group (MP; n = 17). The CON participants conducted normal daily activities and participated in neither organized exercises nor sports training, while those in the MP group received mat Pilates training for 60 min three times/week for 12 weeks. Parameters including blood pressure, cardiovascular function, nitric oxide (NO), tumor necrotic factor-alpha (TNF-α), superoxide dismutase (SOD), and malonaldehyde (MDA) were collected at baseline and the end of 12 weeks. The MP group had significantly decreased blood pressure, improved cardiovascular variables, decreased MDA and TNF-α, and increased NO and SOD compared with the CON group and the pre-training period (p < 0.05). In conclusion, these findings demonstrate the positive effects of 12 weeks of mat Pilates training in terms of reducing blood pressure and increasing blood flow related to improvements in anti-inflammatory and antioxidative markers in hypertensive elderly people. Mat Pilates training might be integrated as an alternative therapeutic exercise modality in clinical practice for hypertensive elderly individuals.

Effects of SNPs on TNF-α and IL-10 cytokine expression in TB and HIV patients in the Capricorn district, Limpopo Province, South Africa.

The impact of Tuberculosis (TB) places an immense burden on the health care system. Infection with Human Immunodeficiency Virus (HIV) is a significant risk factor in the development and progression of TB disease. Single Nucleotide Polymorphisms (SNPs) in the promoter region of Interleukin-10 (IL-10) and Tumour Necrotic Factor-Alpha (TNF-α) may play a major role in the disease mechanism and understanding these mechanisms might prove to be a useful diagnostic tool in evaluating the immune regulation and progression of the disease. This study aimed to determine the relationship between cytokine levels and gene variants of Interleukin-10 and Tumour Necrotic Factor Alpha in TB and HIV-infected participants. Cytokine levels were determined by ELISA, and SNPs were determined by MassArray®. The levels of TNF-α were higher in the TB group than the HIV (p < 0.001) and TB-HIV (p = 0.011) groups, but similar to the TNF-α levels in the control group. In the HIV group, IL-10 levels were higher than those of the TB (p < 0.001) and control groups (p = 0.039), whereas there was no difference between the IL-10 levels in the HIV and the TB-HIV infection groups. The ratio was determined and there were no differences between the four infection groups. In this study, no associations were detected between the circulating plasma levels of TNF-α and IL-10 and their genotypes. Our data showed that the gene variants were not associated with circulating plasma levels of TNF-α and IL-10 in our study population. A pro-inflammatory environment was found in the TB and TB-HIV groups, which is suggesting of bacterial clearance, while an anti-inflammatory environment was found in the HIV group, which suggests the suppression of viral replication.

Serum Levels of Interleukin-1 Beta are Decreased in Patients with Stevens-Johnson Syndrome and Toxic Epidermal Necrolysis at the Time of Hospitalization

BACKGROUND: Stevens–Johnson syndrome (SJS) and toxic epidermal necrolysis (TEN) are severe cutaneous adverse drug reactions. Some immunological and genetic factors are believed to be involved in the pathogenesis of the disease, including tumor necrotic factor-alpha, interferon-gamma, and interleukin (IL)-17. IL-1β is one of the most prominent cytokines associated with the innate immune response. AIMS: The study aimed to evaluate the serum level of IL-1β in SJS/TEN and the relation between it and the progress of SJS/TEN. METHODS: This was a cross-sectional descriptive study conducted at the National Hospital of Dermatology and Venereology, in Hanoi, Vietnam, from October 2017 to September 2019. 48 SJS/TEN patients, 43 erythema multiforme (EM) patients, and 20 healthy controls (HCs) participated. IL-1β levels were measured using the fluorescence covalent microbead immunosorbent assay (ProcartaPlex Immunoassay Panels kit, Thermo Fisher Scientific, USA). The Mann–Whitney U test was used to compare serum IL-1β levels. The Wilcoxon tests were used to compare quantitative variables before and after the treatment. Differences were considered to be statistically significant at p &lt; 0.05. RESULTS: 19 SJS patients (39.5%) and 29 TEN patients (60.5%) participated in our study. The mean age was 49.3 years; the range was 19–77 years (47.9% males; 52.1% females). The most common causative drugs were traditional medicine (29.1%), carbamazepine (12.5%), and allopurinol (12.5%). On the day of hospitalization, the mean serum level of IL-1β of the SJS/TEN group was 26.4 ± 81.7 pg/mL, ranging from 0.5 pg/mL to 447 pg/mL. This level was significantly lower than that of the HCs group (p &lt; 0.001) but not lower than that of the EM group. The mean serum level of IL-1β in the SJS/TEN patients on the day of hospitalization was 26.4 ± 81.7 pg/ml, higher than that on the day of re-epithelialization (1.9 ± 5.6 pg/mL) and the difference was statistically significant with p &lt; 0.01. CONCLUSION: Serum IL-1β level in SJS/TEN patients is lower than in HCs. It is not a good biomarker to differentiate SJS/TEN from EM.

