Biomolecules & Therapeutics最新文献_第10页

Exploring the Potential of Rosemary Derived Compounds (Rosmarinic and Carnosic Acids) as Cancer Therapeutics: Current Knowledge and Future Perspectives. 探索迷迭香衍生化合物（迷迭香酸和肉豆蔻酸）作为癌症治疗药物的潜力：当前知识与未来展望》。

IF 3.7 3区医学

Biomolecules & Therapeutics Pub Date : 2024-01-01 DOI: 10.4062/biomolther.2023.054

Fazila Sirajudeen, Lara J Bou Malhab, Yasser Bustanji, Moyad Shahwan, Karem H Alzoubi, Mohammad H Semreen, Jalal Taneera, Waseem El-Huneidi, Eman Abu-Gharbieh

{"title":"Exploring the Potential of Rosemary Derived Compounds (Rosmarinic and Carnosic Acids) as Cancer Therapeutics: Current Knowledge and Future Perspectives.","authors":"Fazila Sirajudeen, Lara J Bou Malhab, Yasser Bustanji, Moyad Shahwan, Karem H Alzoubi, Mohammad H Semreen, Jalal Taneera, Waseem El-Huneidi, Eman Abu-Gharbieh","doi":"10.4062/biomolther.2023.054","DOIUrl":"10.4062/biomolther.2023.054","url":null,"abstract":"Cancer is a global health challenge with high morbidity and mortality rates. However, conventional cancer treatment methods often have severe side effects and limited success rates. In the last decade, extensive research has been conducted to develop safe, and efficient alternative treatments that do not have the limitations of existing anticancer medicines. Plant-derived compounds have shown promise in cancer treatment for their anti-carcinogenic and anti-proliferative properties. Rosmarinic acid (RA) and carnosic acid (CA) are potent polyphenolic compounds found in rosemary (Rosmarinus officinalis) extract. They have been extensively studied for their biological properties, which include anti-diabetic, anti-inflammatory, antioxidant, and anticancer activities. In addition, RA and CA have demonstrated effective anti-proliferative properties against various cancers, making them promising targets for extensive research to develop candidate or leading compounds for cancer treatment. This review discusses and summarizes the anti-tumor effect of RA and CA against various cancers and highlights the involved biochemical and mechanistic pathways.","PeriodicalId":8949,"journal":{"name":"Biomolecules & Therapeutics","volume":"32 1","pages":"38-55"},"PeriodicalIF":3.7,"publicationDate":"2024-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10762267/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"139039478","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"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

Rosmarinic Acid Inhibits Ultraviolet B-Mediated Oxidative Damage via the AKT/ERK-NRF2-GSH Pathway In Vitro and In Vivo. 迷迭香酸通过体外和体内 AKT/ERK-NRF2-GSH 通路抑制紫外线 B 导致的氧化损伤

IF 3.7 3区医学

Biomolecules & Therapeutics Pub Date : 2024-01-01 DOI: 10.4062/biomolther.2023.179

Mei Jing Piao, Pattage Madushan Dilhara Jayatissa Fernando, Kyoung Ah Kang, Pincha Devage Sameera Madushan Fernando, Herath Mudiyanselage Udari Lakmini Herath, Young Ree Kim, Jin Won Hyun

