Current molecular medicine最新文献

{"title":"Study on the Mechanism of Notch Pathway Mediates the Role of Lenvatinib-resistant Hepatocellular Carcinoma Based on Organoids.","authors":"Weiqing Feng, Haixiong Zhang, Qing Yu, Hao Yin, Xiaowei Ou, Jie Yuan, Liang Peng","doi":"10.2174/0115665240268201231213095302","DOIUrl":"10.2174/0115665240268201231213095302","url":null,"abstract":"<p><strong>Background: </strong>The emergence of treatment resistance has hindered the efficacy of targeted therapies used to treat patients with hepatocellular carcinoma (HCC).</p><p><strong>Objective: </strong>This study aimed to explore the mechanism of organoids constructed from lenvatinib-resistant HCC cells.</p><p><strong>Methods: </strong>Hep3B cell and human HCC organoids were cultured and identified using hematoxylin and eosin staining and Immunohistochemistry. Lenvatinib-sensitive/ resistant Hep3B cells were constructed using lenvatinib (0, 0.1, 1, and 10 μM) and lenvatinib (0, 1, 10, and 100 μM). qRT-PCR and flow cytometry were utilized to determine HCC stem cell markers CD44, CD90, and CD133 expressions. Transcriptome sequencing was performed on organoids. Western blot evaluated Notch pathwayrelated proteins (NOTCH1 and Jagged) expressions. Furthermore, DAPT, an inhibitor of the Notch pathway, was used to investigate the effects of lenvatinib on resistance or stemness in organoids and human HCC tissues.</p><p><strong>Results: </strong>The organoids were successfully cultivated. With the increase of lenvatinib concentration, sensitive cell organoids were markedly degraded and ATP activity was gradually decreased, while there was no significant change in ATP activity of resistant cell organoids. CD44 expressions were elevated after lenvatinib treatment compared with the control group. KEGG showed that lenvatinib treatment of organoids constructed from Hep3B cells mainly activated the Notch pathway. Compared with the control group, NOTCH1 and Jagged expressions elevated, and ATP activity decreased after lenvatinib treatment. However, ATP activity was notably decreased after DAPT treatment. Moreover, DAPT inhibited lenvatinib resistance and the increase in the expressions of CD44 caused by lenvatinib. Besides, 100 μM lenvatinib significantly inhibited the growth and ATP activity of human HCC organoids, and DAPT increased the inhibitory effect of lenvatinib.</p><p><strong>Conclusion: </strong>Lenvatinib regulated resistance and stemness in organoids via the Notch pathway.</p>","PeriodicalId":10873,"journal":{"name":"Current molecular medicine","volume":" ","pages":"343-352"},"PeriodicalIF":2.2,"publicationDate":"2025-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"139424414","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Advances in Molecular Biology and Immunology of Spermatozoa and Fertilization in Domestic Animals: Implications for Infertility and Assisted Reproduction.","authors":"Mounir Adnane, Moussa Ahmed, Aspinas Chapwanya","doi":"10.2174/0115665240306965240802075331","DOIUrl":"10.2174/0115665240306965240802075331","url":null,"abstract":"<p><p>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.</p>","PeriodicalId":10873,"journal":{"name":"Current molecular medicine","volume":" ","pages":"167-186"},"PeriodicalIF":2.2,"publicationDate":"2025-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142686443","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"The Emerging Role of LncRNA AWPPH in Multiple Cancers: A Review Study.","authors":"Mohsen Sheykhhasan, Fateme Dermani, Nematollah Gheibi, Ishwaree Datta, Hamid Sadeghi, Saeideh Gholamzadeh Khoei","doi":"10.2174/1566524023666230816163031","DOIUrl":"10.2174/1566524023666230816163031","url":null,"abstract":"<p><p>Long non-coding RNAs (lncRNAs) are transcribed RNA molecules longer than 200 nucleotides in length that have no protein-coding potential. They are able to react with DNA, RNA, and protein. Hence they involve in regulating gene expression at the epigenetic, transcriptional, post-transcriptional, and translational levels. LncRNAs have been proven to play an important role in human malignancies and prognostic outcomes. In this review, we will comprehensively and functionally discuss the role of a novel identified lncRNA, namely lncRNA WAPPH located on human chromosome 2q13, in various cancers. Increasing research studies have shown that lncRNA AWPPH is deregulated in different malignancies, including breast cancer, gastric cancer, colorectal cancer, ovarian cancer, bladder cancer, leukemia, and others. LncRNA WAPPH serves as an oncogene in tumorigenesis and the development of cancer. Moreover, lncRNA AWPPH is involved in numerous biological processes of solid and blood cancers. Taken together, based on our scrutiny analysis, lncRNA AWPPH can be regarded as a putative biomarker for diagnosis or therapeutic target in human malignancies.