Frontiers in bioscience (Landmark edition)最新文献

{"title":"Adipose Stromal Cell Heterogeneity and Trafficking: Implications for Breast Cancer Metastasis and Obesity.","authors":"Caroline R McCauley, Tamara R Fischer, Nicole M Cullen, Mackenzie L Hawes, Khudeja Salim, Devon R Roeming, Jordan F Wright, Olivia M Mayer, Van T Hoang, Elizabeth C Martin, Matthew E Burow, Bruce A Bunnell","doi":"10.31083/FBL36599","DOIUrl":"https://doi.org/10.31083/FBL36599","url":null,"abstract":"<p><p>Adipose-derived stem cells (ASCs) have been extensively investigated for regeneration and tissue engineering applications owing to their inherent regenerative ability. However, the effects of various species and depot-specific extraction sites on ASC differentiation and renewal capacity have yet to be explored thoroughly, limiting the clinical use of ASCs. Despite promising clinical results, ASCs are also associated with poor disease outcomes, specifically in the context of breast cancer and obesity. Only when ASC-driven obesity and breast cancer are understood separately will the connection between the two diseases and the ASC-associated effects therein be fully established. Therefore, this review aimed to assess the behavioral differences of ASCs from various large mammalian species and human-derived anatomical niches. This review analyzes ASC migration, the role of ASCs in breast cancer progression and immune modulation, and breast cancer-driven ASC dysfunction to further the understanding of ASCs for future clinical applications.</p>","PeriodicalId":73069,"journal":{"name":"Frontiers in bioscience (Landmark edition)","volume":"30 7","pages":"36599"},"PeriodicalIF":3.1,"publicationDate":"2025-07-24","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144790909","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Kir2.1 Channel Contributes to Hypokalemia-Induced Abnormal Pacemaker Activities of Cardiomyocytes With Inward Rectification.","authors":"Jinhua Lv, Yangxin Jiang, Jin Zeng, Dongchuan Zuo","doi":"10.31083/FBL39879","DOIUrl":"https://doi.org/10.31083/FBL39879","url":null,"abstract":"<p><strong>Background: </strong>Hypokalemia induces abnormal spontaneous pacemaker activities of cardiomyocytes, which is strongly associated with fatal cardiac arrhythmias caused by hypokalemia. However, the mechanism remains unclear.</p><p><strong>Methods: </strong>For the study of the mechanisms associated with hypokalemia, optical mapping recordings were performed on isolated murine hearts perfused with hypokalemia solutions, which allows for the concurrent examination of membrane potential and calcium transient morphology and arrhythmogenesis. Human Kir2.1, Kir2.1-E224G mutant, or Kir4.1 channels were constructed with lentiviral vectors. Patch clamp recordings were performed to verify the corresponding currents of these constructed channels in the heterologous expression system chinese hamster ovary (CHO) cells, and to explore how Kir2.1 channels influence the resting membrane potentials of human iPSC-derived cardiomyocytes (hiPSC-CMs) when exposed to low [K⁺]_e.</p><p><strong>Results: </strong>Isolated murine hearts perfused with hypokalemia solution (1 mmol/L) developed a high frequency of spontaneous ventricular tachycardia (VT), which was initiated as an after-depolarization triggered activity associated with Ca²⁺ overload. The VT was maintained by abnormal spontaneous pacemaker activities caused by membrane potential depolarization. In response to 1 mmol/L [K⁺]_e, hiPSC-CMs overexpressing Kir2.1 channels exhibited membrane potential depolarization, leading to the induction of abnormal pacemaker activities. The cells overexpressing rectification-deficient Kir2.1-E224G mutant channels or weak rectification Kir4.1 channels exhibited membrane potential hyperpolarization without the occurrence of abnormal pacemaker activities.</p><p><strong>Conclusions: </strong>Kir2.1 channel-mediated membrane potential depolarization contributes to hypokalemia-induced abnormal spontaneous pacemaker activities of cardiomyocytes. The inward rectification of Kir2.1 channels plays a critical role in this process.