Current Molecular Medicine - Online First
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21 - 40 of 72 results
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Neuroprotective Potential of Conditioned Medium from Adipose and Liver Mesenchymal Stem Cells in a Rat Model of Global Cerebral Ischemia-Reperfusion Injury
Available online: 12 May 2025More LessBackgroundMesenchymal stem cell-derived conditioned medium (MSC-CM) contains bioactive factors that provide neuroprotection in cases of cerebral ischemia-reperfusion (IR) injury. This study aimed to compare the therapeutic potential of rat adipose-derived MSC-CM (rAD-MSC-CM) and chicken embryo liver-derived MSC-CM (cLD-MSC-CM) following global cerebral IR injury in male rats.
Material and MethodsWe harvested rAD-MSC-CM from the adipose tissue surrounding the epididymis of Wistar rats and cLD-MSC-CM from the liver tissue of 10-day-old chicken embryos. To induce global cerebral ischemia, we utilized a four-vessel occlusion (4VO) model in rats. After inducing ischemia, the conditioned media were administered via intravenous injection 30 minutes post-reperfusion. We evaluated the cognitive and non-cognitive functions of the animals using standard behavioral tests. Additionally, we assessed blood-brain barrier (BBB) permeability, brain water content (BWC), oxidative-antioxidative status, and conducted histopathological analyses of the hippocampal tissue in the IR rats.
ResultsOur findings demonstrated that treatment with both rAD-MSC-CM and cLD-MSC-CM significantly improved memory function, reduced anxiety- and depression-like behaviors, and enhanced exploratory activities. These behavioral improvements correlated with decreased BBB permeability and BWC, reduced oxidative stress, and mitigated histopathological changes in the hippocampal tissue.
ConclusionOur findings suggest that both rAD-MSC-CM and cLD-MSC-CM offer protective benefits against IR injury, likely owing to their antioxidant properties.
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Non-coding RNAs PROX1-AS1 and miR-647: Potential Interaction and Prognostic Value in Gastric Cancer
Available online: 05 May 2025More LessBackgroundGastric cancer (GC) remains one of the most common malignancies and the third cause of cancer-related deaths worldwide. Non-coding RNAs (ncRNAs), including microRNAs and long ncRNAs, can contribute to the pathogenesis and progression of GC and therefore could be its potent diagnostic and prognostic biomarkers. The aim of our work was to estimate the expression of PROX1-AS1 (Prospero Homeobox 1 Antisense RNA 1) and miR-647 (microRNA-647) in GC and investigate their potential interaction and clinical significance.
MethodsThe study included tumor and adjacent non-tumor tissues from 110 GC patients and plasma samples from 65 GC patients; 38 sectional normal gastric tissue samples and 49 plasma samples of healthy donors were included as controls. Expression levels of both ncRNAs were quantified in all samples by using real-time polymerase chain reaction (RT-PCR) and their possible correlations with the clinical and pathological characteristics of patients were analyzed. A potential inverse correlation between PROХ1-AS1 and miR-647 expression was addressed by in vitro experiments in a panel of cancer cell lines.
ResultsThe expression of PROX1-AS1 and miR-647 was not significantly different in tissues of GC patients and sectional normal gastric tissue samples. However, they have demonstrated a negative correlation both in the tumor and the adjacent non-tumor tissue of GC patients. PROX1-AS1 expression was significantly decreased in GC tissues, whereas the miR-647 expression was increased. The expression of the ncRNAs was associated with clinical and pathological characteristics of GC patients. The overexpression of miR-647 led to a significant decrease in PROX1-AS1 expression in five cancer cell lines, including the GC cell line SNU-1.
ConclusionWe have demonstrated a negative correlation between PROX1-AS1 and miR-647 in both GC tissues and the cancer cell lines. In addition, expression of both ncRNAs was associated with the primary tumor size. Therefore, these ncRNAs might have potential prognostic value.
