Life sciences最新文献_第3页

Rifaximin alleviates MCD diet-induced NASH in mice by restoring the gut microbiota and intestinal barrier 利福昔明通过恢复肠道微生物群和肠道屏障来缓解 MCD 膳食诱导的小鼠 NASH。

IF 5.2 2区医学

Life sciences Pub Date : 2024-10-03 DOI: 10.1016/j.lfs.2024.123095

{"title":"Rifaximin alleviates MCD diet-induced NASH in mice by restoring the gut microbiota and intestinal barrier","authors":"","doi":"10.1016/j.lfs.2024.123095","DOIUrl":"10.1016/j.lfs.2024.123095","url":null,"abstract":"<div><h3>Aims</h3><div>Due to the increasing global incidence rate of nonalcoholic steatohepatitis (NASH) combined with the lack of effective treatment methods for this disease, there is an urgent need to find new treatment strategies. The aim of this study was to investigate the efficacy of rifaximin in preventing and treating NASH and the related mechanism.</div></div><div><h3>Materials and methods</h3><div>A NASH model was constructed by feeding male C57BL/6 mice a methionine-choline-deficient (MCD) diet for 4 weeks. Rifaximin was administered for 1 week before MCD diet feeding or during the last week of MCD diet feeding to investigate its preventive or therapeutic effects. Liver pathology, hepatic enzyme levels and metabolic indices were measured to evaluate the effects of rifaximin on NASH. Intestinal barrier integrity was measured via the Ussing chamber system and western blotting. 16S rDNA sequencing was conducted to investigate the fecal microbiota composition. Western blotting was performed to evaluate peroxisome proliferator activated receptor (PPAR)α and PPARγ protein levels.</div></div><div><h3>Key findings</h3><div>Rifaximin effectively alleviated MCD diet-induced NASH. The microbiota composition in MCD diet-fed mice was significantly altered, and intestinal barrier integrity was disrupted. Dysbiosis and intestinal barrier dysfunction were reversed by rifaximin. In addition, rifaximin modulated PPARα and PPARγ expression in the liver.</div></div><div><h3>Significance</h3><div>Rifaximin effectively alleviated MCD diet-induced NASH by restoring the gut microbiota and reversing intestinal barrier dysfunction, suggesting that rifaximin treatment is a new approach for preventing and treating NASH.</div></div>","PeriodicalId":18122,"journal":{"name":"Life sciences","volume":null,"pages":null},"PeriodicalIF":5.2,"publicationDate":"2024-10-03","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142378004","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

Roles of noncoding RNAs in diabetic retinopathy: Mechanisms and therapeutic implications 非编码 RNA 在糖尿病视网膜病变中的作用：机理和治疗意义。

IF 5.2 2区医学

Life sciences Pub Date : 2024-10-03 DOI: 10.1016/j.lfs.2024.123092

{"title":"Roles of noncoding RNAs in diabetic retinopathy: Mechanisms and therapeutic implications","authors":"","doi":"10.1016/j.lfs.2024.123092","DOIUrl":"10.1016/j.lfs.2024.123092","url":null,"abstract":"<div><div>Diabetic retinopathy (DR) is a microvascular complication of diabetes that leads to vision loss. The striking features of DR are hard exudate, cotton-wool spots, hemorrhage, and neovascularization. The dysregulated retinal cells, encompassing microvascular endothelial cells, pericytes, Müller cells, and adjacent retinal pigment epithelial cells, are involved in the pathological processes of DR. According to recent research, oxidative stress, inflammation, ferroptosis, pyroptosis, apoptosis, and angiogenesis contribute to DR. Recent advancements have highlighted that noncoding RNAs could regulate diverse targets in pathological processes that contribute to DR. Noncoding RNAs, including long noncoding RNAs, microRNAs (miRNA), and circular RNAs, are dysregulated in DR, and interact with miRNA, mRNA, or proteins to control the pathological processes of DR. Hence, modulation of noncoding RNAs may have therapeutic effects on DR. Small extracellular vesicles may be valuable tools for transferring noncoding RNAs and regulating the genes involved in progression of DR. However, the roles of noncoding RNA in developing DR are not fully understood; it is critical to summarize the mechanisms for noncoding RNA regulation of pathological processes and pathways related to DR. This review provides a fundamental understanding of the relationship between noncoding RNAs and DR, exploring the mechanism of how noncoding RNA modulates different signaling pathways, and pave the way for finding potential therapeutic strategies for DR.</div></div>","PeriodicalId":18122,"journal":{"name":"Life sciences","volume":null,"pages":null},"PeriodicalIF":5.2,"publicationDate":"2024-10-03","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142378005","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