</p>","PeriodicalId":10873,"journal":{"name":"Current molecular medicine","volume":" ","pages":"237-268"},"PeriodicalIF":2.2,"publicationDate":"2025-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"10069991","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Amiodarone Advances the Apoptosis of Cardiomyocytes by Repressing Sigmar1 Expression and Blocking KCNH2-related Potassium Channels.","authors":"Huiqing Liang, Huixian Li, Fangjiang Li, Xiaobo Xiong, Yang Gao","doi":"10.2174/0115665240265771231129105108","DOIUrl":"10.2174/0115665240265771231129105108","url":null,"abstract":"<p><strong>Background: </strong>Heart failure (HF) is the ultimate transformation result of various cardiovascular diseases. Mitochondria-mediated cardiomyocyte apoptosis has been uncovered to be associated with this disorder.</p><p><strong>Objective: </strong>This study mainly delves into the mechanism of the anti-arrhythmic drug amiodarone on mitochondrial toxicity of cardiomyocytes.</p><p><strong>Methods: </strong>The viability of H9c2 cells treated with amiodarone at 0.5, 1, 2, 3, and 4 μM was determined by 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide (MTT) assay, and Sigmar1 expression was examined by quantitative real-time PCR (qRTPCR). After transfection, the viability, apoptosis, reactive oxygen species (ROS) level, mitochondrial membrane potential (MMP), and potassium voltage-gated channel subfamily H member 2 (KCNH2) expression in H9c2 cells were assessed by MTT, flow cytometry, ROS assay kit, mitochondria staining kit, and Western blot.</p><p><strong>Results: </strong>Amiodarone at 1-4 μM notably weakened H9c2 cell viability with IC50 value of 2.62 ± 0.43 μM. Amiodarone at 0.5-4 μM also evidently suppressed the Sigmar1 level in H9c2 cells. Amiodarone repressed H9c2 cell viability and KCNH2 level and triggered apoptosis, ROS production and mitochondrial depolarization, while Sigmar1 upregulation reversed its effects. Moreover, KCNH2 silencing neutralized the effect of Sigmar1 up-regulation on H9c2 cell viability, apoptosis, and ROS production.</p><p><strong>Conclusion: </strong>Amiodarone facilitates the apoptosis of H9c2 cells by restraining Sigmar1 expression and blocking KCNH2-related potassium channels.</p>","PeriodicalId":10873,"journal":{"name":"Current molecular medicine","volume":" ","pages":"69-78"},"PeriodicalIF":2.2,"publicationDate":"2025-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"139416606","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Extracorporeal Shock Wave and Melatonin Alleviate Joint Capsule Fibrosis after Knee Trauma in Rats by Regulating Autophagy.","authors":"Jing Mao, Jin-Niu Zhang, Quan-Bing Zhang, De-Ting Zhu, Xue-Ming Li, Han Xiao, Xiu-Li Kan, Run Zhang, Yun Zhou","doi":"10.2174/0115665240339436240909100847","DOIUrl":"10.2174/0115665240339436240909100847","url":null,"abstract":"<p><strong>Background: </strong>Joint contracture is a common clinical problem affecting joint function. Capsule fibrosis plays a pivotal role in the progression of joint contracture. Previous studies have reported that autophagy plays a regulatory role in visceral fibrosis.</p><p><strong>Objective: </strong>This study aimed to investigate whether extracorporeal shock wave therapy (ESWT) and melatonin alleviate joint capsule fibrosis in rats with extended knee joint contracture by regulating autophagy.</p><p><strong>Methods: </strong>A rat traumatic knee joint extension contracture model was made. Then, the rats were treated with ESWT, melatonin, ESWT + melatonin, or ESWT + melatonin + mTOR agonist for 4 weeks. The range of motion (ROM) of the knee joints was measured. Joint capsules were collected and observed for pathological changes by H&E and Masson staining. LC3B protein expression was evaluated by immunofluorescence staining. TGF-β1, MMP-1, Col-Ⅰ, Col-Ⅲ, LC3, ATG7, Beclin1, p-AMPK, p-mTOR and p-ULK1 protein expressions were measured by Western blot assay.