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Purpose: Chronic inflammation is one of the key mechanisms of depression. Wenyang-Tianjin-Jie Decoction (WTJD) is an effective antidepressant found in the course of diagnosis and treatment, but the mechanism of therapeutic effect is not clear. The study aimed to evaluate the efficacy of WTJD in the kidney yang deficiency (KYD) type of depression rats and reveal its mechanisms. Materials and Methods: We selected forty 6-week-old male Sprague-Dawley rats for the study. We established a KYD [Phellodendron amurense Rupr (Huangbai) solution oral gavage and 4°C environments; 8 weeks] type of depression (chronic unpredictable mild stimulus; 6 weeks) rat model first. After successful modeling, we used WTJD or fluoxetine on rats for 3 weeks. Then we evaluated the depression and KYD behavior. Finally, we observed the expression of key inflammatory factors and proteins in peripheral blood and hippocampus, and further investigated the immune balance of Th17/Treg and Th1/Th2 cells and the activity of their main regulatory pathways JAK2/STAT3 and TLR4/TRAF6/NF-κB. Results: The imbalance of Th17/Treg and Th1/Th2 cells in rats were related to KYD and depressive symptoms. Through this study, we found that WTJD can inhibit the activity of JAK2/STAT3 and TLR4/TRAF6/NF-κB pathways, balance Th17/Treg and Th1/Th2 cell homeostasis, regulate the levels of inflammatory factors in the hippocampus and peripheral blood, and reverse KYD and depression. Conclusion: This study confirmed that WTJD had a reliable effect on depression rats with KYD, and its mechanism was to regulate the immune homeostasis of hippocampal T cells and related inflammatory factors to improve KYD and depression symptoms in rats. [ABSTRACT FROM AUTHOR]

aiming Zhang21Shanxi Key Laboratory of Stem Cells for Immunological Dermatosis, Institute of Dermatology, Taiyuan Central Hospital of Shanxi Medical University, Taiyuan, People's Republic of China; 2Shanxi Key Laboratory of Stem Cells for Immunological Dermatosis, Institute of Dermatology, Taiyuan Central Hospital, Taiyuan, People's Republic of ChinaCorrespondence: Kaiming Zhang, Email [email protected] View the original paper by Dr Zhou and colleagues This is in response to the Letter to the Editor [ABSTRACT FROM AUTHOR]

Vagus nerve stimulation (VNS) is acknowledged as a highly effective therapy for various neurological conditions, including refractory epilepsy, depression, Alzheimer's disease (AD), migraine, and stroke. Presently, there is an increasing focus on understanding the impact of VNS on cognitive aspects. Numerous studies suggest that VNS suppresses the body's inflammatory response, leading to enhanced cognitive function in patients. Vascular cognitive impairment (VCI) is a severe cognitive dysfunction syndrome resulting from prolonged chronic cerebral hypoperfusion (CCH), where the primary pathogenesis is CCH-induced neuroinflammation. In this paper, we present a comprehensive overview of the research advancements in using VNS for treating VCI and discuss that VNS improves cognitive function in VCI patients by suppressing neuroinflammation, offering insights into a potential novel approach for addressing this condition. [ABSTRACT FROM AUTHOR]

Sepsis is a severe systemic inflammatory response commonly occurring in infectious diseases, caused by infection with virulent pathogens. In the pathogenesis of sepsis, the cyclic guanosine monophosphate (GMP)-adenosine monophosphate (AMP) synthase-stimulator of interferon genes (cGAS-STING) signaling pathway serves a crucial role as a fundamental immunoregulatory mechanism. This signaling pathway activates STING upon recognizing intracellular DNA damage and pathogen-derived DNA, subsequently inducing the production of numerous inflammatory mediators, including interferon and inflammatory cytokines, which in turn trigger an inflammatory response. The aim of this paper is to explore the activation mechanism of the cGAS-STING signaling pathway in sepsis and its impact on inflammatory regulation. By delving into the mechanism of action of the cGAS-STING signaling pathway in sepsis, we aim to identify new therapeutic strategies for the treatment and prevention of sepsis. [ABSTRACT FROM AUTHOR]

This paper aims to investigate the impact of CQ on type 2 inflammatory response in MC903-induced AD mice. Methods: An AD mouse model was established via MC903 induction. After CQ treatment, AD mice were intraperitoneally injected with polyinosinic: polycyclic acid [poly (I:C)] or Nigericin. Dermatitis severity was scored, and the thickness of the left ear was measured. The pathological changes in mouse skin tissues were observed by H&E staining. The number of mast cells was counted via TB staining. The content of peripheral blood T-helper 2 (Th2) cells and levels of immunoglobulin E (IgE), thymic stromal-derived lymphopoietin (TSLP), interleukin (IL)-4, IL-13, interferon (IFN)-γ, IL-1β, and IL-18 were assessed by flow cytometry and ELISA. The levels of toll-like receptor 3 (TLR3), NLRP3, ASC, and cleaved caspase-1 proteins in skin tissues were determined by Western blot. Results: CQ treatment abated dermatitis severity and left ear thickness in AD mice, alleviated skin damage, reduced mast cell number, diminished IgE, TSLP, IL-4, and IL-13 levels, and peripheral blood Th2 cell content, with no significant changes in IFN-γ level. CQ alleviated type 2 inflammatory response in AD mice by inhibiting the activation of TLR3. CQ suppressed NLRP3 inflammasome activation. Activating TLR3/NLRP3 annulled CQ-mediated alleviation on type 2 inflammatory response in AD mice. Conclusion: CQ alleviated type 2 inflammatory response in AD mice by inhibiting TLR3 activation and NLRP3 inflammasome activation. [ABSTRACT FROM AUTHOR]

Peri-implantitis is an important cause of oral implant failure. In the past, TLR4 and TLR2 in the Toll-like family were generally considered as the key immune recognition receptors regulating peri-implantitis. However, under the guidance of this theory, there are still some unexplainable peri-implantitis symptoms. With the discovery of novel intracellular LPS receptor Caspase-11, a new understanding of inflammatory signaling and immune regulation in the development of peri-implantitis has been gained. However, the regulatory role of Caspase-11 in peri-implantitis and its crosstalk with the TLR4 pathway remain unclear. The therapeutic effect of drugs targeting Caspase-11 on peri-implantitis is still in its early stages. In view of this situation, this paper reviews the possible role of Caspase-11 in peri-implant inflammation, elaborated the entry process of LPS and the activation mechanism of Caspase-11, and analyzes the differences in Caspase-11 between commonly studied animals, mice and humans. The current research hotspots and challenges are also analyzed to provide new insights and ideas for researchers. [ABSTRACT FROM AUTHOR]

Since the incidence of gouty arthritis (GA) exhibits yearly increases, accurate assessment and early treatment have significant values for improving disease conditions and monitoring prognosis. Neutrophil to lymphocyte ratio (NLR) is a common indicator in blood routine, which has the characteristics of easy access and low cost. In recent years, NLR has been proven to be an effective indicator for guiding the diagnosis, treatment, and prognosis of various diseases. Moreover, NLR has varying degrees of relationship with various inflammatory biomarkers, which can affect and reflect the inflammatory response in the body. This paper reviews the independent value of NLR for GA and its underlying molecular pathological mechanisms, intending to contribute to the further application of NLR. [ABSTRACT FROM AUTHOR]

Cholestasis is a common clinical event in which bile formation and excretion are blocked, leading to retention of bile acids or bile salts; whether it occurs intra- or extrahepatically, primary or secondary, its pathogenesis is still unclear and is influenced by a combination of factors. In a variety of inflammatory and immune cells such as neutrophils, macrophages (intrahepatic macrophages are also known as Kupffer cells), mast cells, NK cells, and even T cells in humoral immunity and B cells in cellular immunity, inflammation can be a "second strike" against cholestatic liver injury. These cells, stimulated by a variety of factors such as bile acids, inflammatory chemokines, and complement, can be activated and accumulate in the cholestatic liver, and with the involvement of inflammatory mediators and modulation by cytokines, can lead to destruction of hepatocytes and bile duct epithelial cells and exacerbate (and occasionally retard) the progression of cholestatic liver disease. In this paper, we summarized the new research advances proposed so far regarding the relationship between inflammation and cholestasis, aiming to provide reference for researchers and clinicians in the field of cholestatic liver injury research. [ABSTRACT FROM AUTHOR]

All humans are universally affected by inflammatory diseases, and there is an urgent need to identify new anti-inflammatory drugs with good therapeutic benefits and minimal side effects to the organism. Recently, it has been found that plant-derived vesicle-like nanoparticles (PDVLNs) have good biocompatibility, with their active ingredients exhibiting good therapeutic effects on inflammation. They can also be used as drug carriers for targeted delivery of anti-inflammatory drugs. Therefore, PDVLNs represent a popular research area for novel anti-inflammatory drugs. This paper details the origin, biological functions, isolation and purification, and identification of PDVLNs, as well as the therapeutic effects of their intrinsic bioactive components on inflammatory diseases. It also introduces their targets as drug carriers to facilitate the development and application of PDVLNs anti-inflammatory drugs. [ABSTRACT FROM AUTHOR]

