Impact of nutritional support on immunity, nutrition, inflammation, and outcomes in elderly gastric cancer patients after surgery.

BACKGROUND: Postoperative rehabilitation of elderly patients with gastric cancer has always been the focus of clinical attention. Whether the intervention by a full-course nutritional support team can have a positive impact on the postoperative immune function, nutritional status, inflammatory response, and clinical outcomes of this special population has not yet been fully verified. AIM: To evaluate the impact of full-course nutritional support on postoperative comprehensive symptoms in elderly patients with gastric cancer. METHODS: This is a retrospective study, including 60 elderly gastric cancer patients aged 70 years and above, divided into a nutritional support group and a control group. The nutritional support group received full postoperative nutritional support, including individualized meal formulation, and intravenous and parenteral nutrition supplementation, and was regularly evaluated and adjusted by a professional nutrition team. The control group received routine postoperative care. RESULTS: After intervention, the proportion of CD4+ lymphocytes (25.3% ± 3.1% vs 21.8% ± 2.9%, P < 0.05) and the level of immunoglobulin G (12.5 G/L ± 2.3 G/L vs 10.2 G/L ± 1.8 G/L, P < 0.01) were significantly higher in the nutritional support group than in the control group; the changes in body weight (-0.5 kg ± 0.8 kg vs -1.8 kg ± 0.9 kg, P < 0.05) and body mass index (-0.2 ± 0.3 vs -0.7 ± 0.4, P < 0.05) were less significant in the nutritional support group than in the control group; and the level of C-reactive protein (1.2 mg/L ± 0.4 mg/L vs 2.5 mg/L ± 0.6 mg/L, P < 0.01) and WBC count (7.2 × 109/L ± 1.5 × 109/L vs 9.8 × 109/L ± 2.0 × 109/L, P < 0.01) were significantly lower in the nutritional support group than in the control group. In addition, patients in the nutritional support group had a shorter hospital stay (10.3 d ± 2.1 d vs 14.8 d ± 3.6 d, P < 0.05) and lower incidence of infection (15% vs 35%, P < 0.05) in those of the control group. CONCLUSION: The intervention by the nutritional support team has a positive impact on postoperative immune function, nutritional status, inflammatory response, and clinical outcomes in elderly patients with gastric cancer.

IGJ depletion suppresses proliferation, inflammation, and motility of rheumatoid arthritis fibroblast-like synoviocytes via targeting NF-κB pathway.

OBJECTIVE: To investigate the impact of IGJ on the proliferation, inflammation, and motility of rheumatoid arthritis (RA) fibroblast-like synoviocytes and elucidate the underlying mechanism. METHODS: The expression of IGJ RA fibroblast-like synoviocytes was assessed using immunoblot and qPCR. Cell growth was evaluated using CCK-8 and FCM assays. The effects on inflammatory response were determined by ELISA and immunoblot assays. Cell motility was assessed using transwell and immunoblot assays. The mechanism was further confirmed using immunoblot assays. RESULTS: IGJ expression was found to be elevated in fibroid synovial cells of RA. IGJ ablation inhibited the growth of MH7A cells and suppressed the inflammatory response. Knockdown of IGJ also blocked cell motility. Mechanically, the knockdown of IGJ suppressed the NF-κB axis in MH7A cells. CONCLUSION: IGJ suppresses RA in fibroblast-like synoviocytes via NF-κB pathway.

Etoposide Therapy of Cytokine Storm Syndromes.

Etoposide has revolutionized the treatment of primary as well as secondary hemophagocytic lymphohistiocytosis (HLH), and it is, together with corticosteroids, the most widely used therapy for HLH. In the early 1980s, long-term survival in primary HLH was <5% but with the etoposide-/dexamethasone-based protocols HLH-94 and HLH-2004, in combination with stem cell transplantation, 5-year survival increased dramatically to around 60% in primary HLH, and based on analyses from the HLH-2004 study, there is likely room for further improvement. Biologically, etoposide administration results in potent selective deletion of activated T cells as well as efficient suppression of inflammatory cytokine production. Moreover, etoposide has also been reported to promote programmed cell death (apoptosis) rather than proinflammatory lytic cell death (pyroptosis), conceivably ameliorating subsequent systemic inflammation, i.e., a treatment very suitable for cytokine storm syndromes (CSS). The combination of etoposide and corticosteroids may also be beneficial in cases of severe or refractory secondary HLH (sHLH) with imminent organ failure, such as infection-associated HLH caused by Epstein-Barr virus (EBV) or malignancy-triggered HLH. In CSS associated with rheumatic diseases (macrophage activation syndrome, MAS or MAS-HLH), etoposide is currently used as second- or third-line therapy. Recent studies suggest that etoposide perhaps should be part of an aggressive therapeutic intervention for patients with severe refractory or relapsing MAS, in particular if there is CNS involvement. Importantly, awareness of sHLH must be further increased since treatment of sHLH is often delayed, thereby missing the window of opportunity for a timely, effective, and potentially life-saving HLH-directed treatment.

