Serum IL-6 Research Articles

Predictive Value of the sFlt-1/PlGF Ratio and Interleukin-6 for the Presence of Placental Lesions in Spontaneous Preterm Labor with Intact Membranes with Delivery within 7 Days.

The aim of the study was to identify predictive values of the soluble fms-like tyrosine kinase/placental growth factor (sFlt-1/PlGF) ratio and interleukin (IL)-6, assessed with a clinically available method in a large-volume biochemistry laboratory, in maternal blood, amniotic fluid, and umbilical cord blood for the presence of the placental lesions consistent with maternal vascular malperfusion (MVM) and acute histological chorioamnionitis (HCA), respectively. This retrospective study included 92 women with preterm labor with intact membranes (PTL) delivered within 7 days of admission with gestational ages between 22+0 and 34+6 weeks. The sFlt-1/PlGF ratio and IL-6 were assessed in stored samples of maternal serum, amniotic fluid, and umbilical cord serum using Elecsys® sFlt-1, PlGF, and IL-6 immunoassays. Women with MVM had a higher sFlt-1/PlGF ratio in the maternal serum, compared to those without MVM (19.9 vs. 4.6; p < 0.0001), but not in the amniotic fluid or umbilical cord blood. A cut-off value of 8 for the sFlt-1/PlGF ratio in maternal serum was identified as optimal for predicting MVM in patients with PTL. Women with HCA had higher concentrations of IL-6 in maternal serum, compared to those without HCA (11.1 pg/mL vs. 8.4 pg/mL; p = 0.03), amniotic fluid (9,216 pg/mL vs. 1,423 pg/mL; p < 0.0001), and umbilical cord blood (20.7 pg/mL vs. 10.7 pg/mL, p = 0.002). Amniotic-fluid IL-6 showed the highest predictive value. A cut-off value of IL-6 concentration in the amniotic fluid of 5,000 pg/mL was found to be optimal for predicting HCA in PTL. Maternal serum sFlt-1/PlGF and amniotic fluid IL-6 concentrations can be used for liquid biopsy to predict placental lesions in women with PTL who deliver within 7 days.

Role of Th2, Th17 and Treg Cells and relevant cytokines in pathogenesis of allergic rhinitis

ObjectiveTo explore the role of different cells and molecules in the pathogenesis of allergic rhinitis (AR) with positive Artemisia allergen by detecting their expression levels.MethodsFrom January 2021 to December 2022,200 AR patients diagnosed in the Otolaryngology Clinic of Ordos Central Hospital were selected as the AR group, and 50 healthy people who underwent physical examination in the hospital during the same period were randomly selected as the healthy control (HC) group. The levels of GATA-3mRNA, RORγtmRNA and FoxP3mRNA in peripheral blood mononuclear cells were detected by real-time fluorescence quantitative PCR (qRT-PCR). The proportions of Th2, Th17 and Treg cells were detected by flow cytometry. The concentrations of IL-4, IL-5, IL-17 and IL-10 in serum were detected by enzyme-linked immunosorbent assay. The differences of transcription gene level, immune cell ratio and cytokine concentration between the two groups were analyzed.ResultsThere was no difference in age and gender between the two groups. The levels of GATA-3mRNA and RORγtmRNA transcription genes in peripheral blood mononuclear cells, the percentage of Th2, Th17 and Treg immune cells, the levels of eosinophils and basophils in peripheral blood, the concentrations of IL-4, IL-5, IL-17, IL-10 cytokines and IgE in serum of AR patients were significantly higher than those in HC group (P < 0.05). IL-4 and IL-17 were positively correlated with total IgE level.ConclusionThe secretion of immune cells and cytokines in peripheral blood of AR patients is abnormal. Th2, Th17, Treg specific transcription factors and related cells and cytokines are involved in the occurrence and development of allergic rhinitis.

Intestinal microbiota and probiotic intervention in children with bronchial asthma

ObjectiveThis study aims to understand the differences in intestinal flora, expression of helper T cells, allergy-related indicators, and cytokine levels between children with bronchial asthma and healthy children. The study seeks to clarify the effectiveness and safety of probiotic preparations in the treatment of bronchial asthma in children, and to provide new methods for the treatment of bronchial asthma. MethodsA total of 66 pediatric patients aged 3–6 years with bronchial asthma and 35 healthy children undergoing physical examination during the same period were enrolled, designated as the asthma group and the healthy group, respectively. The asthma group was further divided into the probiotic group and the non-probiotic group based on whether probiotics were used. The gut microbiota, serum IgE antibody levels, cytokines (IL-4, IL-5, IL-9, IL-13 levels), proportions of helper T cells (Th1, Th2), and hypersensitive C-reactive protein were measured and compared among the groups. ResultsChildren with bronchial asthma had decreased abundance and reduced diversity of intestinal flora compared to the healthy group. At the genus level, the asthma group showed increased abundance of Bacteroides and decreased abundance of Faecalibacterium and Veillonella; The probiotic group demonstrated a significantly higher improvement in the abundance of these genera before and after treatment compared to the non-probiotic group (P < 0.05). Compared to the healthy group, children with asthma had elevated levels of serum IgE, IL-4, IL-5, IL-9, and IL-13, as well as a decreased Th1/Th2 ratio, all of which showed statistical differences (P < 0.05). After treatment, all immune indicators improved. Specifically, the probiotic group exhibited a more significant decrease in serum IgE, IL-4, and IL-13 levels compared to the non-probiotic group (P < 0.05). ConclusionChildren with bronchial asthma exhibit dysbiosis of intestinal flora, characterized by an increased abundance of the Bacteroides and decreased abundance of the Faecalibacterium and Veillonella. This imbalance in intestinal flora increases the risk of allergic diseases. Probiotics can effectively improve dysbiosis of intestinal flora, contributing to the balance of immune function in children, and can be used as an adjunct therapy for the treatment of bronchial asthma.