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Immunohistochemical Analysis of CYP11B2 (Aldosterone Synthase) and Evaluation of the HISTALDO Classification in Patients with Primary Aldosteronism
Authors: Mustafa Karadepe, Hande Yanar, Hülya Binokay, Şeyda Erdoğan and Gamze AkkusAvailable online: 02 May 2025More LessObjectivePrimary Aldosteronism (PA) is the most common cause of secondary hypertension. Immunohistochemical analysis of PA is based on specific monoclonal antibodies targeting CYP11B1 and CYP11B2, which are enzymes responsible for the aldosterone production in the adrenal cortex. The recently proposed HISTALDO classification introduced CYP11B2 immunohistochemistry to define clinically relevant diagnostic categories. We aimed to investigate the relationship between clinical characteristics and immunohistochemistry of CYP11B2 in PA and also evaluate staining in cortisol-producing cells by comparing patients with Cushing’s Syndrome (CS). Consecutive patients diagnosed with PA (n=21) and CS (n=20) were included between 2015-2022. All of them underwent unilateral adrenalectomy in our tertiary center.
MethodsFollowing hematoxylin and eosin (H&E) staining of the pathological specimens, all slides were re-evaluated and immunostained for CYP11B2. A semiquantitative H-score was assessed for each patient and compared with staining intensity. Patients with PA were grouped and classified according to the HISTALDO classification.
ResultsThe mean size of adenoma in patients with PA was much smaller compared to patients with CS (p=0.001). An increase in the immunohistochemical H-score of the patients with PA (121.36 ±81.04 vs 73.94±57.70, p=0.045) was observed in comparison to the patients with CS. When comparing the patients with PA according to HISTALDO criteria, the H-score of the patients with Aldosterone Producing Adenoma (APA, n=10) was 136.6±78.86 compared to the non-APA group, which was 86.81±85.3 (n=11, p=0.05). Moreover, mean preoperative aldosterone levels (p=0.06) and aldosterone-to-renin ratio (ARR, p=0.03) were higher in patients with APA compared to non-APA patients. Response to surgical therapy was more favorable in patients with APA than the patients with non-APA.
ConclusionCYP11B2 is a key enzyme responsible for the synthesis of aldosterone. CYP11B2 expression, as assessed by immunostaining, was associated with the clinical characteristics, severity of PA, and response to the treatment. Hence, immunohistochemical analysis of CYP11B2 should be incorporated into the routine clinical workup to better localize aldosterone-producing cells.
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Innovative Therapeutic Potential of Herbal Extracts Containing Punicic and Ellagic Acid: Addressing Lower Urinary Tract Disorders
Authors: Hrishav Das Purkayastha, Abhishek Bhattacharjee and Ranjit Prasad SwainAvailable online: 02 May 2025More LessThis review highlights the new healing frontiers opened by herbal preparations rich in punicic acid, as well as ellagic acid, in the management of Lower Urinary Tract Disorders (LUTD). New data prove that these bioactive compounds possess strong anti-inflammatory, antioxidant, and antibacterial properties, and therefore, can be helpful in treating LUTD symptoms such as urgency, frequency, and dysuria. We conducted a comprehensive pharmacological assessment of punicic and ellagic acids aimed at determining their role in bladder health through modulation of inflammatory processes and both alteration and maintenance of urothelium integrity, in addition to obtaining some background information and chemical properties of these acids. Furthermore, we evaluated the findings of clinical and preclinical studies that demonstrated the ability of these formulations to improve the basic functions of the organs in the urinary system and the quality of life of patients. The review also reflects on the use of herbal extracts in combination with current therapies as a synergistic approach, particularly on the healing effects of such combinations and the need for solid clinical evidence to support such claims. This paper focuses on the concept of how LUTDs can be treated safely and effectively without the help of drugs by integrating modern scientific strategies with traditional approaches, which will thus increase the comprehensiveness of treatment in urological care. Future research should focus on improving how well these compounds are absorbed in the body and gathering long-term safety data, with the goal of incorporating them into treatment guidelines.
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Analysis of Cytokine mRNA Expression During Zika Virus Infection In Mesocricetus auratus
Available online: 30 April 2025More LessBackgroundThe Orthoflavivirus zikaense (ZIKV), a member of the Flaviviridae family, has been associated with severe neurological issues, particularly microcephaly, due to its ability to infect neural progenitor cells. This study investigates the mRNA expression of cytokines involved in the inflammatory response during ZIKV infection in Mesocricetus auratus. The research aims to understand the immune response to ZIKV in the context of sexual transmission.
