作者: Liu, Aiming ; Yuan, Honglei ; Zhang, Yaqin ; Yang, Yang ; Chang, Xiaoai ; Wang, Jianan ; Chen, Fang ; Shao, Yixue ; Lin, Changsong ; Han, Xiao ; Su, Dongming ; Shao, Shulin ; Wu, Tijun ; Niu, Fandi ; Tang, Wei ; Bi, Yan ; Sun, Peng ; Wu, Jingwen ; Zhu, Yunxia ; Qian, Bin

Pancreatic β-cell dysfunction caused by obesity can be associated with alterations in the levels of miRNAs. However, the role of miRNAs in such processes remains elusive. Here, we show that pancreatic islet miR-27a-5p, which is markedly increased in obese mice and impairs insulin secretion, is mainly delivered by visceral adipocyte–derived extracellular vesicles (EVs). Depleting miR-27a-5p significantly improved insulin secretion and glucose intolerance in db/db mice. Supporting the function of EV miR-27a-5p as a key pathogenic factor, intravenous injection of miR-27a-5p–containing EVs showed their distribution in mouse pancreatic islets. Tracing the injected adeno-associated virus (AAV)-miR-27a-5p (AAV-miR-27a) or AAV-FABP4-miR-27a-5p (AAV-FABP4-miR-27a) in visceral fat resulted in upregulating miR-27a-5p in EVs and serum and elicited mouse pancreatic β-cell dysfunction. Mechanistically, miR-27a-5p directly targeted L-type Ca2+ channel subtype CaV1.2 (Cacna1c) and reduced insulin secretion in β-cells. Overexpressing mouse CaV1.2 largely abolished the insulin secretion injury induced by miR-27a-5p. These findings reveal a causative role of EV miR-27a-5p in visceral adipocyte–mediated pancreatic β-cell dysfunction in obesity-associated type 2 diabetes mellitus.Article Highlights

2024-01-01·Advanced Science

A Novel Bioswitchable miRNA Mimic Delivery System: Therapeutic Strategies Upgraded from Tetrahedral Framework Nucleic Acid System for Fibrotic Disease Treatment and Pyroptosis Pathway Inhibition

Article

作者: Lv, Weitong ; Jiang, Yueying ; Shi, Ruijianghan ; Yin, Wumeng ; Tian, Taoran ; Lin, Yunfeng ; Li, Songhang

AbstractThere has been considerable interest in gene vectors and their role in regulating cellular activities and treating diseases since the advent of nucleic acid drugs. MicroRNA (miR) therapeutic strategies are research hotspots as they regulate gene expression post‐transcriptionally and treat a range of diseases. An original tetrahedral framework nucleic acid (tFNA) analog, a bioswitchable miR inhibitor delivery system (BiRDS) carrying miR inhibitors, is previously established; however, it remains unknown whether BiRDS can be equipped with miR mimics. Taking advantage of the transport capacity of tetrahedral framework nucleic acid (tFNA) and upgrading it further, the treatment outcomes of a traditional tFNA and BiRDS at different concentrations on TGF‐β‐ and bleomycin‐induced fibrosis simultaneously in vitro and in vivo are compared. An upgraded traditional tFNA is designed by successfully synthesizing a novel BiRDS, carrying a miR mimic, miR‐27a, for treating skin fibrosis and inhibiting the pyroptosis pathway, which exhibits stability and biocompatibility. BiRDS has three times higher efficiency in delivering miRNAs than the conventional tFNA with sticky ends. Moreover, BiRDS is more potent against fibrosis and pyroptosis‐related diseases than tFNAs. These findings indicate that the BiRDS can be applied as a drug delivery system for disease treatment.