Effect of whole-grain Tartary buckwheat fermentation with Monascus purpureus on the metabolic syndrome and intestinal flora in mice

This study investigated changes in the composition of fermented whole-grain Tartary buckwheat (FTB) by Monascus purpureus and the therapeutic effects of FTB on metabolic diseases in mice fed high-fat and high-sugar (HFHS) diets. Compared to raw Tartary Buckwheat (RTB), the protein, total phenol, and total flavonoid contents of FTB were significantly increased by 67.88%, 24.97%, and 45.74%, respectively, especially the rutin content reached 2607.31 mg/100g DW (p < 0.05, p < 0.01, p < 0.0001). Meanwhile, it exhibits stronger antioxidant properties of DPPH, ABTS, and FRAP (p < 0.05, p < 0.01). Then, the treatment of low (3 g/kg), medium (6 g/kg), and high (12 g/kg) doses of FTB (FL, FM, FH) could positively regulate weight, blood lipids, pro-inflammatory factors, glucose tolerance, and liver damage in HFHS mice. Among all groups, the levels of weight (35.53 g), fat (0.93 g/100 g), TG (0.77 mmol/L), IL-1β (84.77 ng/L), IL-6 (127.62 pg/L) and insulin (7.06 mIU/L) of serum, IL-1β (74.89 ng/L) and TNF-α (840.32 pg/L) of liver were all the lowest in FH group. Furthermore, the intestinal flora compositions were positively regulated by FTB treatment, including reducing the relative abundance of harmful bacteria (Clostridia_UCG-014, Candidatus_Saccharimonas, and Enterorhabdus) and enhancing the relative abundance of beneficial bacteria (Akkermansia and Eubacterium coprostanoligenes). Particularly, the phyla Firmicutes/Bacteroidetes (F/B) ratio was markedly restored and the abundance of Akkermansia and Eubacterium coprostanoligenes was significantly increased in the FH group (p < 0.0001). In conclusion, FTB can be used as a dietary supplement for improving metabolic syndrome and intestinal flora disorders. This study provides new ideas for the use of whole-grain Tartary buckwheat, new product development, and industry chain enhancement.

Features of the course of the disease, quality of life and cytokine profile in patients with psoriasis vulgaris in the stationary stage and comorbid depression

Aim. To study the characteristics of the course of the disease, quality of life and cytokine profile in patients with psoriasis vulgaris in the stationary stage and depression.Material and methods. A prospective, cross-sectional comparative study involved 154 patients with vulgar psoriasis in the stationary stage; Of these, two groups were formed: 83 patients with comorbid depression and 71 without comorbid depression. The Hamilton scale was used to determine depressive symptoms and severity.Result. Patients with psoriasis vulgaris in the stationary stage and depression were characterized by a younger age (p=0.007), a more severe course of the disease according to the PASI index (p&lt;0.001), visual analogue scale (p=0.014), and a higher frequency of relapses (p=0.012) and a lower level of quality of life according to the DLQI questionnaire (p&lt;0.001), as well as higher values of IL-6 and IL-17 in the blood serum (p=0.011; p=0.001, respectively). An inverse correlation was established between the average total value on the Hamilton scale and the age of the patients (r= –0.61; p=0.002), a direct one – with the average total values on the PASI index (r=0.72; p=0.001), visually analogue scale (r=0.63; p&lt;0.001), DLQI (r=0.69; p=0.001) and IL-17 (r=0.62; p=0.012).Conclusion. In patients with depression, psoriasis vulgaris in the stationary stage is more severe, accompanied by an increase in systemic proinflammatory changes and a more significant decrease in quality of life than in patients without depression. The results obtained must be taken into account when choosing a therapeutic strategy for psoriasis vulgaris, which will personalize treatment and increase its effectiveness.

Effect of Palmitoylethanolamide Compared to a Placebo on the Gut Microbiome and Biochemistry in an Overweight Adult Population: A Randomised, Placebo Controlled, Double-Blind Study.