</p><p><strong>Results: </strong>The intervention groups had significantly improved ROM of knee joint (P < 0.05), significantly improved pathological changes on HE and Masson staining, significantly decreased protein expressions of TGF-β1, MMP-1, Col-Ⅰ, Col-Ⅲ and pmTOR (P < 0.05), and significantly increased protein expressions of LC3B, LC3II/LC3I ratio, ATG7, Beclin1, p-AMPK, and p-ULK1 (P < 0.05). Among these groups, the effects demonstrated by the ESWT + melatonin group were the best. With the mTOR agonist supplement, the therapeutic effects of extracorporeal shock waves and melatonin were significantly reduced.</p><p><strong>Conclusion: </strong>ESWT plus melatonin alleviated knee joint capsule fibrosis in rats by regulating autophagy.</p>","PeriodicalId":10873,"journal":{"name":"Current molecular medicine","volume":" ","pages":"222-236"},"PeriodicalIF":2.2,"publicationDate":"2025-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142281628","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Roles of Mesenchymal Stem Cells in Breast Cancer Therapy: Engineered Stem Cells and Exosomal Cell-Free Based Therapy.","authors":"Mohsen Karami Fath, Seyed Sajjad Zadian, Samaneh Mohammad Bagherzadeh Torbati, Vahid Saqagandomabadi, Omid Yousefi Afshar, Mohammad Khalilzad, Sara Abedi, Afshin Moliani, Ghasem Barati","doi":"10.2174/0115665240274818231207054037","DOIUrl":"10.2174/0115665240274818231207054037","url":null,"abstract":"<p><p>Breast cancer has a high prevalence among women, with a high mortality rate. The number of people who suffer from breast cancer disease is increasing, whereas metastatic cancers are mostly incurable, and existing therapies have unfavorable side effects. For an extended duration, scientists have dedicated their efforts to exploring the potential of mesenchymal stem cells (MSCs) for the treatment of metastatic cancers, including breast cancer. MSCs could be genetically engineered to boost their anticancer potency. Furthermore, MSCs can transport oncolytic viruses, suicide genes, and anticancer medicines to tumors. Extracellular vesicles (EVs) are MSC products that have attracted scientist's attention as a cell-free treatment. This study narratively reviews the current state of knowledge on engineered MSCs and their EVs as promising treatments for breast cancer.</p>","PeriodicalId":10873,"journal":{"name":"Current molecular medicine","volume":" ","pages":"431-444"},"PeriodicalIF":2.2,"publicationDate":"2025-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"139563989","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"NLRP3 Inflammasome Triggers Inflammation of Obstructive Sleep Apnea.","authors":"Xiaoting Yangzhong, Shu Hua, Yiqiong Wen, Xiaoqing Bi, Min Li, Yuanyuan Zheng, Shibo Sun","doi":"10.2174/0115665240294605240426123650","DOIUrl":"10.2174/0115665240294605240426123650","url":null,"abstract":"<p><p>Obstructive sleep apnea (OSA) is widespread in the population and affects as many as one billion people worldwide. OSA is associated with dysfunction of the brain system that controls breathing, which leads to intermittent hypoxia (IH), hypercapnia, and oxidative stress (OS). The number of NOD-like receptor family pyrin domain-containing (NLRP3) inflammasome was increased after IH, hypercapnia, and OS. NLRP3 inflammasome is closely related to inflammation. NLRP3 inflammasome causes a series of inflammatory diseases by activating IL-1β and IL-18. Subsequently, NLRP3 inflammasome plays an important role in the complications of OSA, including Type 2 diabetes (T2DM), coronary heart disease (CHD), hypertension, neuroinflammation, and depression. This review will introduce the basic composition and structure of the NLRP3 inflammasome and focus on the relationship between the NLRP3 inflammasome and OSA and OSA complications. We can deeply understand how NLRP3 inflammasome is strongly associated with OSA and OSA complications.