Current Molecular Medicine[JOURNAL]
Sun
200 papers
Effect of Renal Artery Stenosis on Hind Limb Perfusion and Arteriogenesis After Left Femoral Artery Ligation in Rats: E-RASHEF Study.
Zheng B
Curr Mol Med · 2026 May · PMID 42163682 · Publisher ↗
BACKGROUND/OBJECTIVE: Patients with renal artery stenosis (RAS) exhibit increased risk of cardiovascular death and all-cause death. Our previous finding showed that the presence of RAS is associated with poor coronary co...
BACKGROUND/OBJECTIVE: Patients with renal artery stenosis (RAS) exhibit increased risk of cardiovascular death and all-cause death. Our previous finding showed that the presence of RAS is associated with poor coronary collateral development and adverse 5-year outcome. Impaired arteriogenesis might partly explain the poor prognosis in RAS patients. This study aimed to investigate the impact of RAS on arteriogenesis and explore the possible role of interleukin-6 in this pathophysiological process. METHODS: SHR rat was used as a control, while WKY rat underwent left renal artery coarctation to establish a two-kidney one-clip model with a 0.25mm silver clip at the left renal artery. Seven days after the left renal artery coarctation or sham operation, hind limb ischemia was induced by ligation of the left femoral artery. Blood pressure and heart rate were recorded every week. Laser Doppler perfusion imaging was performed at baseline, immediately after femoral ligation, at 14 and 28 days postfemoral artery ligation. Serum and hind limb tissue were collected for later analysis. RESULTS: At the end of this study, no significant difference in blood pressure or heart rate was found between SHR and RAS rats. However, when treated with tocilizumab (TCZ), blood pressure was significantly lowered in RAS rats. Twenty-eight days after left femoral artery ligation, left hind limb perfusion was significantly worse in RAS rats than in SHR, and angiogenesis in the soleus muscle was similar between the groups, suggesting impaired arteriogenesis in RAS rats compared to SHR. Although the number of adductor muscle arterioles in RAS rats was not less than that of SHR, the mean inner diameter of arterioles in RAS rats was smaller than that of SHR. When treated with the TCZ, left hind limb perfusion in the RAS+TCZ rat was not improved. TCZ lowered serum and tissue levels of IL-6 in RAS+TCZ rats. Serum creatinine was mildly elevated in the RAS group. DISCUSSION: Since blood pressure was similar between SHR and RAS rats, and TCZ failed to improve arteriogenesis in the RAS+TCZ group, we think that IL-6 might not be the primary mediator leading to impaired arteriogenesis in RAS rats. It seems that renal dysfunction induced by renal ischemia might have more chance to impair collateral development than hypertension or IL-6 in RAS rats. CONCLUSION: Existence of RAS is associated with worse arteriogenesis, which might explain the increased risk of cardiovascular death and all-cause death in patients with RAS. IL-6 might not be responsible for impaired arteriogenesis in RAS rats. Possible mechanisms need to be investigated further.
The Role of suPAR in Kidney Injury Progression.
Guo H, Yang J, Ye Q … +3 more , Xiang L, Zhang F, Liu J
Curr Mol Med · 2026 May · PMID 42152651 · Publisher ↗
INTRODUCTION: This article provides a thorough review of how suPAR influences kidney injury. It aims to inform relevant fields, clarify the mechanisms of its effects, and ultimately enhance patient treatment outcomes and...
INTRODUCTION: This article provides a thorough review of how suPAR influences kidney injury. It aims to inform relevant fields, clarify the mechanisms of its effects, and ultimately enhance patient treatment outcomes and quality of life. METHODS: A thorough literature review was conducted, analyzing published research articles, meta-analyses, and clinical studies investigating the structure, function, and pathophysiological roles of suPAR in various forms of kidney injury. Mechanisms were explored through evidence from in vitro studies, animal models, and human observational/clinical trials. The focus was on suPAR's involvement in key processes like inflammation, oxidative stress, apoptosis, and fibrosis within the kidney. RESULTS: suPAR drives AKI progression by promoting inflammation (via NF-κB/NLRP3 activation), oxidative stress (via ROS generation), and apoptosis. In CKD, suPAR induces podocyte injury (via αvβ3 integrin/Rac1 signaling) and renal fibrosis. Elevated suPAR levels predict AKI incidence and CKD progression. suPAR also mediates AKIto- CKD transition. DISCUSSION: suPAR is an important pathogenic mediator in kidney injury. In Acute Kidney Injury (AKI), suPAR drives progression via inflammation, oxidative stress, and apoptosis. In Chronic Kidney Disease (CKD), it promotes renal fibrosis. Furthermore, suPAR facilitates the transition from AKI to CKD. CONCLUSION: suPAR is a critical pathogenic factor and biomarker driving kidney injury progression in AKI (via inflammation/oxidative stress/apoptosis) and CKD (via fibrosis), and facilitates the AKI-to-CKD transition.
Pharmacological Mechanisms of Curcumin and Resveratrol in Inflammation-associated Head and Neck Cancer Progression and Pain Management.
Lu X, Song S
Curr Mol Med · 2026 May · PMID 42152650 · Publisher ↗
Head and Neck Cancer (HNC) represents a significant global health challenge, marked by high incidence, poor prognosis, and frequent association with chronic inflammation. Pain management in HNC is complex and often inade...
