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Among the properties melatonin is claimed to possess, are the immuno-inflammation inductive capacities that would be responsible of some of the paramount of activities melatonin is reported to have in most of the human pathological conditions. In the present paper, we measured the effect of melatonin on established cellular models of immuno-inflammation, and found none. The discrepancies are discussed, especially because those properties are reported at pharmacological concentration (1 μM and beyond) at which the melatonin receptors are desensitized by internalization, leading to putative non-receptor-dependent mechanism of action. • The melatonin enthusiasts are ruining Science reputation, by claiming facts that are often wishful thinking. • Melatonin is not able to boost most of the actors of the immune system, even at pharmacological concentrations. • We hope to be able to show that some of the activities of melatonin are pure fantasies. [ABSTRACT FROM AUTHOR]

To evaluate the effect of eight weeks of combined physical exercise of moderate intensity on inflammatory markers, as well as its relationship with body composition in young women recently admitted to a Public Institution of Higher Education. Longitudinal, intervention study, in which 59 female participants aged 18–25 years were evaluated before and after a combined physical exercise program for eight weeks. Blood samples were collected before and after the intervention for analysis of C-reactive protein and inflammatory cytokines. Weight and height were measured to calculate body mass index and body composition was evaluated by Dual Energy X-Ray Absorptiometry before and after the intervention. Statistical analyzes performed were t -test, Willcoxon test and Spearman's correlation. This study was approved by the Human Research Ethics Committee and the Free and Informed Consent Form was signed by all participants. After the intervention, there was a reduction in the pro-inflammatory cytokines (IL-1β, IL-6, TNF and IL-12), while the anti-inflammatory (IL-10) and CRP did not change; reduction in the total body gynoid fat mass and in the percentage of body fat; increased trunk and total muscle mass. Body composition was negatively correlated with the pro-inflammatory interleukins IL-1β and IL-6 and positively correlated with CRP. Combined physical exercise for eight weeks acted to reduce pro-inflammatory cytokines, fat mass and increase in muscle mass. Inflammatory markers correlated with body fat before the intervention, suggesting the participation of visceral adipose tissue in the release of these markers in female university students. [ABSTRACT FROM AUTHOR]

The tumor microenvironment is importantly shaped by various cytokines, where interleukins (ILs) and interferons (IFNs) shape the balance of immune activity within tumor niche and associated lymphoid organs. Their importance in activation and tuning of both innate and adaptive immune responses prompted their use in several clinical trials, albeit with limited therapeutic efficacy and risk of toxicity due to systemic administration. Increasing preclinical evidence suggests that local delivery of ILs and IFNs could significantly increase their effectiveness, while simultaneously attenuate the known side effects and issues related to their biological activity. A prominent way to achieve this is to use cell-based delivery vehicles. For this purpose, mesenchymal stromal stem cells (MSCs) are considered an almost ideal candidate. Namely, MSCs can be obtained in large quantities and from obtainable sources (e.g. umbilical cord or adipose tissue), their ex vivo expansion is relatively straightforward compared to other cell types and they possess very low immunogenicity making them suitable for allogeneic use. Importantly, MSCs have shown an intrinsic capacity to respond to tumor-directed chemotaxis. This review provides a focused and detailed discussion on MSC-based gene therapy using ILs and IFNs, engineering techniques and insights on potential future advancements. [Display omitted] • MSCs represent one of the most ideal candidates for intratumoral cytokine delivery. • Both ILs and IFNs importantly shape the tumor microenvironment. • Gene delivery of ILs and IFNs can favourably shape the tumor immune contexture. • MSCs can be modified to gain synergistic anti-tumor effects and to inhibit tumor promoting activities of certain cytokines. [ABSTRACT FROM AUTHOR]

Biomarkers for depression in patients with acute coronary syndrome (ACS) have not been identified. This study evaluated multiple serum biomarkers for depressive disorders after ACS. Thirteen serum biomarkers associated with seven functional systems, along with sociodemographic/clinical characteristics, were evaluated in 969 patients within 2 weeks after ACS onset (acute phase). In total, 711 patients were evaluated for depressive disorder using DSM-IV criteria 1 year later (chronic phase). Logistic regression was used for the analysis. Depressive disorders were observed in 378 patients (39.0%) in the acute phase of ACS and 183 patients (25.7%) in the chronic phase. The weighted scores of five serum biomarkers (high-sensitivity C-reactive protein, interleukin-6, homocysteine, troponin I, and creatine kinase-MB) were significantly associated with depressive disorder diagnosis in the acute phase, and the weighted scores of three other biomarkers (tumor necrosis factor-alpha, interleukin-1 beta, and homocysteine) were significantly associated with depressive disorders in the chronic phase, in a dose-dependent manner after adjusting for relevant covariates (all P -values <0.001). The combination of several serum biomarkers exhibited robust associations with depressive disorders in both the acute and chronic phases of ACS. • Biomarkers for depression in acute coronary syndrome (ACS) have not been determined. • Combination of hsCPR, IL-6, homocysteine, troponin I, CK-MB predicted depression at acute phase. • Combination of TNF-α, IL-1β, homocysteine predicted depression at chronic phase. • Multiple serum biomarkers improved identification of depression in ACS. [ABSTRACT FROM AUTHOR]

Patients with colorectal cancer (CRC) are at high risk of frailty, leading to reduced quality of life and survival. Diet is associated with frailty in the elderly through regulating inflammation. Thus, we hypothesized that dietary inflammatory potential (as assessed by dietary inflammatory index [DII]) might be associated with frailty in patients with CRC through regulating inflammatory biomarkers. A total of 231 patients with CRC were included in this cross-sectional study. Dietary intake was evaluated by 3-day, 24-hour dietary recalls, and frailty status was assessed in accordance with the Fried frailty criteria. Plasma inflammatory cytokines were determined in 126 blood samples. A total of 67 patients (29.0%) were frail, with significantly higher DII scores than nonfrail patients, accompanied with significantly increased interleukin-6 (IL-6) and decreased interleukin-10 (IL-10) concentrations. Each 1-point increase of DII was related to a 25.0% increased risk of frailty. IL-6 was positively correlated with frailty and DII, whereas IL-10 was negatively correlated. After adjusting for age, sex, body mass index, education level, smoking status, and energy, mediation analysis revealed that the association between DII and frailty was significantly mediated by IL-6 (average causal mediation effect [ACME], 0.052; 95% confidence interval, 0.020–0.087; P =.002) and IL-10 (ACME, 0.025; 95% confidence interval, 0.004–0.063; P =.016). The ρ values for the sensitivity measure at which estimated ACMEs were zero were 0.3 and –0.2 for IL-6 and IL-10, respectively. Therefore, a pro-inflammatory diet was associated with frailty in patients with CRC possibly in part by affecting circulating IL-6 and IL-10 concentrations. In a sample of 231 patients with colorectal cancer, compared with nonfrail patients, frail patients consumed more pro-inflammatory diets indicated by higher DII scores and had higher plasma IL-6 and lower IL-10 concentrations. Higher DII was associated with increased risk of frailty. IL-6 was positively correlated with frailty and DII, whereas IL-10 was negatively correlated. Mediation analysis showed that the association between DII and frailty might be mediated in part by IL-6 and IL-10. Abbreviations : DII, dietary inflammatory index; IL-6, interleukin 6; IL-10, interleukin 10. [Display omitted] • 29.0% (67/231) patients with colorectal cancer were frail and 71.0% were non-frail. • Frail colorectal cancer patients consumed lower macronutrients and micronutrients. • Frail colorectal cancer patients had a higher dietary inflammatory index score. • A higher dietary inflammatory index was associated with a higher risk of frailty. • IL-6 and IL-10 were mediators in the association between diet and frailty. [ABSTRACT FROM AUTHOR]

The modulation of glucose metabolism through dietary sources has been recognized as 1 of the most sustainable approaches for preventing of cardiometabolic diseases. Although fibers and phenolic compounds derived from jaboticaba (Plinia jaboticaba) peel have demonstrated improvements in metabolic pathways in preclinical models, their beneficial effects in clinical trials remain to be fully determined. This study aimed to assess the impact of jaboticaba peel (JP) powder supplementation on glucose metabolism compared with a placebo in individuals with metabolic syndrome (MetS). A single-blind, parallel, randomized, placebo-controlled trial involving 49 individuals with MetS was conducted. Participants were assigned to receive either a JP supplement (15 g/day) or a matched placebo. Anthropometry measurements, body composition, blood pressure, metabolic and inflammatory parameters, and a mixed-meal tolerance test were assessed at weeks 0 and 5. Daily intake of JP improved the area under the curve of glucose (P =.025) and the interleukin-6 (IL-6) (P =.045). No significant time × treatment effects were observed for blood pressure, body weight, body composition, lipid metabolism, glucagon-like peptide-1, inflammatory cytokines (tumor necrosis factor-α, IL-1β), C-reactive protein, and insulin sensitivity and resistance indexes. JP supplementation may be a promising approach for managing MetS disorders, potentially by reducing the area under the curve for glucose and the proinflammatory cytokine IL-6. This research is registered at the Brazilian Registry of Clinical Trials (RBR-8wwq9t). Obesity constitutes a primary component of metabolic syndrome. Hyperglycemic and hyperlipidemic conditions prompt adipocytes to accumulate lipids. This abnormal lipid accumulation leads to dysfunctional adipose tissue, fostering inflammation, insulin resistance, and the secretion of pro-inflammatory adipokines. The consumption of jaboticaba peel, rich in anthocyanins and fiber, was shown in this study to yield beneficial effects in metabolic syndrome by reducing postprandial glucose and inflammation. Abbreviation: IL-6, interleukin-6. [Display omitted] [ABSTRACT FROM AUTHOR]

Açaí seed extract (ASE) is obtained from Euterpe oleracea Mart. (açaí) plant (Amazon region) has high nutritional and functional value. ASE is rich in polyphenolic compounds, mainly proanthocyanidins. Proanthocyanidins can modulate the immune system and oxidative stress by inhibiting the toll-like receptor-4 (TLR-4)/myeloid differentiation primary response 88 (MyD88)/nuclear factor-κB (NF-κB) pathway. A great deal of evidence suggests that inflammatory cytokines and oxidative stress contribute to the pathogenesis of intestinal mucositis, and these events can lead to intestinal dysmotility. We hypothesized that ASE acts as an anti-inflammatory and antioxidant compound in intestinal mucositis induced by 5-fluorouracil (5-FU) through modulation of the TLR-4/MyD88/phosphatidylinositol-3-kinase α/mechanistic target of rapamycin/NF-κBp65 pathway. The animals were divided into linear 5-FU (450 mg/kg) and 5-FU + ASE (10, 30, and 100 mg/kg) groups. The weight loss of the animals was evaluated daily. Samples from duodenum, jejunum, and ileum were obtained for histopathological, biochemical, and functional analyses. ASE reduced weight loss, inflammatory parameters (interleukin-1β; tumor necrosis factor-α; myeloperoxidase activity) and the gene expression of mediators involved in the TLR-2/MyD88/NF-κB pathway. ASE prevented histopathological changes with beneficial effects on gastrointestinal transit delay, gastric emptying, and intestinal absorption/permeability. In conclusion, ASE protects the integrity of the intestinal epithelial barrier by inhibiting the TLR/MyD88/PI3K/mechanistic target of rapamycin/NF-κBp65 pathway. Açaí is a plant from the Amazon region that has a high nutritional and functional value. A polyphenol-rich açaí seed extract showed protective effects against inflammation and oxidative stress, improved histological lesion, and delayed gastric emptying induced by 5-fluorouracil in mice. These effects were observed through TLR-4/MyD88/PI3K/mTOR/NF-κBp65 signaling pathway. Abbreviations: 5-FU, 5-fluorouracil; ASE, açaí seed extract; mTOR, mechanistic target of rapamycin; MyD88, myeloid differentiation primary response 88; NF-κBp65, nuclear factor-κBp65; PI3K, phosphatidylinositol-3-kinase α; TLR-4, toll-like receptor 4. [Display omitted] [ABSTRACT FROM AUTHOR]

