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关键词： interleukin-6   physical exercise   brain   molecular signaling   neurodegeneration  

摘要： The dual role of interleukin-6 (IL-6) as beneficial in physiological conditions and detrimental in pathological conditions has been a subject of research interest since its discovery. This has surpassed the traditional view of IL-6 as a pro-inflammatory cytokine, primarily due to its multifunctionality. To coordinate this multiple effect, several downstream signaling pathways are involved. Physical exercise mediates these downstream signals and accentuates the pleiotropic effects of IL-6 by enabling cross-talk between various organs, including muscles and the brain. In addition, IL-6 itself is a crucial signaling molecule that enhances exercise performance by maintaining muscle energy homeostasis. However, the specific mechanisms by which this molecule modulates overall brain physiology under different exercise conditions remain unclear. For example, chronic exercise with different exercise protocols could increase chronic plasma levels of IL-6, which could have an impact on brain health. Most studies in the literature have established the beneficial effects of exercise-mediated IL-6, but the impact of chronic elevation of IL-6 by exercise remains unclear. Additionally, the level of IL-6 determines the nature of molecular signaling that underlies all IL-6-mediated functions. This can be achieved by understanding both classic and IL-6 trans-signaling in different physio-pathological conditions. However, the mechanism by which exercise activates these two different classic and IL-6 trans-signaling pathways is less understood. Therefore, this review presents a comprehensive overview of how different exercises mediate IL-6-mediated benefits by discussing the full array of molecular signaling pathways.

关键词： cardiopulmonary bypass   IL-17A   endoplasmic reticulum stress   neuronal apoptosis  

摘要： Cardiopulmonary bypass (CPB) is associated with significant neurological complications, yet the mechanisms underlying brain injury remain unclear. This study investigated the role of interleukin-17A (IL-17A) in exacerbating CPB-induced neuronal apoptosis and identified vulnerable brain regions. Utilizing a rat CPB model and an oxygen-glucose deprivation/reoxygenation (OGD/R) cellular model, we demonstrated that IL-17A levels were markedly elevated in the hippocampus post-CPB, correlating with endoplasmic reticulum stress (ERS)-mediated apoptosis. Transcriptomic analysis revealed the enrichment of IL-17 signaling and apoptosis-related pathways. IL-17A-Neutralizing monoclonal antibody (mAb) and the ERS inhibitor 4-phenylbutyric acid (4-PBA) significantly attenuated neurological deficits and hippocampal neuronal damage. Mechanistically, IL-17A activated the Act1-IRE1-JNK1 axis, wherein heat shock protein 90 (Hsp90) competitively regulated Act1-IRE1 interactions. Co-immunoprecipitation confirmed the enhanced Hsp90-Act1 binding post-CPB, promoting IRE1 phosphorylation and downstream caspase-12 activation. In vitro, IL-17A exacerbated OGD/R-induced apoptosis via IRE1-JNK1 signaling, reversible by IRE1 inhibition. These findings identify the hippocampus as a key vulnerable region and delineate a novel IL-17A/Act1-IRE1-JNK1 pathway driving ERS-dependent apoptosis. Targeting IL-17A or Hsp90-mediated chaperone switching represents a promising therapeutic strategy for CPB-associated neuroprotection. This study provides critical insights into the molecular crosstalk between systemic inflammation and neuronal stress responses during cardiac surgery.

关键词： Cell death   Fenpropathrin   Inflammation   italic>Sambucus Nigra   TNF-alpha   NF-kappa B  

摘要： This research assessed the effectiveness of Sambucus nigra (SN) in alleviating hepatorenal injury caused by fenpropathrin (FNP) in rodents. Six equal groups were created from the 30 Wistar rats: Group 1 was the negative control, Groups 2 and 3 were the SN control groups, Group 4 was the FNP group, and Groups 5 and 6 were the FNP + SN combination groups. The hepatoprotective and renoprotective effects of SN were assessed by quantifying serum enzyme markers, including ALT, AST, ALP, blood urea nitrogen, and creatinine. Oxidative stress indicators, RT-PCR analysis, histological examination, and immunohistochemistry studies were conducted on the liver and kidneys to confirm the previously indicated parameters. The rats administered FNP injections displayed increased blood marker enzyme levels, altered oxidant-antioxidant equilibrium, and significant pathogenic changes in hepatic and renal tissues. Furthermore, these rats exhibited elevated levels of caspase-3 and iNOS, linked to the triggered expression of TNF-alpha and NF-kappa B genes in these tissues. Administering SN enhanced all the aforementioned toxicological parameters. The prospective hepato-renal therapeutic benefits of SN against impairment of the liver and kidneys induced by FNP have been evidenced through its anti-inflammatory, antioxidant, and anti-apoptotic pathways.