{"title":"Rosmarinic Acid Inhibits Ultraviolet B-Mediated Oxidative Damage via the AKT/ERK-NRF2-GSH Pathway In Vitro and In Vivo.","authors":"Mei Jing Piao, Pattage Madushan Dilhara Jayatissa Fernando, Kyoung Ah Kang, Pincha Devage Sameera Madushan Fernando, Herath Mudiyanselage Udari Lakmini Herath, Young Ree Kim, Jin Won Hyun","doi":"10.4062/biomolther.2023.179","DOIUrl":"10.4062/biomolther.2023.179","url":null,"abstract":"Rosmarinic acid (RA) is a phenolic ester that protects human keratinocytes against oxidative damage induced by ultraviolet B (UVB) exposure, however, the mechanisms underlying its effects remain unclear. This study aimed to elucidate the cell signaling mechanisms that regulate the antioxidant activity of RA and confirm its cyto-protective role. To explore the signaling mechanisms, we used the human keratinocyte cell line HaCaT and SKH1 hairless mouse skin. RA enhanced glutamate-cysteine ligase catalytic subunit (GCLC) and glutathione synthetase (GSS) expression in HaCaT cells in a dose- and time-dependent manner. Moreover, RA induced nuclear factor erythroid-2-related factor 2 (NRF2) nuclear translocation and activated the signaling kinases protein kinase B (AKT) and extracellular signal-regulated kinase (ERK). Treatment with the phosphatidylinositol 3-kinase (PI3K) inhibitor LY294002, the ERK inhibitor U0126, and small interfering RNA (siRNA) gene silencing suppressed RA-enhanced GCLC, GSS, and NRF2 expression, respectively. Cell viability tests showed that RA significantly prevented UVB-induced cell viability decrease, whereas the glutathione (GSH) inhibitors buthionine sulfoximine, LY294002, and U0126 significantly reduced this effect. Moreover, RA protected against DNA damage and protein carbonylation, lipid peroxidation, and apoptosis caused by UVB-induced oxidative stress in a concentration-dependent manner in SKH1 hairless mouse skin tissues. These results suggest that RA protects against UVB-induced oxidative damage by activating AKT and ERK signaling to regulate NRF2 signaling and enhance GSH biosynthesis. Thus, RA treatment may be a promising approach to protect the skin from UVB-induced oxidative damage.","PeriodicalId":8949,"journal":{"name":"Biomolecules & Therapeutics","volume":"32 1","pages":"84-93"},"PeriodicalIF":3.7,"publicationDate":"2024-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10762280/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"139039492","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"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

Intermittent Fasting Modulates Immune Response by Generating Tregs via TGF-β Dependent Mechanisms in Obese Mice with Allergic Contact Dermatitis. 间歇性禁食通过TGF-β依赖性机制产生Tregs调节肥胖小鼠过敏性接触性皮炎的免疫反应

IF 3.7 3区医学

Biomolecules & Therapeutics Pub Date : 2024-01-01 Epub Date: 2023-07-10 DOI: 10.4062/biomolther.2023.053

Sang-Chul Han, Jung-Il Kang, Youn Kyung Choi, Hye-Jin Boo, Weon-Jong Yoon, Hee-Kyoung Kang, Eun-Sook Yoo

{"title":"Intermittent Fasting Modulates Immune Response by Generating Tregs via TGF-β Dependent Mechanisms in Obese Mice with Allergic Contact Dermatitis.","authors":"Sang-Chul Han, Jung-Il Kang, Youn Kyung Choi, Hye-Jin Boo, Weon-Jong Yoon, Hee-Kyoung Kang, Eun-Sook Yoo","doi":"10.4062/biomolther.2023.053","DOIUrl":"10.4062/biomolther.2023.053","url":null,"abstract":"People with obesity maintain low levels of inflammation; therefore, their exposure to foreign antigens can trigger an excessive immune response. In people with obesity or allergic contact dermatitis (ACD), symptoms are exacerbated by a reduction in the number of regulatory T cells (Tregs) and IL-10/TGF-β-modified macrophages (M2 macrophages) at the inflammatory site. Benefits of intermittent fasting (IF) have been demonstrated for many diseases; however, the immune responses regulated by macrophages and CD4+T cells in obese ACD animal models are poorly understood. Therefore, we investigated whether IF suppresses inflammatory responses and upregulates the generation of Tregs and M2 macrophages in experimental ACD animal models of obese mice. The IF regimen relieved various ACD symptoms in inflamed and adipose tissues. We showed that the IF regimen upregulates Treg generation in a TGF-β-dependent manner and induces CD4+T cell hypo-responsiveness. IF-M2 macrophages, which strongly express TGF-β and inhibit CD4+T cell proliferation, directly regulated Treg differentiation from CD4+T cells. These results indicate that the IF regimen enhances the TGF-β-producing ability of M2 macrophages and that the development of Tregs keeps mice healthy against ACD exacerbated by obesity. Therefore, the IF regimen may ameliorate inflammatory immune disorders caused by obesity.","PeriodicalId":8949,"journal":{"name":"Biomolecules & Therapeutics","volume":" ","pages":"136-145"},"PeriodicalIF":3.7,"publicationDate":"2024-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10762271/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"9754651","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"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