</p>","PeriodicalId":10873,"journal":{"name":"Current molecular medicine","volume":" ","pages":"522-536"},"PeriodicalIF":2.2,"publicationDate":"2025-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"140956402","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Targeting the Molecules in EMT: A Potential Therapeutic Opportunity in Breast Cancer.","authors":"Siri Chandana Gampa, Sireesha V Garimella","doi":"10.2174/0115665240310780240805114133","DOIUrl":"10.2174/0115665240310780240805114133","url":null,"abstract":"<p><p>Breast Cancer (BC) is one of the most frequently occuring diseases in women, accounting for 90% of cancer-related deaths in women. Tumor cells can invade nearby tissues and spread to distant organs by metastasis. The epithelialmesenchymal transition or EMT, which involves a number of transcription factors and signaling pathways, is a mechanism by which cells of the epithelium change into mesenchymal type capable of motility, invasion, and metastasis. EMT has grown to be a more intriguing target for developing cutting-edge treatment approaches since it is involved in diverse malignant transformation-related activities. Besides preventing tumor cell invasion and spread and the development of metastatic lesions, anti-EMT treatment methods also lessen cancer stemness and improve the efficacy of more traditional chemotherapeutics. EMT is, therefore, a desirable target in oncology. This review gives an overview of EMT, various markers of EMT, and different inhibitors used in therapies targeting EMT in BC.</p>","PeriodicalId":10873,"journal":{"name":"Current molecular medicine","volume":" ","pages":"567-588"},"PeriodicalIF":2.2,"publicationDate":"2025-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142003825","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Exosomes Derived from Astragaloside IV-pretreated Endothelial Progenitor Cells (AS-IV-Exos) Alleviated Endothelial Oxidative Stress and Dysfunction via the miR-210/ Nox2/ROS Pathway.","authors":"Wu Xiong, Xi Zhang, Xiao-Ling Zou, Sai Peng, Hua-Juan Lei, Xiang-Nan Liu, Lan Zhao, Zi-Xin Huang","doi":"10.2174/0115665240262982240109104620","DOIUrl":"10.2174/0115665240262982240109104620","url":null,"abstract":"<p><strong>Background: </strong>Chronic hyperglycemia in diabetes induces oxidative stress, leading to damage to the vascular system. In this study, we aimed to evaluate the effects and mechanisms of AS-IV-Exos in alleviating endothelial oxidative stress and dysfunction caused by high glucose (HG).</p><p><strong>Methods: </strong>Histopathological changes were observed using HE staining, and CD31 expression was assessed through immunohistochemistry (IHC). Cell proliferation was evaluated through CCK8 and EDU assays. The levels of ROS, SOD, and GSH-Px in the skin tissues of each group were measured using ELISA. Cell adhesion, migration, and tube formation abilities were assessed using adhesion, Transwell, and tube formation experiments. ROS levels in HUVEC cells were measured using flow cytometry. The levels of miR-210 and Nox2 were determined through quantitative reverse transcription-polymerase chain reaction (qRT-PCR). The expression of Nox2, SOD, GSH-Px, CD63, and CD81 was confirmed using WB.</p><p><strong>Results: </strong>The level of miR-210 was reduced in diabetes-induced skin damage, while the levels of Nox2 and ROS increased. Treatment with AS-IV increased the level of miR-210 in EPC-Exos. Compared to Exos, AS-IV-Exos significantly reduced the proliferation rate, adhesion number, migration speed, and tube-forming ability of HGdamaged HUVEC cells. AS-IV-Exos also significantly decreased the levels of SOD and GSH-Px in HG-treated HUVEC cells and reduced the levels of Nox2 and GSH-Px. However, ROS levels and Nox2 could reverse this effect.</p><p><strong>Conclusion: </strong>AS-IV-Exos effectively alleviated endothelial oxidative stress and dysfunction induced by HG through the miR-210/Nox2/ROS pathway.</p>","PeriodicalId":10873,"journal":{"name":"Current molecular medicine","volume":" ","pages":"320-329"},"PeriodicalIF":2.2,"publicationDate":"2025-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"139650466","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"An Overview of Invasive Ductal Carcinoma (IDC) in Women's Breast Cancer.","authors":"Adriana E Gallas, Grace O Morenikeji, Raven E King, Muyiwa S Adegbaju, Adeola Ayoola, Godstime Taiwo, Olanrewaju B Morenikeji","doi":"10.2174/0115665240349468241113065031","DOIUrl":"10.2174/0115665240349468241113065031","url":null,"abstract":"<p><p>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.</p>","PeriodicalId":10873,"journal":{"name":"Current molecular medicine","volume":" ","pages":"361-371"},"PeriodicalIF":2.2,"publicationDate":"2025-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142977983","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}