Serum Levels Of IL-6 Research Articles

Saffron improves the efficacy of immunotherapy for colorectal cancer through the IL-17 signaling pathway

Ethnopharmacological relevanceSaffron is one of the traditional medicinal herbs, which contains various active ingredients, such as safranal, crocin, saffron acid, etc. It has anti-inflammatory, antioxidant, and anti-cancer properties, and is widely used in clinical practice. The anti-cancer efficacy of saffron has been previously confirmed, but its anti-cancer mechanism in colorectal cancer remains unclear. ObjectiveWe investigated the effect of active compounds of saffron on the efficacy of immunotherapy for colorectal cancer. MethodsTCMSP and liquid chromatography-mass spectrometry analysis (LC-MS), GeneCards, and DisGeNET databases were used to identify the active compounds of saffron, drug targets and the disease targets of colorectal cancer. They were then subjected to Gene Ontology Enrichment (GO) and Signalling Pathway Enrichment (KEGG) analyses. The core targets and corresponding compounds were selected for molecular docking. The effect of active components of saffron on the proliferation of CT26 and HCT116 cells was investigated using the cell counting kit-8 (CCK-8). In vitro experiments were conducted by subcutaneous injection of CT26 cells to establish a colon cancer model. Enzyme-linked immunosorbent assay (ELISA), western blotting (WB), real-time polymerase chain reaction (RT-PCR), immunohistochemistry (IHC), and flow cytometry (FCM) were employed to validate the effects of saffron on colorectal cancer immunotherapy. Results1. LC-MS analysis revealed that the main active component of saffron extract was crocin. The active chemicals of saffron intersected with 170 colorectal cancer targets, with 17 predicting targets for saffron treatment. GO and KEGG enrichment analyses revealed that the active components of saffron can prevent colorectal cancer development by enhancing Th17 cell differentiation and the IL-17 signaling pathway. 2. In vitro studies revealed that saffron alcohol extract, crocin, and safranal can suppress the proliferation of CT26 and HCT116 cells. 3. In vivo studies showed that crocin and safranal can increase the body mass and decrease the tumor mass of loaded mice, decrease the serum level of IL-17, and lower the mRNA expression level of IL-17, IL-6, TNF-α, TGF-β, and PD-L1 and IL-17, PD-L1 protein in tumors. This inhibitory effect was strengthened after combined immunotherapy. In addition, saffron modulated CD4+ and CD8+ T cells and the CD4+/CD8+T ratio in mouse spleens. ConclusionThe active components of saffron can reduce the expression of inflammatory factors and ameliorate the immunological microenvironment of tumors via the IL-17 signaling pathway, thereby improving the efficacy of immunotherapy for colorectal cancer. This study provides pharmacological support for the application of saffron in enhancing the efficacy of immunotherapy for colorectal cancer.

Systemic Juvenile Idiopathic Arthritis and arthralgia - can it be diagnosed early within the window period? – An observation of serum biomarkers and analysis with other differential conditions in children

Background: Systemic juvenile idiopathic arthritis (sJIA)is a cause of persisting arthralgia which is often missed. Diagnosing sJIA can be challenging, especially when overt arthritis is absent at presentation, highlighting the need for a diagnostic biomarker. Few recent studies have assessed potential biomarkers for sJIA, however, there is no consensus in detecting early. We conducted a study evaluating serum IL-1, IL-6, IL-18, S100A8, and S100A9 as potential diagnostic markers to distinguish sJIA from other conditions presenting as joint pain in children. Methods: A prospective study was conducted in our institute from May-2019 to October-2020 in children under 16 years, who had persisting arthralgia. Serum concentrations of IL-1, IL-6, IL-18, S100A9, and S100A8 were determined using ELISA kits. Receiver operating curve (ROC) analysis was used to determine the cut-off values for IL-1, IL-6, IL-18, S100A8, and S100A9 for differentiating sJIA from other causes of joint pain and fever. Results- Out of 47 children who presented with joint pain and fever 19 of them were eventually diagnosed with sJIA. In the other 28 children, arthralgia and fever was attributed to conditions other than sJIA (non-sJIA). The non-sJIA group comprised children with acute lymphoblastic leukemia, hemophagocytic histiocytosis, systemic lupus erythematosus, Kawasaki disease, Kikuchi disease, and inflammatory bowel disease. Serum levels of IL-18, S100A8, and S100A9 were significantly higher in patients with sJIA compared to the non-sJIA group (p<0.05). The area under the curve (AUC) was significant for IL-18(77.9%), S100A8 (74.9%), and S100A9(71.2%). A serum IL-18 cut-off level of > 2030.45 pg/ml was useful for differentiating between sJIA and other diseases with a sensitivity of 66.67% and specificity of 75.86% for the diagnosis of sJIA. Conclusion- Serum IL-18, S100A8, and S100A9 can be useful in differentiating sJIA early from other causes of persisting arthralgia in children provided with appropriate identification of symptomatology and suspicion.

