Silica-induced pulmonary fibrosis is an irreversible and progressive lung disease with limited treatments available. In this work, FDA-approved cannabidiol (CBD) was studied for its potential medical use in silicosis. In silicosis female C57BL/6 mice model, oral CBD or pirfenidone (PFD) on day 1 after intratracheal drip silica (150 mg/mL) and continued for 42 days. Lung inflammatory and fibrotic changes were studied using ELISA kits, H&E staining and Masson staining. Osteopontion (OPN) and α-smooth muscle actin (α-SMA) expression in lung tissues was determined using immunohistochemical staining. The results indicated that CBD attenuated silica-induced pulmonary inflammation and fibrosis. Human myeloid leukemia mononuclear cells (THP-1) were treated with silica (200 μg/mL) to induce cell damage, then CBD (10 μM, 20 μM) and PFD (100 μM) were incubated. In vitro experiments showed that CBD can effectively reduce the expression of NLRP3 inflammasome in THP-1 cells and subsequently block silica-stimulated transformation of fibromuscular-myofibroblast transition (FMT) by culturing human embryonic lung fibroblasts (MRC-5) in conditioned medium of THP-1 cells. Therefore, CBD exhibited the potential therapy for silicosis through inhibiting the silica-induced pulmonary inflammation and fibrosis via the NLRP3/TGF-β1/Smad2/3 signaling pathway.

2024-11-13·ACS Applied Materials & Interfaces

Stromal Reprogramming Optimizes KRAS-Specific Chemotherapy Inducing Antitumor Immunity in Pancreatic Cancer

Article

作者: Hu, Qinglian ; Jin, Yuanxiang ; Feng, Jiayu ; Qi, Lulu

Pancreatic ductal adenocarcinoma (PDAC) is a clinically challenging cancer and is often characterized with rich stroma and mutated KRAS, which determines the tumor microenvironment (TME) and therapy response. Turning immunologically "cold" PDAC into "hot" is an unmet need to improve the therapeutic outcome. Herein, we propose a programmable strategy by sequential delivery of pirfenidone (PFD) and nanoengineered KRAS specific inhibitor (AMG510) and gemcitabine (GEM) liposomes. PFD could achieve precise reduction of the extracellular matrix (ECM) by reprogramming pancreatic stellate cells (PSCs). Subsequently, targeting the KRAS-directed oncogenic signaling pathway effectively inhibited tumor proliferation and migration, which sensitized a chemotherapeutic drug and promoted immunogenic cell death (ICD). In preclinical mouse models of PDAC, PFD mediated stromal modulation enhanced the deep penetration of nanoparticles and improved their subsequent performance in tumor growth inhibition. The molecular mechanisms elucidated that the stroma intervention and KRAS signal pathway regulation reshaped the immunosuppression of PDAC and optimized cytotoxic T-cell-mediated antitumor immunity with sustained antitumor memory. Overall, our study provides a practical strategy with clinical translational promise for immunologically cold tumor PDAC treatment.

2024-10-02·ACS Applied Materials & Interfaces

Multifunctional Nanofiber Membranes Constructed by Microfluidic Blow-Spinning to Inhibit Scar Formation at Early Intervention Stage

Article

作者: Zhang, Ying ; Cao, Dadong ; Liu, Meijun ; Zhang, Weifen ; Wen, Shengxiu ; Yang, Hongming ; Zhao, Hanqiang

Pathological scarring has been a challenge in skin injury repair since ancient times, and prophylactic treatment in the early stages of wound healing usually results in delayed wound healing. In this study, poly(ethylene oxide) (PEO) and chitosan (CTS) were used as carrier materials to construct multifunctional pirfenidone (PFD)/CTS/PEO (PCP) nanofiber membranes (NFMs) loaded with PFD by microfluidic blow-spinning (MBS). MBS is a good method for quickly, safely, and greenly constructing large-area manufacturing of inexpensive NFMs. PCP NFMs were uniform in external morphology, with diameters ranging from 200 to 500 nm. The encapsulation efficiency of the drug-loaded PCP NFMs was above 80%, which had a good slow release, visualization, water absorption, and biocompatibility. The inhibitory effect of PCP NFMs on normal human dermal fibroblasts was dose-dependent and inhibited the expression of the transforming growth factor-β1/SMAD family member 3 (TGF-β1/SMAD3) signaling pathway. PCP NFMs showed significant antibacterial effects against both Staphylococcus aureus and Escherichia coli. In the rabbit ear scar experiment, the wound healed about 70% on day 5 and almost completely on day 10 after PCP-3 NFMs treatment, with the thinnest scar tissue, skin color, tenderness close to normal tissue, and a Vancouver scar scale score of less than 5. PCP-3 NFMs had good effects on anti-inflammatory, wound healing, and collagen-I deposition reducing effects. In conclusion, PCP-3 NFMs can both promote wound healing and intervene to inhibit pathological scarring in advance, making them a potential multifunctional wound dressing for early prevention and treatment of pathological scarring.