Head and Neck Cancer (HNC) represents a significant global health challenge, marked by high incidence, poor prognosis, and frequent association with chronic inflammation. Pain management in HNC is complex and often inadequate. Curcumin and resveratrol, two naturally occurring polyphenols, have attracted considerable attention for their anti-inflammatory and anti-cancer activities. This review systematically examines the molecular mechanisms by which curcumin and resveratrol modulate key signaling pathways, including NF-κB, STAT3, PI3K/Akt/mTOR, and SIRT1, in the context of HNC progression and pain. Curcumin exerts its effects by inhibiting pro-inflammatory cytokines, suppressing tumor proliferation, and inducing apoptosis, while resveratrol activates SIRT1, inhibits MAPK and mTOR pathways, and enhances apoptosis and anti-metastatic effects. Both compounds influence the tumor microenvironment, potentially enhancing anti-tumor immunity. Combined, they may provide synergistic benefits, including augmented apoptosis and enhanced modulation of inflammatory pathways. Preclinical evidence supports their efficacy in tumor suppression and pain reduction, though clinical translation remains limited due to poor bioavailability. Recent advances in nanoformulations have improved systemic delivery, and initial clinical trials show promising effects in reducing oral mucositis and modulating antioxidant status. However, large, well-designed clinical trials are needed to confirm their therapeutic roles, clarify synergistic mechanisms, and optimize formulations for effective HNC treatment. Dedicated research on pain management and opioid-sparing effects is especially warranted. Together, curcumin and resveratrol represent promising adjuncts to current HNC therapies, with the potential to improve tumor control and patient quality of life.
ATIC Promotes LIHC Progression and Serves as an Independent Prognostic Marker: A Pan-cancer Transcriptomic Analysis.
Li H, Zhang W, Zhou X … +7 more , Wu W, Yao F, Zhong H, Zhan N, Chen J, Zhan Y, Yang X
Curr Mol Med · 2026 May · PMID 42152649 · Publisher ↗
BACKGROUND: 5-aminoimidazole-4-carboxamide ribonucleotide formyltransferase/ IMP cyclohydrolase(ATIC) is a 64-kDa bifunctional enzyme, 5-aminoimidazole- 4-carboxamide ribonucleotide formyltransferase (AICART) and IMP cyc...
BACKGROUND: 5-aminoimidazole-4-carboxamide ribonucleotide formyltransferase/ IMP cyclohydrolase(ATIC) is a 64-kDa bifunctional enzyme, 5-aminoimidazole- 4-carboxamide ribonucleotide formyltransferase (AICART) and IMP cyclohydrolase, respectively. catalyzes the last two steps of the purine ab initio biosynthetic pathway. ATIC has been implicated in cancer progression, but its pan-cancer profile and specific prognostic utility in liver hepatocellular carcinoma (LIHC) remain incompletely defined. METHODS: We analyzed TCGA RNA-seq data across 33 tumor types to assess ATIC expression, diagnostic performance (ROC/AUC), and prognostic associations (OS, DSS, PFI). We correlated ATIC expression with immune infiltration, TMB, MSI, and predicted neoantigen load, and constructed a LIHC-specific prognostic nomogram integrating ATIC and clinicopathologic features. Enrichment analyses (STRING, GO/KEGG, GSEA) and pharmacogenomic correlations (GDSC, CTRP) were performed to explore mechanisms and drug sensitivities. RESULTS: ATIC was significantly upregulated in 16 tumor types, including LIHC (p<0.001). Pan-cancer ROC analyses showed high diagnostic accuracy in several cancers (examples: CHOL AUC=1.000, LIHC AUC=0.936, LUAD AUC=0.947). High ATIC expression associated with poorer OS in ACC, HNSC, LIHC, and PAAD (eg, LIHC: HR=1.39(1.04-1.85), p=0.028). In LIHC, ATIC correlated with advanced T stage, higher grade, elevated AFP, and shorter OS. Multivariable Cox regression identified ATIC expression and pathological T stage as independent predictors; time-dependent ROC for the LIHC nomogram showed AUCs of 0.711, 0.649, and 0.653 at 1, 3, and 5 years, respectively. GSEA indicated enrichment of PI3K-AKT-mTOR, MYC targets, and cell-cycle pathways in ATIC-high LIHC. High ATIC expression correlated with predicted increased sensitivity to sorafenib, doxorubicin, cisplatin, epothilone, and mitomycin in the TCGA-LIHC cohort. DISCUSSION: ATIC upregulation across cancers links to tumor progression, immune modulation, and prognosis (LIHC), suggesting oncogenic roles in pan-cancer contexts. TCGA multi-omics show ATIC associates with immune/molecular subtypes, MSI/TMB/neoantigens, and predicts drug sensitivity, indicating diagnostic/prognostic potential. CONCLUSION: ATIC is broadly upregulated across cancers and functions as an independent prognostic biomarker in LIHC. The ATIC-integrated nomogram shows modest predictive accuracy for LIHC survival. Our results implicate ATIC in oncogenic signaling (PI3K-AKT-mTOR, MYC, and cell-cycle) and suggest ATIC as a candidate biomarker to guide targeted and chemotherapeutic strategies in LIHC. Further in vitro and in vivo validation is warranted.
Construction of an Extracellular Matrix-related Gene Model for Predicting Prognosis and Immune Features in Gastric Cancer.
Xing C, Deng H, Yang C … +4 more , Yang B, Wan Y, Feng J, Yu Y
Curr Mol Med · 2026 May · PMID 42152648 · Publisher ↗
INTRODUCTION: The extracellular matrix (ECM) critically shapes the gastric cancer (GC) microenvironment and influences tumor initiation, proliferation, invasion, and angiogenesis. However, the prognostic significance of...