2024-01-01·International Journal of Medical Sciences

The crucial relationship between miRNA-27 and CSE/H₂S, and the mechanism of action of GLP-1 in myocardial hypertrophy

Article

作者: Wu, Di ; Huo, Qing-Ji ; Cui, Chang-Peng ; Liu, Mei-Ming ; Gao, Shan ; Li, Bai-Yan ; Li, Ying ; Zhang, Rong ; Xiong, Xue ; Li, Ke-Xin ; Sun, Xun

Cardiac hypertrophy is the most prevalent compensatory heart disease that ultimately leads to spontaneous heart failure. Mounting evidence suggests that microRNAs (miRs) and endogenous hydrogen sulfide (H₂S) play a crucial role in the regulation of cardiac hypertrophy. In this study, we aimed to investigate whether inhibition of miR-27a could protect against cardiac hypertrophy by modulating H₂S signaling. We established a model of cardiac hypertrophy by obtaining hypertrophic tissue from mice subjected to transverse aortic constriction (TAC) and from cells treated with angiotensin-II. Molecular alterations in the myocardium were quantified using quantitative real time PCR (qRT-PCR), Western blotting, and ELISA. Morphological changes were characterized by hematoxylin and eosin (HE) staining and Masson's trichrome staining. Functional myocardial changes were assessed using echocardiography. Our results demonstrated that miR-27a levels were elevated, while H₂S levels were reduced in TAC mice and myocardial hypertrophy. Further luciferase and target scan assays confirmed that cystathionine-γ-lyase (CSE) was a direct target of miR-27a and was negatively regulated by it. Notably, enhancement of H₂S expression in the heart was observed in mice injected with recombinant adeno-associated virus vector 9 (rAAV9)-anti-miR-27a and in cells transfected with a miR-27a inhibitor during cardiac hypertrophy. However, this effect was abolished by co-transfection with CSE siRNA and the miR-27a inhibitor. Conversely, injecting rAAV9-miR-27a yielded opposite results. Interestingly, our findings demonstrated that glucagon-like peptide-1 (GLP-1) agonists could mitigate myocardial damage by down-regulating miR-27a and up-regulating CSE. In summary, our study suggests that inhibition of miR-27a holds therapeutic promise for the treatment of cardiac hypertrophy by increasing H₂S levels. Furthermore, our findings unveil a novel mechanism of GLP-1 agonists involving the miR-27a/H₂S pathway in the management of cardiac hypertrophy.

项与 Adva-27a 相关的新闻（医药）

2024-04-01

·BioSpace

Sunshine Biopharma Reports Operating Results for the Fiscal Year Ended December 31, 2023

Sales Grew at an Average Rate of 14% Per Quarter During the Year NEW YORK, NY / ACCESSWIRE / April 1, 2024 / Sunshine Biopharma, Inc. (NASDAQ:SBFM) (the "Company"), a pharmaceutical company offering and researching life-saving medicines in a variety of therapeutic areas including oncology and antivirals today announced that it has filed its 2023 financial results on Form 10-K on Thursday March 28, 2024. The following are highlights of the report: Sales in 2023 grew to a total of $24,092,787, primarily as a result of a full year of revenues generated by the acquisition of Nora Pharma in October 2022. Nora Pharma's revenues for its fiscal year ended June 30, 2022, were $10,766,982. The average 2023 quarter-over-quarter growth rate in sales was 14%. Loss per share decreased from a negative $1.76 per share in 2022 to a negative $0.19 per share in 2023, predominantly due to a one-time write-off of goodwill in 2022. Completed a private placement of approximately $5 million in gross proceeds for use in part for expansion of sales operations. Repurchased 513,723 shares of the Company's common stock on the market for a total of $541,143. The Company's two proprietary drugs in development advanced to the animal testing stage for both SBFM-PL4 targeted for SARS Coronavirus infections and K1.1 mRNA for liver cancer. IND-enabling studies of Adva-27a anticancer compound were halted in November 2023 pending further analysis of unfavorable in vitro results obtained earlier in the year. "We are happy with our 2023 results, as we continue to strive to achieve profitability," said Dr. Steve Slilaty, CEO of Sunshine Biopharma. "We look forward to further growth in 2024 and beyond as we expand our operations and bring more life-saving drugs to market," he added. The following are key items contained in the Company's Income Statement included in the 2023 10-K: 2023 2022 Sales $ 24,092,787 $ 4,345,603 Gross Profit $ 8,339,171 $ 1,696,575 General & Administrative Expenses $ 13,124,470 $ 28,697,325 Goodwill impairment - $ 18,326,719 Net Loss $ 4,506,044 $ 26,744,440 Safe Harbor Forward-Looking Statements This press release may contain "forward-looking statements" within the meaning of Section 27A of the Securities Act of 1933 and Section 21E of the Securities Exchange Act of 1934, each as amended. Forward-looking statements include all statements that do not relate solely to historical or current facts, including without limitation statements regarding the Company's product development and business prospects, and can be identified by the use of words such as "may," "will," "expect," "project," "estimate," "anticipate," "plan," "believe," "potential," "should," "continue" or the negative versions of those words or other comparable words. Forward-looking statements are not guarantees of future actions or performance. These forward-looking statements are based on information currently available to the Company and its current plans or expectations and are subject to a number of risks and uncertainties that could significantly affect current plans. Should one or more of these risks or uncertainties materialize, or the underlying assumptions prove incorrect, actual results may differ significantly from those anticipated, believed, estimated, expected, intended, or planned. Although the Company believes that the expectations reflected in the forward-looking statements are reasonable, the Company cannot guarantee future results, performance, or achievements. Except as required by applicable law, including the securities laws of the United States, the Company does not intend to update any of the forward-looking statements to conform these statements to actual results. For Additional Information Contact: Camille Sebaaly, CFO Direct Line: 514-814-0464 camille.sebaaly@sunshinebiopharma.com SOURCE: Sunshine Biopharma Inc. View the original press release on accesswire.com