Interleukin-27 (IL-27), a potential mediator linking obesity to inflammatory diseases, is considered an important candidate for regulating obesity. The present study evaluated the relationship of IL-27 with obesity and insulin resistance (IR) and further investigated the changes in IL-27 levels after weight loss. The study analyzed 405 participants, of whom 62 with overweight or obesity completed one year of lifestyle intervention. The body compositions, including percent of body fat (PBF), visceral fat area (VFA), skeletal muscle mass (SMM), and visceral fat area to skeletal muscle mass ratio (VSR), were assessed using the bioelectrical impedance analysis method. Serum IL-27 levels were measured using the enzyme-linked immunosorbent assay (ELISA). IL-27 levels increased significantly with the increase in body mass index (BMI) (P < 0.001). Moreover, IL-27 levels were positively correlated with PBF, VFA, and VSR. Homeostatic model assessment for insulin resistance (HOMA-IR), the inverse of hepatic insulin sensitivity (1/HISI), adipose tissue insulin resistance (Adipo-IR), and homeostasis model assessment-adiponectin (HOMA-AD) increased significantly with each quartile of IL-27 levels (all P < 0.001). IL-27 levels significantly decreased after weight loss (P < 0.001). IL-27 was positively correlated with obesity, HOMA-IR, 1/HISI, Adipo-IR, and HOMA-AD. IL-27 levels significantly decreased after weight loss. • We used body composition to assess obesity to avoid the limitations of body mass index (BMI). • Interleukin-27 (IL-27) levels increased significantly with the increase in BMI, percent body fat, visceral fat area (VFA), and the ratio of VFA to skeletal muscle mass. • We initially found that IL-27 was positively correlated with homeostatic model assessment for insulin resistance (HOMA-IR), the inverse of hepatic insulin sensitivity (1/HISI), adipose tissue insulin resistance (Adipo-IR), and homeostasis model assessment-adiponectin (HOMA-AD). • IL-27 levels showed a significant decrease after weight loss. [ABSTRACT FROM AUTHOR]

Anti-inflammatory activities of catechin-rich green tea extract (GTE) in obese rodents protect against metabolic endotoxemia by decreasing intestinal permeability and absorption of gut-derived endotoxin. However, translation to human health has not been established. We hypothesized that GTE would reduce endotoxemia by decreasing gut permeability and intestinal and systemic inflammation in persons with metabolic syndrome (MetS) compared with healthy persons. A randomized, double-blind, placebo-controlled, crossover trial in healthy adults (n = 19, 34 ± 2 years) and adults with MetS (n = 21, 40 ± 3 years) examined 4-week administration of a decaffeinated GTE confection (890 mg/d total catechins) on serum endotoxin, intestinal permeability, gut and systemic inflammation, and cardiometabolic parameters. Compared with the placebo, the GTE confection decreased serum endotoxin (P =.023) in both healthy persons and those with MetS, while increasing concentrations of circulating catechins (P <.0001) and γ-valerolactones (P =.0001). Fecal calprotectin (P =.029) and myeloperoxidase (P =.048) concentrations were decreased by GTE regardless of health status. Following the ingestion of gut permeability probes, urinary lactose/mannitol (P =.043) but not sucralose/erythritol (P >.05) was decreased by GTE regardless of health status. No between-treatment differences (P >.05) were observed for plasma aminotransferases, blood pressure, plasma lipids, or body mass nor were plasma tumor necrosis factor-α, interleukin-6, or the ratio of lipopolysaccharide-binding protein/soluble cluster of differentiation-14 affected. However, fasting glucose in both study groups was decreased (P =.029) by the GTE confection compared with within-treatment arm baseline concentrations. These findings demonstrate that catechin-rich GTE is effective to decrease circulating endotoxin and improve glycemic control in healthy adults and those with MetS, likely by reducing gut inflammation and small intestinal permeability but without affecting systemic inflammation. • A novel green tea extract (GTE) confection was provided to healthy adults and adults with metabolic syndrome. • GTE increased circulating catechins and valerolactones regardless of health status. • GTE decreased intestinal inflammation and small intestinal permeability. • GTE decreased circulating endotoxin. • GTE decreased fasting glucose without affecting systemic inflammation. • Gut-level benefits by GTE support research translation for cardioprotection by green tea. Healthy adults and adults with metabolic syndrome were randomized to a placebo or GTE (1 g; 890 mg catechins) confection for 1 month and then crossed-over to the alternative treatment following a 1-month washout. Regardless of health status, the GTE confection decreased fecal biomarkers of intestinal inflammation (calprotectin and myeloperoxidase) and small intestinal permeability based on a differential sugar absorption test while decreasing serum endotoxin. Abbreviations: GTE, green tea extract; MetS, metabolic syndrome [Display omitted] [ABSTRACT FROM AUTHOR]

Periodontitis is an inflammatory condition of the tooth-supporting structures triggered by the host's immune response towards the bacterial deposits around the teeth. It is well acknowledged that pro-inflammatory interleukin (IL)-6, IL-8, MCP-1 as well as the NOD-like receptor family pyrin domain containing 3 (NLRP3) inflammasome, are the key modulators in the activation of this response. Erbium-doped yttrium-aluminium-garnet (Er:YAG) laser, a solid-state crystal laser have been commonly used in the treatment of periodontal diseases. However, little is understood about the molecular mechanism of the Er:YAG laser, especially in targeting the host immune response brought on by periodontal pathogens. Hence, the current study focused on the protective effects of Er:YAG laser on periodontitis in-vitro in terms of pro-inflammatory cytokines, chemokines and NLRP3 inflammasome expressions. Human periodontal ligament fibroblast (PDLFs) were first stimulated with lipopolysaccharides (LPS) from P. gingivalis (Pg-LPS) to simulate periodontitis. Cells were then irradiated with Er:YAG laser of ascending energy densities (3.6–6.3 J/cm2), followed by cell proliferation and wound healing assay. Next, the effects of Er:YAG laser on the expressions of IL-6, IL-8, MCP-1, NLRP3, and cleaved GSDMD were examined. Pg-LPS was found to reduce cell's proliferation rate and wound healing ability in PDLFs and these were rescued by Er:YAG laser irradiation. In addition, LPS stimuli resulted in a marked upregulation in the secretion of IL-6, IL-8 and MCP-1 as well as the mRNA and protein expression of NLRP3 and cleaved-GSDMD protein whereas Er:YAG laser suppressed the elicited phenomena. To our knowledge, this is the first study to look into the laser's implication on the NLRP3 inflammasome in periodontitis models. Our study reveals a crucial role of Er:YAG laser in ameliorating periodontitis in-vitro through the modulation of IL-6, IL-8, MCP-1 and the NLRP3 inflammasome and highlights that the control of the NLRP3 inflammasome may become a potential approach for periodontitis. [ABSTRACT FROM AUTHOR]

• Fucoidan ameliorated dextran sulfate sodium-induced ulcerative colitis through promoting autophagy. • Fucoidan-induced autophagy improved colon barrier and reshaped gut microbiota. • The present study supported the therapeutic potential of fucoidan for the adjuvant treatment of other autophagy-related diseases. Although previous research has unveiled the remedial effects of fucoidan, an extract from marine algae, on ulcerative colitis (UC), the precise mechanisms remain elusive. Animal studies have suggested a connection between autophagy and the beneficial influences of fucoidan intervention. We hypothesized that fucoidan's alleviative effects on dextran sulfate sodium (DSS)-induced UC could be ascribed to autophagy. For our study, we chose 36 male C57BL/6 mice and administered 100 or 400 mg/(kg/body weight/day) of fucoidan via gavage for 5 consecutive weeks. During the last week, the mice were given 3% DSS in drinking water to induce UC. In contrast to the DSS-induced UC model, fucoidan intervention prevented DSS-induced body weight loss, mitigated colon shortening, improved colon mucosa damage, enhanced the intestinal barrier, and reduced serum inflammatory factor concentrations. Furthermore, fucoidan intervention reshaped the gut microbiota compositions, increased the relative abundance of Bacteroidota, Muribaculaceae_unclassified, Clostridiales_unclassified , and Lachnospiraceae_NK4A136_group , and decreased the relative abundance of Firmicutes, Proteobacteria, and Escherichia-Shigella , which led to a lower Firmicutes/Bacteroidota ratio. Additionally, fucoidan treatment enhanced autophagy, as evidenced by upregulated protein expressions of BECLIN1, ATG5, ATG7, and an increased microtubule-associated-proteinlight-chain-3-II/microtubule-associated-proteinlight-chain-3-I ratio. Our findings corroborated the ameliorating effects of fucoidan intervention on DSS-induced UC through autophagy activation, reorganization of gut microbiota, and fortification of the intestinal barrier. This lends support to the therapeutic potential of fucoidan as a natural bioactive ingredient for future UC treatments in humans. Rapidly increasing incidence of UC imposed an enormous burden on health care. The aim of this study was to investigate the potential mechanisms of fucoidan to ameliorate DSS-induced UC. Fucoidan treatments improved the intestinal barrier, regulated gut microbiota composition, decreased serum inflammatory factors concentrations, and promoted autophagy by inhibiting PI3K/AKT/mTOR signaling pathway, thereby ameliorating DSS-induced UC. Abbreviations: AKT, protein kinase B; ATG5, autophagy-related gene 5; ATG7, autophagy-related gene 7; ATG16L1, autophagy-related protein 16-like 1; DSS, dextran sulfate sodium; IL-1β, interleukin-1β; LC3, microtubule-associated-proteinlight-chain-3; mTOR, mammalian target of rapamycin; MUC-2, mucin-2; PI3K, phosphoinositide-3 kinase; TNF-α, tumor necrosis factor-alpha; UC, ulcerative colitis; ULK1, serine/threonine kinase Unc-51-like kinase 1; ZO-1, zonula occludens-1. [Display omitted] [ABSTRACT FROM AUTHOR]

This review aims to identify in vivo studies investigating the potential of plant substances and their natural molecules in managing inflammatory bowel disease (IBD). Specifically, the objective is to examine the impact of these substances on interleukins and other key inflammatory signaling markers. Relevant articles published up to December 2022 were identified through a search of the PubMed, Scopus, Web of Science, and Embase databases. The search used keywords including "inflammatory bowel disease", "medicinal plants", "natural molecules", "anti-inflammatory", and "ulcerative colitis", and identified 1,878 potentially relevant articles, of which 89 were included in this review after completion of the selection process. This study provides preclinical data on natural products (NPs) that can potentially treat IBD, including ulcerative colitis. The main actions of these NPs relate to their effects on nuclear factor kappa B (NF-κB), the Janus kinase (JAK)/signal transducer and activator of transcription (STAT) signaling pathway, the regulation of T helper 17/regulatory T cells balance, and oxidative stress. The ability of these NPs to inhibit intestinal inflammation appears to be dependent on lowering levels of the pro-inflammatory cytokines tumor necrosis factor-alpha (TNF-α), interleukin (IL)-1β, and IL-17, via the Jun N-terminal kinase (JNK)1, NF-κβ-p65, and STAT3 pathways. In addition, NPs were shown to reduce oxidative stress and the severity of ulcerative colitis, as well as increase the activity of antioxidant enzymes. These actions suggest that NPs represent a promising treatment for IBD, and potentially have greater efficacy and safety than current treatments. [Display omitted] • Preclinical evidence suggests that natural products (NPs) can reduce IBD progression. • NPs decrease pro-inflammatory cytokines and inhibit intestinal inflammation. • NPs can be used to regulate interleukins in the treatment of IBD. • NPs regulate NF-κB, JAK-STAT signaling, and T helper 17/regulatory T cells imbalance. • NPs lessen oxidative stress and ulcerative colitis severity. [ABSTRACT FROM AUTHOR]