Effects of Corticosterone on Beta-Amyloid-Induced Cell Death in SH-SY5Y Cells. 皮质酮对β-淀粉样蛋白诱导的 SH-SY5Y 细胞死亡的影响

IF 3.7 3区医学

Biomolecules & Therapeutics Pub Date : 2024-01-01 DOI: 10.4062/biomolther.2023.133

Bo Kyeong Do, Jung-Hee Jang, Gyu Hwan Park

{"title":"Effects of Corticosterone on Beta-Amyloid-Induced Cell Death in SH-SY5Y Cells.","authors":"Bo Kyeong Do, Jung-Hee Jang, Gyu Hwan Park","doi":"10.4062/biomolther.2023.133","DOIUrl":"10.4062/biomolther.2023.133","url":null,"abstract":"Alzheimer's disease (AD) is a neurodegenerative disease characterized by neuronal cell death and memory impairment. Corticosterone (CORT) is a glucocorticoid hormone produced by the hypothalamic-pituitary-adrenal axis in response to a stressful condition. Excessive stress and high CORT levels are known to cause neurotoxicity and aggravate various diseases, whereas mild stress and low CORT levels exert beneficial actions under pathophysiological conditions. However, the effects of mild stress on AD have not been clearly elucidated yet. In this study, the effects of low (3 and 30 nM) CORT concentration on Aβ25-35-induced neurotoxicity in SH-SY5Y cells and underlying molecular mechanisms have been investigated. Cytotoxicity caused by Aβ25-35 was significantly inhibited by the low concentration of CORT treatment in the cells. Furthermore, CORT pretreatment significantly reduced Aβ25-35-mediated pro-apoptotic signals, such as increased Bim/Bcl-2 ratio and caspase-3 cleavage. Moreover, low concentration of CORT treatment inhibited the Aβ25-35-induced cyclooxygenase-2 and pro-inflammatory cytokine expressions, including tumor necrosis factor-α and interleukin-1β. Aβ25-35 resulted in intracellular accumulation of reactive oxygen species and lipid peroxidation, which were effectively reduced by the low CORT concentration. As a molecular mechanism, low CORT concentration activated the nuclear factor-erythroid 2-related factor 2, a redox-sensitive transcription factor mediating cellular defense and upregulating the expression of antioxidant enzymes, such as NAD(P)H:quinone oxidoreductase, glutamylcysteine synthetase, and manganese superoxide dismutase. These findings suggest that low CORT concentration exerts protective actions against Aβ25-35-induced neurotoxicity and might be used to treat and/or prevent AD.","PeriodicalId":8949,"journal":{"name":"Biomolecules & Therapeutics","volume":"32 1","pages":"77-83"},"PeriodicalIF":3.7,"publicationDate":"2024-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10762270/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"139039477","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"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

Bortezomib Is Toxic but Induces Neurogenesis and Inhibits TUBB3 Degradation in Rat Neural Stem Cells. 硼替佐米有毒，但能诱导神经发生并抑制大鼠神经干细胞中 TUBB3 的降解

IF 3.7 3区医学

Biomolecules & Therapeutics Pub Date : 2024-01-01 Epub Date: 2023-12-11 DOI: 10.4062/biomolther.2023.134

Seung Yeon Sohn, Thin Thin San, Junhyung Kim, Hyun-Jung Kim

{"title":"Bortezomib Is Toxic but Induces Neurogenesis and Inhibits TUBB3 Degradation in Rat Neural Stem Cells.","authors":"Seung Yeon Sohn, Thin Thin San, Junhyung Kim, Hyun-Jung Kim","doi":"10.4062/biomolther.2023.134","DOIUrl":"10.4062/biomolther.2023.134","url":null,"abstract":"Bortezomib (BTZ) is a proteasome inhibitor used to treat multiple myeloma (MM). However, the induction of peripheral neuropathy is one of the major concerns in using BTZ to treat MM. In the current study, we have explored the effects of BTZ (0.01-5 nM) on rat neural stem cells (NSCs). BTZ (5 nM) induced cell death; however, the percentage of neurons was increased in the presence of mitogens. BTZ reduced the B-cell lymphoma 2 (Bcl-2)/Bcl-2 associated X protein ratio in proliferating NSCs and differentiated cells. Inhibition of βIII-tubulin (TUBB3) degradation was observed, but not inhibition of glial fibrillary acidic protein degradation, and a potential PEST sequence was solely found in TUBB3. In the presence of growth factors, BTZ increased cAMP response element-binding protein (CREB) phosphorylation, brain-derived neurotrophic factor (Bdnf) transcription, BDNF expression, and Tubb3 transcription in NSCs. However, in the neuroblastoma cell line, SH-SY5Y, BTZ (1-20 nM) only increased cell death without increasing CREB phosphorylation, Bdnf transcription, or TUBB3 induction. These results suggest that although BTZ induces cell death, it activates neurogenic signals and induces neurogenesis in NSCs.","PeriodicalId":8949,"journal":{"name":"Biomolecules & Therapeutics","volume":" ","pages":"65-76"},"PeriodicalIF":3.7,"publicationDate":"2024-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10762278/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"138797439","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"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

