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2.
J Nanobiotechnology ; 19(1): 173, 2021 Jun 10.
Artigo em Inglês | MEDLINE | ID: mdl-34112203

RESUMO

BACKGROUND: The worldwide pandemic of COVID-19 remains a serious public health menace as the lack of efficacious treatments. Cytokine storm syndrome (CSS) characterized with elevated inflammation and multi-organs failure is closely correlated with the bad outcome of COVID-19. Hence, inhibit the process of CSS by controlling excessive inflammation is considered one of the most promising ways for COVID-19 treatment. RESULTS: Here, we developed a biomimetic nanocarrier based drug delivery system against COVID-19 via anti-inflammation and antiviral treatment simultaneously. Firstly, lopinavir (LPV) as model antiviral drug was loaded in the polymeric nanoparticles (PLGA-LPV NPs). Afterwards, macrophage membranes were coated on the PLGA-LPV NPs to constitute drugs loaded macrophage biomimetic nanocarriers (PLGA-LPV@M). In the study, PLGA-LPV@M could neutralize multiple proinflammatory cytokines and effectively suppress the activation of macrophages and neutrophils. Furthermore, the formation of NETs induced by COVID-19 patients serum could be reduced by PLGA-LPV@M as well. In a mouse model of coronavirus infection, PLGA-LPV@M exhibited significant targeted ability to inflammation sites, and superior therapeutic efficacy in inflammation alleviation and tissues viral loads reduction. CONCLUSION: Collectively, such macrophage biomimetic nanocarriers based drug delivery system showed favorable anti-inflammation and targeted antiviral effects, which may possess a comprehensive therapeutic value in COVID-19 treatment.

3.
Malar J ; 20(1): 265, 2021 Jun 12.
Artigo em Inglês | MEDLINE | ID: mdl-34118950

RESUMO

BACKGROUND: Although avian Plasmodium species are widespread and common across the globe, limited data exist on how genetically variable their populations are. Here, the hypothesis that the avian blood parasite Plasmodium relictum exhibits very low genetic diversity in its Western Palearctic transmission area (from Morocco to Sweden in the north and Transcaucasia in the east) was tested. METHODS: The genetic diversity of Plasmodium relictum was investigated by sequencing a portion (block 14) of the fast-evolving merozoite surface protein 1 (MSP1) gene in 75 different P. relictum infections from 36 host species. Furthermore, the full-length MSP1 sequences representing the common block 14 allele was sequenced in order to investigate if additional variation could be found outside block 14. RESULTS: The majority (72 of 75) of the sequenced infections shared the same MSP1 allele. This common allele has previously been found to be the dominant allele transmitted in Europe. CONCLUSION: The results corroborate earlier findings derived from a limited dataset that the globally transmitted malaria parasite P. relictum exhibits very low genetic diversity in its Western Palearctic transmission area. This is likely the result of a recent introduction event or a selective sweep.

4.
Nat Commun ; 12(1): 2697, 2021 05 11.
Artigo em Inglês | MEDLINE | ID: mdl-33976229

RESUMO

Although human antibodies elicited by the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) nucleocapsid (N) protein are profoundly boosted upon infection, little is known about the function of N-reactive antibodies. Herein, we isolate and profile a panel of 32 N protein-specific monoclonal antibodies (mAbs) from a quick recovery coronavirus disease-19 (COVID-19) convalescent patient who has dominant antibody responses to the SARS-CoV-2 N protein rather than to the SARS-CoV-2 spike (S) protein. The complex structure of the N protein RNA binding domain with the highest binding affinity mAb (nCoV396) reveals changes in the epitopes and antigen's allosteric regulation. Functionally, a virus-free complement hyperactivation analysis demonstrates that nCoV396 specifically compromises the N protein-induced complement hyperactivation, which is a risk factor for the morbidity and mortality of COVID-19 patients, thus laying the foundation for the identification of functional anti-N protein mAbs.


