Cardiovascular disease (CVD), including pericarditis, myocarditis, sudden cardiac death, coronary heart disease, and stroke, are leading contributors to morbidity and mortality in systemic lupus erythematosus (SLE) patients. Emerging evidence highlights mitochondrial dysfunction as a key driver of cardiovascular pathology in SLE, with impaired oxidative phosphorylation, altered membrane potential, and disrupted metabolic processes promoting oxidative stress, inflammatory activation, and endothelial dysfunction. This review critically examines mitochondrial contributions to CVD in SLE, comparing these mechanisms with those in non-SLE CVD to highlight SLE-specific mitochondrial vulnerabilities. Furthermore, we discuss preclinical and clinical findings supporting mitochondrial pathways as potential therapeutic targets, aiming to bridge gaps in current understanding and outline future research directions. By synthesizing current knowledge of mitochondrial dysregulation, this review proposes therapeutic strategies to improve cardiovascular outcomes and advance patient care in SLE.

Triple-negative breast cancer (TNBC) is a biologically aggressive tumor with a strong association with a high recurrence rate and poor prognosis. Although anti-PD-L1 antibody, Tecentriq has been approved by FDA for treating TNBC, the overall response rate (ORR) is still generally less than 20 %. PPAB001 is a novel bispecific antibody simultaneously targeting CD47 and CD24. In the present study, we firstly evaluated the activity of PPAB001 on promoting the phagocytosis of TNBC cell lines. And the efficacy by combination of PPAB001 and Tecentriq was also assessed in TNBC 4T-1 mouse model. Moreover, the expression profiling of macrophage-associated genes and surface markers were evaluated upon the combinatorial treatment by flow cytometry, Western blot and IHC analysis. Cell signaling involved in M1 macrophage polarization was further identified via the analysis of RNA-seq, Western blot and immunofluorescnece. Our results demonstrated that PPAB001 effectively promotes phagocytosis of macrophages against human TNBC cell lines and significantly delayed TNBC tumor growth, especially when combined with Tecentriq treatment which may be attributed to the mechanism that simultaneous blockade of CD47 and CD24 signaling maximized the polarization toward M1 phenotype polarization. Especially, RNA-seq analysis and Western blotting further revealed that CXCL9/10-CXCR3 axis was markedly up-regulated and JAK/STAT1 pathway was activated upon treatment with PPAB001 plus Tecentriq. Overall, our results underscore that simultaneous blockade of CD47 and CD24 is a potential therapeutic option to improve the efficacy of anti-PD-L1 therapy mainly by resetting tumor-associated macrophages toward M1 phenotype.

Inflammatory Bowel Disease (IBD) is increasing worldwide and has become a global emergent disease. Probiotics have been reported to be effective in relieving colitis. Previous studies found ripened Pu-erh tea (RPT) promoted gut microbiota resilience against dextran sulfate sodium (DSS)-induced colitis in mice by increasing relative abundance of Lactobacillus. However, whether and how it alleviated DSS-induced colitis in mice need to be explored. Here, we screened a probiotic Lactobacillus johnsonii GLJ001 from feces of ripened Pu-erh tea (RPT)-administrated mice. In this study, L. johnsonii GLJ001 attenuated symptoms of DSS-induced colitis in mice, including weight loss, increased disease activity index (DAI), colon shortening and colon tissue damage, as well as high expression of inflammatory cytokines and disturbances of intestine barrier function. Furthermore, abundances of short-chain fatty acids (SCFAs)-producing bacteria (i.e. Clostridium cluster IV and XIVa, Lachnospiracea_incertae_sedis and Ruminococcus) were enhanced in the cecum of mice treated with L. johnsonii GLJ001, accompanying by an increase of SCFAs. It was also found that SCFAs inhibited mRNA expression of M1 macrophage markers (Inos and CD86), inflammatory cytokines (TNF-α and Il-1β) and SCFAs receptors (Gpr41 and Gpr43) induced by lipopolysaccharide (LPS) and interferon-γ (IFN-γ) in THP-1 cell line. Collectively, L. johnsonii GLJ001 prevented DSS-induced colitis in mice by inhibiting M1 macrophage polarization via gut microbiota-SCFAs axis, and can be administered for management of colitis.

