Cytomembrane Trafficking Pathways of Connexin 26, 30 and 43: Recent Updates DOI Open Access

Yan-Jun Zong,

Xiaozhou Liu, Lei Tu

et al.

Published: May 16, 2023

The connexin gene family is the most prevalent that contributes to hearing loss. Connexins 26 and 30, encoded by GJB2 GJB6 respectively, are abundant expressed connexins in inner ear. Connexin 43 which GJA1 appears be widely various organs, including heart, skin, brain, mutations arise GJB2, can all result comprehensive or non-comprehensive genetic deafness newborns. As it predicted include at least 20 isoforms humans, biosynthesis, structural composition, degradation of must precisely regulated so gap junctions operate properly. Certain possessing a faulty subcellular localization, failing transport cell membrane preventing junction formation, ultimately leading dysfunction In this review, we provide discussion models for 43, 30 26, affecting trafficking pathways existing controversies connexins, molecules involved their functions. This review contribute new way understanding etiological principles finding therapeutic strategies hereditary deafness.

Language: Английский

Cytoplasmic YAP1‐mediated ESCRT‐III assembly promotes autophagic cell death and is ubiquitinated by NEDD4L in breast cancer DOI Creative Commons
Yan Guo, Yuqing Cui, Yangyang Li

et al.

Cancer Communications, Journal Year: 2023, Volume and Issue: 43(5), P. 582 - 612

Published: April 2, 2023

Abstract Background Nuclear Yes1‐associated transcriptional regulator (YAP1) promotes tumor progression. However, the function of cytoplasmic YAP1 in breast cancer cells and its impact on survival patients remain unclear. Our research aimed to explore biological possibility as a predictive marker survival. Methods We constructed cell mutant models, including NLS‐YAP1 5SA (nuclear localized), S94A (incapable binding TEA domain transcription factor family) S127D (cytoplasmic used Cell Counting Kit‐8 (CCK‐8) assays, 5‐ethynyl‐2’‐deoxyuridine (EdU) incorporation Western blotting (WB) analysis detect proliferation apoptosis. The specific mechanism YAP1‐mediated endosomal sorting complexes required for transport III (ESCRT‐III) assembly was studied by co‐immunoprecipitation, immunofluorescence staining, WB analysis. Epigallocatechin gallate (EGCG) simulate retention cytoplasm vitro vivo experiments study YAP1. NEDD4‐like E3 ubiquitin protein ligase (NEDD4L) identified using mass spectrometry verified vitro. Breast tissue microarrays were analyze relationship between expression patients. Results mainly expressed cells. Cytoplasmic promoted autophagic death bound ESCRT‐III complex subunits charged multivesicular body 2B (CHMP2B) vacuolar 4 homolog B (VPS4B), promoting CHMP2B‐VPS4B activating autophagosome formation. EGCG retained cytoplasm, promote NEDD4L, NEDD4L mediated ubiquitination degradation revealed that high levels beneficial Conclusions complex; furthermore, we established new prediction model based expression.

Language: Английский

Citations

20
Mechanisms and otoprotective strategies of programmed cell death on aminoglycoside-induced ototoxicity DOI Creative Commons
Lei Han, Zijing Wang,

Daqi Wang

et al.

Frontiers in Cell and Developmental Biology, Journal Year: 2024, Volume and Issue: 11

Published: Jan. 8, 2024

Aminoglycosides are commonly used for the treatment of life-threatening bacterial infections, however, aminoglycosides may cause irreversible hearing loss with a long-term clinical therapy. The mechanism and prevention ototoxicity still limited although amounts studies explored widely. Specifically, advancements in programmed cell death (PCD) provide more new perspectives. This review summarizes general signal pathways death, including apoptosis, autophagy, ferroptosis, as well mechanisms aminoglycoside-induced ototoxicity. Additionally, novel interventions, especially gene therapy strategies, also investigated or prospective applications.