Assuntos
Anticorpos Antivirais/farmacologia , COVID-19/imunologia , Ativação do Complemento/efeitos dos fármacos , Proteínas do Nucleocapsídeo de Coronavírus/imunologia , SARS-CoV-2/imunologia , Regulação Alostérica , Anticorpos Monoclonais/química , Anticorpos Monoclonais/imunologia , Anticorpos Antivirais/química , Anticorpos Antivirais/imunologia , Afinidade de Anticorpos , Complexo Antígeno-Anticorpo/química , Convalescença , Proteínas do Nucleocapsídeo de Coronavírus/química , Cristalografia por Raios X , Epitopos , Humanos , Fosfoproteínas/química , Fosfoproteínas/imunologia , Conformação Proteica
5.
Artif Organs ; 2021 May 26.
Artigo em Inglês | MEDLINE | ID: mdl-34037261

RESUMO

In clinical practice, autologous bone transplantation is usually used to treat large-scale bone defects. However, autologous bone can cause complications such as secondary injury to patients, the scarcity of autografts. In this study, the study of using super active platelet lysate (sPL) and allogeneic bone to treat the 15 mm long bone defect in right radius of rabbits, and provide an experimental basis for the next step of clinical bone defect treatment. The critical-size defect of New Zealand white rabbits was made and divided into three groups: autologous bone group, allogeneic bone group, and sPL group. They were euthanized 1, 2, and 3 months after the operation, perform imaging and histological observation on the repair of bone defect area. The results showed that there were varying degrees of new bone in the bone defect. CT data showed that the bone defect repair rate and new bone mass in each group increased month by month (P <.05). Bone tissue (BV) and bone tissue to the total volume (BV/TV, %) in the sPL group > allogeneic bone group, autologous bone group > allogeneic bone group, with statistical significance (P < .05). Compared with the allogeneic bone group, the sPL group can significantly promote the healing of bone defects, enhance the bone density after fracture healing. The repair effect after 3 months was similar to that of the autogenous bone group. The use of allogeneic bone and sPL therapy may become part of a comprehensive strategy for tissue engineering to treat bone defects.

6.
J Cell Mol Med ; 25(12): 5729-5743, 2021 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-33949118

RESUMO

Cyclosporine A (CsA) is an immunosuppressor widely used for the prevention of acute rejection during solid organ transplantation. However, severe nephrotoxicity has substantially limited its long-term usage. Recently, an impaired autophagy pathway was suggested to be involved in the pathogenesis of chronic CsA nephrotoxicity. However, the underlying mechanisms of CsA-induced autophagy blockade in tubular cells remain unclear. In the present study, we observed that CsA suppressed the activation and expression of transcription factor EB (TFEB) by increasing the activation of mTOR, in turn promoting lysosomal dysfunction and autophagy flux blockade in tubular epithelial cells (TECs) in vivo and in vitro. Restoration of TFEB activation by Torin1-mediated mTOR inhibition significantly improved lysosomal function and rescued autophagy pathway activity, suppressing TEC injury. In summary, targeting TFEB-mediated autophagy flux represents a potential therapeutic strategy for CsA-induced nephrotoxicity.

7.
Sci Rep ; 11(1): 9265, 2021 Apr 29.
Artigo em Inglês | MEDLINE | ID: mdl-33927236

RESUMO

Many G protein-coupled receptors (GPCRs) are therapeutic targets, with most drugs acting at the orthosteric site. Some GPCRs also possess allosteric sites, which have become a focus of drug discovery. In the M2 muscarinic receptor, allosteric modulators regulate the binding and functional effects of orthosteric ligands through a mix of conformational changes, steric hindrance and electrostatic repulsion transmitted within and between the constituent protomers of an oligomer. Tacrine has been called an atypical modulator because it exhibits positive cooperativity, as revealed by Hill coefficients greater than 1 in its negative allosteric effect on binding and response. Radioligand binding and molecular dynamics simulations were used to probe the mechanism of that modulation in monomers and oligomers of wild-type and mutant M2 receptors. Tacrine is not atypical at monomers, which indicates that its atypical effects are a property of the receptor in its oligomeric state. These results illustrate that oligomerization of the M2 receptor has functional consequences.

