Smart medicine最新文献

Nitric oxide (NO) has shown great potential in tumor therapy, and the development of a platform for precise and controllable NO release still needs to be explored. Herein, a microfluidic electrospray strategy is proposed for the fabrication of hydrogel microspheres encapsulating NO donors (S-nitrosoglutathione, GSNO) together with black phosphorus (BP) and chemotherapeutic doxorubicin (DOX) as microcarriers for tumor therapy. Based on the excellent photothermal property of BP and thermal sensitivity of GSNO, the microcarriers exhibit a near-infrared light (NIR)-responsive NO release behavior. Besides, the photothermal performance of the microcarriers accelerates the release of DOX. All these contribute to the excellent tumor-killing effect of the microcarriers by combining multiple therapeutic strategies including NO therapy, photothermal therapy, and chemotherapy. Moreover, it was demonstrated that the NIR-responsive NO delivery microcarriers could significantly inhibit tumor growth without apparent side effects in vivo. Therefore, it is believed that the novel NIR-responsive NO microcarriers are promising candidates in clinical tumor therapy applications.

Non-alcoholic fatty liver disease (NAFLD) is a typical chronic liver disease connected to a high risk of developing hepatocellular carcinoma (HCC). The development of NAFLD and HCC has been associated with changes in epigenetics, such as histone modifications and micro RNA (miRNA)-mediated processes. Recently, in the realm of epitranscriptomics, RNA alterations have become important regulators. N6-methyladenosine (m6A) is the most common and crucial alteration for controlling mRNA stability, splicing, and translation. It is particularly important for controlling liver disease progression and hepatic function. This review aims to conclude recent research on the functions of m6A epitranscriptome in the molecular mechanisms behind NAFLD and HCC development, with special attention to the effects of m6A alteration on how HCC develops and its possible roles in the progression of NAFLD to HCC. Additionally, the review discusses the possible effects of m6A alteration on the treatment and diagnostic of NAFLD and HCC. It is crucial to remember that m6A modification is a reversible action controlled via the coordinated functions of the proteins that write and delete, enabling quick adaptability to environmental changes. The review also discusses m6A-binding proteins' function in mRNA alternative splicing, translation, and degradation and their ability to modulate mRNA stability and processing. Understanding RNA modification regulation and its part in the emergence of HCC and NAFLD may provide new avenues for diagnosing and treating these diseases.

Herpes simplex virus type 1 (HSV-1) is a human pathogen that causes recurrent infections. Acyclovir-resistant strains exist and can cause severe complications, which are potentially untreatable with current therapies. We have developed siRNA swarms that target a 653 base pair long region of the essential HSV gene UL29. As per our previous results, the anti-UL29 siRNA swarm effectively inhibits the replication of circulating HSV strains and acyclovir-resistant HSV strains in vitro, while displaying a good safety profile. We investigated a single intranasal therapeutic dose of a siRNA swarm in mice, which were first inoculated intranasally with HSV-1 and given treatment 4 h later. We utilized a luciferase-expressing HSV-1 strain, which enabled daily follow-up of infection with in vivo imaging. Our results show that a single dose of a UL29-targeted siRNA swarm can inhibit the replication of HSV-1 in orofacial tissue, which was reflected in ex vivo HSV titers and HSV DNA copy numbers as well as by a decrease in a luciferase-derived signal. Furthermore, the treatment had a tendency to protect mice from severe clinical symptoms and delay the onset of the symptoms. These results support the development of antiviral siRNA swarms as a novel treatment for HSV-1 infections.

Nerve injury caused by trauma or iatrogenic trauma can lead to loss of sensory and motor function, resulting in paralysis of patients. Inspired by endogenous bioelectricity and extracellular matrix, various external physical and chemical stimuli have been introduced to treat nerve injury. Benefiting from the self-power feature and great biocompatibility, piezoelectric biomaterials have attracted widespread attention in biomedical applications, especially in neural tissue engineering. Here, we provide an overview of the development of piezoelectric biomaterials for neural tissue engineering. First, several types of piezoelectric biomaterials are introduced, including inorganic piezoelectric nanomaterials, organic piezoelectric polymers, and their derivates. Then, we focus on the in vitro and in vivo external energy-driven piezoelectric effects involving ultrasound, mechanical movement, and other external field-driven piezoelectric effects. Neuroengineering applications of the piezoelectric biomaterials as in vivo grafts for the treatment of central nerve injury and peripheral nerve injury are also discussed and highlighted. Finally, the current challenges and future development of piezoelectric biomaterials for promoting nerve regeneration and treating neurological diseases are presented.