Life sciences最新文献_第5页

Agmatine alleviates diabetic-induced hyposalivation in rats: A histological and biochemical study 鸦胆子碱可减轻糖尿病诱发的大鼠唾液分泌过少：组织学和生化研究

IF 5.2 2区医学

Life sciences Pub Date : 2024-11-05 DOI: 10.1016/j.lfs.2024.123220

Heba Fikry , Lobna A. Saleh , Osama A. Mohammed , Ahmed S. Doghish , Elsayed G.E. Elsakka , Abdullah A. Hashish , Jaber Alfaifi , Mohannad Mohammad S. Alamri , Masoud I.E. Adam , Mohammed A. Atti , Faten A. Mahmoud , Hadwa Ali Abd Alkhalek

{"title":"Agmatine alleviates diabetic-induced hyposalivation in rats: A histological and biochemical study","authors":"Heba Fikry , Lobna A. Saleh , Osama A. Mohammed , Ahmed S. Doghish , Elsayed G.E. Elsakka , Abdullah A. Hashish , Jaber Alfaifi , Mohannad Mohammad S. Alamri , Masoud I.E. Adam , Mohammed A. Atti , Faten A. Mahmoud , Hadwa Ali Abd Alkhalek","doi":"10.1016/j.lfs.2024.123220","DOIUrl":"10.1016/j.lfs.2024.123220","url":null,"abstract":"<div><div>Diabetic patients commonly experience hyposalivation, which can cause challenges with eating, swallowing, dry mouth, and speaking. It also raises the likelihood of developing periodontal disease. This study aimed to evaluate if agmatine could improve the rate of salivation in rats with hyposalivation induced by streptozotocin (STZ). Five groups of Wistar rats were utilized with 10 animals in each group. They were classified as follows; Negative control group (G1), agmatine (G2) group, and Nicotinamide (NA)-STZ (G3) group; received a single intraperitoneal dose of 65 mg/kg of STZ after NA injection. NA was administered to protect residual β cells and enhance their insulin secretion; NA-STZ + Metformin (G4) Metformin-treated diabetic group; at day 10 diabetic rats received 50mg/kg orally for 28 days, and NA-STZ + Agmatine (G5) at day 10 diabetic rats received a daily intraperitoneal dose of 300 mg/kg Agmatine for 28 days. The salivary flow rate was assessed weekly. Then, the animals were euthanized, both parotid (PG) and submandibular (SMG) salivary glands were dissected, and the following parameters were assessed; salivary glands' histopathology, aquaporin 5 (AQP5), caspase-3, E-cadherin expressions, inflammatory markers and finally, salivary glands' oxidative stress status. Agmatine has alleviated the salivary glands' dysfunction in STZ-induced diabetic rats. It normalized diabetes mellitus-associated salivary glands' abnormalities including histopathological abnormalities, decreased AQP5 and E-cadherin expressions, increased caspase-3 expression, and oxidative stress and inflammatory parameters. Agmatine alleviates diabetes mellitus-associated hyposalivation. It can promote PGs and SMGs function through its histological and AQP5 expression improvements.</div></div>","PeriodicalId":18122,"journal":{"name":"Life sciences","volume":"359 ","pages":"Article 123220"},"PeriodicalIF":5.2,"publicationDate":"2024-11-05","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142591097","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

引用次数: 0

Does concomitant diazepam and ethanol use modulate age-related cognitive decline in mice? 同时服用地西泮和乙醇是否会调节小鼠与年龄相关的认知能力下降？

IF 5.2 2区医学

Life sciences Pub Date : 2024-11-05 DOI: 10.1016/j.lfs.2024.123216

Louise Carton , Camille Landmann , Florent Auger , Nicolas Durieux , Charlotte Laloux , Maéva Kyheng , Maud Petrault , Kelly Timmerman , Camille Potey , Sandrine Bergeron , Julie Deguil , Régis Bordet

