Current Molecular Medicine[JOURNAL]
Sun
200 papers
Thymoquinone-PLGA-PF68 Nanoparticles Induce S Phase Cell Cycle Arrest and Apoptosis, Leading to the Inhibition of Migration and Colony Formation in Tamoxifen-Resistant Breast Cancer Cells.
Noor NS, Hamid SBS
Curr Mol Med · 2025 · PMID 39819413 · Publisher ↗
BACKGROUND: A biocompatible polymeric nanoparticle, TQ-PLGA-PF68, was developed through the interaction of the phytochemical thymoquinone (TQ) encapsulated in poly(L-lactide-co-glycolide)-b-poly(ethylene glycol) (PLGA-PE...
BACKGROUND: A biocompatible polymeric nanoparticle, TQ-PLGA-PF68, was developed through the interaction of the phytochemical thymoquinone (TQ) encapsulated in poly(L-lactide-co-glycolide)-b-poly(ethylene glycol) (PLGA-PEG) with Pluronics F68. So far, this combination has not been assessed on breast cancer cells resistant to anti-cancer drugs. Therefore, this study aimed to assess the cell death caused by TQ-PLGA-PF68 nanoparticles, particularly in resistant breast cancer cell lines expressing estrogen receptor (ER) positivity, such as TamR MCF-7. METHODS: The antiproliferative activity of TQ-PLGA-PF68 nanoparticles was measured using the MTS assay. The cytotoxic effects were further evaluated through colony formation assay and scratch-wound healing assay. Terminal deoxynucleotidyl transferase dUTP Nick End Labeling (TUNEL) assay was performed to determine the characteristics of the apoptosis as well as cell cycle arrest induced by TQ-PLGA-PF68 nanoparticles. The localization of these nanoparticles in the cells was examined using Transmission Electron Microscopy (TEM). RESULTS: With a TQ concentration of 58.5 μM encapsulated within the nanoparticles, cytotoxicity analysis revealed a significant inhibition of cell proliferation (p<0.05). This finding was corroborated by the results of the colony formation assay. Treatment with TQ-PLGA-PF68 nanoparticles significantly decreased the number of surviving TamR MCF-7 cells by 35% (p<0.001) compared to untreated TamR MCF-7 cells. Concurrently, the scratch-wound healing assay indicated a closure rate of 50% versus >80% (p<0.05) in untreated TamR MCF-7 cells at 12 hours post-wounding. The TUNEL assay successfully confirmed the apoptosis characteristics associated with cell cycle arrest. TEM observation confirmed the cellular internalization of these nanoparticles, suggesting the in vitro therapeutic potential of the formulation. CONCLUSION: In this study, a significant functional change in TamR MCF-7 cells induced by the TQ nanoparticles was observed. The unique incorporation of TQ into the PLGA-PEG and Pluronics F68 formulation preserved its bioactivity, thereby reducing the migratory and proliferative traits of drug-resistant cells. This discovery may pave the way for exploring the application of biocompatible polymeric TQ nanoparticles as a novel therapeutic approach in future studies pertaining to resistant breast cancer.
Reversal of Mucin 1 Reduction-Induced Enterocyte Apoptosis by Retinoic Acid through the PI3K/AKT Signaling Pathway in an In vitro Model of Necrotizing Enterocolitis.
Su Q, Chen L, Xu Y … +5 more , Feng J, Yu J, Zhang Z, Yu Z, Liu D
Curr Mol Med · 2025 · PMID 39819412 · Publisher ↗
OBJECTIVE: This study aimed to investigate the roles of Mucin 1 (MUC1), the PI3K/AKT pathway, and enterocyte apoptosis in Necrotizing Enterocolitis (NEC). METHODS: Using an NEC Caco-2 cell model, retinoic acid treatment...
OBJECTIVE: This study aimed to investigate the roles of Mucin 1 (MUC1), the PI3K/AKT pathway, and enterocyte apoptosis in Necrotizing Enterocolitis (NEC). METHODS: Using an NEC Caco-2 cell model, retinoic acid treatment and MUC1 gene silencing were employed. Flow cytometry was used to assess apoptosis, while quantitative PCR and western blot analyses were conducted to evaluate the gene and protein expressions of MUC1, PI3K, Akt, and factors related to apoptotic modulation. RESULTS: In comparison to the control group, NEC induction resulted in a significant reduction in MUC1 expression, accompanied by an elevation in enterocyte apoptosis. In NEC and Si-MUC1 Caco-2 cells, downregulation of PI3K/AKT signals and Bcl-2 was observed, while upregulation of Bax, CytoC, and Caspase 3 at both mRNA and protein levels was prominent. Retinoic acid supplementation exhibited a noteworthy increase in MUC1, AKT, and Bcl-2 mRNA and protein expressions, coupled with a decrease in Bax, CytoC, and Caspase 3, thereby mitigating apoptosis in NEC. CONCLUSION: Our findings suggested that reduced MUC1 expression in NEC contributes to the upregulation of enterocyte mitochondrial apoptosis through the PI3K/AKT signaling pathway. Retinoic acid supplementation emerges as a potential therapeutic strategy for NEC, demonstrating its ability to upregulate MUC1 expression and attenuate apoptosis via the PI3K/AKT signaling pathway.