Language: Английский

Citations

6
GelMA/PEDOT:PSS Composite Conductive Hydrogel-Based Generation and Protection of Cochlear Hair Cells through Multiple Signaling Pathways DOI Creative Commons
Fei Tan, Xuran Li, Li Xiao

et al.

Biomolecules, Journal Year: 2024, Volume and Issue: 14(1), P. 95 - 95

Published: Jan. 11, 2024

Recent advances in cochlear implantology are exemplified by novel functional strategies such as bimodal electroacoustic stimulation, which the patient has intact low-frequency hearing and profound high-frequency pre-operatively. Therefore, synergistic restoration of dysfunctional hair cells protection from ototoxic insults have become a persistent target pursued for this hybrid system. In study, we developed composite GelMA/PEDOT:PSS conductive hydrogel that is suitable coating implant electrode potential local delivery otoregenerative otoprotective drugs. Various material characterization methods (e.g., 1H NMR spectroscopy, FT-IR, EIS, SEM), experimental models murine organoid aminoglycoside-induced HEI-OC1 cellular model), biological analyses confocal laser scanning microscopy, real time qPCR, flow cytometry, bioinformatic sequencing) were used. The results demonstrated decent properties hydrogel, mechanical high tensile stress Young’s modulus), electrochemical low impedance conductivity), biocompatibility satisfactory cell interaction free systemic toxicity), biosafety minimal hemolysis death) features. addition, CDR medicinal cocktail sustainably released not only promoted expansion stem but also boosted trans-differentiation supporting into cells. Furthermore, hydrogel-based drug protected oxidative various forms programmed death apoptosis ferroptosis). Finally, using large-scale sequencing, enriched complex network signaling pathways potentially downstream to metabolic processes abundant metabolites. conclusion, present bifunctional cocktails, thereby serving solution intracochlear therapy auditory rehabilitation diseases beyond.

Language: Английский

Citations

6
The intestinal epithelial-macrophage-crypt stem cell axis plays a crucial role in regulating and maintaining intestinal homeostasis DOI
Xiaohui Hu, Xinyi Yuan, Guokun Zhang

et al.

Life Sciences, Journal Year: 2024, Volume and Issue: 344, P. 122452 - 122452

Published: March 8, 2024

Language: Английский

Citations

6
Cochlear Marginal Cell Pyroptosis Is Induced by Cisplatin via NLRP3 Inflammasome Activation DOI Creative Commons

Wenting Yu,

Shimin Zong,

Peng Zhou

et al.

Frontiers in Immunology, Journal Year: 2022, Volume and Issue: 13

Published: April 20, 2022

Better understanding the mechanism of cisplatin-induced ototoxicity is great significance for clinical prevention and treatment cisplatin-related hearing loss. However, inflammatory response in cochlear stria vascularis marginal cell (MC) damage have not been fully clarified. In this study, a stable model MC was established vitro, results PCR Western blotting showed increased expressions NLRP3, Caspase-1, IL-1β, GSDMD MCs. Incomplete membranes including many small pores appearing on membrane were also observed under transmission electron microscopy scanning microscopy. addition, downregulation NLRP3 by interfering RNA can alleviate pyroptosis, reducing expression level TXNIP possesses inhibition effect inflammasome activation its mediated pyroptosis. Taken together, our suggest that may mediate pyroptosis vascularis, possible upstream regulator, which be promising therapeutic target alleviating

Language: Английский

Citations

23
Molecular regulation mechanism of intestinal stem cells in mucosal injury and repair in ulcerative colitis DOI Creative Commons
Lie Zheng,

Sheng-Lei Duan

World Journal of Gastroenterology, Journal Year: 2023, Volume and Issue: 29(16), P. 2380 - 2396

Published: April 24, 2023

Ulcerative colitis (UC) is a chronic nonspecific inflammatory disease with complex causes. The main pathological changes were intestinal mucosal injury. Leucine-rich repeat-containing G protein coupled receptor 5 (LGR5)-labeled small intestine stem cells (ISCs) located at the bottom of recess and inlaid among Paneth cells. LGR5+ ISCs are active proliferative adult cells, their self-renewal, proliferation differentiation disorders closely related to occurrence diseases. Notch signaling pathway Wnt/β-catenin important regulators LGR5-positive together maintain function ISCs. More importantly, surviving after injury accelerate division, restore number multiply differentiate into mature epithelial repair damaged mucosa. Therefore, in-depth study multiple pathways transplantation may become new target for treatment UC.