The gut-eye axis has been hypothesized to be a factor in many eye pathologies. This review examines papers from PubMed about this topic. Bacterial commensals could either be protective by regulating the immune system or prove to be damaging to the gut mucosal wall and incite an inflammatory process. The balance between the two appears to be crucial in maintaining eye health. Imbalances have been implicated in ophthalmologic conditions. The use of probiotics, dietary modifications, antibiotics, and faecal microbiota transplant in mice with pathologies such as those encountered in our practice appears to reverse disease course or at least prevent its progression. Clinical trials are currently underway to investigate their clinical significance in diseased patients. [ABSTRACT FROM AUTHOR]

Autophagy is a highly conserved process that maintains cell stability in eukaryotes, participates in the turnover of intracellular substances to maintain cell function, helps to resist pathogen invasion, and improves cell tolerance to environmental changes. Autophagy has been observed in many diseases, and the symptoms of these diseases are significantly improved by regulating autophagy. Autophagy is also involved in the development of lung diseases. Studies have shown that autophagy may play a beneficial or harmful role in acute lung injury (ALI), and ALI has been treated with traditional Chinese medicine designed to promote or inhibit autophagy. In this paper, the molecular mechanism and common pathways regulating autophagy and the relationship between autophagy and ALI are introduced, and the active ingredients of traditional Chinese medicine that improve ALI symptoms by regulating autophagy are summarized. [ABSTRACT FROM AUTHOR]

Acne Vulgaris is a chronic inflammatory skin disease, and one of the most prevalent inflammatory dermatoses among teenagers, affecting more than > 95% of boys and 85% of girls. Adult female acne (AFA) is a subtype of acne, pragmatically defined as affecting women over the age of 25. The clinical presentation of AFA may be distinguished from adolescent acne according to some key clinical and psychosocial characteristics. The etiopathogenic factors and the chronic clinical course that are implicated in AFA make management complex and challenging. A frequent tendency to relapse makes the requirement for maintenance therapy highly likely. Therefore, AFA typically requires a specific, tailored therapeutic approach. This paper presents six challenging case studies that demonstrate the efficacy of azelaic acid gel (AZA) in adult female acne. The six cases use AZA as monotherapy, as part of a combination regimen at treatment initiation, or as maintenance treatment (which is frequently required in this adult population). The positive outcomes achieved in this case series demonstrate that AZA can be efficacious, result in excellent patient satisfaction in mild to moderate adult female acne, and can be effective as a maintenance therapy. [ABSTRACT FROM AUTHOR]

The link between inflammation and cancer is still an attractive subject of many studies because systemic inflammatory response has been proven to play a pivotal role in cancer progression and metastasis. The strongest relationship between chronic inflammation and cancer development is observed in colorectal cancer (CRC). The evaluation of ratios derived from the routinely performed inflammatory biomarkers shows limited performances and limited clinical utility when individually used as prognostic factors for patients with CRC. In this review, we would like to summarize the latest knowledge about the diagnostic utility of systemic inflammatory ratios: neutrophil/lymphocyte (NLR), lymphocyte/monocyte (LMR), and platelet/lymphocyte (PLR) in CRC. We focused on the papers that assessed the diagnostic utility of blood cell parameters on the basis of the area under the ROC curve published in the recent 6 years. Identification of biomarkers that are significantly associated with prognostic in cancer would help the selection of patients with a high risk of poor outcomes. [ABSTRACT FROM AUTHOR]

Purpose: Diabetic nephropathy (DN), a global disease, is the leading cause of end-stage renal disease. There is a lack of specific treatment for this disease, and early intervention in disease progression is essential. In this paper, we used a rat model of early diabetic nephropathy to explore the therapeutic mechanism of sacubitril/valsartan in rats with early diabetic nephropathy. Materials and Methods: Rats were grouped into 1 normal group; 2. Model group (DN group): STZ (45 mg/kg/d) induced early diabetic nephropathy rats; 3. Sac group: DN rats + Sac group (orally, 60 mg/kg/d) for 6 weeks. After 6 weeks, the levels of serum albumin (ALB), glucose (GLU), creatinine (Cr), urea nitrogen (BUN) and 24-h urinary protein excretion were measured. In renal tissue homogenates, NLRP3 inflammasome, proinflammatory factors IL1-β and TNF-α, oxidative stress MDA and pro-fibrotic cytokine TGF-β 1 were performed. Histological analysis of kidneys by hematoxylin and eosin (HE), PAS and Masson trichrome staining. Results: 1. Sacubitril/valsartan (Sac) significantly improved renal hypertrophy, proteinuria and serum albumin levels in rats with early diabetic nephropathy (P < 0.001), and decreased GLU, Scr (P< 0.001), and BUN levels (P < 0.01).2. Light microscopy of renal tissues showed glomerular hypertrophy and interstitial inflammatory cell infiltration, and mean glomerular area (MGA) and mean glomerular volume (MGV) were crucially increased in early diabetic nephropathy (P < 0.001), and the Sac group showed reduced renal pathology and improved MGA and MGV (P < 0.001).3. Kidney tissue homogenate levels of NLRP3, Caspase-1, IL1-β, TNF-α, MDA and TGF-β 1 were critically, increased in DN rats (P < 0.001), and SOD was significantly decreased. All these indicators above were improved after treatment (P < 0.0001). Conclusion: Nlrp3-inflammasome promote progression of diabetic nephropathy through inflammation, fibrosis and oxidative stress; sacubitril/valsartan ameliorated early diabetes-induced renal damage by inhibiting NLRP3 pathway activation. [ABSTRACT FROM AUTHOR]

Non-alcoholic fatty liver disease (NAFLD) is a multifaceted clinicopathological syndrome characterised by excessive hepatic lipid accumulation that causes steatosis, excluding alcoholic factors. Platelet-activating factor (PAF), a biologically active lipid transmitter, induces platelet activation upon binding to the PAF receptor. Recent studies have found that PAF is associated with gamma-glutamyl transferase, which is an indicator of liver disease. Moreover, PAF can stimulate hepatic lipid synthesis and cause hypertriglyceridaemia. Furthermore, the knockdown of the PAF receptor gene in the animal models of NAFLD helped reduce the inflammatory response, improve glucose homeostasis and delay the development of NAFLD. These findings suggest that PAF is associated with NAFLD development. According to reports, patients with NAFLD or animal models have marked platelet activation abnormalities, mainly manifested as enhanced platelet adhesion and aggregation and altered blood rheology. Pharmacological interventions were accompanied by remission of abnormal platelet activation and significant improvement in liver function and lipids in the animal model of NAFLD. These confirm that platelet activation may accompany a critical importance in NAFLD development and progression. However, how PAFs are involved in the NAFLD signalling pathway needs further investigation. In this paper, we review the relevant literature in recent years and discuss the role played by PAF in NAFLD development. It is important to elucidate the pathogenesis of NAFLD and to find effective interventions for treatment. [ABSTRACT FROM AUTHOR]

This study aims to explore the scientific literature on the relationship between psoriasis and endothelial cells using bibliometric analysis, identifying research trends and public interest in this topic.Methods: We analyzed articles on the topic of endothelial cells and psoriasis in the Web of Science (WoS) Core Collection from 1987 to 2022, examining their distribution by publication year, country, organization, author, and journal. We used bibliometric software, including CiteSpace and R package bibliometrix, to visualize co-authorship relations, keyword citation burst analysis, co citation networks, keyword time zone map, burst references and cluster analysis.Results: Our analysis included 993 publications. The bibliometric analysis revealed a steady increase in the number of publications on psoriasis and endothelial cells over the past decade. The United States was the leading contributor to this field. The Journal of Investigative Dermatology was the most high-yield publication journal. Burst references analysis identified key articles that have significantly influenced the field, including studies on the role of endothelial dysfunction in psoriasis pathogenesis and the association between psoriasis severity and cardiovascular outcomes. 9 clusters were grouped in the key-word citation network. "Expression", "inflammation", "endothelial growth factor" and "angiogenesis" were the research focuses, while "cardiovascular disease", "atherosclerosis", "endothelial dysfunction", and "oxidative stress" might be the future research hotspots.Conclusion: This bibliometric analysis sheds light on the growing acknowledgement of the involvement of endothelial cells in psoriasis, with the United States taking the lead. It also emphasizes the necessity for additional research to unravel the underlying mechanisms connecting psoriasis, endothelial dysfunction, and cardiovascular comorbidities. Ultimately, this research will contribute to the development of enhanced management strategies for psoriasis patients. [ABSTRACT FROM AUTHOR]

