Expression Of Interleukin Research Articles

NOD2 contributes to Parvimonas micra-induced bone resorption in diabetic rats with experimental periodontitis.

Type 2 diabetes mellitus (T2DM) may affect the oral microbial community, exacerbating periodontal inflammation; however, its pathogenic mechanisms remain unclear. As nucleotide-binding oligomerization domain 2 (NOD2) plays a crucial role in the activation during periodontitis (PD), it is hypothesized that changes in the oral microbial community due to diabetes enhance periodontal inflammation through the activation of NOD2. We collected subgingival plaque from 180 subjects who were categorized into two groups based on the presence or absence of T2DM. The composition of oral microbiota was detected by 16S rRNA high-throughput sequencing. In animal models of PD with or without T2DM, we assessed alveolar bone resorption by micro-computerized tomography and used immunohistochemistry to detect NOD2 expression in alveolar bone. Primary osteoblasts were cultured in osteogenic induction medium with high or normal glucose and treated with inactivated bacteria. After 24h of inactivated bacteria intervention, the osteogenic differentiation ability was detected by alkaline phosphatase (ALP) staining, and the expressions of NOD2 and interleukin-12 (IL-6) were detected by western blot. The relative abundance of Parvimonas and Filifactor in the T2DM group was increased compared to the group without T2DM. In animal models, alveolar bone mass was decreased in PD, particularly in T2DM with PD (DMPD) group, compared to controls. Immunohistochemistry revealed NOD2 in osteoblasts from the alveolar bone in both the PD group and DMPD group, especially in the DMPD group. In vitro, intervention with inactivated Parvimonas significantly reduced ALP secretion of primary osteoblasts in high glucose medium, accompanied by increased expression of NOD2 and IL-6. The results suggest that T2DM leading to PD may be associated with the activation of NOD2 by Parvimonas.

MiR-21-5p modulates LPS-induced acute injury in alveolar epithelial cells by targeting SLC16A10

Sepsis is a systemic inflammatory response syndrome resulting from the invasion of the human body by bacteria and other pathogenic microorganisms. One of its most prevalent complications is acute lung injury, which places a significant medical burden on numerous countries and regions due to its high morbidity and mortality rates. MicroRNA (miRNA) plays a critical role in the body's inflammatory response and immune regulation. Recent studies have focused on miR-21-5p in the context of acute lung injury, but its role appears to vary in different models of this condition. In the LPS-induced acute injury model of A549 cells, there is differential expression, but the specific mechanism remains unclear. Therefore, our aim is to investigate the changes in the expression of miR-21-5p and SLC16A10 in a type II alveolar epithelial cell injury model induced by LPS and explore the therapeutic effects of their targeted regulation. A549 cells were directly stimulated with 10 µg/ml of LPS to construct a model of LPS-induced cell injury. Cells were collected at different time points and the expression of interleukin 1 beta (IL-1β), tumor necrosis factor-α (TNF-α) and miR-21-5p were measured by RT-qPCR and western blot. Then miR-21-5p mimic transfection was used to up-regulate the expression of miR-21-5p in A549 cells and the expression of IL-1β and TNF-α in each group of cells was measured by RT-qPCR and western blot. The miRDB, TargetScan, miRWalk, Starbase, Tarbase and miR Tarbase databases were used to predict the miR-21-5p target genes and simultaneously, the DisGeNet database was used to search the sepsis-related gene groups. The intersection of the two groups was taken as the core gene. Luciferase reporter assay further verified SLC16A10 as the core gene with miR-21-5p. The expression of miR-21-5p and SLC16A10 were regulated by transfection or inhibitors in A549 cells with or without LPS stimulation. And then the expression of IL-1β and TNF-α in A549 cells was tested by RT-qPCR and western blot in different groups, clarifying the role of miR-21-5p-SLC16A10 axis in LPS-induced inflammatory injury in A549 cells. (1) IL-1β and TNF-α mRNA and protein expression significantly increased at 6, 12, and 24 h after LPS stimulation as well as the miR-21-5p expression compared with the control group (P < 0.05). (2) After overexpression of miR-21-5p in A549 cells, the expression of IL-1β and TNF-α was significantly reduced after LPS stimulation, suggesting that miR-21-5p has a protection against LPS-induced injury. (3) The core gene set, comprising 51 target genes of miR-21-5p intersecting with the 1448 sepsis-related genes, was identified. This set includes SLC16A10, TNPO1, STAT3, PIK3R1, and FASLG. Following a literature review, SLC16A10 was selected as the ultimate target gene. Dual luciferase assay results confirmed that SLC16A10 is indeed a target gene of miR-21-5p. (4) Knocking down SLC16A10 expression by siRNA significantly reduced the expression of IL-1β and TNF-α in A549 cells after LPS treatment (P < 0.05). (5) miR-21-5p inhibitor increased the expression levels of IL-1β and TNF-α in A549 cells after LPS stimulation (P < 0.05). In comparison to cells solely transfected with miR-21-5p inhibitor, co-transfection of miR-21-5p inhibitor and si-SLC6A10 significantly reduced the expression of IL-1β and TNF-α (P < 0.05). MiR-21-5p plays a protective role in LPS-induced acute inflammatory injury of A549 cells. By targeting SLC16A10, it effectively mitigates the inflammatory response in A549 cells induced by LPS. Furthermore, SLC16A10 holds promise as a potential target for the treatment of acute lung injury.