Language: Английский

Citations

11
Research progress in delineating the pathological mechanisms of GJB2-related hearing loss DOI Creative Commons
Yujun Wang, Yuan Jin,

Qiong Zhang

et al.

Frontiers in Cellular Neuroscience, Journal Year: 2023, Volume and Issue: 17

Published: June 2, 2023

Hearing loss is the most common congenital sensory impairment. Mutations or deficiencies of GJB2 gene are genetic cause non-syndromic deafness. Pathological changes such as decreased potential in cochlea, active cochlear amplification disorders, developmental disorders and macrophage activation have been observed various transgenic mouse models. In past, researchers generally believed that pathological mechanisms underlying -related hearing comprised a K + circulation defect abnormal ATP-Ca 2+ signals. However, recent studies shown rarely associated with process loss, while oxidative stress play an important, even critical, role occurrence loss. Nevertheless, these research has not systematically summarized. this review, we summarize including aspects circulation, organ Corti, nutrition delivery, Clarifying mechanism can help develop new prevention treatment strategies.

Language: Английский

Citations

11
Deferoxamine protects cochlear hair cells and hair cell-like HEI-OC1 cells against tert-butyl hydroperoxide-induced ototoxicity DOI Creative Commons
Peiheng Lu, Peng-Wei Ma, Wei‐Long Wang

et al.

Biochimica et Biophysica Acta (BBA) - Molecular Basis of Disease, Journal Year: 2024, Volume and Issue: 1870(3), P. 167024 - 167024

Published: Jan. 17, 2024

Language: Английский

Citations

4
Effect of tumor-derived extracellular vesicle-shuttled lncRNA MALAT1 on proliferation, invasion and metastasis of triple-negative breast cancer by regulating macrophage M2 polarization via the POSTN/Hippo/YAP axis DOI Creative Commons
Xuedong Wang,

Q Jian,

Ziyun Zhang

et al.

Translational Oncology, Journal Year: 2024, Volume and Issue: 49, P. 102076 - 102076

Published: Sept. 1, 2024

Triple-negative breast cancer (TNBC) is the deadliest subtype of (BC). Tumor-derived extracellular vesicles (EVs) trigger tumor progression by promoting M2 polarization. Some lncRNAs can be encapsulated into EVs for intercellular communication. Herein, we investigated mechanism TNBC-derived EV-shuttled lncRNA MALAT1 on macrophage polarization/tumorigenesis.

Language: Английский

Citations

4
Mitophagy and Ferroptosis in Sepsis-Induced ALI/ARDS: Molecular Mechanisms, Interactions and Therapeutic Prospects of Medicinal Plants DOI Creative Commons
Huixin Cheng, Xuehan Wang,

Juyi Yao

et al.

Journal of Inflammation Research, Journal Year: 2024, Volume and Issue: Volume 17, P. 7819 - 7835

Published: Oct. 1, 2024

Sepsis is a common critical illness characterized by high mortality rates and significant disease burden. In the context of sepsis-induced organ dysfunction, lungs are among initial organs affected, which may progress to acute lung injury (ALI) respiratory distress syndrome (ARDS). Recent studies have highlighted crucial roles mitophagy ferroptosis in development progression ALI/ARDS. Identifying key convergence points these processes provide valuable insights for treatment this condition. recent years, certain herbs their bioactive compounds demonstrated unique benefits managing ALI/ARDS modulating or ferroptosis. This review summary mechanisms ferroptosis, explores interactions, emphasizes regulatory Additionally, it offers novel perspective on strategies summarizing various relevant

Language: Английский

Citations

4