{"title":"Does concomitant diazepam and ethanol use modulate age-related cognitive decline in mice?","authors":"Louise Carton , Camille Landmann , Florent Auger , Nicolas Durieux , Charlotte Laloux , Maéva Kyheng , Maud Petrault , Kelly Timmerman , Camille Potey , Sandrine Bergeron , Julie Deguil , Régis Bordet","doi":"10.1016/j.lfs.2024.123216","DOIUrl":"10.1016/j.lfs.2024.123216","url":null,"abstract":"<div><h3>Background</h3><div>Concomitant use of alcohol and benzodiazepines are described among elderly, raising concerns about their combined impact on memory. We aimed to evaluate the long-term impact of chronic diazepam use associated with ethanol intoxication on memory in aging mice.</div></div><div><h3>Methods</h3><div>Twelve-month-old male C57BL6 mice were assigned into 4 groups: ethanol (OH), diazepam (DIA), diazepam + ethanol (DOH) and control (CTL). For 16 weeks, ethanol was available ad libitum and diazepam was mixed with food. Behavioral testing, performed during and after treatment cessation included working memory and visual recognition memory assessment. The second session was implemented with spatial reference learning and memory assessment in the Barnes maze test. In vivo magnetic resonance spectroscopy (MRS) acquisitions were performed to quantify hippocampal metabolites during and after cessation treatment.</div></div><div><h3>Results</h3><div>During treatment, visual recognition memory was significantly different between groups with the DIA group exhibiting the worst performance. MRS acquisition highlighted higher glutamate and choline levels in OH and DOH groups in comparison to CTL and DIA groups. After treatment wash-out, there was no difference between in the different memories evaluated. Only the learning phase of the spatial reference memory test differed significantly with worst performance in OH groups. Three months after treatment cessation, there was no remanent effect of diazepam + ethanol on hippocampal metabolites changes.</div></div><div><h3>Conclusions</h3><div>We did not evidence additive effect of ethanol and diazepam on memory and hippocampal metabolite levels. The disturbances observed during treatment were no remanent, highlighting the benefits of discontinuing these substances.</div></div>","PeriodicalId":18122,"journal":{"name":"Life sciences","volume":"359 ","pages":"Article 123216"},"PeriodicalIF":5.2,"publicationDate":"2024-11-05","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142604980","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

引用次数: 0

Melatonin protects against particulate matter-induced ovarian dysfunction by activating the Nrf2 signaling pathway to alleviate ferroptosis 褪黑素通过激活Nrf2信号通路来缓解铁氧化，从而保护卵巢免受微粒物质诱发的卵巢功能障碍的影响。

IF 5.2 2区医学

Life sciences Pub Date : 2024-11-04 DOI: 10.1016/j.lfs.2024.123200

Xiaoyuan Zhang , Xiaxia Man , Qi Zhang , Laiyu Zhu , Lu Chen , Chao Zhu , Xinxin Ci , Xiaowei Yu

{"title":"Melatonin protects against particulate matter-induced ovarian dysfunction by activating the Nrf2 signaling pathway to alleviate ferroptosis","authors":"Xiaoyuan Zhang , Xiaxia Man , Qi Zhang , Laiyu Zhu , Lu Chen , Chao Zhu , Xinxin Ci , Xiaowei Yu","doi":"10.1016/j.lfs.2024.123200","DOIUrl":"10.1016/j.lfs.2024.123200","url":null,"abstract":"<div><div>Accumulating evidence suggests that exposure to ambient airborne PM2.5 increases the risk of primary ovarian insufficiency (POI). However, whether ferroptosis, a newly discovered type of cell death involved in PM2.5-induced lung injury and fibrosis, is involved in PM2.5-induced POI has not been determined. This study aimed to verify the involvement of PM2.5-induced ferroptosis in ovarian dysfunction and further demonstrate that melatonin inhibits ferroptosis by activating the Nrf2 signaling pathway to ameliorate POI in vivo and in vitro. In our study, PM2.5 promoted iron accumulation and induced lipid peroxidation, thus contributing to ferroptosis in KGN cells and ovaries. However, these effects were eliminated and enhanced in Nrf2-overexpressing and Nrf2-knockdown cells, respectively. In addition, melatonin and ferrostatin-1 (Fer-1) inhibited ferroptosis by activating the NRF2 signaling pathway, as evidenced by the silencing of Nrf2 in vivo and in vitro. Mechanistically, Nrf2-knockout mice were more susceptible to ferroptosis and PM2.5-induced POI than control mice. Moreover, melatonin suppressed changes in morphological and biochemical indicators related to ferroptosis, such as MDA and GSH depletion and GPX4 and XCT downregulation, by enhancing Nrf2 signaling. Here, we first reported that PM2.5 triggered ferroptosis by increasing ROS levels, lipid peroxidation and glutathione depletion. Notably, melatonin significantly decreased ferroptosis levels and improved ovarian function by activating the NRF2 signaling pathway in vivo and in vitro.</div></div>","PeriodicalId":18122,"journal":{"name":"Life sciences","volume":"359 ","pages":"Article 123200"},"PeriodicalIF":5.2,"publicationDate":"2024-11-04","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142591100","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

