Cells最新文献

{"title":"A Cross-Sectional Exploratory Study of Rat Sarcoid (Ras) Activation in Women with and Without Polycystic Ovary Syndrome.","authors":"Sara Anjum Niinuma, Haniya Habib, Ashleigh Suzu-Nishio Takemoto, Priya Das, Thozhukat Sathyapalan, Stephen L Atkin, Alexandra E Butler","doi":"10.3390/cells14050377","DOIUrl":"10.3390/cells14050377","url":null,"abstract":"<p><p><b>Objective</b>: Rat sarcoma (Ras) proteins, Kirsten, Harvey, and Neuroblastoma rat sarcoma viral oncogene homolog (KRAS, HRAS, and NRAS, respectively), are a family of GTPases, which are key regulators of cellular growth, differentiation, and apoptosis through signal transduction pathways modulated by growth factors that have been recognized to be dysregulated in PCOS. This study explores Ras signaling proteins and growth factor-related proteins in polycystic ovary syndrome (PCOS). <b>Methods</b>: In a well-validated PCOS database of 147 PCOS and 97 control women, plasma was batch analyzed using Somascan proteomic analysis for circulating KRas, Ras GTPase-activating protein-1 (RASA1), and 45 growth factor-related proteins. The cohort was subsequently stratified for BMI (body mass index), testosterone, and insulin resistance (HOMA-IR) for subset analysis. <b>Results</b>: Circulating KRas, and RASA1 did not differ between PCOS and control women (<i>p</i> > 0.05). EGF1, EGFR, and EGFRvIII were decreased in PCOS (<i>p</i> = 0.04, <i>p</i> = 0.04 and <i>p</i> < 0.001, respectively). FGF8, FGF9, and FGF17 were increased in PCOS (<i>p</i> = 0.02, <i>p</i> = 0.03 and <i>p</i> = 0.04, respectively), and FGFR1 was decreased in PCOS (<i>p</i> < 0.001). VEGF-D (<i>p</i> < 0.001), IGF1 (<i>p</i> < 0.001), IGF-1sR (<i>p</i> = 0.02), and PDGFRA (<i>p</i> < 0.001) were decreased in PCOS compared to controls. After stratifying for BMI ≤ 29.9 kg/m², EGFR FGF8, FGFR1 VEGF-D, IGF1, and IGF-1sR differed (<i>p</i> < 0.05) though EGF1, EGFRvIII, FGF8, FGFR1, and VEGF-D no longer differed; after subsequently stratifying for HOMA-IR, only FGFR1, VEGF-D, IGF1, and IGF-1sR differed between groups (<i>p</i> < 0.05). <b>Conclusions</b>: Several growth factors that activate Ras differ between women with and without PCOS, and when stratified for BMI and HOMA-IR, only FGFR1, VEGF-D, IGF1, and IGF-1sR differed; these appear to be inherent features of the pathophysiology of PCOS.</p>","PeriodicalId":9743,"journal":{"name":"Cells","volume":"14 5","pages":""},"PeriodicalIF":5.1,"publicationDate":"2025-03-05","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11898917/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143603971","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Few-Layer Graphene-Based Optical Nanobiosensors for the Early-Stage Detection of Ovarian Cancer Using Liquid Biopsy and an Active Learning Strategy.","authors":"Obdulia Covarrubias-Zambrano, Deepesh Agarwal, Joan Lewis-Wambi, Raul Neri, Andrea Jewell, Balasubramaniam Natarajan, Stefan H Bossmann","doi":"10.3390/cells14050375","DOIUrl":"10.3390/cells14050375","url":null,"abstract":"<p><p>Ovarian cancer survival depends strongly on the time of diagnosis. Detection at stage 1 must be the goal of liquid biopsies for ovarian cancer detection. We report the development and validation of graphene-based optical nanobiosensors (G-NBSs) that quantify the activities of a panel of proteases, which were selected to provide a crowd response that is specific for ovarian cancer. These G-NBSs consist of few-layer explosion graphene featuring a hydrophilic coating, which is linked to fluorescently labeled highly selective consensus sequences for the proteases of interest, as well as a fluorescent dye. The panel of G-NBSs showed statistically significant differences in protease activities when comparing localized (early-stage) ovarian cancer with both metastatic (late-stage) and healthy control groups. A hierarchical framework integrated with active learning (AL) as a prediction and analysis tool for early-stage detection of ovarian cancer was implemented, which obtained an overall accuracy score of 94.5%, with both a sensitivity and specificity of 0.94.</p>","PeriodicalId":9743,"journal":{"name":"Cells","volume":"14 5","pages":""},"PeriodicalIF":5.1,"publicationDate":"2025-03-04","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11898886/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143604117","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Advances in Therapy of Adult Patients with Acute Lymphoblastic Leukemia.","authors":"Oscar Sucre, Saagar Pamulapati, Zeeshan Muzammil, Jacob Bitran","doi":"10.3390/cells14050371","DOIUrl":"10.3390/cells14050371","url":null,"abstract":"<p><p>The landscape of adult acute lymphoblastic leukemia (ALL) is dramatically changing. With very promising results seen with novel immunotherapeutics in the setting of relapsed and refractory disease, the prospect of using these agents in first-line therapy has prompted the development of multiple clinical trials addressing this question. This review seeks to outline and expand the current standard of care, as well as new advances, in the treatment of adult patients with ALL and address future areas of research. We expect the frontline integration of immuno-oncology agents such as bispecific T-cell engagers, antibody-drug conjugates, and chimeric antigen receptor (CAR) T cells may maintain or improve outcomes in adults while also minimizing toxicity. Treatment of ALL will continue to evolve as we focus on personalized, patient-centered approaches.