Corticosteroids and non-steroidal anti-inflammatory drugs are commonly used prophylactically to control inflammation after ocular surgery. When prescribed as eye drops, as has been longstanding tradition, anti-inflammatory success is out of surgeons' hands, dependent on patient compliance and proper instillation technique. Sustained-release, intraoperatively administered anti-inflammatory drugs are emerging as another option. DEXYCU (dexamethasone intraocular suspension) 9% is the first and only intraocular corticosteroid FDA-approved for postoperative inflammation, whose sustained-release formulation provides a high initial release of drug, followed by a gradual tapering. Administration of the drug directly into the capsular bag following cataract surgery enables reliable placement proximal to target tissues, ensuring surgeon control and visibility of delivery, safety, and efficiency. This technique also minimizes contact with metabolically active tissues such as the corneal endothelium, iris, and ciliary body. In this paper, we review the available literature on dexamethasone intraocular suspension and summarize surgeons' consensus on best practices for intracapsular administration. [ABSTRACT FROM AUTHOR]

Trillions of microorganisms exist in the human intestine as commensals and contribute to homeostasis through their interactions with the immune system. In this review, we use previous evidence from published papers to elucidate the involvement of commensal-specific T cells (CSTCs) in regulating intestinal inflammatory responses. CSTCs are generated centrally in the thymus or peripherally at mucosal interfaces and present as CD4+ or CD8+ T cells. Bacteria, fungi, and even viruses act commensally with humans, warranting consideration of CSTCs in this critical relationship. Dysregulation of this immunological balance can result in both intestinal inflammation or damaging autoimmune responses elsewhere in the body. Given the relative novelty of CSTCs in the literature, we aim to introduce the importance of their role in maintaining immune homeostasis at barrier sites such as the intestine. [ABSTRACT FROM AUTHOR]

Introduction: COVID-19 poses a chronic threat to inflammatory systems, reinforcing the need for efficient anti-inflammatory strategies. The purpose of this review and analysis was to determine the efficacy of various interventions upon the inflammatory markers most affected by COVID-19. The focus was on the markers associated with COVID-19, not the etiology of the virus itself. Methods: Based on 27 reviewed papers, information was extracted on the effects of COVID-19 upon inflammatory markers, then the effects of standard treatments (Remdesivir, Tocilizumab) and adjunctive interventions (vitamin D3, melatonin, and meditation) were extracted for those markers. These data were used to approximate effect sizes for the disease or interventions via standardized mean differences (SMD). Results: The data that were available indicated that adjunctive interventions affected 68.4% of the inflammatory markers impacted by COVID-19, while standard pharmaceutical medication affected 26.3%. Discussion: Nonstandard adjunctive care appeared to have comparable or superior effects in comparison to Remdesivir and Tocilizumab on the inflammatory markers most impacted by COVID-19. Alongside standards of care, melatonin, vitamin D3, and meditation should be considered for treatment of SARS-COV-2 infection and COVID-19 disease. [ABSTRACT FROM AUTHOR]

aimin Shi,2 Suya Zhou,3 Yue Chen,4 Ming Li21Department of Intensive Care Unit, The First Affiliated Hospital of Soochow University, Soochow, People's Republic of China; 2Laboratory Nephrology, The First Affiliated Hospital of Soochow University, Soochow, People's Republic of China; 3Laboratory Nephrology, Jinshan Hospital of Fudan University, Shanghai, People's Republic of China; 4Laboratory Nephrology, The First People's Hospital of Kunshan, Soochow, People's Republic of China Correspondence: Ming Li, Email [email protected] Purpose: Changes in inflammation, immunity, and nutritional status can promote the development of chronic kidney disease (CKD), and the Naples prognostic score (NPS) reflects changes in these three general clinical parameters. Indoleamine 2.3-dioxygenase (IDO) can block the function of inflammatory cells and inhibit the production of inflammatory cytokines. We examined use of the NPS and IDO activity to predict early-stage CKD. Patients and Methods: Clinical and demographic parameters and the NPS were recorded for 47 CKD patients and 30 healthy controls. A one-way ANOVA or the rank sum test was used to compare variables in the different groups. Spearman or Pearson correlation coefficients were calculated, and logistic regression was used to identify significant factors. Receiver operating characteristic (ROC) analysis was also performed. Results: The NPS had a positive correlation with plasma IDO activity and IDO activity was lowest in controls, and increased with CKD stage. ROC analysis indicated that NPS had an area under the curve (AUC) of 0.779 when comparing controls with all CKD patients. A prediction model for CKD (− 4.847 + [1.234 × NPS] + [6.160 × plasma IDO activity]) demonstrated significant differences between controls and patients with early-stage CKD, and for patients with different stages of CKD. This model had AUC values of 0.885 (control vs CKD1– 4), 0.876 (control vs CKD2), 0.818 (CKD2 vs CKD3), and 0.758 (CKD3 vs CKD4). Conclusion: A prediction model based on the NPS and IDO provided good to excellent predictions of early-stage CKD. [ABSTRACT FROM AUTHOR]

Background: Acute kidney injury (AKI) is a medical concern that is accompanied by the rapid deterioration of kidney function. It can be triggered by lipopolysaccharide (LPS) of gram-negative bacteria as it activates a complicated immune response, resulting in widespread inflammation and potential organ dysfunction. Black seed oil (BSO) is rich in beneficial constituents and has been widely used owing to its nutritional advantages. Purpose: This research is aimed to investigate the potential protective effects of BSO and its nano-formulation on AKI induced by LPS. It also aimed to compare their anti-inflammatory activity with indomethacin, a known synthetic anti-inflammatory drug. Materials and Methods: Forty-eight mice were placed randomly into 8 groups. A single intraperitoneal (i.p.) injection of 2.5 mg/kg B.W. of LPS was used to trigger inflammation, and pretreatment with BSO and its nano-formulation was at 0.2 mL/kg/day for 14 consecutive days. Indomethacin was used as a reference drug and its efficacy was tested alone or in combination with BSO at lower doses. Renal function was assessed using urea, creatinine, neutrophil gelatinase-associated lipocalin (NGAL) and kidney injury molecule-1 (KIM-1). Also, oxidative and inflammatory markers were assessed by measuring levels of reduced glutathione (GSH), nitric oxide (NO), cyclooxygenase-2 (COX-2), tumor necrosis factor alpha (TNF-α), and toll-like receptor-4 (TLR-4). Histopathological examination of the kidney tissues was also performed. Results: The study showed that BSO and its nano-formulation had anti-inflammatory effects comparable to or better than those of indomethacin. They greatly decreased the oxidative stress and inflammatory markers induced by LPS. Their protective effect against pathological alterations in kidney tissues was significantly noticed. Conclusion: BSO and its nano-formulation could be used as nephroprotective and anti-inflammatory supplements. [ABSTRACT FROM AUTHOR]

Introduction: Recombinant humanized collagen, as a novel biomaterial, exhibits multiple excellent biological functions, such as inhibition of inflammation, promotion of cell proliferation and vascular proliferation, and promotion of tissue healing. However, there is a lack of conclusive evidence regarding the specific role of recombinant humanized collagen type 17 (rhCol 17) in oral ulcer healing. This study explored whether rhCol 17 could promote the proliferation of human gingival fibroblasts (HGFs) and inhibit its inflammation, and whether it could promote the healing of oral ulcers in rats by inhibiting inflammation and accelerating tissue healing. Methods: At the cellular level, we investigated the effect of rhCol 17 on the proliferation of (HGFs) by CCK8; HGFs were mixed with lipopolysaccharide (LPS) to investigate the effect of rhCol 17 on HGFs in an inflammatory state. Eighteen adult male Sprague-Dawley rats were randomly distributed into three groups: blank control group, carbomer group (carbomer sprayed only), and rhCol 17 group (carbomer containing rhCol 17 sprayed), 1 time/day. The samples were collected at D3 and D5. At completion, histological staining and PCR were carried out to study its effect on the healing of oral ulcers in rats. Results: Through cellular experiments, we found that rhCol 17 possesses good biocompatibility and anti-inflammatory properties, and can effectively promote the proliferation and migration of HGFs, as well as significantly reduce the inflammation level of the cells. The animal experimental results showed that rhCol 17 could significantly reduce the inflammation level, promote collagen deposition and angiogenesis at the ulcer site, thus effectively accelerating the healing of oral ulcers in rats. Conclusion: In summary, the collagen sprays containing rhCol 17 have excellent anti-inflammatory effects and could accelerate tissue healing and are expected to provide a new effective treatment for patients with recurrent oral ulcers. [ABSTRACT FROM AUTHOR]

