Inflammatory Pathways Research Articles

Mitigative Effect and Mechanism of Caffeic Acid Combined with Umbilical Cord-Mesenchymal Stem Cells on LPS-Induced Mastitis.

Mastitis is an inflammation of the mammary gland tissue that can lead to decreased milk production and altered milk composition, carrying serious implications for the safety of dairy products. Although both caffeic acid (CA) and umbilical cord-mesenchymal stem cells (UC-MSCs) showed potential anti-inflammatory and immunomodulatory properties, little is known about their combined roles in treating mastitis. Here, we report the combined effects and mechanisms of CA and UC-MSCs on lipopolysaccharide (LPS)-induced mastitis. Based on the network pharmacological analysis, the potential relevant genes involved in the alleviating effects of CA on LPS-induced mastitis were inferred. In LPS-treated mammary epithelial cells, CA or/and UC-MSC conditioned medium (UC-MSC-CM) inhibited the phosphorylation of p65, p50, p38, IκB, and MKK3/6 proteins and the expression of downstream inflammatory factors TNF-α, IL-1β, IL-6, IL-8, and COX-2. Additionally, CA or/and hydrogel-loaded UC-MSCs also suppressed the activation of the above inflammatory pathway, leading to the alleviation of pathological damages in the LPS-induced mouse mastitis model. UC-MSCs exhibited more significant effects than CA, and the combined treatment of both was more effective. Our study sheds light on the synergistic and complementary effects of CA and UC-MSCs in alleviating mastitis, offering clues for understanding the regulation of the p38-MAPK/NF-κB↔TNF-α signal transduction loop in the tumor necrosis factor (TNF) pathway as a potential mechanism. This study provides a theoretical basis for developing a novel antibiotic alternative treatment of mastitis that may contribute to reducing economic losses in animal husbandry and protecting public health safety.

Novel Therapeutics and Upcoming Clinical Trials Targeting Inflammation in Cardiovascular Diseases.

Cardiovascular disease (CVD) remains a major health burden despite significant therapeutic advances accomplished over the last decades. It is widely and increasingly recognized that systemic inflammation not only represents a major cardiovascular risk and prognostic factor but also plays pivotal roles in CVD development and progression. Despite compelling preclinical evidence suggesting large potential of anti-inflammatory pharmacological interventions across numerous CVDs, clinical translation remains incomplete, mainly due to (1) yet undefined molecular signaling; (2) challenges of safety and efficacy profile of anti-inflammatory drugs; and (3) difficulties in identifying optimal patient candidates and responders to anti-inflammatory therapeutics, as well as optimal therapeutic windows. Randomized controlled trials demonstrated the safety/efficacy of canakinumab and colchicine in secondary cardiovascular prevention, providing confirmation for the involvement of a specific inflammatory pathway (NLRP3 [NACHT, LRR, and PYD domain-containing protein 3] inflammasome/IL [interleukin]-1β) in atherosclerotic CVD. Colchicine was recently approved by the US Food and Drug Administration for this indication. Diverse anti-inflammatory drugs targeting distinct inflammatory pathways are widely used for the management of other CVDs including myocarditis and pericarditis. Ongoing research efforts are directed to implementing anti-inflammatory therapeutics across a growing number of CVDs, through repurposing of available anti-inflammatory drugs and development of novel anti-inflammatory compounds, which are herein concisely discussed. This review also summarizes the main characteristics and findings of completed and upcoming randomized controlled trials directly targeting inflammation in CVDs and discusses the major challenges and future perspectives in the exciting and constantly expanding landscape of cardioimmunology.

Lymphocytes Change Their Phenotype and Function in Systemic Lupus Erythematosus and Lupus Nephritis.