Improving the effect of Topical and Systemic administration of Probiotic Lactobacillus casei Shirota on Interleukin-10 Expression in Traumatic Ulcer Healing in Wistar Rats (Rattus norvegicus)

Improving the effect of Topical and Systemic administration of Probiotic Lactobacillus casei Shirota on Interleukin-10 Expression in Traumatic Ulcer Healing in Wistar Rats (Rattus norvegicus)

Value of exhaled hydrogen sulfide in early diagnosis of esophagogastric junction adenocarcinoma.

Esophagogastric junction adenocarcinoma (EJA) has increased in recent years, and it exhibits a poor prognosis and a short survival period for patients. Hydrogen sulfide (H2S) plays an important role in the pathogenesis of cancer and has been studied as a diagnostic factor in some tumor diseases. However, few studies have explored the diagnostic value of H2S for EJA. In the present study, a total of 56 patients with early-stage EJA were enrolled while 57 healthy individuals were selected as the healthy control group. Clinical features were recorded, and exhaled H2S and blood samples were collected from both groups. Exhaled H2S and serum interleukin-8 (IL-8) expression levels were detected in both groups. The correlation between exhaled H2S and serum IL-8 levels was analyzed using Pearson's correlation method. Receiver operating characteristic (ROC) curve was used to evaluate the diagnostic value of exhaled H2S combined with IL-8 detection in EJA. The results showed that patients with EJA exhaled more H2S than healthy individuals. In addition, exhaled H2S was positively correlated with increased IL-8 expression. The ROC curve revealed that the exhaled H2S test had an acceptable diagnostic effect and could be used to diagnose EJA. The increase in H2S exhaled by patients with EJA indicated that H2S may be related to the occurrence and development of EJA; however, the in vivo mechanism needs to be further explored. Collectively, it was determined in the present study that exhaled H2S was significantly higher in patients with early-stage EJA than in healthy controls and combined diagnosis with patient serum IL-8 could improve diagnostic accuracy, which has potential diagnostic value for early diagnosis and screening of EJA.

In vitro and in vivo burn healing study of standardized propolis: Unveiling its antibacterial, antioxidant and anti-inflammatory actions in relation to its phytochemical profiling.

Natural propolis has been used since decades owing to its broad-spectrum activities. Burn injuries are a global health problem with negative impacts on communities. Bacterial infections usually accompany burns, which demand implementation of antibiotics. Antibiotics abuse led to emergence of microbial drug resistance resulting in poor treatment outcomes. In such instances, the promising alternative would be natural antimicrobials such as propolis. Full chemical profiling of propolis and evaluation of in vitro antibacterial, antioxidant and anti-inflammatory activities as well as in vivo burn healing properties. Chemical profiling of propolis was performed using Liquid chromatography (UHPLC/MS-PDA and HPLC-PDA). In vitro assessment was done using Disc Diffusion susceptibility test against Staphylococcus aureus and infected burn wound mice model was used for in vivo assessment. In vitro antioxidant properties of propolis were assessed using DPPH, ABTS and FRAP techniques. The anti-inflammatory effect of propolis was assessed against lipopolysaccharide/interferon-gamma mediated inflammation. UHPLC/MS-PDA results revealed identification of 71 phytochemicals, mainly flavonoids. Upon flavonoids quantification (HPLC-PDA), Pinocembrin, chrysin and galangin recorded high content 21.58±0.84, 22.73±0.68 and 14.26±0.70 mg/g hydroalcoholic propolis extract, respectively. Propolis showed concentration dependent antibacterial activity in vitro and in vivo burn healing via wound diameter reduction and histopathological analysis without signs of skin irritation in rabbits nor sensitization in guinea pigs. Propolis showed promising antioxidant IC50 values 46.52±1.25 and 11.74±0.26 μg/mL whereas FRAP result was 445.29±29.9 μM TE/mg. Anti-inflammatory experiment results showed significant increase of Toll-like receptor 4 (TLR4), interleukin-6 (IL-6) and tumor necrosis factor-alpha (TNF-α) mRNA levels. Nitric oxide and iNOS were markedly increased in Griess assay and western blot respectively. However, upon testing propolis against LPS/IFN-γ-mediated inflammation, TLR4, IL-6 and TNF-α expression were downregulated at transcriptional and post-transcriptional levels. Propolis proved to be a promising natural burn healing agent through its antibacterial, antioxidant and anti-inflammatory activities.