At Low Temperature Plasma Preoperative and Postoperative of Chronic Tonsillitis Tonsillectomy

Objective to explore the clinical efficacy of low-temperature plasma tonsillectomy in the treatment of patients with chronic tonsillitis and tonsillar hypertrophy. Methods: 100 patients with chronic tonsillitis and tonsillar hypertrophy admitted to the first affiliated hospital of Xinjiang Medical University from August 2021 to August 2023 were randomly selected as the research subjects. Based on the voluntary principle and different treatment plans, The patients were divided into two groups. 50 patients who underwent dissection tonsillectomy treatment were selected into the control group, and 50 patients who underwent low-temperature plasma tonsillectomy were selected into the observation group. The differences in clinical indicators between the two groups of patients were compared, The pain levels of patients at different postoperative periods were evaluated, and the differences in serum inflammatory factor levels were detected. Results: Compared with the control group, after surgical treatment, the operation time, and intra-operative bleeding volume of the blood observation group were significantly shorter, and the difference was statistically significant (P&lt;0.05); 1, 3, 5 and 7 days after surgery in the observation group. The Visual analogue scale VAS pain scores at 7 days were lower than those in the control group, and the difference was statistically significant (P&lt;0.05); after surgery in the observation group, the patient's high-sensitivity C-reactive protein (hs-CRP) (14.18±0.51) mg/L, Tumor necrotic factor-alpha (TNF-α) (4.23±0.31) pg/ml was significantly less, and the difference was statistically significant (P&lt;0.05); 5 patients in the observation group suffered from postoperative bleeding and complications The incidence rate was 16.00%, which was significantly lower than that of the control group, and the difference was statistically significant (χ2=4.588, P&lt;0.05). Conclusion: From our study it was able to show that tonsillectomy for adults and children with recurrent tonsillitis were widely used which improves health and quality of life and reduces the need to consume medical resources. When low-temperature plasma tonsillectomy is used in the clinical treatment of patients with chronic tonsillitis and tonsillar hypertrophy, the inoperative blood loss of the patients is significantly reduced, the clinical pain of the patients is further relieved, and the serum inflammatory factor levels of the patients are adjusted.

Renoprotective Effect of Thymoquinone against Streptozotocin-Induced Diabetic Nephropathy: Role of NOX2 and Nrf2 Signals.

Diabetic nephropathy is an unavoidable complication of chronic uncontrolled diabetes mellitus. The pathogenesis of diabetic nephropathy is multifactorial, and the development of an effective therapy remains to be elucidated. The aim of the present study was to assess the role of NOX2 and Nrf2 in the protective mechanism of thymoquinone (THQ) against streptozotocin (STZ)-induced diabetic nephropathy. Rats were injected with STZ (55 mg/kg) to induce diabetes. The diabetic rats were orally treated with THQ (10 mg/kg/day) for eight weeks. STZ-treated rats exhibit an elevation of serum creatinine, serum urea, and creatinine clearance. The renal abnormalities were associated with increased NADPH oxidase isoform, NOX2 protein expression, and activity, along with elevated malondialdehyde (MDA). In addition, the tumor necrotic factor-alpha (TNF-α) level and nitric oxide (NO) bioavailability, as well as the transforming growth factor-beta (TGF)-β, were markedly increased. On the other hand, the nuclear factor-E2-related factor (Nrf2) protein expression was significantly reduced in diabetic rats compared to the control. However, treatment with THQ significantly reversed these alterations with subsequent ameliorating renal dysfunction and pathological abnormalities. The present study demonstrates that THQ could protect against STZ-induced diabetic nephropathy by modulating the Nrf2/NOX2 signaling pathway.