The Effect of Monobenzone Cream on Oxidative Stress and Its Relationship With Serum Levels of IL-1β and IL-18 in Vitiligo Patients.

Monobenzyl ether hydroquinone (MEBHQ) is a cream that promotes the spread and evenness of skin patches in vitiligo. Our aim was to investigate the oxidative and inflammatory effects of this cream on vitiligo patients consuming MEBHQ. A case-control study was conducted with three groups of 30 people from the control group, vitiligo patients before and after treatment. The percentage of vitiligo spots was determined by a specialist doctor. The levels of biochemical factors, oxidative stress profile and inflammatory factors were measured by enzymatic, colorimetric and ELISA methods, respectively. Vitiligo patients showed a high level of inflammation and oxidative stress compared to healthy people. Although after 3 months of using MBEHQ cream, the percentage of skin spots in vitiligo patients increased from an average of 63%-91% and the skin color became almost uniform, but it still increased the level of oxidative stress and inflammation in these patients. Although the level of oxidative stress increased significantly in these patients, there was no significant increase in the level of malondialdehyde. The lack of significant differences in the levels of biochemical factors between healthy people and vitiligo patients before and after using the treatment shows the absence of side effects. The use of MBEHQ increased the size of skin spots and uneven skin color in vitiligo patients. Although MBEHQ did not show side effects such as diabetes, liver and kidney diseases, it increased the levels of oxidative stress and inflammatory cytokines, which needs further study.

Royal Jelly Exerts a Potent Anti-Obesity Effect in Rats by Activating Lipolysis and Suppressing Adipogenesis.

Background/Objective: This study examined the anti-obesity effect of royal jelly (RJ) in rats fed with a high-fat diet by targeting the major pathways involved in adipogenesis and lipolysis. In addition, it examined whether this effect is AMPK-dependent. Methods: Five groups of adult male albino rats were used (n = 6 each as 1); the control rats were fed with a normal diet (2.9 kcal), and the other groups were as follows: control + RJ (300 mg/kg), HFD (4.75 kcal), HFD + RJ (300 mg/kg), and HFD + RJ (300 mg/kg) + dorsomorphin (an AMPK inhibitor) (0.2 mg/kg). Results: RJ was administered orally to all rats. With no changes in food and energy intake, RJ significantly reduced gains in body weight, fat weight, body mass index (BMI), the Lee index, abdominal circumference (AC), and the adiposity index (AI). It also reduced fasting glucose and insulin levels, HOMA-IR, and the circulatory levels of free fatty acids (FFAs), triglycerides, cholesterol, and LDL-c in the HFD-fed rats. RJ also increased serum glycerol levels and adiponectin levels, but reduced the serum levels of leptin, IL-6, and TNF-α. Moreover, RJ reduced the secretion of IL-6 and TNF-α from isolated WAT. At the tissue level, the HFD + RJ rats exhibited a smaller adipocyte size compared to the HFD rats. At the molecular level, RJ increased the phosphorylation of AMPK, SREBP1, and ACC-1 and increased the mRNA and protein levels of HSL and ATG in the WAT of the HFD rats. In concomitance, RJ increased the mRNA levels of PGC-α1, reduced the protein levels of PPARγ, and repressed the transcriptional activities of PPARγ, SREBP1, and C/EBPαβ in the WAT of these rats. All the aforementioned effects of RJ were prevented by co-treatment with dorsomorphin. Conclusions: RJ exerts a potent anti-obesity effect in rats that is mediated by the AMPk-dependent suppression of WAT adipogenesis and the stimulation of lipolysis.