Down regulation of C1q tumor necrosis factor-related protein 6 is associated with increased risk of breast cancer

C1q tumor necrosis factor-related protein 6 (CTRP6), a member of the C1q tumor necrosis factor-related protein (CTRP) family, is reported to be associated with the progression of different malignancies, however, its expression levels and role in breast cancer (BC) are yet unknown. In this study, we investigated the levels of circulating CTRP6 in BC patients and evaluated its role as a potential diagnostic biomarker in BC patients. Then we investigated the effect of recombinant CTRP6 on cellular viability in MCF-7 cells along with its effects on the expression of inflammatory cytokines, interleukin 6 (IL-6), tumor necrosis factor alpha (TNF-α) in addition to the expression of vascular endothelial growth factor (VEGF) as a marker of angiogenesis. Our results showed decreased expression of circulating CTRP6 in BC patients with an inverse correlation between CTRP6 and IL-6, TNF-α and VEGF levels. Besides, Receiver operating characteristic (ROC) curve showed that the assessment of CTRP6 levels could be used to predict BC. Moreover, treatment of MCF-7 cells with recombinant CTRP6 protein reduced cellular viability and decreased IL-6, TNF-α and VEGF expression. In conclusion, these results provide new insights into the role of CTRP6 in BC pathogenesis and suggest its potential use as a novel diagnostic biomarker of BC.

Il-6 and MSH3 in colorectal carcinoma: Expression, relationship, and prognostic significance in 171 colorectal carcinoma cases.

Colorectal cancer (CRC), the most common type of gastrointestinal cancer, mostly develops as a result of environmental factors. Inflammation is a relatively uncommon but crucial contributor to its etiology, and inflammation is also thought to pose a risk in patients without a clinical diagnosis of inflammatory bowel disease. In cell lines, the proinflammatory cytokine interleukin-6 (IL-6) causes a cytosolic shift in the mismatch repair protein MSH3, accompanied by functional loss. This study aimed to evaluate IL-6 and MSH3 expression in 171 sporadic CRC samples by immunohistochemistry (IHC). High levels of IL-6 are hypothesized to cause MSH3 expression loss. We also explored the clinical/pathological aspects of IHC-detected MSH3 loss and the relationship between MSH3 expression and tumor-infiltrating lymphocytes (TILs). IL-6 and MSH3 IHC and H and E slides were evaluated by two pathologists. Clinical data were obtained from the institution's database. A relationship between MSH3 loss and IL-6 expression was not proven (P = 0.963). MSH3 staining was significantly reduced in the patient group with high TILs (P = 0.035). We observed 104 CRC cases (60.8%) with IL-6 expression and 85 cases (49.7%) with reduced MSH3 expression. This study did not demonstrate an association between IL-6 and MSH3 expression. As MSH3 is a relatively little-known protein, further large-scale studies are needed. The use of IHC to identify patients who may benefit from anti-IL-6 therapies in CRC in the future may be critical.

IL-6 significantly correlated with the prognosis in low-grade glioma and the mediating effect of immune microenvironment.

To screen immune-related prognostic biomarkers in low-grade glioma (LGG), and reveal the potential regulatory mechanism. The differential expressed genes (DEGs) between alive and dead patients were initially identified, then the key common genes between DEGs and immune-related genes were obtained. Regarding the key DEGs associated with the overall survival (OS), their clinical value was assessed by Kaplan-Meier, RCS, logistic regression, ROC, and decision curve analysis methods. We also assessed the role of immune infiltration on the association between key DEGs and OS. All the analyses were based on the TGCA-LGG data. Finally, we conducted the molecular docking analysis to explore the targeting binding of key DEGs with the therapeutic agents in LGG. Among 146 DEGs, only interleukin-6 (IL-6) was finally screened as an immune-related biomarker. High expression of IL-6 significantly correlated with poor OS time (all P < .05), showing a linear relationship. The combination of IL-6 with IDH1 mutation had the most favorable prediction performance on survival status and they achieved a good clinical net benefit. Next, we found a significant relationship between IL-6 and immune microenvironment score, and the immune microenvironment played a mediating effect on the association of IL-6 with survival (all P < .05). Detailly, IL-6 was positively related to M1 macrophage infiltration abundance and its biomarkers (all P < .05). Finally, we obtained 4 therapeutic agents in LGG targeting IL-6, and their targeting binding relationships were all verified. IL6, as an immune-related biomarker, was associated with the prognosis in LGG, and it can be a therapeutic target in LGG.