INTRODUCTION: The extracellular matrix (ECM) critically shapes the gastric cancer (GC) microenvironment and influences tumor initiation, proliferation, invasion, and angiogenesis. However, the prognostic significance of ECM-related genes in GC has not been systematically elucidated. METHODS: Differentially expressed genes (DEGs) between GC and adjacent normal tissues were extracted from The Cancer Genome Atlas. ECM-related DEGs were identified and incorporated into a prognostic model using LASSO Cox regression. Risk scores were calculated for each patient, and a nomogram integrating clinical variables was developed. Model performance was assessed by receiver operating characteristic (ROC) analysis and validated in two independent external cohorts. RESULTS: The ECM-based risk model stratified GC patients into high- and low-risk groups with significantly different overall survival. ROC analysis demonstrated strong predictive accuracy, and the nomogram showed good concordance between predicted and observed outcomes. Importantly, patients in the high-risk group exhibited elevated expression of immune checkpoint molecules. DISCUSSION: The ECM-related prognostic model provides a novel framework for risk assessment in GC. Beyond prognostication, the model highlights an immunological link: the high-risk group demonstrated upregulation of immune checkpoints. These findings suggest the model not only predicts survival but may also identify subgroups of patients more likely to benefit from immunotherapy. CONCLUSION: We established and validated a robust ECM-related prognostic model and nomogram for GC. This tool provides clinically relevant prognostic information and may inform personalized treatment strategies, particularly in identifying patients who could benefit from immunotherapy.
Sodium Ion Channel Active Agent Deltamethrin Induces Cell Apoptosis and Cell Cycle Arrest through Mitochondrial Dependent Pathway in Human Fetal Lung Fibroblasts.
Wang X, Shen W, Tian T … +2 more , Zhang X, Yang M
Curr Mol Med · 2026 May · PMID 42152647 · Publisher ↗
INTRODUCTION: Pulmonary Fibrosis (PF) is a common outcome of many interstitial lung diseases. Sodium ion channels play an important role in maintaining membrane potential, transmitting ion signals across the membrane, an...
INTRODUCTION: Pulmonary Fibrosis (PF) is a common outcome of many interstitial lung diseases. Sodium ion channels play an important role in maintaining membrane potential, transmitting ion signals across the membrane, and mediating cell proliferation/migration. Deltamethrin (DM) can prevent the closure of voltage-gated sodium ion channels in insect axon membranes. This study aimed to further evaluate the potential effects of DM on Human Fetal Lung Fibroblasts (HFLF). METHODS: The characteristic apoptotic changes were also assessed using DNA fragmentation analysis, terminal deoxynucleotidyl Transferase-Mediated Dutp Nick End Labeling (TUNEL), and annexin V/PI and Hoechst 33342/PI double staining. In addition, DM-induced cell cycle arrest in the G0/G1 phase was detected in a dosedependent manner. Furthermore, transcriptional and translational expression of selected genes under DM stress were used to confirm the analysis. RESULTS: We showed that DM dose-dependently decreased cell viability and inhibited cell proliferation in the HFLF cell line. The data suggested that the effect of DM inhibition was at least partly through regulating the expression of Ras, p53, p21, p27, cyclin D1, cytochrome c, caspase-3, and Bcl-2 family members. DISCUSSION: These results revealed that DM might induce cell apoptosis and cell cycle arrest through a mitochondrial-dependent cytotoxic stress pathway in the HFLF cell line, but there is a lack of animal experiments to verify this. We will continue to follow up on the experiment to further improve it. CONCLUSION: Our study provides insight into assessing the potential anti-pulmonary fibrosis function of DM at the molecular level.
The MAPK/ERK Signaling Pathway in Colorectal Cancer: Recent Advances and Emerging Insights.
Molavand M, Valizadeh A, Yousefi B
Curr Mol Med · 2026 May · PMID 42152646 · Publisher ↗
Colorectal Cancer (CRC) is the third most prevalent malignancy, with a high mortality rate. Ageing is a key risk factor connected with this colon- or rectumaffecting malignancy. Aberrant activation of oncogenic signaling...
Colorectal Cancer (CRC) is the third most prevalent malignancy, with a high mortality rate. Ageing is a key risk factor connected with this colon- or rectumaffecting malignancy. Aberrant activation of oncogenic signaling pathways, such as MAPK/ERK, PI3K/AKT, and Notch, is frequently exhibited in CRC. The MAPK/ERK signaling cascade, as part of a broader cellular signaling network, plays a prominent role in orchestrating many biological processes. Stimulation of receptors implicated in this pathway by a wide spectrum of ligands leads to an upregulation in the expression of target genes by phosphorylated ERK. Cutting-edge molecular profiling has elucidated various mutational alterations within the MAPK/ERK pathway, with a noticeable focus on KRAS and BRAF mutant variants. Various facets of CRC advancement are intricately related to ERK hyperactivity. Prominent developmental phenomena attributed to this signaling cascade encompass elevated cellular proliferation, maintenance of the cancer stem-cell population, drug resistance, facilitation of angiogenesis, and increased invasive and migratory potential in CRC. Due to the profound role of ERK in the evolutionary stages of CRC, solving this problem depends on deepening our understanding of the ERK signaling pathway. In the domain of advancing CRC therapies, the design of personalized treatment plans assumes specific significance. The detection of KRAS and BRAF mutations in patients can be a predictive marker of therapy response and clinical outcome. By integrating recent insights, this article aims to review the complexities of MAPK/ERK's role in CRC progression and its notable potential in the development of more effective, targeted therapeutic approaches.
Effects of 1,8-Cineole on Diabetic Muscular Atrophy.
Al-Quraan LT, Al-Trad B, Alomari G … +2 more , Aljabali AAA, Al-Shwaheen A
Curr Mol Med · 2026 May · PMID 42136276 · Publisher ↗
INTRODUCTION: This study aimed to address the effects of 1,8-cineole on diabetic muscular atrophy in streptozotocin (STZ)-induced diabetic rats. MATERIALS AND METHODS: Adult male rats were divided into three groups (n =...