This study investigates the effects of palmitoylethanolamide (PEA) on the gut microbiome of overweight adults. Fifty-eight participants (twenty males, thirty-eight females) aged 18-65 years with a BMI range of 30-40 kg/m2 were recruited. Participants were randomised to receive PEA (n = 36) or a placebo (n = 22) for 12 weeks. Microbiota composition, richness, diversity, and metabolic functions, faecal short chain fatty acids and calprotectin, pathology markers, and health-related questionnaires were analysed throughout the 12 weeks of supplementation. PEA supplementation significantly reduced triglyceride levels and IL-2 concentrations. No significant differences were found in the overall microbiota composition between the groups, and microbiota richness and diversity remained consistent for both groups. Functional analysis demonstrated no differences in functional richness and diversity, but specific pathways were modified. PEA supplementation resulted in a decrease in the abundance of pathways related to aromatic compound degradation, NAD interconversion, and L-glutamate degradation, while pathways associated with molybdopterin biosynthesis and O-antigen building blocks exhibited increased abundance. Increased production of O-antigen results in smooth LPS associated with reduced pathogenic stealth and persistence. PEA supplementation may influence specific microbial species, metabolic pathways, and reduce serum triglyceride and IL-2 concentration, shedding light on the intricate relationship between PEA, the microbiome, and host health.

Hesperetin Alleviated Experimental Colitis via Regulating Ferroptosis and Gut Microbiota.

Hesperetin (HT) is a type of citrus flavonoid with various pharmacological activities, including anti-tumor, anti-inflammation, antioxidant, and neuroprotective properties. However, the role and mechanism of HT in ulcerative colitis (UC) have been rarely studied. Our study aimed to uncover the beneficial effects of HT and its detailed mechanism in UC. Experimental colitis was induced by 2.5% dextran sodium sulfate (DSS) for seven days. HT ameliorated DSS-induced colitis in mice, showing marked improvement in weight loss, colon length, colonic pathological severity, and the levels of TNFα and IL6 in serum. A combination of informatics, network pharmacology, and molecular docking identified eight key targets and multi-pathways influenced by HT in UC. As a highlight, the experimental validation demonstrated that PTGS2, a marker of ferroptosis, along with other indicators of ferroptosis (such as ACSL4, Gpx4, and lipid peroxidation), were regulated by HT in vivo and in vitro. Additionally, the supplement of HT increased the diversity of gut microbiota, decreased the relative abundance of Proteobacteria and Gammaproteobacteria, and restored beneficial bacteria (Lachnospiraceae_NK4A136_group and Prevotellaceae_UCG-001). In conclusion, HT is an effective nutritional supplement against experimental colitis by suppressing ferroptosis and modulating gut microbiota.

Serum Sirt6 as a Potential Biomarker for Osteoarthritis and its Correlation with IL-6 Alterations.

The study aimed to assess Sirt6 levels in serum of knee osteoarthritis (OA) patients compared to healthy individuals to evaluate its correlation with OA and to understand how Sirt6 is linked with the change in IL-6 levels. The cross-sectional study involved 50 knee OA patients clinically diagnosed as per the American College of Rheumatology guidelines and 50 healthy controls. Radiological examination as per Kellgren-Lawrence (KL) criteria was done to determine the disease severity. Peripheral blood samples were collected from each participant, and serum Sirt6 and IL-6 levels were measured using ELISA. The serum Sirt6 levels in knee OA patients were significantly lower as compared to healthy controls (p = 0.023). Patients with knee OA of KL grade 4 had significantly lower Sirt6 levels as compared to those with KL grade 2 OA (p = 0.031). Individuals of younger age group had higher Sirt6 levels compared to older age group. IL-6 levels in knee OA patients were significantly higher as compared to controls (p = 0.007). A negative correlation was observed between serum Sirt6 and IL-6 levels (r = -0.407; p = 0.035). The study concludes that serum Sirt6 levels are inversely associated with knee OA and may serve as a potential biomarker for the disease. Moreover, a negative correlation between Sirt6 and IL-6 levels was observed in this study. Further investigations are necessary to confirm these findings and to explore the mechanisms by which Sirt6 and IL-6 are involved in OA.

Efficacy of stem cells versus microvesicles in ameliorating chronic renal injury in rats (histological and biochemical study)