Characteristics of Citrate-Esterified Starch and Enzymatically Debranched Starch and Their Effects on Diabetic Mice.

Chickpea has significant benefits as an adjuvant treatment for type 2 diabetes mellitus (T2DM). The properties of chickpea resistant starches (RSs) and their abilities to reduce T2DM symptoms and control intestinal flora were investigated. The RS content in citrate-esterified starch (CCS; 74.18%) was greater than that in pullulanase-modified starch (enzymatically debranched starch (EDS); 38.87%). Compared with those of native chickpea starch, there were noticeable changes in the granular structure and morphology of the two modified starches. The CCS showed surface cracking and aggregation. The EDS particles exhibited irregular layered structures. The expansion force of the modified starches decreased. The CCS and EDS could successfully lower blood glucose, regulate lipid metabolism, lower the levels of total cholesterol (TC) and low-density lipoprotein cholesterol (LDL-C), reduce the expressions of interleukin-6 (IL-6) and interleuki n-10 (IL-10), and decrease diabetes-related liver damage. Moreover, the CCS and EDS altered the intestinal flora makeup in mice with T2DM. The abundance of Bacteroidota increased. Both types of chickpea RSs exhibited significant hypoglycaemic and hypolipidaemic effects, contributing to the reduction in inflammatory levels and the improvement in gut microbiota balance.

Differential responses to heat stress in normal and dwarf chickens: implications for meat quality and immune function

Abstract This study investigated the impact of heat stress (HS) on meat quality, antioxidant ability, and immunity in normal and dwarf-size chickens. A total of 144 chickens, with 72 from the normal yellow chicken (NYC) strain and 72 from the dwarf yellow chicken (DYC) strain, were equally divided into groups exposed to heat stress (35±1°C for 8 hours daily) and those kept at 28±1°C as the control group. After seven days of treatment, meat color parameters, including lightness (L*-value), redness (a*-value), and yellowness (b*-value), were assessed. Histopathological examination was conducted on spleen tissues to assess structural changes. Gene expression analysis determined the expression levels of interleukin-4 (IL-4), IL-6, and liver catalase (CAT) related to immune response and antioxidant capacity. HS significantly affected meat color parameters, with an increase in lightness (L*-value) (P&lt;0.01) and a decrease in redness (a*-value) (P&lt;0.01) observed in breast and thigh muscles. Furthermore, HS led to increased drip loss (P&lt;0.05), cooking loss (P&lt;0.05), and shear force (P&lt;0.01) in breast muscles. Histopathological examination of spleen tissues revealed varying degrees of lymphoid depletion, necrosis, fibrosis, and inflammatory cell infiltration in response to HS. Gene expression analysis showed that HS upregulated the expression of interleukin-4 (IL-4) and IL-6 in the spleen of NYC (P&lt;0.05) but not in DYC. Additionally, HS reduced the expression of liver catalase (CAT) in NYC (P&lt;0.05) but had no significant effect on DYC. These findings indicate that HS adversely affects meat quality, immune response, and antioxidant capacity in broilers, with normal-sized chickens being more susceptible to these effects compared to dwarf chickens. The results provide valuable insights into the differential responses of chicken strains to HS and underscore the importance of considering genetic factors in mitigating the negative impacts of heat stress on poultry production.

Newly Isolated Limosilactobacillus reuteri B1/1 Modulates the Expression of Cytokines and Antimicrobial Proteins in a Porcine ex Vivo Model.

The epithelia of the intestine perform various functions, playing a crucial role in providing a physical barrier and an innate immune defense against infections. By generating a "three-dimensional" (3D) model of cell co-cultures using the IPEC-J2 cell line and porcine blood monocyte-derived macrophages (MDMs), we are getting closer to mimicking the porcine intestine ex vivo.Methods: The effect of Limosilactobacillus reuteri B1/1 and Limosilactobacillus fermentum CCM 7158 (indicator strain) on the relative gene expression of interleukins (IL-1β, IL-6, IL-8, IL-18 and IL-10), genes encoding receptors for TLR4 and TLR2, tight junction proteins such as claudin-1 (CLDN1), occludin (OCLN) and important antimicrobial proteins such as lumican (LUM) and olfactomedin-4 (OLMF-4) was monitored in this model. The results obtained from this pilot study point to the immunomodulatory potential of newly isolated L. reuteri B1/1, as it was able to suppress the enhanced pro-inflammatory response to lipopolysaccharide (LPS) challenge in both cell types. L. reuteri B1/1 was even able to up-regulate the mRNA levels of genes encoding antimicrobial proteins LUM and OLFM-4 and to increase tight junction (TJ)-related genes CLDN1 and OCLN, which were significantly down-regulated in LPS-induced IPEC-J2 cells. Conversely, L. fermentum CCM 7158, chosen as an indicator lactic acid bacteria (LAB) strain, increased the mRNA levels of the investigated pro-inflammatory cytokines (IL-18, IL-6, and IL-1β) in MDMs when LPS was simultaneously applied to basally deposited macrophages. Although L. fermentum CCM 7158 induced the production of pro-inflammatory cytokines, synchronous up-regulation of the anti-inflammatory cytokine IL-10 was detected in both LAB strains used in both cell cultures. The obtained results suggest that the recently isolated LAB strain L. reuteri B1/1 has the potential to alleviate epithelial disruption caused by LPS and to influence the production of antimicrobial molecules by enterocytes.