MethodsThe study utilized hamsters of the species Mesocricetus auratus, divided into four groups: three infected with ZIKV and one control group. The animals were euthanized according to ethical guidelines, and renal tissues were collected. Total RNA was extracted and quantified, and both viral load and cytokine mRNA levels were measured using RT-qPCR. The study targeted cytokines such as TNF-A, RIG-I, RANTES, MDA5, IFN-A, and IFN-B. Statistical analysis was performed using Jamovi v 1.6.
ResultsThe study found that the viral load peaked between 3 and 5 days post-infection and then significantly decreased. The expression of cytokine mRNAs showed distinct patterns, with peaks and declines at various time points post-infection. These patterns differed between male and female subgroups. Pearson correlation analysis revealed negative correlations between mRNA expression and days post-infection in most groups.
ConclusionThe study concludes that ZIKV infection in hamsters induces a robust inflammatory response in the kidneys, with dynamic cytokine expression profiles that could serve as markers for monitoring infection and related pathologies. Gender-specific immune responses highlight the complexity of ZIKV pathogenesis, suggesting potential therapeutic targets for Zika-related complications.
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Association Between Blood Lead Levels and Diabetic Kidney Disease: A Cross-sectional Analysis of NHANES Data (1999-2018)
Authors: Yaxian Ning, Jianqin Wang, Xiaochun Zhou, Gouqin Wang and Lili ZhangAvailable online: 29 April 2025More LessBackgroundThe relationship between heavy metals, particularly lead (Pb), and diabetic kidney disease (DKD) remains unclear, especially regarding exposure thresholds. This study investigates the association between blood Pb levels and DKD risk using data from the National Health and Nutrition Examination Survey (NHANES) from 1999 to 2018.
MethodsA total of 1,343 participants were included, with 508 diagnosed with DKD. Baseline characteristics were compared between DKD and non-DKD groups. Multivariate generalized linear models (GLMs) and weighted logistic regression were used to assess correlations between blood Pb levels and DKD risk. A nomogram was developed to evaluate the predictive power of significant clinical characteristics.
ResultsKey clinical characteristics, including age, marital status, and serum Pb levels, differed significantly between DKD and non-DKD groups. Serum Pb was identified as a significant risk factor (ORs: 1.18–1.39, p < 0.01). The nomogram demonstrated good predictive accuracy (AUC = 0.717).
ConclusionElevated blood Pb levels are significantly associated with DKD, with a non-linear relationship and a defined threshold. These findings highlight the potential role of Pb exposure in DKD pathogenesis and suggest the utility of blood Pb monitoring in diabetic patients.
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Exercise Alleviates Atherosclerosis Through the Modulation of the NLRP3 Inflammasome
Authors: Xuan Liu, Shujuan Hu, Xianwang Wang and Yuqing DingAvailable online: 25 April 2025More LessAtherosclerosis (AS) is a chronic inflammatory disease closely associated with endothelial dysfunction and oxidative stress. The NOD-like receptor protein 3 (NLRP3) inflammasome, a key regulator of inflammatory responses, can exacerbate the progression of AS when activated. Growing evidence suggests that exercise, as a non-pharmacological intervention, can alleviate the progression of AS by modulating the activity of NLRP3 inflammasome. This review discusses how exercise influences the development of AS through the regulation of NLRP3 inflammasome and the underlying molecular mechanism. This study introduces the structure and activation mechanisms of NLRP3 inflammasome, as well as its role in AS. And summarizes how exercise can ameliorate endothelial dysfunction, regulate lipid metabolism, and suppress oxidative stress and inflammation by affecting the expression and activity of NLRP3 inflammasome, thereby exerting a beneficial impact on AS. Additionally, we explore the effects of exercise on the downstream inflammatory cytokines of NLRP3 inflammasome and how this regulation could help to slow the progression of AS. These findings underscore the therapeutic relevance of exercise in the prevention and treatment of AS. It provides new insights into the role of exercise interventions in the management of AS and lays a theoretical foundation for the development of innovative treatment strategies for cardiovascular disease. Given that the NLRP3 inflammatome plays an important role in the pathogenesis and treatment of AS, exercise therapy strategies targeting the NLRP3 inflammatome will help promote the development of precision medicine for AS.