Chronic exposure to heavy metals as aluminum chloride (AlCl3) could result in severe health hazards such as chronic renal injury. The present study aimed to evaluate the therapeutic potential of adipose tissue-derived stem cells (ASCs) in comparison to their microvesicles (MV) in AlCl3-induced chronic renal injury. Forty-eight adult male Wistar rats were divided into four groups: Control group, AlCl3-treated group, AlCl3/ASC-treated group, and AlCl3/MV-treated group. Biochemical studies included estimation of serum urea and creatinine levels, oxidative biomarkers assay, antioxidant biomarkers, serum cytokines (IL-1β, IL-8, IL-10, and IL-33), real time-PCR analysis of renal tissue MALT1, TNF-α, IL-6, and serum miR-150-5p expression levels. Histopathological studies included light and electron microscopes examination of renal tissue, Mallory trichrome stain for fibrosis, Periodic acid Schiff (PAS) stain for histochemical detection of carbohydrates, and immunohistochemical detection of Caspase-3 as apoptosis marker, IL-1B as a proinflammatory cytokine and CD40 as a marker of MVs. AlCl3 significantly deteriorated kidney function, enhanced renal MDA and TOS, and serum cytokines concentrations while decreased the antioxidant parameters (SOD, GSH, and TAC). Moreover, serum IL-10, TNF-α, miR-150-5p, and renal MALT1 expression values were significantly higher than other groups. Kidney sections showed marked histopathological damage in both renal cortex and medulla in addition to enhanced apoptosis and increased inflammatory cytokines immunoexpression than other groups. Both ASCs and MVs administration ameliorated the previous parameters levels with more improvement was detected in MVs-treated group. In conclusion: ASCs-derived MVs have a promising ameliorating effect on chronic kidney disease.

Fevogrit, a polyherbal medicine, mitigates endotoxin (lipopolysaccharide)-induced fever in Wistar rats by regulating pro-inflammatory cytokine levels.

Fever is characterized by an upregulation of the thermoregulatory set-point after the body encounters any pathological challenge. It is accompanied by uncomfortable sickness behaviors and may be harmful in patients with other comorbidities. We have explored the impact of an Ayurvedic medicine, Fevogrit, in an endotoxin (lipopolysaccharide)-induced fever model in Wistar rats. Active phytoconstituents of Fevogrit were identified and quantified using ultra-high-performance liquid chromatography (UHPLC) platform. For the in-vivo study, fever was induced in male Wistar rats by the intraperitoneal administration of lipopolysaccharide (LPS), obtained from Escherichia coli. The animals were allocated to normal control, disease control, Paracetamol treated and Fevogrit treated groups. The rectal temperature of animals was recorded at different time points using a digital thermometer. At the 6-h time point, levels of TNF-α, IL-1β and IL-6 cytokines were analyzed in serum. Additionally, the mRNA expression of these cytokines was determined in hypothalamus, 24 h post-LPS administration. UHPLC analysis of Fevogrit revealed the presence of picroside I, picroside II, vanillic acid, cinnamic acid, magnoflorine and cordifolioside A, as bioactive constituents with known anti-inflammatory properties. Fevogrit treatment efficiently reduces the LPS-induced rise in the rectal temperature of animals. The levels and gene expression of TNF-α, IL-1β and IL-6 in serum and hypothalamus, respectively, was also significantly reduced by Fevogrit treatment. The findings of the study demonstrated that Fevogrit can suppress LPS-induced fever by inhibiting peripheral or central inflammatory signaling pathways and could well be a viable treatment for infection-induced increase in body temperatures.

The antioxidant, anti-inflammatory, and anti-apoptotic effects of sesamin against cisplatin-induced renal and testicular toxicity in rats

Purpose The present study investigated the nephron-testicular protective effects of sesamin against cisplatin (CP)-induced acute renal and testicular injuries. Methods Thirty-two male Wistar rats were allocated to receive carboxymethylcellulose (0.5%, as sesamin vehicle), CP (a single i.p. 5 mg/kg dose), CP plus sesamin at 10 or 20 mg/kg orally for 10 days. Results Data analysis showed significant increases in serum urea, creatinine, interleukin (IL)-1, IL-6, and tumor necrosis factor-α (TNF-α), as well as renal and testicular tissue malondialdehyde and nitric-oxide concentrations in CP-intoxicated rats in comparison to control animals. On the contrary, rats treated with CP only exhibited significantly lower (p < .05) serum testosterone, tissue glutathione, and activities of endogenous antioxidant enzymes compared to control rats. Histopathologically examining CP-intoxicated rats’ tissues using H&E and PAS stains showed atrophied glomeruli, interstitial inflammatory cells, atypic tubular epithelium with focal apoptosis, and reduced mucopolysaccharide content. Further, immunohistochemical staining of the same group revealed an increase in p53 and cyclooxygenase-II (Cox-II) expression in renal and testicular tissues. Treatment with sesamin alleviated almost all the changes mentioned above in a dose-dependent manner, with the 20 mg/kg dose restoring several parameters’ concentrations to normal ranges. Conclusions In brief, sesamin could protect the kidneys and testes against CP toxicity through its antioxidant, anti-inflammatory, and anti-apoptotic effects.