Morinda Citrifolia (Noni) attenuated transcriptional and degenerative markers of cardiac toxicity in bisphenol A treated male wistar rats

Bisphenol A (BPA) is an endocrine disruptor that causes metabolic disruption. It is widely used in the manufacturing industry as an internal protective lining for food and beverage cans. Morinda citrifolia (Noni) is a known ethno-medicinal plant of Pantropical origin. The aim of this study was to investigate the effect of Noni aqueous extract (NAE) on transcriptional and degenerative markers of cardiac toxicity in Bisphenol A treated male Wistar rats. Twenty-four male Wistar rats were randomly assigned into four groups as: Control (Ctr: normal chow + vehicle: Olive oil), BPA (7 g/kg, orally), (NAE:500 mg/kg; orally), and NAE: (500 mg/kg + BPA;7g/kg orally). After six weeks of administration, animals were anesthetized with 0.8 mg Phenobarbitone intraperitoneally and blood was collected by cardiac puncture. Plasma and cardiac homogenate were sampled and data were analyzed using a one-way ANOVA followed by Bonferroni’s Post hoc test. Results are expressed as mean ± standard error of mean (SEM) and p < 0.05 were accepted as significant. Bisphenol A reduced significantly plasma and cardiac histone deacetylate (HDAC), Nitric oxide (NO) and adenosine and increased triglycerides (TG), lipoprotein (a) or Lp(a), tumor necrotic factor alpha (TNF-α), uric acid (UA), and (malondialdehyde) MDA when compared with control and noni-treated group. NAE increased HDAC and NO significantly compared to the control while reducing significantly TNF-α, catalase, MDA, TG, and Lp(a). In conclusion, NAE reduced Bisphenol A worsening cardiovascular risks through a significant positive epigenetic HDAC expression and increased neovascularization activities.

Effect of Radiofrequency on Dorsal Root Ganglion Versus Transforaminal Steroids Injection on Tumor Necrosis Factor-Alpha Level in Lumbar Radicular Pain

BACKGROUND: The mechanism of pain control with pulsed radiofrequency (PRF) is unclear. OBJECTIVES: We aimed to compare the efficacy of combined PRF on dorsal root ganglion (DRG) with transforaminal epidural steroid injection (TFESI) vs TFESI-alone on pain improvement and serum tumor necrosis factor-alpha (TNF-a) level in lumbar disc-related radicular pain. STUDY DESIGN: Prospective, randomized, controlled trial. SETTING: Neurology and Pain Management clinics. METHODS: A total of 80 patients with lumbar disc prolapse were divided into 2 groups: combined PRF on DRG with TFESI group and TFESI-alone group. The Numeric Rating Scale (NRS-11), Oswestry Disability Index (ODI), and Functional Rating Index (FRI) before intervention and at 2 weeks, 1 month, and 3 months after the intervention were observed. Serum TNF-a level was assessed pre- and post-intervention at 3 months. RESULTS: The scores of NRS-11, ODI, and FRI showed a significant improvement at 2 weeks, 1 month, and 3 months following intervention in both combined PRF &amp; TFESI group and TFESI-alone group (P &lt; 0.001 in all comparisons), with no significant difference between the 2 groups. Serum TNF-a levels showed a statistically significant reduction, 3 months following intervention in the combined PRF &amp; TFESI group (P &lt; 0.001), but not in the TFESI-alone group (P = 0.297) (P between groups &lt; 0.001). LIMITATIONS: The main limitation of this study is that TNF-a level was not assessed earlier to see how long the steroids might reduce TNF-a. On the other hand, further study with extended follow-up periods is needed to confirm the long-term lowering effect of TNF-a provided by PRF. CONCLUSIONS: Combined PRF on DRG with TFESI showed similar outcomes to TFESI-alone in relieving pain in patients with lumbar disc prolapse. However, PRF on DRG caused a significant decrease in TNF-a serum levels at 3 months. KEY WORDS: Pulsed radiofrequency, transforaminal steroids injection, tumor necrotic factor-alpha, lumbar disc prolapse