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Prognostic Value and Immunological Role of CBX7 in Lung Adenocarcinoma
Authors: Lingzheng Yang, Yutang Huang, Wenlu Mo, Lanxiang Wu and Chunjie WenAvailable online: 24 April 2025More LessBackgroundChromobox 7 (CBX7) has been implicated in the progression of various malignant tumors, but its clinical relevance in lung adenocarcinoma (LUAD) remains poorly understood. This study aimed to investigate the expression, prognostic value, biological functions, and immunological role of CBX7 in LUAD.
MethodsCBX7 expression in LUAD and adjacent normal tissues was analyzed using The Cancer Genome Atlas (TCGA) and Gene Expression Omnibus (GEO) datasets. Kaplan-Meier curves and Cox risk regression evaluated prognostic significance. Various algorithms assessed the correlation between CBX7 and immune micro-environment. The expression of CBX7 in LUAD tissues was detected by RT-qPCR, western blotting, and immunohistochemistry. The function of CBX7 in LUAD was further investigated by in vitro and in vivo experiments.
ResultsCBX7 expression significantly downregulated LUAD, which was associated with aberrant DNA methylation. Decreased CBX7 expression correlated with advanced tumor stage and poor prognosis. Notably, CBX7 is associated with immune cell infiltration and immune checkpoints, highlighting its potential role in guiding immunotherapy. Functional experiments demonstrated that CBX7 overexpression suppressed the malignant phenotype of LUAD cells, while CBX7 knockdown promoted tumor progression.
ConclusionWe conducted a systematic analysis of the diagnostic, prognostic, and immunological significance of CBX7 in LUAD, and found that it might serve as a diagnostic marker and therapeutic target in the future.
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Ginsenoside Rg1 Attenuates Muscle Atrophy in Hyperglycemic Conditions, Inactivity and Protein Deprivation Models via AKT/mTOR Pathway Activation
Available online: 23 April 2025More LessBackgroundMuscle atrophy, a debilitating condition prevalent in diabetes and extended periods of immobilization, lacks robust therapeutic strategies. This investigation examines ginsenoside Rg1's therapeutic potential in counteracting muscle atrophy under hyperglycemic conditions and in experimental models of immobilization and dietary protein restriction.
MethodsC2C12 murine myoblasts were cultured under variable glucose concentrations and treated with or without Rg1. Multiple cellular parameters were evaluated, including cell viability, apoptotic indices, cell cycle distribution, and protein synthesis rates. The activation status of the protein kinase B (AKT)/mammalian target of rapamycin (mTOR) signaling cascade and expression of atrophy-related markers were quantified using qRT-PCR and Western blot analyses. In parallel animal studies, rats were subjected to either immobilization or protein restriction protocols, with or without Rg1 administration. Muscle function, mass, and relevant biomarkers were evaluated.
ResultsHyperglycemic conditions significantly compromised C2C12 myoblast viability, triggered apoptotic pathways, and disrupted normal cell cycle progression. Rg1 administration effectively attenuated these detrimental effects through enhanced AKT/mTOR pathway activation, upregulation of Myogenin (MyoG) expression, and suppression of atrophy-associated markers. In the rat models, Rg1 supplementation significantly ameliorated muscle deterioration, maintaining muscle mass, contractile force, and exercise tolerance, while simultaneously modulating atrophy signaling pathways and attenuating inflammatory responses. The protective effects of Rg1 were abrogated after the co-treatment with an AKT inhibitor.
ConclusionGinsenoside Rg1 exhibits significant protective properties against muscle atrophy under hyperglycemic conditions and in experimental models of immobilization and protein restriction, primarily mediated through activation of the AKT/mTOR signaling pathway. These findings establish Rg1 as a promising therapeutic candidate for the treatment of muscle atrophy.
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Analysis of Alternative Splicing Events in Melanoma and the Implications for Prognosis
Authors: Hongwei Deng, Xiang Huang, Ji Zhang, Xinyu Xu, Jianglin Wang, Li Liu, Yajun Yu, Jianguo Feng and Yijing HeAvailable online: 07 April 2025More LessIntroductionAlternative splicing (AS) events significantly affect melanoma progression. Therefore, understanding their effect on prognosis is important for developing new treatments.