引用次数: 0

Simvastatin ameliorates adverse pregnancy by inhibiting glycolysis-related NETs in obstetrical antiphospholipid syndrome 辛伐他汀通过抑制产科抗磷脂综合征中与糖酵解相关的NET，改善不良妊娠。

IF 5.2 2区医学

Life sciences Pub Date : 2024-11-04 DOI: 10.1016/j.lfs.2024.123215

Ruiheng Huo , Qipeng Sun , Qingfeng Lv , Yuan Wang , Weiyi Qi , Meihua Zhang , Lei Li , Xietong Wang

{"title":"Simvastatin ameliorates adverse pregnancy by inhibiting glycolysis-related NETs in obstetrical antiphospholipid syndrome","authors":"Ruiheng Huo , Qipeng Sun , Qingfeng Lv , Yuan Wang , Weiyi Qi , Meihua Zhang , Lei Li , Xietong Wang","doi":"10.1016/j.lfs.2024.123215","DOIUrl":"10.1016/j.lfs.2024.123215","url":null,"abstract":"<div><h3>Aims</h3><div>Some patients with Obstetric Antiphospholipid Syndrome (OAPS) still experience miscarriage and placental dysfunction after routine treatment, which is related to an abnormal increase in neutrophil extracellular traps (NETs). The labeling of statins has been revised to remove the contraindication for use during pregnancy. Our aim is to investigate the effect of Simvastatin on pregnancy outcomes in OAPS and its correlation mechanisms with NETs.</div></div><div><h3>Main methods</h3><div>The effect of Simvastatin on pregnancy outcomes was observed. The effect of simvastatin on the function and apoptosis of neutrophils has evaluated. The effect of Simvastatin to NETs and the changes in oxidative stress levels were observed. Different groups of NETs were extracted to intervene the HTR8-Svneo.RNA-seq analysis of the mechanism of which Simvastatin reduces NETs. Seahorse experiment detected the effect of Simvastatin on neutrophil glycolysis levels. Fluorescence co-localization and flow cytometry and Co-IP were used to verify relevant mechanisms.</div></div><div><h3>Key findings</h3><div>In the OAPS mice, Simvastatin can reduce embryo absorption rate, reshape placental blood flow perfusion. Simultaneously reducing the production of NETs both in vivo and <em>vitro</em>, remolding oxidative stress. Simvastatin can improve neutrophil dysfunction caused by aPL-IgG. The reduction of NETs improved HTR8-Svneo's dysfunction. The intervention of Simvastatin on neutrophils under the stimulation of aPL-IgG showed a signature in glycolytic. The key rate limiting enzyme PKM2 in glycolysis interacts with Cit-H2b and PI3K/AKT signaling pathway.</div></div><div><h3>Significance</h3><div>Our study providing basic theoretical support for the treatment of OAPS with Simvastatin.</div></div>","PeriodicalId":18122,"journal":{"name":"Life sciences","volume":"359 ","pages":"Article 123215"},"PeriodicalIF":5.2,"publicationDate":"2024-11-04","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142591102","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

引用次数: 0

Mouse liver blood flow is regulated by hepatic stellate cells in response to the sympathetic neurotransmitter norepinephrine 小鼠肝脏血流量受肝脏星状细胞对交感神经递质去甲肾上腺素的调节。

IF 5.2 2区医学

Life sciences Pub Date : 2024-11-02 DOI: 10.1016/j.lfs.2024.123214

Naoki Dohi , Momoka Yamaguchi , Kyosuke Iwami , Yukiko K. Kaneko , Shin-ya Saito , Tomohisa Ishikawa