Systemic Inflammatory Response Index and the Short-Term Functional Outcome of Patients with Acute Ischemic Stroke: A Meta-analysis.

INTRODUCTION: The systemic inflammatory response index (SIRI) is a novel indicator of systemic inflammation derived from the absolute counts of neutrophils, monocytes, and lymphocytes. The aim of this meta-analysis was to evaluate the association between SIRI and functional outcome in patients with acute ischemic stroke (AIS). METHODS: The Preferred Reporting Items for Systematic Reviews and Meta-Analyses guidelines were followed in this meta-analysis. Relevant cohort studies were retrieved by a search of electronic databases including PubMed, Web of Science, Embase, Wanfang, and China National Knowledge Infrastructure from database inception to February 9, 2024. A poor functional outcome was defined as a modified Rankin Scale ≥ 3 within 3 months after disease onset. A random-effects model was used to combine the data by incorporating the influence of between-study heterogeneity. The protocol of the meta-analysis was not prospectively registered in PROSPERO. RESULTS: Fourteen cohort studies were included. Pooled results showed that a high SIRI at admission was associated with increased risk of poor functional outcome within 3 months (odds ratio [OR]: 1.57, 95% confidence interval: 1.39 to 1.78, p < 0.001; I2 = 0%). Results of the meta-regression analysis suggested that the cutoff for defining a high SIRI was positively related to the OR for the association between SIRI and the risk of poor functional outcome (coefficient = 0.13, p = 0.03), while other variables including sample size, mean age, severity of stroke at admission, percentage of men, current smokers, or patients with diabetes did not significantly modify the results. Subgroup analyses according to study design, main treatments, and study quality scores showed similar results. CONCLUSION: A high SIRI may be associated with a poor functional outcome in patients after AIS.

Elevated cerebrospinal fluid IgG index in herpes simplex encephalitis post-HSV-1 clearance: A preliminary study.

Herpes simplex encephalitis (HSE) is an acute form of encephalitis that can lead to poor neurological outcomes. Although the exact pathogenesis of HSE remains elusive, recent reports suggest a significant role for postinfectious immune-inflammatory processes in the central nervous system (CNS). This study aimed to clarify the association between CNS autoimmune responses and clinical presentation in patients with HSE, focusing on cerebrospinal fluid (CSF) characteristics, particularly the IgG index. We retrospectively analyzed 176 consecutive patients suspected of having aseptic meningitis /encephalitis for chronological changes in CSF findings and clinical presentations. These patients underwent PCR screening for herpesviruses (HV) in their CSF. We identified seven patients positive for herpes simplex virus type 1 (HSV-1), 20 patients positive for varicella-zoster virus, and 17 patients who met the criteria for aseptic meningitis but were PCR-negative for HV. Patients in the HSV-1-positive group exhibited a significant increase in the IgG index at the time of PCR-negative conversion compared with on admission (p = 0.0156), while such a change was not observed in the other two groups. Additionally, all patients in the HSV-1-positive group tested negative for anti-neural autoantibodies in CSF and serum samples collected approximately 3 weeks after onset. This study, therefore, highlights that CSF IgG index elevation occurs even after PCR-confirmed HSV-1 clearance, which might indicate immunopathogenesis that is independent of antibody-mediated mechanisms.

Flusilazole induced developmental toxicity, neurotoxicity, and cardiovascular toxicity via apoptosis and oxidative stress in zebrafish.

Flusilazole is a well-known triazole fungicide applied to various crops and fruits worldwide. Flusilazole residues are frequently detected in the environment, and many researchers have reported the hazardous effects of flusilazole on non-target organisms; however, the developmental toxicity of flusilazole has not been fully elucidated. In this study, we investigated flusilazole-induced developmental defects in zebrafish, which are used in toxicology studies to assess the toxic effects of chemicals on aquatic species or vertebrates. We confirmed that flusilazole exposure affected the viability and hatching rate of zebrafish larvae, and resulted in morphological defects, reduced body length, diminished eye and head sizes, and inflated pericardial edema. Apoptosis, oxidative stress, and inflammation were also observed. These factors interrupted the normal organ formation during early developmental stages, and transgenic models were used to identify organ defects. We confirmed the effects of flusilazole on the nervous system using olig2:dsRed transgenic zebrafish, and on the cardiovascular system using cmlc2:dsRed and fli1:eGFP transgenic zebrafish. Our results demonstrate the developmental toxicity of flusilazole and its mechanisms in zebrafish as well as the detrimental effects of flusilazole.