Experimental Evidence of the Benefits of Acupuncture/ Electroacupuncture for Acute Lung Injury/ Acute Respiratory Distress Syndrome: A Literature Review of Rodent Studies.
Zeng L, Yan J
Curr Mol Med · 2025 · PMID 39817373 · Publisher ↗
Acute lung injury (ALI) and acute respiratory distress syndrome (ARDS) encompass various etiologies and are distinguished by the onset of acute pulmonary inflammation and heightened permeability of the pulmonary vasculat...
Acute lung injury (ALI) and acute respiratory distress syndrome (ARDS) encompass various etiologies and are distinguished by the onset of acute pulmonary inflammation and heightened permeability of the pulmonary vasculature, often leading to substantial morbidity and frequent mortality. There is a scarcity of viable approaches for treating effectively. In recent decades, acupuncture has been proven to be antiinflammatory. This review aims to provide a comprehensive summary of the previously documented mechanisms underlying the beneficial effects of acupuncture in ALI/ARDS, including inhibiting excessive oxidative stress, alleviating pulmonary inflammatory response, suppressing programmed cell death, and protecting the alveolar-capillary membrane. Collectively, these findings indicate that acupuncture yields therapeutic benefits for ALI/ARDS.
Morphine-Induced Elevation of Reactive Oxygen Species Attenuates Chemotherapy Efficacy in Diverse Cancer Cell Types.
Chen G, Zeng S, Wang B … +3 more , Wang D, Ding J, Feng T
Curr Mol Med · 2025 · PMID 39817372 · Publisher ↗
BACKGROUND: Morphine, a mu-opioid receptor (MOR) agonist commonly utilized in clinical settings alongside chemotherapy to manage chronic pain in cancer patients, has exhibited contradictory effects on cancer, displaying...
BACKGROUND: Morphine, a mu-opioid receptor (MOR) agonist commonly utilized in clinical settings alongside chemotherapy to manage chronic pain in cancer patients, has exhibited contradictory effects on cancer, displaying specificity toward certain cancer types and doses. OBJECTIVE: The aim of this study was to conduct a systematic assessment and comparison of the impacts of morphine on three distinct cancer models in a preclinical setting. METHODS: Viability and apoptosis assays were conducted on a panel of cancer cell lines following treatment with morphine, chemotherapy drugs alone, or their combination. Oxidative stress levels, along with the activities of superoxide dismutase and catalase, were measured. Rescue studies were also carried out using antioxidant reagents. RESULTS: Morphine induces resistance to conventional chemotherapeutic agents. It was observed that while morphine affected cell viability differently among ovarian cancer, anaplastic thyroid cancer, and oral squamous cell carcinoma, at concentrations that did not directly impact cancer cell viability, it significantly mitigated the inhibitory effects of chemotherapeutic agents across all tested cancer cells. This phenomenon persisted irrespective of the chemotherapeutic agent used, including cisplatin, doxorubicin, and 5-FU. It remained unaffected by adding naloxone, the MOR receptor antagonist, indicating that morphine's mechanism is independent of the μ- opioid receptor. Moreover, it was demonstrated that morphine heightened cellular reactive oxygen species (ROS) levels and suppressed the activities of superoxide dismutase and catalase. Rescue studies revealed that the addition of antioxidant reversed the protective impact of morphine on cancer cells against chemotherapy. CONCLUSION: These findings hold promise in potentially guiding the clinical application of morphine for cancer patients undergoing chemotherapy.
Mechanisms Underlying the Anti-Atherosclerotic Effects of EGCG.
Wang L, Pan Q, Tang C
Curr Mol Med · 2025 · PMID 39806950 · Publisher ↗
Atherosclerosis (AS) is a chronic inflammatory vascular disease and the primary pathological basis of cardiovascular diseases. Epigallocatechin-3-gallate (EGCG), the most abundant polyphenol compound in green tea, has ga...
Atherosclerosis (AS) is a chronic inflammatory vascular disease and the primary pathological basis of cardiovascular diseases. Epigallocatechin-3-gallate (EGCG), the most abundant polyphenol compound in green tea, has garnered significant attention in recent years for its protective effects against AS. EGCG possesses properties that lower lipid levels, exhibit antioxidant and anti-inflammatory activities, enhance plaque stability, and promote the recovery of endothelial function. The regulatory mechanisms of EGCG in AS primarily involve inhibiting apoptosis, modulating autophagy, improving gut microbiota, and regulating the Nrf2 and inflammatory signaling pathways. This review summarizes the role of EGCG in the prevention and treatment of AS and its potential mechanisms, providing a scientific basis for future research directions and therapeutic applications.
