Korean Journal of Physiology & Pharmacology最新文献_第9页

Differential expression of the enzymes regulating myosin light chain phosphorylation are responsible for the slower relaxation of pulmonary artery than mesenteric artery in rats. 调节肌球蛋白轻链磷酸化的酶的不同表达是导致大鼠肺动脉松弛慢于肠系膜动脉的原因。

IF 2 4区医学

Korean Journal of Physiology & Pharmacology Pub Date : 2024-01-01 DOI: 10.4196/kjpp.2024.28.1.49

Seung Beom Oh, Suhan Cho, Hyun Jong Kim, Sung Joon Kim

{"title":"Differential expression of the enzymes regulating myosin light chain phosphorylation are responsible for the slower relaxation of pulmonary artery than mesenteric artery in rats.","authors":"Seung Beom Oh, Suhan Cho, Hyun Jong Kim, Sung Joon Kim","doi":"10.4196/kjpp.2024.28.1.49","DOIUrl":"10.4196/kjpp.2024.28.1.49","url":null,"abstract":"While arterial tone is generally determined by the phosphorylation of Ser19 in myosin light chain (p-MLC2), Thr18/Ser19 diphosphorylation of MLC2 (pp-MLC2) has been suggested to hinder the relaxation of smooth muscle. In a dual-wire myography of rodent pulmonary artery (PA) and mesenteric artery (MA), we noticed significantly slower relaxation in PA than in MA after 80 mM KCl-induced condition (80K-contraction). Thus, we investigated the MLC2 phosphorylation and the expression levels of its regulatory enzymes; soluble guanylate cyclase (sGC), Rho-A dependent kinase (ROCK) and myosin light chain phosphatase target regulatory subunit (MYPT1). Immunoblotting showed higher sGC-α and ROCK2 in PA than MA, while sGC-β and MYPT1 levels were higher in MA than in PA. Interestingly, the level of pp-MLC2 was higher in PA than in MA without stimulation. In the 80K-contraction state, the levels of p-MLC2 and pp-MLC2 were commonly increased. Treatment with the ROCK inhibitor (Y27632, 10 μM) reversed the higher pp-MLC2 in PA. In the myography study, pharmacological inhibition of sGC (ODQ, 10 μM) slowed relaxation during washout, which was more pronounced in PA than in MA. The simultaneous treatment of Y27632 and ODQ reversed the impaired relaxation in PA and MA. Although treatment of PA with Y27632 alone could increase the rate of relaxation, it was still slower than that of MA without Y27632 treatment. Taken together, we suggest that the higher ROCK and lower MYPT in PA would have induced the higher level of MLC2 phosphorylation, which is responsible for the characteristic slow relaxation in PA.","PeriodicalId":54746,"journal":{"name":"Korean Journal of Physiology & Pharmacology","volume":"28 1","pages":"49-57"},"PeriodicalIF":2.0,"publicationDate":"2024-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10762492/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"139059148","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

引用次数: 0

Naringenin modulates GABA mediated response in a sexdependent manner in substantia gelatinosa neurons of trigeminal subnucleus caudalis in immature mice. 柚皮素以性别依赖的方式调节未成熟小鼠三叉神经尾下核胶质神经元的GABA介导反应

IF 2 4区医学

Korean Journal of Physiology & Pharmacology Pub Date : 2024-01-01 DOI: 10.4196/kjpp.2024.28.1.73