Systemic lupus erythematosus (SLE) is a complex autoimmune disease, characterized by considerable changes in peripheral lymphocyte structure and function, that plays a critical role in commencing and reviving the inflammatory and immune signaling pathways. In healthy individuals, B lymphocytes have a major role in guiding and directing defense mechanisms against pathogens. Certain changes in B lymphocyte phenotype, including alterations in surface and endosomal receptors, occur in the presence of SLE and lead to dysregulation of peripheral B lymphocyte subpopulations. Functional changes are characterized by loss of self-tolerance, intra- and extrafollicular activation, and increased cytokine and autoantibody production. T lymphocytes seem to have a supporting, rather than a leading, role in the disease pathogenesis. Substantial aberrations in peripheral T lymphocyte subsets are evident, and include a reduction of cytotoxic, regulatory, and advanced differentiated subtypes, together with an increase of activated and autoreactive forms and abnormalities in follicular T cells. Up-regulated subpopulations, such as central and effector memory T cells, produce pre-inflammatory cytokines, activate B lymphocytes, and stimulate cell signaling pathways. This review explores the pivotal roles of B and T lymphocytes in the pathogenesis of SLE and Lupus Nephritis, emphasizing the multifaceted mechanisms and interactions and their phenotypic and functional dysregulations.

Advances in Gouty Arthritis Management: Integration of Established Therapies, Emerging Treatments, and Lifestyle Interventions.

Gouty arthritis, a prevalent inflammatory condition characterized by the deposition of monosodium urate crystals within joints, often results in debilitating pain and inflammation. Conventional therapeutic approaches, including nonsteroidal anti-inflammatory drugs, corticosteroids, and urate-lowering agents such as allopurinol and febuxostat, often have limitations such as adverse effects, drug interactions, and suboptimal patient compliance. This review presents a comprehensive overview of both established and emerging therapeutic strategies, developed between 2019 and 2024, for gouty arthritis; the review focuses on their mechanisms of action, efficacy, and safety profiles. Novel therapeutic approaches include pharmaceutical plant additives (e.g., Citrullus colocynthis, Atractylodes lancea), anti-inflammatory agents such as canakinumab and ozone therapy, and complementary therapies such as warm ginger compresses, Qingpeng ointment, and various lifestyle modifications. These strategies offer promising alternatives to conventional treatments by targeting uric acid metabolism, inflammatory pathways, and crystal formation, potentially reducing reliance on standard medications and minimizing adverse effects. Although therapies such as canakinumab have demonstrated significant efficacy in reducing gout flares, others such as polyphenol-rich foods offer favorable safety profiles. Further research, including large-scale clinical trials, is warranted to validate these findings and integrate these strategies into clinical practice to improve patient outcomes and quality of life.

Guidelines for anti‐inflammatory assays in RAW264.7 cells

AbstractIn recent years, research on various bioactive compounds with anti‐inflammation effects has become increasingly active. Evaluating anti‐inflammatory activity is well established in cell models represented by RAW264.7 cells. Methylthiazolyldiphenyl‐tetrazolium bromide (MTT) and cell counting kit‐8 (CCK‐8) assays are commonly used to detect the effects of drugs or deleterious substances on cytotoxicity, cell viability, and survival. RAW264.7 cells release nitric oxide (NO) when exposed to inflammatory stimuli, so their anti‐inflammatory capacity can be assessed by detecting the NO content in cell culture supernatants, and the Griess method is one of the commonly used methods for determining NO concentration. RAW264.7 cells release a variety of inflammation‐associated cytokines, such as the TNF‐α and IL‐1β, with ELISA being the standard method to detect the release of these inflammatory factors. For mRNA expression levels of genes associated with inflammation, real‐time PCR (Quantitative Real‐time PCR, qPCR) is commonly used. In addition, the well‐known western blotting assay can be used to detect the expression levels of proteins associated with inflammatory signaling pathways. In this guideline, we discuss the basic principles and practices of the above experimental methods, which provide a valuable reference for the anti‐inflammatory experimental methods in cellular models such as the RAW264.7 cells.

Amlexanox reduces new-onset atrial fibrillation risk in sepsis by downregulating S100A12: a Mendelian randomization study.