项与苯替酪胺相关的新闻（医药）

2021-02-02

·BioSpace

Annovis Bio's Lead Candidate ANVS401 Improves Cognitive and Functional Outcomes in Stroke Mice Study

Berwyn, Pennsylvania--(News - February 2, 2021) - Annovis Bio Inc. (NYSE American: ANVS), a clinical-stage drug platform company addressing Alzheimer's disease (AD), Parkinson's disease (PD) and other neurodegenerative diseases, today announced study data showing that a combination treatment using the Company's lead candidate ANVS401 and pifithrin-α (PFT-α) after stroke improved mice locomotor activity and cognitive function more so than treatment with just one or the other agent. The published study, "Sequential combined Treatment of Pifithrin-α and Posiphen Enhances Neurogenesis and Functional Recovery After Stroke," was conducted by Yu "Agnes" Luo, MD, Associate Professor, Department of Neurological Surgery, School of Medicine at Case Western Reserve University in Cleveland, Ohio. The study challenged mice with MCAo-induced stroke (middle carotid artery occlusion induced stoke) and after four weeks, the number of surviving neurons was quantified and the locomotor function, behavior, and cognition of the mice were evaluated. While both treatments yielded improvements in locomotor and cognitive function, the combined ANVS401/PFT-α treatment proved able to enhance stroke-induced endogenous neurogenesis and improve the functional recovery in stroke animals. The combined treatment also significantly improved cognitive function more than the single treatment with PFT-α alone. "This study adds another animal model of neurodegenerative disorders to our existing panel of animal models," commented Maria Maccecchini, Ph.D., CEO of Annovis Bio. "To date we have shown that ANVS401 fully recovers memory and learning in animals with Alzheimer's disease, Down syndrome and traumatic brain injury, fully recovers function in animals with Parkinson's disease and frontotemporal dementia, and recovers sight in rats with glaucoma. In this study we have found that our drug fully recovers cognition and function in stroke mice. Each successful study further supports our plans to move into late-stage studies of ANVS401." About Annovis Bio Headquartered in Berwyn, Pennsylvania, Annovis Bio, Inc. (Annovis) is a clinical-stage, drug platform company addressing neurodegeneration, such as Alzheimer's disease (AD), Parkinson's disease (PD) and Alzheimer's in Down Syndrome (AD-DS). We believe that we are the only company developing a drug for AD, PD and AD-DS that inhibits more than one neurotoxic protein and, thereby, improves the information highway of the nerve cell, known as axonal transport. When this information flow is impaired, the nerve cell gets sick and dies. We expect our treatment to improve memory loss and dementia associated with AD and AD-DS, as well as body and brain function in PD. We have two ongoing Phase 2a studies: one in AD patients and one in both AD and PD patients. For more information on Annovis, please visit the company's website: . Forward-Looking Statements Statements in this press release contain "forward-looking statements" that are subject to substantial risks and uncertainties. Forward-looking statements contained in this press release may be identified by the use of words such as "anticipate," "expect," "believe," "will," "may," "should," "estimate," "project," "outlook," "forecast" or other similar words, and include, without limitation, statements regarding the timing, effectiveness and anticipated results of ANVS401 clinical trials. Forward-looking statements are based on Annovis Bio, Inc.'s current expectations and are subject to inherent uncertainties, risks and assumptions that are difficult to predict. Further, certain forward-looking statements are based on assumptions as to future events that may not prove to be accurate, including that clinical trials may be delayed. These and other risks and uncertainties are described more fully in the section titled "Risk Factors" in the Annual Report on Form 10-K for the year ended December 31, 2019 filed with the Securities and Exchange Commission. Forward-looking statements contained in this announcement are made as of this date, and Annovis Bio, Inc. undertakes no duty to update such information except as required under applicable law. Investor Relations: Dave Gentry, CEO RedChip Companies Inc. 407-491-4498 Dave@redchip.com SOURCE: Annovis Bio, Inc. To view the source version of this press release, please visit

100 项与苯替酪胺相关的药物交易

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