</p>","PeriodicalId":73069,"journal":{"name":"Frontiers in bioscience (Landmark edition)","volume":"30 7","pages":"39879"},"PeriodicalIF":3.1,"publicationDate":"2025-07-24","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144790924","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Transient <i>Staphylococcus aureus</i> Infection Promotes Sustained Intervertebral Disc Degeneration Through the ATF-3/CHOP Pathway.","authors":"Lemeng Ren, Yichen Li, Jianlin Yin, Xiaopei Sun, Jiancheng Zheng, Yuehuan Zheng, Yazhou Lin, Zhenjin Ju, Zhe Chen, Peng Cao","doi":"10.31083/FBL39167","DOIUrl":"https://doi.org/10.31083/FBL39167","url":null,"abstract":"<p><strong>Background: </strong>Infection with <i>Staphylococcus aureus</i> (<i>S. aureus</i>) is an important contributor to intervertebral disc degeneration (IDD). Endoplasmic reticulum stress (ERS) is a major pathway through which bacteria regulate cell fate. The aim of this study was to examine the role of ERS in <i>S. aureus</i>-induced IDD.</p><p><strong>Methods: </strong>We assessed the <i>S. aureus</i>-induced degeneration, apoptosis, and senescence of nucleus pulposus cells (NPCs) <i>in vitro</i> by Western blot, flow cytometry, and staining for β-galactosidase, and <i>in vivo</i> by magnetic resonance imaging/computed tomography (MRI/CT) imaging, terminal deoxynucleotidyl transferase dUTP nick end labeling (TUNEL) and histological staining. RNA sequencing was conducted to identify differentially expressed genes, while siRNA, lentiviral vectors, and <i>Atf3-knockout</i> (Atf3-KO) mice were utilized to confirm the role of ATF3 in persistent IDD following transient <i>S. aureus</i> infection.</p><p><strong>Results: </strong>Following the eradication of <i>S. aureus</i> <i>in vitro</i>, the expression of Aggrecan and collagen II in NPCs continued to decline, accompanied by an increase in the proportion of apoptotic and senescent cells. <i>Transient S. aureus</i> infection was shown to activate the Activating Transcription Factor 3 (ATF3)-CCAAT/Enhancer-Binding Protein Homologous Protein (CHOP) signaling pathway, leading to sustained swelling of the endoplasmic reticulum in NPCs. <i>In vivo</i> experiments further demonstrated that transient <i>S. aureus</i> infection resulted in progressive IDD, activation of the ATF3-CHOP pathway, increased numbers of TUNEL-positive cells, and elevated P21 expression. Knockdown of ATF3 expression <i>in vitro</i> attenuated the <i>S. aureus</i>-mediated increase in apoptotic and senescent cells, while <i>Atf3</i>-KO mice exhibited milder IDD compared to wild type (WT) mice, with fewer apoptotic cells and reduced P21 expression.</p><p><strong>Conclusion: </strong><i>Transient S. aureus</i> infection may lead to progressive IDD by triggering sustained ER stress and activating related signaling pathways. The ATF3-CHOP pathway may be an important target for alleviating the sustained disc degeneration caused by transient <i>S. aureus</i> infection.</p>","PeriodicalId":73069,"journal":{"name":"Frontiers in bioscience (Landmark edition)","volume":"30 7","pages":"39167"},"PeriodicalIF":3.1,"publicationDate":"2025-07-24","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144790933","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"The Emerging Roles of Metabolic Reprogramming in Non-Small Cell Lung Cancer Progression.","authors":"Beatriz P Peixoto, Rebecca A Clague, Joshua P Reddy, Hiromi I Wettersten","doi":"10.31083/FBL31363","DOIUrl":"https://doi.org/10.31083/FBL31363","url":null,"abstract":"<p><p>Lung cancer remains a leading cause of cancer-related mortality due to its capacity for silent metastasis and the significant challenges in achieving effective treatment. Currently, targeted therapies and chemotherapies are the primary options for advanced or inoperable lung cancer; however, their efficacy is often undermined by the cancer's ability to develop resistance through both genetic and non-genetic mechanisms. This review explores recent advances in understanding metabolic reprogramming in non-small cell lung cancer (NSCLC), focusing on its critical role in cancer progression. NSCLC cells exhibit heterogeneous activation of metabolic pathways influenced by their oncogenic mutations. Notably, their metabolic phenotypes evolve in response to environmental stressors and therapeutic pressures. Moreover, NSCLC cells engage in metabolic crosstalk with their microenvironment to enhance survival, leveraging distinct metabolic adaptations at both primary and metastatic sites. Despite extensive preclinical studies evaluating novel therapeutic strategies targeting these metabolic pathways, many have failed in clinical trials due to severe adverse effects. This is because the targeted pathways are crucial not only for cancer cells but also for normal cellular functions. Future research must prioritize approaches that selectively disrupt cancer-specific metabolic regulation to improve therapeutic outcomes.