Sepsis is characterized by high morbidity and mortality rates, alongside limited therapeutic efficacy. Atrial fibrillation (AF), the most common arrhythmia, has been closely linked to sepsis in prior research. However, the specific mechanisms through which sepsis leads to new-onset AF remain poorly understood. This study focuses on identifying critical genes that are dysregulated in the development of new-onset AF within the context of sepsis, with the goal of uncovering new potential targets for its diagnosis and prevention. Our study began by applying Mendelian Randomization (MR) to assess the causal link between sepsis and AF. We then sourced sepsis and AF datasets from the Gene expression Omnibus (GEO) database. Using Weighted Gene Co-expression Network Analysis (WGCNA), we pinpointed key modules and genes associated with both sepsis and AF conditions. Protein-protein interaction (PPI) network was constructed. The Transcriptional Regulatory Relationships Unravelled by Sentence-based Text-mining (TRRUST) database helped build the transcription factor (TF) interaction network. Key genes were scrutinized through Gene Ontology (GO), Kyoto Encyclopedia of Genes and Genomes (KEGG), Gene Set Enrichment Analysis (GSEA) and Gene Set Variation Analysis (GSVA) to delve into their roles in new-onset AF's pathophysiology during sepsis. We employed the CIBERSORT algorithm to evaluate immune infiltration and the association between key genes and immune cells. The Connectivity Map (CMap) database facilitated the prediction of potential small molecule compounds targeting key genes. To culminate, an acute sepsis mouse model was developed to validate the implicated mechanisms of key genes involved in new-onset AF during sepsis, and to assess the prophylactic effectiveness of identified drug candidates. MR revealed potential independent risk factors for new-onset AF in sepsis. S100A12 was identified as a core interaction gene with elevated levels in sepsis and AF, underscoring its diagnostic and predictive significance. S100A12, along with associated genes, was mainly linked to immune and inflammatory response signaling pathways, correlating with immune cell levels. Targeting S100A12 identifies five potential small molecule therapeutics: amlexanox, balsalazide, methandriol, olopatadine, and tiboloe. In animal studies, acute sepsis increased S100A12 expression in serum and atrial tissues, correlating positively with inflammatory markers (IL-1β, IL-6, TNF-α) and negatively with heart rate, indicating a predisposition to AF. Early amlexanox administration can reduced S100A12 expression, dampened inflammation, and lessened new-onset AF risk in sepsis. This study demonstrates that sepsis may independently increase the risk of new-onset AF. We identified S100A12 as a key gene influencing the new-onset AF in sepsis through immune regulation, presenting considerable diagnostic and predictive value. Notably, amlexanox, by targeting S100A12 emerges as the most clinical relevant intervention for managing new-onset AF in sepsis patients.

Tungsten-rosmarinic acid nanoenzyme with SOD mimetic activity for the treatment of psoriasis by eliminating ROS and relieving inflammation

Psoriasis is a refractory skin disease that seriously affects the physical and mental health of patients. It is easy to relapse and cannot be cured, which seriously harms the physical and mental health of patients. Oxidative stress, driven by increased reactive oxygen species (ROS), plays a critical role in excessive keratinocyte proliferation and local inflammation in psoriasis. In this study, we successfully synthesized a tungsten-rosmarinic acid nanoenzyme (WRA-PEG), which demonstrates promising therapeutic potential for psoriasis. Our findings demonstrate that WRA-PEG effectively scavenges ROS, reduces the proliferation of keratinocytes, and mitigates the release of pro-inflammatory cytokines in vitro. In a psoriasis-like mouse model induced by imiquimod (IMQ), WRA-PEG significantly improved clinical manifestations and prevented recurrence, as evidenced by reduced epidermal thickness and inhibited inflammatory cytokine expression, outperforming traditional treatments like Benvitimod. Bioinformatics analysis revealed the modulation of key inflammatory and oxidative stress-related pathways, highlighting the involvement of crucial genes such as CCL20 and TNFSF10 in its mechanism of action. Furthermore, WRA-PEG exhibited excellent biocompatibility and stability without adverse effects on liver or kidney function. These results underscore the potential of WRA-PEG as a novel therapeutic strategy for managing psoriasis.