Purpose: Total Knee Arthroplasty (TKA) is a highly invasive procedure causing severe postoperative pain, which hampers early mobility. Effective pain management is crucial for optimal recovery. This study aimed to evaluate how adductor canal block (ACB) and femoral nerve block (FNB) affect opioid use and inflammation factor levels in elderly TKA patients. Methods: This prospective observational study included 120 patients who received TKA, and divided them into three groups, based on the different nerve block technique: ACB, FNB, and no intervention before general anesthesia (CON). Postoperative opioid consumption, pain assessment, inflammation factor, knee function recovery and other clinical indicators were recorded. Results: The CON group had significantly higher cumulative sufentanil consumption compared to the ACB and FNB groups at both 12 h and 48h postoperative (P< 0.001). Compared with the CON group, the ACB and FNB groups persistently had lower pain scores until 12 h at rest and 24 h during motion after surgery. The ACB group showed significantly lower serum concentrations of C-reactive protein (CRP) and interleukin-6 (IL-6) compared to the CON group at 24 h postoperative (P=0.017, P=0.009), and IL-6 levels remained significantly lower at 72 h postoperative (P=0.005). Both ACB and FNB groups achieved earlier ambulation compared to the CON group (P=0.002). On the first day postoperative, both the ACB and FNB groups showed significantly better knee motion (P< 0.001), quadriceps strength (P< 0.001), and daily mobilization (P< 0.001) compared to the CON group. Additionally, the ACB group exhibited superior quadriceps strength (P< 0.001) and daily mobilization (P< 0.001) compared to the FNB group. Conclusion: The ACB and FNB groups exhibited comparable clinical efficacy outcomes in terms of pain scores and opioid consumption. However, the ACB group experienced reduced postoperative inflammation and improved knee recovery, especially in quadriceps strength. [ABSTRACT FROM AUTHOR]

Jianpi Qingre Tongluo Recipe (JQP) has been widely used in clinical practice, and its anti-Osteoarthritis (OA) effectiveness and specific mechanism have been concerned. This study aims to explore the clinical effect of JQP in reducing inflammation and dyslipidemia in OA and the molecular mechanism. Methods: The clinical efficacy of JQP in OA treatment was assessed through data mining. Through the network pharmacology technology, the interactive network of "active component-target-disease" was developed, the interaction relationship of the related proteins was analyzed, and enrichment analysis of gene pathway biological process was conducted. Molecular docking was carried out with PyMOL and AutodockTools-1.5.7. Finally, cell experiments were used to verify JQP's delay of immune inflammation in OA. Results: We found that JQP could ameliorate the immune inflammatory and lipid metabolism indicators; reduce VAS and SAS score in OA. A total of 98 genes overlapped between target genes of JQP and OA. TNF, IL-6, IL-1β, and AKT1 shared the highest centrality among all target genes. KEGG analysis unveiled that 98 intersection genes were predominantly enriched in PI3K/AKT pathway in the anti-OA system. In vitro, after peripheral blood mononuclear cell (PBMC) stimulation, inflammatory cytokines imbalances and the expressions of adiponectin (APN) were decreased in osteoarthritis-chondrocytes (OA-CH). Furthermore, JQP-containing serum protected OA-CHs through down-regulating HOTAIR levels, thereby up-regulating APN and depressing PI3K/AKT pathway. Conclusion: This study suggests that JQP might reduce inflammation and improve lipid metabolism of OA by regulating HOTAIR/APN/PI3K/AKT. Our results bring a new solution for OA. [ABSTRACT FROM AUTHOR]

Background: Inflammatory arthritis refers to a group of diseases that have a common presentation of joint pain, stiffness, and inflammation. Meanwhile, major depressive disorder is a mental health disorder characterized by anhedonia and low mood. Inflammatory arthritis patients have high rates of major depressive disorder, estimated at being up to 38.8%. Depression leads to a significant reduction in patient's health-related quality of life, treatment adherence, and many other measures of health, both subjective and clinical. Purpose: This literature review explores the effect that depression has on treatment response for the drugs used in inflammatory arthritis. Methods: A systematic search using PubMed was conducted identifying articles which were each reviewed for relevance and eligibility. Results: Depression was negatively associated with treatment response to all classes of drugs used to manage inflammatory arthritis, with an increased disease activity and/or number of swollen/tender joints, as well as a reduced rate of remission being recorded for patients with depression compared to those without. However, this effect on treatment response was less clear when conventional synthetic Disease Modifying Anti-rheumatic Drugs were studied, possibly because their anti-inflammatory effects have wide impacts on the whole immune system, whereas biologic Disease Modifying Anti-rheumatic Drugs have very specific targets. Conclusion: Inflammatory arthritis patients have a significantly lowered response to most drugs when they have depression. Screening and treating depression may attenuate this association. It is recommended that further research focuses on screening for and treating depression in inflammatory arthritis patients. [ABSTRACT FROM AUTHOR]

Background: Post-operative delirium (POD) is a common complication, especially in elderly patients who underwent vascular surgery procedures. The aim of this study was to evaluate the relation of inflammatory biochemical markers as neutrophil-to-lymphocyte ratio (NLR), platelet-to-lymphocyte ratio (PLR) and systemic inflammation index (SII) with POD occurrence. Methods: This was a single-center, retrospective, observational study. We analyzed the perioperative data of patients who had undergone elective vascular surgery procedures. The occurrence of delirium after procedure was used to divide the population in two groups: POD-pos and POD-neg group. ROC curves were performed to find the appropriate cut-off values of NLR, PLR and SII. Multivariate analysis was used to identify the independent predictors for POD. Results: A total of 646 patients were enrolled. Mean age was 76.2± 9.8 years, 68.4% were male. Seventy-three patients (11.3%) developed POD. Mean hospital stay was significantly increased in the POD-pos group (6.1± 5.4 vs 3.2± 2.8 days, p=0.0001). In-hospital reinterventions were more frequent in the POD-pos group (8.2% vs 3.8%). Blood values analysis reported significant differences: Hb, NLR, PLR, SII, creatinine and RCP were strongly increased (p< 0.05) in the POD-pos group. ROC curves identified cut-off values for NLR> 3.57, PLR> 139.2 and SII> 676.4. Multivariate analysis revealed that age, Renal Failure, peripheral revascularization procedures, major amputation, general anesthesia, hospitalization in the previous month, NLR> 3.57 and SII> 676.4 were independent risk factors for POD. Conclusion: POD represents a common complication of vascular surgery patients. Our study demonstrated that NLR, PLR and SII are reliable and readily available laboratory predictors of POD in vascular surgery that could help in POD risk-stratification. [ABSTRACT FROM AUTHOR]

This study aimed to explore the impact of a combination of hyperuricemia (HUA) and excessive high-sensitivity C-reactive protein (hs-CRP) levels on the likelihood of developing cardiac conduction block (CCB). Additionally, it sought to assess whether the influence of uric acid (UA) on CCB is mediated by hs-CRP. Methods: A prospective study was executed utilizing data from the Kailuan cohort, including 81,896 individuals initially free from CCB. The participants were categorized into four groups depending on the existence of HUA and low-grade inflammation (hs-CRP> 3 mg/L). Cox regression analysis was employed to ascertain hazard ratios (HRs) and 95% confidence intervals (CIs) for the risk of incident CCB. A mediation analysis was performed to determine if hs-CRP functioned as a mediator in the connection between UA levels and the incidence of CCB. Results: During a median observation period of 11.8 years, we identified 3160 cases of newly occurring CCB. Compared with the low UA/low CRP group, the combination of HUA and low-grade inflammation elevated the CCB risks (HR:1.56, 95% CI:1.22– 1.99), atrioventricular block (AVB) (HR:1.88, 95% CI:1.27– 2.77), and right bundle branch block (HR:1.47, 95% CI:1.02– 2.12), respectively. Mediation analysis revealed that in the HUA group, compared with the non-HUA group, the risk of CCB elevated by 14.0%, with 10.3% of the increase mediated through hs-CRP. Conclusion: HUA combined with elevated hs-CRP increased the risk of CCB, especially AVB. The connection between UA and the CCB risk was partly mediated by hs-CRP. [ABSTRACT FROM AUTHOR]