Seon Ah Park, Thao Thi Phuong Nguyen, Soo Joung Park, Seong Kyu Han

{"title":"Naringenin modulates GABA mediated response in a sexdependent manner in substantia gelatinosa neurons of trigeminal subnucleus caudalis in immature mice.","authors":"Seon Ah Park, Thao Thi Phuong Nguyen, Soo Joung Park, Seong Kyu Han","doi":"10.4196/kjpp.2024.28.1.73","DOIUrl":"10.4196/kjpp.2024.28.1.73","url":null,"abstract":"The substantia gelatinosa (SG) within the trigeminal subnucleus caudalis (Vc) is recognized as a pivotal site of integrating and modulating afferent fibers carrying orofacial nociceptive information. Although naringenin (4',5,7-thrihydroxyflavanone), a natural bioflavonoid, has been proven to possess various biological effects in the central nervous system (CNS), the activity of naringenin at the orofacial nociceptive site has not been reported yet. In this study, we explored the influence of naringenin on GABA response in SG neurons of Vc using whole-cell patch-clamp technique. The application of GABA in a bath induced two forms of GABA responses: slow and fast. Naringenin enhanced both amplitude and area under curve (AUC) of GABA-mediated responses in 57% (12/21) of tested neurons while decreasing both parameters in 33% (7/21) of neurons. The enhancing or suppressing effect of naringenin on GABA response have been observed, with enhancement occurring when the GABA response was slow, and suppression when it was fast. Furthermore, both the enhancement of slower GABA responses and the suppression of faster GABA responses by naringenin were concentration dependent. Interestingly, the nature of GABA response was also found to be sex-dependent. A majority of SG neurons from juvenile female mice exhibited slower GABA responses, whereas those from juvenile males predominantly displayed faster GABA responses. Taken together, this study indicates that naringenin plays a partial role in modulating orofacial nociception and may hold promise as a therapeutic target for treating orofacial pain, with effects that vary according to sex.","PeriodicalId":54746,"journal":{"name":"Korean Journal of Physiology & Pharmacology","volume":"28 1","pages":"73-81"},"PeriodicalIF":2.0,"publicationDate":"2024-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10762483/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"139059152","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

引用次数: 0

ACY-241, a histone deacetylase 6 inhibitor, suppresses the epithelial-mesenchymal transition in lung cancer cells by downregulating hypoxia-inducible factor-1 alpha. 组蛋白去乙酰化酶 6 抑制剂 ACY-241 通过下调缺氧诱导因子-1 alpha 抑制肺癌细胞的上皮-间质转化。

IF 2 4区医学

Korean Journal of Physiology & Pharmacology Pub Date : 2024-01-01 DOI: 10.4196/kjpp.2024.28.1.83

Seong-Jun Park, Naeun Lee, Chul-Ho Jeong

{"title":"ACY-241, a histone deacetylase 6 inhibitor, suppresses the epithelial-mesenchymal transition in lung cancer cells by downregulating hypoxia-inducible factor-1 alpha.","authors":"Seong-Jun Park, Naeun Lee, Chul-Ho Jeong","doi":"10.4196/kjpp.2024.28.1.83","DOIUrl":"10.4196/kjpp.2024.28.1.83","url":null,"abstract":"Hypoxia-inducible factor-1 alpha (HIF-1α) is a transcription factor activated under hypoxic conditions, and it plays a crucial role in cellular stress regulation. While HIF-1α activity is essential in normal tissues, its presence in the tumor microenvironment represents a significant risk factor as it can induce angiogenesis and confer resistance to anti-cancer drugs, thereby contributing to poor prognoses. Typically, HIF-1α undergoes rapid degradation in normoxic conditions via oxygen-dependent degradation mechanisms. However, certain cancer cells can express HIF-1α even under normoxia. In this study, we observed an inclination toward increased normoxic HIF-1α expression in cancer cell lines exhibiting increased HDAC6 expression, which prompted the hypothesis that HDAC6 may modulate HIF-1α stability in normoxic conditions. To prove this hypothesis, several cancer cells with relatively higher HIF-1α levels under normoxic conditions were treated with ACY-241, a selective HDAC6 inhibitor, and small interfering RNAs for HDAC6 knockdown. Our data revealed a significant reduction in HIF-1α expression upon HDAC6 inhibition. Moreover, the downregulation of HIF-1α under normoxic conditions decreased zinc finger E-box-binding homeobox 1 expression and increased E-cadherin levels in lung cancer H1975 cells, consequently suppressing cell invasion and migration. ACY-241 treatment also demonstrated an inhibitory effect on cell invasion and migration by reducing HIF-1α level. This study confirms that HDAC6 knockdown and ACY-241 treatment effectively decrease HIF-1α expression under normoxia, thereby suppressing the epithelial-mesenchymal transition. These findings highlight the potential of selective HDAC6 inhibition as an innovative therapeutic strategy for lung cancer.","PeriodicalId":54746,"journal":{"name":"Korean Journal of Physiology & Pharmacology","volume":"28 1","pages":"83-91"},"PeriodicalIF":2.0,"publicationDate":"2024-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10762487/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"139059145","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