{"title":"Mouse liver blood flow is regulated by hepatic stellate cells in response to the sympathetic neurotransmitter norepinephrine","authors":"Naoki Dohi , Momoka Yamaguchi , Kyosuke Iwami , Yukiko K. Kaneko , Shin-ya Saito , Tomohisa Ishikawa","doi":"10.1016/j.lfs.2024.123214","DOIUrl":"10.1016/j.lfs.2024.123214","url":null,"abstract":"<div><h3>Background</h3><div>There is no clear information on the regulation of liver blood flow by the autonomic nervous system. We conducted this study to investigate whether quiescent hepatic stellate cells (qHSCs) regulate liver blood flow in response to the sympathetic neurotransmitter norepinephrine (NE).</div></div><div><h3>Methods</h3><div>qHSCs isolated from mice were cultured in Dulbecco's modified Eagle medium without fetal bovine serum for 1 day on collagen gel. NE-induced qHSC contraction was evaluated using the quantitative single-cell contraction measurement method that we had developed previously. For the measurement of liver perfusion pressure <em>in situ</em>, a buffer solution was perfused from the portal vein in mice.</div></div><div><h3>Results</h3><div>NE-induced a reversible contraction of qHSCs. This contraction was suppressed by the nonmuscle myosin II inhibitor blebbistatin, the myosin light chain kinase inhibitor ML-9, the Rho kinase inhibitor H-1152, the calmodulin inhibitor W-7, the store-operated calcium channel inhibitor YM-58483, and the IP<sub>3</sub> receptor inhibitor xestospongin C. In contrast, the transient receptor potential C channel inhibitor SKF96365 did not affect the NE-induced contraction.</div></div><div><h3>Conclusion</h3><div>These results suggest that qHSCs contract in response to NE.</div></div><div><h3>New & noteworthy</h3><div>The present study provides direct evidence for the first time that norepinephrine (NE) induces a reversible contraction of isolated single quiescent hepatic stellate cells (qHSCs) and further suggests that the NE-mediated qHSC contraction participates in the regulation of liver blood flow <em>in vivo</em>.</div></div>","PeriodicalId":18122,"journal":{"name":"Life sciences","volume":"359 ","pages":"Article 123214"},"PeriodicalIF":5.2,"publicationDate":"2024-11-02","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142568489","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

引用次数: 0

Metabolic disorders, inter-organ crosstalk, and inflammation in the progression of metabolic dysfunction-associated steatotic liver disease 代谢紊乱、器官间串联和炎症在代谢功能障碍相关性脂肪肝进展过程中的作用。

IF 5.2 2区医学

Life sciences Pub Date : 2024-11-02 DOI: 10.1016/j.lfs.2024.123211

Shendong Wang , Junhao Yin , Zhaojun Liu , Xin Liu , Ge Tian , Xijian Xin , Yiming Qin , Xiujing Feng

引用次数: 0

Defective macrophage efferocytosis in advanced atherosclerotic plaque and mitochondrial therapy 晚期动脉粥样硬化斑块中巨噬细胞排泄功能缺陷与线粒体疗法。

IF 5.2 2区医学

Life sciences Pub Date : 2024-11-02 DOI: 10.1016/j.lfs.2024.123204

Wanling Li , Yaqing Huang , Jun Liu , Yue Zhou , Hongyu Sun , Yonghong Fan , Feila Liu

{"title":"Defective macrophage efferocytosis in advanced atherosclerotic plaque and mitochondrial therapy","authors":"Wanling Li , Yaqing Huang , Jun Liu , Yue Zhou , Hongyu Sun , Yonghong Fan , Feila Liu","doi":"10.1016/j.lfs.2024.123204","DOIUrl":"10.1016/j.lfs.2024.123204","url":null,"abstract":"<div><div>Atherosclerosis (AS) is a chronic inflammatory disease primarily affecting large and medium-sized arterial vessels, characterized by lipoprotein disorders, intimal thickening, smooth muscle cell proliferation, and the formation of vulnerable plaques. Macrophages (MΦs) play a vital role in the inflammatory response throughout all stages of atherosclerotic development and are considered significant therapeutic targets. In early lesions, macrophage efferocytosis rapidly eliminates harmful cells. However, impaired efferocytosis in advanced plaques perpetuates the inflammatory microenvironment of AS. Defective efferocytosis has emerged as a key factor in atherosclerotic pathogenesis and the progression to severe cardiovascular disease. Herein, this review probes into investigate the potential mechanisms at the cellular, molecular, and organelle levels underlying defective macrophage efferocytosis in advanced lesion plaques. In the inflammatory microenvironments of AS with interactions among diverse inflammatory immune cells, impaired macrophage efferocytosis is strongly linked to multiple factors, such as a lower absolute number of phagocytes, the aberrant expression of crucial molecules, and impaired mitochondrial energy provision in phagocytes. Thus, focusing on molecular targets to enhance macrophage efferocytosis or targeting mitochondrial therapy to restore macrophage metabolism homeostasis has emerged as a potential strategy to mitigate the progression of advanced atherosclerotic plaque, providing various treatment options.</div></div>","PeriodicalId":18122,"journal":{"name":"Life sciences","volume":"359 ","pages":"Article 123204"},"PeriodicalIF":5.2,"publicationDate":"2024-11-02","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142568209","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