8.
Nat Metab ; 3(5): 701-713, 2021 May.
Artigo em Inglês | MEDLINE | ID: mdl-33859429

RESUMO

Obesity is mainly due to excessive food intake. IRX3 and IRX5 have been suggested as determinants of obesity in connection with the intronic variants of FTO, but how these genes contribute to obesity via changes in food intake remains unclear. Here, we show that mice doubly heterozygous for Irx3 and Irx5 mutations exhibit lower food intake with enhanced hypothalamic leptin response. By lineage tracing and single-cell RNA sequencing using the Ins2-Cre system, we identify a previously unreported radial glia-like neural stem cell population with high Irx3 and Irx5 expression in early postnatal hypothalamus and demonstrate that reduced dosage of Irx3 and Irx5 promotes neurogenesis in postnatal hypothalamus leading to elevated numbers of leptin-sensing arcuate neurons. Furthermore, we find that mice with deletion of Irx3 in these cells also exhibit a similar food intake and hypothalamic phenotype. Our results illustrate that Irx3 and Irx5 play a regulatory role in hypothalamic postnatal neurogenesis and leptin response.

9.
J Transl Med ; 19(1): 176, 2021 04 28.
Artigo em Inglês | MEDLINE | ID: mdl-33910562

RESUMO

BACKGROUND: Window of implantation (WOI) displacement is one of the endometrial origins of embryo implantation failure, especially repeated implantation failure (RIF). An accurate prediction tool for endometrial receptivity (ER) is extraordinarily needed to precisely guide successful embryo implantation. We aimed to establish an RNA-Seq-based endometrial receptivity test (rsERT) tool using transcriptomic biomarkers and to evaluate the benefit of personalized embryo transfer (pET) guided by this tool in patients with RIF. METHODS: This was a two-phase strategy comprising tool establishment with retrospective data and benefit evaluation with a prospective, nonrandomized controlled trial. In the first phase, rsERT was established by sequencing and analyzing the RNA of endometrial tissues from 50 IVF patients with normal WOI timing. In the second phase, 142 patients with RIF were recruited and grouped by patient self-selection (experimental group, n = 56; control group, n = 86). pET guided by rsERT was performed in the experimental group and conventional ET in the control group. RESULTS: The rsERT, comprising 175 biomarker genes, showed an average accuracy of 98.4% by using tenfold cross-validation. The intrauterine pregnancy rate (IPR) of the experimental group (50.0%) was significantly improved compared to that (23.7%) of the control group (RR, 2.107; 95% CI 1.159 to 3.830; P = 0.017) when transferring day-3 embryos. Although not significantly different, the IPR of the experimental group (63.6%) was still 20 percentage points higher than that (40.7%) of the control group (RR, 1.562; 95% CI 0.898 to 2.718; P = 0.111) when transferring blastocysts. CONCLUSIONS: The rsERT was developed to accurately predict the WOI period and significantly improve the pregnancy outcomes of patients with RIF, indicating the clinical potential of rsERT-guided pET. Trial registration Chinese Clinical Trial Registry: ChiCTR-DDD-17013375. Registered 14 November 2017, http://www.chictr.org.cn/index.aspx.


Assuntos
Implantação do Embrião , Transcriptoma , Biomarcadores , Transferência Embrionária , Endométrio , Feminino , Humanos , Gravidez , Estudos Prospectivos , Estudos Retrospectivos , Transcriptoma/genética
10.
J Cardiothorac Surg ; 16(1): 82, 2021 Apr 15.
Artigo em Inglês | MEDLINE | ID: mdl-33858463

RESUMO

BACKGROUND: Blood glucose variability is associated with poor prognosis after cardiac surgery, but the relationship between glucose variability and postoperative delirium in patients with acute aortic dissection is unclear. The study aims to investigate the association of blood glucose variability with postoperative delirium in acute aortic dissection patients. METHODS: We prospectively analyzed 257 patients including 103 patients with delirium. The patients were divided into two groups according to whether delirium was present. The outcome measures were postoperative delirium, the length of the Intensive Care Unit stay, and the duration of hospital stay. Multivariable Cox competing risk survival models was used to assess. RESULTS: A total of 257 subjects were enrolled, including 103 patients with delirium. There were statistically significant differences between the two groups in body mass index, history of cardiac surgery, first admission blood glucose, white blood cell counts, Acute Physiology and Chronic Health Evaluation II score, hypoxemia, mechanical ventilation duration, and the length of Intensive Care Unit stay(P < 0.05). The delirium group exhibited significantly higher values of the mean of blood glucose (MBG) and the standard deviation of blood glucose (SDBG) than in the non-delirium group(P < 0.05). In model 1, the adjusted hazard ratio (AHR) of the standard deviation of blood glucose was 1.436(P < 0.05). In Model 2, the standard deviation of blood glucose (AHR = 1.418, 95%CI = 1.195-1.681, P < 0.05) remained significant after adjusting for confounders. The area under the curve of the SDBG was 0.763(95%CI = 0.704-0.821, P < 0.01). The sensitivity was 81.6%, and the specificity was 57.8%. CONCLUSIONS: Glucose variability is associated with the risk of delirium in patients after aortic dissection surgery, and high glycemic variability increases the risk of postoperative delirium.