Obesity is a metabolic complication linked with bad eating habits and a sedentary lifestyle, and the heart is one of the target organs damaged by it. Estrogen deficiency during menopause worsens the situation. Calorie restriction (CR) can contribute to reducing cardiovascular disease (CVD) in postmenopausal conditions. Thus, the effects of CR on inflammation and apoptosis in ovariectomized rats' hearts with obesity were studied. Female Wistar rats were categorized into Sham and OVX (ovariectomized) groups and received a standard diet (SD) or high-fat diet (60%HFD) or calorie restriction (30% CR) for 16 weeks. The real-time PCR method was used to evaluate the inflammatory markers and estrogen receptors gene expression. Western-blot and ELISA methods were respectively used for the measurement of apoptosis and SIRT1 protein expression. HFD led to the elevation of body weight, IL-6 (interleukin-6) and TNF-α (tumor necrosis factor-α) and reduction of IL-10 (interleukin-10) gene expressions, and also an increment in protein levels of cleaved caspase-3, Bax and Bax/Bcl2 ratio and decrement in Bcl-2 in OVX rats (P < 0.001). Additionally, HFD reduced SIRT1 (sirtuin1) protein levels, ERα (estrogen receptor α), and ERβ (estrogen receptor β) gene expressions (P < 0.001). In contrast, CR declined body weight, IL-6 and TNF-α (P < 0.001), increased IL-10 expressions (P < 0.05), decreased cleaved caspase-3 (P < 0.001), Bax (P < 0.01), and Bax/Bcl2 ratio (P < 0.05), enhanced Bcl-2 (P < 0.001), increased SIRT1 (P < 0.05) and ERα (P < 0.001) and ERβ (P < 0.01) expressions. CR through the SIRT1 regulation and estrogen receptors attenuate obesity-induced-cardiac inflammation and apoptosis. CR can be a cardioprotective candidate in postmenopausal conditions. • Obesity elevates cardiac inflammation and apoptosis in postmenopausal conditions. • Calorie restriction via SIRT1 regulation can attenuate cardiac damage in OVX rats. • Calorie restriction through ERα and ERβ expression promotes cardioprotective effects. [ABSTRACT FROM AUTHOR]

Little is known about how combining a probiotic with prebiotic dietary fiber affects the ability of either biotic to improve health. We hypothesized that prebiotic, high-amylose maize type 2–resistant starch (RS) together with probiotic Lactiplantibacillus plantarum NCIMB8826 (LP) as a complementary synbiotic results in additive effects on the gut microbiota in diet-induced obese mice and other body sites. Diet-induced obese C57BL/6J male mice were fed a high-fat diet adjusted to contain RS (20% by weight), LP (109 cells every 48 hours), or both (RS+LP) for 6 weeks. As found for mice fed RS, cecal bacterial alpha diversity was significantly reduced in mice given RS+LP compared with those fed LP and high-fat controls. Similarly, both RS+LP and RS also conferred lower quantities of cecal butyrate and serum histidine and higher ileal TLR2 transcript levels and adipose tissue interleukin-6 protein. As found for mice fed LP, RS+LP–fed mice had higher colonic tissue TH17 cytokines, reduced epididymal fat immune and oxidative stress responses, reduced serum carnitine levels, and increased transcript quantities of hepatic carnitine palmitoyl transferase 1α. Notably, compared with RS and LP consumed separately, there were also synergistic increases in colonic glucose and hepatic amino acids as well antagonistic effects of LP on RS-mediated increases in serum adiponectin and urinary toxin levels. Our findings show that it is not possible to fully predict outcomes of synbiotic applications based on findings of the probiotic or the prebiotic tested separately; therefore, studies should be conducted to test new synbiotic formulations. Diet-induced obese (DIO) mice received a combination of type 2–resistant starch (RS) and Lactiplantibacillus plantarum (LP) while continuing a high-fat diet (HF). RS+LP effects on systemic and local responses were compared with the effects of RS and LP fed separately, and HF controls. RS+LP effects were attributed to RS (blue arrows), LP (orange arrows), or RS+LP (arrows with both blue and orange colors). Interaction effects between RS and LP resulting in restoration to the control levels are shown with horizontal head-to-head arrows. CPT-α, carnitine palmitoyltransferase α; IL-6, interleukin 6; IL-10, interleukin 10; iNOS, inducible nitric oxide synthase; LPL, lipoprotein lipase; NADPH-ox, nicotinamide adenine dinucleotide phosphate oxidase; PYY, peptide YY. [Display omitted] [ABSTRACT FROM AUTHOR]

Both cortisol and interleukins appear at abnormal levels in schizophrenia. Our previous study has shown that cortisol and interleukins are associated with psychopathology and response to antipsychotic medications in a relatively small sample size of patients with schizophrenia. The current study was designed to investigate how cortisol, interleukins (ILs) and their interactions would correlate with clinical presentation in a relatively large sample size of patients with schizophrenia. We compared serum cortisol, IL-2, IL-6, and IL-8 levels in 162 medicated schizophrenia patients (including 27 patients in remission) and 62 healthy controls. Serum levels of cortisol and interleukins were measured by radioimmunoassay and quantitative ELISA, respectively. Clinical symptoms were assessed according to the Positive and Negative Syndrome Scale (PANSS). Patients with schizophrenia had significantly higher levels of cortisol and IL-2 compared to controls. Patients in remission had higher levels of IL-6 than non-remitting patients. PANSS positive symptoms, general psychopathology, cortisol and IL-2 were the most central nodes in the cortisol-IL-symptom network. The interaction between cortisol and IL-2 was associated with PANSS positive symptoms, general psychopathology and depressive factor. For patients with cortisol level above the median, IL-2 was negatively associated with PANSS positive symptoms and general psychopathology. Our results indicated that the interaction between cytokines and cortisol may be associated with the pathophysiology of some symptoms in chronic schizophrenia. In particular, the interaction between cortisol and IL-2 is associated with the clinical phenotypes of schizophrenia. • Chronic schizophrenia had significantly higher cortisol and IL-2 levels. • Cortisol and IL-2 were negatively correlated in patients with chronic schizophrenia. • Interaction between cortisol and IL-2 was associated with PANSS positive symptoms. • Interaction between cortisol and IL-2 was associated with PANSS general psychopathology. • Patients in remission had higher IL-6 levels than non-remitting patients. [ABSTRACT FROM AUTHOR]

The relationship between anthocyanin intake and obesity-related inflammatory markers remains unclear in existing research. To investigate this, we hypothesized that anthocyanin supplementation could reduce plasma concentrations of inflammatory markers, including C-reactive protein (CRP), tumor necrosis factor alpha (TNF-α), interleukin-6 (IL-6), vascular cell adhesion molecule-1, and other cytokines in obesity. We conducted a systematic search of PubMed, Web of Science, Scopus, SinoMed, and other related literature and identified 16 randomized controlled trials that met our inclusion criteria. Our findings showed that anthocyanin intake was significantly associated with a reduction in vascular cell adhesion molecule-1 mean plasma concentrations (–53.56 ng/mL; 95% confidence interval [CI], –82.10 to –25.03). We also observed a modest decrease in CRP (–0.27 ng/mL; 95% CI, –0.58 to 0.05), TNF-α (–0.20 ng/mL; 95% CI, –0.54 to 0.15), and IL-6 (–0.53 ng/mL; 95% CI, –1.16 to 0.10) mean plasma concentrations. Subgroup analysis revealed that anthocyanin intake tended to decrease CRP and IL-6 concentrations in overweight or dyslipidemic individuals. Additionally, the intervention duration subgroup analysis showed that anthocyanin supplementation had a stronger effect on plasma IL-6 and TNF-α in participants after 8 to 12 weeks of intervention. In conclusion, our meta-analysis indicated that anthocyanin supplementation can effectively reduce obesity-related inflammatory markers associated with chronic low-grade inflammation. Our meta-analysis of 16 randomized controlled trials found that anthocyanin intake significantly reduced plasma vascular cell adhesion molecule-1 (VCAM-1) concentration. Although the reductions in C-reactive protein (CRP), tumor necrosis factor (TNF-α), and interleukin-6 (IL-6) were not statistically significant, subgroup analysis produced meaningful results indicating that anthocyanins have the potential to improve obesity-related inflammatory characteristics. [Display omitted] [ABSTRACT FROM AUTHOR]

Protein restriction (PR) leads to bone marrow hypoplasia with changes in stromal cellularity components of the extracellular matrix in hematopoietic stem cells (HSCs). However, the underlying signaling mechanisms are poorly understood. We hypothesize that PR impairs the HSC mitogen-activated protein kinase (MAPK) signaling pathway response activation. Our aim is to evaluate the activation of MAPK and interleukin-3 (IL-3) proteins in HSC to explain PR-induced bone marrow hypoplasia, which causes altered proliferation and differentiation. C57BL/6 male mice were subjected to a low-protein diet (2% protein) or normoproteic (12% protein). PKC, PLCγ2, CaMKII, AKT, STAT3/5, ERK1/2, JNK, and p38d phosphorylation were evaluated by flow cytometry, and GATA1/2, PU.1, C/EBPα, NF-E2, and Ikz-3 genes (mRNAs) assessed by quantitative real-time-polymerase chain reaction. Pathway proteins, such as PLCγ2, JAK2, STAT3/5, PKC, and RAS do not respond to the IL-3 stimulus in PR, leading to lower activation of ERK1/2 and Ca2+ signaling pathways, consequently lowering the production of hematopoietic transcription factors. Colony forming units granulocyte-macrophage and colony forming units macrophage formation are impaired in PR even after being stimulated with IL-3. Long-term hematopoietic stem cells, short-term hematopoietic stem cells, granulocyte myeloid progenitor, and megakaryocyte-erythroid progenitor cells were significantly reduced in PR animals. This study shows for the first time that activation of MAPK pathway key proteins in HSCs is impaired in cases of PR. Several pathway proteins, such as PLCγ2, JAK2, STAT3, PKC, and RAS do not respond to IL-3 stimulation, leading to lower activation of extracellular signal-regulated protein kinase 1/2 and consequently lower production of hematopoietic transcription factors GATA1/2, PU.1, C/EBPa, NF-E2, and Ikz3. These changes result in a reduction in colony-forming units, proliferation, and differentiation, leading to hypocellularity. This study shows for the first time that activation of mitogen-activated protein kinase pathway key proteins in hematopoietic stem cells is impaired in cases of protein restriction. Several pathway proteins, such as PLCγ2, JAK2, STAT3, PKC, and RAS do not respond to interleukin-3 (IL-3) stimulation, leading to lower activation of extracellular signal-regulated protein kinase 1/2 (ERK1/2) and consequently lower production of hematopoietic transcription factors GATA1/2, PU.1, C/EBPa, NF-E2, and Ikz3. This results in a reduction in colony-forming units, leading to hypocellularity. Red arrows mean decreased activation. [Display omitted] [ABSTRACT FROM AUTHOR]

Accumulating evidence has suggested that curcumin may protect against cerebral ischemia-reperfusion injury (CIRI). However, biological mechanisms vary across studies, limiting the clinical applicability of these findings. We performed a meta-analysis on publications evaluating curcumin administration in rat models of CIRI. Furthermore, we sought to test the hypothesis that curcumin alleviates CIRI through diminishing oxidation and inflammation. We searched PubMed, Embase, Web of Science, and Cochrane from the starting date of each database to May 2022 for experimental rat studies exploring the use of curcumin after ischemia reperfusion. Included articles were assessed for bias using SYRCLE's risk of bias tool. Data were aggregated by a random effects model. Curcumin administration significantly reduced neurological deficit score (20 studies; pooled mean difference [MD] = –1.57; 95% CI, –1.78 to –1.36, P <.00001), infarct volume (18 studies; pooled MD = –17.56%; 95% CI, –20.92% to –14.20%; P < 0.00001), and brain water content (8 studies, pooled MD = -11.29%, 95% CI: -16.48%, -6.11%, P <.00001). Compared with control, the levels of superoxide dismutase, glutathione, and glutathione peroxidase were significantly higher, whereas the levels of reactive oxygen species, malondialdehyde, interleukin-1β, interleukin-6, interleukin-8, and nuclear factor kappa B were significantly lower (P <.05). Subgroup analysis raised the possibility that intervention affections differed by curcumin's dose. To our knowledge, this is the first meta-analysis of curcumin's neuroprotection and mechanisms in rat CIRI models. Our analysis suggests the neuroprotective potential of curcumin in CIRI via antioxidant activity and anti-inflammatory effect. More research is required to further confirm the effectiveness and safety of curcumin on ischemic stroke therapy. A meta-analysis including 29 experimental rat studies reveals curcumin's neuroprotection for cerebral ischemia-reperfusion injury (CIRI) via diminishing oxidation and inflammation in rat models. Indeed, curcumin may be a promising supplementary agent against CIRI. BCCAO, bilateral common carotid artery occlusion; BWC, brain water content; IV, infarct volume; MCAO, middle cerebral artery occlusion; NDE, neurological deficit evaluation. [Display omitted] [ABSTRACT FROM AUTHOR]