引用次数: 0

Mechanism of Wenshen Xuanbi Decoction in the treatment of osteoarthritis based on network pharmacology and experimental verification. 基于网络药理学和实验验证的温神宣肺汤治疗骨关节炎的机理。

IF 2 4区医学

Korean Journal of Physiology & Pharmacology Pub Date : 2024-01-01 DOI: 10.4196/kjpp.2024.28.1.59

Hankun You, Siyuan Song, Deren Liu, Tongsen Ren, Song Jiang Yin, Peng Wu, Jun Mao

{"title":"Mechanism of Wenshen Xuanbi Decoction in the treatment of osteoarthritis based on network pharmacology and experimental verification.","authors":"Hankun You, Siyuan Song, Deren Liu, Tongsen Ren, Song Jiang Yin, Peng Wu, Jun Mao","doi":"10.4196/kjpp.2024.28.1.59","DOIUrl":"10.4196/kjpp.2024.28.1.59","url":null,"abstract":"To investigate the mechanism of Wenshen Xuanbi Decoction (WSXB) in treating osteoarthritis (OA) via network pharmacology, bioinformatics analysis, and experimental verification. The active components and prediction targets of WSXB were obtained from the TCMSP database and Swiss Target Prediction website, respectively. OA-related genes were retrieved from GeneCards and OMIM databases. Protein-protein interaction and functional enrichment analyses were performed, resulting in the construction of the Herb-Component-Target network. In addition, differential genes of OA were obtained from the GEO database to verify the potential mechanism of WSXB in OA treatment. Subsequently, potential active components were subjected to molecular verification with the hub targets. Finally, we selected the most crucial hub targets and pathways for experimental verification in vitro. The active components in the study included quercetin, linolenic acid, methyl linoleate, isobergapten, and beta-sitosterol. AKT1, tumor necrosis factor (TNF), interleukin (IL)-6, GAPDH, and CTNNB1 were identified as the most crucial hub targets. Molecular docking revealed that the active components and hub targets exhibited strong binding energy. Experimental verification demonstrated that the mRNA and protein expression levels of IL-6, IL-17, and TNF in the WSXB group were lower than those in the KOA group (p < 0.05). WSXB exhibits a chondroprotective effect on OA and delays disease progression. The mechanism is potentially related to the suppression of IL-17 and TNF signaling pathways and the down-regulation of IL-6.","PeriodicalId":54746,"journal":{"name":"Korean Journal of Physiology & Pharmacology","volume":"28 1","pages":"59-72"},"PeriodicalIF":2.0,"publicationDate":"2024-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10762491/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"139059151","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

引用次数: 0

Inhibition of Wnt/β-catenin signaling by monensin in cervical cancer. 莫能菌素抑制宫颈癌中的 Wnt/β-catenin 信号传导

IF 2 4区医学

Korean Journal of Physiology & Pharmacology Pub Date : 2024-01-01 DOI: 10.4196/kjpp.2024.28.1.21