An Overview of Invasive Ductal Carcinoma (IDC) in Women's Breast Cancer.
Gallas AE, Morenikeji GO, King RE … +4 more , Adegbaju MS, Ayoola A, Taiwo G, Morenikeji OB
Curr Mol Med · 2025 · PMID 39806949 · Publisher ↗
Invasive ductal carcinoma (IDC) is the most common type of breast cancer, primarily affecting women in the United States and across the world. This review summarizes key concepts related to IDC causes, treatment approach...
Invasive ductal carcinoma (IDC) is the most common type of breast cancer, primarily affecting women in the United States and across the world. This review summarizes key concepts related to IDC causes, treatment approaches, and the identification of biological markers for specific prognoses. Furthermore, we reviewed many studies, including those involving patients with IDC and ductal carcinoma in situ (DCIS) that progressed to IDC. We reported various studies on the causes of IDC, including mutations on BRCA1 and BRCA2, different levels of expression of specific genes in signaling pathways, menopause status, alcohol consumption, aging, and hormone imbalances that cause IDC while p-SMAD4 expressions, DNA methylation, regulations of hub genes, and underestimation of IDC affecting prognoses. Prompt IDC diagnosis and early intervention have been reported to demonstrate a greater probability of eradicating IDC and preventing further recurrence in the future. It is crucial for physicians and researchers to equip patients with the best information possible to proactively manage their health, whether it be for IDC prevention or treatment. Overall, our review provided a comprehensive understanding of IDC that enables patients to grasp the nature of the disease with the hope of mitigating IDC risk, decrease the anxiety of a cancer diagnosis, and encourage patients to become more involved in making informed decisions for their healthcare.
KDM4A Silencing Reverses Cisplatin Resistance in Ovarian Cancer Cells by Reducing Mitophagy SNCA Transcriptional Inactivation.
Xing Y, Mao M, Zhu T … +2 more , Shi H, Ding H
Curr Mol Med · 2025 · PMID 39791159 · Publisher ↗
BACKGROUND: Ovarian cancer is one of the deadliest gynecologic cancers, with chemotherapy resistance as the greatest clinical challenge. Autophagy occurrence is associated with cisplatin (DDP)-resistant ovarian cancer ce...
BACKGROUND: Ovarian cancer is one of the deadliest gynecologic cancers, with chemotherapy resistance as the greatest clinical challenge. Autophagy occurrence is associated with cisplatin (DDP)-resistant ovarian cancer cells. Herein, the role and mechanism of alpha-synuclein (SNCA), the autophagy-related gene, in DDP resistance of ovarian cancer cells are explored. METHODS: Differentially expressed genes in DDP resistance of ovarian cancer cells were analyzed by GEO2R tools. DDP-resistant ovarian cancer cells (A2780/DDP) were transfected and treated with 2.5 μg/mL DDP for 72 h, followed by the determination of cell viability, proliferation, apoptosis, and expressions of SNCA, lysine demethylase 4A (KDM4A), histone H3 lysine 9 trimethylation (H3K9me3), and mitophagy-related proteins. The H3K9me3 demethylation of SNCA by KDM4A was confirmed by chromatin immunoprecipitation. RESULTS: SNCA and KDM4A were highly expressed in DDP-resistant ovarian cancer cells and their parental cells. KDM4A knockdown diminished expressions of KDM4A and SNCA and elevated H3K9me3 expression and H3K9me3 enrichment on SNCA promoter in A2780/DDP cells. SNCA or KDM4A knockdown inhibited cell viability, proliferation, and levels of LC3-II/LC3-I and Parkin while inducing cell apoptosis and upregulating Cyt-C expression of A2780/DDP cells with/without DDP treatment; however, SNCA overexpression not only did conversely but also reversed the effects of KDM4A knockdown on DDP-treated A2780/DDP cells and vice versa. CONCLUSION: Silencing of KDM4A-mediated transcription inactivation of SNCA reduces mitophagy, thus inhibiting the resistance of ovarian cancer cells to cisplatin. KDM4A may be a promising drug target for DDP-resistant ovarian cancer cells.
Cancer Stem Cell and Tumor Immune Microenvironment (TIME): Dangerous Crosstalk.
Moussa S
Curr Mol Med · 2025 · PMID 39781721 · Publisher ↗
Cancer stem cells (CSCs) are the key drivers of tumorigenesis and relapse. A growing body of evidence reveals the tremendous power of CSCs to directly resist innate and adaptive anti-tumor immune responses. The immunomod...