</p>","PeriodicalId":73069,"journal":{"name":"Frontiers in bioscience (Landmark edition)","volume":"30 7","pages":"31363"},"PeriodicalIF":3.1,"publicationDate":"2025-07-08","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144790931","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Adenovirus-Based Single-Dose Vaccines for SARS-CoV-2: A Review.","authors":"Vivek P Chavda, Anita A Mehta, Hajra Zafar, Faisal Raza, Ana Cláudia Paiva-Santos, Pankti C Balar, Vasso Apostolopoulos, Lalitkumar Vora","doi":"10.31083/FBL25094","DOIUrl":"https://doi.org/10.31083/FBL25094","url":null,"abstract":"<p><p>The severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) outbreak has many unexpected implications, but the scientific community remains optimistic about overcoming these obstacles. Adenoviruses (Ad) are considered the most suitable vectors for transferring specific antigens to mammalian cells since they can induce both innate and adaptive immune responses. Ad-based coronavirus disease 2019 (COVID-19). vaccines were granted emergency use authorization in the COVID-19 pandemic. Many features of the Ad vector render it an appealing vaccine carrier for contagious diseases, including high titer, ease of processing, high effectiveness, low immunogenicity in clinical trials, and consistency in pharmaceutical packaging and shipment processes. Ad-based vaccines are generally effective and have few side effects since Ad induces minor infections in humans, and genetic modifications can block viral replication. These single-dose vaccines are effective not only in young individuals but also in adults. Clinical trials of these single-dose vaccines are commendable and have shown excellent safety and efficacy profiles. This review provides a summary of the development of single-dose vaccines against SARS-CoV-2.</p>","PeriodicalId":73069,"journal":{"name":"Frontiers in bioscience (Landmark edition)","volume":"30 7","pages":"25094"},"PeriodicalIF":3.1,"publicationDate":"2025-07-07","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144790908","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Alpha-Synuclein Dysregulation in Systemic Pathophysiology of Synucleinopathies.","authors":"Hallie H Dolin, Bowen Zhou, Robert W Maitta","doi":"10.31083/FBL27178","DOIUrl":"https://doi.org/10.31083/FBL27178","url":null,"abstract":"<p><p>Alpha-synuclein (α-syn) has long been identified as the etiologic agent of multiple neurodegenerative diseases, the most common and well-known of which are Parkinson's disease (PD) and Lewy body dementia (LBD). While it is known that the pathophysiology of these synucleinopathies involves aggregation of improperly-folded α-syn, the mechanisms leading to its accumulation have not been fully identified. However, multiple pathways have been proposed, any or all of which may contribute to synucleinopathies. The role of α-syn in normal homeostasis and in other organ systems, especially the hematopoietic system, has been reported recently. Research within the last decade has shown that α-syn plays many vital and conserved roles in the cell biology of various organ systems, such as packaging of cell products, exocytosis, membrane stabilization, and more. This protein has been recognized as an essential factor in normal hematopoietic and immune systems function, and its deficiency leads to an abnormal phenotype, in hematopoietic and immune cell lineages. Similar phenotypes in synucleinopathies not only emphasize the conserved nature of the synuclein family but suggest a bimodal pathophysiology in which aggregated α-syn leads to cellular toxicity while causing derangement of systems that require it. Research into specific molecular mechanisms and potential treatments may provide further understanding of neurodegenerative diseases as well as lead to novel therapies. However, elucidation of the systemic roles of α-syn in addition to its toxicity in excess is essential to prevent treatment-induced deprivation, which paradoxically harms the patient. Here, we address recent advances in systemic synucleinopathies and putative interconnectedness of these compartments. While previous studies and reviews have focused on the mechanisms of α-syn synthesis, transport, and aggregation within systems, this review focuses on the potential inter-systemic nature of synucleinopathies and their possible synergistic origins.