Bingbing Fu, Lixia Fang, Ranran Wang, Xueling Zhang

{"title":"Inhibition of Wnt/β-catenin signaling by monensin in cervical cancer.","authors":"Bingbing Fu, Lixia Fang, Ranran Wang, Xueling Zhang","doi":"10.4196/kjpp.2024.28.1.21","DOIUrl":"10.4196/kjpp.2024.28.1.21","url":null,"abstract":"The challenging clinical outcomes associated with advanced cervical cancer underscore the need for a novel therapeutic approach. Monensin, a polyether antibiotic, has recently emerged as a promising candidate with anti-cancer properties. In line with these ongoing efforts, our study presents compelling evidence of monensin's potent efficacy in cervical cancer. Monensin exerts a pronounced inhibitory impact on proliferation and anchorage-independent growth. Additionally, monensin significantly inhibited cervical cancer growth in vivo without causing any discernible toxicity in mice. Mechanism studies show that monensin's anti-cervical cancer activity can be attributed to its capacity to inhibit the Wnt/β-catenin pathway, rather than inducing oxidative stress. Monensin effectively reduces both the levels and activity of β-catenin, and we identify Akt, rather than CK1, as the key player involved in monensin-mediated Wnt/β-catenin inhibition. Rescue studies using Wnt activator and β-catenin-overexpressing cells confirmed that β-catenin inhibition is the mechanism of monensin's action. As expected, cervical cancer cells exhibiting heightened Wnt/β-catenin activity display increased sensitivity to monensin treatment. In conclusion, our findings provide pre-clinical evidence that supports further exploration of monensin's potential for repurposing in cervical cancer therapy, particularly for patients exhibiting aberrant Wnt/β-catenin activation.","PeriodicalId":54746,"journal":{"name":"Korean Journal of Physiology & Pharmacology","volume":"28 1","pages":"21-30"},"PeriodicalIF":2.0,"publicationDate":"2024-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10762490/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"139059149","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

引用次数: 0

Aurantio-obtusin exerts an anti-inflammatory effect on acute kidney injury by inhibiting NF-κB pathway. 橙黄决明素通过抑制 NF-κB 通路对急性肾损伤产生抗炎作用。

IF 2 4区医学

Korean Journal of Physiology & Pharmacology Pub Date : 2024-01-01 DOI: 10.4196/kjpp.2024.28.1.11

Haiyan Xiang, Yun Zhang, Yan Wu, Yaling Xu, Yuanhao Hong

{"title":"Aurantio-obtusin exerts an anti-inflammatory effect on acute kidney injury by inhibiting NF-κB pathway.","authors":"Haiyan Xiang, Yun Zhang, Yan Wu, Yaling Xu, Yuanhao Hong","doi":"10.4196/kjpp.2024.28.1.11","DOIUrl":"10.4196/kjpp.2024.28.1.11","url":null,"abstract":"Acute kidney injury (AKI) is one of the major complications of sepsis. Aurantio-obtusin (AO) is an anthraquinone compound with antioxidant and anti-inflammatory activities. This study was developed to concentrate on the role and mechanism of AO in sepsis-induced AKI. Lipopolysaccharide (LPS)-stimulated human renal proximal tubular epithelial cells (HK-2) and BALB/c mice receiving cecal ligation and puncture (CLP) surgery were used to establish in vitro cell model and in vivo mouse model. HK-2 cell viability was measured using MTT assays. Histological alterations of mouse renal tissues were analyzed via hematoxylin and eosin staining. Renal function of mice was assessed by measuring the levels of serum creatinine (SCr) and blood urea nitrogen (BUN). The concentrations of pro-inflammatory cytokines in HK-2 cells and serum samples of mice were detected using corresponding ELISA kits. Protein levels of factors associated with nuclear factor kappa-B (NF-κB) pathway were measured in HK-2 cells and renal tissues by Western blotting. AO exerted no cytotoxic effect on HK-2 cells and AO dose-dependently rescued LPS-induced decrease in HK-2 cell viability. The concentrations of pro-inflammatory cytokines were increased in response to LPS or CLP treatment, and the alterations were reversed by AO treatment. For in vivo experiments, AO markedly ameliorated renal injury and reduced high levels of SCr and BUN in mice underwent CLP operation. In addition, AO administration inhibited the activation of NF-κB signaling pathway in vitro and in vivo. In conclusion, AO alleviates septic AKI by suppressing inflammatory responses through inhibiting the NF-κB pathway.","PeriodicalId":54746,"journal":{"name":"Korean Journal of Physiology & Pharmacology","volume":"28 1","pages":"11-19"},"PeriodicalIF":2.0,"publicationDate":"2024-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10762489/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"139059146","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

