Biomedical research最新文献

Involvement of interaction of Cav3.2 and nociceptive TRPA1 in pathological pain transmission Cav3.2 和痛觉 TRPA1 相互作用参与病理痛觉传递

Biomedical research Pub Date : 2024-02-06 DOI: 10.2220/biomedres.45.45

Minami NAKAGAWA, Kenji TAKAHASHI, Yuki NISHIZAWA, Toshio OHTA

{"title":"Involvement of interaction of Cav3.2 and nociceptive TRPA1 in pathological pain transmission","authors":"Minami NAKAGAWA, Kenji TAKAHASHI, Yuki NISHIZAWA, Toshio OHTA","doi":"10.2220/biomedres.45.45","DOIUrl":"https://doi.org/10.2220/biomedres.45.45","url":null,"abstract":"T-type Ca2+ channels and TRPA1 expressed in sensory neurons are involved in pain. We previously demonstrated a functional interaction of these channels under physiological conditions. Here we investigated the possible involvement of these channels in inflammatory pain condition. We also evaluated the relationship of these channels endogenously expressed in RIN-14B, a rat pancreatic islet tumor cell line. In dorsal root ganglion (DRG) neurons innervated inflammatory side, [Ca2+]i increases induced by 15 mM KCl (15K) were enhanced in neurons responded to AITC. This enhancement was not observed in genetically TRPA1-deficient neurons. The T-type and AITC-induced currents were larger in neurons of the inflammatory side than in those of the control one. In DRGs of the inflammatory side, the protein expression of Cav3.2, but not TRPA1, was increased. In RIN-14B, 15K-induced [Ca2+]i increases were decreased by blockers of T-type Ca2+ channel and TRPA1, and by TRPA1-silencing. Immunoprecipitation suggested the coexistent of these channels in sensory neurons and RIN-14B. In mice with inflammation, mechanical hypersensitivity was suppressed by blockers of both channels. These data suggest that the interaction of Cav3.2 with TRPA1 in sensory neurons is enhanced via the augmentation of the activities of both channels under inflammatory conditions, indicating that both channels are therapeutic targets for inflammatory pain.\u0000","PeriodicalId":8925,"journal":{"name":"Biomedical research","volume":null,"pages":null},"PeriodicalIF":0.0,"publicationDate":"2024-02-06","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"139689927","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

引用次数: 0

Cell cycle dependence of cell survival following exposure to X-rays in synchronous HeLa cells expressing fluorescent ubiquitination-based cell cycle indicators 在表达基于荧光泛素化的细胞周期指示剂的同步 HeLa 细胞中，细胞暴露于 X 射线后的存活与细胞周期有关

Biomedical research Pub Date : 2024-02-06 DOI: 10.2220/biomedres.45.25

Ryosuke SEINO, Hiroto UNO, Kevin M PRISE, Hisanori FUKUNAGA

{"title":"Cell cycle dependence of cell survival following exposure to X-rays in synchronous HeLa cells expressing fluorescent ubiquitination-based cell cycle indicators","authors":"Ryosuke SEINO, Hiroto UNO, Kevin M PRISE, Hisanori FUKUNAGA","doi":"10.2220/biomedres.45.25","DOIUrl":"https://doi.org/10.2220/biomedres.45.25","url":null,"abstract":"The cell cycle dependence of radiosensitivity has yet to be fully determined, as it is technically difficult to achieve a high degree of cell cycle synchronization in cultured cell systems and accurately detect the cell cycle phase of individual cells simultaneously. We used human cervical carcinoma HeLa cells expressing fluorescent ubiquitination-based cell cycle indicators (FUCCI), and employed the mitotic harvesting method that is one of the cell cycle synchronization methods. The imaging analysis confirmed that the cell cycle is highly synchronized after mitotic cell harvesting until 18–20 h of the doubling time has elapsed. Also, flow cytometry analysis revealed that the S and G2 phases peak at approximately 12 and 14–16 h, respectively, after mitotic harvesting. In addition, the clonogenic assay showed the changes in surviving fractions following exposure to X-rays according to the progress through the cell cycle. These results indicate that HeLa-FUCCI cells become radioresistant in the G1 phase, become radiosensitive in the early S phase, rapidly become radioresistant in the late S phase, and become radiosensitive again in the G2 phase. Our findings may contribute to the further development of combinations of radiation and cell cycle-specific anticancer agents.\u0000","PeriodicalId":8925,"journal":{"name":"Biomedical research","volume":null,"pages":null},"PeriodicalIF":0.0,"publicationDate":"2024-02-06","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"139689926","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

引用次数: 0

Fish oil consumption prevents hepatic lipid accumulation induced by high-cholesterol feeding in obese KK mice 食用鱼油可防止高胆固醇喂养诱发肥胖 KK 小鼠肝脏脂质积累