NF-κB pathway as a molecular target for curcumin in diabetes mellitus treatment: Focusing on oxidative stress and inflammation.

Diabetes mellitus (DM) is a collection of metabolic disorder that is characterized by chronic hyperglycemia. Recent studies have demonstrated the crucial involvement of oxidative stress (OS) and inflammatory reactions in the development of DM. Curcumin (CUR), a natural compound derived from turmeric, exerts beneficial effects on diabetes mellitus through its interaction with the nuclear factor kappa B (NF-κB) pathway. Research indicates that CUR targets inflammatory mediators in diabetes, including tumor necrosis factor α (TNF-α) and interleukin-6 (IL-6), by modulating the NF-κB signaling pathway. By reducing the expression of these inflammatory factors, CUR demonstrates protective effects in DM by improving pancreatic β-cells function, normalizing inflammatory cytokines, reducing OS and enhancing insulin sensitivity. The findings reveal that CUR administration effectively lowered blood glucose elevation, reinstated diminished serum insulin levels, and enhanced body weight in Streptozotocin -induced diabetic rats. CUR exerts its beneficial effects in management of diabetic complications through regulation of signaling pathways, such as calcium-calmodulin (CaM)-dependent protein kinase II (CaMKII), peroxisome proliferator-activated receptor gamma (PPAR-γ), NF-κB, and transforming growth factor β1 (TGFB1). Moreover, CUR reversed the heightened expression of inflammatory cytokines (TNF-α, Interleukin-1 beta (IL-1β), IL-6) and chemokines like MCP-1 in diabetic specimens, vindicating its anti-inflammatory potency in counteracting hyperglycemia-induced alterations. CUR diminishes OS, avert structural kidney damage linked to diabetic nephropathy, and suppress NF-κB activity. Furthermore, CUR exhibited a protective effect against diabetic cardiomyopathy, lung injury, and diabetic gastroparesis. Conclusively, the study posits that CUR could potentially offer therapeutic benefits in relieving diabetic complications through its influence on the NF-κB pathway.

Blocking the MIR155HG/miR-155 axis reduces CTGF-induced inflammatory cytokine production and α-SMA expression via upregulating AZGP1 in hypertrophic scar fibroblasts

Hypertrophic scarring (HS) is a pathological condition characterized by excessive fibrosis and inflammation, resulting in excessive extracellular matrix formation in the skin. MIR155HG, a long non-coding RNA, is abnormally upregulated in fibrotic tissues; however, its underlying mechanism is poorly understood. Using single-cell sequencing data, we analyzed connective tissue growth factor (CTGF) expression in various cell types in HS and normal skin tissues and MIR155HG expression in clinical samples. To investigate the mechanism of fibrosis, an in vitro model using CTGF-treated hypertrophic scar fibroblasts (HSFBs) was established and qRT-PCR, western blotting and ELISA assays were performed to investigate the expression of interleukin (IL)-1β, IL-6, and mesenchymal markers α-smooth muscle actin (α-SMA). CTGF stimulates MIR155HG level through phosphorylated STAT3 binding to the MIR155HG promoter. We analyzed the methylation of MIR155HG, assessed the levels of miR-155-5p/−3p in CTGF-treated HSFBs and identified differentially expressed genes among HS and NS samples using the Gene Expression Omnibus RNA sequencing data. The binding between miR-155-5p/−3p and AZGP1 was confirmed using a dual-luciferase assay and inflammatory cytokine production and α-SMA expression were investigated in rescue experiments. The findings revealed that CTGF elevated inflammatory cytokine production, α-SMA and MIR155HG expression in HSFBs. MIR155HG is upregulated in HS tissues due to low DNA methylation. Mechanistically, miR-155-5p/−3p was directly bound to MIR155HG 3’UTR. MIR155HG silencing inhibited cytokine production and α-SMA expression by repressing the generation of miR-155-5p/−3p in CTGF-treated HSFBs. Bioinformatics analysis and luciferase reporter assays revealed that miR-155-5p/−3p targets AZGP1. In addition, transfection with plasmids carrying AZGP1 cDNA significantly inhibited the signaling activity of miR-155-5p/−3 p-overexpressing HSFBs. Our findings highlight the importance of the MIR155HG/miR-155/AZGP1 axis in regulating cytokine production and α-SMA in HS.