MethodsUnivariate Cox regression analysis and LASSO regression were carried out to identify key AS events, build an AS risk model, and classify sample risk levels. Pearson correlation analysis was also performed to analyze the relationship between AS events and RNA-binding protein (RBP) genes or indicators of immune infiltration. Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway enrichment analyses were performed using gene expression data from patients with varying risk levels. Univariate and multivariable Cox regression analyses were also carried out to examine the association between immune cell infiltration and prognosis.
ResultsA total of 41446 AS events were identified; among them, 446 AS events were identified as significantly associated with melanoma prognosis. An AS risk model for prognosis was established using seven key AS events. A close correlation was found between 137 AS events and 1013 RBP genes, suggesting that these genes may participate in the regulation of AS events. KEGG enrichment analysis revealed that the genes involved in AS were closely associated with immune system functions, which may explain why AS events affect the prognosis of melanoma. Finally, by combining the AS risk score and clinical indicators, we developed a nomogram model that could effectively predict melanoma prognosis.
ConclusionThis analysis of AS events and regulation may aid in developing novel prognostic biomarkers and therapeutic targets for melanoma.
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Metabolomic Profiling Reveals Distinct Pathways in Degenerated and Non-degenerated Rotator Cuff Tears: Implications for Pathogenesis and Treatment
Available online: 07 April 2025More LessBackgroundTissue metabolomics is a promising technology for evaluating in situ changes in disease pathogenesis. It addresses a significant knowledge gap in the study of both degenerated and non-degenerated supraspinatus (SSp) tendons. This study analyzed the metabolomic profiles associated with rotator cuff tears (RCTs).
PurposeRCTs cause loss of function and shoulder pain, with the SSp muscle being the most frequently affected. Inflammation and complex metabolic changes may play roles in its etiology. Evaluation of the metabolomic differences between the degenerated and non-degenerated SSp tissues of RCT patients was aimed.
MethodsA cross-sectional study of 14 patients with RCTs, diagnosed through physical examination and magnetic resonance imaging, was conducted. Degenerate and non-degenerate SSp tissue debris were collected during arthroscopy. Untargeted metabolomic analysis of these samples was performed using liquid chromatography quadrupole time-of-flight mass spectrometry (LC-Q-ToF-MS). Metabolic peaks were identified, matched, and normalized before further analysis. Partial least squares-discriminant analysis (PLS-DA), heatmap generation, unsupervised volcano plots, and fold-change analyses were conducted. A putative metabolite list was subsequently compiled to elucidate pathways of degeneration. These metabolites were matched with metabolic pathways using the RaMP-DB metabolite set library.
ResultsThe tyrosine metabolism (p=4.93 x10-4), ferroptosis (p=1.25 x10-3), steroidogenesis (p=9.89 x10-4), and cholesterol biosynthesis (p=3.05 x10-3) were altered in the degenerated RCTs.
ConclusionThese findings suggest that metabolomic alterations may be associated with the development of RCTs, with changes in tyrosine metabolism, ferroptosis, and lipid metabolism potentially contributing to muscle degeneration and inflammation. Identified disruptions in steroidogenesis provide new insights into the role of hormonal factors in RCT development. Understanding these metabolic pathways is clinically relevant in sports medicine, as it enables targeted therapies and personalized treatment strategies, ultimately enhancing recovery and improving outcomes for athletes.
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Enhancement of Platinum-Based Drug Sensitivity in Ovarian Cancer Cells Through Hyperthermia-Induced Activation of the TGF-β1/β-Catenin Signaling Pathway
Authors: Xiaogang Lv, Wenjuan Wu, Gaoting Huang, Xiaowen Yao, Shirong Zeng and Yifeng WangAvailable online: 07 April 2025More LessBackgroundPlatinum-based drugs like cisplatin are key in treating ovarian cancer, but resistance frequently leads to treatment failure. The TGF-β1/β-catenin signaling pathway has been implicated in tumor resistance. This study investigates whether hyperthermiaenhances ovarian cancer cell sensitivity to platinum-based drugs by activating the TGF-β1/β-catenin pathway.
MethodsIn vitro and in vivo models of ovarian cancer were treated with hyperthermia and cisplatin. Changes in TGF-β1 and β-catenin expression were measured using Western blotting, qPCR, immunohistochemistry, and cell viability assays to determine the impact of hyperthermia on drug sensitivity.