The macrophage polarization in Entamoeba histolytica infection modulation by the C fragment of the intermediate subunit of Gal/GalNAc-inhibitable lectin.

The protozoan parasite Entamoeba histolytica is the causative agent of amebiasis, with clinical outcomes ranging from asymptomatic infections to severe invasive diseases. The innate immune system, particularly macrophages, is of paramount importance in resisting the invasion of host tissues and organs by the trophozoites of E. histolytica. Parasite-derived pathogenic factors, such as lectins, play a pivotal role in the promotion of macrophage polarization phenotypes that have undergone alteration. Nevertheless, the precise mechanisms by which E. histolytica modulates immune polarization remain largely unknown. The current study focused on the immunomodulatory effects of the Igl-C fragment of E. histolytica Gal/GalNAc lectin on macrophage polarization. These results demonstrated that Igl-C could induce the secretion of IL-1ß, IL-6, and other cytokines, activating a mixed M1/M2 polarization state. M1 polarization of macrophages occurs in the early stages and gradually transitions to M2 polarization in the later stages, which may contribute to the persistence of the infection. Igl-C induces the macrophage M1 phenotype and causes the release of immune effector molecules, including iNOS and cytokines, by activating the NF-κB p65 and JAK-STAT1 transcription factor signaling pathways. Furthermore, Igl-C supports the macrophage M2 phenotype via JAK-STAT3 and IL-4-STAT6 pathways, which activate arginase expression in later stages, contributing to the tissue regeneration and persistence of the parasite. The involvement of distinct signaling pathways in mediating this response highlights the complex interplay between the parasite and the host immune system. These findings enhance our understanding of the Igl-C-mediated pathogenic mechanisms during E. histolytica infection.

Prognostic value of nutrition and immune­related biomarkers in patients with locally advanced rectal cancer treated with chemoradiotherapy.

The ability of nutrition and immune-related biomarkers to predict outcomes in patients with locally advanced rectal cancer (LARC) treated with neoadjuvant therapy followed by surgery remains controversial due to the lack of evidence regarding the accuracy and reliability of these biomarkers in predicting outcomes for such patients. Therefore, the present study aimed to investigate the prognostic potential of nutrition and immune-related biomarkers in patients with LARC who underwent chemoradiotherapy followed by curative surgery. The clinical data of patients with LARC treated with neoadjuvant therapy followed by surgery between January 2010 and December 2019 were analyzed. In total, 214 consecutive patients were enrolled into the present study, who were then categorized into low and high prognostic nutritional index (PNI) groups. The X-tile 3.6.1 program was used to calculate and then determine the optimal cut-off values for PNI. Disease-free survival (DFS) and overall survival (OS) were compared between the low and high PNI groups. Cox regression analysis demonstrated that low PNI and high post-chemoradiotherapy carcinoembryonic antigen levels were significantly associated with reduced disease-free survival and overall survival. Specifically, a low PNI was associated with inferior 5-year DFS (P=0.025) and OS (P=0.018). These findings suggest that amongst the nutritional and immune-related biomarkers, PNI is a significant predictive factor for disease recurrence and mortality in patients with LARC treated with neoadjuvant therapy followed by surgery.

Association of systemic inflammatory response index and clinical outcome in acute traumatic spinal cord injury patients.

Systemic inflammatory response index (SIRI) has been proven to be associated with the prognosis of coronary artery disease and many other diseases. However, the relationship between SIRI and acute traumatic spinal cord injury (tSCI) has rarely been evaluated. The study aims to assess the prognostic value of SIRI for clinical outcomes in individuals with acute tSCI. A total of 190 patients admitted within eight hours after tSCI between January 2021 and April 2023 were enrolled in our study. Logistic regression analysis was used to analyze the association between SIRI and American Spinal Injury Association Impairment Scale (AIS) grade at admission and discharge, as well as neurological improvement in tSCI patients, and receiver operating characteristic (ROC) analysis was performed to assess the discriminative ability of SIRI in predicting AIS grade at discharge. After adjusting for confounding factors, SIRI positively correlated with the AIS grade (A to C) at admission and discharge, and negatively correlated with neurological improvement. The area under the curve values in ROC analysis was 0.725 (95% CI 0.647, 0.803). The study suggests that SIRI is significantly associated with an increased risk of poor clinical outcome at discharge in tSCI patients and has a certain discriminative value.