Osteosarcoma is a common primary malignant bone tumor with a high incidence in children and adolescents, with high invasiveness and lung metastases. Even after traditional surgical excision, chemoradiotherapy, and comprehensive treatment, the survival rate of patients is still low, and the prognosis is not ideal. As an important part of non-coding RNA family, lncRNA and miRNA have significant regulatory effects on the growth, proliferation, metastasis and apoptosis of osteosarcoma cells. Therefore, exploring the roles of lncRNAs and miRNAs in the occurrence and development of osteosarcoma is of great help for the subsequent diagnosis, treatment, and prognosis of osteosarcoma. This paper mainly reviews the current research progress on the effects and mechanisms of lncRNAs and miRNAs on osteosarcoma cells, in order to provide new ideas for future research on the development process, treatment methods, and prognosis of osteosarcoma.

Gastric cancer (GC) mesenchymal stromal cells (GCMSCs) are the predominant components of the tumor microenvironment (TME) and play a role in the occurrence, development, and metastasis of tumors. However, GCMSCs exhibit phenotypic and functional heterogeneity. The key population of GCMSCs which are vital to tumor progression remains elusive. The expression of fibroblast activation protein (FAP) in gastric cancer was analyzed and verified using clinical pathology data and single-cell RNA sequencing database of gastric cancer patients. FAP positive GCMSCs (FAP GCMSCs) were isolated via flow cytometry and characterized through transcriptomic sequencing. The impact of conditioned medium from FAP GCMSCs on gastric cancer cell lines was assessed using Enzyme-linked immunosorbent assay (ELISA) and Western blot analyses. Additionally, immunohistochemistry (IHC) and Masson's trichrome staining were employed to explore the association between FAP GCMSCs and extracellular matrix (ECM) deposition in gastric cancer tissues. Our study demonstrates that FAP is predominantly expressed in the mesenchymal stromal cells within the gastric cancer milieu. FAP GCMSCs exhibited enhanced proliferation, migration, contraction, and tumor-promoting capabilities compared to their FAP counterparts. These cells significantly increased proliferation and migration of gastric cancer cells through the paracrine secretion of Inhibin Subunit Beta A (INHBA) and activation of the SMAD2/3 signaling pathway. Moreover, FAP GCMSCs also induced collagen deposition in ECM and then up-regulated invasion and stemness of GC cells. Mechanistically, this process was mediated by the interaction of collagen with Integrin Subunit Beta 1 (ITGB1), triggering the phosphorylation of Focal Adhesion Kinase (FAK) and Yes Associated Transcriptional Regulator (YAP). Our findings reveal that FAP GCSMCs enhanced the GC progression via releasing cytokine INHBA and remodeling ECM providing a theoretical basis for further exploration of tumor stromal-targeting therapy of gastric cancer.

Although recent studies have reported that obesity is a protective factor for survival in patients with advanced cancers treated with immune checkpoint inhibitors (ICIs), the prognostic value of CT-derived adipose composition parameters remains unclear. This study aimed to assess the association between CT-derived adipose composition parameters and clinical outcomes in cancer patients undergoing ICIs treatment.

Chronic prostatitis and Pelvic Pain syndrome (CP/CPPS) is an autoimmune inflammatory disease characterized by pelvic or perineal pain and infiltration of inflammatory cells in the prostate. C-X-C chemokine receptor type 7 (CXCR7) is an atypical chemokine receptor that has been shown to play a key role in inflammatory processes in prostate cancer. However, the role of CXCR7 in autoimmune prostate and immune regulation in CP/CPPS along with the mechanism of action for CXCR7 remains unclear. In this study, a mouse model of experimental autoimmune prostatitis (EAP) was constructed by subcutaneous injection of antigen, and CXCR7 agonist was administered to investigate the effects of CXCR7 on the proportion of immune cells and fibrosis in CP/CPPS. Western blotting, immunohistochemical staining and immunofluorescence, flow cytometry, and masson's trichrome staining were used to study the regulatory mechanisms of CXCR7 in immune regulation. CXCR7 agonists can significantly reduce pain and prostatic inflammation, and in vivo flow cytometry studies showed that the antagonists restored the imbalance of the Th17/Treg cell ratio. To elucidate the potential mechanisms by which CXCR7 influences the pathogenesis of CP/CPPS, we conducted simultaneous RNA-seq and non-targeted metabolome sequencing. Our findings suggest that CXCR7 agonists alleviate fibrosis in autoimmune prostatitis by inhibiting the TGFβ/SMAD pathway. This study provides the foundation to target the immunological function of CXCR7 as a novel therapy for CP/CPPS.