INTRODUCTION: This study aimed to address the effects of 1,8-cineole on diabetic muscular atrophy in streptozotocin (STZ)-induced diabetic rats. MATERIALS AND METHODS: Adult male rats were divided into three groups (n = 15): nondiabetic control (ND), diabetic (D), and diabetic rats treated with 1,8-cineole intraperitoneally for 21 days. A single low-dose intraperitoneal injection of STZ (50 mg/kg) was used to induce diabetes. At the end of the experiment, blood and muscle tissue samples were collected for analysis. RESULTS: There was a significant increase in blood glucose levels in diabetic rats, which coincided with significant increases in the skeletal muscles' mRNA expression levels of two inflammatory markers, transforming growth factor-β1 (TGF-β1) and tumor necrosis factor-α (TNF‑α), and in two biomarkers of skeletal muscle atrophy, F-boxonly protein 32 (FBXO32) and muscle RING-finger protein-1 (MuRF1). Additionally, diabetic rats showed a significant decrease in the expression of skeletal muscle glucose transporter 4 (GLUT4) levels. The malondialdehyde (MDA) level was increased, while the activity of superoxide dismutase (SOD) was not changed in the skeletal muscle of the D group compared to the ND group. Cineol treatment reversed the diabetes-induced changes in the relative mRNA expression levels of TGF-β1, TNF- α, FBXO32, MuRF1, and GLUT4 in the skeletal muscle and significantly decreased MDA levels with a non-significant increase in skeletal muscle SOD activity. DISCUSSION: These results suggest that 1,8-cineole protects diabetic skeletal muscles in multiple ways, including reducing oxidative stress, inhibiting the generation of inflammatory cytokines, and preventing the expression of proteolytic genes. Its capacity to increase GLUT4 levels enhances glucose absorption and insulin sensitivity. Therefore, in diabetic situations, 1,8-cineole may help maintain muscle structure and function. These findings add to the increasing amount of data indicating that 1,8- cineole is a viable option for treating diabetes-induced muscle problems brought on by diabetes. To fully understand its therapeutic potential, further research is necessary, including studies on muscle mass, myostatin levels, and protein expression. CONCLUSION: 1,8-cineole tr1eatment decreased blood glucose levels and attenuated oxidative stress and inflammation in the skeletal muscles of diabetic rats, thereby protecting rats against diabetic muscle atrophy.
Recovery Kinetics and Persistent Hepatic Alterations in a Xenobiotic-induced Murine Model of Chronic Cholestatic Liver Disease.
Valero-Breton M, Portal-Rodriguez M, Tacchi F … +7 more , Salgado-Valdovinos J, Monsalves-Álvarez M, Hidalgo C, Stoore C, Paredes R, Cabrera D, Cabello-Verrugio C
Curr Mol Med · 2026 May · PMID 42136275 · Publisher ↗
INTRODUCTION/OBJECTIVE: Chronic cholestatic liver disease (CCLD) is characterized by impaired bile production and excretion due to its inflammatory nature and potential progression to biliary cirrhosis. Murine models mim...
INTRODUCTION/OBJECTIVE: Chronic cholestatic liver disease (CCLD) is characterized by impaired bile production and excretion due to its inflammatory nature and potential progression to biliary cirrhosis. Murine models mimic cholestatic-type human liver diseases, such as the 3,5- diethoxycarbonyl-1,4-dihydrocholidine (DDC) model. Nonetheless, the timeline for liver regeneration following cessation of the DDC diet remains unclear. This study aimed to evaluate the duration of hepatic alterations after cessation of the DDC diet. METHODS: C57BL/6J male mice (16-17 weeks old) were randomly assigned to Control (standard diet) and CCLD (DDC-supplemented diet) groups. After six weeks of diet exposure, the DDC group transitioned to a standard diet. Liver parameters were evaluated at 3-, 18-, and 36-days post-diet cessation. Analysis included liver damage and weight, histopathology, and biochemical markers. RESULTS: Liver damage remained elevated until day 36, whereas liver weight remained elevated until day 18. Histological analysis confirmed that bile duct obstruction and fibrosis scores in the DDC group remained significantly higher than in controls up to 36 days after the DDC diet. Serum bile acid levels remained elevated for up to 18 days, while GGT levels did not differ across time points. AST levels were markedly increased at 3 days, whereas ALT levels remained elevated at 3 and 18 days. DISCUSSION/CONCLUSION: Total cholesterol and triglyceride levels increased until day 18, highlighting changes in lipid metabolism. Our study demonstrates hepatic effects in the DDCinduced CCLD model, with alterations persisting beyond cessation of hepatotoxin exposure. These findings show the temporal dynamics of CCLD after diet cessation through different liver parameters.
Molecular Mechanisms of New and Re-purposed Synthetic as well as Natural Bioactive Molecules Against Breast Cancer: Elucidating Targets, Signaling Pathways, Resistance Modulation, and Synergistic Combinations for Prevention.
Samajdar S, Julekha K, Mishra S … +1 more , Guhu D
Curr Mol Med · 2026 May · PMID 42136274 · Publisher ↗
Breast cancer remains a major public health challenge in India, with rising incidence and the limited efficacy of conventional chemotherapeutics driven by multidrug resistance (MDR), systemic toxicity, and therapeutic re...
Breast cancer remains a major public health challenge in India, with rising incidence and the limited efficacy of conventional chemotherapeutics driven by multidrug resistance (MDR), systemic toxicity, and therapeutic relapse. This review synthesizes emerging mechanistic evidence on repurposed synthetic agents and bioactive natural compounds, presenting a unified framework for mechanism-guided anti-cancer intervention. The selective estrogen receptor modulator (SERM) ormeloxifene exemplifies the promise of drug repurposing, exerting multi-target cytotoxicity through mitochondrial membrane depolarization, G0/G1 cell-cycle arrest, caspase-dependent apoptosis, ERα modulation, and disruption of proliferative signaling circuits. In parallel, potent natural products-including ellagitannins (corilagin, castalin, punicalagin) and triterpenoid saponins (α-hederin, D-rhamnose-β-hederin, quillaic acid, hederagenin)-demonstrate complementary mechanisms by enhancing intracellular ROS accumulation, suppressing PI3K/Akt and mTOR signaling, inhibiting NF-κB activation, and triggering intrinsic and extrinsic apoptotic pathways. Integrating these mechanistic axes, this review highlights a key innovation: both synthetic and phytochemical scaffolds converge on actionable molecular nodes governing survival signaling, metabolic rewiring, and MDR modulation. This convergence underscores their translational potential for developing combination or sequential regimens that enhance selectivity, circumvent drug resistance, and minimize off-target toxicity. Collectively, these mechanistically validated agents represent promising leads for preclinical optimization and rational design of next-generation, pathway-directed breast cancer therapeutics.