Capmatinib, a MET inhibitor, showed substantial antitumour activity with manageable side effects in patients with MET exon 14 (MET ex14)-mutated advanced non-small cell lung cancer (aNSCLC) in the GEOMETRY mono-1 study. We report patient-reported outcomes (PROs) from this study. Enrolled treatment-naïve (1L) or pre-treated (2L+) patients with aNSCLC with a MET ex14-skipping mutation received 400 mg capmatinib twice daily during 21-day treatment cycles. PROs were collected at baseline and every six weeks thereafter using EORTC QLQ-C30 global health status/quality of life (GHS/QoL), QLQ-LC13 symptoms, and EQ-5D-5L visual analogue scale (VAS) questionnaires. As of 6 January 2020, 27/28 1L and 65/69 2L+ patients had completed PROs at baseline; compliance rates remained >70%. Cough improved early, with meaningful improvements (≥10-point change from baseline) observed throughout cycles (mean change from baseline [SD] by week 7: 1L −13.0 [39.9], 2L+ −8.2 [28.4]; week 43: 1L −28.2 [26.7], 2L+ −10.5 [27.3]). QoL, assessed by GHS/QoL and VAS, improved by week 7 in 1L and 2L+ patients, with improvements generally sustained over time. Median time to definitive deterioration (TTDD) in GHS/QoL was 16.6 months (95% CI: 9.7, not estimable [NE]) in 1L and 12.4 months (95% CI: 4.2, 19.4) in 2L+ patients. Median TTDD for dyspnoea was 19.4 months (95% CI: 12.4, NE) and 22.1 months (95% CI: 9.9, NE) for 1L and 2L+ patients, respectively, and NE for cough and chest pain. Capmatinib was associated with clinically meaningful improvements in cough and preserved QoL, further supporting its use in patients with MET ex14-mutated aNSCLC. ClinicalTrials.gov registry number: NCT02414139. • Capmatinib is indicated for advanced NSCLC with MET exon 14 skipping alterations. • We present the analysis of the patient-reported outcomes from the GEOMETRY mono-1 trial. • Patient-reported outcomes included the EORTC QLQ-C30, EORTC QLQ-LC13, and EQ-5D-5L. • Capmatinib led to clinically meaningful improvements in cough and preserved QoL. • Benefit was observed for both treatment-naïve and previously treated patients. [ABSTRACT FROM AUTHOR]

As crucial mediators and regulators of our immune system, cytokines are involved in a broad range of biological processes and are implicated in various disease pathologies. The field of cytokine therapeutics has gained much momentum from the maturation of conventional protein engineering methodologies such as structure-based designs and/or directed evolution, which is further aided by the advent of in silico protein designs and characterization. Just within the past 5 years, there has been an explosion of proof-of-concept, preclinical, and clinical studies that utilize an armory of protein engineering methods to develop cytokine-based drugs. Here, we highlight the key engineering strategies undertaken by recent studies that aim to improve the pharmacodynamic and pharmacokinetic profile of interferons and other cytokines as therapeutics. Cytokines influence a broad range of physiological processes, including inflammatory responses to injurious stimuli, regulation of cellular proliferation, differentiation and cell death, and homeostasis after molecular perturbation via repair and remodeling processes. Several known cytokines, including interferons, interleukins, and growth factors, are implicated in human diseases, presenting as potential therapeutic targets. Developing successful cytokine drugs entails deconvolution of inherent pleiotropy, reduction of off-target toxicity, and/or improved drug-like properties. Recent studies highlight the importance of protein engineering in cytokine therapeutics, encompassing many varied approaches from structure-guided and in silico protein designs to site-directed drug delivery and half-life extension as conjugates. Despite the early promise from proof-of-concept and preclinical research, it remains to be seen how these novel cytokine-based drugs will perform in clinical trials against various diseases. [ABSTRACT FROM AUTHOR]

The incidence of childhood overweight and obesity has been increasing in recent years. Immune dysregulation has been demonstrated as a condition related to childhood obesity. Whether the neonatal immune status is related to infant overweight and obesity at 1 year of age is unclear. To explore the relationship between neonatal cytokines and infant overweight and obesity, we conducted a prospective study in Suzhou Municipal Hospital Affiliated to Nanjing Medical University from 2015 to 2016. 514 neonates were recruited and their dried blood spots were collected after birth. Infants were grouped into normal size groups and overweight and obesity groups based on BMI at 1 year of age. 27 neonatal cytokines levels were compared between the two groups. 370 infants were included in final analysis. Granulocyte colony stimulating factor (GCSF), interleukin-17A (IL17A) and platelet derived growth factor-BB (PDGF-BB) levels were independently associated with childhood overweight and obesity (OR =1.27, 95%CI 1.03, 1.57; OR =1.29, 95%CI: 1.06, 1.60; OR =0.69, 95%CI: 0.49, 0.96). Additionally, neonatal GCSF and IL17A levels were positively associated with increased BMI (β = 0.11, 95%CI: 0.02, 0.19; β = 0.07, 95%CI 0.01, 013) and BMI z-scores (β = 0.10, 95%CI: 0.02, 0.18; β = 0.06, 95%CI 0.01, 0.13). Neonatal PDGF-BB levels were negatively associated with BMI (β = −0.12, 95%CI: −0.23, −0.01) and BMI z-scores (β = −0.12, 95%CI: −0.23, −0.01). The inverse probability weighting (IPW) was performed to account for potential selection bias of this study, and the results were consistent with the above mentioned findings. Neonatal GCSF, IL17A and PDGF-BB levels were correlated with infant overweight and obesity at 1 year of age, suggesting that early life immune status play a significant role of late obesity. [ABSTRACT FROM AUTHOR]

• Bempedoic acid (BA) reduces hsCRP with minimal effect on fibrinogen, IL-6, or Lp(a). • No correlation between lipid changes and hsCRP changes with BA. • Findings for BA are almost identical to that of statin therapy. • BA may be an option to treat residual inflammatory and residual cholesterol risk. While bempedoic acid (BA), an inhibitor of ATP citrate lyase, lowers high-sensitivity C-reactive protein (hsCRP) and low-density lipoprotein cholesterol (LDL-C), the mechanisms underlying the potential anti-inflammatory effects of BA are uncertain, as are effects of this agent on lipoprotein(a). To address these issues, we conducted a secondary biomarker analysis of the randomized placebo-controlled multi-center CLEAR Harmony trial which included 817 patients with known atherosclerotic disease and/or heterozygous familial hypercholesterolemia who were taking maximally tolerated statin therapy and had residual inflammatory risk, defined as a baseline hsCRP ≥2 mg/L. Participants were randomly allocated in a 2:1 ratio to oral BA 180 mg once daily or matching placebo. Placebo-corrected median percent changes (95% CI) from baseline to 12 weeks associated with BA were −21.1% (−23.7 to −18.5) for LDL-C; −14.3% (−16.8 to −11.9) for non–high-density lipoprotein cholesterol; −12.8% (−14.8 to −10.8) for total cholesterol; −8.3% (−10.1 to −6.6) for high-density lipoprotein cholesterol (HDL-C); −13.1% (−15.5 to −10.6) for apolipoprotein B; 8.0% (3.7 to 12.5) for triglycerides; −26.5% (−34.8 to −18.4) for hsCRP; 2.1% (−2.0 to 6.4) for fibrinogen, −3.7% (−11.5, 4.3) for interleukin-6; and 2.4% (0.0 to 4.8) for lipoprotein(a). There was no correlation between BA associated lipid changes and BA associated change in hsCRP (all r <0.05), except for a weak correlation with HDL-C (r = 0.12). Thus, the pattern of lipid lowering and inflammation inhibition with BA is almost identical to what is observed with statin therapy suggesting that BA could be a useful treatment option to address both residual cholesterol risk and residual inflammatory risk. ClinicalTrials.gov Identifier: NCT02666664; https://clinicaltrials.gov/ct2/show/NCT02666664. [ABSTRACT FROM AUTHOR]

MicroRNAs have been shown to play a role in the pathogenesis of apical periodontitis. Upregulation of miR-10a-5p and downregulation of miR-891a-5p were previously reported in apical periodontitis samples. This study aims to perform a functional characterization of miR-10a-5p, investigating its capacity to regulate the expression of inflammatory cytokines and growth factors, as well as a possible co-regulation mechanism with miR-891a-5p in the development of apical periodontitis. miR-10a-5p mimics/controls and miR-891a-5p inhibitors/controls were introduced to human K-562 cells in the presence or absence of lipopolysaccharide. Total RNA was extracted from cell lysates, and target genes were examined via quantitative reverse transcription-polymerase chain reaction. Cell lysates were also subjected to proteomics analysis. Furthermore, mimics of miR-10a-5p and inhibitors of miR-891a-5p were co-transfected into K-562 cells. RNA sequencing and quantitative reverse transcription-polymerase chain reaction were carried out to examine their target genes. Overexpression of miR-10a-5p led to downregulation of tumor necrosis factor-alpha and interleukin-1 beta mRNA and upregulation of transforming growth factor-beta 1 (TGFB1) mRNA expression, whereas interleukin 3 and TGF-β1 proteins were upregulated. Simultaneous overexpression of miR-10a-5p and inhibition of miR-891a-5p further increased TGFB1 mRNA transcript levels. RNA sequencing revealed that genes co-regulated by miR-10a-5p and miR-891a-5p may be involved in apical periodontitis-related pathways such as tumor necrosis factor, transient receptor potential, and vascular endothelial growth factor signaling pathways. miR-10a-5p may modulate the expression of multiple inflammatory cytokines and growth factors such as tumor necrosis factor-alpha, IL-1β, interleukin 3, and TGF-β1. In addition, miR-10a-5p and miR-891a-5p cooperatively regulate TGFB1 gene expression, and the gene network of this co-regulation is integrated with many pathways in apical periodontitis. [ABSTRACT FROM AUTHOR]

Background: Peripheral cytokines were found to be involved in the pathophysiology of neurocognition in individuals with major depressive disorder (MDD). However, whether there are sex differences in this association between cytokines and cognition in MDD remains unknown. Our aim is to examine sex differences in the relationship between plasma cytokines and cognition in MDD.Method: One hundred and twenty-seven first episode drug naïve patients with MDD and sixty healthy controls (HCs) were recruited for present study. The MATRICS Consensus Cognitive Battery was administered to measure the cognition. Plasma concentrations of nineteen cytokines were measured using high sensitivity multiplex bead-based assays.Results: Both female and male patients with MDD had significant cognitive impairment in verbal learning and visual learning and had higher levels of a range of cytokines than HCs (all p < 0.05). Female patients performed worse in trail making (F = 4.442, p = 0.018) and had higher concentration of interleukin (IL)-4 (F = 7.775, p = 0.006) than males. In female MDD, a significant positive association between category frequency and level of IL-4 was observed (B = 8.040, p = 0.031). However, this association was not present in male MDD or HCs (p > 0.05).Limitation: Present study used a cross-sectional design.Conclusion: Female MDD patients had worse trail making performance and higher level of IL-4 than males. The elevated IL-4 in female MDD was positively associated with category fluency, suggesting that IL-4 may be involved in the pathophysiology related to specific cognitive domain in female MDD patients. [ABSTRACT FROM AUTHOR]

[Display omitted] Despite advances in stent technologies, restenosis remains a serious problem of interventional cardiology and is considered as a consequence of the progressing inflammation within the vessel wall. Thus, attempts to extinguish this inflammatory process undoubtedly motivate the development of a coating that exhibits immunomodulatory properties. Hence, we propose a polydopamine-based-coating functionalized with an anti-inflammatory interleukin is reported. By the ATR-FTIR spectroscopy and AFM examination the incorporation of cytokines into the coating structure is confirmed, thus effective functionalization is proved. The gradual delivery of cytokines allows to limit the influence of IL-4 and IL-10 deficiency, which is recognized as a restenosis risk factor. A relatively steady cytokine release profile exhibits therapeutic potential in the first days after implantation and in preventing late complications on cellular model. In vitro coating studies prove the promotion of endothelialization in the initial stage after implantation, being consistent with present treatment strategies. The limitation of IL-8 and MCP-1 daily release by coating-interacted-endothelium significantly reduce another risk factor of restenosis. Finally, by assessing the changes in THP-1 differentiation, the coating immunological activity is confirmed, so the binding procedure do not impair biological properties of the interleukin. Therefore, it can be concluded that proposed anti-inflammatory coating can reduce the probability of restenosis to a minimum. [ABSTRACT FROM AUTHOR]

