Ischemic Stroke: Pathophysiology and Evolving Treatment Approaches DOI Creative Commons
Dhriti Majumder

Neuroscience Insights, Journal Year: 2024, Volume and Issue: 19

Published: Jan. 1, 2024

Stroke remains a leading cause of mortality and disability, with ischemic stroke being the most common type. It occurs due to reduced cerebral blood flow, cascade events initiated by oxygen nutrient deprivation, triggering excitotoxicity, oxidative stress, inflammation finally culminating in neuronal injury death. Key molecular players include glutamate receptors, acid-sensing ion channels, purinergic exacerbating cellular damage through calcium influx, mitochondrial dysfunction. Understanding these mechanisms has shaped therapeutic strategies, such as neuroprotective agents stem cell therapies. Current treatments tissue plasminogen activator (tPA) emphasize timely intervention, yet challenges persist patient-specific variability accessibility. This review provides an overview pathophysiology, emphasizing responses ischemia current future approaches including therapies aimed at mitigating stroke-induced disabilities improving long-term outcomes.

Language: Английский

Matrix stiffness affects tumor-associated macrophage functional polarization and its potential in tumor therapy DOI Creative Commons
Jiaqiang Xiong, Rourou Xiao, Jiahui Zhao

et al.

Journal of Translational Medicine, Journal Year: 2024, Volume and Issue: 22(1)

Published: Jan. 21, 2024

The extracellular matrix (ECM) plays critical roles in cytoskeletal support, biomechanical transduction and biochemical signal transformation. Tumor-associated macrophage (TAM) function is regulated by stiffness solid tumors often associated with poor prognosis. ECM stiffness-induced mechanical cues can activate cell membrane mechanoreceptors corresponding mechanotransducers the cytoplasm, modulating phenotype of TAMs. Currently, tuning TAM polarization through stimulation has received increasing attention, whereas its effect on fate rarely been summarized. A better understanding relationship between will contribute to development new strategies for cancer therapy. In this review, we first introduced overall stiffness, analyzed changes mediated tumor progression, finally summarized effects targeting prognosis provide insight into field.

Language: Английский

Citations

20
TRP Channels in Cancer: Signaling Mechanisms and Translational Approaches DOI Creative Commons
Matilde Marini, Mustafa Titiz, Daniel Souza Monteiro de Araújo

et al.

Biomolecules, Journal Year: 2023, Volume and Issue: 13(10), P. 1557 - 1557

Published: Oct. 22, 2023

Ion channels play a crucial role in wide range of biological processes, including cell cycle regulation and cancer progression. In particular, the transient receptor potential (TRP) family has emerged as promising therapeutic target due to its involvement several stages development dissemination. TRP are expressed large variety cells tissues, by increasing cation intracellular concentration, they monitor mechanical, thermal, chemical stimuli under physiological pathological conditions. Some members superfamily, namely vanilloid (TRPV), canonical (TRPC), melastatin (TRPM), ankyrin (TRPA), have been investigated different types cancer, breast, prostate, lung, colorectal cancer. involved processes such proliferation, migration, invasion, angiogenesis, drug resistance, all related mechanistically associated with signaling pain. Understanding cellular molecular mechanisms which influence provides new opportunities for targeted strategies. Selective inhibitors initial scrutiny experimental animals anti-cancer agents. In-depth knowledge these their regulatory may lead strategies treatment, providing perspectives effective therapies.

Language: Английский

Citations

26
Re-evaluating TRP channel mechanosensitivity DOI
Charles D. Cox, Kate Poole, Boris Martinac

et al.

Trends in Biochemical Sciences, Journal Year: 2024, Volume and Issue: 49(8), P. 693 - 702

Published: June 12, 2024

Language: Английский

Citations

10
The Multifaceted Functions of TRPV4 and Calcium Oscillations in Tissue Repair DOI Open Access
Dongsheng Jiang,

Ruiji Guo,

Ruoxuan Dai

et al.