11.
Cancer Invest ; : 1-14, 2021 Apr 22.
Artigo em Inglês | MEDLINE | ID: mdl-33888005

RESUMO

PURPOSE: The present study aimed to investigate whether the single nucleotide polymorphism (SNP) rs1801552 C/T in CDH1 gene is correlated with the risk of esophageal squamous cell carcinoma (ESCC) and gastric cardiac adenocarcinoma (GCA), as a preliminary study. METHODS: The rs1801552 C/T polymorphism was genotyped by the method of polymerase chain reaction-restriction fragment length polymorphism (PCR-RFLP) in 1316 cancer patients (810 ESCC and 506 GCA) and 1966 controls in north China. We performed two case-control studies, each of which included a population-based set and a hospital-based set. RESULTS: The data showed that the rs1801552 C/T polymorphism was associated with the risk of ESCC. Allelotype and genotype distributions of the rs1801552 C/T polymorphism in ESCC patients of high-incidence region and hospital were significantly different from that in their respective controls (P < 0.05). Compared with C/C genotype, T/T genotype increased the risk of ESCC in high-incidence region and hospital (age, sex, smoking status and family history of UGIC adjusted odds ratio (OR) = 1.79 and 2.10, 95% confidence interval (CI) = 1.23 - 2.60 and 1.10 - 4.04, respectively). Allelotype and genotype distributions of the rs1801552 C/T polymorphism in GCA patients were not significantly different from that in their controls, respectively (P > 0.05). CONCLUSIONS: The findings in the present pilot study suggest that the rs1801552 C/T polymorphism was associated with the risk of ESCC, but was not associated with the risk of GCA in high-incidence region and hospital.

13.
ACS Appl Mater Interfaces ; 13(18): 20995-21006, 2021 May 12.
Artigo em Inglês | MEDLINE | ID: mdl-33930273

RESUMO

COVID-19 has been diffusely pandemic around the world, characterized by massive morbidity and mortality. One of the remarkable threats associated with mortality may be the uncontrolled inflammatory processes, which were induced by SARS-CoV-2 in infected patients. As there are no specific drugs, exploiting safe and effective treatment strategies is an instant requirement to dwindle viral damage and relieve extreme inflammation simultaneously. Here, highly biocompatible glycyrrhizic acid (GA) nanoparticles (GANPs) were synthesized based on GA. In vitro investigations revealed that GANPs inhibit the proliferation of the murine coronavirus MHV-A59 and reduce proinflammatory cytokine production caused by MHV-A59 or the N protein of SARS-CoV-2. In an MHV-A59-induced surrogate mouse model of COVID-19, GANPs specifically target areas with severe inflammation, such as the lungs, which appeared to improve the accumulation of GANPs and enhance the effectiveness of the treatment. Further, GANPs also exert antiviral and anti-inflammatory effects, relieving organ damage and conferring a significant survival advantage to infected mice. Such a novel therapeutic agent can be readily manufactured into feasible treatment for COVID-19.


Assuntos
Anti-Inflamatórios/uso terapêutico , Antivirais/uso terapêutico , Ácido Glicirrízico/uso terapêutico , Inflamação/tratamento farmacológico , Nanopartículas/uso terapêutico , Viroses/tratamento farmacológico , Animais , Anti-Inflamatórios/química , Antioxidantes/química , Antioxidantes/uso terapêutico , Antivirais/química , COVID-19/tratamento farmacológico , Proteínas do Nucleocapsídeo de Coronavírus/farmacologia , Citocinas/metabolismo , Feminino , Ácido Glicirrízico/química , Humanos , Fígado/patologia , Pulmão/patologia , Camundongos , Camundongos Endogâmicos BALB C , Vírus da Hepatite Murina/efeitos dos fármacos , Nanopartículas/química , Fosfoproteínas/farmacologia , Células RAW 264.7 , SARS-CoV-2/química , Células THP-1 , Carga Viral/efeitos dos fármacos , Viroses/patologia , Replicação Viral/efeitos dos fármacos
14.
Front Cell Infect Microbiol ; 11: 629836, 2021.
Artigo em Inglês | MEDLINE | ID: mdl-33928042