</p>","PeriodicalId":73069,"journal":{"name":"Frontiers in bioscience (Landmark edition)","volume":"30 7","pages":"27178"},"PeriodicalIF":3.1,"publicationDate":"2025-07-07","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144790910","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Bronchoalveolar Lavage Derived Fibroblasts From Interstitial Lung Disease Patients: A Chance to Exploit 2D/3D Model of Pulmonary Fibrosis <i>In Vitro</i>.","authors":"Paolo Giannoni, Emanuela Barisione, Marco Grosso, Maria Bertolotto, Paola Altieri, Federico Carbone, Fabrizio Montecucco, Daniela de Totero","doi":"10.31083/FBL38726","DOIUrl":"https://doi.org/10.31083/FBL38726","url":null,"abstract":"<p><strong>Background: </strong>Bronchoalveolar lavage (BAL) constitutes a valuable diagnostic approach for the differential diagnosis of various pulmonary fibrotic diseases. BAL fluids from patients with interstitial lung diseases (ILDs) can also be utilized for research purposes, offering cell populations suitable for functional and phenotypical studies. In this study, we demonstrate the feasibility of isolating a discrete number of fibroblasts/myofibroblasts <i>in vitro</i> from the BAL fluid from ILD patients, a procedure typically performed during the early stages of disease when high-resolution computed tomography does not yield a definitive diagnosis.</p><p><strong>Methods: </strong>We obtained BAL samples from a total of 43 patients. Fibroblasts were successfully derived <i>in vitro</i> from 20 patients, with larger quantities of cells from 11 patients. Whenever possible, the cells were cultured and expanded until passage 12-15. Fibroblasts could be expanded to passage 36 in only one case. The expression of typical fibrotic markers, such as type I collagen, α-smooth muscle actin, and fibronectin-extra domain A or B (FN-EDA/-EDB), was therefore compared in fibroblasts obtained from ILD-patients with fibroblasts derived from non-diseased controls by quantitative RT-PCR, immunofluorescence, and cytofluorographic analysis. The rate of proliferation, migration, and response to the anti-fibrotic drug pirfenidone was further determined in 2D and in 3D models of <i>in vitro</i> cultures.</p><p><strong>Results: </strong>A specific morphological heterogeneity among fibroblasts/myofibroblasts derived from patients with fibrotic or non-fibrotic ILD was observed, such as enlarged and flattened shaped cells <i>vs</i> spindle-shaped cells. Moreover, a higher expression of α-smooth muscle actin (α-SMA), type I collagen (collagen I), and fibronectin was demonstrated in ILD fibroblasts than in control fibroblasts. The anti-fibrotic drug pirfenidone was effective in inhibiting the growth and migration of ILD-fibroblasts both in 2D and 3D <i>in vitro</i> models.</p><p><strong>Conclusions: </strong>Collectively, the present study suggests that BAL-derived fibroblasts from ILD patients may serve as a useful <i>in vitro</i> model for studying and assaying pulmonary fibrosis. This approach has the potential to improve our understanding of ILD pathogenesis and overcome ethical and availability concerns associated with biopsy-derived tissues.</p>","PeriodicalId":73069,"journal":{"name":"Frontiers in bioscience (Landmark edition)","volume":"30 7","pages":"38726"},"PeriodicalIF":3.1,"publicationDate":"2025-07-07","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144790914","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"HCAR2 Exerts Anti-Depressive Effects on Corticosterone-Induced Depression in Mice by Modulating Microglial Activity.","authors":"Zhao Pan, Li Jiang, Jiacheng Chen, Sicong Xu, Ping Zhang, Yili Yi, Yangzhi Xie, Yongjun Chen","doi":"10.31083/FBL39311","DOIUrl":"https://doi.org/10.31083/FBL39311","url":null,"abstract":"<p><strong>Background: </strong>The metabolites derived from judicious dietary choices play a crucial role in the management and treatment of depression. Hydroxy-carboxylic acid receptor 2 (HCAR2) functions as a receptor for various diet-derived metabolites. Although a growing body of evidence indicates these metabolites exert beneficial effects on depression, the precise mechanisms underlying these benefits require further investigation.