The United Arab Emirates (UAE), with its characteristic local population, geography, and history, presents several risk factors for cardiovascular diseases (CVDs) in obese individuals. Obesity and its associated complications, including diabetes, atherogenic dyslipidemia, and CVDs leading to significant health risks. In the present study, "Youths" defined as young people between 18 and 22 years. We assessed dyslipidemia, inflammation, and oxidative stress biomarker levels and their association with endothelial dysfunction (ED) in both overweight/obese and normal weight youths of UAE. Methods: There were 160 youths with overweight/obese (BMI ≥ 25 kg/m2) patients and healthy age- and sex-matched normal weight (BMI ≤ 24.9 kg/m2) as controls participated in this study. The anthropometric data and blood samples were collected to assess the biomarkers for dyslipidemia, inflammation, oxidative stress, ED from all the youths. Results: The overall mean age and male-to-female ratio were 20± 1.5years and 1.0:1.2, respectively. There was statistically significant difference in HDL-C (p< 0.001), triglycerides (TG) (p< 0.001), ApoA (p=0.002), ApoB/ApoA ratio (p=0.009) between the overweight/obese and normal weight youths. Among, inflammatory markers: hs-CRP, IL-6, TNF-α also showed significant p< 0.001 and oxidative stress markers: DNA/RNA Damage, catalase and nitric oxide (NO) showed significant p< 0.001 between groups. Spearman correlation of ED markers with lipid profile markers showed Vitamin C levels positively correlated with HDL-C (p< 0.001) and negatively correlated with glucose (p< 0.001). ICAM-1showed significant negative correlation with HDL-C (p< 0.01) and ApoA (p< 0.001) but positive correlation with TG (p< 0.01) and HbA1c (p< 0.001) among groups. Spearman correlation of ED markers with inflammatory/oxidative stress biomarkers showed Vitamin C levels negatively correlated with ferritin (p < 0.001), NO (p < 0.001), GGT (p < 0.001), and ALT (p < 0.001) levels. The ICAM-1showed significant positive correlation with hs-CRP (p < 0.01), IL-6 (p < 0.001), TNF-α (p < 0.01), GGT (p < 0.05), and ALT (p < 0.05) in both groups. Conclusion: This study revealed a strong link between the biomarkers of dyslipidemia, inflammation, and oxidative stress with ED in overweight/obese patients. This study might be used to predict future cardiovascular events in this population. [ABSTRACT FROM AUTHOR]

Purpose: We aimed to investigate the efficacy of a combined herbal formula and electroacupuncture (EA) for mild cognitive impairment (MCI), a neurodegenerative disease leading to dementia, and its underlying mechanisms of action. Patients and Methods: This was a prospective open-label observational pilot study at Daejeon Korean Medicine Hospital of Daejeon University in South Korea from March 2022 to March 2023. We included six Korean patients (50% male) aged ≥ 45 years and < 85 years with MCI, a clinical dementia rating score of 0.5, and a Montreal Cognitive Assessment-Korea (MoCA-K) score ≤ 22. The exclusion criterion was impaired cognitive function. Patients received combined therapy, including a herbal formula and EA, for 12– 24 weeks. We prescribed the herbal formulas Gamiguibi-tang, Yukmijihwang-tang, and Banhasasim-tang to the patients for at least 70% of the treatment period, in combination with EA. Moreover, we investigated changes in cognitive and cognition-related symptoms and cytokine expression in the blood following combined traditional medicine therapy. At baseline and after 12 and 24 weeks, we administered the MoCA-K and cognitive-related questionnaires. We analyzed network pharmacology to reflect the herbal formula intervention mechanism comprehensively. Results: The median score [interquartile range] of MoCA-K at baseline was 19.5 [16.0, 22.0], which improved significantly (24.5 [24.0, 26.0], p < 0.01) over 24 weeks following combined therapy. We obtained no significant conclusion regarding cytokine changes due to the small sample size. In network pharmacology, we analyzed the brain, head, heart, peripheral nerves, peripheral nervous system, and pancreas as the enriched organs from the common targets of the three herbal formulas. Conclusion: Combined herbal medicine and EA improved cognitive function in patients with MCI. We assume the underlying mechanism of herbal formulas to be antioxidative and anti-inflammatory changes in cytokine expression. Combined traditional medicine has potential therapeutic application in preventing MCI progression to dementia. Plain Language Summary: This was a single-centered study focusing on the therapeutic effect of combined herbal medicine and electroacupuncture in patients with mild cognitive impairment, including a small number of participants, a relatively long treatment intervention of 12 weeks, and a follow-up assessment of 24 weeks. The intervention was a combination of a herbal formula and electroacupuncture treatment customized for each participant. The blood cytokine analyses of the participants were compared with the network analysis of the predicted target organs and pathways for the herbal formulas administered. Because each participant was not given the exact same intervention, we were unable to identify the specific treatment that produced the predicted effect. The observational study design of the study limited the ability to accurately assess causation between intervention and outcome. However, combined traditional medicine has potential therapeutic application in preventing mild cognitive impairment progression to dementia. [ABSTRACT FROM AUTHOR]

Purpose: Vitamin D deficiency is a common finding in geriatric patients. The ESPEN micronutrient guideline states that vitamin D serum levels significantly decrease in the presence of inflammation and should be interpreted with caution. This is of great interest for hospital care and would imply a significant change to the current approach to hospitalized patients with suspected vitamin D deficiency. Patients and methods: To evaluate the association of vitamin D and inflammation, we reanalyzed the data set of serum 25(OH)D-Levels of 687 consecutive geriatric hospitalized patients of a previously published study. Results: We found that vitamin D deficiency (< 20 ng/dl) was prevalent in 78.0% and vitamin D insufficiency (20– 30 ng/dl) in 9.9% of patients. Sperman's correlation showed a significant but very weak correlation (R = − 0.100, P < 0.01) of serum vitamin D and C-reactive protein. However, linear regression with the inclusion of age and gender revealed no significant association (beta-coefficient − 0.070; p=0.067). Conclusion: In this study, we could not confirm a significant and clinically relevant association between serum vitamin D levels and inflammation, contrasting with a previous study. However, longitudinal studies need to be performed to draw a final conclusion. [ABSTRACT FROM AUTHOR]

In recent years, obesity has become one of the major diseases that affect human health and consume human health resources, especially when it causes comorbidities such as hypertension, diabetes, cardiovascular disease and kidney disease. Many studies have demonstrated that obesity is associated with the development of chronic kidney disease and can exacerbate the progression of end-stage renal disease. This review described the mechanisms associated with the development of obesity-associated nephropathy and the current relevant therapeutic modalities, with the aim of finding new therapeutic targets for obesity-associated nephropathy. The mechanisms of obesity-induced renal injury include, in addition to the traditional alterations in renal hemodynamics, the involvement of various mechanisms such as macrophage infiltration in adipose tissue, alterations in adipokines (leptin and adiponectin), and ectopic deposition of lipids. At present, there is no "point-to-point" treatment for obesity-induced kidney injury. The renin-angiotensin-aldosterone system (RAAS) inhibitors, sodium-dependent glucose transporter 2 (SGLT-2) inhibitors and bariatric surgery described in this review can reduce urinary protein to varying degrees and delay the progression of kidney disease. In addition, recent studies on the therapeutic effects of intestinal flora on obesity may reduce the incidence of obesity-related kidney disease from the perspective of primary prevention. Both of these interventions have their own advantages and disadvantages, so the continuous search for the mechanism of obesity-induced related kidney disease will be extremely helpful for the future treatment of obesity-related kidney disease. [ABSTRACT FROM AUTHOR]

Background: Intrahepatic cholangiocarcinoma (ICC) correlates with poor outcomes, necessitating the identification of prognostic factors from an inflammation-nutritional perspective in locally advanced ICC patients after R0 resection. Methods: We retrospectively reviewed the medical records of 159 locally advanced ICC patients from Sun Yat-sen University Cancer Center. Univariate and multivariate Cox regression analysis, as well as competing risk analysis, were conducted to explore prognostic variables for locally advanced ICC following surgery. To validate the robustness of our findings, we performed propensity score matching (PSM) analyses to evaluate survival differences based on inflammation-nutritional indexes. Results: Considering non-cancer-specific death as competing risk factors, both systemic immune-inflammation index (SII, HR: 1.934) and prognostic nutrition index (PNI, HR: 0.604) emerged as significant prognostic variables for locally advanced ICC after R0 resection (P < 0.05). After PSM, the survival benefit between the low and high PNI sets remained clear (median survival time: 15.7 months vs 35.1 months, P = 0.002). Although the 5-year overall survival (OS) rate of the low SII group was higher than that of the high SII group, the difference was not statistically significant (17.5% VS 27.4%, P = 0.112). Other influencing factors included tumor number, tumor diameter, preoperative carcinoembryonic antigen (CEA)and carbohydrate antigen 19– 9 (CA19-9) levels, and postoperative adjuvant therapy. Conclusion: Individual inflammatory and nutritional status significantly impact the prognosis of locally advanced ICC undergoing R0 hapectomy. Oncologists should consider incorporating inflammation-nutritional conditions into the decision-making process for this subset of advanced ICC. [ABSTRACT FROM AUTHOR]

