Levels Of Interleukin Research Articles

Assessing the hepatoprotective efficacy of Vitis gracilis Wall. against doxorubicin-induced hepatic injury in rats

Context: Doxorubicin is an anticancer drug that can adversely affect the liver. Therefore, seeking medical attention to manage pain and minimize side effects is crucial. Aims: To evaluate the hepatoprotective potential of Vitis gracilis Wall. nanoherbs against doxorubicin-induced hepatotoxicity. Methods: The study included five treatment groups: T0 (negative control), T+ (positive control with doxorubicin alone), TC (doxorubicin + vitamin C at 0.2 mg/kg body weight/day), T125 (doxorubicin + V. gracilis at 125 mg/kg body weight/day), and T150 (doxorubicin + V. gracilis at 150 mg/kg body weight/day). Doxorubicin, administered intraperitoneally at 0.0019 mg/kg body weight once a week for three weeks, induced hepatotoxicity in the T+ group. Results: Serum transaminases were significantly reduced in the T125 and T150 groups, indicative of the hepatoprotective effects of V. gracilis. Immunohistochemical analysis demonstrated the modulation of key markers, with decreased levels of pro-inflammatory tumor necrosis factor-α and increased levels of anti-inflammatory interleukin 10 in the T125 and T150 groups. The activities of oxidative stress markers, including superoxide dismutase and caspase 3, were favorably influenced by V. gracilis nanoherb treatment. Conclusions: These findings suggest that V. gracilis nanoherbs may effectively attenuate doxorubicin-induced hepatotoxicity, evidenced by biochemical and immunohistochemical changes. This study provides a foundation for further exploration of V. gracilis nanoherbs as a potential adjunctive therapy in preventing chemotherapy-associated liver damage.

Exosome-like nanovesicle targeting visceral adipose tissue inflammation mitigates heart failure with preserved ejection fraction

Abstract Introduction Heart failure (HF) with preserved ejection fraction (HFpEF) is associated with chronic systemic inflammation and obesity, with limited therapies. Inflammation in visceral adipose tissue (VAT) was significantly evoked in obese mice; while mesenchymal stem cell (MSC), especially atorvastatin (ATV)-pretreated MSC, could promote anti-inflammatory phenotype switch of immunocytes (e.g. macrophages), serving as a promising therapy for obesity-related HFpEF. Thus, the study was designed to prepare a novel ATV-pretreated MSC-derived exosome-like nanovesicles (ELNVs) and assess the anti-inflammatory and cardioprotective effects of ELNVs. Methods ELNVs derived from unpretreated MSC (ELNVM) or ATV-pretreated MSC (ELNVMA) were prepared and characterized (Figure 1). PKH-26-labelled ELNVs were incubated with THP1 cells for cell uptake assay. For anti-inflammatory studies in vitro, ELNVs (5×1010/mL) were added into the medium, followed by the induction of M1 or M2 polarization. The expressions of iNOS and Arg1 were measured by immunofluorescence (IF) staining. A 2-hit preclinical mice model of HFpEF, established by a 12-week high-fat diet (HFD) and Nω-Nitro-L-arginine methyl ester hydrochloride administration (0.5 g/L), was applied and received normal saline (NS) or ELNVs (i.p., 5×1011/kg body weight, 3 times a week). Functional and histological analysis including echocardiography, exhaustion test, WGA staining for hearts and western blot for VAT were performed. Quantitative polymerase chain reaction (qPCR) of key long non-coding RNAs (lncRNAs) was used to identify the mediator in ELNVs. Results The mean diameters of ELNVM and ELNVMA were 109.5 and 114.6 nm respectively and both ELNV types could be taken by THP1 cells. VAT inflammation was activated in HFpEF mice compared to the control in terms of the protein levels of iNOS and Arg1. An elevated expression of Arg1 and a decreased level of iNOS was observed in THP1 cells in vitro and VAT in vivo in both ELNV groups (P<0.05, Figure 1 and 2). Consistently, levels of interleukin (IL)-1β were increased in VAT of HFpEF mice, which were downregulated in ELNVM and ELNVMA groups. Both ELNVs could reduce the E/E’, and attenuate cardiac hypertrophy (heart weight to tibial length) and pulmonary congestion (lung weight [wet to dry]) (all P<0.05), with more pronounced improvements in ELNVMA group (Figure 2). Results of qPCR indicated three lncRNA candidates (TARID, H19 and KLF3-AS1) that were previously reported to inhibit M1 polarization or promote M2 polarization, were elevated in ELNVMA compared to ELNVM (P<0.05). Conclusion VAT inflammation was evoked in HFpEF mice and contributed to the development of HFpEF. This pilot study developed a novel ATV-pretreated ELNVs, which might serve as a promising tool for alleviating HFpEF due to the charming anti-inflammatory and cardioprotective effects mediated by regulating VAT macrophages.Figure 1.ELNVs’ PreparationFigure 2.Anti-inflammation of ELNVs