Evaluation of Interleukin-6 Levels in Patients with Type 2 Diabetes Mellitus

Background: It has been suggested that inflammatory processes play an important role in the pathogenesis of type 2 diabetes. Individuals who develop type 2 diabetes show signs of low-grade inflammation years before disease onset. This low-grade inflammation has been assumed to be implicated in the pathogenetic mechanisms that cause type 2 Diabetes Mellitus. Inflammatory mediators such as the IL-6 family of cytokines have been proposed to be involved in the events that lead to type 2 diabetes. IL-6 has immunoregulatory actions been proposed to affect glucose homeostasis and metabolism directly and indirectly by action on skeletal muscle cells, adipocytes, hepatocytes, pancreatic b-cells and neuroendocrine cells. Many studies have suggested the role of IL-6 in the pathogenesis of type 2 diabetes mellitus. However, no references have been observed in Bangladesh regarding IL-6 and its association with type 2 diabetes mellitus. It thus may highlight the importance of low-grade inflammation in the pathophysiology of type 2 diabetes mellitus. The purpose of this study was to evaluate type 2 diabetes patients' levels of interleukin-6. Materials and methods: A hospital-based cross-sectional observational study was carried out in the Department of Biochemistry Chittagong Medical College, Department of Endocrinology of Chittagong Medical College Hospital and Chattogram Diabetic Hospital. One hundred (100) type 2 diabetes mellitus patient was included in the study by nonprobability consecutive sampling. Important variables in this study were serum IL-6, BMI, waist circumference and duration of Diabetes Mellitus. Results: The mean serum IL-6 level was 10.08±0.39 pg/ml in patients with type 2 Diabetes Mellitus. Serum IL-6 was positively correlated (r 0.33, p <0.01) with waist circumference and duration of diabetes mellitus (r 0.26, p <0.05). The mean IL-6 was significantly different between BMI groups (F (2,97) =5.39, p=0.006) and was higher in the obese group (10.52±4.00) compared to the overweight and normal BMI (6.78±1.95) and overweight (8.08±3.15) group. Conclusion: It can be concluded that type 2 diabetes mellitus patients had increased serum levels of IL-6. It can give an insight into the possible role of sub clinical inflammation among patients with type 2 Diabetes Mellitus. IAHS Medical Journal Volume 6(2) December 2023; 53-57

Putative role of 6-chogaol against tramadol-induced hepatotoxicity in albino rats via anti-inflammatory, antifibrotic, and antiapoptotic effects

Tramadol is a commonly used drug to relieve pain and avoid premature ejaculation in males with hepatotoxic effects, and 6-chogaol has potent anti-inflammatory and hepatoprotective properties.The work impetus is probing the hepatoprotective mechanisms of 6-chogaol against tramadol hepatoxicity. Twenty adult male rats were enrolled to obtain four equal groups [control group (G1), 6-chogaol group (G2), tramadol group (G3), and 6-chogaol+tramadol group (G4)]. Liver specimens were excised and processed to evaluate hepatocyte injury through histopathological (HP), immunohistochemical (IHC), flow cytometry, and biochemical investigations. The HP study exhibited hepatic injury in G3 hepatocytes (inflammatory cell infiltration, hepatic fibrosis, and disturbed liver structure). The IHC study showed a significant rise in caspase-3 and reduced PCNA immuno-expression (IE). Likewise, the flow cytometry and biochemical experiments exhibited a substantial elevation of apoptotic hepatocytes and the serum levels of IL-1β, IL-6, TNF-α, ALP, ALT, and AST in G3. In contrast, G4 rats significantly improved in all HP, IHC, flow cytometry, and biochemical parameters. Collectively, tramadol intake exerted harmful toxic effects on hepatocytes, whereas 6-Shogaol hampered these changes and served as a natural hepatoprotective agent. Therefore, we advise concurrent intake of 6-Shogaol supplement with tramadol to preserve the integrity of hepatic tissues.

The effect of vitamin C on the recovery of activity and survival of autografted ovaries through inhibition of oxidation and inflammation

Ovarian tissue autografting is a valuable clinical option to help restore fertility in women with cancer. However, many follicles are lost due to ischemia-reperfusion (IR) injury, which depletes follicles after grafting. We aimed to investigate the effect of vitamin C, an antioxidant with anti-apoptotic and anti-inflammatory properties, on improving the structure and function of autografted ovaries in mice. Thirty-six female NMRI mice (4–5 weeks old) were divided into three groups of 12: control (no grafting), autograft + vitamin C (50 mg/kg/day intraperitoneally), and autograft + saline (100 µl/day/animal, intraperitoneally). After the ovarian autografting and before the start of the experiment, each group was further divided into 7-day and 28-day subgroups. Seven days after ovary autografting, serum levels of malondialdehyde (MDA), total antioxidant capacity (TAC), and inflammatory factors were measured. On day 28, ovarian histology, DNA fragmentation, and estradiol and progesterone levels were assessed. Results were analyzed using one-way ANOVA and Tukey’s test, with significance set at p<0.05. In the autograft + vitamin C group, there were significant increases in the mean total volume of the ovary, cortex (p<0.05), medulla, number of follicles, and levels of IL-10, progesterone, estradiol, and TAC (p<0.001), compared to the autograft group. Conversely, the rate of apoptosis and serum levels of MDA, IL-6, and TNF-α were notably reduced in the autograft + vitamin C group (p<0.001). These results suggest that vitamin C can significantly enhance the recovery of autografted ovaries through its antioxidant, anti-inflammatory, and anti-apoptotic effects.