Beyond Depression and Anxiety in IBD: Forging a Path Towards Emotional Healing.

Inflammatory Bowel Diseases (IBD) are chronic, often debilitating diseases characterized by inflammation of the digestive tract. IBDs affect up to 1% of the world's population and tend to be diagnosed in the second and third decades of life. In addition to physical burdens, IBDs have significant psychological manifestations stemming from bidirectional inflammatory and coping pathways and thus, are best understood from a biopsychosocial perspective. Though previous IBD literature has predominantly focused on traditional psychological comorbidities, such as anxiety and depression, recent studies have uncovered adjustment disorders, post-traumatic stress, and disordered eating as prevalent manifestations of the disease. This review will summarize the rates and postulated biopsychosocial mechanisms underlying these conditions to frame how cultivating resilience can protect against IBD symptoms and help forge a path towards emotional healing. We will also provide guidance to aid clinicians in screening for these conditions and creating a trauma-informed healthcare environment.

Modulation of Inflammation in Heart Failure: The Role of Ziltivekimab and Canakinumab

This article examines the role of inflammation in heart failure pathogenesis and explores novel therapeutic strategies targeting inflammatory pathways. The increasing prevalence of heart failure, particularly those with preserved ejection fraction (HFpEF), highlights the urgent demand for effective treatments. Canakinumab, a monoclonal antibody targeting interleukin-1β, has shown promise in reducing cardiovascular events by modulating inflammation, while Ziltivekimab, a newer monoclonal antibody targeting interleukin-6, demonstrates potential in heart failure patients with elevated inflammatory markers. The article reviews clinical trials, including CANTOS and RESCUE, providing evidence of the efficacy of patient outcomes. The findings underscore the importance of personalized treatment strategies on heart failure, with a focus on inflammation-driven pathways, positioning anti-inflammatory therapies as a significant advancement in cardiovascular disease management. Future research will determine the broader clinical applicability of these therapies in managing heart failure, its complications, and fostering more favorable outcomes.

Single-cell transcriptomics reveals aberrant skin-resident cell populations and identifies fibroblasts as a determinant in rosacea

Rosacea is a chronic inflammatory skin disorder, whose underlying cellular and molecular mechanisms remain obscure. Here, we generate a single-cell atlas of facial skin from female rosacea patients and healthy individuals. Among keratinocytes, a subpopulation characterized by IFNγ-mediated barrier function damage is found to be unique to rosacea lesions. Blocking IFNγ signaling alleviates rosacea-like phenotypes and skin barrier damage in mice. The papulopustular rosacea is featured by expansion of pro-inflammatory fibroblasts, Schwann, endothelial and macrophage/dendritic cells. The frequencies of type 1/17 and skin-resident memory T cells are increased, and vascular mural cells are characterized by activation of inflammatory pathways and impaired muscle contraction function in rosacea. Most importantly, fibroblasts are identified as the leading cell type producing pro-inflammatory and vasodilative signals in rosacea. Depletion of fibroblasts or knockdown of PTGDS, a gene specifically upregulated in fibroblasts, blocks rosacea development in mice. Our study provides a comprehensive understanding of the aberrant alterations of skin-resident cell populations and identifies fibroblasts as a key determinant in rosacea development.

Unwinding the Threads of Mesoporous Silica Nanoparticles as Cutting-Edge for the Management of Inflammation: An Updated Review.