Partial deletion of the Akap1 gene promotes abnormalities in gut barrier function, gut microbiota composition and cardiac function during cardiovascular aging in mice

Abstract Background Cardiovascular aging is characterized by mitochondrial dysfunction, changes in intestinal permeability and microbiota composition. Mitochondria-targeted A-kinase anchoring proteins (mitoAKAPs) are a group of structurally diverse proteins binding the regulatory subunits of protein kinase A (PKA), and targeting PKA at discrete intracellular locations. We analyzed the effects of global partial genetic deletion of Akap1 on intestinal barrier permeability, microbiota composition, inflammation, and cardiac function during aging in mice. Purpose The proposal of this study was to determine the role of mitoAKAPs in the gut-heart axis during cardiovascular aging. Methods Young (4-6-month) and old (18-24-month) genetically modified Akap1+/+ and Akap1+/− mice of either sex underwent evaluation of cardiac function by transthoracic echocardiography. To evaluate gut barrier integrity, we analyzed expression levels of intestinal junction proteins occludin (Ocln), zonulin (Tjp1) in colonic samples and FITC-dextran permeability in vivo, circulating levels of Tumor Necrosis Factor-alpha (TNF-alpha), Lipopolysaccharide (LPS), Interleukin-1 (IL-1) and Interleukin-10 (IL-10). Fecal microbial composition was evaluated by Illumina Mi-Seq, Gut microbiota differences based on 16S rDNA sequencing at genus and species taxonomic levels were identified using linear discriminant analysis (LDA) combined with effect size (LEfSe) algorithm. Finally, faecal microbiota transplantation (FMT) was performed for five weeks to test whether modification of gut microbiota composition can affect cardiac function. Results A reduction in % left ventricular shortening (FS%) was observed in young and old Akap1+/- mice compared to Akap1+/+ mice. This finding was associated to increased intestinal permeability, as indicated by reduced mRNA levels of Ocln and Tjp1, increased LPS traslocation across intestinal epitelium into blood in 24m Akap1+/- mice compared to Akap1+/+. Through the analysis of the microbial signature, we observed the different bacterial species present in the microbiota of the experimental groups. FMT of bacteria species from old Akap1+/− to young Akap1+/+ mice induced gut abnormalities and cardiac dysfunction, while FMT from young Akap1+/+ donors ameliorated cardiac dysfunction in old Akap1+/+ mice. Conclusions MitoAKAPs play a crucial role in the maintenance of intestinal barrier function, gut microbiota composition and cardiac function during aging. Modulation of the composition of the intestinal microbiota influences intestinal permeability and cardiac function. MitoAKAPs could represent an important diagnostic and therapeutic target for cardiac and intestinal dysfunction.

Shen-Bai-Jie-Du decoction suppresses the progression of colorectal adenoma to carcinoma through regulating gut microbiota and short-chain fatty acids

BackgroundShen-Bai-Jie-Du decoction (SBJDD), a traditional Chinese herb formula developed based on evidence-based medicine, is efficacy to reduce the recurrence and carcinogenesis of colorectal adenoma. However, the mechanism of SBJDD to treat colorectal adenoma remains unclear. The present study aims to investigate the efficacy and mechanism of SBJDD on colorectal adenoma carcinogenesis from the aspects of regulating gut microbiota and short-chain fatty acids (SCFAs).MethodsTwenty-one patients diagnosed with colorectal adenoma were recruited in the study and required to take SBJDD for four consecutive weeks. Analysis of gut microbiota was conducted using 16S rRNA gene amplicon sequencing, while levels of SCFAs in fecal and serum samples were determined through HPLC–MS/MS. Additionally, twenty-four Apcmin/+ mice were randomly assigned to normal diet (ND), high-fat diet (HFD), and SBJDD groups. The pharmacological effects and mechanism of SBJDD on colorectal adenoma carcinogenesis were assessed using RT-qPCR, HE staining, IHC staining, Western blot, IF staining, and Flow cytometry assays.ResultsOur clinical study has shown that SBJDD can regulate the gut microbiota composition and enhance SCFAs production in patients with colorectal adenoma. SBJDD alleviated colorectal adenoma formation and carcinogenesis, as well as protected the integrity of the intestinal barrier in the Apcmin/+ mice model compared to the HFD group. Additionally, SBJDD was found to regulate gut microbiota capable of producing SCFAs. G protein-coupled receptors GPR43, GPR41, and GPR109a were effectively activated in the SBJDD group, while HDAC1 and HDAC3 were inhibited. Furthermore, decreased expression levels of interleukin 1 beta (IL-1β) and interleukin 6 (IL-6), along with elevated expression level of interleukin 10 (IL-10), were observed in the colorectal tissue of the SBJDD group. Finally, SBJDD exhibited the ability to reduce the proportion of M1-type macrophages while increasing the proportion of M2-type macrophages.ConclusionsOur study objectively demonstrated the pharmacological effects of SBJDD in inhibiting the progression of colorectal adenoma and investigated its mechanisms in terms of regulating gut microbiota, increasing SCFAs, and reducing colorectal inflammation.