Cancer stem cells (CSCs) are the key drivers of tumorigenesis and relapse. A growing body of evidence reveals the tremendous power of CSCs to directly resist innate and adaptive anti-tumor immune responses. The immunomodulatory property gives CSCs the ability to control the tumor immune microenvironment (TIME). CSCs hijack the anti-tumor capacity of immune cells to provide self-protection from immune attack and enhance the pro-tumor immune cell infiltration and activity. To date, cancer immunotherapy strategies have largely been designed without taking into account the immunosuppressive properties of CSCs. As a result, the clinical efficacy of cancer immunotherapy is altered, perpetuating tumor progression and relapse. Therefore, targeting the signals underlying CSC immune evasion is essential to improve immunotherapy efficacy and reduce tumor relapse. The aim of this mini-view is to comprehensively summarize the key immune escape mechanisms adopted by CSCs. This will provide necessary clues for the development of more effective cancer immunotherapy strategies.
Ionizing Radiation Combined with Gold Complex Compounds Causes Apoptosis in Colorectal Cancer Cells by Increasing the Level of Caspase-3.
Sano N, Yoshino H, Sato Y … +3 more , Honma H, Cordonier CEJ, Kashiwakura I
Curr Mol Med · 2025 · PMID 39779551 · Publisher ↗
BACKGROUND: The anticancer activity and radiosensitizing effect of Auranofin, an an-tirheumatic and an approved gold metallic drug, have been investigated from multiple perspectives. In this study, the action of the new...
BACKGROUND: The anticancer activity and radiosensitizing effect of Auranofin, an an-tirheumatic and an approved gold metallic drug, have been investigated from multiple perspectives. In this study, the action of the new gold complex compound TPN-Au(I)-MM4 was compared with that of auranofin. METHODS: The inhibitory effect of 10 μM and 50 μM concentrations on cell proliferation was investigated using the human colon cancer cell lines HCT116 and SW480. The radiosensitizing effect of HCT116 cells was evaluated by measuring the ability to induce apoptotic cell death. The mechanism of action was qualitatively determined via western blotting analysis of the level of cleaved caspase-3 protein. RESULTS: Auranofin completely inhibited cell proliferation in both cell lines at both concentrations. In contrast, only 50 μM of TPN-Au(I)-MM4 significantly inhibited the proliferation of SW480 cells, but did not affect the proliferation of HCT116 cells. On the other hand, both compounds effectively increased the apoptotic cell death rate when combined with 4 Gy of X-ray irradiation. This mechanism was caused by a significant increase in the level of caspase-3, which is an apoptosis execution factor, by the combination of these two treatments. CONCLUSION: Both compounds promoted the significant expression of caspase-3, an apoptosis execution factor, and exhibited radio-sensitizing effects. In particular, TPNAu( I)-MM4 showed no inhibitory effect on cell proliferation alone, but had a significant radiosensitising effect on HCT116 cells. Therefore, TPN-Au(I)-MM4 has the potential for use as a new radiosensitizer.
Macrophages and Pulmonary Fibrosis.
Chen S, Song X, Lv C
Curr Mol Med · 2025 · PMID 39779550 · Publisher ↗
Most chronic respiratory diseases often lead to the clinical manifestation of pulmonary fibrosis. Inflammation and immune disorders are widely recognized as primary contributors to the onset of pulmonary fibrosis. Given...
Most chronic respiratory diseases often lead to the clinical manifestation of pulmonary fibrosis. Inflammation and immune disorders are widely recognized as primary contributors to the onset of pulmonary fibrosis. Given that macrophages are predominantly responsible for inflammation and immune disorders, in this review, we first focused on the role of different subpopulations of macrophages in the lung and discussed the crosstalk between macrophages and other immune cells, such as neutrophils, regulatory T cells, NKT cells, and B lymphocytes during pulmonary fibrogenesis. Subsequently, we analyzed the interaction between macrophages and fibroblasts as a possible new research direction. Finally, we proposed that exosomes, which function as a means of communication between macrophages and target cells to maintain cellular homeostasis, are a strategy for targeting lung drugs in the future. By comprehending the mechanisms underlying the interplay between macrophages and other lung cells, we aim to enhance our understanding of pulmonary fibrosis, leading to improved diagnostics, preventative measures, and the potential development of macrophage-based therapeutics.
The Diverse Roles of Long Non-Coding RNA HOTTIP in Breast and Gynecological Cancer Progression.
Dari MAG, Radmehr S, Khodadadi A … +4 more , Shooshtari MK, Kempisty B, Farzaneh M, Sheykhi-Sabzehpoush M
Curr Mol Med · 2025 · PMID 39779549 · Publisher ↗
Long non-coding RNAs (lncRNAs) play vital roles in the development and progression of various tumors through multiple mechanisms. Among these, HOTTIP (HOXA transcript at the distal tip) stands out as an intriguing candid...