The Usefulness of Serum Interleukin-6 as a Predictor of Response to Atezolizumab plus Bevacizumab Combination Treatment in Hepatocellular Carcinoma

Introduction: In atezolizumab plus bevacizumab (Atezo/Bev) combination treatment, both drugs act on the immune system. Previously, we reported that immunological changes after Atezo/Bev administration for unresectable hepatocellular carcinoma (uHCC) revealed significant alterations in interleukin (IL)-6, soluble IL-2 receptor, tumor necrosis factor-alpha, and programmed cell death-1 levels. Among these variable factors, serum levels of IL-6 can be easily measured on a commercial basis. Therefore, this study aimed to investigate the utility of serum IL-6 as a predictor of tumor response to Atezo/Bev treatment for uHCC. Method: The study included 44 patients with HCC treated with Atezo/Bev. Blood samples were collected before and 3 weeks after treatment, and tumor response was assessed using contrast-enhanced computed tomography 6 weeks after treatment. Results: Significant changes in serum IL-6 levels were observed in patients treated with Atezo/Bev as first-line therapy but not in those treated with it as second-line or later-line therapy. In patients treated with Atezo/Bev as first-line therapy, serum IL-6 levels increased significantly after treatment in patients with a complete or partial response but not in patients with stable or progressive disease. Furthermore, compared to other tumor markers such as alpha-fetoprotein, Lens culinaris agglutinin-reactive fraction of alpha-fetoprotein, and des-gamma-carboxyprothrombin, serum IL-6 levels exhibited the highest sensitivity in predicting tumor response during the treatment period. Conclusion: In patients with uHCC treated with Atezo/Bev, serum IL-6 levels could serve as a potential predictor of tumor response. Elevated levels after treatment may indicate a favorable tumor response and prognosis.

Interleukin-21 and Interleukin-23 levels in familial Mediterranean Fever before and after treatment: the role of cytokines in disease pathogenesis.

In a previous study, it has been shown that the population of Th17 lymphocytes was increased in patients with FMF. IL-21 and IL-23 play significant roles in the production and differentiation of Th17 cells. In this study, we aimed to evaluate serum levels of IL-21 and IL-23 in FMF patients both at diagnosis and after treatment, and to compare these levels with those of healthy controls. Twenty-seven newly diagnosed patients with FMF in attack-free periods and twenty-seven healthy volunteers enrolled in the study. The groups were comparable with respect to age and gender. IL-21 and IL-23 levels in serum samples from patients at the time of diagnosis, in remission after treatment, and from the control groups were analysed using the ELISA method. There was no significant difference between the cytokine levels of the patient group at the time of diagnosis and the cytokine levels of the control group (for IL-21, p: 0.28 and for IL-23, p: 0.56). Similarly, there was no significant difference between the patients' cytokine levels at the time of diagnosis and after treatment (for IL-21, p: 0.99 and for IL-23, p: 0.08). Interleukin levels at the time of diagnosis did not differ among patient groups based on the presence of clinical findings or the M694V genotype. Our results suggest that IL-21 and IL-23 do not play a role in the pathogenesis of the disease. However, while interpreting these findings, it should be considered that patients with active episodes were excluded and cytokine levels were not measured in tissue samples.

Evaluation of lyophilized bacteriophage cocktail efficiency against multidrug-resistant Salmonella in broiler chickens

Currently, phage biocontrol is increasingly used as a green and natural technology for treating Salmonella and other infections, but phages exhibit instability and activity loss during storage. Therefore, in this study, the effects of lyophilization on the activity and stability of phage cocktails for the control of multidrug-resistant Salmonella in broiler chickens were determined. Eight serotypes of Salmonella were isolated and identified from broiler chicken farms, and bacteriophages against multidrug-resistant Salmonella enterica subsp. enterica serovar Kentucky, Salmonella enterica subsp. enterica serovar Typhimrium and Salmonella enterica subsp. enterica serovar Enteritidis were isolated. The bacteriophage cocktail was prepared and lyophilized, and it was subjected to in vitro and in vivo examinations. A reconstituted lyophilized bacteriophage cocktail was used for the oral treatment of chicks before and after challenge with multidrug-resistant S. Kentucky. The colonization of cecum by S. Kentucky was detected by using real-time PCR, and the serum levels of IgM, IgA and IL-4 and pathological changes in the different groups were detected. Three Caudovirales phages families were identified including Autographiviridae, Straboviridae and Drexlerviridae against multidrug-resistant S. Kentucky, S. Typhimrium and S. Enteritidis. The groups treated with the bacteriophage cocktail showed no clinical signs, no postmortem lesions, and a mortality rate of 0%, which improved the growth performance parameters. Additionally, the estimated serum levels of IgM, IgA and IL-4 were significantly greater in the bacteriophage cocktail-treated groups. Lyophilization effectively preserves the long-term storage stability of phages. Therefore, lyophilized bacteriophage cocktail therapy is a valuable approach for controlling multidrug-resistant Salmonella infections in broiler chickens.

Role of Interleukins in Pancreatic Cancer: A Literature Review.