The role of IL15 in angiotensin II-mediated cardiac remodelling

Abstract Hypertension (HTN) mediated target organ damage, such as cardiac remodelling, is a major cause of death and disability. Cytokines are important regulators of cardiac function, inflammation, and remodelling in cardiovascular disease. Increased levels of interleukin 15 (IL15) have been noted in HTN, but its role in HTN heart disease remains unknown. This study investigates the role of the IL15 axis in the pathogenesis of cardiac remodelling in HTN. Male 12-week-old IL15 receptor α knock-out (IL15RAKO), IL15 knock-out (IL15KO) and matching wild type (WT) mice were administered vehicle or angiotensin II (AngII) (490 ng/min/kg) for 2 weeks by osmotic minipump. Blood pressure was measured by tail cuff (n=5-8). Cardiac function was analysed by echocardiography (n=3-4). Cardiac infiltrating immune cells were analysed by flow cytometry (n=2-3 for IL15RAKO, n=6-10 for IL15KO). Cardiac remodelling was assessed by picrosirius red, WGA staining (n=5-8) and expression of markers of remodelling using RT-qPCR and western blots (n=5-8). Data are presented as mean±SEM and analysed using two-way ANOVA. AngII infusion caused a significant increase in systolic blood pressure in WT and IL15KO animals. In contrast, in IL15RAKO, the response to AngII was blunted. This was in line with a decrease in ejection fraction, however only WT mice had an increase in global longitudinal strain (-20.3±2.0 vs -10.9±1.2, p=0.0039 in WT and 19.9±0.8 vs -16.0±2.1, p=0.1878 in IL15RAKO). HTN was associated with increased cardiac IL15 protein levels in mice. The heart-to-body ratio, along with cardiomyocyte cross-sectional, were significantly increased in WT, but not in IL15RAKO HTN mice. Furthermore, histological analysis showed significantly higher cardiac collagen accumulation in WT but not IL15RAKO upon AngII infusion (5.8±1.0% in WTvvs. 2.1±0.5% in IL15RAKO, p=0.0021). This was in line with a higher expression of col1a1 in WT but not IL15RAKO HTN hearts (20.0±6.0 vs 4.5±1.7, p=0.0173). Similarly, the FN1 protein level was significantly increased in WT but not IL15RAKO AngII-treated mice. These changes were associated with a higher number of Cd11b+ macrophages accumulated in WT hypertensive hearts only. In contrast to IL15RAKO, mice lacking IL15 showed similar increases in global longitudinal strain, heart hypertrophy, and cardiomyocyte cross-sectional area as WT mice upon AngII infusion. Similarly, IL15KO hypertensive hearts showed a significant increase of col1a1 and FN1 in comparison to vehicle-treated mice. A similar level of Cd11b+ macrophages was found in hypertensive IL15KO and WT mice's hearts. In conclusion, IL15RA, but not IL15, plays a critical role in cardiac remodelling mediated by AngII infusion. This suggests that the IL15-IL15RA axis may play an important yet complex role in hypertensive heart disease.

Assessment of the Therapeutic Potential of Enhancer of Zeste Homolog 2 Inhibition in a Murine Model of Bronchiolitis Obliterans Syndrome

Bronchiolitis obliterans syndrome (BOS) is a chronic complication following lung transplantation that limits the long-term survival. Although the enhancer of zeste homolog 2 (EZH2) is involved in post-transplantation rejection, its involvement in BOS pathogenesis remains unclear. We aimed to investigate the therapeutic potential of EZH2 inhibition in BOS. 3-deazaneplanocin A (DZNep) was administered intraperitoneally to heterotopic tracheal transplant recipient model mice. Tracheal allografts were obtained on days 7, 14, 21, and 28 after transplantation. The obstruction ratios of the DZNep and control groups on days 7, 14, 21, and 28 were 15.1% ± 0.8% vs. 20.4% ± 3.6% (p = 0.996), 16.9% ± 2.1% vs. 67.7% ± 11.5% (p < 0.001), 47.8% ± 7.8% vs. 92.2% ± 5.4% (p < 0.001), and 60.0% ± 9.6% vs. 95.0% ± 2.3% (p < 0.001), respectively. The levels of interleukin (IL)-6 and interferon-γ on day 7 and those of IL-2, tumor necrosis factor, and IL-17A on days 14, 21, and 28 were significantly reduced following DZNep treatment. DZNep significantly decreased the number of infiltrating T-cells on day 14. In conclusion, DZNep-mediated EZH2 inhibition suppressed the inflammatory reactions driven by pro-inflammatory cytokines and T cell infiltration, thereby alleviating BOS symptoms.