关键词： 清热润肠方   坐浴疗法   肛裂   创面愈合   炎症因子  

摘要： 目的：观察清热润肠方坐浴疗法对肛裂术后创面愈合和炎性因子IL-6、TNF-α水平的影响。方法：将300例肛裂患者分为研究组和对照组，每组150例。两组均采用肛裂切除术治疗，对照组采用1:5000高锰酸钾液坐浴，研究组采用清热润肠方坐浴。均给予常规换药，直到创面愈合。对比两组治疗效果，比较术后1d、7d创面疼痛、分泌物以及肉芽生长积分的情况，对比术后1d、7d的IL-6、TNF-α浓度水平，比较创面愈合时间和创面感染率情况。结果：研究组治疗后愈显率为91.33%，高于对照组78.00%（P＜0.05）；创面分泌物、疼痛以及肉芽生长积分方面，研究组术后7d相较于对照组更低（P＜0.05）；研究组术后7d血清炎性因子IL-6、TNF-α水平低于对照组（P＜0.05）；研究组创面愈合时间和感染率均低于对照组（P＜0.05）。结论：清热润肠方熏洗对肛裂术后创面愈合具有促进作用，可降低炎症反应和感染发生率，提高临床治疗疗效，值得推广应用。

关键词： 养血口服液   阿尔茨海默病   PI3K/Akt/TNF-α   认知功能障碍  

摘要： 目的：探究养血口服液改善AD小鼠认知功能的疗效及潜在作用机制。方法：将40只APP/PS1双转基因小鼠随机分为模型组（Model组）、养血口服液低剂量组（YX-D组）、养血口服液中剂量组（YX-Z组）、养血口服液高剂量组（YX-G组），10只同系背景非转基因C57BL/6小鼠为空白组（Control组）。连续灌胃14d后，Morris水迷宫检测认知功能，海马组织进行刚果红染色，WB、RT-qPCR法检测小鼠海马区PI3K/Akt/TNF-α通路上蛋白及mRNA表达量的变化情况。结果：与Model组相比，YX-G、YX-Z组小鼠游泳总路程及上平台潜伏期均减少，穿越平台次数增多，具有统计学差异（P<0.05）；YX-G组老年斑（SP）减少最为明显；YX-G组小鼠海马组织中PI3K、AKT mRNA表达水平升高，TNF-α基因表达水平降低，具有统计学差异（P<0.05）；YX-G组小鼠海马组织中PI3K、Akt蛋白表达水平无差异，p-PI3K蛋白表达水平升高，TNF-α蛋白表达水平降低，具有统计学差异（P<<0.05）。结论：养血口服液可以改善AD小鼠的认知功能，减少海马区SP沉积，其机制可能与调控PI3K/Akt/TNF-α信号通路有关，且有剂量依赖性趋势，高剂量组效果优于低中剂量组。

关键词： total flavonoids of Dracocephalum moldavica L   vascular dementia   network pharmacology   neuroinflammation   TNF-alpha/NF-kappa B p65 signaling pathway   blood-brain barrier  

摘要： Objective This study aims to elucidate the neuroprotective effects and underlying mechanisms of total flavonoids of Dracocephalum moldavica L. (TFDM) in VaD by using network pharmacology and in vivo *** The network pharmacology was used to explore the mechanism of TFDM to improve VaD. A rat model of VaD was established using permanent bilateral common carotid artery occlusion (2VO). The Morris water maze test assessed spatial learning and memory capacities. Nissl staining was used to examine the neuronal damage. Western blot and Immunofluorescence analysis was employed to evaluate protein levels of factors associated with neuroinflammation, blood-brain barrier integrity, and *** The network pharmacology suggests TFDM may combat VaD through TNF-alpha/NF-kappa B p65 signaling pathways. TFDM treatment may attenuate memory deficits associated with 2VO and reduce neuronal damage. TFDM improved blood-brain barrier integrity and promoted angiogenesis by downregulating MMP-9 and upregulating ZO-1 and VEGFA. Moreover, TFDM exhibited anti-inflammatory properties by inhibiting TNF-alpha and NF-kappa B p65 production, thereby mitigating the neuroinflammatory response in VaD *** TFDM demonstrated significant improvement in cognitive function in VaD rats. This improvement was attributed to the multifaceted effects, including the improvement of blood-brain barrier integrity, promotion of angiogenesis, and reduction of neuroinflammation. These findings suggest that TFDM may represent a promising therapeutic approach for VaD management.

关键词： HLA   genes   multiple sclerosis  

摘要： Multiple sclerosis (MS) is a chronic autoimmune disease characterized by the immune system attacking the central nervous system, leading to demyelination and neurodegeneration. This work investigates the relationship between specific human leukocyte antigen (HLA) polymorphisms and MS, aiming to reveal the immunogenetic background of this disease for more individualized management approaches. This study employed a case-control design, analyzing HLA allele frequencies in 179 MS patients and 200 control subjects using next-generation sequencing, The key findings indicate significant associations between several HLA Class I and II alleles and MS, including HLA-B*35:03:01:03, HLA-C*04:01:01:14, HLA-DRB1*15:01:01:26, and HLA-DQA1*05:05:01:02. These findings emphasize the critical role of HLA molecules in MS Romanian patients.