Inflammation serves as a protective response to combat cellular and tissue damage. There is currently a wide array of synthetic and traditional therapies available for the treatment of inflammatory diseases. However, it is necessary to create a drug delivery system based on nanotechnology that can improve the solubility, permeability, and bioavailability of current treatments. Mesoporous silica nanoparticles (MSNPs) are inorganic materials known for their organised porous interiors, high pore volumes, substantial surface area, exceptional selectivity, permeability, low refractive index, and customisable pore sizes. This review offers concise insights into the progression of the pathophysiology of inflammation, as well as the inducers, mediators, and effectors that are involved in the inflammatory pathway. This study focuses on the growing significance of MSNPs in the treatment of neuroinflammation, inflammatory bowel disease, arthritic inflammation, lung inflammation, and wound healing applications. This review also presents the latest information on the crucial role of MSNPs in delivering herbal medicines for the treatment of inflammation. A comprehensive literature search was conducted for this aim, utilising the Google Scholar, PubMed, and ScienceDirect databases. A systematic review was undertaken utilising scholarly articles published in peer-reviewed journals from 2000 to 2024. The inflammatory mediators involved in the pathophysiology of inflammation include platelet-activating factor, lipoxygenase, cyclooxygenase, Interferon-α, interleukin-6, interleukin- 1β, matrix metalloproteinases, inducible nitric oxide synthase, nuclear factor-κB, prostaglandins, nitric oxide, and phospholipase A2. MSNPs have the potential to be used in the treatment of neuroinflammation, inflammatory bowel disease, arthritic inflammation, lung inflammation, and wound healing. The investigation of the MSNPs of plant-based compounds such as berberine, tetrahydrocannabinol, curcumin, and resveratrol has shown successful results in recent years for the purpose of managing inflammation. This review demonstrates that MSNPs have a strong potential to play a positive role in delivering synthetic and plant-based therapies for the treatment of inflammatory illnesses.

Inflammatory Trajectory of Type 2 Diabetes: Novel Opportunities for Early and Late Treatment.

Low-grade inflammation (LGI) represents a key driver of type 2 diabetes (T2D) and its associated cardiovascular diseases (CVDs). Indeed, inflammatory markers such as hs-CRP and IL-6 predict the development of T2D and its complications, suggesting that LGI already increases before T2D diagnosis and remains elevated even after treatment. Overnutrition, unhealthy diets, physical inactivity, obesity, and aging are all recognized triggers of LGI, promoting insulin resistance and sustaining the pathogenesis of T2D. Once developed, and even before frank appearance, people with T2D undergo a pathological metabolic remodeling, with an alteration of multiple CVD risk factors, i.e., glycemia, lipids, blood pressure, and renal function. In turn, such variables foster a range of inflammatory pathways and mechanisms, e.g., immune cell stimulation, the accrual of senescent cells, long-lasting epigenetic changes, and trained immunity, which are held to chronically fuel LGI at the systemic and tissue levels. Targeting of CVD risk factors partially ameliorates LGI. However, some long-lasting inflammatory pathways are unaffected by common therapies, and LGI burden is still increased in many T2D patients, a phenomenon possibly underlying the residual inflammatory risk (i.e., having hs-CRP > 2 mg/dL despite optimal LDL cholesterol control). On the other hand, selected disease-modifying drugs, e.g., GLP-1RA, seem to also act on the pathogenesis of T2D, curbing the inflammatory trajectory of the disease and possibly preventing it if introduced early. In addition, selected trials demonstrated the potential of canonical anti-inflammatory therapies in reducing the rate of CVDs in patients with this condition or at high risk for it, many of whom had T2D. Since colchicine, an inhibitor of immune cell activation, is now approved for the prevention of CVDs, it might be worth exploring a possible therapeutic paradigm to identify subjects with T2D and an increased LGI burden to treat them with this drug. Upcoming studies will reveal whether disease-modifying drugs reverse early T2D by suppressing sources of LGI and whether colchicine has a broad benefit in people with this condition.

Phlebotomy-induced anemia reduces oxygen-induced retinopathy severity and dampens retinal developmental transcriptomic pathways in rats.