Immunological role of zinc in preterm neonates

Zinc (Zn), an essential trace element, plays a significant role in fetal development and biological defense during the embryonic and neonatal periods. Therefore, exploring the kinetics of Zn related to immune disturbances in preterm neonates is important. We here performed the measurement of Zn concentration along with immunological analysis of neonates and investigated the role of Zn in the neonatal period. Serum Zn concentrations were measured immediately after birth in neonates (329 cases). Moreover, for 25 cases, the kinetics of various immune cells and cytokines were measured by flow cytometry and electrochemiluminescence. We observed that Zn levels were inversely correlated with gestational weeks. Immune cell and cytokine analysis revealed an inverse correlation between HLA-DR on monocytes and Zn levels and between inflammatory cytokine interleukin-12 and Zn levels. Furthermore, oxidative stress status was inversely correlated with Zn levels. Our results suggested that the Zn dynamics immediately after birth, which show a negative correlation with the gestational week, can provide an anti-inflammatory and anti-oxidative environment for preterm neonates. The increased Zn concentration in the blood of preterm neonates may consequently protect neonates from perinatal stress.

Sleep is altered during menstruation but not inflammatory parameters: Results from polysomnography of EPISONO database.

Menstruation is an inflammatory process that involves changes in women's physiology leading to mental and physical complaints. Sleep is essential for optimal hormonal release, immune response, and wellbeing, becoming an important factor to be evaluated. We compared sleep, inflammatory mediators, fatigue, anxiety and depression symptoms, and quality of life in menstruating and non-menstruating women. We used the polysomnographic data of 232 women from EPISONO 2007, an epidemiological study from São Paulo city, Brazil. Women were distributed into menstruating (N = 61) and non-menstruating groups (N = 171). We applied questionnaires related to sleep quality, sleepiness, insomnia, fatigue, anxiety and depression symptoms, and quality of life. The serum levels of interleukin 6, tumour necrosis factor-alpha, and C-reactive protein were analysed. For statistical analysis the significance level adopted was p < 0.05. Sleep efficiency was statistically lower in menstruating women (81% ± 13) compared with the non-menstruating group (84.2% ± 13.3, p < 0.023). No statistical differences between the two groups were found in respect to the other parameters analysed. Both groups scored for fatigue symptoms, but no statistical significance was observed between the groups. Our findings indicate that menstruation was associated with lower objective sleep efficiency, suggesting that menstruation may be a physiological factor impairing sleep. Further studies evaluating menstrual variables, and each phase of the menstrual cycle, should be undertaken to detect the main factors associated with sleep complaints, fatigue, and objective parameters of sleep.

Genetic insights into the causal linkage between systemic inflammatory regulators and frailty

ObjectivesPrevious studies have suggested the associations between systemic inflammation and the risk of frailty, but causal relationships between them remain not well established. We conducted a bi-directional Mendelian randomization (MR) analysis to investigate the causal links between systemic inflammatory regulators and frailty. MethodsGenetic variants associated with systemic inflammatory regulators were obtained from a comprehensive genetic study on 41 circulating cytokines, such as interleukin-4 (IL-4), eotaxin, and macrophage inflammatory protein-1β (MIP1β). We integrated summary-level data on frailty from two independent genetic studies on frailty index (FI) and Fried frailty score (FFS). The inverse-variance weighted method was used to assess the causal estimate. Sensitivity and heterogeneity analysis was performed to evaluate the stability of the estimates. The false discovery rate (FDR) method was used for P value adjustment of multiple comparisons. ResultsGenetically elevated levels of MIP1β and decreased levels of eotaxin were suggestively associated with increased FI (MIP1β: β = 0.016, Praw = 0.006, PFDR = 0.083; eotaxin: β = -0.030, Praw = 0.007, PFDR = 0.083) and FFS (MIP1β: β = 0.008, Praw = 0.027, PFDR = 0.247; eotaxin: β = -0.015, Praw = 0.014, PFDR = 0.247). In contrast, genetically predicted FI was suggestively associated with decreased levels of IL-4 (β = -0.395, Praw = 0.040, PFDR = 0.638) and platelet-derived growth factor BB (PDGF-BB, β = -0.385, Praw = 0.047, PFDR = 0.638) and increased levels of stem cell factor (SCF, β = 0.527, Praw = 0.005, PFDR = 0.204). Similar results were obtained from different sensitivity analysis. ConclusionsThe present study demonstrates that increased MIP-1β levels and decreased eotaxin levels might lead to a higher risk of frailty, whereas frailty might reduce the levels of IL-4 and PDGF-BB and increase the levels of SCF.