Retinal pericytes are mural cells surrounding capillaries to maintain the integrity of blood-retina barrier and regulate vascular behaviors. Pericyte loss has been considered as the hallmark of diabetic retinopathy (DR), which is a major complication of diabetes and the leading cause of blindness in adults. However, the precise function of pericytes in regulating the retinal microenvironment and the underlying mechanism remains largely unknown. In this study, we observed a secretory phenotype of pericytes with elevated inflammatory cytokines in response to Interleukin-1β (IL-1β), a canonical inflammatory cytokine which significantly increases during the initial stages of diabetic retinopathy. This phenotype is also accompanied by reduced expression of adherent junction proteins and contractile proteins. Paracrine cytokines derived from pericytes further induce the chemotaxis of microglia cells and trigger detrimental changes in endothelial cells, including reduced expression of tight junction protein Occludin and increased apoptosis. Mechanically, the secretion potential in pericytes is partially mediated by Hes1/STAT3 signaling pathway. Moreover, co-injection of stattic, an inhibitor targeting STAT3 activation, could effectively attenuate IL-1β-induced retinal inflammation and microglial activation in retina tissues. Collectively, these findings demonstrate the potential of retinal pericytes as an initial inflammatory sensor prior to their anatomical pathological loss, via undergoing phenotypic changes and secreting paracrine factors to amplify local inflammation and damage endothelial cells in vitro. Furthermore, inhibition of STAT3 activation by inhibitors significantly ameliorates IL-1β-induced retinal inflammation, suggesting STAT3 in retinal pericytes as a promising target for alleviating DR and other IL-1β-induced ocular diseases.

The presence of neutrophil infiltration around the pancreatic ducts has been found to be associated with type 2 autoimmune pancreatitis (AIP). However, the functional role and clinical significance of neutrophil migration in the progression of pancreatitis is not fully understood. Here, we found that neutrophil extracellular traps (NETs) are abundant around the pancreatic duct in patients with type 2 AIP. We also observed an increased expression of toll-like receptor 9 (TLR9) in pancreatic ductal epithelial cells (HPDEC) in type 2 AIP patients compared to other pancreatic diseases. TLR9 acts as the DNA component of NETs (NET-DNA) receptor in HPDEC, which senses extracellular DNA and subsequently activates the NF-κB pathway to promote neutrophil recruitment and induce NET formation. In addition, our results indicated that the hydroxychloroquine (HCQ), acting as a TLR9 antagonist, could effectively inhibit the activation of inflammatory pathways, reduce neutrophil migration and block the positive feedback loop. The intervention positions HCQ acts as a potential target drug for the clinical treatment of type 2 AIP.

Proton pump inhibitors (PPIs) represent a commonly prescribed class of medications. Triggered by findings indicating a correlation between PPI usage and susceptibility to infectious or autoimmune diseases, we studied the impact of a pharmacological concentration of omeprazole on human CD4+ T-cells.

This study aimed to screen an immune-related gene (IRG) panel and develop a novel approach for diagnosing pulmonary arterial hypertension (PAH) utilizing bioinformatics and machine learning (ML).