Chlorella vulgaris algae ameliorates chlorpyrifos toxicity in Nile tilapia with special reference to antioxidant enzymes and Streptococcus agalactiae infection

BackgroundChlorpyrifos (CPF) is a widely used pesticide in the production of plant crops. Despite rapid CPF biodegradation, fish were exposed to wastewater containing detectable residues. Recently, medicinal plants and algae were intensively used in aquaculture to replace antibiotics and ameliorate stress impacts.Methods and resultsAn indoor experiment was conducted to evaluate the deleterious impacts of CPF pollution on Nile tilapia health and the potential mitigation role of Chlorella vulgaris algae. Firstly, the median lethal concentration LC50 − 72 h of CPF was determined to be 85.8 µg /L in Nile tilapia (35.6 ± 0.5 g body weight) at a water temperature of 27.5 °C. Secondly, fish were exposed to 10% of LC50 − 72 h for six weeks, and tissue samples were collected and examined every two weeks. Also, Nile tilapia were experimentally infected with Streptococcus agalactiae. Exposed fish were immunosuppressed expressed with a decrease in gene expressions of interleukin (IL) 1β, IL-10, and tumor necrosis factor (TNF)-α. Also, a decline was recorded in glutathione peroxidase (GPx), superoxide dismutase (SOD), and catalase (CAT) gene expression in the head kidney tissue. A high mortality rate (MR) of 100% was recorded in fish exposed to CPF for six weeks and challenged with S. agalactiae. Fish that received dietary C. vulgaris could restore gene expression cytokines and antioxidants compared to the control. After six weeks of CPF exposure, fish suffered from anemia as red blood cell count (RBCs), hemoglobin (Hb), and packed cell volume (PCV) significantly declined along with downregulation of serum total protein (TP), globulin (GLO), and albumin (ALB). Liver enzymes were significantly upregulated in fish exposed to CPF pollution, alanine aminotransferase (ALT) (42.5, 53.3, and 61.7 IU/L) and aspartate aminotransferase (AST) (30.1, 31.2, and 22.8) after 2, 4, and 6 weeks, respectively. On S. agalactiae challenge, high MR was recorded in Nile tilapia exposed to CPF (G3) 60%, 60%, and 100% in week 2, week 4, and week 6, and C. vulgaris provided a relative protection level (RPL) of 0, 14.29, and 20%, respectively.ConclusionsIt was concluded that CPF pollution induces immunosuppressed status, oxidative stress, and anemic signs in Nile tilapia. In contrast, C. vulgaris at a 50 g/kg fish feed dose could partially ameliorate such withdrawals, restoring normal physiological parameters.

Genetic Polymorphism of Interleukin-6 in Asymptomatic and ICU-Admitted COVID-19 Patients in Sulaymaniyah Province, Kurdistan Region of Iraq.

Background: The global pandemic of Coronavirus Disease 2019 (COVID-19) has resulted in significant fatality rates. Clinical outcomes for affected individuals range from being asymptomatic to severe illnesses requiring intensive care unit (ICU) admission. Among the various factors contributing to the variation in clinical outcomes, host genetics play a prominent role. Interleukin-6 (IL6), a key player in immune responses, has been identified as having a crucial impact on viral infections, including the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2). Specifically, certain variations known as single nucleotide polymorphisms (SNPs) in the IL6 promoter region have been found to significantly influence IL6 expression and the severity of viral infections. Materials and Methods: To explore the relationship between these genetic variations and COVID-19 in asymptomatic and ICU-admitted Kurdish patients, genetic sequencing was performed to determine the genotypes of nine IL6 SNPs. Results: The study findings revealed that although the proportion of the GG genotype of rs1800795 was slightly higher in asymptomatic COVID-19 cases, the difference was not statistically significant (chi2 = 2.666, p = 0.236). Notably, Kurdish patients displayed a uniform genetic makeup (monomorphic) for the dominant alleles of rs2069830 (C), rs142759801 (C), rs2069857 (C), rs2069829 (G), rs2234683 (G), rs13447446 (T), rs527770772 (C), and rs13447445 (C). Furthermore, patients carrying the haplotype GCGGCTCCC were found to have a 0.481-fold higher likelihood of being asymptomatic with COVID-19 (p = 0.016, OR = 0.481). Conclusions: This study demonstrates that the rs1800795 SNP is not statistically associated with COVID-19 at the genotype level. However, the presence of the dominant G allele of rs1800795 in the haplotype was found to be statistically associated with asymptomatic COVID-19 patients.