Ferulic acid alleviates cardiac injury by inhibiting avermectin-induced oxidative stress, inflammation and apoptosis

Avermectin (AVM) is a broad-spectrum antibiotic from the macrolide class, extensively employed in fisheries and aquaculture. Nevertheless, its indiscriminate utilisation has resulted in a substantial accumulation of remnants in the aquatic ecosystem, potentially inflicting significant harm to the cardiovascular system of aquatic species. Ferulic acid (FA) is a naturally occurring compound in wheat grain husks. It possesses potent anti-inflammatory and antioxidant properties, which can help reduce cardiovascular damage. Additionally, its affordability makes it an excellent option for aquaculture usage as a feed additive. This article explored the potential of FA as a feed additive to protect against AVM-induced heart damage in carp. We subjected carp to AVM for 30 days and provided them with a diet of 400 mg/kg of FA. FA substantially reduced the pathogenic damage to heart tissue caused by AVM, as shown through hematoxylin-eosin staining. The biochemical analysis revealed that FA markedly enhanced the activity of antioxidant enzymes catalase (CAT), glutathione (GSH), and total antioxidant capacity (T-AOC) while reducing the malondialdehyde (MDA) content. Furthermore, qPCR analysis demonstrated a substantial increase in the mRNA levels of transforming growth factor-β1 (tgf-β1) and interleukin-10 (il-10) simultaneously, significantly reducing the expression levels of interleukin-10 (il-6), interleukin-1β (il-1β), tumor necrosis factor-α (tnf-α) and inductible nitric oxide synthase (inos). Through the mitochondrial apoptotic route, FA reduced AVM-induced cell death in carp heart cells by upregulating bcl-2 while downregulating the mRNA expression levels of bax, fas, caspase8 and caspase9. In summary, FA alleviated cardiac injury by inhibiting AVM-induced oxidative stress, inflammatory response, and apoptosis in carp heart tissue.

Heat shock protein 70 promotes the progression of type 2 diabetic nephropathy by inhibiting T-cell immunoglobulin and mucin domain-3 and thereby promoting Th17/Treg imbalance.

Diabetic nephropathy (DN) is the most common complication of diabetes mellitus. We aimed to investigate the role of regulatory T cells (Tregs) and helper T cells 17 (Th17) in the development and progression of DN. A mouse type 2 diabetic nephropathy (T2DN) model was established. Immunohistochemistry was used to detect the expression of HSP70 and Tim-3 in mouse kidney tissues, and western blotting was used to detect the expression levels of HSP70 and Tim-3. PAS staining and Masson's trichrome staining were used to detect the degree of kidney injury. Flow cytometry was used to detect the number of Th17 and Treg cells in blood and kidney tissues. The expression levels of interleukin 17 (IL-17) and interleukin 10 (IL-10) in the serum were measured via ELISA. The expression of HSP70 was significantly increased while the expression of Tim-3 was significantly decreased in the kidneys of mice in the T2DN group compared with those in the control (NC) group. Additionally, the inhibition of HSP70 upregulated the expression of Tim-3 in T2DN mice. The Th17/Treg ratio was significantly greater in the blood and kidneys of the mice in the T2DN group than in those of the NC group, the expression of serum IL-17 was increased, and the expression of IL-10 was decreased. Increased HSP70 inhibits Tim-3 expression in T2DN mouse kidney tissues, and subsequently causes a Th17/Treg imbalance and an inflammatory response, ultimately leading to kidney injury. The inhibition of HSP70 may alleviate the progression of T2DN.

Serum interleukin-10 level is increased and correlated positively with disease severity in patients with dipeptidyl peptidase-4 inhibitor-related bullous pemphigoid.

Bullous pemphigoid (BP) is an autoimmune subepidermal blistering disease with a linear deposit of autoantibodies at the epidermal basement membrane zone. It was reported that diabetes patients who took a dipeptidyl peptidase-4 inhibitor (DPP4i), an oral antidiabetic drug, had an increased incidence of BP. However, data on DPP4i-related BP are limited. In our study, we measured serum levels of various cytokines using LEGENDplex and assessed correlations of these serum levels with clinical severity and laboratory data. Serum samples obtained from BP patients who visited our hospital from June 2016 to February 2023 were collected in this study. Patients' background, characteristics, and clinical data were retrospectively collected from their charts. Serum samples from 27 patients with DPP4i-unrelated BP, 17 patients with DPP4i-related BP, and 13 healthy controls were analyzed. Patients with DPP4i-related BP had lower score of Bullous Pemphigoid Disease Area Index (BPDAI)-erythema/urticaria, lower number of circulating eosinophils, and lower titer of anti-BP180 antibody than patients with DPP4i-unrelated BP. The serum interleukin (IL)-6 level was significantly higher in patients with DPP4i-related BP than in healthy controls (P = 0.0037). The serum IL-10 level was significantly higher in patients with DPP4i-related BP than in patients with DPP4i-unrelated BP and in healthy controls (P = 0.0006, P = 0.0448), and was positively correlated with the BPDAI-blister/erosions score (r = 0.757, P = 0.001), BPDAI-erythema/urticaria score (r = 0.616, P = 0.013), and BPDAI-total score (r = 0.833, P < 0.001) in patients with DPP4i-related BP. In conclusion, patients with DPP4i-related BP had increased serum levels of IL-6 and IL-10 compared with healthy controls and positive correlations between the serum IL-10 level and BPDAI scores reflecting clinical severity, indicating that the serum IL-10 level is a potential objective biomarker of disease severity in patients with DPP4i-related BP.