Drugs targeting SHIP2 demonstrate potent antiproliferative effects irrespective of SHIP2 inhibition 无论是否抑制 SHIP2，靶向 SHIP2 的药物都能显示出强大的抗增殖作用。

IF 5.2 2区医学

Life sciences Pub Date : 2024-10-02 DOI: 10.1016/j.lfs.2024.123101

引用次数: 0

Tetra aniline-based polymers ameliorate BPA-induced cardiotoxicity in Sprague Dawley rats, in silico and in vivo analysis. 基于四苯胺的聚合物可改善双酚 A 诱导的 Sprague Dawley 大鼠心脏毒性，这是在硅学和体内进行的分析。

IF 5.2 2区医学

Life sciences Pub Date : 2024-10-02 DOI: 10.1016/j.lfs.2024.123104

Ayesha Ishtiaq, Irrum Mushtaq, Hina Rehman, Iqra Mushtaq, Iram Mushtaq, Sumra Wajid Abbasi, Faroha Liaqat, Ammarah Rasheed, Sajjad Ahmad, Zareen Akhtar, Iram Murtaza

{"title":"Tetra aniline-based polymers ameliorate BPA-induced cardiotoxicity in Sprague Dawley rats, in silico and in vivo analysis.","authors":"Ayesha Ishtiaq, Irrum Mushtaq, Hina Rehman, Iqra Mushtaq, Iram Mushtaq, Sumra Wajid Abbasi, Faroha Liaqat, Ammarah Rasheed, Sajjad Ahmad, Zareen Akhtar, Iram Murtaza","doi":"10.1016/j.lfs.2024.123104","DOIUrl":"10.1016/j.lfs.2024.123104","url":null,"abstract":"<p><strong>Aims: </strong>Bisphenol A (BPA), xenoestrogen, is an environmental toxicant, that generates oxidative stress leading to, cardiotoxicity, The oxidative stress can be neutralized by natural and synthetic antioxidants. The present study elucidates the highly selective antioxidative potential of synthetic tetra aniline polymers Es-37 and L-37 against Bisphenol A-induced cardiac cellular impairments and the role of miRNA-15a-5p in the regulation of different apoptotic proteins.</p><p><strong>Materials and methods: </strong>The molecular docking of L-37 and Es-37 with three proteins (p53, Cytochrome c, and Bcl-2) were performed. The dose of 1 mg/kg BW of BPA, 1 mg/kg BW Es-37 and L-37 and 50 mg/kg BW N-acetyl cysteine (NAC) was administered to Sprague Dawley rats. The miRNA and target gene expression were confirmed by qRt-PCR and Immunoblotting.</p><p><strong>Key findings: </strong>In our results, BPA administration significantly elevated the reactive oxygen species (ROS), p53, cytochrome c, and particularly miRNA-15a-5p expression; however: these changes were notably averted and reversed by Es-37 and L-37 treatment. Additionally, molecular docking of synthetic polymers validated that L-37 has a greater binding affinity with the target proteins compared to Es-37, with the highest binding values reported for the enzymatic protein cytochrome c.</p><p><strong>Significance: </strong>These results suggest that both synthetic polymers Es-37 and L-37 have the potential to scavenge free radicals, boost-up antioxidant enzyme activities, and avert (BPA-induced) toxicity, thus, may serve as cardioprotective agents. Moreover, this study first time proposes that miRNA-15a-5p overexpression is associated with oxidative stress and coincides with BPA induced cardiotoxicity, thus may serve as potential therapeutic target in future.</p>","PeriodicalId":18122,"journal":{"name":"Life sciences","volume":null,"pages":null},"PeriodicalIF":5.2,"publicationDate":"2024-10-02","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142375672","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