Synergistic berberine chloride and Curcumin-Loaded nanofiber therapies against Methicillin-Resistant Staphylococcus aureus Infection: Augmented immune and inflammatory responses in zebrafish wound healing.

BACKGROUND: Wound healing pivots on a finely orchestrated inflammatory cascade, critical for tissue repair. Chronic wounds, compounded by persistent inflammation and susceptibility to infection, pose formidable clinical challenges. Nanofiber dressings offer promising avenues for wound care, yet their interaction with inflammation and infection remains elusive. We aim to delineate the inflammatory cascade preceding wound closure and assess Cu@Bbc nanofibers' therapeutic efficacy in mitigating inflammation and combating infection. Their unique attributes suggest promise in modulating inflammation, fostering tissue regeneration, and preventing microbial colonization. Investigating the intricate interplay between nanofiber scaffolds, inflammation, and infection may unveil mechanisms of enhanced wound healing. Our findings could stimulate the development of tailored dressings, urgently needed for effective wound management amidst immune dysregulation, infection, and inflammation. METHODS: In this investigation, we synthesized Cu@Bbc nanofibers, incorporating curcumin and berberine chloride, for wound healing applications. We evaluated their individual and combined antibacterial, anti-biofilm, and antioxidant activities, alongside binding affinity with pro-inflammatory cytokines through molecular docking. Morphological characterization was conducted via SEM, FTIR assessed functional groups, and wettability contact angle measured hydrophobic properties. The physical properties, including tensile strength, swelling behavior, and thermal stability, were evaluated using tensile testing, saline immersion method and thermogravimetric analysis. Biodegradability of the nanofibers was assessed through a soil burial test. Biocompatibility was determined via MTT assay, while wound healing efficacy was assessed with in vitro scratch assays. Controlled drug release and antibacterial activity against MRSA were examined, with in vivo assessment in a zebrafish model elucidating inflammatory responses and tissue remodeling. RESULTS: In this study, the synergistic action of curcumin and berberine chloride exhibited potent antibacterial efficacy against MRSA, with significant anti-mature biofilm disruption. Additionally, the combination demonstrated heightened antioxidant potential. Molecular docking studies revealed strong binding affinity with pro-inflammatory cytokines, suggesting a role in expediting the inflammatory response crucial for wound healing. Morphological analysis confirmed nanofiber quality, with drug presence verified via FTIR spectroscopy. Cu@Bbc demonstrated higher tensile strength, optimal swelling behavior, and robust thermal stability as evaluated through tensile testing and thermogravimetric analysis. Additionally, the Cu@Bbc nanofiber showed enhanced biodegradability, as confirmed by the soil burial test. Biocompatibility assessments showed favorable compatibility, while in vitro studies demonstrated potent antibacterial activity. In vivo zebrafish experiments revealed accelerated wound closure, re-epithelialization, and heightened immune response, indicative of enhanced wound healing. CONCLUSION: In summary, our investigation highlights the efficacy of Cu@Bbc nanofibers, laden with curcumin and berberine chloride, in displaying robust antibacterial and antioxidant attributes while also modulating immune responses and inflammatory cascades essential for wound healing. These results signify their potential as multifaceted wound dressings for clinical implementation.

Immunoregulatory paracrine effect of mesenchymal stem cells and mechanism in the treatment of osteoarthritis.

Osteoarthritis (OA) is a degenerative joint disease caused by chronic inflammation that damages articular cartilage. At present, the treatment of OA includes drug therapy to relieve symptoms and joint replacement therapy for advanced OA. However, these palliatives cannot truly block the progression of the disease from the immunological pathogenesis of OA. In recent years, bone marrow mesenchymal stem cell (BMSC) transplantation has shown great potential in tissue engineering repair. In addition, many studies have shown that BMSC paracrine signals play an important role in the treatment of OA through immune regulation and suppressing inflammation. At present, the mechanism of inflammation-induced OA and the use of BMSC transplantation in joint repair have been reviewed, but the mechanism and significance of BMSC paracrine signals in the treatment of OA have not been fully reviewed. Therefore, this article focused on the latest research progress on the paracrine effects of BMSCs in the treatment of OA and the related mechanisms by which BMSCs secrete cytokines to inhibit the inflammatory response, regulate immune balance, and promote cell proliferation and differentiation. In addition, the application potential of BMSC-Exos as a new type of cell-free therapy for OA is described. This review aimed to provide systematic theoretical support for the clinical application of BMSC transplantation in the treatment of OA.