Analysis of the clinical characteristics of 25 cases with parenchymal neuro-Behcet's disease

Objective: To retrospectively investigate the clinical data, radiological characteristics, treatment, and outcome of patients with parenchymal neuro-Behcet's disease (P-NBD) with particular emphasis on dizziness. Methods: This was a cross-sectional study of clinical data from 25 patients with a confirmed diagnosis of P-NBD who were admitted to the Department of Neurology of the First Medical Center of Chinese People's Liberation Army General Hospital between 2010 and 2022. The median age of the population was 37 years (range: 17-85 years). Clinical data were retrospectively analyzed, including gender, age of onset, disease duration, clinical manifestations, serum immune indicators, cerebrospinal fluid (CSF) routine biochemical and cytokine levels, cranial and spinal magnetic resonance imaging (MRI) findings, treatment, and outcome. Results: The majority of patients were male (16 cases; 64.0%), the mean age of onset was (28±14) (range: 4-58 years), and the disease course was acute or subacute. Fever was the most common clinical presentation, and the complaint of dizziness was not uncommon (8/25 patients). Analysis of serum immune indices, including complement (C3 and C4), erythrocyte sedimentation rate, interleukin-1 (IL-1), IL-6, IL-8 and tumor necrotic factor-alpha were abnormal in 80.0% of patients (20/25). Most of the 16/25 patients who underwent lumbar puncture tests had normal intracranial pressure and increased CSF white cell count and protein [median values were 44 (15-380) ×106/L and 0.73 (0.49-2.81) g/L, respectively]. Of the five patients who underwent CSF cytokine tests, four patients had abnormal results; of these, an elevated level of IL-6 was most common, followed by IL-1 and IL-8. The most common site of involvement in cranial MRI was the brainstem and basal ganglia (60.0% respectively), followed by white matter (48.0%) and the cortex (44.0%). Nine cases (36.0%) showed lesions with enhancement and six cases (24.0%) showed mass-like lesions. Three patients (12.0%) patients had lesions in the spinal cord, most frequently in the thoracic cord. All patients received immunological intervention therapy; during follow up, the majority had a favorable outcome. Conclusions: P-NBD is an autoimmune disease with multiple system involvement and diverse clinical manifestations. The symptom of dizziness is not uncommon and can be easily ignored. Early treatment with immunotherapy is important and can improve the outcome of these patients.

Zinc protects against lead-induced testicular damage via modulation of steroidogenic and xanthine oxidase/uric acid/caspase 3-mediated apoptotic signaling in male Wistar rats

Aim This study evaluated the effect of lead, with or without zinc co-administration, on steroidogenic and xanthine oxidase (XO)/uric acid (UA)/caspase 3-mediated apoptotic signaling in the testis. Materials and methods Forty male Wistar rats were divided into four groups at random; vehicle-treated control, zinc-treated, lead-treated, and lead + zinc-treated groups. Results Lead exposure significantly lowered overall weight gain, testicular, epididymal, seminal vesicle, and prostate weights. Also, lead decreased sperm count, viability and motility but increased the fraction of sperm with aberrant morphology. In addition, lead caused a marked rise in the level of UA and XO activity but a decrease in nuclear factor erythroid 2-related factor 2 (Nrf2), reduced glutathione (GSH) as well as total antioxidant capacity (TAC) levels, and superoxide dismutase (SOD) and catalase activities. Furthermore, lead increased the testicular levels of nuclear factor kappa B (NFkB), interleukin-1beta (IL-1β), and tumour necrotic factor-alpha (TNF-α), which were associated with an increase in testicular caspase 3 activity and DNA fragmentation as well as a decline in circulating gonadotropin releasing hormone (GnRH), luteinizing hormone (LH), follicle-stimulating hormone (FSH), testosterone, and testicular 3β-hydroxysteroid dehydrogenase (3β-HSD) and 17β-hydroxysteroid dehydrogenase (17β-HSD). These were associated with lead-induced degenerative changes in testicular tissues evidenced by shrunken seminiferous tubules, degeneration and sloughing of germ cells. Co-administration of zinc prevented lead-induced testicular injury by ameliorating oxidative stress, apoptosis, and inflammation through downregulation of XO/UA/caspase 3 pathway and upregulation of testicular 3β-HSD/17β-HSD. Conclusion This study demonstrated that zinc protected against lead-induced testicular toxicity via the downregulation of XO/UA/caspase 3 signaling.