Mechanism analysis of essential oil from Radix Bupleuri for the treatment of asthma through regulation of ectopic olfactory receptor

Ethnopharmacological relevanceRadix Bupleuri is the root of Bupleurum chinense DC. (BC) and a classic aromatic traditional Chinese medicine. The traditional pharmacological effects of Radix Bupleuri are alleviating bronchial spasms, dilating airways, and promoting the resolution of respiratory inflammation, thereby reducing asthma symptoms. Aim of the studyStudies have demonstrated the efficacy of water extracts from BC in asthma treatment. However, the potential role of volatile oil, another active constituent in BC, remains unexplored with asthma. Notably, volatile oil is renowned for its ease of absorption and direct targeting of affected areas, offering distinct advantages in alleviating airway inflammation. This study aims to explain the anti-asthmatic mechanism of BC-oil through in vivo and in vitro pharmacological experiments. Materials and methodsFirstly, the OVA-induced SD rat asthma model was utilized to evaluate the pharmacological effect of BC-oil by lung function monitoring, HE staining, flow cytometry, ELISA, and RT-qPCR. The anti-asthmatic mechanism was further analyzed by combining transcriptomic analysis of lung tissue from rat model and airway smooth muscle tissue from public database. Initially, GC-MS was used to analyze the components of BC-oil. The anti-asthmatic activity was evaluated in 16-HBE, RBL-2H3, and ASMC cells using CAMKII inhibitors to explore of the critical signal transduction regulated by BC-oil. Furthermore, molecular docking and calcium flow assay were utilized to screen and identify the active components from BC-oil. ResultsOral administration of BC-oil significantly enhanced pulmonary function in asthmatic SD rats by reducing airway resistance and elastic resistance. Additionally, BC-oil inhibited inflammatory cytokines, including serum IL-2, pulmonary Il1b, Tnf, and Cxcl13, demonstrating potent anti-inflammatory and immunomodulatory effects. In this study, we analyzed the significant role of OR2W3 in asthma using public transcriptomic data. Furthermore, we indicated that BC-oil regulated the expression of Olr1433 and GNAL in rat lung tissue. BC-oil reduced degranulation and inhibited gene expression of Il3 and Tnf in RBL-2H3 cells and suppressed gene expression of IL8 and TNF in 16-HBE cells. BC-oil also attenuated airway smooth muscle cell proliferation and expression of Acta2 and Ccnd1. Furthermore, BC-oil regulates asthma-related cellular processes by activating CAMKII. GC-MS analysis identified 11 components of BC-oil, and n-hexadecanoic acid, linoleic acid and oleic acid from BC-oil were identified to interact with OR2W3 by molecular docking. The calcium flow assay revealed linoleic acid as a significant activator of OR2W3 and indicated that BC-oil alleviated asthma through the ectopic olfactory signaling pathway. ConclusionsThe mechanism of BC-oil in treating asthma through signal transduction of OR2W3 is revealed at the molecular and cellular levels.

Effects of Sea-Buckthorn Flavonoids on Growth Performance, Serum Inflammation, Intestinal Barrier and Microbiota in LPS-Challenged Broilers.

The experiment investigated the effects of sea-buckthorn flavonoids (SF) on lipopolysaccharide (LPS)-challenged broilers. A total of 288 one-day-old male broilers were randomly assigned to 4 groups, with 6 replicates of 12 broilers each. The experiment lasted for 20 days. The diet included two levels of SF (0 or 1000 mg/kg) and broilers intraperitoneally injected with 500 μg/kg LPS on 16, 18, and 20 days, or an equal amount of saline. LPS challenge decreased final body weight, average daily gain, and average daily feed intake, increased feed-to-gain ratio, and elevated serum IL-1β, IL-2, TNF-α, D-LA, and endotoxin levels. Moreover, it resulted in a reduction in the IL-10 level. LPS impaired the intestinal morphology of the duodenum, jejunum, and ileum, down-regulated the mRNA relative expression of Occludin, ZO-1, and MUC-2 in the jejunum mucosa, up-regulated the mRNA relative expression of TLR4, MyD88, NF-κB, and IL-1β, and increased the relative abundance of Erysipelatoclostridium in broilers (p < 0.05). However, SF supplementation mitigated the decrease in growth performance, reduced serum IL-1β, IL-2, and D-LA levels, increased IL-10 levels, alleviated intestinal morphological damage, up-regulated mRNA expression of Occludin and ZO-1, down-regulated the mRNA expression of TLR4, NF-κB, and IL-lβ in jejunum mucosal (p < 0.05), and SF supplementation presented a tendency to decrease the relative abundance of proteobacteria (0.05 < p < 0.1). Collectively, incorporating SF can enhance the growth performance, alleviate serum inflammation, and improve the intestinal health of broilers, effectively mitigating the damage triggered by LPS-challenges.

Association of interleukin6 rs1800796 gene polymorphism and serum level with bladder cancer in Egyptian population.