ResultsHyperthermia significantly reduced TGF-β1 and β-catenin expression in ovarian cancer cells and tumor tissues, suppressing the pathway. This led to increased cisplatin sensitivity and higher apoptosis rates in vitro, while in vivo, tumor growth was significantly suppressed, and cisplatin's antitumor effects were enhanced.
ConclusionHyperthermia boosts the effectiveness of platinum-based drugs in ovarian cancer by suppressing the TGF-β1/β-catenin pathway, presenting a potential strategy to overcome chemoresistance and improve patient outcomes.
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Bone Marrow Mesenchymal Stem Cell Senescence in the Development of Osteoporosis: Mechanisms, Interventions, and Future Directions
Authors: Chengen Li, Bo Li, Jiuchao Zhang, Kun Liu, Gang Du, Cunliang Guo and Zhenguo YangAvailable online: 27 March 2025More LessOsteoporosis, a significant age-related disease, is marked by diminished bone density and an elevated risk of fractures, representing a considerable global health challenge. Bone marrow mesenchymal ste
m cells (BMSCs) are essential in maintaining bone integrity through their differentiation into osteoblasts, which are crucial for bone formation. Nevertheless, the aging of BMSCs diminishes their regenerative abilities and intensifies inflammation, thereby playing a critical role in osteoporosis pathogenesis. This review explores the intricate mechanisms of BMSC senescence and its influence on osteoporosis, detailing cellular and molecular markers, such as oxidative stress, the senescence-associated secretory phenotype (SASP), and pivotal signaling pathways, including P53, PI3K/mTOR, and autophagy. We assess current interventions aimed at reducing BMSC senescence, with an emphasis on pharmacological methods like melatonin and antioxidants, alongside non-pharmacological strategies, such as exercise and dietary supplementation with omega-3 fatty acids. Furthermore, the challenges and limitations of translating these strategies into clinical applications are addressed, highlighting the necessity for personalized medicine to accommodate treatment outcome variability. Future research directions should focus on emerging therapeutic targets and novel interventions, such as gene editing technologies and advanced tissue engineering techniques. By integrating these strategies, this review endeavors to enhance the understanding and treatment of osteoporosis, emphasizing the critical need to target BMSC senescence to develop effective therapies.
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High Glycolysis and Lipid Metabolism Status Predicts Poor Prognosis in Colorectal Cancer Patients
Available online: 25 March 2025More LessBackgroundThe prognosis of patients with stage III colorectal cancer (CRC) shows significant variations. The purpose of this study was to investigate the role of key regulatory proteins in glycolysis and lipid metabolism for the prognostic evaluation of stage III CRC patients.
MethodsUtilizing the Cancer Genome Atlas (TCGA) database, we analyzed the expression of various key regulatory genes in glycolysis and lipid metabolism pathways in CRC, as well as the relationship between gene expression levels and overall survival. We selected the top two key genes exhibiting differential expression patterns in glycolysis and lipid metabolism, namely, glucose transporter type 1 (GLUT1), pyruvate kinase M2 (PKM2), fatty acid synthase (FASN), and stearoyl-CoA desaturase 1 (SCD1), as targets for subsequent exploration. We analyzed the effects of GLUT1, PKM2, FASN, and SCD1 on the proliferation, migration, and drug sensitivity of CRC cells in vitro. These proteins were detected by immunohistochemistry (IHC) in the clinical tissues of stage III CRC patients. Based on the intensity of IHC staining for GLUT1, PKM2, FASN and SCD1, the cumulative score from these 4 target proteins for each sample was calculated (score range from 0 to 8). The relationships between high (scores of 6-8) or low (scores of 0-5) expression of glycolysis and lipid metabolism molecules and the clinicopathological characteristics, and survival of patients were analyzed.
ResultsThe expression disparities of the GLUT1, PKM2, FASN, and SCD1 genes were the most prominent between tumor and normal tissues. Overexpression of GLUT1, PKM2, FASN, or SCD1 significantly promoted CRC cell growth and migration, as evidenced by CCK-8, colony formation, and Transwell assays. Exogenous introduction of GLUT1, PKM2, FASN, or SCD1 increased oxaliplatin IC50 values, enhanced cell survival, and reduced early apoptosis in CRC cells exposed to oxaliplatin. High glycolysis and lipid metabolism status were associated with poor tumor differentiation, vascular or nerve invasion, and shorter overall survival. The status of glycolysis and lipid metabolism was an independent prognostic factor for stage III CRC patients.