Therapeutic enhancing potential of piracetam with diethylstilbestrol in prevention of grand-mal seizures in rats: inhibition of PI3K/Akt/mTOR signaling pathway and IL-1β, IL-6, TNF-α cytokines levels.

Epilepsy, a neurodegenerative disorder, continues to throw challenges in the therapeutic management. The current study sought to ascertain if the therapeutic interactions between piracetam and diethylstilbestrol may prevent grand-mal seizures in rats. Piracetam (PIR; 10 and 20 mg/kg) and diethylstilbestrol (DES; 10 and 20 mg/kg) alone as a low-dose combination were administered to rats for 14 days. The electroshock (MES; 180 mA, 220 V for 0.20 s) was delivered via auricular electrodes on the last day of treatment and rats were monitored for convulsive behavior. To elucidate the mechanism, hippocampal mechanistic target of rapamycin (mTOR) and interleukin (IL)-1β, IL-6 and tumor necrotic factor-alpha (TNF-α) levels were quantified. Hippocampal histopathology was conducted to study the neuroprotective effect of drug/s. In vitro studies and in silico studies were conducted in parallel. To our surprise, the low dose of the combination regimen of PIR (10 mg/kg) and DES (10 mg/kg) unfolded synergistic anti-seizure potential, with brimming neuroprotective properties. The mechanism could be related to a significant reduction in the levels of hippocampal mTOR and proinflammatory cytokines. The docking scores revealed higher affinities for phosphatidylinositol 3-kinase (PI3K) in co-bound complex, and when docking DES first, while better affinities for protein kinase B (Akt) were revealed when docking PIR first (both drugs bind cooperatively as well). This indicated that the entire PI3K/Akt/mTOR signaling pathway is intercepted by the said combination. In addition, the % of cell viability of HEK-293 cells [pre-exposed to pentylenetetrazol (PTZ)] was increased by 327.29% compared to PTZ-treated cells (toxic control; 85.16%). We are the first to report the promising efficacy of the combination (PIR 10 mg/kg + DES 10 mg/kg) to restrain seizures and epileptogenic changes induced by electroshock by a novel mechanism involving inhibiting the PI3K/Akt/mTOR signaling.

Role of saffron and chamomile in Parkinson diseases.

Madam, Parkinson's disease (PD) is a distinctive neurodegenerative disorder with a multifactorial range of etiology and symptoms. The pathophysiology behind the condition is a complex array of abnormal alpha-synuclein aggregation, mitochondrial dysfunction, oxidative stress, and neuroinflammation that leads to reduced dopaminergic expression, and neuronal cell death (1, 2). In multitudinous preclinical studies, Saffron and Chamomile are effective in treating PD. Saffron can mitigate the neurodegenerative progression of the disease by curtailing dopaminergic and neuronal loss and inhibiting alpha-synuclein aggregation. It also possesses antioxidant and anti-inflammatory activities (3). In-silico studies also demonstrated the action of active compounds of Saffron, including crocin, crocetin, and safranal, against potential targets of PD (1). Chamomile and its active compound Apigenin are beneficial in movement disorders in Parkinson's disease (4). It possesses neuroprotective, anti-inflammatory and antioxidant activities. It also has demonstrated activity against potential biomarkers of PD, including: Interleukin-6, Tumor Necrotic factor-alpha, Malonaldehyde, alpha-synuclein, Glial fibrillary acidic protein and also on Tyrosine Hydroxylase and dopamine receptors expression (2). Prolonged use of pharmacotherapy is not very beneficial in managing PD. Currently, dopamine-related drugs, including Levodopa, are considered first-line therapy. Despite temporarily alleviating the symptoms they cannot alter the degenerative process of PD (1). It warrants a crucial need for novel therapeutic agents working with diverse mechanisms. Pre-clinically, Saffron and chamomile are efficacious in altering potential disease biomarkers. Both herbs have been easily accessible and utilized since ancient times with numerous benefits and better tolerability. Clinical studies specifically for PD are yet to be analyzed; in different neurological disorders, daily oral consumption of 30mg of Saffron and 1gm to 1.5gm of Chamomile is recommended (3,5). Considering the high cost, a blended intake of saffron and Chamomile could be cost-effective and beneficial in treating the disease. Therefore, though clinical trials are needed for further elaboration, Parkinson's disease and related neurological disorders can be managed by synergising both drugs.