This review article summarizes the pathophysiological aspects of interleukins (ILs) including IL-1, IL-2, IL-3, IL-4, IL-5, IL-6, IL-7, IL-8, IL-9, and IL-10 in pancreatic cancer (PC). Science Direct, PubMed, and Google Scholar were used for the literature review. The search was conducted until August 12, 2024, and particular keywords such as "Pancreatic Cancer," "Interleukins," "Pathophysiological Aspects," "Immunosuppression," "Invasiveness," and "Metastasis" were used. Focusing on interleukins related to pancreatic cancer, 61 original studies were included: 32 studies for human patients, 16 studies for animal models, and 13 studies for both animal models and human patients. All types of PC were considered. The timeframe of 1991 to 2024 was chosen for clinical studies. In epithelial pancreatic tumors, IL-1 is a major inflammation factor. Serum concentrations of soluble interleukin-2-receptor were considerably greater in patients with PC and chronic pancreatitis than in healthy individuals. In comparison to controls, pancreatic cancer patients had considerably greater levels of macrophage colony-stimulating factor and significantly lower levels of stem cell factor and IL-3. The tissues and cells of pancreatic cancer have higher concentrations of IL-4 receptors. IL-5 has a role in the accumulation of pancreatic fibrosis. For individuals with pancreatic ductal adenocarcinoma (PDAC), a high serum level of IL-6 may be a separate risk factor for the development of widespread liver metastases. PDAC patients' peripheral blood mononuclear cells exhibit a substantial upregulation of IL-7 receptor. The role of IL-8 in the growth and spread of PC in humans. The miR-200a/β-catenin axis may be the mechanism by which IL-9 stimulates the proliferation and metastasis of PC cells. Blocking IL-10 in the local microenvironment appears to result in a significant reversal of tumor-induced immunosuppression. The article concludes that interleukins 1, 2, 3, 4, 5, 6, 7, 8, 9, and 10 played significant roles in the pathogenesis of PC.

Associations between Various Inflammatory Markers and Carotid Findings in a Voluntary Asymptomatic Population Sample.

Cardiovascular disease (CVD) is the leading cause of morbidity and mortality worldwide, and atherosclerosis is the key factor promoting its development. Carotid intima-media thickening and the presence of carotid plaques are important indices of cardiovascular risk. In addition, inflammation is a major and complex factor in the development of atherosclerosis. The relationships between carotid atherosclerosis and certain inflammatory markers have rarely been studied in healthy individuals. Therefore, we aimed to investigate the associations between subclinical carotid atherosclerosis and various inflammatory biomarkers in a large Caucasian population free of evident CVD. In addition to recording study participants' demographic characteristics, anthropometric characteristics, and atherosclerotic risk factors, laboratory tests were performed to measure levels of hemoglobin A1c (HbA1c), high-sensitivity C-reactive protein, and inflammatory cytokines/chemokines, including interleukin (IL)-1β, IL-6, IL-8, IL-10, IL-12p70, IL-17A, IL-18, IL-23, IL-33, interferon (IFN)-α2, IFN-γ, tumor necrosis factor-α, and monocyte chemoattractant protein (MCP)-1. This study included 264 asymptomatic individuals with a median age of 61.7 years (interquartile range, 54.5-67.5 years); 45.7% of participants were male. Participants were divided into two groups according to their carotid status: the normal carotid group, comprising 120 participants; and the pathological carotid group, comprising 144 participants. Compared with the normal carotid group, hypertension and diabetes mellitus were significantly more common and serum levels of HbA1c, IL-8, and MCP-1 were significantly higher in the pathological carotid group. Multivariate regression analysis revealed significant positive associations between pathological carotid findings and serum levels of IL-8 (highest tertile, OR: 2.4, p = 0.030) and MCP-1 (highest tertile, OR: 2.4, p = 0.040). Our results suggest that IL-8 and MCP-1 may serve as early indicators of subclinical atherosclerosis, thereby helping to identify individuals at increased risk of CVD before the onset of clinical symptoms.

Differential expression of plasma cytokines in sepsis patients and their clinical implications.

