Phase 0 open, single-center clinical study to evaluate the safety, tolerability and anti-tumor effects of JN101 injection combined with radiotherapy in patients with malignant solid tumors

开始日期2021-08-30

申办/合作机构-

100 项与 JN-101 相关的临床结果

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100 项与 JN-101 相关的转化医学

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100 项与 JN-101 相关的专利（医药）

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项与 JN-101 相关的文献（医药）

2023-03-01·Diabetes

miR-210-3pPromotes Obesity-Induced Adipose Tissue Inflammation and Insulin Resistance by Targeting SOCS1-Mediated NF-κB Pathway

Article

作者: Roy, Soumyajit ; Kabeer, Shaheen Wasil ; Kumar, Aditya ; Tikoo, Kulbhushan ; Pal, Durba ; Dey, Upalabdha ; Arora, Leena ; Dasgupta, Suman ; Banerjee, Dipanjan ; Patra, Debarun ; Singh, Satpal ; Sinha, Archana

Under the condition of chronic obesity, an increased level of free fatty acids along with low oxygen tension in the adipose tissue creates a pathophysiological adipose tissue microenvironment (ATenv), leading to the impairment of adipocyte function and insulin resistance. Here, we found the synergistic effect of hypoxia and lipid (H + L) surge in fostering adipose tissue macrophage (ATM) inflammation and polarization. ATenv significantly increased miR-210-3p expression in ATMs which promotes NF-κB activation–dependent proinflammatory cytokine expression along with the downregulation of anti-inflammatory cytokine expression. Interestingly, delivery of miR-210-3p mimic significantly increased macrophage inflammation in the absence of H + L co-stimulation, while miR-210-3p inhibitor notably compromised H + L–induced macrophage inflammation through increased production of suppressor of cytokine signaling 1 (SOCS1), a negative regulator of the NF-κB inflammatory signaling pathway. Mechanistically, miR-210 directly binds to the 3′-UTR of SOCS1 mRNA and silences its expression, thus preventing proteasomal degradation of NF-κB p65. Direct delivery of anti–miR-210-3p LNA in the ATenv markedly rescued mice from obesity-induced adipose tissue inflammation and insulin resistance. Thus, miR-210-3p inhibition in ATMs could serve as a novel therapeutic strategy for managing obesity-induced type 2 diabetes.

2023-01-01·Nephron

MicroRNA-155-5p Aggravates Adriamycin-Induced Focal Segmental Glomerulosclerosis through Targeting Nrf2

Article

作者: Yang, Xiaomeng ; She, Jian ; Tang, Lingling ; He, Liyu ; Shi, Wei ; Wei, Jiali ; Liu, Guoyong

Introduction: Focal segmental glomerulosclerosis (FSGS) is characterized by focal and segmental obliteration of glomerular capillary tufts with increased matrix and usually associated with nephrotic range proteinuria. FSGS is a huge burden to society; however, the mechanisms remain unclear and treatment is still lacking. Methods: Adriamycin nephropathy was induced by Adriamycin injection and some mice were also injected with Anti-miR-155-5p LNA or YC-1 (a pharmacological inhibitor of HIF-1). At 6 weeks, the mice were sacrificed, and kidneys, blood and urine samples were collected for further analysis. Results: We demonstrated a significant increase of miR-155-5p in kidney tissues in Adriamycin-induced FSGS mouse models. We also found Adriamycin treatment led to the activation of HIF-1, and inhibition of HIF-1 using YC-1 partly prevented the induction of miR-155-5p. Functionally, anti-miR-155-5p attenuated kidney injury and delayed the progression of renal fibrosis. Further, anti-miR-155-5p also enhanced the expression of Nrf2 following Adriamycin treatment. Further, our luciferase microRNA target reporter assay verified Nrf2 as a direct target of miR-155-5p. Our further results indicated anti-miR-155-5p could suppress kidney oxidative stress and inflammation, also supporting Nrf2 was the direct target of miR-155-5p. Finally, we also found miR-155-5p did not increase in serum but significantly increased in urine, indicating urinary miR-155-5p may be useful for FSGS diagnosis. Conclusion: This study identified a HIF-1/miR-155-5p/Nrf2 axis which can promote kidney oxidative stress and inflammation, finally aggravating kidney injury and accelerating the progression of renal fibrosis in FSGS. Moreover, the increase in urinary miR-155-5p may be useful for the diagnosis of FSGS.

2021-09-01·Molecular Therapy - Nucleic Acids2区 · 医学

Protective effect of LNA-anti-miR-132 therapy on liver fibrosis in mice

2区 · 医学

ArticleOA

作者: Catalano, Donna ; Talis, Austin ; Momen-Heravi, Fatemeh ; Szabo, Gyongyi ; Bala, Shashi

microRNAs (miRs) are small regulatory RNAs that are frequently deregulated in liver disease. Liver fibrosis is characterized by excessive scarring caused by chronic inflammatory processes. In this study, we determined the functional role of miR-132 using a locked nucleic acid (LNA)-anti-miR approach in liver fibrosis. A significant induction in miR-132 levels was found in mice treated with CCl₄ and in patients with fibrosis/cirrhosis. Inhibition of miR-132 in mice with LNA-anti-miR-132 caused decreases in CCl₄-induced fibrogenesis and inflammatory phenotype. An attenuation in collagen fibers, α SMA, MCP1, IL-1β, and Cox2 was found in LNA-anti-miR-132-treated mice. CCl₄ treatment increased caspase 3 activity and extracellular vesicles (EVs) in control but not in anti-miR-132-treated mice. Inhibition of miR-132 was associated with augmentation of MMP12 in the liver and Kupffer cells. In vivo and in vitro studies suggest miR-132 targets SIRT1 and inflammatory genes. Using tumor cancer genome atlas data, an increase in miR-132 was found in hepatocellular carcinoma (HCC). Increased miR-132 levels were associated with fibrogenic genes, higher tumor grade and stage, and unfavorable survival in HCC patients. Therapeutic inhibition of miR-132 might be a new approach to alleviate liver fibrosis, and treatment efficacy can be monitored by observing EV shedding.

100 项与 JN-101 相关的药物交易

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研发状态

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适应症	最高研发状态	国家/地区	公司	日期
心肌缺血	临床前	美国	Jaan Biotherapeutics LLC	-
再灌注损伤	临床前	美国	Jaan Biotherapeutics LLC	-
心肌疾病	药物发现	美国	Jaan Biotherapeutics LLC	-