The aim of this study was to verify the effects of ultrasound on dorsal root ganglion (DRG) neurons at the injury site in a rat model of sciatic nerve crush injury. We evaluated the mRNA expression of neurotrophic and pro-inflammatory factors by quantitative reverse transcription polymerase chain reaction 7 and 14 d post-injury. We also evaluated the protein levels of brain-derived neurotrophic factor (BDNF) 7 and 14 d post-injury. Axon regeneration and motor function analyses were performed 21 days after injury to confirm the facilitative effect of ultrasound on nerve regeneration. In the ultrasound group, BDNF and interleukin-6 mRNA expression of the DRG was significantly reduced 7 d post-injury. Compared with the sham group, the BDNF protein expression of the DRG in the ultrasound group remained at a higher level 14 d post-injury. Motor function, myelinated fiber density and myelin sheath thickness were significantly higher in the ultrasound group than in the sham group 21 d post-injury. These results indicate that ultrasound therapy at the injury site promotes nerve regeneration and modulates gene and protein expression in the DRG of a rat model of a sciatic nerve crush injury. [ABSTRACT FROM AUTHOR]

Objective/background: This pilot study aims to assess the effect of Cognitive Behavioral Therapy for insomnia (CBTi) in individuals with cannabis use disorder and insomnia. It also aims to investigate the effect of CBTi on levels of serum inflammatory markers in relation to insomnia symptoms.Methods/patients: Individuals with cannabis use disorder and insomnia symptoms were recruited over 18 months. Data collected included demographics, self-reported sleep parameters, and cannabis use. Blood samples were drawn to measure IL-2, IL-6, CRP, and cortisol. Participants completed the Insomnia Severity Index questionnaire (ISI) and the Patient Health Questionnaire-4 (PHQ-4), and they were provided with an actigraphy (wrist) device for 1 week before CBTi and a subsequent week after completing the 4 CBTi sessions.Results: Nineteen participants were enrolled in the study. The mean ISI score decreased from moderately severe insomnia at baseline to no clinically significant insomnia after CBTi with a sustained decrease at 3- and 6-months follow-up. Actigraphy showed a significant decrease in sleep onset latency (SOL) after CBTi. Three months after CBTi, 80% of participants reported a decrease in their cannabis use. There was also a significant and sustained decrease in mean PHQ-4 scores after CBTi. Although only trending towards significance, the levels of three out of four biomarkers (IL-2, IL-6, CRP) were decreased 6 months after CBTi.Conclusions: CBTi is effective as a short- and long-term treatment of insomnia and comorbid anxiety/depression in individuals who regularly use cannabis. A potential added benefit is a reduction in cannabis consumption and inflammatory serum biomarkers. [ABSTRACT FROM AUTHOR]

Several clinical trials have reported that patients with cancer cachexia can benefit from n-3 polyunsaturated fatty acids (n-3 PUFAs) supplements; however, the results have been conflicting. This systematic review and meta-analysis aimed to evaluate the effect of n-3 PUFAs on cancer cachexia. A search of the PubMed, Embase, and Cochrane Library databases was performed to identify the included randomized controlled trials. Trials including patients with cancer cachexia who were administered a course of n-3 PUFAs were included. A meta-analysis on body weight, lean body weight, proinflammatory factors, quality of life, and median duration of survival was conducted. A total of 12 randomized controlled trials with 1184 patients were included. No effect on body weight (standard mean difference [SMD], 0.10; 95% CI, –0.06 to 0.26; P =.236), lean body weight (SMD, –0.17; 95% CI, –0.36 to 0.03, P =.095), or proinflammatory factors (interleukin-6: SMD, 0.31; 95% CI, –0.14 to 0.75; P =.18; tumor necrosis factor-α: SMD, –0.85; 95% CI, –2.39 to 0.69; P =.28) was observed. The use of n-3 PUFAs was associated with a significant improvement in quality of life (SMD, 0.70; 95% CI, 0.01-1.40; P =.048) and median duration of survival (median survival ratio, 1.10; 95% CI, 1.02-1.19; P =.014). For patients with cancer cachexia, our meta-analysis indicated that n-3 PUFAs improved quality of life and survival, but not body weight. Whether cancer cachexia patients can benefit from n-3 polyunsaturated fatty acids (n-3 PUFAs) supplements remains unknown. This current meta-analysis of 12 randomized controlled trials showed that n-3 PUFAs had no effect on body weight, lean body weight, or proinflammatory factors. The use of n-3 PUFAs was associated with a significant improvement in quality of life and median duration of survival [Display omitted]. [ABSTRACT FROM AUTHOR]

Background: In current intensive care treatment, some patients with severe burns cannot be saved due to progressive organ failure. Further investigation of the pathogenesis of severe burns is needed to improve the mortality rate. In burns, inflammatory cytokines form a network that leads to an inflammatory response. Adipocytes secrete physiologically active substances (adipokines). The roles of adipokines have not been completely clarified in burn patients. This study aimed to determine the relation between serial changes of adipokines and clinical course in severely burned patients.Methods: This was a single-center, retrospective, observational study. Patients' blood samples were collected on the day of injury and around 1 week later. Adipokines (adiponectin, angiotensinogen, chemerin, CXCL-12/SDF-1, leptin, resistin, vaspin, visfatin), various inflammatory cytokines, syndecan-1 and C1 esterase inhibitor were measured.Results: Thirty-eight patients were included. Resistin levels were significantly higher in the non-survivors versus survivors on Day 1 after burn injury. Hierarchical clustering analysis showed common clusters on Day 1 and at 1 Week after burn injury (resistin, IL-6, IL-8, IL10 and MCP-1). The correlation coefficient of resistin to SOFA score at 1 Week was significant. Logistic regression analysis showed a significant relation of resistin levels on Day 1 with prognosis; the area under the ROC curve for resistin was 0.801.Conclusions: In the acute phase of burns, resistin was associated with other pro-inflammatory cytokines and was related to the severity and prognosis of major burns. [ABSTRACT FROM AUTHOR]

Introduction: Premenstrual syndrome (PMS) and primary dysmenorrhea (PD) are common gynecological complications and there is evidence that inflammation may be an important factor in their etiology. There is a relationship between PMS and PD with susceptibility to allergic disorders. We aimed to assess the effect of curcumin co-administered with piperine on serum IL-10, IL-12 and IgE levels in patients with PD and PMS.Materials and Methods: A sample of 80 patients were recruited to this triple-blind, placebo-controlled clinical trial. Participants were randomly allocated to curcumin (n = 40) and control groups (n = 40). Each participant received one capsule (500 mg of curcuminoid plus piperine, or placebo) daily, from 7 days before until 3 days after menstruation for three consecutive menstrual cycles.Results: Serum IgE, IL-10 and IL-12 levels were quantified by using an ELISA kit. No significant differences were found between the two groups at baseline, including: age, BMI, and dietary intakes (P > 0.05). Curcumin + piperine treatment was associated with a significant reduction in the mean serum levels of IgE [from 223.6 ± 258.7 IU/mL to 161.3 ± 240.7; P = 0.001]; but there were no significant changes in the placebo group (P = 0.12). Serum concentrations of IL-10 and IL-12 before and after the trial period did not differ significantly between the two groups (P > 0.05).Conclusion: Curcumin plus piperine might be have positive effect on serum IgE levels with no significant changes on serum IL-10 and IL-12 in healthy young women with PMS and PD. Studies with higher doses and longer durations of treatment with curcumin are required to confirm these findings. [ABSTRACT FROM AUTHOR]

Background: Individualised positive end-expiratory pressure (PEEP) may optimise pulmonary compliance, thereby potentially mitigating lung injury. This meta-analysis aimed to determine the impact of individualised PEEP vs fixed PEEP during abdominal surgery on postoperative pulmonary outcomes.Methods: Medical databases (PubMed, Embase, Web of Science, ScienceDirect, Google Scholar, and the China National Knowledge Infrastructure) were searched for RCTs comparing fixed vs individualised PEEP. The composite primary outcome of pulmonary complications comprised hypoxaemia, atelectasis, pneumonia, and acute respiratory distress syndrome. Secondary outcomes included oxygenation (PaO2/FiO2) and systemic inflammatory markers (interleukin-6 [IL-6] and club cell protein-16 [CC16]). We calculated risk ratios (RRs) and mean differences (MDs) with 95% confidence interval (CI) using DerSimonian and Laird random effects models. Cochrane risk-of-bias tool was applied.Results: Ten RCTs (n=1117 patients) met the criteria for inclusion, with six reporting the primary endpoint. Individualised PEEP reduced the incidence of overall pulmonary complications (141/412 [34.2%]) compared with 183/415 (44.1%) receiving fixed PEEP (RR 0.69 [95% CI: 0.51-0.93]; P=0.016; I2=43%). Risk-of-bias analysis did not alter these findings. Individualised PEEP reduced postoperative hypoxaemia (74/392 [18.9%]) compared with 110/395 (27.8%) participants receiving fixed PEEP (RR 0.68 [0.52-0.88]; P=0.003; I2=0%) but not postoperative atelectasis (RR 0.93 [0.81-1.07]; P=0.297; I2=0%). Individualised PEEP resulted in higher PaO2/FiO2 (MD 20.8 mm Hg [4.6-36.9]; P=0.012; I2=80%) and reduced systemic inflammation (lower plasma IL-6 [MD -6.8 pg ml-1; -11.9 to -1.7]; P=0.009; I2=6%; and CC16 levels [MD -6.2 ng ml-1; -8.8 to -3.5]; P<0.001; I2=0%) at the end of surgery.Conclusions: Individualised PEEP may reduce pulmonary complications, improve oxygenation, and reduce systemic inflammation after abdominal surgery.Clinical Trial Registration: CRD42021277973. [ABSTRACT FROM AUTHOR]

The hypothesis of the present study was that nitro-fatty acids (NO 2 -FAs) would suppress inflammation associated with periodontal disease. To test this hypothesis, we investigated the influence of nitrooleic acid, a prototypical NO 2 -FA, on the inflammatory response of murine macrophages activated with lipopolysaccharide (LPS) from Prevotella intermedia , a pathogen associated the etiology of different types of periodontal diseases. LPS was prepared from P. intermedia cells by using phenol-water protocol. Culture supernatants were assayed for nitric oxide (NO), interleukin-1β (IL-1β), and IL-6. Real-time polymerase chain reaction and immunoblotting analyses were performed to quantify messenger RNA and protein expression, respectively. The secreted embryonic alkaline phosphatase reporter assay was performed to measure NF-κB activation. The transcription factor assay kit was used to measure DNA-binding of NF-κB subunits. Findings obtained from the present study revealed that nitrooleic acid suppresses the generation and messenger RNA expression of inducible NO synthase-derived NO, IL-1β, and IL-6 in RAW264.7 cells activated with P. intermedia LPS and promotes macrophage polarization toward anti-inflammatory M2 phenotype. We also found that nitrooleic acid exerts its effect via heme oxygenase-1 induction and suppression of NF-κB signaling. The inhibition of NO and proinflammatory cytokine production by nitrooleic acid was independent from PPAR-γ, JNK, p38, and STAT1/3. Nitrooleic acid may represent a novel class of agent as a host modulator which has therapeutic benefit in periodontal disease, though more work is needed to confirm this. Proposed cellular mechanisms involved in the inhibition of Prevotella intermedia lipopolysaccharide (LPS)-induced production of nitric oxide (NO), interleukin-1β (IL-1β), and IL-6 by nitrooleic acid (OA-NO 2) in RAW264.7 cells. The generation and messenger RNA expression of inducible NO synthase-derived NO, IL-1β, and IL-6 induced by P. intermedia LPS were suppressed by OA-NO 2. OA-NO 2 encouraged the switch from proinflammatory M1 macrophages to anti-inflammatory M2 macrophage phenotype in cells activated with LPS. OA-NO 2 exerts its effect via heme oxygenase-1 induction and suppression of NF-κB signaling. [Display omitted] [ABSTRACT FROM AUTHOR]