GDF-15 is an essential member of the transforming growth factor-beta superfamily. Its functions mainly involve in tissue injury, inflammation, fibrosis, regulation of appetite and weight, development of tumor, and cardiovascular disease. GDF-15 is involved in various signaling pathways, such as MAPK pathway, PI3K/AKT pathway, STAT3 pathway, RET pathway, and SMAD pathway. In addition, several factors such as p53, ROS, and TNF-α participate the regulation of GDF-15. However, the specific mechanism of these factors regulating GDF-15 is still unclear and more research is needed to explore them. GDF-15 mainly improves the function of kidneys in CKD and plays an important role in the prediction of CKD progression and cardiovascular complications. In addition, the role of GDF-15 in the kidney may be related to the SMAD and MAPK pathways. However, the specific mechanism of these pathways remains unclear. Accordingly, more research on the specific mechanism of GDF-15 affecting kidney disease is needed in the future. In conclusion, GDF-15 may be a therapeutic target for kidney disease. [ABSTRACT FROM AUTHOR]

Introduction: Diabetes and obesity are momentous risk factors threatening people's lives and health. Currently available incretin analogue glucagon-like peptide 1 (GLP-1) possesses huge hypoglycemic effect with the unsatisfactory effect of weight loss. Co-agonists targeting GLP-1R plus glucagon receptor (GCGR) or gastric inhibitory polypeptide receptor (GIPR) show synergistic benefits in glycaemic control and weight loss. Here, we describe a novel dual GIP and GLP-1 receptor agonist, DR10627, and performed a preclinical assessment of it. Methods: The agonistic ability of DR10627 was indirectly assessed by inducing cAMP accumulation in Chinese hamster ovary (CHO) cells transfected with GLP-1R or GIPR in vitro. The plasma pharmacokinetics of DR10627 were analysed in cynomolgus monkeys. The OGTTs were performed in Sprague‑Dawley (SD) rats. The glucose lowering effects were evaluated by repeated administration of DR10627 in diabetic (db/db) mice for 4 weeks. The effects of anti-obesity and improving metabolism of DR10627 were evaluated by repeated administration of DR10627 in diet-induced obesity (DIO) mice for 57 days. Results: DR10627 had the capacity to activate both GLP-1R and GIPR in vitro. The terminal half-life of DR10627 was found to be approximately 4.19– 5.8 h in cynomolgus monkeys. DR10627 had a great improvement in oral glucose tolerance in SD rats. Moreover, DR10627 had a potent glucose-lowering effect in db/db mice, and the hypoglycemic effect of 18 nmol/kg DR10627 was better than that of 50 nmol/kg liraglutide. In addition, 10 and 30 nmol/kg DR10627 possessed the ability of potentiating the weight-loss, lipid-lowing efficacy and improving metabolism to a greater extent than 80 nmol/kg liraglutide. Conclusion: Preclinical assessment demonstrated that administration of DR10627 resulted in glucose lowering in SD rats and db/db mice, and substantial body weight reduction and metabolism improvement in DIO mice. DR10627 is a promising agent deserving further investigation for the treatment of type 2 diabetes and obesity. [ABSTRACT FROM AUTHOR]

Background: Frostbite is a chemia resulting from cold-induced skin damage. The process of frostbite is often accompanied by inflammation, and the therapeutic strategies focusing on anti-inflammation are the main direction to data. Tat-CIRP is a 15 amino acid peptide containing HIV protein and cold-inducible RNA-binding protein (CIRP), which is believed to compete with endogenous CIRP for myeloid differentiation 2 (MD2) binding. This study aims to investigate the efficacy of Tat-CIRP in the treatment of frostbite. Methods: A mouse model of frostbite was established, and on the first day after frostbite occurrence, Tat-CIRP peptide was administered intravenously via the tail with a dosage interval of one day for a total of three doses. Frozen mouse skin sections were subjected to histological analysis, including hematoxylin–eosin (HE) staining, Masson staining, and immunohistochemical examination. Western blotting was performed to detect the expression level of Ki-67 in mouse skin tissue. Results: One day after frostbite, mice exhibited skin swelling and a solid appearance. From day 1 to 5 after frostbite, MD2 expression was significantly upregulated, while CIRP expression was downregulated. Compared to the frostbite group, mice treated with Tat-CIRP showed accelerated frostbite recovery, reduced levels of inflammatory factors and MD2. Furthermore, the expression of cell proliferation-associated protein Ki-67 and angiogenesis-related protein CD31 was upregulated. Conclusion: Tat-CIRP promotes frozen wound healing via inhibiting inflammation and promoting angiogenesis in frostbitten mice. [ABSTRACT FROM AUTHOR]

Purpose: The activation of the inflammatory response is regarded as a pivotal factor in the pathogenesis of TBI. Central nervous system infection often leads to the exacerbation of neuroinflammation following TBI, primarily caused by Gram-negative bacteria. This study aims to elucidate the effects of the novel anti-inflammatory drug TAK-3 on LPS-induced neuroinflammation in TBI rats. Methods: In conjunction with the rat controlled cortical impact model, we administered local injections of Lipopolysaccharide to the impact site. Subsequently, interventions were implemented through intraperitoneal injections of TAK-3 and NF-κB activitor2 to modulate the TLR4/NF-κB axis The impact of LPS on neurological function was assessed using mNSS, open field test, and brain water content measurement. Inflammatory markers, including TNF-α, IL-1β, IL-6 and IL-10 were assessed to evaluate the condition of neuritis by Elisa. The activation of the TLR-4/NF-κB signaling pathway was detected by immunofluorescence staining and Western blot to assess the anti-inflammatory effects of TAK-3. Results: The administration of LPS exacerbated neurological damage in rats with TBI, as evidenced by a reduction in motor activity and an increase in anxiety-like behavior. Furthermore, LPS induced disruption of the blood-brain barrier integrity and facilitated the development of brain edema. The activation of microglia and astrocytes by LPS at the cellular and molecular levels has been demonstrated to induce a significant upregulation of neuroinflammatory factors. The injection of TAK-3 attenuated the neuroinflammatory response induced by LPS. Conclusion: The present study highlights the exacerbating effects of LPS on neuroinflammation in TBI through activation of the TLR-4/NF-κB signaling pathway. TAK-3 can modulate the activity of this signaling axis, thereby attenuating neuroinflammation and ultimately reducing brain tissue damage. [ABSTRACT FROM AUTHOR]

Objective of this study is to investigate GAC1 effect on neutrophil-dominant, steroid-resistant asthma in a murine model. Methods: In this study, Balb/c mice were systematically sensitized with ragweed (RW) and alum and intranasally challenged with ragweed. Unsensitized/PBS challenged mice served as normal controls. Post sensitization, mice were given 4 weeks of oral treatment with GAC1 or acute dexamethasone (Dex) treatment at 48 hours prior to challenge. Pulmonary cytokines were measured by ELISA, and lung sections were processed for histology by H&E staining. Furthermore, GAC1 effect on MUC5AC expression and on reactive oxygen species (ROS) production in human lung epithelial cell line (NCI-H292) was determined by qRT-PCR and ROS assay kit, respectively. Computational analysis was applied to select potential targets of GAC1 in steroid-resistant neutrophil-dominant asthma. Molecular docking was performed to predict binding modes between GAC1 and Dex with TNF-α. Results: The result of the study showed that chronic GAC1 treatment, significantly reduced pulmonary inflammation (P < 0.01– 0.001 vs Sham) and airway neutrophilia (P < 0.01 vs Sham), inhibited TNF-α, IL-4 and IL-5 levels (P < 0.05– 0.001 vs Sham). Acute Dex treatment reduced eosinophilic inflammation and IL-4, IL-5 levels, but had no effect on neutrophilia and TNF-α production. GAC1 treated H292 cells showed decreased MUC5AC gene expression and production of ROS (P < 0.001 vs stimulated/untreated cells). Molecular docking results showed binding energy of complex GAC1-TNF was − 10.8 kcal/mol. Discussion: GAC1 may be a promising anti-asthma botanical drug for treatment of steroid-resistant asthma. [ABSTRACT FROM AUTHOR]

Objectives of this approach are to mitigate postoperative pain, enhance patient satisfaction, and diminish overall opioid usage. Nevertheless, there is a scarcity of research on the use of remote ischemia preconditioning aimed at mitigating postoperative pain. Recent Findings: Transient stoppage of blood flow to an organ has been found to elicit remote ischemia preconditioning (RIPC), which serves as a potent intrinsic mechanism for protecting numerous organs. In addition to its established role in protecting against reperfusion injury, RIPC has recently been identified as having potential benefits in the context of postoperative analgesia. Summary: In addition to traditional perioperative analgesia, RIPC provides perioperative analgesia and organ protection. [ABSTRACT FROM AUTHOR]