Sepsis, which is characterized by acute systemic inflammation and is associated with high rates of morbidity and mortality, presents a significant challenge in health care. Some scholars have found that the sequential organ failure assessment (SOFA) and quick SOFA scores are not ideal for predicting severe sepsis and mortality. Microbial culture takes a long time (2-3 d) and provides no information for early diagnosis and treatment. Therefore, new diagnostic methods for sepsis need to be explored. To assess cytokine levels in the plasma of sepsis patients and identify potential biomarkers for diagnosing sepsis. Ten sepsis patients admitted to the emergency department within 24 h of onset were enrolled as the observation group, whereas ten noninfected patients served as the control group. Of the 10 noninfected patients, 9 hypertension combined with cerebral infarction, 1 patients with vertiginous syndrome. Plasma Cytokines were measured using the Bio-Plex Pro™ Human Chemokine Panel 40-plex. Differentially expressed cytokines in plasma of sepsis and nonsepsis patients were analyzed using Gene Ontology (GO) functional enrichment and Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway analyses. Interleukin (IL)-16, granulocyte-macrophage granulocyte-macrophage colony-stimulating factor (GM-CSF), CX3CL1, CXCL9, CXCL16, CCL25, and CCL23 plasma levels were significantly increased in sepsis patients. GO analysis revealed that these cytokines were mainly associated with cellular structures such as intermediates, nuclear plaques, adhesion plaques, lateral plasma membranes, and cell matrix junctions. These genes were involved in various molecular functions, such as cytokine activity, receptor ligand activity, and signal receptor activator activity, contributing to various biological functions, such as leukocyte chemotaxis, migration, and chemotaxis. KEGG analysis indicated involvement in cytokine cytokine receptor interactions, chemokine signaling pathways, virus-protein interactions with cytokines and cytokine receptors, and the tumor necrosis factor signaling pathway. Elevated serum levels of IL-16, GM-CSF, CX3CL1, CXCL9, CXCL16, CCL25, and CCL23 in sepsis patients suggest their potential as diagnostic biomarkers for sepsis.

Effects of intravenous pulse methylprednisolone in neuromyelitis optica during the acute phase.

Neuromyelitis optica spectrum disorder (NMOSD) is an anti-aquaporin 4 (anti-AQP4) autoantibodies-mediated idiopathic inflammatory demyelinating disease of the central nervous system. While intravenous pulse methylprednisolone (IVMP) is the recommended initial treatment option for acute onset NMOSD, its therapeutic mechanism remains unclear. We hypothesized that IVMP would reduce the expression of pro-inflammatory factors and increase the resolution of inflammation in patients with NMOSD. Mendelian randomization (MR) analysis was used to screen meaningful inflammatory and resolution factors for inclusion. Three MR methods with inverse variance weighting (IVW) were primarily used to identify positive results. Interleukin (IL)-10, IL-1β, IL-6, C-X-C motif chemokine ligand 12 (CXCL12), and tumor necrosis factor-related apoptosis-inducing ligand (TRAIL) were screened from 41 inflammatory factors, and resolvin D1 (RvD1), maresin 1 (MaR1), and lipoxin A4 (LXA4) were screened from 6 resolution markers for inclusion. Subsequently, 12 patients with NMOSD were enrolled and treated with IVMP. Serum levels of the aforementioned inflammatory and resolution markers were measured by enzyme-linked immunosorbent assay before and after IVMP treatment. High levels of TRAIL, CXCL12, and IL-1β were associated with an increased risk of NMOSD (TRAIL: odds ratio [OR], 1.582; 95% confidence interval [CI], 1.003-2.495; CXCL12: OR, 3.610; 95% CI, 1.011-12.889; IL-1β: OR, 4.500; 95% CI, 1.129-17.927). High levels of RvD1, MaR1, and LXA4 were associated with a reduced risk of NMOSD (RvD1: OR, 0.725; 95% CI, 0.538-0.976; MaR1: OR, 0.985; 95% CI, 0.970-0.999; LXA4: OR, 0.849; 95% CI, 0.727-0.993). Among patients with NMOSD, serum levels of IL-6, CXCL12, and TRAIL significantly decreased following IVMP treatment, compared with pretreatment levels, while levels of IL-1β, LXA4, and MaR1 significantly increased after IVMP treatment (p < 0.05). A significant positive correlation was observed between CXCL12 levels and Expanded Disability Status Scale (EDSS) scores (r = 0.451, p < 0.05). Several systemic inflammatory regulators associated with the pathogenesis of NMOSD were identified. The protective roles of LXA4 and MaR1 may be indispensable components of glucocorticoid treatment. Therefore, the use of resolution markers may be a potential strategy for improving central nervous system injury in individuals with NMOSD.

Impacts of gentamycin toxicity: nephroprotective role of guarana through different signaling pathways.

Gentamicin is a widely used aminoglycosidic antibiotic since its discovery. Like any other medication gentamicin causes unwanted side effects such as hepatotoxicity and nephrotoxicity. This study aims to examine the antioxidant effect of the guarana seed extract in protecting renal tissue. Forty male mice were divided into four groups (group one was control with free access to food and water, group two was treated orally with 300mg/kg of guarana seed extract daily, group three was injected intraperitoneally with 100mg/kg of gentamicin daily and the fourth group was co-treated with both 300mg/kg of guarana seed extract orally and injected intraperitoneally with 100mg/kg of gentamicin daily) for two weeks. Serum levels of urea, creatinine, AST, ALT, IL-1β and IL-6 have significantly elevated in the gentamicin treated group and those changes were not found in the guarana co-treated group. In gentamicin treated mice, a significant reduction was observed in two antioxidants SOD and GPX accompanied by downregulation of Ho-1 and Nrf2 while, that did not happen in the guarana seed extract co-treated group. Histopathology and immunohistochemistry slides show that the guarana seed extract prevents degenerative and necrotic events in tubular epithelial tissues caused by gentamicin toxicity. In conclusion, current data suggest that gentamicin can damage renal tissues when given at 100mg/kg/day, however, the guarana seed extract may be capable of preventing that event when cotreated with the gentamicin as a supplement.