引用次数: 0

Carvacrol improves blood lipid and glucose in rats with type 2 diabetes mellitus by regulating short-chain fatty acids and the GPR41/43 pathway. 香芹酚通过调节短链脂肪酸和 GPR41/43 通路改善 2 型糖尿病大鼠的血脂和血糖。

IF 2 4区医学

Korean Journal of Physiology & Pharmacology Pub Date : 2024-01-01 DOI: 10.4196/kjpp.2024.28.1.1

Yan Sun, Hai Qu, Xiaohong Niu, Ting Li, Lijuan Wang, Hairui Peng

{"title":"Carvacrol improves blood lipid and glucose in rats with type 2 diabetes mellitus by regulating short-chain fatty acids and the GPR41/43 pathway.","authors":"Yan Sun, Hai Qu, Xiaohong Niu, Ting Li, Lijuan Wang, Hairui Peng","doi":"10.4196/kjpp.2024.28.1.1","DOIUrl":"10.4196/kjpp.2024.28.1.1","url":null,"abstract":"Type 2 diabetes mellitus (T2DM) is characterized by hyperglycemia and dyslipidemia. Carvacrol (CAR) has demonstrated the potential to mitigate dyslipidemia. This study aims to investigate whether CAR can modulate blood glucose and lipid levels in a T2DM rat model by regulating short-chain fatty acids (SCFAs) and the GPR41/43 pathway. The T2DM rat model was induced by a high-fat diet combined with low-dose streptozocin injection and treated with oral CAR and/or mixed antibiotics. Fasting blood glucose, oral glucose tolerance, and insulin tolerance tests were assessed. Serum lipid parameters, hepatic and renal function indicators, tissue morphology, and SCFAs were measured. In vitro, high glucose (HG)-induced IEC-6 cells were treated with CAR, and optimal CAR concentration was determined. HG-induced IEC-6 cells were treated with SCFAs or/and GPR41/43 agonists. CAR significantly reduced blood lipid and glucose levels, improved tissue damage, and increased SCFA levels in feces and GPR41/43 expression in colonic tissues of T2DM rats. CAR also attenuated HG-induced apoptosis of IEC-6 cells and enhanced GPR41/43 expression. Overall, these findings suggest that CAR alleviates blood lipid and glucose abnormalities in T2DM rats by modulating SCFAs and the GPR41/43 pathway.","PeriodicalId":54746,"journal":{"name":"Korean Journal of Physiology & Pharmacology","volume":"28 1","pages":"1-10"},"PeriodicalIF":2.0,"publicationDate":"2024-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10762484/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"139059147","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

引用次数: 0

Store-operated calcium entry in the satellite glial cells of rat sympathetic ganglia. 大鼠交感神经节卫星神经胶质细胞中的储能钙离子通道

IF 2 4区医学

Korean Journal of Physiology & Pharmacology Pub Date : 2024-01-01 DOI: 10.4196/kjpp.2024.28.1.93