The Pathological Development of EndMT in Lung Diseases and its Regulatory Mechanisms.
Huang J, Wang P, You Y … +3 more , Liu Y, Bao X, Zhu X
Curr Mol Med · 2026 May · PMID 42136273 · Publisher ↗
Endothelial-to-Mesenchymal Transition (EndMT) is a regulatory mechanism integral to the normal developmental processes of the organism, playing a pivotal role in sustaining the homeostasis of the intravascular milieu. Ho...
Endothelial-to-Mesenchymal Transition (EndMT) is a regulatory mechanism integral to the normal developmental processes of the organism, playing a pivotal role in sustaining the homeostasis of the intravascular milieu. However, when the internal environment exceeds the endothelium's compensatory capacity, excessive EndMT can precipitate pathological alterations. EndMT is particularly significant in the pathogenesis of pulmonary diseases, including pulmonary fibrosis, pulmonary hypertension, and lung cancer. The regulatory mechanisms underlying EndMT are intricate and multifaceted. Numerous signaling pathways have been implicated in EndMT modulation, with the TGF-β pathway emerging as a central inducer. Furthermore, research has identified that epigenetic modifications, metabolic processes, hypoxia, inflammatory cytokines, and oxidative stress all contribute to the regulation of EndMT. This complexity renders the interplay between EndMT and pulmonary vascular diseases exceedingly intricate. In this manuscript, we provide a comprehensive overview of the signaling pathways and other influencing factors that govern EndMT. Concurrently, we meticulously delineate potential therapeutic targets to offer novel avenues and insights for the management of pulmonary diseases. Our synthesis of the current understanding of EndMT regulation is intended to inform future research and clinical strategies, potentially leading to more effective interventions for patients afflicted with pulmonary disorders.
Diagnostic and Prognostic Significance of the S100 Biomarker in Blast-related Closed Traumatic Brain Injury.
Balakin EI, Yurku KA, Pustovoyt VI
Curr Mol Med · 2026 May · PMID 42136272 · Publisher ↗
INTRODUCTION: Traumatic Brain Injury (TBI) is a frequent cause of long‑term disability in service members who have been exposed to blast, and clinicians often lack reliable tools to quantify the actual burden of damage e...
INTRODUCTION: Traumatic Brain Injury (TBI) is a frequent cause of long‑term disability in service members who have been exposed to blast, and clinicians often lack reliable tools to quantify the actual burden of damage early after injury. Among available candidates, S100B is a calcium‑binding protein of astroglial origin that appears in the bloodstream when the blood-brain barrier is disrupted, and neuronal structures are injured. Its diagnostic and prognostic properties in the specific setting of blast‑related closed TBI, however, remain incompletely defined. The present study, therefore, focuses on military personnel with blast‑related closed TBI and examines the diagnostic and prognostic significance of serum S100 by tracking its concentration at several post‑injury time points across predefined severity groups. METHODS: A prospective cohort of military patients with blast‑related closed TBI was examined, and serum S100 concentrations were measured at 1, 3, 6, and 12 hours after injury. Patients were stratified into mild, moderate, and severe TBI categories, and S100 dynamics were analysed in relation to these severity groups using standard descriptive statistics, group‑comparison tests, ROC analysis, correlation analysis, and K‑means clustering, as detailed in the Methods section. RESULTS: Serum S100 levels peaked at 6 hours after trauma and showed a moderate correlation with TBI severity (r = 0.65, p < 0.001). Statistically significant differences in S100 concentrations were found between severity groups at all investigated time points (p < 0.001), and ROC analysis yielded an AUC of 0.81 for severity discri-mination. Diagnostic performance indices (AUC, optimal cutoff, sensitivity, specificity, positive and negative predictive values, and overall accuracy with 95% confidence intervals) are summarised in the Results, and K‑means clustering revealed distinct patient subgroups with different temporal S100 profiles, indicating the feasibility of more personalized risk stratification and management. DISCUSSION: These findings support the use of S100 as a clinically relevant biomarker for early grading of blast‑related closed TBI and short‑term outcome prediction. Incorporating S100 into multimodal assessment algorithms may improve risk stratification and guide timely therapeutic decisions in affected patients. CONCLUSION: S100 can be considered a useful biomarker for early grading of brain injury severity and outcome prediction in blast‑related closed TBI. Integration of S100 into multimodal diagnostic algorithms has the potential to improve stratification of patients, inform therapeutic decision‑making, and enhance outcomes in military and civilian populations exposed to blast trauma.
Apolipoprotein A2 Influences ANGPTL3 in Modulating TG Catabolism and Inflammatory Cytokines Secretion.
Cheng Y, Wang S
Curr Mol Med · 2026 May · PMID 42099146 · Publisher ↗
INTRODUCTION: Apolipoprotein A2 (ApoA2) and ANGPTL3 modulate LPL activity and inflammatory cytokine secretion, resultantly influencing TG metabolism and inflammatory response. However, any associations that exist between...