引用次数: 0

Recent pharmacological insights on abating toxic protein species burden in neurological disorders: Emphasis on 26S proteasome activation 关于减轻神经系统疾病中有毒蛋白质负担的最新药理学见解：重点关注 26S 蛋白酶体的激活。

IF 5.2 2区医学

Life sciences Pub Date : 2024-11-01 DOI: 10.1016/j.lfs.2024.123206

Mahmoud A. Desouky, Haidy E. Michel, Doaa A. Elsherbiny, Mina Y. George

{"title":"Recent pharmacological insights on abating toxic protein species burden in neurological disorders: Emphasis on 26S proteasome activation","authors":"Mahmoud A. Desouky, Haidy E. Michel, Doaa A. Elsherbiny, Mina Y. George","doi":"10.1016/j.lfs.2024.123206","DOIUrl":"10.1016/j.lfs.2024.123206","url":null,"abstract":"<div><div>Protein homeostasis (proteostasis) refers to the plethora of mechanisms that safeguard the proper folding of the newly synthesized proteins. It entails various intricately regulated cues that demolish the toxic protein species to prevent their aggregation. The ubiquitin-proteasome system (UPS) is recognized as a salient protein degradation system, with a substantial role in maintaining proteostasis. However, under certain circumstances the protein degradation capacity of the UPS is overwhelmed, leading to the accumulation of misfolded proteins. Several neurodegenerative disorders, such as Alzheimer's disease, Parkinson's disease, Huntington disease, and amyotrophic lateral sclerosis are characterized with the presence of protein aggregates and proteinopathy. Accordingly, enhancing the 26S proteasome degradation activity might delineate a pioneering approach in targeting various proteotoxic disorders. Regrettably, the exact molecular approaches that enhance the proteasomal activity are still not fully understood. Therefore, this review aimed to underscore several signaling cascades that might restore the degradation capacity of this molecular machine. In this review, we discuss the different molecular components of the UPS and how 26S proteasomes are deleteriously affected in many neurodegenerative diseases. Moreover, we summarize different signaling pathways that can be utilized to renovate the 26S proteasome functional capacity, alongside currently known druggable targets in this circuit and various classes of proteasome activators.</div></div>","PeriodicalId":18122,"journal":{"name":"Life sciences","volume":"359 ","pages":"Article 123206"},"PeriodicalIF":5.2,"publicationDate":"2024-11-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142568495","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

引用次数: 0

Exploring the molecular underpinnings of macrosomia in gestational diabetes mellitus: The role of EGFR signaling and placental syncytiotrophoblast 探索妊娠期糖尿病大畸形的分子基础：表皮生长因子受体信号转导和胎盘合体滋养细胞的作用。

IF 5.2 2区医学

Life sciences Pub Date : 2024-11-01 DOI: 10.1016/j.lfs.2024.123207

Peng Xu , Zewen Sun , Shu Zheng , Lin Pan , Shuai Dong , Jin He , Peng Chen , Chang Shu