Context: Inflammation is proposed to influence tumor response in radiotherapy (RT). Clinical studies to investigate the relationship between inflammatory markers and RT response is warranted to understand the variable RT efficacy in patients with painful bone metastases.Objectives: To evaluate the association between inflammatory markers and analgesic response to RT in patients with painful bone metastases.Methods: Adult patients from 7 European study sites undergoing RT for painful bone metastases were included in this prospective and longitudinal analysis. The association between RT response and 17 inflammatory markers at baseline, as well as the association between RT response and the changes observed in inflammatory markers between baseline and three and eight weeks after RT, was analyzed with univariate regression analyses. Baseline analyses were adjusted for potential clinical predictors of RT response.Results: None of the inflammatory markers were significantly associated with an upcoming RT response in the analysis of 448 patients with complete baseline data. In patients available for follow-up, the three-week change in TNF (P 0.017), IL-8 (P 0.028), IP-10 (P 0.032), eotaxin (P 0.043), G-CSF (P 0.033) and MCP-1 (P 0.002) were positively associated with RT response, while the three-week change in CRP (P 0.006) was negatively associated.Conclusion: Results from this study show an association between RT response and change in pro-inflammatory mediators and indicate that inflammation may be important to achieve an analgesic RT response in patients with painful bone metastases. None of the investigated inflammatory markers were found to be pre-treatment predictors of RT response. [ABSTRACT FROM AUTHOR]

Purpose: The immunoinflammatory state has been shown to be associated with poor outcomes after radiation therapy (RT). We conducted an a priori designed validation study using serum specimens from Radiation Therapy Oncology Group (RTOG) 0521. It was hypothesized the pretreatment inflammatory state would correlate with clinical outcomes.Methods and Materials: Patients on RTOG 0521 had serum banked for biomarker validation. This study was designed to validate previous findings showing an association between elevations in C-reactive protein (CRP) and shorter biochemical disease free survival (bDFS). CRP levels were measured in pretreatment samples. An exploratory panel of related cytokines was also measured including: monocyte chemotactic protein-1, granulocyte-macrophage colony-stimulating factor, interferon-γ, interleukin (IL)-1b, IL-2, IL-4, IL-5, IL-6, IL-8, IL-10, IL-12, IL-13, IL-17A, IL-23, and tumor necrosis factor. The primary endpoint examined was bDFS. Additional exploratory endpoints included overall survival, distant metastases, and toxicity events attributed to RT.Results: Two hundred and two patients in RTOG/NRG 0521 had serum samples available. Median age was 66 years (48-83), and 90% of patients were White. There was not an association between CRP and bDFS (adjusted hazard ratio [HR], 1.07 per 1 log increase in CRP; 95% confidence interval, 0.83-1.38; P = .60). In the exploratory, unplanned analysis, pretreatment IL-10 was significantly associated with worse bDFS (adjusted HR, 1.61 per log increase; P = .0027) and distant metastases (HR, 1.55 per log increase; P = .028). The association of IL-10 with bDFS was maintained on a multiplicity adjustment. The exploratory analyses of pretreatment levels of interferon-γ, IL-1b, IL-2, IL-13, IL-23 were negatively associated with grade 2 or higher pollakiuria (adjusted odds ratio, 0.64, 0.65, 0.71, 0.72, and 0.74, respectively, all P < .05), and IL-6 was negatively associated with grade 2 or higher erectile dysfunction (odds ratio, 0.62; P = .027).Conclusions: Pretreatment CRP was not associated with a poorer bDFS after RT. In a hypothesis- generating analysis, higher baseline levels of IL-10 were associated with lower rates of bDFS. These findings require additional prospective evaluation. [ABSTRACT FROM AUTHOR]

Atherosclerosis is the primary cause of cardiovascular diseases (CVDs), contributing to more than 33% of the annual deaths globally. Westernized dietary patterns, a high prevalence (50%) of overweight and obesity, and an increased incidence of glucose intolerance and type-2 diabetes are related to atherosclerosis. However, increased demand for functional foods has boosted the production of different foods to improve people's life quality and decrease the CVDs' risk. Nonetheless, functional foods targeting CVDs are scarce in the marketplace. To perform a multidisciplinary and cross-sectoral approach by linking atherosclerosis biomarkers, potential bioactive compounds (e.g., phenolics), and food technology, besides scientific limitations, we propose a practical step-by-step guide to designing functional foods. First, a comprehensive and up-to-date overview of atherosclerosis is provided, focusing on the inflammation markers to counteract its onset and progression. Then, a structure-based–(SBDD) or ligand-based drug design (LBDD) approach is presented, and illustrated by the incorporation of vescalagin, a phenolic compound from jaboticaba seed, into a functional food to mitigate atherosclerosis. Tailored functional foods added with phenolic compounds can be designed through computational approaches predicting their bioactivity. Together with chemical analyses, mathematical models can explore a vast array of molecular mechanisms, allowing the discovery of novel bioactive compound sources. Altogether, food science/technology, nutrition, and structure- and ligand-based approaches should be combined to support the design of tailor-made functional foods/nutraceuticals to contribute to public health interventions related to atherosclerosis and other cardiometabolic diseases. [Display omitted] • Cardiovascular diseases (CVDs) are the main cause of death but can be prevented. • Consumers look for functional foods to decrease the risk of CVDs but few are available. • Food/Pharma companies should consider developing new foods and nutraceuticals. • Food science, CVD therapy and in silico modelling should be linked to produce functional foods to mitigate atherosclerosis. [ABSTRACT FROM AUTHOR]

Background: General anaesthesia in the neonatal period has detrimental effects on the developing mammalian brain. The impact of underlying inflammation on anaesthesia-induced developmental neurotoxicity remains largely unknown.Methods: Postnatal day 7 (PND7) rats were randomly assigned to receive sevoflurane (3 vol% for 3 h) or carrier gas 12 h after bacterial lipopolysaccharide (LPS; 1 μg g-1) or vehicle injection. Pharmacological inhibition of caspase-1 by Vx-765 (two doses of 50 μg g-1 body weight) was used to investigate mechanistic pathways of neuronal injury. Histomorphological injury and molecular changes were quantified 2 h after the end of anaesthesia. Long-term functional deficits were tested at 5-8 weeks of age using a battery of behavioural tests in the memory and anxiety domains.Results: Sevoflurane or LPS treatment increased activated caspase-3 and caspase-9 expression in the hippocampal subiculum and CA1, which was greater when sevoflurane was administered in the setting of LPS-induced inflammation. Neuronal injury induced by LPS+sevoflurane treatment resulted in sex-specific behavioural outcomes when rats were tested at 5-8 weeks of age, including learning and memory deficits in males and heightened anxiety-related behaviour in females. Hippocampal caspase-1 and NLRP1 (NLR family pyrin domain containing 1), but not NLRP3, were upregulated by LPS or LPS+sevoflurane treatment, along with related proinflammatory cytokines, interleukin (IL)-1β, and IL-18. Pretreatment with Vx-765, a selective caspase-1 inhibitor, led to reduced IL-1β in LPS and LPS+sevoflurane groups. Caspase-1 inhibition by Vx-765 significantly decreased activated caspase-3 and caspase-9 immunoreactivity in the subiculum.Conclusions: Systemic inflammation promotes developmental neurotoxicity by worsening anaesthesia-induced neuronal damage with sex-specific behavioural outcomes. This highlights the importance of studying anaesthesia-induced neurotoxicity in more clinically relevant settings. [ABSTRACT FROM AUTHOR]

This study aimed to explore the influence mechanism of Tuina on anxiety-like behavior in immature rats with allergic airway inflammation (AAI). A total of 27 Sprague-Dawley male rats (aged ∼5 weeks) were divided randomly into control, AAI, and AAI with Tuina groups (9 rats per group). The anxiety-like behavior was assessed by an open field test and elevated plus-maze test. Allergic airway inflammation was assessed based on the pathological score of the lung, plasma ovalbumin-specific immunoglobulin E, interleukin 4, interleukin 5, and tumor necrosis factor-alpha levels. Glucocorticoid receptor (GR) messenger RNA and protein expression in the hippocampus and lung were detected by polymerase chain reaction and immunohistochemistry, respectively. Meanwhile, corticotropin-releasing hormone (CRH) messenger RNA in the hypothalamus, the plasma levels of adrenocorticotropic hormone and corticosterone were also determined respectively by polymerase chain reaction and enzyme-linked immunosorbent assay for hypothalamic-pituitary-adrenal axis (HPA) function. The AAI group had obvious anxiety-like behavior and hyperactive HPA axis, along with decreased GR expression in the hippocampus and lung. Following Tuina, AAI and the anxiety-like behavior were efficiently reduced, and the hyperactivity of HPA axis was efficiently inhibited, along with enhanced GR expression in the hippocampus and lung. Glucocorticoid receptor expression in the hippocampus and lung was enhanced, and anxiety-like behavior was reduced following Tuina in rats with AAI. [ABSTRACT FROM AUTHOR]

Background/purpose: Both psoriasis and periodontal diseases are characterized by an exaggerated immune response to the microbiota residing on epithelial surfaces. This study aimed to explore the associations between the severity of psoriasis and periodontal destruction in patients with psoriasis.Methods: Thirty-three patients diagnosed with psoriasis were referred from the dermatology clinic of National Taiwan University Hospital. Full-mouth periodontal examination was performed and saliva was collected after patients signed informed consent forms. The Psoriasis Area Severity Index (PASI) as well as clinical periodontal parameters including probing depth (PD), plaque index (PI), gingival index (GI), and clinical attachment level (CAL) were evaluated. Salivary cytokines including interleukin (IL)-1β, IL-12, IL-17, interferon-γ, and tumor necrosis factor (TNF)-α were tested with the Luminex Bio-Plex system. Anti-inflammatory medication, tobacco use, and underlying comorbidities were included in the analysis.Results: Baseline PASI was significantly associated with PI. PASI at follow-up was positively correlated with CAL ≥ 4 mm (%) and saliva IL-1β levels. Psoriasis patients who used non-steroidal anti-inflammatory drugs or topical steroids had significantly lower GI, PD ≥ 4 mm (%), and saliva IL-1β and TNF-α levels. Moreover, a history of tobacco use was associated with higher PD ≥ 4 mm (%).Conclusion: PI, CAL, and salivary IL-1β were associated with PASI. Periodontal severity was associated with psoriasis involvement. Periodontal inflammation in psoriasis may be modified by anti-inflammatory medication and tobacco use. Additional large-scale longitudinal and mechanistic studies are needed. [ABSTRACT FROM AUTHOR]

Yiqitongmai decoction (YQTMD), a classic TCM, has been widely used in clinical treatment for MI. However, it is still difficult to clarify the potential active compounds and pharmacological mechanisms of it in treating MI. To explore the active ingredients, pharmacological effects, potential targets and mechanisms of YQTMD against MI. Serum pharmacochemistry by UPLC-MS/MS was applied to analyze the phytochemical components in serum from YQTMD. These components were then used to predict the potential targets using network pharmacology approach and molecular dynamics simulations, and then the protective effect of them on H9c2 cells following hypoxic conditions was assessed. Afterwards, the pharmacological effects of YQTMD on MI in mice were tested by determining electrocardiogram (ECG), echocardiography, cardiac biomarkers, oxidative stress, inflammation and pathophysiological changes. The protein levels involving STAT3 signal were detected using Western blot and immunofluorescence assays. Furthermore, STAT3 inhibitor Sttatic was employed to further elucidate the underlying mechanisms. Totally, 26 compounds derived from YQTMD were identified in mice serum, and 201 genes associated with the compounds were collected. The compounds including safflomin A, ferulic acid, gypenoside XVII, ginsenoside Rg1 and glycyrrhizic acid were identified as the critical compounds of YQTMD to regulate STAT3 pathway. In vitro , compounds combination significantly enhanced the viability of H9c2 cells and reduced ROS level compared to model cells. The in vivo results showed that YQTMD effectively reduced myocardial injury, as evidenced by the decreased serum cardiac injury markers, reduction in the size of myocardial infarct, restoration of abnormal alterations in ECG and decrease in cardiomyocyte apoptosis. Additionally, YQTMD attenuated MI-induced cardiac dysfunction, alleviated pathological changes, reduced MDA levels, and enhanced SOD and GSH levels compared with model mice. Significantly, the levels of IL-6, IL-1β, and TNF-α were observed to decrease in the YQTMD group. The expression levels of key proteins (p-STAT3, HIF-1α, NOX2, TLR5 and Caspase3) in STAT3 pathway were also regulated by YQTMD. However, the cardioprotective effects of YQTMD on MI were attenuated by STAT3 inhibitor Sttatic. This study investigated the active ingredients and potential mechanisms of YQTMD for MI treatment based on serum pharmacochemistry and network pharmacology approaches, revealing that YQTMD exerts its therapeutic effects on MI by alleviating oxidative stress, inflammation and apoptosis through adjusting STAT3 signaling pathway. [Display omitted] • Yiqitongmai decoction showed protective effects against myocardial infarction. • The critical compounds of YQTMD against MI were identified. • YQTMD regulated STAT3-mediated oxidative stress, inflammation and apoptosis. [ABSTRACT FROM AUTHOR]