International Journal of Molecular Sciences, Journal Year: 2024, Volume and Issue: 25(2), P. 1179 - 1179

Published: Jan. 18, 2024

The transient receptor potential vanilloid 4 (TRPV4) specifically functions as a mechanosensitive ion channel and is responsible for conveying changes in physical stimuli such mechanical stress, osmotic pressure, temperature. TRPV4 enables the entry of cation ions, particularly calcium into cell. Activation channels initiates oscillations, which trigger intracellular signaling pathways involved plethora cellular processes, including tissue repair. Widely expressed throughout body, can be activated by wide array physicochemical stimuli, thus contributing to sensory physiological multiple organs. This review focuses on how senses environmental cues thereby maintains critical responses organ injury, repair, fibrosis. We provide summary TRPV4-induced oscillations distinct systems, along with upstream downstream involved. In addition, we delineate current animal disease models supporting research shed light therapeutic targets modulating oscillation promote repair while reducing

Language: Английский

Citations

8
The IGF2BP2-lncRNA TRPC7-AS1 axis promotes hepatocellular carcinoma cell proliferation and invasion DOI Creative Commons

Xu Zhang,

Zilin Li, Huizong Nie

et al.

Cellular Signalling, Journal Year: 2024, Volume and Issue: 117, P. 111078 - 111078

Published: Feb. 4, 2024

Hepatocellular carcinoma(HCC) is one of the most common tumors in world. Human insulin-like growth factor 2(IGF2) mRNA binding protein 2(IGF2BP2) plays an important role progression hepatocellular carcinoma. Additionally, long non-coding RNA(lncRNA) has been confirmed as a key regulator carcinoma occurrence. However, function TRPC7-AS1 not verified The research results revealed that high IGF2BP2 expression was associated with decreased survival rate patients Furthermore, knockdown inhibited and overexpression promoted cell proliferation invasion cells. illuminated regulated TRPC7-AS1, correlation observed between expression. silencing repressed its After or overexpressing high-mobility group AT-hook 2 (HMGA2) gene increased, respectively. enhanced thus affected HMGA2, thereby promoting progression.

Language: Английский

Citations

8
Ion channels in osteoarthritis: emerging roles and potential targets DOI
Renpeng Zhou, Wenyu Fu,

Dmytro V. Vasylyev

et al.

Nature Reviews Rheumatology, Journal Year: 2024, Volume and Issue: 20(9), P. 545 - 564

Published: Aug. 9, 2024

Language: Английский

Citations

8
The Molecular Biology of Placental Transport of Calcium to the Human Foetus DOI Open Access
Valerie Walker

International Journal of Molecular Sciences, Journal Year: 2025, Volume and Issue: 26(1), P. 383 - 383

Published: Jan. 4, 2025

From fertilisation to delivery, calcium must be transported into and within the foetoplacental unit for intracellular signalling. This requires very rapid, precisely located Ca2+ transfers. In addition, from around eighth week of gestation, increasing amounts routed directly maternal blood foetus bone mineralisation through a flow-through system, which does not impact concentration. These different processes are mediated by numerous membrane-sited channels, transporters, exchangers. Understanding mechanisms is essential direct interventions optimise foetal development postnatal health protect mother pre-eclampsia. Ethical issues limit availability human tissue study. Our insight placental handling advancing rapidly, enabled developing genetic, analytical, computer technology. Because their diverse sources, reports new findings scattered. review aims pull data together highlight areas uncertainty. Areas needing clarification include trafficking, membrane expression, recycling channels transporters in microvilli; metabolism vitamin D gestational diabetes pre-eclampsia; vascular effects increased endothelial Orai expression pregnancy-specific beta-1-glycoproteins PSG1 PSG9.

Language: Английский

Citations

1
Proteome-Wide Identification and Comparison of Drug Pockets for Discovering New Drug Indications and Side Effects DOI Creative Commons

Renxin Zhang,

Zhiyuan Chen, Shuhan Li

et al.