Urinary bladder cancer (UBC)is a common tumor of the urinary tract. To assess the diagnostic significance of IL6 rs1800796 gene polymorphism and IL6 serum level among Egyptian patients with UBC. One hundred patients with UBC were selected from the Mansoura Urology and Nephrology Center, in addition to 100 healthy control subjects; using PCR and ELISA techniques for IL6 detection. The rs1800796 GC, CC genotypes, and C allele were significantly more prevalent in the cases with bladder cancer compared to the healthy group (p < 0.001, = 0.021, < 0.001 respectively). There was a clear association between elevated levels of IL6 and bladder cancer versus the control group (median = 4.2, 0.89 respectively, p < 0.001). Serum IL6 levels showed significantly higher levels in patients carrying CC, followed by GC then GG genotypes. No significant association was found between IL6 rs1800796 gene polymorphism or serum level with demographic or laboratory data. It is suggested that there is a clear link between elevated IL6 levels as well as IL6 rs1800796 gene polymorphism with bladder cancer, suggesting their potential utility as biomarkers for the disease.

Ameliorative effect of nano-pregabalin in gastrocnemius muscle of gamma irradiated rats with an experimental model of fibromyalgia: Crosstalk of Sirt3, IL-1β and PARP1 pathways

BackgroundFibromyalgia (FM) is a complex syndrome with somatic symptoms connected to the operational state of muscles. Although radiotherapy is a cornerstone in cancer treatment, it is implicated in the aggravation of FM. Lately, formulation of medicines in nano-forms become of great prominence due to their prospective applications in medicine. So, this study aimed to assess possible therapeutic benefits of formulating pregabalin in a nono-form (N-PG) for managing FM during exposure to gamma radiation. MethodsGamma rays administered in fractionated doses (2 Gy/day) to male rats after one hour of s.c. injection of reserpine (1 mL/kg per day) to induce FM, then treated with single daily dose of (30 mg/kg, p.o.) PG or N-PG for ten successive days. Rats were subjected to behavioral tests, then sacrificed to obtain serum and gastrocnemius muscles. ResultsN-PG significantly antagonized reserpine-induced FM as proved by; the immobility and performance times in forced swim and rotarod performance tests, respectively were restored near to the normal time, serum IL-8 and MCP-1 chemokines were nearby the normal levels, mitigated oxidative stress through increasing total thiol, Sirt3, CAT enzyme and decreasing COX-1, inhibition of inflammation via IL-1β and MIF significant reduction, it possessed anti-apoptotic effect verified by decreasing PARP-1 and increasing Bcl-XL, gastrocnemius muscles had minimal fibrosis levels as seen after Masson trichrome staining. Histopathological results were coincidence with biochemical inspection. ConclusionThis study identifies N-PG as a novel drug that could be of a value in the management of FM particularly in cancer patients undergoing radiotherapy.

Integrating network pharmacology and experimental models to investigate the efficacy and mechanism of Tiansha mixture on xerosis.

Epidermal Growth Factor Receptor Inhibitors (EGFRIs) is a common cancer therapy, but they occasionally cause severe side effects such as xerosis. Tiansha mixture (TM), a traditional Chinese medicines formulation, is develpoed to treat xerosis. This study aims to understand mechanisms of TM on xerosis. Bio-active compounds were selected from databases (TCMSP, TCM-ID, HERB, ETCM) and removed for poor oral bioavailability and low drug likeness. Then a network-based approach filtered out potential active compounds against xerosis. KEGG enrichment analysis identified PI3K/AKT and ERK/MAPK pathways, which were further verified by molecular docking. Afterwards, the effect of TM on activation of PI3K/AKT and ERK/MAPK pathways was validated in gefitinib-induced xerosis rats, where AKT-activator SC79 and MAPK-activator CrPic were also applied. Skin damage was assessed by dorsal score and HE and Tunel stainings. the levels of inflammation factors IL-6 and TNF-α in serum and skin tissue were measured by ELISA. Western blot was used to detect protein levels in the pathways. Network pharmacology identified 111 bio-active compounds from TM and 14 potential targets. Docking simulation showed apigenin, luteolin, and quercetin bio-active compounds in TM bound to IKBKG, INSR, and RAF-1 proteins. In xerosis model rats, TM mitigated xerosis damage, decreased inflammation factors, and phosphorylation of PI3K/AKT and ERK/MAPK proteins. SC79 or CrPic or their combination reversed TM's effect. The current study identified potential targets and PI3K/AKT and ERK/MAPK pathways involved in the effect of TM on xerosis, thus providing a foundation for TM clinical application.