Antiproliferative Activity of Piceamycin by Regulating Alpha-Actinin-4 in Gemcitabine-Resistant Pancreatic Cancer Cells. 通过调节吉西他滨耐药胰腺癌细胞中的α-Actinin-4，皮塞霉素具有抗增殖活性

IF 3.7 3区医学

Biomolecules & Therapeutics Pub Date : 2024-01-01 DOI: 10.4062/biomolther.2023.109

Jee-Hyung Lee, Jin Ho Choi, Kyung-Min Lee, Min Woo Lee, Ja-Lok Ku, Dong-Chan Oh, Yern-Hyerk Shin, Dae Hyun Kim, In Rae Cho, Woo Hyun Paik, Ji Kon Ryu, Yong-Tae Kim, Sang Hyub Lee, Sang Kook Lee

{"title":"Antiproliferative Activity of Piceamycin by Regulating Alpha-Actinin-4 in Gemcitabine-Resistant Pancreatic Cancer Cells.","authors":"Jee-Hyung Lee, Jin Ho Choi, Kyung-Min Lee, Min Woo Lee, Ja-Lok Ku, Dong-Chan Oh, Yern-Hyerk Shin, Dae Hyun Kim, In Rae Cho, Woo Hyun Paik, Ji Kon Ryu, Yong-Tae Kim, Sang Hyub Lee, Sang Kook Lee","doi":"10.4062/biomolther.2023.109","DOIUrl":"10.4062/biomolther.2023.109","url":null,"abstract":"Although gemcitabine-based regimens are widely used as an effective treatment for pancreatic cancer, acquired resistance to gemcitabine has become an increasingly common problem. Therefore, a novel therapeutic strategy to treat gemcitabine-resistant pancreatic cancer is urgently required. Piceamycin has been reported to exhibit antiproliferative activity against various cancer cells; however, its underlying molecular mechanism for anticancer activity in pancreatic cancer cells remains unexplored. Therefore, the present study evaluated the antiproliferation activity of piceamycin in a gemcitabine-resistant pancreatic cancer cell line and patient-derived pancreatic cancer organoids. Piceamycin effectively inhibited the proliferation and suppressed the expression of alpha-actinin-4, a gene that plays a pivotal role in tumorigenesis and metastasis of various cancers, in gemcitabine-resistant cells. Long-term exposure to piceamycin induced cell cycle arrest at the G0/G1 phase and caused apoptosis. Piceamycin also inhibited the invasion and migration of gemcitabine-resistant cells by modulating focal adhesion and epithelial-mesenchymal transition biomarkers. Moreover, the combination of piceamycin and gemcitabine exhibited a synergistic antiproliferative activity in gemcitabine-resistant cells. Piceamycin also effectively inhibited patient-derived pancreatic cancer organoid growth and induced apoptosis in the organoids. Taken together, these findings demonstrate that piceamycin may be an effective agent for overcoming gemcitabine resistance in pancreatic cancer.","PeriodicalId":8949,"journal":{"name":"Biomolecules & Therapeutics","volume":"32 1","pages":"123-135"},"PeriodicalIF":3.7,"publicationDate":"2024-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10762279/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"139039472","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"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

Licochalcone C Inhibits the Growth of Human Colorectal Cancer HCT116 Cells Resistant to Oxaliplatin. 甘草查尔酮 C 可抑制对奥沙利铂耐药的人类结直肠癌 HCT116 细胞的生长。