</p>","PeriodicalId":9743,"journal":{"name":"Cells","volume":"14 5","pages":""},"PeriodicalIF":5.1,"publicationDate":"2025-03-04","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11898990/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143603975","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Extracellular Signaling Molecules from Adipose-Derived Stem Cells and Ovarian Cancer Cells Induce a Hybrid Epithelial-Mesenchymal Phenotype in a Bidirectional Interaction.","authors":"Vinícius Augusto Simão, Juliana Ferreira Floriano, Roberta Carvalho Cesário, Karolina da Silva Tonon, Larissa Ragozo Cardoso de Oliveira, Flávia Karina Delella, Fausto Almeida, Lucilene Delazari Dos Santos, Fábio Rodrigues Ferreira Seiva, Débora Aparecida Pires de Campos Zuccari, João Tadeu Ribeiro-Paes, Russel J Reiter, Luiz Gustavo de Almeida Chuffa","doi":"10.3390/cells14050374","DOIUrl":"10.3390/cells14050374","url":null,"abstract":"<p><p>Ovarian cancer (OC) is characterized by high mortality rates due to late diagnosis, recurrence, and metastasis. Here, we show that extracellular signaling molecules secreted by adipose-derived mesenchymal stem cells (ASCs) and OC cells-either in the conditioned medium (CM) or within small extracellular vesicles (sEVs)-modulate cellular responses and drive OC progression. ASC-derived sEVs and CM secretome promoted OC cell colony formation, invasion, and migration while upregulating tumor-associated signaling pathways, including TGFβ/Smad, p38MAPK/ERK1/2, Wnt/β-catenin, and MMP-9. Additionally, OC-derived sEVs and CM induced a pro-tumorigenic phenotype in ASCs, enhancing their invasiveness and expression of tumor-associated factors. Notably, both ASCs and OC cells exhibited increased expression of E-cadherin and Snail/Slug proteins, key markers of epithelial/mesenchymal hybrid phenotype, enhancing cellular plasticity and metastatic potential. We also demonstrated that these cellular features are, at least in part, due to the presence of tumor-supportive molecules such as TNF-α, Tenascin-C, MMP-2, and SDF-1α in the CM secretome of ASCs and OC cells. In silico analyses linked these molecular changes to poor prognostic outcomes in OC patients. These findings highlight the critical role of sEVs and tumor/stem cell-derived secretome in OC progression through bidirectional interactions that impact cellular behavior and phenotypic transitions. We suggest that targeting EV-mediated communication could improve therapeutic strategies and patient outcomes.</p>","PeriodicalId":9743,"journal":{"name":"Cells","volume":"14 5","pages":""},"PeriodicalIF":5.1,"publicationDate":"2025-03-04","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11899480/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143604102","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Development and Validation of AAV-Mediated Liver, Liver-VAT, and Liver-Brain SORT and Therapeutic Regulation of FASN in Hepatic De Novo Lipogenesis.","authors":"Ratulananda Bhadury, Mohammad Athar, Pooja Mishra, Chayanika Gogoi, Shubham Sharma, Devram S Ghorpade","doi":"10.3390/cells14050372","DOIUrl":"10.3390/cells14050372","url":null,"abstract":"<p><p>Hepatic lipogenesis combined with elevated endoplasmic reticulum (ER) stress is central to non-alcoholic steatohepatitis (NASH). However, the therapeutic targeting of key molecules is considerably less accomplished. Adeno-associated virus (AAV)-mediated gene therapies offer a new solution for various human ailments. Comprehensive bio-functional validation studies are essential to assess the impact of AAVs in the target organ for developing both preclinical and clinical gene therapy programs. Here, we have established a robust and efficient protocol for high-titer AAV production to enable detailed Selective ORgan Targeting (SORT) of AAV1, 5, 7, and 8 in vivo. Our results for in vivo SORT showed single organ (liver) targeting by AAV8, no organ targeting by AAV1, and dual organ transduction (liver-brain and liver-VAT) by AAV5 and AAV7. Using a human dataset and preclinical murine models of NASH, we identified an inverse correlation between ER stress-triggered CRELD2 and the de novo lipogenesis driver FASN. Furthermore, liver-specific silencing of CRELD2 via AAV8-shCreld2 strongly supports the contribution of CRELD2 to de novo lipogenesis through FASN regulation. Thus, our study demonstrates a robust method for producing clinically translatable AAVs that could be readily adapted for liver and/or liver-VAT or liver-brain targeted gene therapy.