HER3: Updates and current biology function, targeted therapy and pathologic detecting methods HER3：最新进展和当前的生物学功能、靶向治疗和病理学检测方法。

IF 5.2 2区医学

Life sciences Pub Date : 2024-10-02 DOI: 10.1016/j.lfs.2024.123087

{"title":"HER3: Updates and current biology function, targeted therapy and pathologic detecting methods","authors":"","doi":"10.1016/j.lfs.2024.123087","DOIUrl":"10.1016/j.lfs.2024.123087","url":null,"abstract":"<div><div>Being a member of the EGFR tyrosine kinase family, HER3 has been shown to be overexpressed in a number of cancers, including breast cancer (BC). The kinase activity of HER3 is extremely low, and it forms heterodimers with partners, HER2 in particular, that promote biological processes like cell migration, survival, and proliferation by activating downstream carcinogenic signaling pathways. The overexpression of HER3 is also directly linked to tumor invasion, metastasis, and a poor prognosis. Despite the relatively low expression of HER3 compared to EGFR and HER2, a lot of targeted drugs are making their way into clinical trials and seem to have a bright further. This review aims to summarize the relationship between HER3 overexpression, mutations, and carcinogenicity and drug resistance, starting from the unique structure and kinase activity of HER3. Simultaneously, numerous approaches to HER3 targeted therapy are enumerated, and the clinical detection methods for HER3 that are commonly employed in pathology are sorted and contrasted to offer physicians a range of options. We think that a better knowledge of the mechanisms underlying HER3 in tumors and the advancement of targeted HER3 therapy will contribute to an improved prognosis for cancer patients and an increase in the efficacy of anticancer therapies.</div></div>","PeriodicalId":18122,"journal":{"name":"Life sciences","volume":null,"pages":null},"PeriodicalIF":5.2,"publicationDate":"2024-10-02","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142375671","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

Acupuncture improves neuroendocrine defects in a preclinical rat model of reproductive aging 针灸可改善生殖衰老临床前大鼠模型的神经内分泌缺陷。