IF 3.7 3区医学

Biomolecules & Therapeutics Pub Date : 2024-01-01 DOI: 10.4062/biomolther.2023.167

Seung-On Lee, Sang Hoon Joo, Jin-Young Lee, Ah-Won Kwak, Ki-Taek Kim, Seung-Sik Cho, Goo Yoon, Yung Hyun Choi, Jin Woo Park, Jung-Hyun Shim

{"title":"Licochalcone C Inhibits the Growth of Human Colorectal Cancer HCT116 Cells Resistant to Oxaliplatin.","authors":"Seung-On Lee, Sang Hoon Joo, Jin-Young Lee, Ah-Won Kwak, Ki-Taek Kim, Seung-Sik Cho, Goo Yoon, Yung Hyun Choi, Jin Woo Park, Jung-Hyun Shim","doi":"10.4062/biomolther.2023.167","DOIUrl":"10.4062/biomolther.2023.167","url":null,"abstract":"Licochalcone C (LCC; PubChem CID:9840805), a chalcone compound originating from the root of Glycyrrhiza inflata, has shown anticancer activity against skin cancer, esophageal squamous cell carcinoma, and oral squamous cell carcinoma. However, the therapeutic potential of LCC in treating colorectal cancer (CRC) and its underlying molecular mechanisms remain unclear. Chemotherapy for CRC is challenging because of the development of drug resistance. In this study, we examined the antiproliferative activity of LCC in human colorectal carcinoma HCT116 cells, oxaliplatin (Ox) sensitive and Ox-resistant HCT116 cells (HCT116-OxR). LCC significantly and selectively inhibited the growth of HCT116 and HCT116-OxR cells. An in vitro kinase assay showed that LCC inhibited the kinase activities of EGFR and AKT. Molecular docking simulations using AutoDock Vina indicated that LCC could be in ATP-binding pockets. Decreased phosphorylation of EGFR and AKT was observed in the LCC-treated cells. In addition, LCC induced cell cycle arrest by modulating the expression of cell cycle regulators p21, p27, cyclin B1, and cdc2. LCC treatment induced ROS generation in CRC cells, and the ROS induction was accompanied by the phosphorylation of JNK and p38 kinases. Moreover, LCC dysregulated mitochondrial membrane potential (MMP), and the disruption of MMP resulted in the release of cytochrome c into the cytoplasm and activation of caspases to execute apoptosis. Overall, LCC showed anticancer activity against both Ox-sensitive and Ox-resistant CRC cells by targeting EGFR and AKT, inducing ROS generation and disrupting MMP. Thus, LCC may be potential therapeutic agents for the treatment of Ox-resistant CRC cells.","PeriodicalId":8949,"journal":{"name":"Biomolecules & Therapeutics","volume":"32 1","pages":"104-114"},"PeriodicalIF":3.7,"publicationDate":"2024-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10762277/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"139039480","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"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

Therapeutic Effects of (+)-Afzelechin on Particulate Matter-Induced Pulmonary Injury. (+)-Afzelechin 对微粒物质引起的肺损伤的治疗作用

IF 3.7 3区医学

Biomolecules & Therapeutics Pub Date : 2024-01-01 DOI: 10.4062/biomolther.2023.187