Molecules, Journal Year: 2025, Volume and Issue: 30(2), P. 260 - 260

Published: Jan. 10, 2025

Drug development faces significant financial and time challenges, highlighting the need for more efficient strategies. This study evaluated druggability of entire human proteome using Fpocket. We identified 15,043 druggable pockets in 20,255 predicted protein structures, significantly expanding estimated from 3000 to over 11,000 proteins. Notably, many were found less studied proteins, suggesting untapped therapeutic opportunities. The results a pairwise pocket similarity analysis 220,312 similar pairs, with 3241 pairs across different families, indicating shared drug-binding potential. In addition, 62,077 matches between 1872 known drug pockets, candidates repositioning. repositioned progesterone ADGRD1 pemphigus breast cancer, as well estradiol ANO2 shingles medulloblastoma, which validated via molecular docking. Off-target effects analyzed assess safety drugs such axitinib, linking newly targets side effects. For 127 new identified, 46 out 48 documented linked these targets. These findings demonstrate utility repositioning, target expansion, improved evaluation, offering avenues discovery indications existing drugs.

Language: Английский

Citations

1
Deciphering mechanical cues in the microenvironment: from non-malignant settings to tumor progression DOI Creative Commons
Yi‐Cheng Zhu,

Jiaoshun Chen,

Chen Chen

et al.

Biomarker Research, Journal Year: 2025, Volume and Issue: 13(1)

Published: Jan. 23, 2025

The tumor microenvironment functions as a dynamic and intricate ecosystem, comprising diverse array of cellular non-cellular components that precisely orchestrate pivotal behaviors, including invasion, metastasis, drug resistance. While unraveling the interplay between behaviors represents tremendous challenge, recent research illuminates crucial biological phenomenon known mechanotransduction. Within microenvironment, mechanical cues like tensile stress, shear stiffness play role by activating mechanosensitive effectors such PIEZO proteins, integrins, Yes-associated protein. This activation initiates cascades intrinsic signaling pathways, effectively linking physical properties tissues to their physiological pathophysiological processes morphogenesis, regeneration, immunity. mechanistic insight offers novel perspective on how within impact behaviors. intricacies are yet be fully elucidated, it exhibits distinct attributes from non-malignant tissues, elevated solid stresses, interstitial hypertension, augmented matrix stiffness, enhanced viscoelasticity. These traits exert notable influences progression treatment responses, enriching our comprehension multifaceted nature microenvironment. Through this innovative review, we aim provide new lens decipher contexts, broadening knowledge these factors promote or inhibit thus offering valuable insights identify potential targets for anti-tumor strategies.

Language: Английский

Citations

1
Impact of cannabinoids on cancer outcomes in patients receiving immune checkpoint inhibitor immunotherapy DOI Creative Commons

MariaLuisa Vigano,

Lixing Wang,

Alia As’sadiq

et al.

Frontiers in Immunology, Journal Year: 2025, Volume and Issue: 16

Published: March 5, 2025

Cannabinoids relieve pain, nausea, anorexia and anxiety, improve quality of life in several cancer patients. The immunotherapy with checkpoint inhibitors (ICIs), although very successful a subset patients, is accompanied by moderate to severe immune-related adverse events (ir-AE) that often necessitate its discontinuation. Because their role symptomatic relief, cannabinoids have been used combination immune inhibitor (ICI) immunotherapy. A few studies strongly suggest the use medicinal cannabis patients attenuates many ir-AE associated ICI increase tolerability. However, no significant beneficial effects on overall survival, progression free survival or relapses were observed; rather, some noted concurrent administration clinical benefits latter. cannabinoids' well documented immunosuppressive mediated through cannabinoid recptor-2 (CB2), we propose considering this receptor as an inhibitory per se. simultaneous neutralization CB2, treatment, may lead better outcomes receiving In regard, such cannabidiol (CBD) cannabigerol (CBG), little agonism for be therapeutic choices. Additional strategies e.g., monoacylglycerol lipase (MAGL) degrade endocannabinoids lipogenesis formation lipid bilayers cells also explored. Future should take into consideration gut microbiota, CYP450 polymorphism haplotypes, cannabinoid-drug interactions genetic somatic variations occurring receptors signaling pathways personalized cannabis-based therapies ICIs. This rational knowledge-based regimens tailored individual

Language: Английский

Citations

1