IF 5.2 2区医学

Life sciences Pub Date : 2024-10-02 DOI: 10.1016/j.lfs.2024.123102

{"title":"Acupuncture improves neuroendocrine defects in a preclinical rat model of reproductive aging","authors":"","doi":"10.1016/j.lfs.2024.123102","DOIUrl":"10.1016/j.lfs.2024.123102","url":null,"abstract":"<div><h3>Aims</h3><div>Clinical data supports electroacupuncture (EA) as an effective treatment for female reproductive disorders especially gonadotropin abnormalities. This study aims to detect the mechanism of EA that improves the neuroendocrine defects particularly the luteinizing hormone (LH) surge failure in early reproductive aging females.</div></div><div><h3>Materials and methods</h3><div>Middle-aged ovariectomized rats primed with hormone were treated by EA at acupoints CV4 and SP6 and undergone LH assay. Morphological experiments detected the activation of Kiss1 cells in the anteroventral periventricular nucleus (AVPV). Using targeted liquid chromatography with tandem mass spectrometry (LC-MS/MS) and RNA-sequencing, we determined the concentrations of neurotransmitter metabolites and transcriptomics in AVPV.</div></div><div><h3>Key findings</h3><div>EA significantly increased c-Fos and c-Fos-positive Kiss1 cells in the middle-aged AVPV as well as the total and peak LH release. Targeted LC-MS/MS and RNA-sequencing of AVPV identified differential neurotransmitters in the middle-aged females including Acetylcholine chloride, 5-Hydroxyindole-3-aceticacid, Kynurenine, Histamine, L-Histidine and L-Glycine, while EA decreased the concentration of Acetylcholine chloride. Totally 1255 differentially expressed genes modulated by EA were strongly implicated in neurotransmitter transport and KEGG pathways involved neuroactive ligand-receptor interaction, glutamatergic and gamma-aminobutyric acid-mediated synapse. Specifically, the mRNAs associated with the LH surge such as hormone receptor <em>Pgr</em>, adrenoceptor <em>Adra1a</em>, neurotransmitter transporters <em>Slc17a6</em> and <em>Slc32a1</em>, glutamate decarboxylase <em>Gad2</em> and <em>Kiss1</em> were markedly altered by EA.</div></div><div><h3>Significance</h3><div>These findings showed that the age-related reduction of LH surge occurred via differential neurotransmitter metabolisms and altered transcriptions in AVPV, which proposed EA-based therapy for improving responsiveness of the hypothalamus to hormone in women with advanced age.</div></div>","PeriodicalId":18122,"journal":{"name":"Life sciences","volume":null,"pages":null},"PeriodicalIF":5.2,"publicationDate":"2024-10-02","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142375669","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

Cerliponase alfa decreases Aβ load and alters autophagy- related pathways in mouse hippocampal neurons exposed to fAβ1–42 Cerliponase alfa 能降低暴露于 fAβ1-42 的小鼠海马神经元的 Aβ 负荷并改变自噬相关通路。

IF 5.2 2区医学

Life sciences Pub Date : 2024-10-01 DOI: 10.1016/j.lfs.2024.123105

{"title":"Cerliponase alfa decreases Aβ load and alters autophagy- related pathways in mouse hippocampal neurons exposed to fAβ1–42","authors":"","doi":"10.1016/j.lfs.2024.123105","DOIUrl":"10.1016/j.lfs.2024.123105","url":null,"abstract":"<div><div>Extracellular aggregation of amyloid-beta (Aβ) in the brain plays a central role in the onset and progression of Alzheimer's disease (AD). Moreover, intraneuronal accumulation of Aβ via oligomer internalization might play an important role in the progression of AD. Deficient autophagy, which is a lysosomal degradation process, occurs during the early stages of AD. Tripeptidyl peptidase-1 (TPP1) functions as a lysosomal enzyme, and TPP1 gene mutations are associated with type 2 late infantile neuronal ceroid lipofuscinosis (LINCL). Nevertheless, there is little information about the role of TPP1 in the pathogenesis of AD; therefore, the present study aimed to measure the decrease in intraneuronal Aβ accumulation by a recombinant analog of the TPP1 enzyme, cerliponase alfa (CER) (Brineura®), and to determine whether autophagy pathways play a role in this decrease. In this study, endogenous Aβ accumulation was induced by fAβ<sub>1–42</sub> (a toxic fragment of full-length Aβ) exposure, and mouse hippocampal neuronal cells (HT-22) were treated with CER (human recombinant rhTPP1 1 mg mL<sup>−1</sup>). Soluble Aβ, TPP1, and the proteins involved in autophagy, including mammalian target of rapamycin (p-mTOR/mTOR), p62/sequestosome-1 (p62/SQSTM1), and microtubule-associated protein 1 A/1B-light chain 3 (LC3), were evaluated using western blotting. The sirtuin-1, beclin-1, and Atg5 genes were also studied using RT-PCR. Aβ and TPP1 localizations were observed via immunocytochemistry. CER reduced the Aβ load in HT-22 cells by inducing TPP1 expression and converting pro-TPP1 into the mature form. Furthermore, exposure to CER and fAβ<sub>1–42</sub> induced the autophagy-regulatory/related pathways in HT-22 cells and exposure to CER alone increased sirtuin-1 activity. Based on the present findings, we suggest that augmentation of TPP1 with enzyme replacement therapy may be a potential therapeutic option for the treatment of AD.</div></div>","PeriodicalId":18122,"journal":{"name":"Life sciences","volume":null,"pages":null},"PeriodicalIF":5.2,"publicationDate":"2024-10-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142372240","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