Phlebotomy-induced-anemia (PIA), which induces tissue hypoxia and angiogenesis, occurs universally among infants at risk for severe retinopathy of prematurity (ROP). We hypothesized that PIA exacerbates pathologic retinal neovascularization in ROP. We induced PIA to a hematocrit of 18% among rats undergoing the established 50/10 oxygen-induced retinopathy (OIR) model. Rats were euthanized at P15 and P20, during the avascular and neovascular phases of OIR, respectively. Retinal vascular morphometry, cytokine/chemokine concentrations, transcriptomes, and mRNA expression of angiogenic and iron-deficiency markers were compared to non-PIA controls. In OIR, PIA decreased percent avascular area at P15 by 35%, percent neovascular area at P20 by 42%, and select pro-inflammatory cytokine/chemokine concentrations at both time points. At P20, PIA increased mRNA expression of angiopoietin 2/ vascular endothelial growth factor-A 2-fold and transferrin and transferrin receptor 5-fold. RNA sequencing showed dampened pathways of angiogenesis, inflammation, and neural development in anemic OIR females. Contrary to our hypothesis, PIA decreased OIR severity and retinal cytokine and chemokine levels and dampened transcriptomic pathways central to retinal vascular and neural development in neonatal rats. These data suggest PIA provides a protective effect from OIR. Further investigation into the functional effect of these molecular changes is warranted. This is the first preclinical study to investigate the impact of neonatal anemia on oxygen-induced retinopathy (OIR) outcomes. This study adds to the literature that anemia decreases neovascularization, decreases cytokine and chemokine levels, and dampens angiogenic and neural transcriptomic pathways in the rat 50/10 OIR model. The study identifies a sex-specific transcriptomic response to anemia in the 50/10 OIR model, with females primarily impacted.

Causal links between circulatory inflammatory cytokines and risk of digestive polyps: a Mendelian randomization analysis.

There is a high morbidity of polyps in the digestive tract, and certain subtypes of polyps are thought to induce cancer progression and often recur, which may be associated with chronic inflammation. Mendelian randomization (MR) can help identify potential causative relationships and inform early treatment action. We performed a bidirectional two-sample MR analysis implementing the results from genome-wide association studies for 41 serum cytokines from 8,293 Finnish individuals, and three types of polyps from European ancestry, respectively, including gastric polyp (6,155 cases vs. 341,871 controls), colonic polyp (22,049 cases vs. 332,368 controls) and gallbladder polyp (458 cases vs. 340,083 controls). Inverse-variance weighted (IVW), weight median (WM), and MR-Egger methods were used for calculating causal estimates. Furthermore, Bayesian model averaging MR (MR-BMA) method was employed to detect the dominant causal circulatory cytokines with adjustment for pleiotropy effects. Our univariable MR using inverse-variance weight method identified causal associations of IL-2ra (OR: 0.892, 95%CI: 0.828-0.961, p = 0.003), MIG (OR: 1.124, 95%CI: 1.046-1.207, p = 0.001) and IL-18 (OR: 0.912, 95%CI: 0.852-0.977, p = 0.008) with gastric polyp, MIP1b (OR: 0.956, 95%CI: 0.927-0.987, p = 0.005) and IL-6 (OR: 0.931, 95%CI: 0.870-0.995, p = 0.035) with colonic polyp and IL-9 (OR: 0.523, 95%CI: 0.345-0.794, p = 0.0007) with gallbladder polyp. Finally, our MR-BMA analysis prioritized MIG (MIP = 0.332, MACE = 0.022; PP: 0.264, MSCE = 0.059), IL-18 (MIP = 0.302, MACE = -0.020; PP: 0.243, MSCE = -0.059) and IL-2ra (MIP: 0.129; MACE: -0.005; PP: 0.112, MSCE: -0.031) for gastric polyp, and MIP1b (MIP = 0.752, MACE = -0.033; PP: 0.665, MSCE = -0.044) and IL-6 (MIP: 0.196; MACE: -0.012; PP: 0.140, MSCE: -0.064) for colonic polyp, and IL-9 (MIP = 0.936, MACE = -0.446; PP: 0.781, MSCE = -0.478) for gallbladder polyp as the top-ranked protective factors. Our research advances the current understanding of the function of certain inflammatory biomarker pathways in the genesis and malignant mutation of polyps in the digestive tract. Deeper substantiation is necessary to assess the potential of these cytokines as pharmacological or lifestyle targets for digestive polyps prevention.

Inflammatory profile of eosinophils in asthma-COPD overlap and eosinophilic COPD: a multi-omics study.