Diabetic nephropathy (DN) is the most common microvascular complication of diabetes mellitus and a major cause of end-stage renal disease. Isoferulic acid (IFA) is a phenolic compound that has strong antioxidant, anti-inflammatory, and hypoglycemic effects. Researches and our previous study showed the potential anti-diabetic capacity and anti- oxidative stress damage targeting podocytes of IFA. The purpose of this study was to investigate whether IFA protects MPC5 podocytes from high glucose damage and alleviates DN symptoms in STZ-induced mice, as well as to explore the mechanism. The findings revealed that IFA (10, 25, 50 μM) significantly reduced high glucose-mediated toxicity, abnormal motility and morphology, ROS release, Ca elevation with MPTP opening, apoptotic alterations with Caspase-3/7 activity increase and CXCL12 chemotaxis and interaction with CXCR4 in MPC5 podocytes. Furthermore, IFA increased Podocalyxin and LC3 II/I ratio. Meanwhile, IFA suppressed p53, mTOR, CASK, and p62. Furthermore, IFA has the ability to directly influence downstream mTOR, p53, and CASK apoptotic and podocyte motility regulatory targets when inhibiting the CXCL12/CXCR4 signaling pathway. In the sequent in vivo experiment, the results showed STZ-induced DN mice had higher kidney index, urination, UACR, lipid metabolism abnormalities and renal dysfunction, raised blood glucose, and podocyte damage than normal C57BL/6 mice. However, IFA treatment (50 mg/kg, 25 mg/kg, and 12.5 mg/kg) for 10 weeks restored the DN symptoms in the mice. IFA treatment elevated LC3B and LC3 II/I ratios and decreased p62 via suppressing chemokine axis CXCL12/CXCR4 with PI3K/Akt/mTOR, MMP9, and NF-κB p65 and activating podocyte markers WT1, nephrin, and Podocalyxin, thereby inducing autophagy and mitigating apoptosis in the DN mice kidneys. These findings suggest that IFA protective mechanism on kidney and podocytes simulating DN symptoms is primarily mediated by the CXCL12/CXCR4 pathways with the inactivation of apoptotic pathways and activation of autophagy.

Immunoglobulin G (IgG) N-glycans have been shown to regulate the inflammatory response in the context of disease. In recent years, it has been found to be associated with several neurodegenerative disorders. In this study, we examined the relationship between IgG N-glycans and mild cognitive impairment (MCI) in a high-risk population for MCI, specifically patients with cerebrovascular stenosis.

Transcranial focused ultrasound stimulation (tFUS) has emerged as a promising therapeutic strategy for mitigating brain injury in animal models. In this study, the effects and mechanisms of tFUS on ischemic stroke were explored in a transient middle cerebral artery occlusion (MCAO) rat model. Low-intensity tFUS was administered to the ischemic hemisphere 24 h post-MCAO for seven consecutive days. Neurological function was evaluated through neurobehavioral assessments following tFUS treatment. Western blotting, immunofluorescence staining, and quantitative real-time PCR were performed to examine the impact of tFUS on NLRP3-related neuroinflammation using brain tissues from MCAO rats and BV2 cells subjected to oxygen glucose deprivation/reperfusion (OGD/R). Additionally, RNA sequencing and cell transient transfection were employed to elucidate the underlying mechanisms. The findings revealed that tFUS improved neurobehavioral performance, reduced infarct size, and suppressed NLRP3 inflammasome activation seven days post-MCAO. Notably, Nespas expression was significantly elevated in tFUS-treated rats, whereas Nespas silencing exacerbated neurological deficits and enhanced NLRP3 activation. Moreover, Nespas positively regulated src homology 2 domain-containing tyrosine phosphatase-2 (SHP2), and SHP2 inhibition significantly amplified NLRP3 activation. Mechanistic in vitro studies further demonstrated that Nespas attenuated microglial NLRP3 activation via the Nespas/miR-383-3p/SHP2 pathway. These results suggest that the neuroprotective effects of tFUS are likely mediated through the upregulation of Nespas and suppression of NLRP3 via the Nespas/miR-383-3p/SHP2 axis, offering new insights into the molecular mechanisms supporting tFUS as a potential therapeutic approach for stroke-induced brain injury.

Diabetes mellitus, a globally prevalent condition, often complicates wound healing, leading to chronic, non-healing wounds. This study explores a novel combination therapy using Dapagliflozin and Cycas media extract for treating experimentally induced diabetic wounds in rats. By targeting the Notch signaling pathway, a critical pathway in wound healing, this research investigates the efficacy of this combination therapy in accelerating wound repair. Forty-two male Wistar albino rats were divided into control and treatment groups, receiving various Dapagliflozin and Cycas media gel combinations. The study evaluated wound healing, biochemical markers, gene expression, and histopathological changes. The findings suggest that the combination therapy significantly enhances wound healing, modulates oxidative stress, alters inflammatory responses, and influences key genes in the Notch pathway. This research provides a new perspective on diabetic wound management and underlines the potential of combining Dapagliflozin and Cycas media as a therapeutic approach.