Huperzine a ameliorates sepsis-induced acute lung injury by suppressing inflammation and oxidative stress via α7 nicotinic acetylcholine receptor.

Sepsis, characterized by high mortality rates, causes over 50 % of acute lung injury (ALI) cases, primarily due to the heightened susceptibility of the lungs during this condition. Suppression of the excessive inflammatory response is critical for improving the survival of patients with sepsis; nevertheless, no specific anti-sepsis drugs exist. Huperzine A (HupA) exhibits neuroprotective and anti-inflammatory properties; however, its underlying mechanisms and effects on sepsis-induced ALI have yet to be elucidated. In this study, we demonstrated the potential of HupA for treating sepsis and explored its mechanism of action. To investigate the in vivo impacts of HupA, a murine model of sepsis was induced through cecal ligation and puncture (CLP) in both wild-type (WT) and α7 nicotinic acetylcholine receptor (α7nAChR) knockout mice. Our results showed that HupA ameliorates sepsis-induced acute lung injury by activating the α7nAChR. We used the CLP sepsis model in wild-type and α7nAChR -/- mice and found that HupA significantly increased the survival rate through α7nAChR, reduced the pro-inflammatory cytokine levels and oxidative stress, ameliorated histopathological lung injury, altered the circulating immune cell composition, regulated gut microbiota, and promoted short-chain fatty acid production through α7nAChR in vivo. Additionally, HupA inhibited Toll-like receptor NF-κB signaling by upregulating the α7nAChR/protein kinase B/glycogen synthase kinase-3 pathways. Our data elucidate HupA's mechanism of action and support a "new use for an old drug" in treating sepsis. Our findings serve as a basis for further in vivo studies of this drug, followed by application to humans. Therefore, the findings have the potential to benefit patients with sepsis.

Activation of retinoid X receptors protects retinal neurons and pigment epithelial cells from BMAA-induced death.

Exposure to the non-protein amino acid cyanotoxin ß-N-methylamino-L-alanine (BMAA), released by cyanobacteria found in many water reservoirs has been associated with neurodegenerative diseases. We previously demonstrated that BMAA induced cell death in both retina photoreceptors (PHRs) and amacrine neurons by triggering different molecular pathways, as activation of NMDA receptors and formation of carbamate-adducts was only observed in amacrine cell death. We established that activation of Retinoid X Receptors (RXR) protects retinal cells, including retina pigment epithelial (RPE) cells from oxidative stress-induced apoptosis. We now investigated the mechanisms underlying BMAA toxicity in these cells and those involved in RXR protection. BMAA addition to rat retinal neurons during early development in vitro increased reactive oxygen species (ROS) generation and polyADP ribose polymers (PAR) formation, while pre-treatment with serine (Ser) before BMAA addition decreased PHR death. Notably, RXR activation with the HX630 agonist prevented BMAA-induced death in both neuronal types, reducing ROS generation, preserving mitochondrial potential, and decreasing TUNEL-positive cells and PAR formation. This suggests that BMAA promoted PHR death by substituting Ser in polypeptide chains and by inducing polyADP ribose polymerase activation. BMAA induced cell death in ARPE-19 cells, a human epithelial cell line; RXR activation prevented this death, decreasing ROS generation and caspase 3/7 activity. These findings suggest that RXR activation prevents BMAA harmful effects on retinal neurons and RPE cells, supporting this activation as a broad-spectrum strategy for treating retina degenerations.

Effects of Dietary Chitosan on Growth Performance, Serum Biochemical Indices, Antioxidant Capacity, and Immune Response of Juvenile Tilapia (Oreochromis niloticus) under Cadmium Stress.