Dual N-linked glycosylation at residues 133 and 158 in the hemagglutinin are essential for the efficacy of H7N9 avian influenza virus like particle vaccine in chickens and mice

H7N9 subtype avian influenza virus (AIV) poses a great challenge to poultry industry. Virus-like particle (VLP) is a prospective alternative for the traditional egg-based influenza vaccines. N-linked glycosylation (NLG) regulates the efficacy of influenza vaccines, whereas the impact of NLG modifications on the efficacy of influenza VLP vaccines remains unclear. Here, H7N9 VLPs were assembled in insect cells through co-infection with the baculoviruses expressing the NLG-modified hemagglutinin (HA), neuraminidase and matrix proteins, and the VLP vaccines were assessed in chickens and mice. NLG modifications significantly enhanced hemagglutination-inhibition and virus neutralization antibody responses in mice, rather than in chickens, because different immunization strategies were used in these animal models. The presence of dual NLG at residues 133 and 158 significantly elevated HA-binding IgG titers in chickens and mice. The VLP vaccines conferred complete protection and significantly suppressed virus replication and lung pathology post challenge with H7N9 viruses in chickens and mice. VLP immunization activated T cell immunity-related cytokine response and inhibited inflammatory cytokine response in mouse lung. Of note, the presence of dual NLG at residues 133 and 158 optimized the capacity of the VLP vaccine to stimulate interleukin-4 expression, inhibit virus shedding or alleviate lung pathology in chickens or mice. Intriguingly, the VLP vaccine with NLG addition at residue 133 provided partial cross-protection against the H5Nx subtype AIVs in chickens and mice. In conclusion, dual NLG at residues 133 and 158 in HA can be potentially used to enhance the efficacy of H7N9 VLP vaccines in chickens and mammals.

The improvement of inflammatory infiltration and pregnancy outcome in mice with recurrent spontaneous abortion by human amniotic mesenchymal stem cells.

Recurrent spontaneous abortion is thought to be mostly triggered by immune-related causes. Mesenchymal stem cells, which exhibit the traits of multi-directional differentiation capacity and low immunogenicity, have recently been recommended as a viable treatment for spontaneous abortion-prone mice to increase the success of pregnancy. Amniotic membrane tissue is a byproduct of pregnancy and delivery that has a wide range of potential uses due to its easy access to raw materials and little ethical constraints. To construct an abortion-prone mouse model for this investigation, CBA/J female mice were coupled with male DBA/2 mice, while CBA/J female mice were paired with male BALB/c mice as a control. The identical volume of human amniotic mesenchymal stem cells or phosphate buffer was injected intraperitoneally on the 4.5th day of pregnancy. CBA/J female mice were sacrificed by cervical dislocation on the 13.5th day of pregnancy, the embryo absorption rate was calculated, and the uterus, decidua tissues and placenta were gathered for examination. Through detection, it was discovered that human amniotic mesenchymal stem cells significantly increased the expression of interleukin 10 and transforming growth factor beta, while they significantly decreased the expression of interleukin 1 beta and interleukin 6, improved vascular formation and angiogenesis, and minimized the embryo absorption rate and inflammatory cell infiltration in the recurrent spontaneous abortion + human amniotic mesenchymal stem cells group. In any case, human amniotic mesenchymal stem cells regulate inflammatory factors and cell balance at the maternal-fetal interface, which result in a reduction in the rate of embryo absorption and inflammatory infiltration and provide an innovative perspective to the clinical therapy of recurrent spontaneous abortion.

Effects of Dietary Callicarpa nudiflora Aqueous Extract Supplementation on Growth Performance, Growth Hormone, Antioxidant and Immune Function, and Intestinal Health of Broilers.