Effects of Zhoutian moxibustion on pain symptoms and inflammatory factors in patients with ankylosing spondylitis of cold-damp obstruction

To observe the effects of Zhoutian moxibustion on pain symptoms and serum inflammatory factors in patients with ankylosing spondylitis of cold-damp obstruction. Eighty-four patients with ankylosing spondylitis of cold-damp obstruction were randomly divided into a Zhoutian moxibustion group (42 cases, 2 cases dropped out) and a governor vessel moxibustion group (42 cases, 2 cases dropped out, 1 case discontinued). Both groups were given oral administration of sulfasalazine enteric-coated tablets as basic treatment. The governor vessel moxibustion group was treated with moxibustion box from Dazhui (GV 14) to Yaoyangguan (GV 3), one hour per treatment; the Zhoutian moxibustion group was treated with moxibustion box from Tiantu (CV 22) to Zhongji (CV 3) in addition to the governor vessel moxibustion group, two hours per treatment. Both groups were treated once every 3 days, twice a week, for a total of 9 weeks. The pain symptom scores of the two groups were observed before treatment and at the 3rd, 6th, and 9th weeks into treatment. ELISA was used to detect the levels of serum interleukin (IL)-1β, IL-18, and tumor necrosis factor-α (TNF-α) before and after treatment, and the clinical efficacy of the two groups was evaluated after treatment. Except for the joint pain scores at the 3rd week into treatment, the total scores and the each sub-item score of pain symptom in the two groups were lower than those before treatment at the 3rd, 6th, and 9th weeks into treatment (P<0.05); at the 3rd, 6th, and 9th weeks into treatment, the total scores of pain symptom and the scores of lumbar sacral pain, back pain, joint cold pain, and limited mobility in the Zhoutian moxibustion group were lower than those in the governor vessel moxibustion group (P<0.05). After treatment, the levels of serum IL-1β, IL-18 and TNF-α in both groups were lower than those before treatment (P<0.05), and the levels of serum IL-1β, IL-18, and TNF-α in the Zhoutian moxibustion group were lower than those in the governor vessel moxibustion group (P<0.05). The total effective rate was 90.0% (36/40) in the Zhoutian moxibustion group, which was higher than 76.9% (30/39) in the governor vessel moxibustion group (P<0.05). Zhoutian moxibustion could effectively improve various pain symptoms in patients with ankylosing spondylitis of cold-damp obstruction, and reduce the expression of inflammatory factors.

Intersecting Blood Cytokines With Cholesterol Parameters to Profile Patients With Advanced Solid Tumors Receiving Immune Checkpoint Inhibitors.

The study investigated the relationship between serum proinflammatory cytokine levels, cholesterol metabolism, and clinical outcome in cancer patients undergoing immune checkpoint inhibitors (ICIs). Peripheral blood was collected before therapy from ICI-treated advanced cancer patients. We retrospectively assessed plasma total cholesterol (TC), ABCA1- and ABCG1-mediated cholesterol efflux (CE), passive diffusion (PD), cholesterol loading capacity (CLC), and serum IL-6, IL-10, and TNF-α. The association between blood cholesterol parameters and inflammatory cytokines and their effect on overall survival (OS), progression-free survival (PFS), and clinical benefit (CB) from ICIs were statistically assessed. Among 70 consecutively enrolled patients (nonsmall cell lung cancer: 94%; renal cell carcinoma: 6%), TC, CLC, and cholesterol PD resulted significantly higher in IL-6 low and IL-10 low cases ( P <0.05), whereas ABCA1-mediated CE was increased in IL-10 high patients ( P =0.018). Uni- and multivariable analysis revealed meaningfully longer OS and PFS in IL-6 low (HR 2.13 and 2.97, respectively) and IL-10 low (HR 3.17 and 2.62) groups. At univariate analysis all cholesterol-related indices significantly correlated with OS and PFS, whereas at multivariate only high PD was validated as a protection factor (OS, HR 0.75; PFS, HR 0.84). Finally, uni- and multivariable showed a statistically significant inverse association of CB with ABCG1-CE (OR 0.62), as with IL-6 (OR 0.13) and IL-10 (OR 0.10). In-depth characterization of the interplay between blood cholesterol metabolism and immune-inflammatory cytokines might provide novel insights into the complex relationship among cancer, inflammation, lipids profile, and response to immunotherapy.

Gleditsiae Sinensis Fructus ingredients and mechanism in anti-asthmatic bronchitis research