Botulinum Toxin Treatment of Psoriasis-A Comprehensive Review.

A literature search on the subject of botulinum toxin treatment in psoriasis found 15 relevant articles, 11 on human subjects and 4 on animal studies. Of the human data, eight were clinical trials and three were single case reports. Seven out of eight clinical trials, all open-label, reported improvement in psoriasis following intradermal or subcutaneous botulinum toxin injections. One double-blind, placebo-controlled study, which used a smaller dose than the open-label studies, did not note a healing effect. Animal studies have shown that injection of botulinum toxins in the skin heals psoriatic skin lesions and can reduce the level of interleukins (ILs) and cytokines as well as inflammatory cells in psoriatic plaques. There is a need for controlled, blinded studies conducted in larger numbers of patients with doses that have shown promise in open-label studies.

Systemic inflammation is associated with myocardial fibrosis in patients with obstructive hypertrophic cardiomyopathy.

Chronic low-grade inflammation, often observed in hypertrophic cardiomyopathy (HCM), promotes adverse ventricular remodelling. This study aimed to investigate the relationship between inflammatory markers and myocardial fibrosis (MF) in patients with HCM. This study included 102 patients with complete baseline data who underwent septal myectomy. Myocardial samples were stained with Masson's trichrome and analysed to determine myocardial collagen content and MF levels. Plasma levels of inflammatory markers were measured using standard laboratory procedures. Univariate and multivariate logistic regression analyses were performed to explore the relationship between the inflammatory markers and MF. Among the 102 participants included in the analysis, the mean age was 48.9years, with 69 [67.6%] being men. The overall MF ranged from 2.5% to 40.7% (mean=15.2±8.1%, median=13.0%, IQR=9.9%-18.4%). Participants were divided into two groups based on a median MF of 13%. The high MF group had a larger left atrial diameter and left ventricular ejection fraction. Levels of interleukin (IL)-2, tumour necrosis factor (TNF)-α and interferon (IFN)-α were significantly higher in patients with high MF compared to those with low MF (2.3 vs. 4.0pg/mL, 3.1 vs. 3.9pg/mL, 4.2 vs.4.7pg/mL, respectively; all P<0.05). In multivariate models adjusted for age, sex and other clinical features, IL-2, IL-5 and TNF-α, were correlated with increased interstitial MF [odds ratio (OR): 1.54, 95% confidence interval (CI): 1.10-2.14; OR: 1.42, 95% CI: 1.02-1.98; OR: 1.33, 95% CI: 1.04-1.70]. After additional adjustment for imaging indicators, IL-2 and TNF-α remained significant (OR: 1.49, 95% CI: 1.06-2.09, P=0.021; OR:1.35, 95% CI: 1.01-1.80, P=0.044). The correlation analysis between inflammation and replacement fibrosis assessed by CMR in 97 patients revealed that 72 (74.2%) showed late gadolinium enhancement (LGE). No significant correlation was found between inflammatory markers and the presence or extent of LGE. Higher levels of IL-2 and TNF-α were associated with increased histopathological interstitial MF in patients with HCM. Given the gradual progression of MF in HCM, initiating anti-inflammatory treatment in the early stages may delay its progression.

SiLOXL2 inhibits endothelial inflammatory response and EndMT induced by Ox-LDL.

Our research aimed to investigate the potential role and mechanism of lysyl oxidase (LOX)-like-2 (LOXL2) in atherosclerosis (AS) by using the human umbilical vein endothelial cells (HUVECs) stimulated by oxidized low-density lipoprotein (ox-LDL). HUVECs were treated with ox-LDL at different concentrations (0, 10, 25, 50, and 100 μg/mL) and incubated for 24 hours. The transfection efficacy of siLOXL2 was investigated by western blot and RT-qPCR. Cell migration, intracellular ROS measurement, oxidative stress, ELISA, and adhesion assays were carried out to examine the ox-LDL-induced HUVECs injury. RT-qPCR and Western blot were used to determine gene and protein expression levels. LOXL2 protein expression increased in ox‑LDL‑induced endothelial cells. Ox-LDL+siLOXL2 significantly inhibited the migration ability of HUVECs and reduced the expression of vascular endothelial growth factor A (VEGFA) and matrix metalloproteinase 9 (MMP-9) gene expressions (all, P &lt;0.05). The ox-LDL+siLOXL2 significantly reduced intracellular ROS production and inhibited the expression of Malondialdehyde (MDA), whereas it markedly enhanced superoxide dismutase (SOD) and catalase (CAT) (all, P &lt;0.05). Supernatant levels of Interleukin-1 beta (IL-1β), Interleukin 6 (IL-6), and Tumor necrosis factor alpha (TNF-α) were significantly attenuated by the ox-LDL+siLOXL2 treatment (all, P &lt;0.05). Ox-LDL+siLOXL2 markedly suppressed the expression of intercellular adhesion molecule-1 (ICAM-1) and vascular cell adhesion molecule-1 (VCAM-1) (all, P &lt;0.05). ox-LDL+siLOXL2 treatment remarkably reduced the expression of α-smooth muscle actin (α‑SMA) and Vimentin, while increased CD31 and von Willebrand factor (vWF) gene expression (all, P &lt;0.05). LOXL2 silencing is protected against ox-LDL-induced endothelial cell dysfunction, and the mechanism may be related to the inhibition of the EndMT pathway.