Sohyun Kim, Seong Jun Kang, Huu Son Nguyen, Seong-Woo Jeong

{"title":"Store-operated calcium entry in the satellite glial cells of rat sympathetic ganglia.","authors":"Sohyun Kim, Seong Jun Kang, Huu Son Nguyen, Seong-Woo Jeong","doi":"10.4196/kjpp.2024.28.1.93","DOIUrl":"10.4196/kjpp.2024.28.1.93","url":null,"abstract":"Satellite glial cells (SGCs), a major type of glial cell in the autonomic ganglia, closely envelop the cell body and even the synaptic regions of a single neuron with a very narrow gap. This structurally unique organization suggests that autonomic neurons and SGCs may communicate reciprocally. Glial Ca2+ signaling is critical for controlling neural activity. Here, for the first time we identified the machinery of store-operated Ca2+ entry (SOCE) which is critical for cellular Ca2+ homeostasis in rat sympathetic ganglia under normal and pathological states. Quantitative realtime PCR and immunostaining analyses showed that Orai1 and stromal interaction molecules 1 (STIM1) proteins are the primary components of SOCE machinery in the sympathetic ganglia. When the internal Ca2+ stores were depleted in the absence of extracellular Ca2+, the number of plasmalemmal Orai1 puncta was increased in neurons and SGCs, suggesting activation of the Ca2+ entry channels. Intracellular Ca2+ imaging revealed that SOCE was present in SGCs and neurons; however, the magnitude of SOCE was much larger in the SGCs than in the neurons. The SOCE was significantly suppressed by GSK7975A, a selective Orai1 blocker, and Pyr6, a SOCE blocker. Lipopolysaccharide (LPS) upregulated the glial fibrillary acidic protein and Toll-like receptor 4 in the sympathetic ganglia. Importantly, LPS attenuated SOCE via downregulating Orai1 and STIM1 expression. In conclusion, sympathetic SGCs functionally express the SOCE machinery, which is indispensable for intracellular Ca2+ signaling. The SOCE is highly susceptible to inflammation, which may affect sympathetic neuronal activity and thereby autonomic output.","PeriodicalId":54746,"journal":{"name":"Korean Journal of Physiology & Pharmacology","volume":"28 1","pages":"93-103"},"PeriodicalIF":2.0,"publicationDate":"2024-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10762485/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"139059153","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

引用次数: 0

Multiple consecutive-biphasic pulse stimulation improves spatially localized firing of retinal ganglion cells in the degenerate retina. 多个连续的双相脉冲刺激改善了退化视网膜中视网膜神经节细胞的空间局部放电。

IF 2 4区医学

Korean Journal of Physiology & Pharmacology Pub Date : 2023-11-01 DOI: 10.4196/kjpp.2023.27.6.541

Jungryul Ahn, Yongseok Yoo, Yong Sook Goo

{"title":"Multiple consecutive-biphasic pulse stimulation improves spatially localized firing of retinal ganglion cells in the degenerate retina.","authors":"Jungryul Ahn, Yongseok Yoo, Yong Sook Goo","doi":"10.4196/kjpp.2023.27.6.541","DOIUrl":"10.4196/kjpp.2023.27.6.541","url":null,"abstract":"Retinal prostheses have shown some clinical success in restoring vision in patients with retinitis pigmentosa. However, the post-implantation visual acuity does not exceed that of legal blindness. The reason for the poor visual acuity might be that (1) degenerate retinal ganglion cells (RGCs) are less responsive to electrical stimulation than normal RGCs, and (2) electrically-evoked RGC spikes show a more widespread not focal response. The single-biphasic pulse electrical stimulation, commonly used in artificial vision, has limitations in addressing these issues. In this study, we propose the benefit of multiple consecutive-biphasic pulse stimulation. We used C57BL/6J mice and C3H/HeJ (rd1) mice for the normal retina and retinal degeneration model. An 8 × 8 multi-electrode array was used to record electrically-evoked RGC spikes. We compared RGC responses when increasing the amplitude of a single biphasic pulse versus increasing the number of consecutive biphasic pulses at the same stimulus charge. Increasing the amplitude of a single biphasic pulse induced more RGC spike firing while the spatial resolution of RGC populations decreased. For multiple consecutive-biphasic pulse stimulation, RGC firing increased as the number of pulses increased, and the spatial resolution of RGC populations was well preserved even up to 5 pulses. Multiple consecutive-biphasic pulse stimulation using two or three pulses in degenerate retinas induced as much RGC spike firing as in normal retinas. These findings suggest that the newly proposed multiple consecutive-biphasic pulse stimulation can improve the visual acuity in prosthesis-implanted patients.","PeriodicalId":54746,"journal":{"name":"Korean Journal of Physiology & Pharmacology","volume":"27 6","pages":"541-553"},"PeriodicalIF":2.0,"publicationDate":"2023-11-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10613570/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"54232353","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