ConclusionHigh glycolysis and lipid metabolism status are correlated with a poor prognosis in patients with stage III colorectal cancer.
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Potential Effects of Opium on Pro-Inflammatory Cytokines in Coronary Artery Disease by Interfering with Anti-inflammatory Drugs
Available online: 10 March 2025More LessBackgroundOpium is one of the factors that may interfere with coronary artery disease (CAD). This study aimed to investigate the role of opium in certain pro-inflammatory and anti-inflammatory cytokines in CAD patients with and without opium dependence on regular prescription medicines.
MethodsSeventy-seven patients with suspected CAD were selected as candidates for coronary angiography in this case-control study. They were categorized into three groups:1) CAD opium-addicted (CAD+OA, n=30); 2) CAD non-opium-addicted (CAD, n=30); and 3) non-opium-addicted with no CAD individuals as a control group (Ctrl, n=17). Routine medications, including aspirin, atorvastatin, bisoprolol, valsartan, losartan, clopidogrel, metoprolol, isosorbide, trinitrate glyceryl, captopril, and carvedilol, were administered to these patients. ELISA was performed to quantify plasma levels of interleukin-23 (IL-23), IL-17, IL-1β, transforming growth factor beta (TGF-β), and IL-10.
ResultsA significantly higher level of IL-23 was found in the CAD+OA group than in the CAD and control groups. In addition, in the CAD+OA group, the mean difference in TGF-β levels was significantly lower than that in CAD patients, whereas no significant difference was found between the Ctrl group and the CAD+OA and CAD groups. No significant differences were observed in the mean levels of IL-17, IL-1β, or IL-10 among the groups.
ConclusionOpium was found to contribute to the induction of inflammation by interfering with cardiovascular medications, resulting in deterioration of CAD complications. Additionally, certain medications, including aspirin, glyceryl trinitrate, atorvastatin, and clopidogrel, played a significant role in regulating the expression of cytokines.
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Proteomic Analysis of Molecular Mechanisms Involved in TGF-β-Induced Epithelial-Mesenchymal Transition in Human Lung Adenocarcinoma A549 Cells
Authors: Wen-Hui Tang, Dong-Mei Wang, Zi’e Zhan, Da-Hai Kang, Tai Wan and Zhuo-Fan LiuAvailable online: 07 March 2025More LessObjectiveThis study aimed to examine the molecular mechanisms involved in transforming growth factor-β (TGF-β)-induced epithelial-mesenchymal transition (EMT) in human lung adenocarcinoma (LUAD) A549 cells.
MethodsProteins were extracted from cultured human LUAD A549 cells cultured under two conditions: untreated and treated with TGF-β (5 ng/ml) for 48 hours. The expression levels of EMT-related proteins, including E-cadherin, Vimentin, and α-smooth muscle actin, were assessed using western blotting. Proteomic analysis was performed using isobaric tags for relative and absolute quantification combined with two-dimensional liquid chromatography-tandem mass spectrometry. Differentially expressed proteins were subjected to bioinformatics analysis, including functional annotation and interaction network studies.
ResultsA total of 122 proteins were identified as differentially expressed between the untreated and TGF-β-treated A549 cells. Of these, 55 proteins were upregulated, while 67 were downregulated following TGF-β treatment. Bioinformatics and interaction network analyses highlighted six proteins—GAPDH, TP53, MAPK1, IGF1, SRC, and MYC—as being closely associated with the EMT in human LUAD.
ConclusionThis study provides new insights into the processes of invasion and metastasis in LUAD by examining the molecular mechanisms underlying TGF-β-induced EMT in A549 cells.
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ESM-1 Promotes the Process of Diabetic Nephropathy by Promoting the Expression of CXCL3
Authors: Ping Zhao, Tingting Deng and Jialing ZengAvailable online: 05 March 2025More LessBackgroundThe analysis of diabetic nephropathy (DN)-related gene dataset demonstrated that C-X-C motif chemokine ligand 3 (CXCL3) is highly expressed in DN. Exploring the impact of CXCL3 in the course of DN is the core goal of this study.