</p><p><strong>Methods: </strong>We established a mouse model of corticosterone (Cor)-induced depression to evaluate the therapeutic potential of HCAR2 activation on depression. A series of behavioral experiments were conducted to investigate whether HCAR2 activation could alleviate depressive-like behaviors in mice. The neuroprotective effects of HCAR2 in the hippocampus were examined using Nissl and hematoxylin-eosin (HE) staining. The levels of monoamine neurotransmitters in mouse serum were quantified, as well as the cell viability and lactate dehydrogenase (LDH) activity of hippocampal neurons co-cultured with primary microglia. Microglia-associated neuroinflammation was evaluated by quantifying pro-inflammatory cytokines using ELISA, and by assessing the polarization state of M1 microglia, including the mRNA expression levels of M1 markers and double fluorescence staining for inducible nitric oxide synthase/ionized calcium-binding adapter molecule 1 (iNOS/Iba1). The expression level of proteins in the protein kinase B-inhibitor of nuclear factor kappa-B kinase subunits alpha and beta-nuclear factor kappa-light-chain-enhancer of activated B cells (AKT-IKKαβ-NFκB) pathway in primary microglia was analyzed using western blot. Transcriptomic changes in microglia induced by HCAR2 activation were examined through RNA sequencing. Mice were fed PLX5622 chow to deplete microglia <i>in vivo</i>.</p><p><strong>Results: </strong>Activation of HCAR2 by its agonist MK-6892 in a Cor-induced model of depression significantly alleviated depressive-like behaviors, attenuated hippocampal neuronal injury, increased serum monoamine levels, reduced microglia-associated neuroinflammation, and inhibited the expression of proteins in the AKT-IKKαβ-NFκB pathway in primary microglia. Additionally, HCAR2 activation markedly enhanced hippocampal neuronal viability and decreased LDH activity in this co-culture system. Importantly, these protective effects were abolished in HCAR2 knockout mice. RNA sequencing revealed that HCAR2 activation induced changes in multiple signaling pathways. Moreover, the depletion of microglia also eliminated the protective effects of MK-6892.</p><p><strong>Conclusion: </strong>Activation of HCAR2 can reduce depressive-like behaviors, neuronal injury, and neuroinflammation. Our findings suggest these neuroprotective effects are, at least in part, mediated through modulation of microglial activity by HCAR2.</p>","PeriodicalId":73069,"journal":{"name":"Frontiers in bioscience (Landmark edition)","volume":"30 7","pages":"39311"},"PeriodicalIF":3.1,"publicationDate":"2025-06-30","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144790920","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Sodium-Dependent Glucose Transporter-2 Inhibitor Enhances the Hypotensive Effect of Renal Denervation by Inhibiting Sympathetic Activity and Inflammatory Reaction.","authors":"Hao Zhang, Zhuqing Li, Wei Cai, Yanxin Wang, Jiaxin Feng, Xuemei Yin, Qi Li, Ning Yang, Chengzhi Lu, Yuming Li","doi":"10.31083/FBL31309","DOIUrl":"https://doi.org/10.31083/FBL31309","url":null,"abstract":"<p><strong>Background: </strong>Sodium-dependent glucose transporter-2 inhibitors (SGLT-2i) have potential hypotensive effects, enhancing the hypotensive effect of renal denervation (RDN). Spontaneously hypertensive rats (SHRs) were used to verify this hypothesis and explore the associated underlying pathways.