Thyroid Autoantibodies in Type -1 Diabetic Mellitus Patients and their Correlation with Thyroid function and Tumor Necrotic Factor-Alpha

Type 1 Diabetes Mellitus (T1DM) is a complicated autoimmune disorder initiated by T-cell-mediated damage of pancreatic beta cells, resulting in insulin deficiency and the development of hyperglycaemia. This disease is most common in childhood and adolescence and frequently co-occurs with other autoimmune conditions like autoimmune thyroiditis. This work aimed to investigate thyroid autoantibodies and their correlation with thyroid functions and tumour necrosis factor-alpha (TNF-α) in T1DM patients. Eighty participants were enrolled in a case-control study, including sixty T1DM patients and twenty healthy controls. Peripheral blood specimens were taken from individuals with proven T1DM and healthy individuals (control group). Body mass index (BMI), fasting blood sugar (FBS), glycated hemoglobulin (HbA1c), thyroid-stimulating hormone (TSH), free triiodothyronine (FT3), free thyroxine (FT4), thyroid autoantibodies, including anti-thyroid peroxidase (anti-TPO) in addition to anti-thyroglobulin (anti-Tg), and TNF- α concentrations were evaluated in T1DM and control groups. Our findings revealed that thyroid autoantibodies were significantly more prevalent in T1DM patients, elevated TSH, and significantly higher TNF-α levels than in the control group, indicating an increased risk for inflammation based on cytokine levels. The current study proved that in T1DM patients' sera compared to the healthy control, thyroid autoantibodies and TNF-α levels were positively correlated. In conclusion, poor diabetes management and high TSH levels may indicate subclinical hypothyroidism, which impacts diabetes control. This is possibly linked to thyroid autoimmunity. Future research is needed to understand how TNF- αcontributes to the progression of diabetes disease and its complications.

Flavonoids from Scutellaria amoena C. H. Wright alleviate mitochondrial dysfunction and regulate oxidative stress via Keap1/Nrf2/HO-1 axis in rats with high-fat diet-induced nonalcoholic steatohepatitis

BackgroundNonalcoholic steatohepatitis (NASH) is among the most common liver diseases in the world. Flavonoids from Scutellaria amoena (SAF) are used in the treatment of hepatopathy in China. However, the effect and mechanism against NASH remain unclear. We investigated the alleviating effect of SAF on NASH via regulating mitochondrial dysfunction and oxidative stress. MethodsThe effects of SAF on NASH were evaluated using in vitro and in vivo methods. L02 cells were induced by fat emulsion to establish an adipocytes model, followed by treatment with SAF for 24 h. NASH rat models were established by the administration of a high-fat diet for 12 weeks and were administered SAF for six weeks. Changes in body weight, organ indexes, lipid levels, inflammatory cytokines, mitochondrial indicators, and fatty acid metabolism were investigated. ResultsSAF significantly improved body weight, organ indexes, lipid levels, liver injury, and inflammatory infiltration in NASH rats. SAF notably regulated interleukin-6, tumor necrotic factor-alpha, superoxide dismutase (SOD), glutathione (GSH), malondialdehyde (MDA), kelch-like ECH-associated protein 1 (Keap1), nuclear factor-erythroid factor 2-related factor 2 (Nrf2), and heme oxygenase-1 (HO-1). Additionally, SAF improved mitochondrial dysfunction, increased the levels of GSH, SOD, ATP synthase, complex I and II, and decreased the level of MDA in liver mitochondria. SAF regulated the expression of β-oxidation genes, including peroxisome proliferator-activated receptor -gamma coactivator-1alpha (PGC-1α), carnitine palmitoyltransferase-1 (CPT1) A, CPT1B, medium-chain acyl-CoA dehydrogenase, long-chain acyl-CoA dehydrogenase, very long-chain acyl-CoA dehydrogenase, and PPARα. ConclusionSAF can alleviate NASH by regulating mitochondrial function and oxidative stress via the Keap1/Nrf2/HO-1 axis.