Long non-coding RNAs (lncRNAs) play vital roles in the development and progression of various tumors through multiple mechanisms. Among these, HOTTIP (HOXA transcript at the distal tip) stands out as an intriguing candidate with diverse functions in several malignancies, including breast cancer and gynecologic cancers such as ovarian, cervical, and endometrial cancers, which are significant global health concerns. HOTTIP interacts with key signaling pathways associated with these cancers, including Wnt/β-catenin, PI3K/AKT, and MEK/ERK pathways, enhancing their activation and downstream effects. Its influence extends to crucial aspects of cancer biology, such as cell proliferation, apoptosis, migration, invasion, angiogenesis, and epithelial-mesenchymal transition (EMT). Additionally, HOTTIP plays a pivotal role in the pathogenesis of breast and gynecologic tumors by sponging various microRNAs (miRNAs) and regulating the expression of mRNAs involved in critical molecular processes. This dysregulation is often associated with poor clinical outcomes, advanced disease stages, and distant metastases. Understanding the functional roles of HOTTIP in these cancers is essential for developing targeted therapeutic strategies. This review aims to explore the emerging roles of HOTTIP in breast and gynecologic cancers.
Proteomic Analysis of Mesenchymal Stem Cell-derived Exosomes in Psoriasis.
Wang S, Han Q, Wang J … +3 more , Peng X, Zhou L, Niu X
Curr Mol Med · 2025 · PMID 39779548 · Publisher ↗
PURPOSE: This study aims to investigate the unique proteins in exosomes from mesenchymal stem cells derived from psoriatic lesions and compare them with those from healthy human skin. It seeks to identify potential regul...
PURPOSE: This study aims to investigate the unique proteins in exosomes from mesenchymal stem cells derived from psoriatic lesions and compare them with those from healthy human skin. It seeks to identify potential regulatory factors that may influence the differential effects observed in these exosomes. METHODS: Dermal mesenchymal stem cell exosomes were isolated from healthy human skin (HDMSCs-EXO) and psoriatic lesion of patient (PDMSCs-EXO). The extracted exosomes were analyzed through label-free quantitative proteomics to identify differential proteins. Bioinformatics analyses, including GO and KEGG enrichment, were conducted. RESULTS: The comparative analysis using HDMSCs-EXO as a control group revealed 13 differential proteins. Notably, proteins such as B2R4D5, MFGE8, and MFAP5 are associated with the inflammatory mechanisms of psoriasis. CONCLUSION: The study identifies several differentially expressed proteins in exosomes may play roles in the development of psoriasis. These finding offer valuable insights for further exploration of the inflammatory processes in psoriasis.
Predictive Value and Potential of Targeting Complement Factor C3 in Patients with Renal Injury in Preeclampsia.
Ni C, Zhang S, Bai W
Curr Mol Med · 2025 · PMID 39779547 · Publisher ↗
AIMS: The activation of the complement system is accompanied by the occurrence and development of preeclampsia, as well as kidney diseases. Here, the role of complement C3 [C3] in renal injury in preeclampsia was explore...
AIMS: The activation of the complement system is accompanied by the occurrence and development of preeclampsia, as well as kidney diseases. Here, the role of complement C3 [C3] in renal injury in preeclampsia was explored, and its potential application as an early diagnostic biomarker or drug target to ameliorate kidney injury induced by preeclampsia was preliminarily evaluated. METHODS: A total of 48 subjects were included in the present study, and the complement C3 levels and renal function were analyzed. RESULTS: Patients with preeclampsia with severe features [sPe] had poorer renal function compared with the patients with preeclampsia. Urinary C3 levels could be used to distinguish between healthy controls, patients with preeclampsia, and patients with sPe. Increased renal inflammation and oxidative stress were notably increased in the preeclampsia mice with impaired renal function and attenuation of C3 activity using a C3 receptor antagonist, which reduced Pe-like symptoms and renal impairment, decreased serum blood urea nitrogen, creatinine, and urinary albumin levels, and decreased expression of the oxidative stress marker malondialdehyde, whilst increasing superoxide dismutase activity. In addition, activation of the nuclear factor erythroid 2-related factor 2 (Nrf2)/heme oxygenase-1 ([HO-1) pathway was involved in the inhibition of complement C3 in the kidney. CONCLUSION: Higher urinary C3 levels could be used to predict kidney damage in preeclampsia, and inhibition of C3 activity might ameliorate the renal impairment in preeclampsia through activation of Nrf2/HO-1 pathway.
miR-34 as a Critical Regulator in Ovarian Cancer.
Dari MAG, Jaberian Asl B, Dayer D … +3 more , Azizidoost S, Farzaneh M, Salehi AM
Curr Mol Med · 2025 · PMID 39773049 · Publisher ↗
Ovarian cancer (OC) is a gynecologic disease characterized by the uncontrolled growth and proliferation of abnormal cells in the ovaries, fallopian tubes, or peritoneum. Emerging evidence has shown the pivotal role of no...