Hypoxia activates FGF-23-ERK / MAPK signaling pathway in ischemia-reperfusion induced acute kidney injury.

Both hypoxia and fibroblast growth factor-23 (FGF-23) are key factors in ischemia-reperfusion (I/R)-induced acute kidney injury (AKI). This study aimed to explore the relationship between hypoxia and FGF-23 in AKI. An I/R-AKI animal model was established using male BALB/c mice. HK-2 cells, a part of the human proximal tubular epithelial cell line, were subjected to hypoxia/reoxygenation (H/R). qPCR was used to measure FGF-23 and HIF-1α, ELISA was used to measure inflammatory and oxidative stress cytokines. Western blotting used to measure the phosphorylation of ERK level. In I/R mice, the levels of interleukin-6 (IL-6), tumor necrosis factor (TNF-α), malondialdehyde (MDA), and the phosphorylation of extracellular signal-regulated kinase (ERK) were increased, whereas the levels of interleukin-10 (IL-10), superoxide dismutase (SOD), glutathione peroxidase (GPx), and klotho were decreased, compared to the sham operated mice. Silencing the FGF-23 expression in I/R mice normalized the levels of IL-6, IL-10, TNF-α, MDA, SOD, Gpx, and ERK phosphorylation (p-ERK). In HK-2 cells, hypoxia-reperfusion (H/R) elevated the levels of IL-6, TNF-α, MDA, and ERK phosphorylation, but reduced IL-10, SOD, GPx, and klotho levels. Hypoxia induced apoptosis in HK-2 cells but silencing of FGF-23 expression blocked the effects of hypoxia on cell apoptosis, proinflammatory factors levels, oxidative stress response, and p-ERK levels. FGF-23 is a key molecule in AKI, and hypoxia plays a crucial role in AKI by inducing cell apoptosis; however, its role is regulated by FGF-23. FGF-23 affects oxidative stress and the inflammatory response of kidney tissues by activating the ERK/mitogen-activated protein kinase (MAPK) signaling pathway.

Efficacy of multimodal analgesia based on the concept of enhanced recovery after surgery in laparoscopic radical gastrectomy for gastric cancer

Objective: To explore the effect of multimodal analgesia based on the concept of enhanced recovery after surgery (ERAS) in patients undergoing laparoscopic radical gastrectomy (LRG) for gastric cancer (GC). Methods: Clinical data of 128 patients undergoing LRG for GC, admitted to Sir Run Run Shaw Hospital, Zhejiang University School of Medicine from March 2021 to March 2022, were retrospectively analyzed. Among them, 66 patients received a multimodal analgesic management based on ERAS (ERAS group), and 62 patients were treated with conventional mode of analgesia (control group). Pain levels, rehabilitation status, as well as inflammatory factors and stress response indicators before and after surgery were compared between the two groups. Results: There was no significant difference in baseline data between the two groups (P&gt;0.05). The postoperative pain and recovery in the ERAS group were better than those in the control group (P&lt;0.05). After the surgery, serum levels of tumor necrosis factor-alpha (TNF-α), Interleukin 6 (IL-6), and C-reactive protein (CRP) in both groups increased compared to before the surgery, but were significantly lower in the ERAS group compared to the control group (P&lt;0.05). After the surgery, serum malondialdehyde (MDA) and xanthine oxidase (XOD) levels in both groups increased, while superoxide dismutase (SOD) levels decreased compared to preoperative levels. The observed postoperative levels of serum MDA and XOD were significantly lower in the ERAS group, while the postoperative SOD levels were higher compared to the control group (P&lt;0.05). Conclusions: Patients undergoing LRG for GC can benefit from a multimodal pain management plan based on ERAS to reduce postoperative pain, alleviate inflammation, stress responses, and shorten the postoperative recovery process. doi: https://doi.org/10.12669/pjms.40.10.10088 How to cite this: Xu L, Yao L, Qin J, Xu H. Efficacy of multimodal analgesia based on the concept of enhanced recovery after surgery in laparoscopic radical gastrectomy for gastric cancer. Pak J Med Sci. 2024;40(10):2190-2195. doi: https://doi.org/10.12669/pjms.40.10.10088 This is an Open Access article distributed under the terms of the Creative Commons Attribution License (http://creativecommons.org/licenses/by/3.0), which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited.