Biomedical research Pub Date : 2024-02-06 DOI: 10.2220/biomedres.45.33

Satoshi HIRAKO, HyounJu KIM, Yuzuru IIZUKA, Akiyo MATSUMOTO

{"title":"Fish oil consumption prevents hepatic lipid accumulation induced by high-cholesterol feeding in obese KK mice","authors":"Satoshi HIRAKO, HyounJu KIM, Yuzuru IIZUKA, Akiyo MATSUMOTO","doi":"10.2220/biomedres.45.33","DOIUrl":"https://doi.org/10.2220/biomedres.45.33","url":null,"abstract":"Fish oil (FO) is rich in the n-3 polyunsaturated fatty acids. It has been demonstrated that FO intake possesses lipid-lowering properties. Conversely, a high-cholesterol (CH) diet promotes lipid accumulation in the liver and induces fatty liver. This study investigated the effects of FO feeding on hepatic lipid accumulation induced by high-cholesterol feeding in KK mice. All experimental diets had a fat energy ratio of 25%, the SO group had all fat sources as safflower oil (SO), the 12.5 FO group had half of the SO replaced with FO, and the 25 FO group had all of the SO replaced with FO, each with or without 2 weight % (wt%) cholesterol (SO/CH, 12.5 FO/CH, and 25 FO/CH groups, respectively), for 8 weeks. The hepatic triglyceride and total cholesterol levels were significantly lower in the 25 FO/CH group than in the SO/CH group. The hepatic mRNAs of fatty acid synthesis-related genes were downregulated by the FO feeding groups. In view of importance to establish the benefit of FO for preventing severe NAFLD, our results suggest that FO intake prevents excessive hepatic fat accumulation induced by a high-cholesterol diet in obese KK mice through the inhibition of fatty acid synthesis.\u0000","PeriodicalId":8925,"journal":{"name":"Biomedical research","volume":null,"pages":null},"PeriodicalIF":0.0,"publicationDate":"2024-02-06","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"139690140","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

引用次数: 0

Rutin promotes M2 phenotype microglia polarization by suppressing the JAK/STAT3 signaling to protect against retinal ischemia-reperfusion injury 芦丁通过抑制 JAK/STAT3 信号传导促进 M2 表型小胶质细胞极化，保护视网膜免受缺血再灌注损伤

Biomedical research Pub Date : 2024-02-06 DOI: 10.2220/biomedres.45.13

An-Le SU, Shuai ZHAO, Hong-Na ZHU, Ying QIAO, Ting ZHANG

{"title":"Rutin promotes M2 phenotype microglia polarization by suppressing the JAK/STAT3 signaling to protect against retinal ischemia-reperfusion injury","authors":"An-Le SU, Shuai ZHAO, Hong-Na ZHU, Ying QIAO, Ting ZHANG","doi":"10.2220/biomedres.45.13","DOIUrl":"https://doi.org/10.2220/biomedres.45.13","url":null,"abstract":"We aimed to investigate the neuroprotective effect of rutin on retinal ganglion cells (RGCs) under ischemia-reperfusion (I/R) conditions and the underlying mechanisms involving microglia polarization and JAK/STAT3 signaling. RGCs isolated from C57/Bl6 mice were co-cultured with BV2 microglial cells under normal or in vitro oxygen-glucose deprivation and reoxygenation (OGD/R) conditions. Rutin’s effects were evaluated by assessing cell viability, apoptosis rates, cytokine levels, microglial polarization markers and JAK/STAT3 phosphorylation levels. The specific target is confirmed through the inhibitory effect of rutin on the respectively activated signaling factors. Furthermore, molecular docking analyses elucidated rutin-JAK1 interactions. OGD/R conditions significantly reduced RGC viability, exacerbated by BV2 co-culture. However, both 1 μM and 5 μM rutin treatment dose-dependently enhanced RGC viability, reduced apoptosis, and suppressed pro-inflammatory cytokine levels. Western blot analysis indicated that rutin promoted the M2 microglial phenotype and suppressed JAK/STAT3 signaling. Notably, rutin selectively inhibited JAK1 phosphorylation without affecting STAT3. Molecular docking highlighted potential interaction sites between rutin and specific JAK1 pseudokinase domain. Rutin exerts neuroprotective effects against retinal I/R injury by promoting M2 microglial polarization, potentially through the selective inhibition of JAK1 phosphorylation within the JAK/STAT3 signaling pathway. These findings provide a foundation for the therapeutic potential of rutin in retinal I/R injuries.\u0000","PeriodicalId":8925,"journal":{"name":"Biomedical research","volume":null,"pages":null},"PeriodicalIF":0.0,"publicationDate":"2024-02-06","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"139690287","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

引用次数: 0