RESUMO

Genome scale mutagenesis identifies many genes required for mycobacterial infectivity and survival, but their contributions and mechanisms of action within the host are poorly understood. Using CRISPR interference, we created a knockdown of ppe31Mm gene in Mycobacterium marinum (M. marinum), which reduced the resistance to acid medium. To further explore the function of PPE31, the ppe31 mutant strain was generated in M. marinum and Mycobacterium tuberculosis (M. tuberculosis), respectively. Macrophages infected with the ppe31Mm mutant strain caused a reduced inflammatory mediator expressions. In addition, macrophages infected with M. marinum Δppe31Mm had decreased host cell death dependent on JNK signaling. Consistent with these results, deletion of ppe31Mtb from M. tuberculosis increased the sensitivity to acid medium and reduced cell death in macrophages. Furthermore, we demonstrate that both ppe31 mutants from M. marinum and M. tuberculosis resulted in reduced survival in macrophages, and the survivability of M. marinum was deceased in zebrafish due to loss of ppe31Mm . Our findings confirm that PPE31 as a virulence associated factor that modulates innate immune responses to mycobacterial infection.

15.
Cell Rep ; 34(13): 108903, 2021 Mar 30.
Artigo em Inglês | MEDLINE | ID: mdl-33789112

RESUMO

Across the animal kingdom, adult tissue homeostasis is regulated by adult stem cell activity, which is commonly dysregulated in human cancers. However, identifying key regulators of stem cells in the milieu of thousands of genes dysregulated in a given cancer is challenging. Here, using a comparative genomics approach between planarian adult stem cells and patient-derived glioblastoma stem cells (GSCs), we identify and demonstrate the role of DEAD-box helicase DDX56 in regulating aspects of stemness in four stem cell systems: planarians, mouse neural stem cells, human GSCs, and a fly model of glioblastoma. In a human GSC line, DDX56 localizes to the nucleolus, and using planarians, when DDX56 is lost, stem cells dysregulate expression of ribosomal RNAs and lose nucleolar integrity prior to stem cell death. Together, a comparative genomic approach can be used to uncover conserved stemness regulators that are functional in both normal and cancer stem cells.

17.
Ann Palliat Med ; 10(3): 3135-3141, 2021 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-33752431

RESUMO

BACKGROUND: Intravenous (IV) catheter insertion may cause adverse reactions. It is necessary to investigate optimal methods for reducing blood return and extending the usage time of IV catheter by existing technologies. We investigated the efficacy of the PosiFlow regulator with an infusion clip for preventing IV catheter plugging due to venous blood return. METHODS: From January 2017 to August 2017, 960 patients requiring IV catheterization were recruited and by using the block randomization method randomly allocated to 4 groups (n=240 in each group): a control group receiving IV catheter with infusion clip; experimental group A receiving IV catheter without infusion clip; experimental group B receiving an IV catheter with the PosiFlow regulator; and experimental group C receiving an IV catheter with a PosiFlow regulator and infusion clip. The rates of catheter plugging and blood return were compared among groups. RESULTS: In different reasons for needle pulling, The rates of catheter plugging and blood return in experimental group C (Received IV catheterization with an infusion clip and PosiFlow regulato) were the lowest among all groups (P<0.05). In different puncture sites, forearm puncture further reduced IV catheter plugging in all groups compared to other puncture sites. CONCLUSIONS: Catheter plugging and blood return can be significantly reduced by combining the PosiFlow regulator and an infusion clip, resulting in reduced medical costs and patient distress from catheter reinsertion.