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2023-09-21

·BioSpace

Sunshine Biopharma Receives 180-Day Extension To Achieve Nasdaq Minimum Bid Compliance

No Immediate Effect on Nasdaq Listing or Trading of the Company's Common Stock MONTREAL, QC / ACCESSWIRE / September 21, 2023 / Sunshine Biopharma Inc. (NASDAQ:SBFM) (the "Company"), a pharmaceutical company offering and researching life-saving medicines in a variety of therapeutic areas including oncology and antivirals today announced that it has received a 180-day extension, until March 18, 2024, to achieve compliance with the Nasdaq $1.00 minimum bid price rule. The Nasdaq staff has determined that Sunshine Biopharma is eligible, based on the Company meeting the continued listing requirements for market value of publicly held shares and all other applicable requirements for initial listing on the Capital Market with the exception of the bid price requirement, and the Company's written notice of its intention to cure the deficiency during the second compliance period by effecting a reverse stock split, if necessary. If at any time before March 18, 2024, the closing bid price of the Company's common stock is at least $1.00 per share for a minimum of 10 consecutive business days, the Company will regain compliance with this Nasdaq rule and this matter will be closed. This current notification from Nasdaq has no immediate effect on the listing or trading of the Company's common stock, which will continue to trade on the Nasdaq Capital Market under the symbol "SBFM." About Sunshine Biopharma Sunshine Biopharma recently acquired Nora Pharma Inc. and as a result the Company now has 50 generic prescription drugs on the market in Canada and 41 additional employees. The Company is planning to expand its product offering to 77 generic prescription drugs over the next 18 months. In parallel, Sunshine Biopharma is continuing its proprietary drug development program which is comprised of (i) K1.1 mRNA for liver cancer, (ii) Adva-27a, a small chemotherapy molecule for pancreatic cancer, and (iii) PLpro protease inhibitor for COVID-19. For more information, please visit: Safe Harbor Forward-Looking Statements This press release contains forward-looking statements which are based on current expectations, forecasts, and assumptions of Sunshine Biopharma, Inc. (the "Company") that involve risks as well as uncertainties that could cause actual outcomes and results to differ materially from those anticipated or expected. These statements appear in this release and include all statements that are not statements of historical fact regarding the intent, belief or current expectations of the Company, including statements related to the Company's drug development activities, financial performance, and future growth. These risks and uncertainties are further described in filings and reports by the Company with the U.S. Securities and Exchange Commission (SEC). Actual results and the timing of certain events could differ materially from those projected in or contemplated by the forward-looking statements due to a number of factors detailed from time to time in the Company's filings with the SEC. Reference is hereby made to cautionary statements and risk factors set forth in the Company's most recent SEC filings. For Additional Information: Sunshine Biopharma Contact: Camille Sebaaly, CFO Direct Line: 514-814-0464 camille.sebaaly@sunshinebiopharma.com SOURCE: Sunshine Biopharma, Inc. View source version on accesswire.com:

并购信使RNA

2023-08-11

·BioSpace

Sunshine Biopharma Reports 2023 Second Quarter Results: Revenues Up 3,600%

MONTREAL, Aug. 11, 2023 (GLOBE NEWSWIRE) -- Sunshine Biopharma Inc. (NASDAQ: “SBFM”) (the “Company”), a pharmaceutical company offering and researching life-saving medicines in a variety of therapeutic areas including oncology and antivirals today announced that it has filed its quarterly report for the 2023 second quarter. The Company reported gross revenues of $5,560,865 for the quarter ended June 30, 2023, an increase of 3,600% over the same period in 2022. The increase was largely due to the prescription drugs sales of Nora Pharma Inc., a generic pharmaceuticals company that Sunshine Biopharma acquired in October 2022. In addition, the Company’s second quarter revenues of $5,560,865 represent a 13.6% increase over first quarter results. “We are thrilled with our second quarter revenue results and look forward to continued quarter over quarter growth for the rest of 2023 and beyond,” said Dr. Steve Slilaty, CEO of Sunshine Biopharma. About Sunshine Biopharma Sunshine Biopharma recently acquired Nora Pharma Inc. and as a result the Company now has 50 generic prescription drugs on the market in Canada and 41 additional employees. The Company is planning to expand its product offering to 77 generic prescription drugs over the next 18 months. In parallel, Sunshine Biopharma is continuing its proprietary drug development program which is comprised of (i) K1.1 mRNA for liver cancer, (ii) Adva-27a, a small chemotherapy molecule for pancreatic cancer, and (iii) PLpro protease inhibitor for COVID-19. For more information, please visit: . Safe Harbor Forward-Looking Statements This press release contains forward-looking statements which are based on current expectations, forecasts, and assumptions of Sunshine Biopharma, Inc. (the “Company”) that involve risks as well as uncertainties that could cause actual outcomes and results to differ materially from those anticipated or expected. These statements appear in this release and include all statements that are not statements of historical fact regarding the intent, belief or current expectations of the Company, including statements related to the Company’s drug development activities, financial performance, and future growth. These risks and uncertainties are further described in filings and reports by the Company with the U.S. Securities and Exchange Commission (SEC). Actual results and the timing of certain events could differ materially from those projected in or contemplated by the forward-looking statements due to a number of factors detailed from time to time in the Company’s filings with the SEC. Reference is hereby made to cautionary statements and risk factors set forth in the Company’s most recent SEC filings. For Additional Information: Sunshine Biopharma Contact: Camille Sebaaly, CFO Direct Line: 514-814-0464 camille.sebaaly@sunshinebiopharma.com

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100 项与 Adva-27a 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
乳腺癌	临床前	-	The Jewish General Hospital	-
女性生殖器官肿瘤	临床前	-	Central State University Of New York Inc	-
女性生殖器官肿瘤	临床前	-	The Jewish General Hospital	-
女性生殖器官肿瘤	临床前	-	Sunshine Biopharma, Inc.	-
胰腺癌	临床前	-	Central State University Of New York Inc	-
胰腺癌	临床前	-	Sunshine Biopharma, Inc.	-
胰腺癌	临床前	-	The Jewish General Hospital	-
小细胞肺癌	临床前	-	Sunshine Biopharma, Inc.	-
小细胞肺癌	临床前	-	The Jewish General Hospital	-
小细胞肺癌	临床前	-	Central State University Of New York Inc	-