引用次数: 0

Three sesquiterpene lactones suppress lung adenocarcinoma by blocking TMEM16A-mediated Ca²⁺-activated Cl^- channels. 三种倍半萜内酯通过阻断TMEM16A介导的Ca2+激活的Cl-通道来抑制肺腺癌。

IF 2 4区医学

Korean Journal of Physiology & Pharmacology Pub Date : 2023-11-01 DOI: 10.4196/kjpp.2023.27.6.521

Ruilian Xiu, Jie Jia, Qing Zhang, Fengjiao Liu, Yaxin Jia, Yuanyuan Zhang, Beibei Song, Xiaodan Liu, Jingwei Chen, Dongyang Huang, Fan Zhang, Juanjuan Ma, Honglin Li, Xuan Zhang, Yunyun Geng

{"title":"Three sesquiterpene lactones suppress lung adenocarcinoma by blocking TMEM16A-mediated Ca2+-activated Cl- channels.","authors":"Ruilian Xiu, Jie Jia, Qing Zhang, Fengjiao Liu, Yaxin Jia, Yuanyuan Zhang, Beibei Song, Xiaodan Liu, Jingwei Chen, Dongyang Huang, Fan Zhang, Juanjuan Ma, Honglin Li, Xuan Zhang, Yunyun Geng","doi":"10.4196/kjpp.2023.27.6.521","DOIUrl":"10.4196/kjpp.2023.27.6.521","url":null,"abstract":"Transmembrane protein TMEM16A, which encodes calcium-activated chloride channel has been implicated in tumorigenesis. Overexpression of TMEM16A is associated with poor prognosis and low overall survival in multiple cancers including lung adenocarcinoma, making it a promising biomarker and therapeutic target. In this study, three structure-related sesquiterpene lactones (mecheliolide, costunolide and dehydrocostus lactone) were extracted from the traditional Chinese medicine Aucklandiae Radix and identified as novel TMEM16A inhibitors with comparable inhibitory effects. Their effects on the proliferation and migration of lung adenocarcinoma cells were examined. Whole-cell patch clamp experiments showed that these sesquiterpene lactones potently inhibited recombinant TMEM16A currents in a concentration-dependent manner. The half-maximal concentration (IC50) values for three tested sesquiterpene lactones were 29.9 ± 1.1 μM, 19.7 ± 0.4 μM, and 24.5 ± 2.1 μM, while the maximal effect (Emax) values were 100.0% ± 2.8%, 85.8% ± 0.9%, and 88.3% ± 4.6%, respectively. These sesquiterpene lactones also significantly inhibited the endogenous TMEM16A currents and proliferation, and migration of LA795 lung cancer cells. These results demonstrate that mecheliolide, costunolide and dehydrocostus lactone are novel TMEM16A inhibitors and potential candidates for lung adenocarcinoma therapy.","PeriodicalId":54746,"journal":{"name":"Korean Journal of Physiology & Pharmacology","volume":"27 6","pages":"521-531"},"PeriodicalIF":2.0,"publicationDate":"2023-11-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10613571/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"54232355","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

引用次数: 0