Effects of acupuncture on serotonin, histamine, substance P, and tryptase levels at sensitized points in model rats with knee osteoarthritis

ObjectiveTo elucidate the differences in manual acupuncture effectiveness at sensitized points by investigating the mechanisms of local skin action at different sensitization points in rats with knee osteoarthritis (KOA). MethodsForty Sprague–Dawley rats were equally divided into control, model (1 mg of monoiodoacetate into the right knee joint cavity), sham operation, manual acupuncture at right Tianjing acupoint (MAR-SJ 10), and left SJ 10 groups. Safranine-O and fast green staining were used to assess the modeling. The morphological and functional changes in mast cells (MCs) were assessed during acupoint sensitization using toluidine blue and immunofluorescence staining. The levels of serotonin, histamine, substance P (SP), and tryptase at skin acupoints and serum levels of IL-β, IL-6, and TNF-α were detected using ELISA. ResultsAfter 14 days of treatment, the number of MCs and their degranulation rates were statistically higher in the model group than in the control group (both P < .001). After applying acupuncture, the levels of 5-HT, HA, and SP at skin acupoints were lower than those in the model group (all P < .05), and tryptase level was higher (both P < .05). Tryptase level was higher on the skin at the MAL-SJ 10 acupoint than that on the MAR-SJ 10 acupoint (P = .004). Compared with the model group, the serum levels of IL-1β, IL-6, and TNF-α in the MAR-SJ 10 and MAL-SJ 10 groups were lower (all P < .05). ConclusionAcupuncture at KOA-sensitized acupoints mitigates joint injury in KOA rats and may bidirectionally regulate local MCs of these acupoints. This finding not only enhances the reference value of sensitizing points in clinical diagnosis and treatment, but also contributes to the understanding of the biological mechanisms underlying acupuncture intervention at sensitizing points.

Evaluation of Regulatory B Cells and Serum IL-10 Concentration in Peripheral Blood of Women with Recurrent Pregnancy Loss

Background: Although the role of B cells in normal pregnancy has been recently highlighted, their importance and function are not completely clarified. Until now, some investigations have shown that during pregnancy, regulatory B cells (Breg), a subset of B cells, are one of the key players in immune regulation by both producing IL-10 and cell-cell interactions. Therefore, any decrease in the number or function of these cells may lead to recurrent pregnancy loss (RPL). Thus, the objective of this study was to characterize Breg cell frequency and function in women who suffered from RPL in comparison with healthy non-pregnant and pregnant women (under twenty weeks of gestational age) as controls. Method: In this study, peripheral blood samples of women suffering from RPL (n=8), women with normal pregnancy under 20 weeks of gestational age (n=14), and healthy nonpregnant women (n=10) were collected. The frequency of Breg cells (CD19+CD24hiCD38hi) was measured by flow cytometry. The serum level of the IL-10 cytokine, as a marker of Breg cell function, was measured by ELISA. Results: The Percentage of Breg cells in women who suffered from RPL was significantly lower than that of women who had normal pregnancies (P=0.0016). The percentages of Breg cells in women who suffered from RPL were also significantly lower than in non-pregnant women (P=0.0001). Furthermore, no significant differences were observed in Breg cell percentages between normal pregnant and non-pregnant women. Evaluation of IL-10 concentration in the serum of women who had participated in this study showed no significant differences between the three groups. Conclusion: Based on our results, the number of Breg cells was significantly lower in RPL women than in healthy non-pregnant and normal-pregnant women, which shows the significance of these cells in the maintenance of normal pregnancy. However, we could not detect significant differences in the serum levels of IL-10, bringing to mind the notion that the beneficial and supportive function of these cells during pregnancy might be independent of IL-10 secretion. by these cells. Thus, screening of Breg cells in women with pregnancy complications, especially RPL, could be helpful for predicting a healthy pregnancy.

Serum IFN-γ Predicts the Therapeutic Effect of Belimumab in Refractory Lupus Nephritis Patients.