Sanghee Cho, Yun Jin Park, Jong-Sup Bae

{"title":"Therapeutic Effects of (+)-Afzelechin on Particulate Matter-Induced Pulmonary Injury.","authors":"Sanghee Cho, Yun Jin Park, Jong-Sup Bae","doi":"10.4062/biomolther.2023.187","DOIUrl":"10.4062/biomolther.2023.187","url":null,"abstract":"Particulate matter (PM) constitutes a hazardous blend of organic and inorganic particles that poses health risks. Inhalation of fine airborne PM with a diameter of ≤ 2.5 μm (PM2.5) can lead to significant lung impairments. (+)-afzelechin (AZC), a natural compound sourced from Bergenia ligulata, boasts a range of attributes, including antioxidant, antimicrobial, anticancer, and cardiovascular effects. However, knowledge about the therapeutic potential of AZC for patients with PM2.5-induced lung injuries remains limited. Thus, in this study, we investigated the protective attributes of AZC against lung damage caused by PM2.5 exposure. AZC was administered to the mice 30 min after intratracheal instillation of PM2.5. Various parameters, such as changes in lung tissue wet/dry (W/D) weight ratio, total protein/total cell ratio, lymphocyte counts, levels of inflammatory cytokines in bronchoalveolar lavage fluid (BALF), vascular permeability, and histology, were evaluated in mice exposed to PM2.5. Data demonstrated that AZC mitigated lung damage, reduced W/D weight ratio, and curbed hyperpermeability induced by PM2.5 exposure. Furthermore, AZC effectively lowered plasma levels of inflammatory cytokines produced by PM2.5 exposure. It reduced the total protein concentration in BALF and successfully alleviated PM2.5-induced lymphocytosis. Additionally, AZC substantially diminished the expression levels of Toll-like receptors 4 (TLR4), MyD88, and autophagy-related proteins LC3 II and Beclin 1. In contrast, it elevated the protein phosphorylation of the mammalian target of rapamycin (mTOR). Consequently, the anti-inflammatory attribute of AZC positions it as a promising therapeutic agent for mitigating PM2.5-induced lung injuries by modulating the TLR4-MyD88 and mTOR-autophagy pathways.","PeriodicalId":8949,"journal":{"name":"Biomolecules & Therapeutics","volume":"32 1","pages":"162-169"},"PeriodicalIF":3.7,"publicationDate":"2024-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10762276/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"139039493","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"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

Biased Dopamine D₂ Receptors Exhibit Distinct Intracellular Trafficking Properties and ERK Activation in Different Subcellular Domains. 有偏向的多巴胺 D2 受体在不同的亚细胞区表现出不同的胞内贩运特性和 ERK 激活。

IF 3.7 3区医学

Biomolecules & Therapeutics Pub Date : 2024-01-01 Epub Date: 2023-07-19 DOI: 10.4062/biomolther.2023.033

Shujie Wang, Lulu Peng, Kyeong-Man Kim

{"title":"Biased Dopamine D2 Receptors Exhibit Distinct Intracellular Trafficking Properties and ERK Activation in Different Subcellular Domains.","authors":"Shujie Wang, Lulu Peng, Kyeong-Man Kim","doi":"10.4062/biomolther.2023.033","DOIUrl":"10.4062/biomolther.2023.033","url":null,"abstract":"Biased signaling or functional selectivity refers to the ability of an agonist or receptor to selectively activate a subset of transducers such as G protein and arrestin in the case of G protein-coupled receptors (GPCRs). Although signaling through arrestin has been reported from various GPCRs, only a few studies have examined side-by-side how it differs from signaling via G protein. In this study, two signaling pathways were compared using dopamine D2 receptor (D2R) mutants engineered via the evolutionary tracer method to selectively transduce signals through G protein or arrestin (D2G and D2Arr, respectively). D2G mediated the inhibition of cAMP production and ERK activation in the cytoplasm. D2Arr, in contrast, mediated receptor endocytosis accompanied by arrestin ubiquitination and ERK activation in the nucleus as well as in the cytoplasm. D2Arr-mediated ERK activation occurred in a manner dependent on arrestin3 but not arrestin2, accompanied by the nuclear translocation of arrestin3 via importin1. D2R-mediated ERK activation, which occurred in both the cytosol and nucleus, was limited to the cytosol when cellular arrestin3 was depleted. This finding supports the results obtained with D2Arr and D2G. Taken together, these observations indicate that biased signal transduction pathways activate distinct downstream mechanisms and that the subcellular regions in which they occur could be different when the same effectors are involved. These findings broaden our understanding on the relation between biased receptors and the corresponding downstream signaling, which is critical for elucidating the functional roles of biased pathways.","PeriodicalId":8949,"journal":{"name":"Biomolecules & Therapeutics","volume":" ","pages":"56-64"},"PeriodicalIF":3.7,"publicationDate":"2024-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10762269/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"10190071","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"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

Anti-Inflammatory Herbal Extracts and Their Drug Discovery Perspective in Atopic Dermatitis. 抗炎草药提取物及其在特应性皮炎中的药物发现前景。

IF 3.7 3区医学

Biomolecules & Therapeutics Pub Date : 2024-01-01 DOI: 10.4062/biomolther.2023.102

Jae-Won Lee, Eun-Nam Kim, Gil-Saeng Jeong

引用次数: 0