Both Autophagy and FAT atypical cadherin 1 (FAT1) regulates the chemosensitivity and immune escape of tumour cells. Our previous paper showed that FAT1 decreased acute myeloid leukemia (AML) autophagy by inhibiting the TGFβ-Smad2/3 pathway. This study builds upon our previous paper and aims to explore whether FAT1-inhibited autophagy is involved in regulating chemosensitivity and immune escape in AML.

Immunoglobulin A Nephropathy (IgAN) is a leading cause of end-stage renal disease (ESRD), but its pathogenesis remains unclear, and specific therapies are currently lacking. Consequently, identifying novel differentially expressed genes (DEGs) and therapeutic targets is of paramount importance to IgAN.

Panlongqi Tablet (PLQT), a proprietary Chinese medicine composed of 29 herbs, has been included in the Chinese Medical Insurance List and has shown promising therapeutic effects on patients with rheumatoid arthritis (RA) in clinical practice. However, the molecular mechanisms of PLQT against RA have not been fully elucidated. This study aimed to further decipher the active ingredients and molecular mechanism of PLQT anti-RA.

Osteoarthritis (OA) is a prevalent, degenerative joint disease that requires effective treatments to prevent its progression. Therefore, the development of novel therapeutic strategies to address this unmet clinical challenge is paramount. Marein (MA), the principal active compound of Coreopsis tinctoria Nutt, exhibits anti-inflammatory and anti-oxidant properties in various diseases, indicating its potential as a therapeutic agent for OA. In this study, we assessed the ability of marein to mitigate the inflammatory response in OA and reverse cartilage degradation. The results demonstrated that MA exerted a concentration -dependent effect (10, 25, 50 μM), facilitating the nuclear translocation of nuclear factor erythroid 2-related factor 2 (Nrf2), reversing the suppression of nuclear factor kappa B (NF-κB) activation, and mitigating the inflammatory response, ultimately alleviating joint cartilage damage. In cellular assays, MA (10, 25, 50 μM) markedly decreased the expression of cyclooxygenase-2 (COX-2), inducible nitric oxide synthase (iNOS), matrix metalloproteinase-13 (MMP-13) and a metalloproteinase with thrombospondin motifs 5 (ADAMTS-5), simultaneously decreasing reactive oxygen species production by enhancing Nrf2 nuclear translocation. Furthermore, in animal models, MA (50 μM) significantly improved knee joint cartilage damage and effectively reduced OA progression. Further studies are needed to determine the long-term safety and therapeutic potential of MA and to expand its application scope. Moreover, preclinical studies are required to evaluate the efficacy of MA in humans. Overall, MA is a promising therapeutic candidate and may be an effective treatment for patients with OA.

The interleukin-33(IL-33) - group 2 innate lymphoid cells (ILC2s) - interleukin-13(IL-13) - monocytic myeloid-derived suppressor cells (M-MDSCs) axis plays a critical role in promoting immune evasion in tumors; however, its specific function in cervical cancer remains poorly understood. In this study, we observed that the proportion of IL-33-ILC2s-IL-13-M-MDSCs were significantly elevated in both cervical cancer patients and the subcutaneous U14 cervical cancer mouse model, compared to normal controls. Our results suggest that IL-33 stimulates ILC2s to secrete IL-13, which, in turn, regulates M-MDSCs to enhance their immune evasion capabilities. Notably, in vitro blockade of IL-33 and IL-13 partially restored the levels and functions of both ILC2s and M-MDSCs. In conclusion, these findings imply that the overactivation of the IL-33-ILC2s-IL-13-M-MDSCs axis may contribute to cervical cancer progression. However, further in vivo blockade studies are required to fully elucidate the precise mechanisms underlying this interaction and to assess its potential therapeutic implications for cervical cancer.