{"title":"Exploring the molecular underpinnings of macrosomia in gestational diabetes mellitus: The role of EGFR signaling and placental syncytiotrophoblast","authors":"Peng Xu , Zewen Sun , Shu Zheng , Lin Pan , Shuai Dong , Jin He , Peng Chen , Chang Shu","doi":"10.1016/j.lfs.2024.123207","DOIUrl":"10.1016/j.lfs.2024.123207","url":null,"abstract":"<div><div>Macrosomia, which is frequently associated with gestational diabetes mellitus (GDM), is linked to maternal glycemic control during gestation. When GDM is complicated by macrosomia (GDMM), the placenta exhibits increased mass, underscoring its role as a critical nexus for maternal-fetal nutrient exchange. Despite this recognized correlation, the underlying mechanisms propelling placental hypertrophy have remained elusive. Our study leveraged single-cell RNA transcriptome sequencing of GDMM placental tissues to pinpoint the specific syncytiotrophoblast (SCT) subsets that regulate placental dimensions. Notably, we observed pronounced upregulation of the epidermal growth factor receptor (EGFR) and its corresponding ligands, with a particular emphasis on the autoregulatory cascade involving the glycoprotein hormone alpha subunit (CGA), EGFR, and the transcription factor GATA binding protein 2 (GATA2), as well as perturbations in hormonal homeostasis within the SCT. Furthermore, our cell interaction analysis revealed an enhanced interplay between myeloid cells and SCT3, augmenting the EGFR signaling pathway. These molecular exchanges underscore the pivotal role of the placental immune microenvironment in the etiology of macrosomia, shedding light on the pathophysiology of GDMM and paving the way for novel therapeutic approaches.</div></div>","PeriodicalId":18122,"journal":{"name":"Life sciences","volume":"359 ","pages":"Article 123207"},"PeriodicalIF":5.2,"publicationDate":"2024-11-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142568292","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

引用次数: 0

AMP kinase: A promising therapeutic drug target for post-COVID-19 complications AMP 激酶：有希望成为治疗 COVID-19 后并发症的药物靶点。

IF 5.2 2区医学

Life sciences Pub Date : 2024-11-01 DOI: 10.1016/j.lfs.2024.123202

Mohammad Saquib Ashraf , Kanika Tuli , Shadman Moiz , Satish Kumar Sharma , Deepa Sharma , Mohd Adnan

{"title":"AMP kinase: A promising therapeutic drug target for post-COVID-19 complications","authors":"Mohammad Saquib Ashraf , Kanika Tuli , Shadman Moiz , Satish Kumar Sharma , Deepa Sharma , Mohd Adnan","doi":"10.1016/j.lfs.2024.123202","DOIUrl":"10.1016/j.lfs.2024.123202","url":null,"abstract":"<div><div>The COVID-19 pandemic, caused by SARS-CoV-2, has resulted in severe respiratory issues and persistent complications, particularly affecting glucose metabolism. Patients with or without pre-existing diabetes often experience worsened symptoms, highlighting the need for innovative therapeutic approaches. AMPK, a crucial regulator of cellular energy balance, plays a pivotal role in glucose metabolism, insulin sensitivity, and inflammatory responses. AMPK activation, through allosteric or kinase-dependent mechanisms, impacts cellular processes like glucose uptake, fatty acid oxidation, and autophagy. The tissue-specific distribution of AMPK emphasizes its role in maintaining metabolic homeostasis throughout the body. Intriguingly, SARS-CoV-2 infection inhibits AMPK, contributing to metabolic dysregulation and post-COVID-19 complications. AMPK activators like capsaicinoids, curcumin, phytoestrogens, cilostazol, and momordicosides have demonstrated the potential to regulate AMPK activity. Compounds from various sources improve fatty acid oxidation and insulin sensitivity, with metformin showing opposing effects on AMPK activation compared to the virus, suggesting potential therapeutic options. The diverse effects of AMPK activation extend to its role in countering viral infections, further highlighting its significance in COVID-19. This review explores AMPK activation mechanisms, its role in metabolic disorders, and the potential use of natural compounds to target AMPK for post-COVID-19 complications. Also, it aims to review the possible methods of activating AMPK to prevent post-COVID-19 diabetes and cardiovascular complications. It also explores the use of natural compounds for their therapeutic effects in targeting the AMPK pathways. Targeting AMPK activation emerges as a promising avenue to mitigate the long-term effects of COVID-19, offering hope for improved patient outcomes and a better quality of life.</div></div>","PeriodicalId":18122,"journal":{"name":"Life sciences","volume":"359 ","pages":"Article 123202"},"PeriodicalIF":5.2,"publicationDate":"2024-11-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142568113","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

引用次数: 0