</p>","PeriodicalId":9743,"journal":{"name":"Cells","volume":"14 5","pages":""},"PeriodicalIF":5.1,"publicationDate":"2025-03-04","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11899426/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143603982","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Diabetic Retinopathy (DR): Mechanisms, Current Therapies, and Emerging Strategies.","authors":"Hyewon Seo, Sun-Ji Park, Minsoo Song","doi":"10.3390/cells14050376","DOIUrl":"10.3390/cells14050376","url":null,"abstract":"<p><p>Diabetic retinopathy (DR) is one of the most prevalent complications of diabetes, affecting nearly one-third of patients with diabetes mellitus and remaining a leading cause of blindness worldwide. Among the various diabetes-induced complications, DR is of particular importance due to its direct impact on vision and the irreversible damage to the retina. DR is characterized by multiple pathological processes, primarily a hyperglycemia-induced inflammatory response and oxidative stress. Current gold standard therapies, such as anti-VEGF injections and photocoagulation, have shown efficacy in slowing disease progression. However, challenges such as drug resistance, partial therapeutic responses, and the reliance on direct eye injections-which often result in low patient compliance-remain unresolved. This review provides a comprehensive overview of the underlying molecular mechanisms in DR, the current therapies, and their unmet needs for DR treatment. Additionally, emerging therapeutic strategies for improving DR treatment outcomes are discussed.</p>","PeriodicalId":9743,"journal":{"name":"Cells","volume":"14 5","pages":""},"PeriodicalIF":5.1,"publicationDate":"2025-03-04","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11898816/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143603986","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Research Progress on the Immune Function of Liver Sinusoidal Endothelial Cells in Sepsis.","authors":"Xinrui Wang, Zhe Guo, Yuxiang Xia, Xuesong Wang, Zhong Wang","doi":"10.3390/cells14050373","DOIUrl":"10.3390/cells14050373","url":null,"abstract":"<p><p>Sepsis is a complex clinical syndrome closely associated with the occurrence of acute organ dysfunction and is often characterized by high mortality. Due to the rapid progression of sepsis, early diagnosis and intervention are crucial. Recent research has focused on exploring the pathological response involved in the process of sepsis. Liver sinusoidal endothelial cells (LSECs) are a special type of endothelial cell and an important component of liver non-parenchymal cells. Unlike general endothelial cells, which mainly provide a barrier function within the body, LSECs also have important functions in the clearance and regulation of the immune response. LSECs are not only vital antigen-presenting cells (APCs) in the immune system but also play a significant role in the development of infectious diseases and tumors through their specific immune regulatory pathways. However, in certain disease states, the functions of LSECs may be impaired, leading to immune imbalance and the development of organ failure. Investigating the immune pathways of LSECs in sepsis may provide new solutions for the prevention and treatment of sepsis and is crucial for maintaining microcirculation and improving patient outcomes.</p>","PeriodicalId":9743,"journal":{"name":"Cells","volume":"14 5","pages":""},"PeriodicalIF":5.1,"publicationDate":"2025-03-04","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11899273/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143603977","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"mir-276a Is Required for Muscle Development in <i>Drosophila</i> and Regulates the FGF Receptor <i>Heartless</i> During the Migration of Nascent Myotubes in the Testis.","authors":"Mathieu Preußner, Maik Bischoff, Susanne Filiz Önel","doi":"10.3390/cells14050368","DOIUrl":"10.3390/cells14050368","url":null,"abstract":"<p><p>MicroRNAs function as post-transcriptional regulators in gene expression and control a broad range of biological processes in metazoans. The formation of multinucleated muscles is essential for locomotion, growth, and muscle repair. microRNAs have also emerged as important regulators for muscle development and function. In order to identify new microRNAs required for muscle formation, we have performed a large microRNA overexpression screen. We screened for defects during embryonic and adult muscle formation. Here, we describe the identification of mir-276a as a regulator for muscle migration during testis formation. The mir-276a overexpression phenotype in testis muscles resembles the loss-of-function phenotype of <i>heartless</i>. A GFP sensor assay reveals that the 3'UTR of <i>heartless</i> is a target of mir-276a. Furthermore, we found that mir-276a is essential for the proper development of indirect flight muscles and describe a method for determining the number of nuclei for each of the six longitudinal muscle fibers (DLMs), which are part of the indirect flight muscles.