INTRODUCTION: Apolipoprotein A2 (ApoA2) and ANGPTL3 modulate LPL activity and inflammatory cytokine secretion, resultantly influencing TG metabolism and inflammatory response. However, any associations that exist between those modulators were not explored. The study aimed to elucidate the functions of ApoA2 in modulating ANGPTL3 on the metabolism of TG and inflammatory cytokine secretion. METHOD: A case-control hospital-based clinical study was conducted. A total of 50 patients with diagnosed CAD and 50 healthy control individuals were enrolled. Levels of ApoA2, ANGPTL3, and several pro-inflammatory cytokines were measured. RESULT: The levels of ANGPTL3 and ApoA2 exhibited no significant discordance between the CAD group and control group. Both ANGPTL3 and ApoA2 were associated with TG (r = 0.249, P = 0.002; r = 0.379, P = 0.001, respectively). Additionally, ApoA2 were inversely associated with hs-CRP (r = -0.079, P =0.003), TNF-α (r = -0.119, P = 0.001), and IL-1β (r = -0.103, P = 0.004). Regression analysis confirmed that ApoA2 was an independent modulator of TG and inflammatory cytokines independent of ANGPTL3 (standardized β = 0.196, P < 0.001). DISCUSSION: ANGPTL3 and ApoA2 correlate with TG levels, with ApoA2 identified as an independent contributor via stepwise regression, and ANGPTL3 exerts its TGregulating effect mainly by inhibiting LPL activity through multiple mechanisms, suggesting its potential anti-inflammatory role, though conflicting findings in existing studies indicate the need for further clarification of this relationship. CONCLUSION: ApoA2 influences ANGPTL3 in modulating catabolism of TG and atherosclerotic-related inflammatory cytokines, suggesting a vital role of ApoA2 in promoting pathological progression of CAD.
The Effect of mascRNA on the Phenotype Transition and Mitophagy in Vascular Smooth Muscle Cells Exposed to Hypoxia.
Hou J, Weng R, Li X … +3 more , Gu X, Zhao J, Liu S
Curr Mol Med · 2026 May · PMID 42099145 · Publisher ↗
INTRODUCTIONS: A primary complication of atherosclerosis(AS) is characterized by chronic inflammatory and mitochondrial dysfunction, both of which play critical roles in the disease's progression. This study aims to inve...
INTRODUCTIONS: A primary complication of atherosclerosis(AS) is characterized by chronic inflammatory and mitochondrial dysfunction, both of which play critical roles in the disease's progression. This study aims to investigate the regulatory role of mascRNA in mediating the hypoxia-induced phenotypic transition of vascular smooth muscle cells (VSMCs). METHODS: An AS model was established, and the aortic plaque area was assessed by Oil Red O staining. Human VSMCs were divided into five groups: normoxia, hypoxiainduced, negative control (pGV-NC), mascRNA overexpression (pGV-mascRNA), and inhibitor-treated. Quantitative PCR (qPCR) was utilized to detect the expression of mascRNA, vWF, and MMP2. Western blotting was performed to detect the expression of phenotypic transformation-related proteins. RESULTS AND DISCUSSION: In high-fat diet (HFD)-fed mice, the expression of mascRNA was significantly decreased in the aortas (P < 0.05). Hypoxia led to a reduction in mascRNA levels, an upregulation of synthetic markers, and increased reactive oxygen species (ROS) in VSMCs. Overexpression of mascRNA suppressed VSMC migration and proliferation, enhanced mitophagy, and inhibited the PI3K-AKT pathway. Our study has been the first to demonstrate mascRNA play a crucial role in VSMC phenotypic transformation and functions via regulation of mitophagy. These findings highlight mascRNA's role in AS development and provide a theoretical basis for its clinical applications, but in vivo experiments are called for to validate its anti-AS effect. CONCLUSION: MascRNA suppressed hypoxia-induced phenotypic transformation of VSMCs, potentially through the modulation of the PI3K-AKT signaling pathway and the enhancement of mitochondrial autophagy. These findings indicate a prospective therapeutic application of mascRNA in AS.
Beyond Conventional Therapy: A Comprehensive Review of Herbal, Traditional, and Emerging Interventions for Polycystic Ovary Syndrome.
Bashir S, Shah IM, Javeed S … +5 more , Rafiquee A, Mir B, Hassan Mir R, Geer MI, Ganie MA
Curr Mol Med · 2026 Apr · PMID 42083350 · Publisher ↗
Polycystic ovary syndrome (PCOS) is the most common and multifactorial endocrine disorder that leads to significant changes in the reproductive, metabolic, and psychological domains of women's health in their reproductiv...
Polycystic ovary syndrome (PCOS) is the most common and multifactorial endocrine disorder that leads to significant changes in the reproductive, metabolic, and psychological domains of women's health in their reproductive years. In addition, the conventional therapies (lifestyle modification, metformin, oral contraceptives, and ovulation-inducing agents) that are the mainstay of management of the syndrome may still not be able to fully address the diverse pathophysiology of PCOS as well as the long-term risks associated with it. This narrative review highlights clinical and mechanistic data from studies on various complementary and alternative medicine (CAM) modalities as first-line treatments for PCOS, in addition to conventional therapy. Correspondingly, herbal and botanical agents (berberine, cinnamon, licorice, Vitex agnus-castus, curcumin, and epigallocatechin gallate) modulate insulin signalling, androgen synthesis, inflammatory pathways, and oxidative stress, with initial clinical trials reporting improvements in metabolism and hormones to a similar extent as standard therapies in selected populations. Traditional Chinese Medicine (TCM), both multi-herb prescriptions and acupuncture, provides tailored formulas that might not only regulate ovulation and endocrine parameters but also lower metabolic indices, despite the high variability across studies. Stress reduction, physical fitness, and the quality of life are among the achievements of mind-body interventions (yoga, tai chi, qigong, and mindfulness-based stress reduction). Improvements in hyperinsulinemia, hypolipidemia, ovulation, and hyperandrogenemia, along with the related insulinresistant and vitamin D-deficient phenotypes, have been steadily reported with the use of the nutraceutical combinations of inositols, vitamin D, omega-3 fatty acids, Nacetylcysteine, coenzyme Q10, and resveratrol. New non-conventional methods, such as fecal and vaginal microbiota transplantation, platelet-rich plasma, and kisspeptin analogues, have been identified as potential therapeutic routes but are still in their infancy in terms of development. Although CAM therapies have multiple advantages in controlling many PCOS domains, the official integration into clinical practice would require standardization, rigorous randomized controlled trials, and continuous safety monitoring. If correctly and cautiously applied, CAM may be useful as an adjunct alongside established therapy, rendering PCOS management more holistic and personalized.