Immunoglobulin A nephropathy (IgAN) is the most common primary glomerulonephritis in the world, it is one of the most common causes of kidney disease and can lead to end-stage kidney disease, however, its pathogenesis is still complicated. The Shen-yan-yi-hao oral solution (SOLI) is an effective prescription for the clinical treatment of IgAN while its specific mechanism remains to be further elucidated. This study investigates SOLI's effects on IgAN in rats, particularly on the intestinal mucosal barrier, and identifies potential therapeutic targets through network pharmacology and molecular docking, validated experimentally. Target genes for SOLI in IgAN were identified and analysed through molecular docking and KEGG pathway enrichment. An IgAN rat model examined SOLI's effect on renal biomarkers and cytokines involved in specific pathways, ileum mucosal lesions, and the intestinal immune system. The IL-17 pathway's role was studied in IEC-6 cells with SOLI in vitro. Rats developed increased proteinuria and kidney damage marked by IgA deposition and inflammation. SOLI treatment significantly ameliorated these symptoms, reduced galactose-deficient Ig A1 (Gd-IgA1), and decreased cytokines like IL-17, TNF-α, IL-6 and IL-1β etc. SOLI also normalized intestinal tight junction protein expression, ameliorated intestinal damage, and regulated intestinal immune response (focused on IL-17/NF-κB signal pathway). SOLI moderated the abnormally activated IL-17 pathway, which damages intestinal epithelial cells, suggesting IgAN treatment potential. SOLI reduces proteinuria and enhances intestinal mucosal function in IgAN rats, kidney protection in the IgAN rat model may initiate from modulating the intestinal IL-17/NF-κB pathway and subsequent Gd-IgA1 accumulation. [Display omitted] • IL-17/NF-κB pathway might be implicated in the pathogenesis of IgA nephropathy. • SOLI improves renal function in rats with IgA nephropathy. • SOLI blocks intestinal IL-17/NF-κB in rats, improving gut function in IgA nephropathy. • SOLI suppresses circulatory inflammation response. [ABSTRACT FROM AUTHOR]

Evidence has demonstrated that Chinese medicine formula Xuefu Zhuyu decoction can markedly promote the formation of new hair in patients and mice with alopecia areata (AA). Amygdalin is one of the active components of Xuefu Zhuyu decoction, but its therapeutic effects and the underlying mechanisms on AA remains largely unrevealed. Therefore, this study aims to investigate the therapeutic effects and to probe its molecular mechanisms of inflammation and immune regulation on AA model of C3H/HeJ mice. The C3H/HeJ female mice were divided into control, AA, rusolitinib (60 mg/kg), and amygdalin groups (60, 90, and 120 mg/kg, 0.2 ml/10 g, i.g.). The optical microscope was used to observe the feature of the local skin, and the number of lanugo and terminal hair. H&E staining was performed to determine the degree of pathological damage to the skin. ELISA was performed to detect levels of interleukin-6 (IL-6), tumor necrosis factor-α (TNF-α) and interferon-γ (IFN-γ) in mice serum. Flow cytometry was carried out to analyze the CD4+CD25+FOXP3+, CD4+ and CD8+ of skin tissue. And the levels of CD4+ and CD8+, p-JAK/JAK2, p-STAT3/STAT, and SOCS3 were detected by immunohistochemistry. Western blot and qRT-PCR were employed to examine the expression levels of IL-6, TNF-α, IFN-γ, JAK2, p-JAK, STAT, p-STAT3 and SOCS3 proteins and genes in skin tissues. Compared with AA group, amygdalin immensely increased the number of vellus hairs and decreased the number of terminal hairs determined by skin microscopy and H&E staining. ELISA, Western blot and qRT-PCR data showed that the levels of IL-6, TNF-α and IFN-γ in serum and skin tissues of AA mice were significantly increased, while amygdalin administration dramatically restrained the contents of the three pro-inflammatory factors. Flow cytometry and immunohistochemistry hinted that amygdalin observably enhanced the number of CD4+CD25+FOXP3+ and CD4+ cells, while inhibited the number of CD8+ positive cells in mice with AA. Moreover, amygdalin signally reduced JAK2/STAT3 pathway-related protein and gene levels in AA mice. Amygdalin could inhibit inflammatory response and improve immune function in the treatment of AA. The underlying molecular mechanism may be related to inhibition of JAK2/STAT3 pathway. Amygdalin showed a certain therapeutic effect on AA by reducing the inflammatory infiltration of CD4+CD25+FOXP3+, CD4+ and CD8+ T cells in hair follicles, reducing the release of cytokines such as IL-6, TNF-α and interferon IFN-γ, and improving hair follicle damage. Meanwhile, amygdalin can inhibit the activation of JAK2/STAT3 pathway by reducing the phosphorylation of JAK2 and STST3, contributing to the suppression of inflammatory response in AA disease. [Display omitted] [ABSTRACT FROM AUTHOR]

Many ethnopharmacological properties (anti-tumor, etc.) have been credited to Plectranthus esculentus tuber but the scientific basis has not been established. Aim of the study : To evaluate the effect of methanol extract of P. esculentus tuber (MEPET) (phase 1) and its fractions (phase 2) on benign prostatic hyperplasia (BPH) in rats. The study was conducted in two phases. Phase 1, thirty-five male albino rats (6 weeks old) were divided into seven groups of five rats each: normal control (NC) received olive oil (subcutaneously) and water (orally); disease control (DC) received testosterone propionate (TP) (3 mg/kg) and water; test groups (1,2,3 and 4) received TP + MEPET at 100, 200, 400, 600 mg/kg respectively; positive control, received TP + finasteride (5 mg/70 kg). After 28 days, their relative prostate weights (RPW) and prostate specific antigen (PSA) were determined. Phase 2, thirty rats were divided into 6 groups of 5 rats each: NC received olive oil (subcutaneously daily) and dimethyl sulfoxide (DMSO) (orally); DC received TP (3 mg/kg), and DMSO; test group 1 received TP and aqueous fraction of MEPET (400 mg/kg); test group 2 received TP and methanol fraction of MEPET (400 mg/kg); test group 3 received TP, and ethyl acetate fraction of MEPET (400 mg/kg); positive control received TP and finasteride (5 mg/70 kg). After 28 days, their erythrocyte sedimentation rates, RPW, prostate levels of PSA, DHT, inflammatory, apoptotic markers and prostate histology were determined. Ethyl acetate fraction of MEPET modulated most of the parameters of BPH in the rats in a manner akin to finasteride as corroborated by prostate histology. EFPET could be useful in the treatment of BPH. [Display omitted] • Overdose of testosterone-propionate increases the concentraton of dihydrotestosterone and Bcl-2 in rat prostate. • Overdose of exogenous testosterone administration induces prostate hyperplasia via activation of inflammatory cytokines. • Ethylacetate fraction of Plectranthus esculentus tuber ameliorates benign prostatic hyperplasia. • Plectranthus esculentus tuber possess 5-alpha reductase inhibitory activity. • Plectranthus esculentus tuber ameliorates prostatic inflammation via inhibition of interleukin-6 and C-reactive proteins. [ABSTRACT FROM AUTHOR]

The traditional Chinese medicine (TCM) Xiaoer-Feire-Qing granules (XEFRQ) has been used to treat pyretic pulmonary syndrome (PPS) in children for many years. The function of the lungs is considered to be closely related to the large intestine in TCM. Purpose: We aimed to investigate the effects of XEFRQ on PPS and the underlying mechanisms via network pharmacology and animal experiments. The TCMSP platform was used to identify the ingredients and potential targets of XEFRQ. The GeneCards, OMIM, and TTD databases were used to predict PPS-associated targets. Cytoscape 3.9.1 was employed to construct the protein–protein interaction network, and target prediction was performed by GO and KEGG analyses. For the animal experiment, a PPS model was constructed by three cycles of nasal drip of Streptococcus pneumoniae (STP; 0.5 mL/kg). The animals were randomly divided into the following four groups according to their weight (n = 10 rats per group): the blank group, the model group, the XEFRQ-L (16.3 g/kg) group, and the XEFRQ-H (56.6 g/kg) group. Rats in the blank group and the model group were given 0.5% CMC-Na by gavage. The general conditions of the rats were observed, and their food-intake, body weight, and body temperature were recorded for 14 days. After the intervention of 14 days, serum was collected to detect inflammatory cytokines (TNF-α, IL-1β, and PGE2) and neurotransmitters (5-HT, SP, and VIP). H&E staining was used to observe the pathological morphology of lung and colon tissue. AQP3 expression was detected by Western blot. In addition, the gut microbiota in cecal content samples were analyzed by 16S rDNA high-throughput sequencing. Our network analysis revealed that XEFRQ may alleviate PPS injury by affecting the levels of inflammatory cytokines and neurotransmitters and mitigating STP-induced PPS. In vivo validation experiments revealed that XEFRQ improved STP-induced PPS and reduced the expression of inflammatory cytokines and neurotransmitters. Notably, XEFRQ significantly decreased the protein expression levels of AQP3, which was associated with dry stool. Our gut microbiota analysis revealed that the relative abundance of [Eubacterium]_ruminantium_group , Colidextribacter , Romboutsia , and Oscillibacter was decreased, which means XEFRQ exerts therapeutic effects against PPS associated with these bacteria. Our results demonstrate that XEFRQ alleviates PPS by affecting the lungs and intestines, further guiding its clinical application. [Display omitted] [ABSTRACT FROM AUTHOR]

The Sang Yu granule (SY), a traditional Chinese medicine prescription of Xijing Hospital, was developed based on the Guanyin powder in the classical prescription "Hong's Collection of Proven Prescriptions" and the new theory of modern Chinese medicine. It has been proved to have a certain therapeutic effect on drug-induced liver injury (DILI), but the specific mechanism of action is still unclear. Aim of the study was to explore the effect of SangYu granule on treating drug-induced liver injury induced by acetaminophen in mice. The chemical composition of SY, serum, and liver tissue was analyzed using ultrahigh-performance liquid chromatography quadrupole time-of-flight mass spectrometry. To assess hepatic function, measurements were taken using kits for total bile acids, as well as serum AST, ALT, and ALP activity. Concentrations of IL-1β and TNF-α in serum were quantified using ELISA kits. Transcriptome Sequencing Analysis and 2bRAD-M microbial diversity analysis were employed to evaluate gene expression variance in liver tissue and fecal microbiota diversity among different groups, respectively. Western blotting was performed to observe differences in the activation levels of FXR, SHP, CYP7A1 and PPARα in the liver, and the levels of FXR and FGF-15 genes and proteins in the ileum of mice. Additionally, fecal microbiota transplantation (FMT) experiments were conducted to investigate the potential therapeutic effect of administering the intestinal microbial suspension from mice treated with SY on drug-induced liver injury. SY treatment exhibited significant hepatoprotective effects in mice, effectively ameliorating drug-induced liver injury while concurrently restoring intestinal microbial dysbiosis. Furthermore, SY administration demonstrated a reduction in the concentration of total bile acids, the expression of FXR and SHP proteins in the liver was up-regulated, CYP7A1 protein was down-regulated, and the expressions of FXR and FGF-15 proteins in the ileum were up-regulated. However, no notable impact on PPARα was observed. Furthermore, results from FMT experiments indicated that the administration of fecal suspensions derived from mice treated with SY did not yield any therapeutic benefits in the context of drug-induced liver injury. The aforementioned findings strongly suggest that SY exerts a pronounced ameliorative effect on drug-induced liver injury through its ability to modulate the expression of key proteins involved in bile acid secretion, thereby preserving hepato-enteric circulation homeostasis. [Display omitted] • A way to evaluate the effects and mechanism of Sang Yu granule. • Sang Yu granule improves acetaminophen-induced liver injury. • Sang Yu granule promotes the liver function through the FXR-SHP and FXR-FGF15/19 pathway. [ABSTRACT FROM AUTHOR]