A biochemical and histology experimental approach to investigate the adverse effect of chronic lead acetate and dietary furan on rat lungs.

Despite lead widespread environmental pollution, its effect on humans and livestock's respiratory systems remains inadequately investigated. Similarly, furan is industrially relevant with enormous environmental presence. Lead and furan can be ingested -via lead pipes contaminated water and heat-treated food respectively. Thus, humans are inadvertently exposed continuously. Lead toxicity is well studied, and furan have earned a position on the IARC's list of carcinogens. Here, we evaluate the effect of co-exposure to lead and furan on rat lungs. Thirty Wistar rats were grouped randomly into six cohorts (n = 6) consisting of a control group, furan alone group, lead acetate (PbAc) alone group and three other groups co-exposure to graded PbAc (1, 10 & 100µg/L) alongside a constant furan (8mg/kg) dose. After twenty-eight days, enzymatic and non-enzymatic antioxidant, oxidative stress and inflammatory biomarkers were biochemically evaluated. The ELISA-based technique was used to measure oxidative-DNA damage (8-OHG), tumour protein 53 (TP53) expressed and tumour necrotic factor-alpha (TNF-α) level. Dose-dependent increases (p < 0.05) in reactive oxygen and nitrogen species, malondialdehyde, nitric oxide, myeloperoxidase, TNF-α and TP53 level, with an associated decrease (p < 0.05) in enzymatic and non-enzymatic antioxidants were observed in the furan, PbAc and the co-treated rats relative to the control. In addition, PbAc and furan treatment impaired the histoarchitectural structures of rat lungs, exemplified by pro-inflammatory cell infiltration and trafficking into the bronchioles and alveolar spaces. Co-exposure to furan and PbAc may contribute to lung dysfunction via loss of redox balance, genomic damage/instability, inflammation and disrupted histoarchitectural features.

High Serum Level of TNF-α in Stevens-Johnson Syndrome and Toxic Epidermal Necrolysis

BACKGROUND: Stevens-Johnson syndrome (SJS) and toxic epidermal necrolysis are severe cutaneous adverse drug reactions. Some immunological and genetic factors are believed to be involved in the pathogenesis of SJS/TEN, including tumor necrotic factor-alpha (TNF-α). Activated T-cells secrete high amounts of TNF-α and interferon-gamma that both cytokines lead to increased expression and activity of keratinocyte inducible nitric oxide synthase playing an important role in the apoptosis of keratinocytes. AIM: This study aims to evaluate the serum level of TNF-α in SJS/TEN and the relation between it and the progress of SJS/TEN. METHODS: This was a sectional descriptive study conducted at the National Hospital of Dermatology and Venereology, in Hanoi, Vietnam, from October 2017 to September 2019. Forty-eight SJS/TEN patients, 43 erythema multiforme (EM) patients, and 20 healthy controls (HCs) participated. TNF-α levels were measured using the fluorescence covalent microbead immunosorbent assay (FCMIA) (ProcartaPlex Immunoassay Panels kit, Thermo Fisher Scientific, USA). The Mann–Whitney U-test was used to compare serum TNF-α levels of two groups. The Wilcoxon tests were used to compare quantitative variables before and after the treatment. Differences were considered to be statistically significant at p &lt; 0.05. RESULTS: Nineteen SJS patients (39.5%) and 29 TEN patients (60.5%) participated in our study. The mean age was 49.3, range 19−77 years (47.9% of males and 52.1% of females). The most common causative drugs were traditional medicine (29.1%), carbamazepine (12.5%), and allopurinol (12.5%). On the day of hospitalization, the mean serum level of the SJS/TEN group was 32.6 pg/ml with a range from 1.3 pg/ml to 771.2 pg/ml. This level was significantly higher than that of the HCs group (p &lt; 0.05) but not higher than that of the EM group. The mean serum level of TNF-α in the SJS/TEN patients on the day of hospitalization was 32.6 pg/ml, higher than that on the day of re-epithelialization (2.7 pg/ml) and the difference was statistically significant with p &lt; 0.05. CONCLUSION: Serum TNF-α levels are a good biomarker to evaluate the progress of SJS/TEN but it is not good to differentiate SJS/TEN from EM.