Nephroprotective effects of hyperbaric oxygen therapy in murine models of acute kidney injury: A systematic review and meta-analysis 高压氧疗法在急性肾损伤小鼠模型中的肾保护作用：系统综述和荟萃分析。

IF 5.2 2区医学

Life sciences Pub Date : 2024-10-01 DOI: 10.1016/j.lfs.2024.123098

{"title":"Nephroprotective effects of hyperbaric oxygen therapy in murine models of acute kidney injury: A systematic review and meta-analysis","authors":"","doi":"10.1016/j.lfs.2024.123098","DOIUrl":"10.1016/j.lfs.2024.123098","url":null,"abstract":"<div><h3>Aims</h3><div>Acute kidney injury (AKI) is a life-threatening condition marked by sudden kidney function loss and azotemia. While its management is limited to supportive care, the effects of hyperbaric oxygen therapy (HBO) on AKI remain a subject of conflicting animal research. This study aimed to systematically review and meta-analyze HBO's effects on renal function biomarkers serum creatinine (SCr) and blood urea nitrogen (BUN) in murine AKI models, also exploring tissue-level nephroprotection.</div></div><div><h3>Main methods</h3><div>The PUBMED, SciELO, and LILACS databases were searched until September 5, 2024. Effect sizes of HBO on SCr and BUN levels were expressed as standardized mean difference (SMD) alongside 95 % confidence interval (CI), calculated by random-effects model. Extracted data also included murine specie/strain, HBO parameters, AKI induction method (toxic, ischemic, others), and histological findings. Study quality and publication bias were respectively assessed using the CAMARADES checklist and Egger's test. This review adhered to PRISMA guidelines and was registered in PROSPERO (CRD42022369804).</div></div><div><h3>Key findings</h3><div>Data synthesis from 21 studies demonstrates that HBO effectively reduces azotemia in AKI-affected animals (SCr's SMD = −1.69, 95 % CI = −2.38 to −0.99, <em>P</em> < 0.001; BUN's SMD = −1.51, 95 % CI = −2.32 to −0.71, P < 0.001) while mitigating histological damage. Subgroup analyses indicate that HBO particularly benefits ischemic and other AKI types (<em>P</em> < 0.05). In contrast, data from toxic AKI models were inconclusive due to insufficient statistical power (<em>P</em> > 0.05, 1-β < 30 %).</div></div><div><h3>Significance</h3><div>This meta-analysis provides compelling evidence supporting the adjunctive use of HBO in AKI management.</div></div>","PeriodicalId":18122,"journal":{"name":"Life sciences","volume":null,"pages":null},"PeriodicalIF":5.2,"publicationDate":"2024-10-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142372245","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

TRESK channel activation ameliorates migraine-like pain via modulation of CGRP release from the trigeminovascular system and meningeal mast cells in experimental migraine models 通过调节实验性偏头痛模型中三叉神经血管系统和脑膜肥大细胞的 CGRP 释放，激活 TRESK 通道可改善偏头痛样疼痛。