Xihuang pills, a time-honored Chinese compound formula with a history spanning thousands of years, have demonstrated remarkable efficacy in treating various cancers, such as breast cancer, colon cancer, and liver cancer. Clinical applications over the years have established their effectiveness. Several scholars conducting experimental studies have elucidated the potent tumor-suppressing effects of Xihuang pills. While the inhibition of tumor vascular development and prevention of tumor cell invasion and metastasis have been well-explored mechanisms, the impact on the tumor immune microenvironment has received less attention. This study focuses on investigating the immune microenvironment adjustments induced by Xihuang pills in hepatocellular carcinoma. Tumour cells will find an escape phenomenon during tumour immunotherapy, which will affect immunotherapy results. We will research the regulation of the tumour immune microenvironment, to provide a more complete and precise basis for the elucidation of the mechanism of Xihuang pills in treating cancers. It provides new research ideas for people to treat liver cancer. Through in vivo and in vitro assessments confirming the intervention effects of Xihuang pills, we observed alterations in T cell typing, macrophage polarization, and tumor-associated cytokine levels. The primary active ingredients of Xihuang pills were identified using UPLC-MS/GC-MS, and relevant pathways in the treatment of hepatocellular carcinoma were predicted through network pharmacology. Combining the network pharmacology approach, we predicted the pathways relevant to Xihuang pills in treating hepatocellular carcinoma and experimentally validated the involvement of PD-1/PD-L1, a key immunity-related axis. Xihuang Pill has a regulatory effect on the tumor immune microenvironment. The results indicated that Xihuang pills could impact splenic lymphocyte phenotyping, macrophage polarization, and IL-6 cytokine expression in liver cancer mice. The mechanism of action was associated with the regulation of the PD-1/PD-L1 signaling pathway by the STAT3 protein. [Display omitted] [ABSTRACT FROM AUTHOR]

Polycystic ovary syndrome (PCOS) is a common endocrine disorder associated with reproductive dysfunction and metabolic abnormalities, particularly characterized by insulin resistance and chronic low-grade inflammation. Multiple clinical studies have clearly demonstrated the significant efficacy and safety of the combination of Bailing capsules (BL) in the treatment of PCOS, but its pharmacological effects and mechanisms still require further study. To evaluate the effect of BL on improving PCOS in mice and explore the mechanism. In this study, Dehydroepiandrosterone (DHEA) injection was administered alone and in combination with a high-fat and high-sugar diet to induce PCOS-like mouse. They were randomly divided into five groups: normal group (N), PCOS group (P), Bailing capsule low-dose group (BL-L), Bailing capsule high-dose group (BL-H) and Metformin + Daine-35 group (M + D). Firstly, the effects of BL on ovarian lesions, serum hormone levels, HOMA-IR, intestinal barrier function, inflammation levels, along with the expression of IRS1, PI3K, AKT, TLR4, Myd88, NF-κB p65, TNF-α, IL-6, and Occludin of the ovary, liver and colon were investigated. Finally, the composition of the gut microbiome of fecal was tested. The administration of BL significantly reduced body weight, improved hormone levels, improved IR, and attenuated pathological damage to ovarian tissues, up-regulated the expression of IRS1, PI3K, and AKT in liver. It also decreased serum LPS, TNF-α, and IL-6 levels, while downregulating the expression of Myd88, TLR4, and NF-κB p65. Additionally, BL improved intestinal barrier damage and upregulated the expression of Occludin. Interestingly, the abundance of norank_f__Muribaculacea and Lactobacillus was down-regulated, while the abundance of Akkermansia was significantly up-regulated. The results of the study showed that BL exerts a treatment PCOS effect, which may be related to the modulation of the gut microbiota, the improvement of insulin resistance and the intestinal-derived LPS-TLR4 inflammatory pathway. Our research will provide a theoretical basis for the clinical treatment of PCOS. [Display omitted] • Bailing capsule has the effect of tonifying the kidney and benefiting qi, and can be clinically used for the adjuvant treatment of PCOS. • Bailing capsule administration affects changes in intestinal flora in PCOS-like mice. • Bailing capsule ameliorates insulin resistance and inflammatory response in PCOS-like mice through the gut-derived LPS-TLR4 inflammatory pathway. [ABSTRACT FROM AUTHOR]

Da-Jian-Zhong decoction (DJZD) is a herbal formula clinically used for abdominal pain and diarrhea induced by spleen-Yang deficiency syndrome. Recently, treatment of diarrhea-predominant irritable bowel syndrome (IBS-D) with DJZD has received increasing attention, but the underlying mechanism of action remains elusive. We aimed to evaluate the therapeutic effect of DJZD on IBS-D rats and to elucidate the underlying mechanisms. An IBS-D rats model was constructed using a two-factor superposition method of neonatal maternal separation and Senna folium aqueous extract lavage. Moreover, the effect of DJZD was evaluated based on the body weight, rectal temperature, abdominal withdrawal reflex (AWR), and Bristol stool scale score (BSS). The factors that regulate the DJZD effects on IBS-D were estimated using whole microbial genome, transcriptome sequencing (RNA-Seq), flow cytometry, and quantitative reverse transcription polymerase chain reaction (RT-qPCR) analyses. We found that DJZD alleviated the symptoms of IBS-D rats, with the low-dose (2.4 g/kg) as the better ones, as shown by the higher body weight and lower AWR score and BSS. At the phylum level, the relative abundance of Bacteroidetes was obviously increased, and at the genus level, Lactobacillus and Parabacteroides were increased, while that of Firmicutes_bacterium_424 and Ruminococcus gnavus was decreased in DJZD group. Furthermore, the significantly enriched GO terms after treatment with DJZD mainly included the immune response, positive regulation of activated T cell proliferation, and positive regulation of interleukin-17 (IL-17) production. Importantly, flow cytometry analysis further revealed that the T helper cell type 17/regulatory T cell (Th17/Treg) balance contributed to the DJZD-induced alleviation of IBS-D symptoms, as DJZD downregulated Th17/Treg ratio and Th17 cell-related cytokines IL-17 and IL-6 levels in the colon. These results demonstrated that DJZD has a good therapeutic effect on IBS-D rats, probably by maintaining the homeostasis of gut microbiota and regulating Th17/Treg balance and its related inflammatory factors. [Display omitted] [ABSTRACT FROM AUTHOR]

Uncaria rhynchophylla (Miq.) Miq.ex Havil. was a classical medicinal plant exhibiting the properties of extinguishing wind, arresting convulsions, clearing heat and pacifying the liver. Clinically, it could be utilized for the treatment of central nervous system-related diseases, such as Alzheimer's disease. U. rhynchophylla (UR) and its major ingredient alkaloid compounds (URA) have been proved to exert significant neuroprotective effects. However, the potential mechanism aren't fully understood. This study systematically examined the therapeutic effects of URA on AD pathology in APP-PS1 mice, and revealed the potential mechanism of action. The cognitive ability was evaluated by morris water maze test in APP-PS1 mice. The H&E staining was used to observe the tissue pathological changes. The ELISA kits were used to detect the level of inflammatory factors. The flow cytometry was used to analyze the percentage of CD4+ effector T cells (Teffs) in spleen. The immunofluorescent staining was performed to count the Teffs and microglia in brain. The protein expression was analyzed by western blot. In vitro , the lymphocyte proliferation induced by ConA was performed by CCK-8 kits. The IFN-γ, IL-17, and TNF-α production were detected by ELISA kits. The effects of URA on glycolysis and the involvement of PI3K/Akt/mTOR signaling pathway was analyzed by Lactic Acid assay kit and western blot in ConA-induced naive T cell. URA treatment improved AD pathology effectively as demonstrated by enhanced cognitive ability, decreased Aβ deposit and Tau phosphorylation, as well as reduced neuron apoptosis. Also, the neuroinflammation was significantly alleviated as evidenced by decreased IFN-γ, IL-17 and increased IL-10, TGF-β. Notably, URA treatment down-regulated the percentage of Teffs (Th1 and Th17) in spleen, and reduced the infiltration of Teffs and microglia in brain. Meanwhile, the Treg cell was up-regulated both in spleen and brain. In vitro , URA was capable of attenuating the spleen lymphocyte proliferation and release of inflammatory factors provoked by ConA. Interestingly, glycolysis was inhibited by URA treatment as evidenced by the decrease in Lactic Acid production and expression of HK2 and GLUT1 via regulating PI3K/Akt/mTOR signaling pathway in ConA-induced naive T cell. This study proved that URA could improve AD pathology which was possibly attributable to the restraints of CD4+ T cell mediated neuroinflammation via inhibiting glycolysis. [Display omitted] • URA improves AD pathology by restraining neuroinflammation in APP-PS1 mice. • URA alleviates neuroinflammation via regulating CD4+ Teffs/Treg balance. • URA restrains ConA-induced T cell activation via inhibiting glycolysis. • URA inhibits the glycolysis by suppressing the PI3K/Akt/mTOR pathway. [ABSTRACT FROM AUTHOR]

Dahuang Huanglian Xiexin Decoction (XXD), derived from Zhang Zhongjing's Treatise on Typhoid Fever, has a long history of medicinal use and is widely used for digestive system diseases. It is mainly composed of three natural medicines, including Dahuang (Rheum palmatum L.), Huanglian (Coptis chinensis Franch.), and Huangqin (Scutellaria baicalensis Georgi). Modern pharmacological research shows that the active ingredients of XXD can have a positive effect on intestinal flora regulatory effect, but its mechanism of action is unclear. Clarify the effect of XXD on regulating dysbiosis, and elucidate the mechanism of XXD in alleviating dysbiosis based on network pharmacology, molecular docking and experimental verification. Histopathological observation and intestinal high-throughput sequencing were used to observe the effect. Preliminary prediction of the mechanism of action of XXD in treating dysbiosis through network pharmacology and molecular docking. Finally, the effect of XXD on the IL-17 signaling pathway was verified through in vivo experiments. Histopathology and high-throughput sequencing of intestinal flora indicated that XXD has a good regulatory effect on bacterial dysbiosis. At the same time, network pharmacology identified a total of 40 active compounds, 14 of which may be key compounds for XXD to treat dysbiosis. In addition, the study also revealed 14 potential key targets as well as the top 5 therapeutic targets: IL-6, TNF- α , IL-1 β , TP53 and PTGS2. GO and KEGG predicted the key pathway for IL-17 signaling pathway to play a role in XXD. In the verification of the prediction results, it was found that the above targets and the IL-17 target showed strong activity in molecular docking. Furthermore, it was found that XXD can reduce the levels of IL-17, IL-6, TNF- α , IL-1 β , p53 and COX-2 in serum, while inhibiting the expression of IL-17, IL-17RA, Act-1 and NF- κ B protein and the mRNA expression of IL-17, IL-17RA and Act-1 in colon tissue. This study found that XXD has a good regulatory effect on dysbiosis and its induced symptoms. Network pharmacology was used to predict the key compounds and therapeutic targets of XXD, and preliminary experiments confirmed that XXD may regulate bacterial dysbiosis by inhibiting the IL-17 signaling pathway. [Display omitted] • Dahuang Huanglian Xiexin Decoction (XXD) can relieve symptoms caused by dysbiosis. • XXD can regulate the diversity and richness of intestinal flora. • XXD regulates dysbiosis by inhibiting the IL-17 signaling pathway. [ABSTRACT FROM AUTHOR]