Association Between Bilirubin and Klotho Levels in US Middleaged and Older Adults: NHANES 2007-2016.
Ling C, Tian L, Sun J … +2 more , Yin Y, Cheng X
Curr Mol Med · 2026 · PMID 42083349 · Publisher ↗
OBJECTIVE AND METHODS: Bilirubin, a potent endogenous antioxidant, protects against multiple diseases. This cross-sectional study explored the relationship between Serum Total Bilirubin (STB) and Serum Klotho (S-Klotho,...
OBJECTIVE AND METHODS: Bilirubin, a potent endogenous antioxidant, protects against multiple diseases. This cross-sectional study explored the relationship between Serum Total Bilirubin (STB) and Serum Klotho (S-Klotho, an anti-aging biomarker) in 40-79-year-olds from the 2007-2016 NHANES survey. Statistical analysis used a multivariable regression model; a Restricted Cubic Spline (RCS) model evaluated potential non-linear STB-S-Klotho associations. Subgroup analyses and sensitivity tests ensured the robustness. RESULTS: The analysis included 4,562 individuals aged 40-79. Both unadjusted and adjusted models showed a significant positive association between STB and S-Klotho (β = 2.84, P = 0.02 in the weighted, fully adjusted model). The RCS curve indicated no significant non-linearity (P for non-linearity = 0.211). Subgroup analyses revealed stronger associations in females, normal-weight individuals, and those without diabetes mellitus (DM) or hypertension. DISCUSSION: This is the first study exploring the STB-S-Klotho relationship. While human studies on bilirubin's role in aging have inconsistent conclusions, animal and mechanistic research show that elevated bilirubin reduces oxidative stress and inflammation, potentially protecting against age-related conditions. CONCLUSION: Our findings confirm a positive STB-S-Klotho correlation in middle-aged and older adults, suggesting bilirubin may be a potential S-Klotho biomarker and reflect biological aging processes.
Effect of hucMSC-derived Exosomes on the Pressure Ulcers in Mice.
Yan F, Yang J, Gong M … +2 more , Li G, Yu L
Curr Mol Med · 2026 Apr · PMID 42059215 · Publisher ↗
INTRODUCTION: Pressure ulcers (PUs) are a result of sustained compression of the local skin, leading to impaired blood circulation and subsequent nutritional deficiencies in the skin and subcutaneous tissues. Exosomes ar...
INTRODUCTION: Pressure ulcers (PUs) are a result of sustained compression of the local skin, leading to impaired blood circulation and subsequent nutritional deficiencies in the skin and subcutaneous tissues. Exosomes are one type of extracellular vesicle with a size range of 40 to 160 nm. Currently, the effects of Human umbilical cord mesenchymal stem cell-derived exosomes (hucMSC-exos) on the PUs and the underlying mechanisms remain largely unexplored. METHODS: In this study, a PUs model was constructed using BALB/c mice, and the effect of hucMSC-exos on the PUs mice was evaluated by using histopathological examination, quantitative real-time polymerase chain reaction (qRT-PCR), and western blotting. RESULTS: The results of HE staining and Masson staining demonstrated that the treatment of hucMSC-exos could alleviate the histopathological changes of mice. Furthermore, the results of qPCR demonstrated that hucMSC-exos decreased the levels of collagen I, collagen III, and α-SMA in PUs mice; and the results of western blotting demonstrated that the expressions of HMGB1 and α-SMA could be decreased by the administration of hucMSC-exos. DISCUSSION: The data in the manuscript suggest that hucMSC-exos are both safe and effective in the treatment of PUs. It is recommended that large-scale animal experiments and long-term administration time of hucMSC-exos should be conducted to further verify the effect of hucMSC-exos in PUs. CONCLUSION: The findings of this study demonstrated that hucMSC-exos alleviated the symptoms of PU mice by regulating HGMB1 and α-SMA, thus demonstrating the therapeutic potential of hucMSC-exos in PUs.
Sulfur Dioxide Inhibits TNF-α-induced Photoreceptor Cell Apoptosis Through Sulfenylation of Caspase-3 at Cysteine 163.
Du J, Huang Y, Li K … +2 more , Yu X, Lv B
Curr Mol Med · 2026 Apr · PMID 41968518 · Publisher ↗
INTRODUCTION/OBJECTIVE: Photoreceptor cell apoptosis contributes significantly to vision loss in retinal degenerative diseases. Gasotransmitter sulfur dioxide (SO2) has been implicated in the regulation of apoptotic proc...