The objective of this study was to examine the effects of varying levels of dietary chitosan supplementation on mitigating cadmium stress and its influence on growth performance, serum biochemical indices, antioxidant capacity, immune response, inflammatory response, and the expression of related genes in juvenile Genetically Improved Farmed Tilapia (GIFT, Oreochromis niloticus). Five groups of juvenile tilapias (initial body weight 21.21 ± 0.24 g) were fed five diets with different levels (0%, 0.5%, 1.0%, 1.5%, and 2.0%) of chitosan supplementation for 60 days under cadmium stress (0.2 mg/L Cd2+). The findings indicated that, compared with the 0% chitosan group, dietary chitosan could significantly increase (p < 0.05) the final weight (Wf), weight gain rate (WGR), specific growth rate (SGR), daily growth index (DGI), and condition factor (CF), while the feed conversion ratio (FCR) expressed the opposite trend in juvenile GIFT. Dietary chitosan could significantly increase (p < 0.05) the activities (contents) of cholinesterase (CHE), albumin (ALB), lactate dehydrogenase (LDH), alkaline phosphatase (ALP), acid phosphatase (ACP), and lysozyme (LZM), while glutamic pyruvic transaminase (GPT), glutamic oxaloacetic transaminase (GOT), and complement 3 (C3) in the serum of juvenile GIFT expressed the opposite trend. Dietary chitosan could significantly increase (p < 0.05) the activities of superoxide dismutase (SOD) and catalase (CAT) and significantly decrease (p < 0.05) the activities (contents) of glutathione S-transferase (GST), glutathione peroxidase (GSH-Px), and malondialdehyde (MDA) in the serum of juvenile GIFT. Dietary chitosan could significantly increase (p < 0.05) the activities (contents) of CAT, GST, GSH-Px, and total antioxidant capacity (T-AOC) and significantly decrease (p < 0.05) the contents of MDA in the liver of juvenile GIFT. Dietary chitosan could significantly increase (p < 0.05) the activities (contents) of SOD, GSH-Px, T-AOC, Na+-K+-ATPase, and Ca2+-ATPase and significantly decrease (p < 0.05) the activities (contents) of CAT, GST, and MDA in the gills of juvenile GIFT. Dietary chitosan could significantly up-regulate (p < 0.05) the gene expression of cat, sod, gst, and gsh-px in the liver of juvenile GIFT. Dietary chitosan could significantly up-regulate (p < 0.05) the gene expression of interferon-γ (inf-γ) in the gills and spleen and significantly down-regulate (p < 0.05) the gene expression of inf-γ in the liver and head kidney of juvenile GIFT. Dietary chitosan could significantly down-regulate (p < 0.05) the gene expression of interleukin-6 (il-6), il-8, and tumor necrosis factor-α (tnf-α) in the liver, gills, head kidney, and spleen of juvenile GIFT. Dietary chitosan could significantly up-regulate (p < 0.05) the gene expression of il-10 in the liver, gills, head kidney, and spleen of juvenile GIFT. Dietary chitosan could significantly up-regulate (p < 0.05) the gene expression of transforming growth factor-ß (tgf-ß) in the liver and significantly down-regulate (p < 0.05) the gene expression of tgf-ß in the head kidney and spleen of juvenile GIFT. In conclusion, dietary chitosan could mitigate the impact of cadmium stress on growth performance, serum biochemical indices, antioxidant capacity, immune response, inflammatory response, and related gene expression in juvenile GIFT. According to the analysis of second-order polynomial regression, it was found that the optimal dietary chitosan levels in juvenile GIFT was approximately 1.42% to 1.45%, based on its impact on Wf, WGR, SGR, and DGI.

MiR-20a-5p Targeting the TGFBR2 Gene Regulates Inflammatory Response of Chicken Macrophages Infected with Avian Pathogenic E. coli.

Avian pathogenic E. coli (APEC) causes localized and systemic infections and are a threat to human health. microRNAs (miRNAs) play critical roles in inflammation and immune regulation following pathogen invasion. However, the related regulatory mechanism remains unclear. This study aimed to elucidate the involvement of chicken microRNA-20a-5p (gga-miR-20a-5p) in host defense against APEC in chickens and the underlying mechanisms. We evaluated the expression levels of gga-miR-20a-5p in chicken tissues and cells and observed a significant decrease in expression following APEC infection. Dual luciferase reporter assays showed that gga-miR-20a-5p directly targeted transforming growth factor-beta receptor 2 (TGFBR2), specifically by binding to the 3'-untranslated region (3'UTR) of TGFBR2. Overexpression of gga-miR-20a-5p markedly reduced both the mRNA and protein levels of TGFBR2, whereas inhibition of gga-miR-20a-5p significantly increased expression. Mechanistic investigations revealed that overexpression of gga-miR-20a-5p also attenuated the expression levels of the pro-inflammatory cytokines IL8, TNFα, IL6, and IL1ß, whereas inhibition of gga-miR-20a-5p had the opposite effects. Collectively, our findings suggest that gga-miR-20a-5p regulates the immune response during APEC infection by targeting TGFBR2, thereby suppressing inflammatory cytokine production. This study provides valuable insights into the role of gga-miR-20a-5p in the host defense against APEC.

Pharmacological mechanisms of Ma Xing Shi Gan Decoction in treating influenza virus-induced pneumonia: intestinal microbiota and pulmonary glycolysis.