To clarify the potential mechanism of PCs to HUVECs induced by the serum of HSP patients. Methods: HUVECs were randomly divided into blank, control, model, and low-, medium-, and high-concentration PCs group. Then, 25% HSP serum was assigned to the latter four groups, while 25% serum from healthy subjects to control group and serum-free culture medium to blank one. The last three groups separately received different concentrations of PCs. In addition, TAK-242, a TLR4 inhibitor, was applied to investigate the effect of TLR4-related signals in PCs against HSP serum-induced damage. Finally, inflammatory and OS-related parameters were detected by using cytological/molecular-biological techniques. Results: Treated with HSP serum later, the levels of immuno-inflammatory and oxidative indicators obviously went up (P < 0.05), and those of antioxidants remarkably went down (P < 0.05). PCs, however, reversed above phenomena (P < 0.05). Moreover, TLR4, MyD88 and NF-κB proteins/genes highly expressed in the model group; but significantly fell off in the presence of PCs (P < 0.05). Amazingly, all of above indicators showed no significant difference among the groups of different PCs concentrations (P > 0.05). These alterations likewise occurred after TAK-242 pretreatment with or without PCs, ie a notable drop of TLR4, MyD88 and NF-κB appeared in TAK-242 presence, few differences existing when compared to the PCs groups. Conclusion: PCs effectively protect HUVECs from inflammatory and OS damage provoked by HSP serum via blocking TLR4/MyD88/NF-κB signals. [ABSTRACT FROM AUTHOR]

Gouty arthritis (GA) is an immune-mediated disorder characterized by severe inflammation due to the deposition of monosodium urate (MSU) crystals in the joints. The pathophysiological mechanisms of GA are not yet fully understood, and therefore, the identification of effective therapeutic targets is of paramount importance. Neutrophil extracellular traps (NETs), an intricate structure of DNA scaffold, encompassing myeloperoxidase, histones, and elastases - have gained significant attention as a prospective therapeutic target for gouty arthritis, due to their innate antimicrobial and immunomodulatory properties. Hence, exploring the therapeutic potential of NETs in gouty arthritis remains an enticing avenue for further investigation. During the process of gouty arthritis, the formation of NETs triggers the release of inflammatory cytokines, thereby contributing to the inflammatory response, while MSU crystals and cytokines are sequestered and degraded by the aggregation of NETs. Here, we provide a concise summary of the inflammatory processes underlying the initiation and resolution of gouty arthritis mediated by NETs. Furthermore, this review presents an overview of the current pharmacological approaches for treating gouty arthritis and summarizes the potential of natural and synthetic product-based inhibitors that target NET formation as novel therapeutic options, alongside elucidating the intrinsic challenges of these inhibitors in NETs research. Lastly, the limitations of HL-60 cell as a suitable substitute of neutrophils in NETs research are summarized and discussed. Series of recommendations are provided, strategically oriented towards guiding future investigations to effectively address these concerns. These findings will contribute to an enhanced comprehension of the interplay between NETs and GA, facilitating the proposition of innovative therapeutic strategies and novel approaches for the management of GA. [ABSTRACT FROM AUTHOR]

The purpose of the study was to investigate the expression levels and correlation of inflammatory factors such as miR-377-3p and TGF-β in patients with diabetic kidney disease (DKD), and to investigate the regulatory mechanism of transfection of miR-377-3p on the inflammatory response of HK-2 cell induced by high glucose. Methods: According to UACR, patients were divided into normal albuminuria group (Con, n = 29), microalbuminuria group (Micro, n = 31) and macroalbuminuria group (Macro, n = 30), analyzed the correlation and influencing factors between DKD and inflammatory factor. HK-2 cells were randomly divided into four groups: normal control group (NC), high glucose group (HG), miR-377-3p overexpression group (MIN), and miR-377-3p inhibition group (IN). After transfection of miR-377-3p mimics and inhibitors, the contents of TGF-β, IL-6 and IL-18 were detected by RT-PCR and Western blot. Results: The levels of miR-377-3p, TGF-β, IL-6 and IL-18 in both Micro group and Macro group were significantly higher than those in Con group (P < 0.05); Pearson correlation analysis showed that miR-377-3p was positively correlated with UACR, TG, TGF-β, IL-6 and IL-18, and negatively correlated with GFR (P < 0.05). Cell experiment: RT-PCR and Western blot results showed that miR-377-3p, TGF-β, IL-6 and IL-18 in HG group were significantly higher than those in NC group (P < 0.05). After transfection with miR-377-3p inhibitor, the levels of miR-377-3p, TGF-β, IL-6 and IL-18 in IN group were significantly decreased compared with HG group and MIN group. Conclusion: miR-377-3p expression was elevated both in serum of DKD patients and in HK-2 cells with high glucose induced injury, overexpression of miR-377-3p exacerbates the damage to HK-2 cells and promotes the progression of DKD. Silencing miR-377-3p can potentially regulate the levels of inflammatory factors in HK-2 cells by targeting downregulation of TGF-β expression, thereby mitigating the damage to HK-2 cells and delaying the development of diabetic kidney disease. [ABSTRACT FROM AUTHOR]

After exposure to a viral pathogen, the host–pathogen interaction is essential to determine whether or not infection will ensue, and what the clinical outline of the infection will be. Recent research has shown that the patient with obesity presents a set of particular pathophysiological changes that lead to higher severity of viral infections, and this is particularly true for infection with influenza viruses. Herein, we describe the main metabolic, endocrine, and immune dysregulations that occur in the presence of obesity and their impact on driving intra-host viral diversity, leading to heightened severity and virulence of influenza. We show that obesity is linked to modified responses of both the innate and adaptive immune systems during viral infections, including influenza. Due to chronic inflammation and metabolic, endocrine, and signaling pathway disruptions, individuals with obesity have a suboptimal immune response. This results in longer illness duration, increased virus shedding, higher risk of hospitalization and complications, and greater mortality rates. Additionally, they may have a blunted response to vaccination and a higher likelihood of genetic mutation selection. Understanding the intricate interplay between obesity and viral pathogenesis is crucial for developing efficacious therapeutic approaches and public health policies, particularly in light of the escalating worldwide incidence of obesity. [ABSTRACT FROM AUTHOR]

Background: Psoriasis is a frequent form of chronic inflammation in dermatology that is unmistakably linked to the metabolic syndrome (MetS) and its elements. This study was to explore the current status and new developments in the global research, and the holistic landscape of this field more intuitively through bibliometric analysis of scientific output and activity. Methods: Publications regarding psoriasis and MetS were searched and chosen from the database of the Web of Science Core Collection. Excel 2019, VOSviewer, and CiteSpace software were utilized to conduct bibliometric analysis. Results: There were 1096 publications included. The scientific outputs in this field had increased from 2004 to 2022, and the expansion could continue in the following years. The United States contributed the most publications (241, 21.99%) and had the most citation frequency (13,489 times). The University of California System was the most productive affiliation. Girolomoni G., Armstrong A.W., Gisondi P. and Gelfand J.M. were key and influential researchers. Journal of the European Academy of Dermatology and Venereology published the greatest number of articles (65 articles). By analyzing keyword frequency and clustering, we have identified the following areas of research interest and frontiers: prevalence, risk, association, gene expression, waist circumference, adipose tissue inflammation, vascular inflammation, cardiovascular disease, psoriatic arthritis, and fibrosis. Conclusion: This bibliometric analysis elucidates research domain of psoriasis and MetS, portraying present hotspots and future emerging trends. This field has generated significant interest and displays potential for further growth. The United States has made distinguished contributions, and currently dominates this field. [ABSTRACT FROM AUTHOR]

Substantial evidence has recently been gathered to substantiate the epidemiological correlation between this oral inflammatory ailment and several systemic health disorders, such as cardiovascular diseases (CVDs). It is worth noting that certain shared factors exist among individuals with periodontal disease (PD) and CVDs, like obesity or overweight, minimal physical activities, smoking habits, male gender, low socioeconomic position, advanced age, and limited educational attainment. Moreover, recent research suggests a distinct and separate relationship between PD and CVDs. This literature review discusses the association between CVDs and PD and their underlying mechanisms and connections. Current literature strongly confirms a correlation between cardiovascular risk and PD. The underlying mechanisms involve inflammation, epigenetics, epithelial dysfunction, oral microbiome dysbiosis, and the efficacy of periodontitis treatment. Future investigations are required to comprehend these complex interactions and develop targeted interventions for oral health improvement and reduction in cardiovascular risk. [ABSTRACT FROM AUTHOR]