INTRODUCTION/OBJECTIVE: Photoreceptor cell apoptosis contributes significantly to vision loss in retinal degenerative diseases. Gasotransmitter sulfur dioxide (SO2) has been implicated in the regulation of apoptotic processes. This study investigated changes in the endogenous SO2/aspartate aminotransferase (AAT) system during tumor necrosis factor-α (TNF-α)-induced photoreceptor cell apoptosis. METHODS: We examined the effect of endogenous SO2 on the TNF-α-stimulated apoptosis in 661 W photoreceptor cells and investigated the underlying molecular mechanisms. TNF-α-stimulated 661 W photoreceptor cells served as a cellular model to assess apoptosis via a TdT-mediated dUTP nick-end labeling (TUNEL) assay. We evaluated caspase-3 activation using western blotting and quantified its activity using a colorimetric assay. Site-directed mutagenesis and biotin-switch assays were performed to detect the effects of caspase-3 sulfenylation. RESULTS: During TNF-α-induced apoptosis in photoreceptor cells, the endogenous SO₂ system was markedly upregulated, which correlated with the effective inhibition of apoptosis. SO2 directly suppresses caspase-3 activity in retinal photoreceptor cells and recombinant proteins. Importantly, site-directed mutagenesis revealed that the C163S mutation in caspase-3 abolished SO2-mediated sulfenylation, thereby reducing its anti-apoptotic effects. These findings indicate that endogenous SO2 exerts its protective effects by sulfenylating caspase-3 at cysteine 163. DISCUSSION: Our study demonstrates that upregulation of the endogenous SO2 system directly inhibits caspase-3 activation through sulfenylating cysteine 163 in caspase-3, effectively reducing TNF-α-induced apoptosis in 661 W cells. These findings highlight the precise regulatory role of SO2 in apoptosis. CONCLUSION: This study provides novel insights into potential therapeutic targets for retinal degenerative diseases.
The Synergistic Effect of Nutlin-3a and a Wip1 Inhibitor in Inducing p53 Activity.
Alburghaif AH, Al-Hussaniy HA, Al-Samydai AM … +2 more , Saleem ZM, Jabbar AA
Curr Mol Med · 2026 Mar · PMID 41936118 · Publisher ↗
INTRODUCTION: The p53 protein plays a major role in maintaining genome stability as well as the response of cells to stress. One of the principal things that regulates p53 is MDM2, and the way it interacts with p53 is of...
INTRODUCTION: The p53 protein plays a major role in maintaining genome stability as well as the response of cells to stress. One of the principal things that regulates p53 is MDM2, and the way it interacts with p53 is of great significance in the degradation of p53. This dephosphorylation of p53 by Wip1 increases its affinity to MDM2, which causes p53 degradation. Wip1 is used to increase the growth of tumors by undermining the p53 pathway. However, the active form of p53 can be retained with the help of preventing Wip1, and this fact makes it useful as a target of cancer treatment. An ever-increasing body of preclinical evidence suggests the possibility that Wip1 inhibitors would be used alongside potent MDM2 inhibitors to enhance p53 activity and enhance treatment outcomes. The purpose of the review was to examine studies pertaining to the action of a Wip1 inhibitor and Nutlin-3a in order to induce p53 functionality. METHOD: We searched Google Scholar, PubMed, and other search engines using such terms as MDM2 inhibitors, Wip1 inhibitors, and Nutlin. Newer articles published after 2020 were chosen to ensure that the recent findings are included. RESULTS: Wip1, an attractive antineoplastic target to control the p53 pathway, is a dephosphorylator of p53 at serine-15. Nutlin-3a with a Wip1 inhibitor appears to act synergistically to push p53 half-maximal inhibitory concentrations (IC50) into the low micromolar range. This combination greatly stimulates downstream p53-dependent response, which leads to a strong reduction of cell proliferation. DISCUSSION: We find that MDM2 inhibitors in combination with Wip1 inhibitors are synergistic in stimulating p53 activity. The results emphasize the need to use a combination of p53 induction and the inactivation of its suppressors in the treatment of cancer. CONCLUSION: As p53 is the most commonly mutated gene across a broad range of tumors, enhancing p53 activity is a prerequisite for achieving potent therapeutic effects. We envision that combination therapies involving Nutlin-3a, Wip1 inhibitors, and other effective cancer treatments may synergistically improve p53 activity and enhance therapeutic outcomes.
A Systematic Review and Meta-Analysis of Immune Signatures Involved in the Prevalence of Exhaustion in Humans, Mice, and Bovine Species.
Sharma K, Sharma S, Dhanda S … +5 more , Gupta S, Mukartal SY, Rustagi S, Chaubey KK, Kumar S
Curr Mol Med · 2026 Mar · PMID 41936117 · Publisher ↗
INTRODUCTION: Immune exhaustion is known to occur in chronic infections as well as cancer, and is characterized by constant antigenic stimulation and gradual loss of T cell function and upregulation of immune exhaustion...
INTRODUCTION: Immune exhaustion is known to occur in chronic infections as well as cancer, and is characterized by constant antigenic stimulation and gradual loss of T cell function and upregulation of immune exhaustion markers. This systematic review aims to explore conserved and divergent exhaustion signatures across humans, mice, and bovines to advance our understanding for better translational outcomes. METHODS: Following PRISMA 2020 guidelines, studies from 2011-2023 were analyzed using a random-effects model (metaprop, logit transformation). Subgroup analyses (species, disease type), sensitivity and heterogeneity (I²) analyses were performed. Publication bias was performed to evaluate biomarker variability. RESULTS: Meta-analysis identified an almost consistent role of IL-6 (48%), IL-2 (51%), TNF-α (46%), IFN-γ (41%), and IL-10 (48%) in immune exhaustion throughout various chronic disease conditions. Co-inhibitory receptors such as PD-1 (51%), TIM-3 (54%), LAG-3 (59%), and CTLA-4 (64%) were highly upregulated. Extreme heterogeneity (I² >95%) pointed towards considerable variation mainly due to species differences, disease category, and methodological factors, with fewer murine and bovine studies compared to human literature. DISCUSSION: The confluence of pro-inflammatory cytokines with elevated checkpoint receptor expression highlights the fact that immune exhaustion is conserved across mammals. However, the limitation in extrapolation attributed to high heterogeneity and species imbalance exists in the study. Furthermore, the variations in disease models and technical differences in detection methods point towards a need for standardization and integrated comparative analyses to boost biomarker interpretation. CONCLUSION: Co-inhibitory receptors and various cytokines appear to be the conserved contributors to immune exhaustion across species. Further, enriching cross-species data sets and accounting for methodological variability will improve the translational importance and support in developing more precise therapeutic interventions.
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