Study of the Effects of Alfalfa Bioactive Substances and Polysaccharides on the Lactation Performance and Immune Function of Dairy Cows

Background: The aim of this study was to investigate the effects of alfalfa polysaccharides on the lactation performance and immune function of dairy cows. Methods: A total of 84 healthy Holstein cows were selected and randomly divided into 7 groups, including the control Group A0, the alfalfa polysaccharide groups (AP1, AP2, AP3) and the alfalfa extract groups (AE1, AE2, AE3). Each group had three replicates and each replicate had four cows. The daily rations of the dairy cows in the AP group and the AE group were supplemented with alfalfa polysaccharide powder and alfalfa extract at concentrations of 1, 2 and 3 kg/t, those in the A0 group served as a control. Result: (1) the milk production of dairy cows in the AE groups was extremely significantly greater (p less than 0.01) than that in A0 group and AP groups. The milk protein content of cows in the AP2 and AE2 groups was significantly greater (P less than 0.05) than that in the A0 group (2) The interleukin-2 (IL-2) levels in the serum of cows in the AP2, AP3, AE2 and AE3 groups were greater than those in the A0 and AP1 groups and the IgM antibody levels in the AP group and the AE group were extremely significantly greater than those in the A0 and AP1 groups (P less than 0.01). The IgA antibody level in the serum of dairy cows in the AP2, AP3, AE2 and AE3 groups was significantly (P less than 0.01) greater than that in the A0, AP1 and AE1 groups. In summary, the alfalfa extract improved both the lactation performance and immunity of dairy cows, indicating comprehensive effects. Alfalfa polysaccharides at a concentration of 2 kg/t improved the immunity of dairy cows.

Analysis of the effect of CICARE communication nursing on the improvement of serum IL-10, IL-6, IL-4, IL-2 and lung function in outpatients with acute bronchitis

Abstract: OBJECTIVE: The objective of the study was to investigate the impact of CICARE communication nursing on the improvement of serum interleukin-10 (IL-10), interleukin-6 (IL-6), interleukin-4 (IL-4), and interleukin-2 (IL-2) and lung function in outpatients with acute bronchitis (AB). METHODS: One hundred and twenty suffers with AB who are treated in the outpatient department during Revised to 2021 to March 2023 are chosen and grouped according to the time of admission and different nursing practices. The control group consists of 60 patients from March 2021 to March 2022 who receive routine outpatient care; the experimental group consists of 60 patients from April 2022 to March 2023, and CICARE communication nursing is implemented additionally. Before and after intervention, the cognitive level of self-care knowledge, the level of peripheral blood inflammatory factors, and the improvement of lung function are compared. RESULTS: Before intervention, there were no remarkable differences in self-care knowledge cognition scores, peripheral blood inflammatory factors, and lung function levels between them (P &gt; 0.05). After intervention, the cognitive scores of treatment coordination, medication method, daily attention, diet, and activity in experimental groups are superior to control group (P &lt; 0.05). The levels of IL-10, IL-6, IL-4, and IL-2 in test groups are inferior to control group (P &lt; 0.05). Forced vital capacity, forced expiratory volume in 1 s, maximum air volume, and peak flow rate in test groups are superior to control group (P &lt; 0.05). CONCLUSION: CICARE communication nursing can improve the cognition level of self-care knowledge of patients with AB, reduce the inflammatory response of the body, and promote the recovery of lung function.

The Impact and Mechanism of Action of Peptostreptococcus anaerobius on Chemotherapy Resistance in Human Colorectal Cancer.

Peptostreptococcus anaerobius plays an important role in the development of colorectal cancer, and previous studies by our group have demonstrated that Peptostreptococcus anaerobius promotes resistance to 5-Fu chemotherapy in animal models of colorectal cancer. In this study, the effects of Peptostreptococcus anaerobius on chemotherapy resistance in colorectal cancer and its possible mechanism of action were investigated from the clinical point of view. Patients were selected according to exclusion and inclusion criteria and divided into sensitive and chemotherapy groups (n = 20/group). Fecal samples were collected from the patients. The bacterial 16S rRNA genes in the samples were sequenced and the abundance and varieties in the fecal bacteria were compared between the 2 groups. Immunohistochemistry and Western blotting were used to assess interleukin 23 levels in tumor tissues. Significantly elevated abundance of Peptostreptococcus was observed in fecal samples from chemoresistant colorectal cancer patients compared to those from chemosensitive individuals. Immunohistochemistry and Western blotting results showed that chemoresistant patients had higher levels of interleukin 23 relative to chemosensitive patients and the levels were positively associated with Peptostreptococcus. Peptostreptococcus may mediate the development of chemoresistant colorectal cancer by promoting the upregulation of interleukin 23. Efforts to target Peptostreptococcus thus have the potential to alter the prognosis of colorectal cancer patients.