Ovarian cancer (OC) is a gynecologic disease characterized by the uncontrolled growth and proliferation of abnormal cells in the ovaries, fallopian tubes, or peritoneum. Emerging evidence has shown the pivotal role of non-coding RNAs (ncRNAs), such as miRNAs, in driving the pathogenesis of OC. miRNAs are recognized as small ncRNAs that play critical roles in regulating gene expression in normal development and in disease states, including OC. Among miRNAs, the expression of miR-34a was found to be downregulated in OC. Elevated levels of this miRNA are associated with the induction of apoptosis and the inhibition of OC cell proliferation by targeting various signaling pathways, including NOTCH1, P21/P53, STAT3, and BCL2 in OC. Therefore, miR-34a can be a therapeutic target in the management of OC. In this review, we summarized the functional significance of this miRNA in the treatment of OC.
A Comprehensive Analysis of the Clinical Significance and Underlying Oncogenic Roles of Specific MMPs in Gastric Carcinoma Reveals their Potential Roles in Prognosis and Therapy.
Jin S, Wang J, Wang K
Curr Mol Med · 2025 · PMID 39773048 · Full text
BACKGROUND: Gastric cancer is a major global cause of cancer-related deaths, necessitating investigation into Matrix Metalloproteinases' (MMPs) diagnostic and prognostic value. Our study aimed to analyze their significan...
BACKGROUND: Gastric cancer is a major global cause of cancer-related deaths, necessitating investigation into Matrix Metalloproteinases' (MMPs) diagnostic and prognostic value. Our study aimed to analyze their significance in gastric cancer. METHODS: We evaluated MMP family genes' mRNA and protein expression using the University of Alabama at Birmingham (UALCAN) and Human Protein Atlas (HPA) databases. Then, we analyzed the relationship between their mRNA expression and gastric cancer staging and survival using Gene Expression Profiling Interactive Analysis (GEPIA) and Kaplan-Meier plotter. Furthermore, we assessed this family's gene mutation rates in gastric cancer patients using Search Tool for the Retrieval of Interaction Genes/Proteins (STRING) and explored potential pathways and mechanisms via Database for Annotation, Visualization, and Integrated Discovery (DAVID), cBioPortal, and R. Finally, we established a predictive model for gastric cancer based on these analyses to understand these genes' roles in cancer. RESULTS: Our findings revealed significantly upregulated mRNA expression of MMP1/2/3/7/9/10/11/12/13/14 in gastric cancer tissues (p<0.05). Higher levels of MMP2/7/10-encoded proteins (middle or high) were observed in tumor tissues, with MMP2/11/14 closely associated with different cancer stages (p<0.05). Additionally, MMP2/7/11/14/20 mRNA levels correlated with short-term overall survival (about 20 months), while MMP1/3/9/12/13 expression was associated with favorable overall survival (about 30 months). Gastric cancer patients exhibited a 21% mutation rate of MMP family genes, which correlated with favorable overall survival. Enrichment analysis and protein-protein interaction results underscored the close association of MMPs with gastric cancer development. The MMP2 model demonstrated a significant decline in survival rates for the high expression group, with a Hazard Ratio (HR) of 1.78 (95% CI 1.47-2.16) and a log-rank P value of 2.9e-09. Statistical significance was set at p < 0.05. Univariate Cox regression identified MMP2 as a risk factor for gastric cancer patients. CONCLUSION: Our findings highlighted MMPs' essential role in gastric cancer progression, impacting patient survival. MMP2 emerged as a promising target for gastric carcinoma detection and treatment.
Benzopyrene Aggravates Nonalcoholic Liver Fatty Diseases in Female Mice Via the AHR/ERα Axis.
Wu Y, Xie J, Tao Q … +3 more , Tan L, Zhu X, Yong J
Curr Mol Med · 2025 · PMID 39757651 · Publisher ↗
OBJECTIVE: Nonalcoholic fatty liver disease (NAFLD) is a prevalent liver condition worldwide, and the statistics show that men have a higher incidence and prevalence than women, but its toxicological mechanism is not com...