BackgroundGleditsiae Sinensis Fructus (GSF) is commonly used in traditional medicine to treat respiratory diseases such as bronchial asthma. However, there is a lack of research on the chemical composition of GSF and the pharmacological substance and mechanism of action for GSF in treating bronchial asthma. PurposeThe chemical constituents of GSF were analyzed using ultrahigh-performance liquid chromatography-quadrupole-Orbitrap high-resolution mass spectrometry (UHPLC-Q-Orbitrap HRMS). In this study, we combined network pharmacology, molecular docking techniques, and experimental validation to explore the therapeutic efficacy and underlying mechanism of GSF in the treatment of bronchial asthma. MethodsCharacterization of the chemical constituents of GSF was conducted using UHPLC-Q-Orbitrap HRMS. The identified chemical components were subjected to screening for active ingredients in the Swiss Absorption, Distribution, Metabolism, and Excretion (ADME) database. Relevant databases were utilized to retrieve target proteins for the active ingredients and targets associated with bronchial asthma disease, and the common targets between the two were selected. Subsequently, the protein-protein interaction (PPI) network was constructed using the String database and Cytoscape software to identify key targets. Gene Ontology (GO) and the Kyoto Encyclopedia of Genes and Genomes (KEGG) enrichment analyses were performed using the Metascape database. The "component-common target" network was constructed using Cytoscape to identify the primary active ingredients. Molecular docking validation was conducted using AutoDock software. The bronchial asthma mouse model was established using ovalbumin (OVA), and the lung organ index of the mice was measured. Lung tissue pathological changes were observed using hematoxylin and eosin (HE), Periodic Acid-Schiff (PAS), and Masson staining. The respiratory resistance (Penh) of the mice was assessed using a pulmonary function test instrument. An enzyme-linked immunosorbent assay (ELISA) was used to determine the levels of IgE, IL-4, IL-5, and IL-13 in the mouse serum. Immunofluorescence staining was performed to detect the protein expression levels of AKT and PI3K in the lung tissues. An in vitro experiment was performed to observe the effects of echinocystic acid (EA) on IL-4 stimulated Human ASMCs (hASMCs). Cell viability was measured using a CCK-8 assay to calculate the IC50 value of the EA. A wound healing test was conducted to observe the effect of EA on degree of healing. RT-qPCR was performed to detect the influence of EA on the mRNA expression levels of ALB, SRC, TNF-α, AKT1, and IL6 in the cells. ResultsA total of 95 chemical constituents were identified from the GSF. Of these, 37 were identified as active ingredients. There were 169 overlapping targets between the active ingredients and the disease targets. A topological analysis of the protein-protein interaction (PPI) network identified the core targets as IL6, TNF, ALB, AKT1, and SRC. An enrichment analysis revealed that the treatment of bronchial asthma with GSF primarily involved the AGE-RAGE signaling pathway and the PI3K-Akt signaling pathway, among others. The primary active ingredients included 13(s)-HOTRE, linolenic acid, and acacetin. The molecular docking results demonstrated a favorable binding activity between the critical components of GSF and the core targets. Animal experimental studies indicated that GSF effectively improved symptoms, lung function, and lung tissue pathological changes in the OVA-induced asthmatic mice, while alleviating inflammatory responses. GSF decreased the fluorescent intensity of the AKT and PI3K proteins. The IC50 value of EA was 30.02μg/ml. EA (30) significantly promoted the proliferation of IL4-stimulated hASMCs cells. EA (30) significantly increased the expression of ALB and SRC mRNA and decreased the expressions of TNF-α, AKT, and IL6 mRNA. ConclusionThe multiple active ingredients found in GSF exerted their anti-inflammatory effects through multiple targets and pathways. This preliminary study revealed the core target and the mechanism of action underlying its treatment of bronchial asthma. These findings provided valuable insights for further research on the pharmacological substances and quality control of GSF.

HGF ameliorates cardiomyocyte apoptosis and inflammatory response in sepsis via the phosphatidylinositol 3-kinase (PI3K)/protein kinase B (AKT) pathway

ObjectiveThis study aimed to analyze the impact of HGF on cardiomyocyte injury, apoptosis, and inflammatory response induced by lipopolysaccharide (LPS). MethodsEnzyme-linked immunosorbent assay (ELISA) was utilized to quantify the levels of HGF, interleukin (IL)-6, IL-10, creatine phosphokinase-isoenzyme-MB (CK-MB), and cardiac troponin I (cTnI) in the samples. qPCR and Western blotting (WB) were employed to assess the mRNA and protein expressions of HGF, IL-10, IL-6, PI3K, AKT, p-PI3K, and p-AKT. ResultsThe outcomes of the in vivo experiment revealed that serum levels of IL-6, IL-10, HGF and SOFA scores in the SC group were elevated in contrast to the non-SC group. The correlation analysis indicated a substantial and positive association among serum HGF, IL-6, and IL-10 levels and SOFA scores. Relative to IL-6, IL-10 levels, and SOFA scores, serum HGF demonstrated the highest diagnostic value for SC. Following LPS administration to stimulate H9c2 cells across various periods (0, 12, 24, 48, and 72 h), the levels of myocardial injury markers (CK-MB and cTnI) in the cell supernatants, intracellular inflammatory factors (mRNA and protein levels of IL-10 and IL-6), apoptosis and ROS levels, exhibited a gradual increase followed by a subsequent decline. Following the overexpression of HGF, there was an increase in cell viability, and a decrease in apoptosis, inflammation, oxidative stress injuries, and the protein phosphorylation expressions of PI3K and AKT. After knockdown of HGF expression, the activity of LPS-induced H9c2 cells was further reduced, leading to increased cell injury, apoptosis, inflammation, oxidative stress,and the expression levels of PI3K and Akt protein phosphorylation were further elevated. ConclusionHGF was associated with decreased LPS-induced H9c2 apoptosis and inflammation in H9c2 cells, alongside an improvement in cell viability, indicating potential cytoprotective effects. The mechanism underlying these impacts may be ascribed to the suppression of the PI3K/AKT signaling pathway.