</p>","PeriodicalId":9743,"journal":{"name":"Cells","volume":"14 5","pages":""},"PeriodicalIF":5.1,"publicationDate":"2025-03-03","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11898445/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143604213","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Isolation and Functional Characterization of Endophytic Bacteria from Muscadine Grape Berries: A Microbial Treasure Trove.","authors":"Meenakshi Agarwal, Mehboob B Sheikh","doi":"10.3390/cells14050369","DOIUrl":"10.3390/cells14050369","url":null,"abstract":"<p><p>Muscadine grapes are renowned for their unique traits, natural disease resistance, and rich bioactive compounds. Despite extensive research on their phytochemical properties, microbial communities, particularly endophytic bacteria, remain largely unexplored. These bacteria play crucial roles in plant health, stress tolerance, and ecological interactions. This study represents the first comprehensive effort to isolate, identify, and functionally characterize the bacterial endophytes inhabiting muscadine grape berries using a culture-dependent approach. We isolated diverse bacterial species spanning six genera-<i>Bacillus</i>, <i>Staphylococcus</i>, <i>Paenibacillus</i>, <i>Calidifontibacillus</i>, <i>Curtobacterium</i>, and <i>Tatumella</i>. Microscopic and physiological analysis revealed variations in bacterial morphology, with isolates demonstrating adaptability to varied temperatures. Cluster-based analysis indicated functional specialization among the isolates, with species from <i>Pseudomonadota</i> and <i>Actinomycetota</i> exhibiting superior plant growth-promoting abilities, whereas <i>Bacillota</i> species displayed potential biocontrol and probiotic properties. Among them, <i>Tatumella ptyseos</i> demonstrated exceptional plant growth-promoting traits, including indole-3-acetic acid production, nitrogen fixation, phosphate solubilization, and carbohydrate fermentation. Additionally, <i>Bacillus</i> spp. showed presumptive biocontrol potential, while <i>Paenibacillus cineris</i> emerged as a potential probiotic candidate. The identification of <i>Calidifontibacillus erzurumensis</i> as a novel endophytic species further expands the known biodiversity of grape-associated microbes. These findings provide insights into the metabolic diversity and functional roles of muscadine grape-associated endophytes, highlighting their potential for agricultural and biotechnological applications.</p>","PeriodicalId":9743,"journal":{"name":"Cells","volume":"14 5","pages":""},"PeriodicalIF":5.1,"publicationDate":"2025-03-03","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11899604/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143604204","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"THz Waves Improve Spatial Working Memory by Increasing the Activity of Glutamatergic Neurons in Mice.","authors":"Lequan Song, Zhiwei He, Ji Dong, Haoyu Wang, Jing Zhang, Binwei Yao, Xinping Xu, Hui Wang, Li Zhao, Ruiyun Peng","doi":"10.3390/cells14050370","DOIUrl":"10.3390/cells14050370","url":null,"abstract":"<p><p>Terahertz (THz) waves, a novel type of radiation with quantum and electronic properties, have attracted increasing attention for their effects on the nervous system. Spatial working memory, a critical component of higher cognitive function, is coordinated by brain regions such as the infralimbic cortex (IL) region of the medial prefrontal cortex and the ventral cornu ammonis 1 (vCA1) of hippocampus. However, the regulatory effects of THz waves on spatial working memory and the underlying mechanisms remain unclear. In this study, the effects of 0.152 THz waves on glutamatergic neuronal activity and spatial working memory and the related mechanisms were investigated in cell, brain slice, and mouse models. Cellular experiments revealed that THz waves exposure for 60 min significantly increased the intrinsic excitability of primary hippocampal neurons, enhanced glutamatergic neuron activity, and upregulated the expression of molecules involved in glutamate metabolism. In brain slice experiments, THz waves markedly elevated neuronal activity, promoted synaptic plasticity, and increased glutamatergic synaptic transmission within the IL and vCA1 regions. Molecular dynamics simulations found that THz waves could inhibit the ion transport function of glutamate receptors. Moreover, Y-maze tests demonstrated that mice exposed to THz waves exhibited significantly improved spatial working memory. Multiomics analyses indicated that THz waves could induce changes in chromatin accessibility and increase the proportion of excitatory neurons. These findings suggested that exposure to 0.152 THz waves increased glutamatergic neuronal activity, promoted synaptic plasticity, and improved spatial working memory, potentially through modifications in chromatin accessibility and excitatory neuron proportions.</p>","PeriodicalId":9743,"journal":{"name":"Cells","volume":"14 5","pages":""},"PeriodicalIF":5.1,"publicationDate":"2025-03-03","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11898596/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143604225","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}