OBJECTIVE: Nonalcoholic fatty liver disease (NAFLD) is a prevalent liver condition worldwide, and the statistics show that men have a higher incidence and prevalence than women, but its toxicological mechanism is not completely clear. This research is intended to explore the role of BaP in NAFLD and to study how the environmental pollutant BaP influences the AHR/ERα axis to mediate the progression of NAFLD. METHODS: In this study, we established NAFLD models in vivo and in vitro by treating HepG2 cells with a high-fat diet and Oleic acid (OA) in C57BL/6J mice. Liver injury indexes ALT, AST, and lipid metabolism indexes TG and TC were evaluated to verify the success of modeling. Then, the model was treated with BaP, and the mRNA and protein expressions of CYP1A1, ERα, and SREBP-1c were evaluated by RT-PCR and WB, and the changes of liver fat were evaluated by HE and oil red O staining. Next, BaP was added into the cells treated with or without estradiol (E2), and the lipid metabolism in the cells was evaluated by oil red O staining, and whether the above levels of CYP1A1, ERα and SREBP-1c were changed. RESULTS: Our results show that after exposure to BaP, ERα protein levels in mice and cells are inhibited, mRNA and protein levels of SREBP-1c are reduced, and lipid metabolism processes are obstructed. The addition of E2 can reduce the increase of SREBP-1c mRNA and protein expression induced by OA, and reduce the deposition of lipids in cells. However, BaP treatment can weaken the action of E2 and destroy the protection of E2 in cells. CONCLUSION: The results showed that E2 could reduce SREBP-1c mRNA and protein levels. BaP can stimulate AHR, leading to the degradation of ERα protein, reducing the binding of E2 to ERα, and aggravating the progression of NAFLD. This reveals the toxicological mechanism by which environmental pollutant BaP influences E2 to mediate NAFLD, and provides strong evidence for differences in NAFLD between the sexes.
SUMOylation Inhibitors Exert a Protective Effect on Oxidative Damage in Retinal Pigment Epithelial Cells Through the Keap1/Nrf2/ARE Signaling Pathway.
Liang Y, Jia X, Zheng F … +5 more , Wang Y, Fan Y, Zhang H, Dang Z, Wang L
Curr Mol Med · 2025 · PMID 39757650 · Publisher ↗
PURPOSE: To investigate the effect of the SUMOylation inhibitor TAK981 on hydrogen peroxide (HO)-induced oxidative damage in human retinal pigment epithelial cells (ARPE-19) and its regulatory mechanism. METHODS: An oxid...
PURPOSE: To investigate the effect of the SUMOylation inhibitor TAK981 on hydrogen peroxide (HO)-induced oxidative damage in human retinal pigment epithelial cells (ARPE-19) and its regulatory mechanism. METHODS: An oxidative damage model of ARPE-19 cells induced by HO was established, and 1, 2, and 5 µM TAK981 solutions were administered for intervention respectively. Normal cells were used as the control group. The viability of the cells in each group was detected by the methyl thiazolyl tetrazolium (MTT) method. The levels of superoxide dismutase (SOD) and malondialdehyde (MDA) in each group of cells were detected by biochemical methods. The levels of IL-1β and TNF-α produced by each group of cells were detected by enzyme-linked immunosorbent assay (ELISA). The protein expression levels of Nrf2, HO-1, NQO-1, Keap1, and Sumo1 in each group of cells were detected by Western blotting. In addition, 2 µM TAK981 and 2 µM TAK981 combined with 10 µM ML385 (an Nrf2 inhibitor) were administered to HO-induced ARPE-19 cells, and the levels of SOD and MDA, IL-1β and TNF-αwere detected again. RESULTS: The viability of the ARPE-19 cells decreased with increasing HO concentration (F=19.158, P<0.001). HO treatment at 350 µM was the concentration at which the cells essentially reached half inhibition (IC50), and the cell oxidative damage model was successfully established. After intervention with TAK981, cell survival increased significantly (F=0.098, P<0.001). The differences between the 2 µM and 5 µM TAK981 groups and the model group were statistically significant (all P<0.01). Compared with those in the normal group, the MDA content in the model group increased, the SOD activity decreased, and the release levels of IL-1β and TNF-α increased (all P<0.01). Compared with those in the model group, the MDA content in the TAK981 group decreased, the SOD activity increased, and the release levels of IL-1β and TNF-α decreased. The differences between the 2 µM and 5 µM TAK981 groups were statistically significant (P<0.05). Compared with those in the normal group, the protein expression levels of Nrf2, HO-1 and NQO-1 in the model group were greater, whereas the protein expression levels of Keap1 and Sumo1 were lower (all P<0.05). Compared with those in the model group, the protein expression levels of Nrf2, HO-1 and NQO-1 in the TAK981-treated group continued to increase, whereas the protein expression levels of Keap1 and Sumo1 continued to decrease. The differences in the 5 µM TAK981 group were statistically significant (P<0.05). In addition, after the combined intervention of TAK981 and ML385 on HO-induced cells, compared with the TAK981-only intervention on HO-induced cells, the cell viability increased, the MDA content increased, the SOD activity decreased, and the IL-1β and TNF-α release levels increased. The differences were statistically significant (P<0.05). CONCLUSION: The SUMOylation inhibitor TAK981 activates the Keap1/Nrf2/ARE signaling pathway, enhances the activity of antioxidant enzymes, and reduces the production of oxidative stress products and inflammatory factors, thereby exerting a protective effect on HO-induced oxidative damage in ARPE-19 cells. Therefore, it is suggested that intervention in SUMO regulation can be used as a new therapeutic target in the AMD disease model, in order to delay the development of AMD by reducing the oxidative damage of RPE.