Rhinosinusitis (RS) is an acute (ARS) or chronic (CRS) inflammatory disease of the nasal and paranasal sinus mucosa. CRS is a heterogeneous condition characterized by distinct inflammatory patterns (endotypes) and phenotypes associated with the presence (CRSwNP) or absence (CRSsNP) of nasal polyps. Mucosal barrier and mucociliary clearance dysfunction, inflammatory cell infiltration, mucus hypersecretion, and tissue remodeling are the hallmarks of CRS. However, the underlying factors, their priority, and the mechanisms of inflammatory responses remain unclear. Several hypotheses have been proposed that link CRS etiology and pathogenesis with host (eg, "immune barrier") and exogenous factors (eg, bacterial/fungal pathogens, dysbiotic microbiota/biofilms, or staphylococcal superantigens). The abnormal interplay between these factors is likely central to the pathophysiology of CRS by triggering compensatory immune responses. Here, we discuss the role of the sinonasal microbiota in CRS and its biofilms in the context of mucosal zinc (Zn) deficiency, serving as a possible unifying link between five host and "bacterial" hypotheses of CRS that lead to sinus mucosa remodeling. To date, no clear correlation between sinonasal microbiota and CRS has been established. However, the predominance of Corynebacteria and Staphylococci and their interspecies relationships likely play a vital role in the formation of the CRS-associated microbiota. Zn-mediated "nutritional immunity", exerted via calprotectin, alongside the dysregulation of Zn-dependent cellular processes, could be a crucial microbiota-shaping factor in CRS. Similar to cystic fibrosis (CF), the role of SPLUNC1-mediated regulation of mucus volume and pH in CRS has been considered. We complement the biofilms' "mechanistic" and "mucin" hypotheses behind CRS pathogenesis with the "structural" one – associated with bacterial "corncob" structures. Finally, microbiota restoration approaches for CRS prevention and treatment are reviewed, including pre- and probiotics, as well as Nasal Microbiota Transplantation (NMT). [ABSTRACT FROM AUTHOR]

Purpose: The purpose of this study was to analyze the nasal lymphatic system in order to uncover novel factors that might be involved in pathogenesis of chronic rhinosinusitis (CRS) with (CRSwNP) and without nasal polyps (CRSsNP). Patients and Methods: Lymphatic vessels (LVs) and macrophages were localized and counted in the inferior and middle turbinate, the uncinate process and the ethmoid of CRSwNP and CRSsNP patients, the NP and the inferior turbinate of controls (n≥ 6 per group). Lysates of the same tissue types (n=7 per group) were analyzed for lymphatic vessel endothelial receptor 1 (LYVE-1), for matrix metalloproteinase 14 (MMP-14) and for Hyaluronic acid (HA) using ELISA. HA was localized in sections of CRSwNP NP, CRSsNP ethmoid and control inferior turbinate (n=6 per group). The results of HA levels were correlated to the number of macrophages in tissues. The nasal secretions of CRSwNP (n=28), CRSsNP (n=30), and control (n=30) patients were analyzed for LYVE-1 and HA using ELISA. Results: The number of LVs was significantly lower in tissues of both CRS groups compared to the control. In the tissue lysates, LYVE-1 expression differed significantly between the CRSwNP tissues with a particularly high level in the NP. MMP-14 was significantly overexpressed in CRSwNP uncinate process. There were no significant differences in tissue HA expression. In the mucus LYVE-1 was significantly underexpressed in CRSsNP compared to CRSwNP and control, while HA was significantly underexpressed in both CRS groups. In the NP, HA and macrophages were accumulated particularly below the epithelium. Tissue levels of HA revealed a significant positive correlation with the number of macrophages. Conclusion: CRS might be associated with an insufficient clearing of the nasal mucosa through the lymphatics. The accumulation of HA and macrophages might promote inflammation, fluid retention, and polyp formation. These results may provide novel CRS-associated factors. [ABSTRACT FROM AUTHOR]

Background: Granulomatous lobular mastitis (GLM) is a chronic inflammatory breast disease, and abscess formation is a common complication of GLM. The process of abscess formation is accompanied by changes in multiple inflammatory markers. The present study aimed to construct a diagnosis model for the early of GLM abscess formation based on multiple inflammatory parameters. Methods: Based on the presence or absence of abscess formation on breast magnetic resonance imaging (MRI), 126 patients with GLM were categorised into an abscess group (85 patients) and a non-abscess group (41 patients). Demographic characteristics and the related laboratory results for the 9 inflammatory markers were collected. Logistics univariate analysis and collinearity test were used for selecting independent variables. A regression model to predict abscess formation was constructed using Logistics multivariate analysis. Results: The univariate and multivariate analysis showed that the N, ESR, IL-4, IL-10 and INF-α were independent diagnostic factors of abscess formation in GLM (P< 0. 05). The nomogram was drawn on the basis of the logistics regression model. The area under the curve (AUC) of the model was 0.890, which was significantly better than that of a single indicator and the sensitivity and specificity of the model were high (81.2% and 85.40%, respectively). These results predicted by the model were highly consistent with the actual diagnostic results. The results of this calibration curve indicated that the model had a good value and stability in predicting abscess formation in GLM. The decision curve analysis (DCA) demonstrated a satisfactory positive net benefit of the model. Conclusion: A predictive model for abscess formation in GLM based on inflammatory markers was constructed in our study, which may provide a new strategy for early diagnosis and treatment of the abscess stage of GLM. [ABSTRACT FROM AUTHOR]

Purpose: There are some challenges to diagnosis in the context of similar diagnostic criteria for late-life depression (LLD) and adult depression due to cognitive impairment and other clinical manifestations. The association between gut microbiota and inflammation remains unclear in LLD. We analyzed gut microbiota characteristics and serum inflammatory cytokines in individuals with LLD to explore the combined role of these two factors in potential biomarkers of LLD. Methods: This was an observational cross-sectional study. Fecal samples and peripheral blood from 29 patients and 33 sex- and age-matched healthy controls (HCs) were collected to detect gut microbiota and 12 inflammatory factors. We analyzed differences in diversity and composition of gut microbiota and evaluated relations among gut microbiota, inflammatory factors, and neuropsychological scales. We extracted potential biomarkers using receiver-operating characteristic curve analysis to predict LLD utilizing the combination of the microbiota and inflammatory cytokines. Results: Elevated systemic inflammatory cytokine levels and gut microbiota dysbiosis were found in LLD patients. Relative abundance of Verrucomicrobia at the phylum level and Megamonas, Citrobacter, and Akkermansia at the genus level among LLD patients was lower than HCs. Abundance of Coprococcus, Lachnobacterium, Oscillospira, and Sutterella was higher in LLD patients. Notably, IL6, IFNγ, Verrucomicrobia, and Akkermansia levels were correlated with depression severity. Our study identified IL6, Akkermansia, and Sutterella as predictors of LLD, and their combination achieved an area under the curve of 0.962 in distinguishing LLD patients from HCs. Conclusion: This research offers evidence of changes within gut microbiota and systemic inflammation in LLD. These findings possibly help elucidate functions of gut microbiota and systemic inflammation in LLD development and offer fresh ideas on biomarkers for clinical practise in the context of LLD. [ABSTRACT FROM AUTHOR]

Purpose: Acute lung injury (ALI) is a severe pulmonary disease characterized by damage to the alveoli and pulmonary blood vessels, leading to severe impairment of lung function. Studies on the effect of capsaicin (8-methyl-N-geranyl-6-nonamide, CAP) on lipopolysaccharide (LPS)-induced ALI in bronchial epithelial cells transformed with Ad12-SV40 2B (BEAS-2B) are still limited. This study aimed to investigate the effect and specific mechanism by which CAP improves LPS-induced ALI.Methods: The present study investigated the effect of CAP and the potential underlying mechanisms in LPS-induced ALI in vitro and vivo via RNA sequencing, Western blotting (WB), quantitative real-time reverse transcription PCR (qRT‒PCR), enzyme-linked immunosorbent assay (ELISA), and transmission electron microscopy (TEM). The TRPV1 inhibitor AMG9810 and the AKT agonist SC79 were used to confirm the protective effect of the TRPV1/AKT axis against ALI. The autophagy agonist rapamycin (Rapa) and the autophagy inhibitors 3-methyladenine (3-MA) and bafilomycin A1 (Baf-A1) were used to clarify the characteristics of LPS-induced autophagy.Results: Our findings demonstrated that CAP effectively suppressed inflammation and autophagy in LPS-induced ALI, both in vivo and in vitro. This mechanism involves regulation by the TRPV1/AKT signaling pathway. By activating TRPV1, CAP reduces the expression of P-AKT, thereby exerting its anti-inflammatory and inhibitory effects on pro-death autophagy. Furthermore, prior administration of CAP provided substantial protection to mice against ALI induced by LPS, reduced the lung wet/dry ratio, decreased proinflammatory cytokine expression, and downregulated LC3 expression.Conclusion: Taken together, our results indicate that CAP protects against LPS-induced ALI by inhibiting inflammatory responses and autophagic death through the TRPV1/AKT signaling pathway, presenting a novel strategy for ALI therapy. [ABSTRACT FROM AUTHOR]

The text "The authors report no conflicts of interest in this work" should read "Virgil I Stenberg reports that he is the Research Director at the Helen Foundation. Read the original articlePrevious corrigendum has been published Irwin JB, Baldwin AL, Stenberg VI. [Extracted from the article]