IF 5.2 2区医学

Life sciences Pub Date : 2024-10-01 DOI: 10.1016/j.lfs.2024.123091

{"title":"TRESK channel activation ameliorates migraine-like pain via modulation of CGRP release from the trigeminovascular system and meningeal mast cells in experimental migraine models","authors":"","doi":"10.1016/j.lfs.2024.123091","DOIUrl":"10.1016/j.lfs.2024.123091","url":null,"abstract":"<div><h3>Aims</h3><div>Accumulating evidence indicates the involvement of TRESK potassium channels in migraine, however, effects of TRESK activation on migraine-related mechanisms remain unclear. We explored effects of TRESK channel modulation on migraine-related behavioral and molecular markers in in-vivo and ex-vivo rat models of migraine.</div></div><div><h3>Main methods</h3><div>The selective TRESK activator cloxyquin at different doses, the TRESK inhibitor A2764, and the migraine drug sumatriptan were tested alone or in different combinations in nitroglycerin (NTG)-induced in-vivo model, and in ex-vivo meningeal, trigeminal ganglion and brainstem preparations in which CGRP release was induced by capsaicin. Mechanical allodynia, CGRP and c-fos levels in trigeminovascular structures and meningeal mast cells were evaluated.</div></div><div><h3>Key findings</h3><div>Cloxyquin attenuated NTG-induced mechanical allodynia, brainstem c-fos and CGRP levels, trigeminal ganglion CGRP levels and meningeal mast cell degranulation and number, in-vivo. It also diminished capsaicin-induced CGRP release from ex-vivo meningeal, trigeminal ganglion and brainstem preparations. Specific TRESK inhibitor A2764 abolished all effects of cloxyquin in in-vivo and ex-vivo. Combining cloxyquin and sumatriptan exerted a synergistic effect ex-vivo, but not in-vivo.</div></div><div><h3>Significance</h3><div>Our findings provide the experimental evidence for the anti-migraine effect of TRESK activation in migraine-like conditions. The modulation of TRESK channels may therefore be an attractive alternative strategy to relieve migraine pain.</div></div>","PeriodicalId":18122,"journal":{"name":"Life sciences","volume":null,"pages":null},"PeriodicalIF":5.2,"publicationDate":"2024-10-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142372247","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

Immunological challenges and opportunities in glioblastoma multiforme: A comprehensive view from immune system lens 多形性胶质母细胞瘤的免疫学挑战与机遇：从免疫系统视角看问题。

IF 5.2 2区医学

Life sciences Pub Date : 2024-10-01 DOI: 10.1016/j.lfs.2024.123089

{"title":"Immunological challenges and opportunities in glioblastoma multiforme: A comprehensive view from immune system lens","authors":"","doi":"10.1016/j.lfs.2024.123089","DOIUrl":"10.1016/j.lfs.2024.123089","url":null,"abstract":"<div><div>Glioblastoma multiforme (GBM), also known as grade IV astrocytoma, is the most common and deadly brain tumour. It has a poor prognosis and a low survival rate. GBM cells' immunological escape mechanism helps them resist advanced multimodal therapy. In physiological homeostasis, brain astrocytes and microglia suppress infections and clear the potential pathogen from the system. However, in severe pathological conditions like cancer, the immune response fails to eliminate mutated and rapidly over-proliferating GBM cells. The malignant cells' interactions with immune cells and the neoplasm's immunosuppressive environment enable the avoidance and their clearance. Immunotherapy efficiently addresses these difficulties, as shown by sufficient evidence. This review discusses how GBM cells inhibit and elude the immune system. These include MHC molecule expression alteration and PD-L1 and CTLA-4 immune checkpoint overexpression. Without co-stimulation, these changes induce effector T-cell tolerance and anergy. The review also covers how MDSCs, TAMs, Herpes Virus Entry Mediators, and Human cytomegalovirus protein decrease the effector immune response against glioblastoma. The latter part discusses various therapies that are available in the market or under clinical trials which revolves around combating resistance against the available multimodal therapies. The recent trends indicate that there are various monoclonal antibodies and peptide-based vaccines that can be utilized to overcome the immune evasion technique harbored by GBM cells.</div><div>A strategic development of Immunotherapy considering these hallmarks of immune evasion may help in designing a therapy that may prove to be effective in killing the GBM cells thereby, improving the overall survival of GBM-affected patients.</div></div>","PeriodicalId":18122,"journal":{"name":"Life sciences","volume":null,"pages":null},"PeriodicalIF":5.2,"publicationDate":"2024-10-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142372244","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