关键词： high resolution   HLA alleles   HLA haplotypes   NGS  

摘要： HLA typing of 9126 haematopoietic stem cell donors living in the Asian and European parts of Russia and identifying themselves as Russians was performed using NGS technology in 2-field resolution at the HLA-A, HLA-B, HLA-C, HLA-DRB1, and HLA-DQB1 loci. The study of donors in the Asian part of Russia disclosed 77 alleles at the HLA-A locus, 111 at the HLA-B locus, 58 at the HLA-C locus, 54 at the HLA-DRB1 locus, and 26 at the HLA-DQB1 locus. Donors of the European part of Russia are characterised by the following allelic diversity: 87 alleles at the HLA-A locus, 136 at the HLA-B locus, 72 at the HLA-C locus, 67 at the HLA-DRB1 locus, and 37 at the HLA-DQB1 locus. The most common five-locus haplotype in both populations is HLA-A*01:01 similar to HLA-C*07:01 similar to HLA-B*08:01 similar to HLA-DRB1*03:01 similar to HLA-DQB1*02:01. Throughout the study, 26 new alleles were revealed.

关键词： COX2   kaempferol   mesothelial-mesenchymal transition   network pharmacology   postoperative peritoneal adhesions  

摘要： Postoperative peritoneal adhesion (PA) formation is a common complication after abdominal surgery and can result in various severe outcomes. Inflammation and fibrosis are important processes in PA formation. The effectiveness of kaempferol (KF), a common component of several medications used to reduce inflammation and prevent fibrotic diseases, in preventing postoperative PA formation is unknown. This study explored the effectiveness and mechanism of KF in preventing PA formation following surgery. The animal adhesion model revealed that KF could effectively prevent adhesions formation and inhibit mesothelial-mesenchymal transition (MMT). Protein-protein interaction and pathway enrichment analyses revealed that TNF-alpha may be the key target through which KF prevents adhesion formation. Here, KF was found to inhibit TNF-alpha-induced MMT. Furthermore, Kyoto Encyclopedia of Genes and Genomes pathway enrichment analyses revealed that common genes between KF and PA are enriched in the TNF signalling pathway. Moreover, cyclooxygenase 2 (COX2) was identified as a downstream target of TNF-alpha whose expression is positively correlated with adhesion formation. Most importantly, COX2 small interfering RNA (siRNA) and overexpression plasmid (OE) transfection experiments confirmed that KF inhibits MMT by blocking the TNF-alpha/COX2 signalling pathway. Finally, molecular docking revealed that TNF-alpha is a binding target of KF. In conclusion, these results suggest that KF inhibits MMT by blocking the TNF-alpha/COX2 signalling pathway, thus attenuating adhesion formation. These results provide new insights into the development of antiadhesion drugs.

关键词： topical IgY therapy   thermosensitive hydrogel   sustained-release delivery   skin anti-inflammation   cutaneous healing  

摘要： With the progression of biomedical therapies, antibodies have emerged as promising agents for treating inflammatory skin disorders due to their specificity and antigen-targeting capabilities. Antibodies play a crucial role in epidermal injury repair by precisely regulating inflammatory pathways and neutralizing key inflammatory factors. Notably, conventional IgG antibodies face limitations including poor stability, immunogenicity, and reduced efficacy in epidermal environments. Therefore, developing an alternative antibody delivery system capable of overcoming these limitations has become a critical issue to address. Egg yolk antibody (IgY), with its unique Fc structure, exhibits excellent thermal stability and biosafety, making it ideal for treating skin and mucosal diseases. Here, this study proposes an innovative topical IgY hydrogel sustained-release system (IgY-Gel) to deliver TNF alpha-specific IgY (anti-TNF alpha IgY), which is demonstrated to effectively reduce the levels of inflammatory factors like IL-6 in LPS-stimulated RAW264.7 cells. The system synergizes with thermosensitive chitosan/beta-glycerophosphate (CS/beta-GP) hydrogels exhibiting controlled-release properties to enhance the proliferation and migration of human umbilical vein endothelial cells (HUVECs) under pro-inflammatory conditions. In addition, this system demonstrates accelerated wound healing in a mouse wound model, with a significantly higher healing rate of 95.7% in the anti-TNF alpha IgY-Gel group after 14 days, compared to the respective rates of 73.7%, 77.6%, and 81.7% in control, blank-Gel, and ns IgY-Gel groups, respectively. In conclusion, our IgY-Gel system highlights the anti-inflammatory and wound-healing potential of topical IgY therapy. This innovative system promotes the translational application of antibody therapies toward engineered biologics with enhanced efficacy and safety profiles in tissue repair processes.