To evaluate belimumabf's efficacy in refractory lupus nephritis (LN) patients and identify predictive serum biomarkers for treatment response. In this single-arm retrospective study,we assessed clinical responses in LN patients at baseline and six months after initiating belimumab. Serum cytokines (IL-2, IL-4, IL-6, IL-10, TNF-α, IFN-γ) were quantified using multiplex magnetic bead flow immunoassay before and after treatment. Fourteen patients with various subtypes of refractory LN participated in the study: seven with class III and V LN, three with type V alone, two with class III, and two with class IV+V and V LN. Post six months of belimumab therapy, all participants exhibited a reduction in the Systemic Lupus Erythematosus Disease Activity Index (SLEDAI)-2K scores from their respective baseline values. Notably, most patients showed a decrease in the dosage of prednisone, levels of 24-hour urinary protein, immunoglobulins, erythrocyte sedimentation rate (ESR), and anti-double-stranded DNA antibody IgM, along with serum levels of IL-4, IL-6, IL-10, and IFN-γ. Meanwhile, levels of C3, C4, IL-2, and TNF-α were observed to increase. Of the participants, nine (64.29%) achieved a complete renal response, one (7.14%) showed a partial response, and four (28.57%) exhibited no response. Significantly, higher baseline serum IFN-γ levels were found in patients who did not achieve complete renal response (CR) compared to those who did (p = 0.009). Receiver operating characteristic (ROC) curve analysis demonstrated that baseline IFN-γ levels had an area under curve (AUC) of 0.96 (0.70-1.00), with a sensitivity of 0.89 and a specificity of 1.00 (p < 0.001). Belimumab shows potential efficacy in treating refractory LN. Baseline serum IFN-γ levels may predict response to belimumab therapy, potentially enabling more targeted treatment approaches for this challenging condition.

Anticancer and Immunomodulatory Activities of Prodigiosin Extracted and Purified from Serratia marcescens.

Prodigiosin is a naturally occurring compound produced by various bacteria, including Serratia marcescens. It is known for its diverse biological properties. The present study was conducted to extract and purify prodigiosin from Serratia marcescens and investigate its anticancer and immunomodulatory activities. S. presence was isolated from soil samples and characterized. Different solvents were used to extract prodigiosin from Serratia marcescens. The cytotoxic activity of prodigiosin was tested against human rhabdomyosarcoma (RD), rat embryo fibroblasts (REF), and human breast cancer MDA-MB-231 (MDA) epithelial cell lines. Albino mice were divided into six groups: Negative control (normal saline); positive control (injected with 100 µ l of Serratia marcesence); groups A-D were injected with 100 µ l of prodigiosin (1, 3, 6, and 9 µ g/mouse, respectively). After 14 days of treatment, whole blood samples were collected for immunomodulatory analysis. The study found that the highest yield of prodigiosin (65-230 mg/l) was obtained with methanol as the extraction solvent. Prodigiosin had a cytotoxic effect on cancer cells, particularly against MDA epithelial cells. However, it did not have a cytotoxic effect on normal cells. Immunological analysis revealed significant differences (p ≤ 0.01) in absolute neutrophil counts between the positive control and prodigiosin-treated groups, with the highest value in group C and the lowest in group A. Immunological analysis showed significant differences in neutrophil counts, IL-4, and IL-10 levels between prodigiosin-treated groups and the control group. Serratia marcescens prodigiosin showed cytotoxic effects on cancer cells and boosted IL-10 and IL-4 serum levels, acting as an immunomodulator.

IL-4, IL-7, IL-9, NT, NRP1 May Be Useful Markers in the Diagnosis of Endometrial Cancer.

The search for novel endometrial cancer diagnostic biomarkers is pertinent. The purpose of this study was to determine if IL-4, IL-7, IL-9, IL-10, NT, TSP-2, and NRP1 could be used as novel, helpful markers for the detection of endometrial cancer. Ninety-three women diagnosed with endometrial cancer (EC) and sixty-six patients with noncancerous endometrial lesions (NCEL) were included in this study. ELISA was used to measure the concentrations of the proteins tested. Median serum levels of IL-4, IL-7, IL-9, NT, and NRP1 were significantly higher in the EC group compared with NCEL. The cut-off level of IL-4 was set at 802.26 pg/mL with a sensitivity of 83.87% and a specificity of 50% (AUC = 0.7, p = 0.000023). The cut-off level of IL-7 was set at 133.63 ng/L with a sensitivity of 96.77% and a specificity of 75.76% (AUC = 0.91, p < 0.000001). The cut-off level of IL-9 was set at 228.79 pg/mL with a sensitivity of 69.89% and a specificity of 81.82% (AUC = 0.8, p < 0.000001). The cut-off level of NT was set at 275.43 pmol/L with a sensitivity of 94.62% and a specificity of 59.09% (AUC = 0.83, p < 0.000001). The cut-off level of NRP1 was set at 30.37 ng/mL with a sensitivity of 81.72% and a specificity of 57.58% (AUC = 0.71, p = 0.000004). This study suggests the clinical utility of IL-4, IL-7, IL-9, NT, and NRP1 in the diagnosis of endometrial cancer. Nevertheless, these biomarkers may also have prognostic or predictive value, which should be tested in future studies.