C. nudiflora is notably rich in flavonoids and phenylethanoid glycosides, making it a significant natural source of antioxidants. We examined the effects of C. nudiflora aqueous extract (CNE) on growth performance, antioxidant function, immunity, intestinal barrier function, nutrient transporters, and microbiota of broilers. A total of 360 one-day-old broilers were randomly assigned to four treatment groups: a basal diet with 0 (control, CON), 300 mg/kg (CNEL), 500 mg/kg (CNEM), and 700 mg/kg (CNEH) CNE for 42 days. CNEL and CNEM groups quadratically increased body weight and average daily gain but decreased feed-to-gain ratios during the starter and whole phases. Regarding the immune response of broilers, CNE treatment linearly down-regulated jejunal myeloid differentiation factor 88 (MyD88) expression and interleukin-1β (IL-1β) and interferon-γ expression in the liver (d 21), while decreasing jejunal IL-1β expression and the concentration of serum tumor necrosis factor-α and interleukin-6 (d 42). The CNEM and CNEH groups had lower MyD88 and nuclear factor kappa B expression in the liver (d 21) compared to the CON group. Broilers in the CNEL and CNEM groups had higher spleen index and thymus index (d 21) and interleukin-10 expression from the liver and jejunal mucosa (d 42) than that in the CON group. For the antioxidant capacity of broilers, CNE treatment linearly decreased the content of malonaldehyde and increased the activity of total antioxidant capacity in serum (d 42). CNEM and CNEH groups linearly increased the activity of superoxide dismutase in serum and heme oxygenase-1 expression in the liver, while increasing the activity of glutathione peroxidase in serum, jejunal nuclear factor E2-related factor 2 expression, and NAD(P)H quinone oxidoreductase 1 expression in the liver (d 42). As for the growth hormone of broilers, CNEM group increased the level of serum insulin-like growth factor 1 and up-regulated jejunal glucagon-like peptide 2 (GLP-2) expression (d 21). Broilers in the CNEM and CNEH groups had higher jejunal GLP-2 expression and growth hormone (GH) expression in the liver and the level of serum GH (d 42) than that in the CON group. Additionally, the villus height and jejunal Occludin and Claudin-1 expression in the CNEM group increased. CNE-containing diets resulted in a linear increase in the expression of jejunal zonula occluden-1 (d 21), villus height to crypt depth ratio, jejunal Occludin, excitatory amino acid transporters-3, and peptide-transporter 1 (d 42). The regulation of Oscillospira, Ruminococcaceae_Ruminococcus, and Butyricicoccus genera indicated that CNEH altered the composition of the cecal microbiota. In general, supplementing broilers with C. nudiflora aqueous extract could boost hormones, immune and antioxidant function, and gut health, improving their growth performance. Hence, CNE was a promising poultry feed additive, with 500 mg/kg appearing to be the optimal dose.

Primary cilia abnormalities participate in the occurrence of spontaneous abortion through TGF-β/SMAD2/3 signaling pathway.

Spontaneous abortion is the most common complication in early pregnancy, the exact etiology of most cases cannot be determined. Emerging studies suggest that mutations in ciliary genes may be associated with progression of pregnancy loss. However, the involvement of primary cilia on spontaneous abortion and the underlying molecular mechanisms remains poorly understood. We observed the number and length of primary cilia were significantly decreased in decidua of spontaneous abortion in human and lipopolysaccharide (LPS)-induced abortion mice model, accompanied with increased expression of proinflammatory cytokines interleukin (IL)-1β, IL-6, and tumor necrosis factor (TNF)-α. The length of primary cilia in human endometrial stromal cell (hESC) was significantly shortened after TNF-α treatment. Knocking down intraflagellar transport 88 (IFT88), involved in cilia formation and maintenance, promoted the expression of TNF-α. There was a reverse regulatory relationship between cilia shortening and TNF-α expression. Further research found that shortened cilia impair decidualization in hESC through transforming growth factor (TGF)-β/SMAD2/3 signaling. Primary cilia were impaired in decidua tissue of spontaneous abortion, which might be mainly caused by inflammatory injury. Primary cilia abnormalities resulted in dysregulation of TGF-β/SMAD2/3 signaling transduction and decidualization impairment, which led to spontaneous abortion.

Protective effects of paeonol against cognitive impairment in lung diseases

Pulmonary inflammation may lead to neuroinflammation resulting in neurological dysfunction, and it is associated with a variety of acute and chronic lung diseases. Paeonol is a herbal phenolic compound with anti-inflammatory and anti-oxidative properties. The aim of this study is to understand the beneficial effects of paeonol on cognitive impairment, pulmonary inflammation and its underlying mechanisms. Pulmonary inflammation-associated cognitive deficit was observed in TNFα-stimulated mice, and paeonol mitigated the cognitive impairment by reducing the expressions of interleukin (IL)-1β, IL-6, and NOD-like receptor family pyrin domain-containing 3 (NLRP3) in hippocampus. Moreover, elevated plasma miR-34c-5p in lung-inflamed mice was also reduced by paeonol. Pulmonary inflammation induced by intratracheal instillation of TNFα in mice resulted in immune cells infiltration in bronchoalveolar lavage fluid, pulmonary edema, and acute fibrosis, and these inflammatory responses were alleviated by paeonol orally. In MH-S alveolar macrophages, tumor necrosis factor (TNF) α- and phorbol myristate acetate (PMA)-induced inflammasome activation was ameliorated by paeonol. In addition, the expressions of antioxidants were elevated by paeonol, and reactive oxygen species production was reduced. In this study, paeonol demonstrates protective effects against cognitive deficits and pulmonary inflammation by exerting anti-inflammatory and anti-oxidative properties, suggesting a powerful benefit as a potential therapeutic agent.