Clock-Sleep Communication.
Pandi-Perumal SR, Paul S, Saravanan KM … +2 more , Namasivayam GP, Chidambaram SB
Curr Mol Med · 2025 · PMID 39694958 · Publisher ↗
Rhythmicity is a characteristic feature of the inanimate universe. The organization of biological rhythms in time is an adaptation to the cyclical environmental changes brought on by the earth's rotation on its axis and...
Rhythmicity is a characteristic feature of the inanimate universe. The organization of biological rhythms in time is an adaptation to the cyclical environmental changes brought on by the earth's rotation on its axis and around the sun. Circadian (L. Circa = "around or approximately"; diem = "a day") rhythms are biological responses to the geophysical light/dark (LD) cycle in which an organism adjusts to alterations in its internal physiology or external environment as a function of the time of day. Sleep has been considered a biological rhythm. Normal human sleep, an essential physiologic process, comprises two distinct phases: non-rapid eye movement (NREM) sleep and rapid eye movement (REM) sleep. A mature adult human's sleep/wake cycle displays a circadian rhythm with a ~24-hour cycle. According to the two-process model of sleep regulation, the human sleep/wake cycle is orchestrated by circadian and homeostatic processes. Sleep homeostasis (a sleep-dependent process) and circadian rhythm (a sleep-independent process) are two biological processes controlling the sleep/wake cycle. There are also ultradian (< 24-hour) rhythms, including the NREM-REM sleep cycle, which has been extensively studied. The clock and sleep genes both influence sleep. In this overview, we have reviewed the circadian genes and their role in regulating sleep. Besides, the gene expression and biological pathways associated with sleep and circadian rhythm-associated diseases also have been highlighted.
Advances in Molecular Biology and Immunology of Spermatozoa and Fertilization in Domestic Animals: Implications for Infertility and Assisted Reproduction.
Adnane M, Ahmed M, Chapwanya A
Curr Mol Med · 2025 · PMID 39572916 · Publisher ↗
Unlocking the secrets of reproductive success in domestic animals requires a deep understanding of the molecular biology and immunology of spermatozoa, capacitation, fertilization, and conception. This review highlights...
Unlocking the secrets of reproductive success in domestic animals requires a deep understanding of the molecular biology and immunology of spermatozoa, capacitation, fertilization, and conception. This review highlights the complex processes involved in spermatogenesis and sperm capacitation, including changes in membrane properties, signaling pathways, and the crucial acrosome reaction. The interaction with the zona pellucida in species-specific gamete recognition and binding is emphasized. The implications of fertilization defects for infertility and assisted reproduction are discussed, underscoring the challenges faced in breeding programs. The future directions for research in this field involve advancements in molecular techniques, understanding the immune regulation of spermatozoa, investigating environmental factors' impact, and integrating multi-omics approaches to enhance assisted reproduction techniques in domestic animals. This review contributes to our understanding of the intricate mechanisms underlying successful reproduction and provides insights into potential strategies for improving fertility outcomes in domestic animals.
KIAA1429 Promotes Keloid Formation Through the TGF-Β1/Smad Pathway.
Ren S, Ji Y, Wang M … +3 more , Ye M, Huang L, Cai X
Curr Mol Med · 2025 · PMID 39513311 · Publisher ↗
BACKGROUND: Keloid formation is characterized by excessive production of extracellular matrix, leading to dysregulated fibroproliferative collagen response. N6- methyl-adenosine (m6A) modification plays an essential role...
BACKGROUND: Keloid formation is characterized by excessive production of extracellular matrix, leading to dysregulated fibroproliferative collagen response. N6- methyl-adenosine (m6A) modification plays an essential role in this process. OBJECTIVE: Our objective in this study was to explore the mechanism of m6A methyltransferase KIAA1429 in keloid formation. METHODS: We examined the impact of m6A methyltransferase KIAA1429 on keloid formation using qRT-PCR, Western blot, immunofluorescence, Transwell migration assay, and MeRIP-qPCR. RESULTS: KIAA1429 was downregulated in keloid tissue. Overexpression of KIAA1429 suppressed fibroblast migration and reduced COL1A1 and α-SMA levels. Conversely, the knockdown of KIAA1429 promoted fibroblast migration and COL1A1 and α-SMA levels. Additionally, overexpression of KIAA1429 inhibited the TGF-β1/Smad pathway. Mechanistic experiments suggested that KIAA1429 regulated TGF-β1 m6A modification, maintained TGF-β1 mRNA stability, and participated in the regulation of keloid formation. Furthermore, TGF-β1 could reverse the effects of KIAA1429 overexpression on fibroblast migration and collagen deposition. CONCLUSION: Taken together, our study suggested that KIAA1429 promoted keloid formation through the TGF-β1/Smad pathway, providing new insights for the treatment of keloid.
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