Background: Influenza virus is one of the most common pathogens that cause viral pneumonia. During pneumonia, host immune inflammation regulation involves microbiota in the intestine and glycolysis in the lung tissues. In the clinical guidelines for pneumonia treatment in China, Ma Xing Shi Gan Decoction (MXSG) is a commonly prescribed traditional Chinese medicine formulation with significant efficacy, however, it remains unclear whether its specific mechanism of action is related to the regulation of intestinal microbiota structure and lung tissue glycolysis. Objective: This study aimed to investigate the mechanism of action of MXSG in an animal model of influenza virus-induced pneumonia. Specifically, we aimed to elucidate how MXSG modulates intestinal microbiota structure and lung tissue glycolysis to exert its therapeutic effects on pneumonia. Methods: We established a mouse model of influenza virus-induced pneumoni, and treated with MXSG. We observed changes in inflammatory cytokine levels and conducted 16S rRNA gene sequencing to assess the intestinal microbiota structure and function. Additionally, targeted metabolomics was performed to analyze lung tissue glycolytic metabolites, and Western blot and enzyme-linked immunosorbent assays were performed to assess glycolysis-related enzymes, lipopolysaccharides (LPSs), HIF-1a, and macrophage surface markers. Correlation analysis was conducted between the LPS and omics results to elucidate the relationship between intestinal microbiota and lung tissue glycolysis in pneumonia animals under the intervention of Ma Xing Shi Gan Decoction. Results: MXSG reduced the abundance of Gram-negative bacteria in the intestines, such as Proteobacteria and Helicobacter, leading to reduced LPS content in the serum and lungs. This intervention also suppressed HIF-1a activity and lung tissue glycolysis metabolism, decreased the number of M1-type macrophages, and increased the number of M2-type macrophages, effectively alleviating lung damage caused by influenza virus-induced pneumonia. Conclusion: MXSG can alleviate glycolysis in lung tissue, suppress M1-type macrophage activation, promote M2-type macrophage activation, and mitigate inflammation in lung tissue. This therapeutic effect appears to be mediated by modulating gut microbiota and reducing endogenous LPS production in the intestines. This study demonstrates the therapeutic effects of MXSG on pneumonia and explores its potential mechanism, thus providing data support for the use of traditional Chinese medicine in the treatment of respiratory infectious diseases.

Origin recognition complex subunit 6 (ORC6) is a key mediator of LPS-induced NFκB activation and the pro-inflammatory response.

Lipopolysaccharide (LPS)-activated pro-inflammatory responses play a critical role in sepsis, a life-threatening condition. This study investigates the role of origin recognition complex subunit 6 (ORC6) in LPS responses in macrophages and monocytes. Silencing ORC6 using targeted shRNA significantly reduced LPS-induced expression and production of IL-1ß (interleukin-1 beta), TNF-α (tumor necrosis factor alpha), and IL-6 (interleukin-6) in THP-1 human macrophages, peripheral blood mononuclear cells (PBMCs), and bone marrow-derived macrophages (BMDMs). Additionally, ORC6 knockout (KO) via the CRISPR/Cas9 method in THP-1 macrophages inhibited LPS-induced pro-inflammatory responses, while ectopic overexpression of ORC6 enhanced LPS-induced expression and production of pro-inflammatory cytokines. ORC6 is crucial for the activation of the nuclear factor kappa B (NFκB) signaling cascade in macrophages and monocytes. LPS-induced NFκB activation was largely inhibited by ORC6 silencing or KO, but potentiated following ORC6 overexpression. Mechanistically, ORC6 associated with nuclear p65 after LPS stimulation, an interaction necessary for NFκB activation. Overexpression of ORC6 did not recover the reduced pro-inflammatory response to LPS in THP-1 macrophages with silenced p65. Furthermore, the NFκB inhibitor BMS-345,541 nearly eliminated the pro-inflammatory response enhanced by ORC6 overexpression in response to LPS. Further studies revealed that ORC6 depletion inhibited NFκB activation induced by double-stranded RNA (dsRNA) and high mobility group box 1 (HMGB1) in THP-1 macrophages. In vivo experiments demonstrated that macrophage-specific knockdown of ORC6 protected mice from LPS-induced septic shock and inhibited LPS-stimulated production of IL-1ß, TNF-α, and IL-6 in mouse serum. ORC6 silencing also inhibited LPS-induced NFκB activation in ex vivo cultured PBMCs following macrophage-specific knockdown of ORC6. These findings highlight ORC6 as a pivotal mediator in LPS-induced NFκB activation and the pro-inflammatory response in sepsis, suggesting that targeting ORC6 could be a novel therapeutic strategy for managing sepsis and related inflammatory conditions.