Quercetin Abates Aluminum Trioxide Nanoparticles and Lead Acetate Induced Altered Sperm Quality, Testicular Oxidative Damage, and Sexual Hormones Disruption in Male Rats.

This study examined the effects of exposure to lead acetate (PbAc) and/or aluminum trioxide nanoparticles (Al2O3NPs) on testicular function. Additionally, the probable reproprotective effects of quercetin (QTN) against Al2O3NPs and PbAc co-exposure in male Sprague Dawely rats were assessed. Al2O3NPs (100 mg/kg b.wt.), PbAc (50 mg/kg b.wt.), and QTN (20 mg/kg b.wt.) were orally administered for 60 days. Then, spermiogram, histopathological examinations of the testis and accessory glands, and immunohistochemical detection of androgen receptors (AR) and tumor necrotic factor alpha (TNF-α) were achieved. Moreover, serum levels of male sex hormones and testicular levels of antioxidant indices were estimated. The results showed that Al2O3NPs and/or PbAc caused significant sperm abnormalities, testicular oxidative stress, and histopathological changes. Furthermore, serum testosterone, LH, and FSH levels significantly decreased, while estradiol levels significantly increased. The Al2O3NPs and/or PbAc co-exposed group had more obvious disturbances. Furthermore, QTN co-administration significantly reversed the Al2O3NPs and PbAc-induced testicular histopathological alterations, reduced antioxidant defenses, and altered AR and TNF-α immune expression in testicular tissues. Conclusively, Al2O3NPs and/or PbAc evoked testicular dysfunction by inducing oxidative injury and inflammation. However, QTN oral dosing effectively mitigated the negative effects of Al2O3NPs and PbAc by suppressing oxidative stress and inflammation and improving the antioxidant defense system.

Tumour Necrotic Factor Alpha level and Some Biochemical Parameters as a Measure of Health Risks Due to Exposure to Liquefied Petroleum Gas on Vendors in Calabar, Nigeria

Background: The human body is constantly exposed to chemicals and other substances injurious to health from the environments, foods etc. These substances are taken into the body either consciously or unconsciously through the mouth, nose, and skin which often lead to oxidative stress, gene mutation, direct injury on cells and tissue, alteration of immune system etc, resulting in cancer development and other chronic and acute health challenges and death. This study is aimed at assessing the health risks due to chronic exposure to non-combusted Liquefied Petroleum Gas (LPG) and appraising the potential inflammatory and liver problem among its vendors who did not wear Personal Protective Equipments (PPE).&#x0D; Methods: Forty-one apparently healthy Liquefied Petroleum Gas sellers and Forty-one apparently healthy non Liquefied Petroleum Gas sellers/user (control), aged 18 to 50 years were recruited for this study. The Body Mass Index (BMI) was determined by taking the ratio of weights in Kg to the square of heights in meters. Tumor Necrosis Factor Alpha (TNF-α) was estimated by Enzyme Linked Immunosorbent Assay (ELISA), 2-butanol was estimated using High Performance Liquid Chromatography (HPLC), ALT and AST were estimated using Colorimetric method. Data were analyzed using Student’s t-test and Pearson’s correlation at p&lt;0.05.&#x0D; Results: From the results obtained, AST, ALT and BMI did not show significant variation but TNF-α and 2-butanol showed a significant variation compared to control. TNF-α and 2-butanol showed a significant positive correlation among the exposed group. The duration of exposure does not appear to cause a significant difference in the levels of the biochemical parameters.&#x0D; Conclusion: This study therefore showed that exposure to Liquefied Petroleum Gas has no effect on anthropometric and liver parameter but appears to cause significant elevation of TNF-α and 2-butanol, meaning that sellers may be predisposed to inflammation. It is therefore recommended that vendors of Liquefied Petroleum Gas (LPG) always wear their PPE to avoid deleterious effect on their health.