MethodsThe cell model used in this study was CIHP-1 cells induced by high glucose (HG). qRT-PCR and western blot analysis were carried out to determine the expression difference of CXCL3. After down-regulating the CXCL3 level, we analyzed HG-induced CIHP-1 cell viability by MTT assay, proliferation by EdU staining, apoptosis by flow cytometry, and changes in related protein expression by western blot. In order to analyze the possible regulatory relationship between endothelial cell-specific molecule 1 (ESM-1) and CXCL3 in DN, we constructed an over-expressed ESM-1 plasmid and carried out a rescue experiment.
ResultsCXCL3 and ESM-1 were highly expressed in HG-induced podocytes (p<0.05). Silenced CXCL3 (siCXCL3) increased the viability and proliferation of CIHP-1 cells induced by HG, reduced the proportion of apoptosis, and produced corresponding protein changes (p<0.01). After the overexpression of ESM-1, the effects of siCXCL3 were partially offset (p<0.05).
ConclusionIn this study, ESM-1 increased HG-induced podocyte damage by promoting CXCL3 expression.
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2-DG Promotes the Proliferation, Differentiation, Migration, and Resistance to Oxidative Stress of Mesenchymal Stem Cells through Hippo Signaling
Authors: Liang Dong and Lang LiAvailable online: 26 February 2025More LessBackgroundHippo signaling regulates the behavior and fate of mesenchymal stem cells (MSCs), which are crucial for the repair and cure of acute respiratory distress syndrome (ARDS). However, whether 2-deoxy-D-glucose (2-DG), a specific activator of Hippo signaling, would further enhance the reparative effect of MSCs in ARDS remains unclarified.
ObjectiveThis study aimed to determine whether 2-DG could promote the proliferation, differentiation, migration, and resistance to oxidative stress of mouse bone marrow-derived MSCs (mBMSCs).
MethodsmBMSCs were isolated from C57BL/6 mice and differentiated into alveolar type II epithelial (ATII) cells by noncontact coculture. The specific activator and inhibitor 2-DG and 4-[(5,10-dimethyl-6-Oxo-6,10-dihydro-5h-pyrimido[5,4-B]thieno[3,2-E][1,4]diazepin-2-Yl)amino]benzenesulfonamide (XMU-MP-1) were used to activate and inhibit Hippo signaling, respectively. Oxidative stress-induced injuries were induced by H2O2 treatment.
ResultsWe observed that 2-DG activated Hippo signaling and promoted mBMSC proliferation in a dose-dependent manner. 2-DG also promoted the differentiation of mBMSCs into ATII cells and enhanced not only the horizontal and vertical migration of mBMSCs but also mBMSC homing to injured lung tissue. H2O2 treatment inhibited Hippo signaling and reduced the viability of mBMSCs by decreasing the Bcl-2/Bax ratio, but 2-DG activated Hippo signaling and conferred mBMSCs with resistance to oxidative stress by increasing the Bcl-2/Bax ratio. However, XMU-MP-1 suppressed these effects to some extent.
ConclusionThrough Hippo signaling, 2-DG promoted the proliferation, migration, differentiation, and resistance to oxidative stress of mBMSCs, suggesting a novel strategy for enhancing the reparative effects of MSCs in ARDS.
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Recent Accomplishments in Exhaled Breath Condensate Analysis - Molecular Aspects
Authors: Sergey V. Silkin, Stanislav I. Pekov, Konstantin V. Bocharov and Igor A. PopovAvailable online: 20 February 2025More LessNowadays, the research of exhaled breath condensate (EBC) analysis is widely discussed in the scientific community. The growing interest in EBC analysis results is related to the ample advantages of non-invasive techniques in healthcare and related fields. In particular, EBC analysis can be used to diagnose respiratory diseases, monitor the disease’s course during therapy, and monitor drug intake and metabolism. This review aims to systematize the accumulated knowledge on EBC collection, concentration, storage, and analysis methods and compare them with similar procedures for exhaled breath (EB). We proposed a generalized chemical classification of EBC compounds that are biomarkers for various diseases. The potential transformation of substances during EB condensation was considered, and EBC analysis methods were systematically categorized based on this classification. Methods for EBC analysis using chromatographic separation with mass spectrometric detection (hyphenated methods) were separately discussed as the most promising methods for future research applications.
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