</p><p><strong>Methods: </strong>Seven Wistar-Kyoto (WKY) rats and 35 SHRs were divided into 6 groups. The blank WKY control (W) group consisted of all 7 WKY rats, whereas the SHRs were divided into the following groups, each containing 7 rats: sham operation (Sham), renal denervation (RDN), SGLT-2 inhibitor treatment (SGLT-2i), and the combination of renal denervation with SGLT-2 inhibitor treatment (RDN+SGLT-2i). The rats in the RDN+SGLT-2i and SGLT-2i groups were gavaged with dapagliflozin (DAPA) before RDN. The sham group was subjected to a sham operation. One-week post-operation, rat tail manometry, and echocardiography were subsequently performed, and peripheral blood inflammatory cells were detected via flow cytometry before sample collection. Following sample collection, the serum, including interleukin-6, angiotensin-II, renin, and norepinephrine, was tested via enzyme-linked immunosorbent assay. Pathological testing included Masson staining of the myocardial tissue, tyrosine hydroxylase (TH) immunohistochemistry, and Fos protooncogene (<i>C-Fos</i>) immunofluorescence staining of the hypothalamus tissue.</p><p><strong>Results: </strong>Compared with RDN alone, RDN following intragastric DAPA administration reduced systolic blood pressure (SBP) in SHRs, independent of its hypoglycemic effect. Compared with the RDN group, the pathological results of the RDN+SGLT-2i group revealed a greater improvement in the intensity of TH staining in the hypothalamus tissue, closer to the normal level of the cross-sectional area in myocardial cells. Furthermore, we observed enhanced sympathetic inhibition in the brain and a reduction in the fibrotic area within myocardial cells. Additionally, the proportions of inflammatory mononuclear cell subsets and the levels of inflammatory factors improved. Although DAPA reduced inflammation and sympathetic nerve overexcitation alone, it could not completely reverse blood pressure (BP) or cardiac function. Similarly, the alleviation of inflammation and BP reduction in RDN-treated rats were inferior to those in rats treated with RDN combined with DAPA.</p><p><strong>Conclusions: </strong>Compared with RDN alone, DAPA addition before RDN can considerably reduce the BP of SHRs. The enhancement of the hypotensive effect may be attributed to the inhibition of sympathetic activity and the reduction in inflammatory reactions.</p>","PeriodicalId":73069,"journal":{"name":"Frontiers in bioscience (Landmark edition)","volume":"30 6","pages":"31309"},"PeriodicalIF":3.3,"publicationDate":"2025-06-30","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144562152","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Cellular Senescence: A Pathogenic Driver for Pulmonary Fibrosis.","authors":"Sihan Wang, Rongrong Wang, Qiyuan He, Yicheng Ma, Yanyuan Fang, Jin Yang, Hui Zhao, Lin Fu, Danlei Chen","doi":"10.31083/FBL37811","DOIUrl":"https://doi.org/10.31083/FBL37811","url":null,"abstract":"<p><p>Pulmonary fibrosis is a life-threatening progressive lung disease characterized by increased fibrogenesis and decreased lung function. Pulmonary fibrosis has a poor prognosis and a low patient survival rate, with no effective treatments currently available. Cellular senescence is thought to contribute to the pathogenesis of this aging-related disease. Cellular senescence and premature aging are involved in the development of pulmonary fibrosis, which affects various cellular processes such as proliferation, apoptosis, and inflammatory responses. Multiple pathways contribute to cellular senescence and participate in the pathogenesis of pulmonary fibrosis, such as tumor protein p53 (p53)/cyclin dependent kinase inhibitor 1A (p21) and cyclin dependent kinase inhibitor 2A (p16)/retinoblastoma protein (pRB). However, many unanswered questions remain concerning the relationship between cellular senescence and pulmonary fibrosis. In this review, we first summarize the common causes of lung cell senescence and pulmonary fibrosis, including aging, inflammation, chemotherapy drugs, and environmental pollutants. We also discuss the enriched signaling pathways and epigenetic factors (e.g., non-coding RNAs) that are important during cell senescence and the progression of pulmonary fibrosis. Finally, we discuss current strategies for treating pulmonary fibrosis by targeting cellular senescence, including relevant preclinical and clinical studies. This review provides new mechanistic insights for understanding the role of cellular senescence in the development of pulmonary fibrosis and its treatment by targeting cellular senescence.</p>","PeriodicalId":73069,"journal":{"name":"Frontiers in bioscience (Landmark edition)","volume":"30 7","pages":"37811"},"PeriodicalIF":3.1,"publicationDate":"2025-06-30","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144790915","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}