Elevated blood eosinophil levels in patients with chronic obstructive pulmonary disease (COPD) with or without asthma are linked to increased exacerbations and the effectiveness of inhaled corticosteroid treatment. This study aimed to delineate the inflammatory cellular properties of eosinophils in patients with asthma-COPD overlap (ACO) and eosinophilic COPD (eCOPD). Eosinophils were isolated from the peripheral blood of healthy volunteers, patients with non-eCOPD, and those with ACO/eCOPD. Multi-omics analysis involving transcriptomics, proteomics, and lipidomics was performed, followed by bioinformatic data analyses. In vitro experiments using eosinophils from healthy volunteers were conducted to investigate the molecular mechanisms underlying cellular alterations in eosinophils. Proteomics and transcriptomics analyses revealed cellular characteristics in overall COPD patients represented by viral infection (elevated expression of sterol regulatory element-binding protein-1) and inflammatory responses (elevated levels of IL1 receptor-like 1, Fc epsilon receptor Ig, and transmembrane protein 176B). Cholesterol metabolism enzymes were identified as ACO/eCOPD-related factors. Gene Ontology and pathway enrichment analyses demonstrated the key roles of antiviral responses, cholesterol metabolism, and inflammatory molecules-related signaling pathways in ACO/eCOPD. Lipidomics showed the impaired synthesis of cyclooxygenase-derived mediators including prostaglandin E2 (PGE2) in ACO/eCOPD. In vitro assessment confirmed that IL-33 or TNF-α stimulation combined with IL-5 and IFN-γ stimulation induced cellular signatures in eosinophils in ACO/eCOPD. Atorvastatin, dexamethasone, and PGE2 differentially modulated these inflammatory changes. ACO/eCOPD is associated with viral infection and an inflammatory milieu. Therapeutic strategies using statins and inhaled corticosteroids are recommended to control these pathogenic changes.

IMPC-based screening revealed that ROBO1 can regulate osteoporosis by inhibiting osteogenic differentiation.

The utilization of denosumab in treating osteoporosis highlights promising prospects for osteoporosis intervention guided by gene targets. While omics-based research into osteoporosis pathogenesis yields a plethora of potential gene targets for clinical transformation, identifying effective gene targets has posed challenges. We first queried the omics data of osteoporosis clinical samples on PubMed, used International Mouse Phenotyping Consortium (IMPC) to screen differentially expressed genes, and conducted preliminary functional verification of candidate genes in human Saos2 cells through osteogenic differentiation and mineralization experiments. We then selected the candidate genes with the most significant effects on osteogenic differentiation and further verified the osteogenic differentiation and mineralization functions in mouse 3T3-E1 and bone marrow mesenchymal stem cells (BMSC). Finally, we used RNA-seq to explore the regulation of osteogenesis by the target gene. We identified PPP2R2A, RRBP1, HSPB6, SLC22A15, ADAMTS4, ATP8B1, CTNNB1, ROBO1, and EFR3B, which may contribute to osteoporosis. ROBO1 was the most significant regulator of osteogenesis in both human and mouse osteoblast. The inhibitory effect of Robo1 knockdown on osteogenic differentiation may be related to the activation of inflammatory signaling pathways. Our study provides several novel molecular mechanisms involved in the pathogenesis of osteoporosis. ROBO1 is a potential target for osteoporosis intervention.

A Review on Nanotechnologically Derived Phytomedicines for the Treatment of Hepatocellular Carcinoma: Recent Advances in Molecular Mechanism and Drug Targeting.