Assuntos
Cateteres , Humanos , Infusões Intravenosas
18.
J Int Med Res ; 49(3): 300060521997326, 2021 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-33752475

RESUMO

OBJECTIVES: Cancer is a threat to human health, and many molecules are involved in the transformation of malignant cells. Hepatocyte nuclear factor 1A (HNF1A) is an important transcription factor that regulates multiple biological processes. Our research focused on elucidating the expression and function of HNF1A in cancer through bioinformatic analysis. METHODS: UALCAN, Kaplan-Meier plotter, COSMIC, Tumor IMmune Estimation Resource, and Cancer Regulome were used to obtain relevant data for HNF1A. RESULTS: HNF1A was abnormally expressed in multiple cancers, and its expression was associated with differences in overall survival in patients with cancer. HNF1A mutations widely exist in tumors and interact with different genes involved in various processes. Additionally, we found that HNF1A was associated with the infiltration of immune cells, and it affected the prognostic value of these cells in some cancers. CONCLUSIONS: HNF1A plays a crucial role in cancer, and it may represent a biomarker and target for future cancer immunotherapy.


Assuntos
Fator 1-alfa Nuclear de Hepatócito , Neoplasias , Linhagem Celular Tumoral , Biologia Computacional , Fator 1-alfa Nuclear de Hepatócito/genética , Humanos , Neoplasias/genética , Prognóstico
19.
Environ Mol Mutagen ; 62(4): 273-283, 2021 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-33723872

RESUMO

The T-cell immunoglobulin and mucin domain containing molecule 3 (TIM-3), a crucial immune regulatory molecule, is an emerging immune checkpoint target for cancer therapy. Our study aimed to investigate the association between TIM-3 polymorphisms (rs10053538 C > A, rs10515746 C > A, and rs1036199 A > C) and the susceptibility and prognosis of esophageal squamous cell carcinoma (ESCC). We further detect the effects of polymorphisms on TIM-3 expression. Two independent case-control sets (population-based and hospital-based sets) were performed in total 994 ESCC patients and 998 controls. TIM-3 polymorphisms were genotyped by polymerase chain reaction-ligase detection reaction (PCR). Survival data were available for 198 patients who received platinum-based chemotherapy after surgery. The regulation on TIM-3 expression by the polymorphisms was investigated in 35 patients using real-time quantitative PCR. The association between mRNA level of TIM-3 and survival was detected by using Kaplan-Meier plotter database. We found that for rs10053538 C > A polymorphisms, A allele was associated with significant increased risk of ESCC (odds ratios [OR] = 1.34, 95%CI = 1.05-1.72), and CA/AA genotypes enhanced susceptibility to ESCC for smokers (adjusted OR = 1.61, 95%CI = 1.00-2.59). The patients with AA genotypes had significantly poor prognosis (adjusted HR = 4.98, 95%CI = 1.14-21.71). The patients carrying CA/AA genotypes had significantly higher mRNA levels of TIM-3 than those carrying the CC genotype. Furthermore, high mRNA level of TIM-3 had a shorter overall survival in patients (HR = 2.56, 95%CI = 1.04-6.28). For rs10515746 C > A and rs1036199 A > C polymorphisms, there were no statistical correlation with the progression of ESCC. These data demonstrate that rs10053538 C > A polymorphisms may be associated with the susceptibility and prognosis of ESCC patients through regulating expression of TIM-3.

20.
Trends Pharmacol Sci ; 42(5): 367-384, 2021 May.
Artigo em Inglês | MEDLINE | ID: mdl-33752907

RESUMO

Force is everywhere. Through cell-intrinsic activities and interactions with the microenvironment, cells generate, transmit, and sense mechanical forces, such as compression, tension, and shear stress. These forces shape the mechanical properties of cells and tissues. Akin to how balanced biochemical signaling safeguards physiological processes, a mechanical optimum is required for homeostasis. The brain constructs a mechanical optimum from its cellular and extracellular constituents. However, in brain cancer, the mechanical properties are disrupted: tumor and nontumoral cells experience dysregulated solid and fluid stress, while tumor tissue develops altered stiffness. Mechanosensitive (MS) ion channels perceive mechanical cues to govern ion flux and cellular signaling. In this review, we describe the mechanical properties of the brain in healthy and cancer states and illustrate MS ion channels as sensors of mechanical cues to regulate malignant growth. Targeting MS ion channels offers disease insights at the interface of cancer, neuroscience, and mechanobiology to reveal therapeutic opportunities in brain tumors.

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