Phase angle as a potential tool to evaluate chronic inflammatory state and predict quality of life deterioration in women with breast cancer and obesity: A narrative review.

The interaction between lifestyle--defined more specifically in health care as the personal exposome--and its implications on obesity and breast cancer development highlights the critical role of body composition and inflammation in these patients. There is clear evidence that the personal and internal exposome triggers biochemical, inflammatory, and metabolic reprogramming, which might favor ectopic lipid accumulation within the body, such as muscles. Additionally, the presence of excessive adipose tissue exacerbates these alterations in the internal exposome, resulting in cell damage and modifying body composition. Understanding the nexus between these lifestyle-induced exposome modifications, such as inflammation, and the resultant changes in body composition is crucial to assess the association with breast cancer progression and treatment responses. Various techniques can be used to evaluate body composition; one of those most used currently is bioelectrical impedance analysis. This analysis provides parameters, including phase angle (PhA), by which cellular health and metabolic activity can be assessed. In addition, PhA is a potential indicator of nutritional status and disease prognosis, as it has been linked to survival and quality of life in patients with cancer. Therefore, PhA might be used in daily oncology practice to implement an accurate nutritional intervention, reducing side effects and complications of oncology management, and improving quality of life during treatment and survival, even in patients with breast cancer with obesity or overweight. The aim of this review is to analyze the existing information on the current application of PhA in patients with breast cancer and its potential use as a tool to assess inflammatory response, identify malnutrition, and predict the deterioration of quality of life so that it could be proposed as an early indicator for nutritional interventions in this group of patients.

Use of topical rSm29 in combination with intravenous meglumine antimoniate in the treatment of cutaneous leishmaniasis: a randomized controlled trial.

BACKGROUND: Cutaneous leishmaniasis (CL) caused by Leishmania (Viannia) braziliensis is associated with an inflammatory response. Granzyme (GzmB) and IL-1ß play a key role in the pathology. Meglumine antimoniate (MA) is the first-choice drug for the treatment of CL, but therapy failure is observed in up to 50% of the cases. The protein, rSm29 of Schistosoma mansoni, down modulates pro-inflammatory cytokine production. We evaluate if the combination of topical rSm29 plus MA increases the cure rate of CL. METHODS: In this randomized clinical trial, 91 CL patients were allocated in 3 groups. All cases received MA (20mg/Kg/weight) for 20 days. Group 1 used topical rSm29 (10ug), group 2 a placebo topically applied, and group 3 received only MA. RESULTS: The cure rate on day 90 was 71% in subjects treated with rSm29 plus MA, and 43% in patients who received MA plus placebo or MA alone (P<0.05). There was a decrease in GzmB and an increase in IFN-γ (P<0.05) in supernatants of skin biopsies of the lesions obtained on D7 of therapy (P<0.05) in patients who received rSm29. CONCLUSION: rSm29 associated with MA reduces GzmB levels, is more effective than MA alone and decreases CL healing time. CLINICAL TRIALS REGISTRATION: ClinicalTrial.gov under NCT06000514.

Dynamics of the thymic transcriptome at stages of acute thymic involution in Japanese Black calves with a poor prognosis.

Transcriptome analysis was performed on the thymus of Japanese Black calves that were necropsied due to poor prognosis, to characterize changes associated with acute thymic involution. Gene expression profiles obtained by DNA microarray analysis of eight calf thymuses were classified into three patterns that correlated with the histopathological stage of acute thymic involution. Using principal component analysis, the first principal component of the global gene expression levels in the calf thymus was associated with the stage of acute thymic involution, suggesting that histopathological changes greatly influence the gene expression profile. Gene ontology enrichment analysis revealed that genes related to cell proliferation, wound healing, and inflammatory responses were the main contributors to the first principal component. Real-time RT-PCR showed that the thymus had lower expression of PCNA, KIFC1, and HES6, and higher expression of SYNPO2, PDGFRB, and TWIST1 during acute thymic involution. Immunohistochemistry demonstrated a decrease in the rate of Ki67-positive cells in the thymic cortex during the late stage of acute thymic involution. The rate of cleaved caspase-1-positive cells increased in the thymic cortex at an earlier stage than the increase in the rate of cleaved caspase-3-positive cells. Vimentin, which was almost absent in the non-involuted thymic cortex, appeared in the thymic cortex during acute thymic involution. These results suggest that in farmed calves with a poor prognosis, inflammatory responses and impaired thymocyte proliferation are primarily involved in acute thymic involution.