The second largest cause of cancer-related death worldwide, Hepatocellular Carcinoma (HCC) is also the most common primary liver cancer. HCC typically arises in patients with liver cirrhosis. Existing synthetic medicines for treating chronic liver disease are ineffective and come with undesirable side effects. Although herbal remedies have widespread popularity, there is still a long road ahead before they are fully accepted by the scientific community. Secondary metabolites and phytochemicals found in plants are abundant in both the human diet and the non-human environment. Natural plant chemicals have been shown to be beneficial as therapeutic and chemopreventive treatments for a wide variety of chronic disorders. Many diseases, including HCC, can be effectively treated with the help of phytochemicals found in food. Resveratrol, curcumin, urolithin A, silibinin, quercetin, N-trans-feruloyl octopamine, emodin, lycopene, caffeine, and phloretin are all examples. Approximately, 60% of all anticancer medications are determined to be derived from natural substances, according to recent studies. Plant derivatives have played an important role in cancer due to their capacity to scavenge free radicals, limit cell proliferation, and set off apoptosis. The progression of HCC is linked to inflammatory signaling pathways, and this study sought to look at how novel approaches, such as phytomedicines, are being used to fight cancer. Recent advancements in molecular mechanisms and drug targeting for HCC have been discussed in this review.

Mini Review: The gut microbiota as a link between Alzheimer's disease and obesity.

Alzheimer's disease (AD) is a degenerative disease that causes a progressive decline in memory and thinking skills. Over the past few years, diverse studies have shown that there is no single cause of AD; instead, it has been reported that factors such as genetics, lifestyle, and environment contribute to the pathogenesis of the disease. In this sense, it has been shown that obesity during middle age is one of the most prominent modifiable risk factors for AD. Of the multiple potential mechanisms linking obesity and AD, the gut microbiota (GM) has gained increasing attention in recent years. However, the underlying mechanisms that connect the GM with the process of neurodegeneration remain unclear. Through this narrative review, we present a comprehensive understanding of how alterations in the GM of people with obesity may result in systemic inflammation and affect pathways related to the pathogenesis of AD. We conclude with an analysis of the relationship between the GM and insulin resistance, a risk factor for AD that is highly prevalent in people with obesity. Understanding the crosstalk between obesity, the GM, and the pathogenesis of AD will help to design new strategies aimed at preventing neurodegeneration.

The Association of Interleukin-36 Staining Intensity and Response to Biologic Therapy in Patients With Psoriasis: A Retrospective Immunohistochemical and Chart Review Pilot Study.

There are limited surrogate biomarkers to identify the active inflammatory pathway in psoriasis to direct treatment with targeted biologic therapies. We investigated the association of interleukin (IL)-36 epidermal expression, a diagnostic marker of psoriasis, with response to biologic therapy in patients with psoriasis. Retrospective immunohistochemical and chart review pilot study. Patients with psoriasis with low (scores 0-2) vs. high (scores 3-4) IL-36 expression did not have significantly different response rates to tumor necrosis factor α (TNFα), IL-17, and IL-12/23 or IL-23 inhibitors; and similarly, mean IL-36 expression scores did not significantly differ among responders vs. non-responders to each treatment mechanism. However, in patients with psoriasis treated with IL-12/23 or IL-23 inhibitors, there was a marked absolute difference in response rates in those with high vs. low IL-36 (84% vs. 50%, p = 0.12) and in mean IL-36 scores in responders vs. non-responders (3.35 vs. 2.57, p = 0.19). Patients with psoriasis with high IL-36 expression were more likely to respond to IL-12/23 and IL-23 inhibition than those with low IL-36, though these findings were not statistically significant. Additional studies with larger sample sizes are needed to validate and expand upon these findings.

Interplay between Lung Diseases and Viral Infections: A Comprehensive Review.

The intricate relationship between chronic lung diseases and viral infections is a significant concern in respiratory medicine. We explore how pre-existing lung conditions, including chronic obstructive pulmonary disease, asthma, and interstitial lung diseases, influence susceptibility, severity, and outcomes of viral infections. We also examine how viral infections exacerbate and accelerate the progression of lung disease by disrupting immune responses and triggering inflammatory pathways. By summarizing current evidence, this review highlights the bidirectional nature of these interactions, where underlying lung diseasesincrease vulnerability to viral infections, while these infections, in turn, worsen the clinical course. This review underscores the importance of preventive measures, such as vaccination, early detection, and targeted therapies, to mitigate adverse outcomes in patients with chronic lung conditions. The insights provided aim to inform clinical strategies that can improve patient management and reduce the burden of chronic lung diseases exacerbated by viral infections.