Customizable Zr-MOF nanoantidote-based multieffective arsenic detoxification and its extended low-toxic therapy.

Arsenic (As) poisoning has become a global public problem threatening human health. Chelation therapy (CT) is the preferred treatment for arsenic poisoning. Nevertheless, efficient and safe arsenic removal in vivo remains a daunting challenge due to the limitations of chelators, including weak affinity, poor cell membrane penetration, and short half-life. Herein, a mercapto-functionalized and size-tunable hierarchical porous Zr-MOF (UiO-66-TC-SH) is developed, which possesses abundant arsenic chemisorption sites, effective cell uptake ability, and long half-life, thereby efficiently removing toxic arsenic in vivo. Moreover, the strong binding affinity of UiO-66-TC-SH for arsenic reduces systemic toxicity caused by off-target effects. In animal trials, UiO-66-TC-SH decreases the blood arsenic levels of acute arsenic poisoning mice to a normal value within 48 h, and the efficacy is superior to clinical drugs 2,3-dimercaptopropanesulfonic acid sodium salt (DMPS). Meanwhile, UiO-66-TC-SH also significantly mitigates the arsenic accumulation in the metabolic organs of chronic arsenic poisoning mice. Surprisingly, UiO-66-TC-SH also accelerates the metabolism of arsenic in organs of tumor-bearing mice and alleviates the side effects of arsenic drugs antitumor therapy. STATEMENT OF SIGNIFICANCE: Arsenic (As) contamination has become a global problem threatening public health. The present clinical chelation therapy (CT) still has some limitations, including the weak affinity, poor cell membrane permeability and short half-life of hydrophilic chelators. Herein, a metal-organic framework (MOF)-based multieffective arsenic removal strategy in vivo is proposed for the first time. Mercapto-functionalized and size-tunable hierarchical porous Zr-MOF nanoantidote (denoted as UiO-66-TC-SH) is accordingly designed and synthesized. After injection, UiO-66-TC-SH can form Zr-O-As bonds and As-S bonds with arsenic, thus enhancing arsenic adsorption capacity, cycling stability and systemic safety simultaneously. The acute arsenic poisoning model results indicate that UiO-66-TC-SH shows superior efficacy to the clinical drug sodium dimercaptopropanesulfonate (DMPS). More meaningfully, we find that UiO-66-TC-SH also accelerates the metabolism of arsenic in organs of tumor-bearing mice and alleviates side effects of arsenic drugs anti-tumor therapy.

Activities of proteases in deep eutectic solvents and removal of protein from chitin by subtilisin A in betaine/glycerol.

This research intended to remove residual protein from chitin with proteases in deep eutectic solvents (DESs). The activities of some proteases in several DESs, including choline chloride/p-toluenesulfonic acid, betaine/glycerol (Bet/G), choline chloride/malic acid, choline chloride/lactic acid, and choline chloride/urea, which are capable of dissolving chitin, were tested, and only in Bet/G some proteases were found to be active, with subtilisin A, ficin, and bromelain showing higher activity than other proteases. However, the latter two proteases caused degradation of chitin molecules. Further investigation revealed that subtilisin A in Bet/G did not exhibit "pH memory", which is a universal characteristic displayed by enzymes dispersed in organic phases, and the catalytic characteristics of subtilisin A in Bet/G differed significantly from those in aqueous phase. The conditions for protein removal from chitin by subtilisin A in Bet/G were determined: Chitin dissolved in Bet/G with 0.5 % subtilisin A (442.0 U/mg, based on the mass of chitin) was hydrolyzed at 45 °C for 30 min. The residual protein content in chitin decreased from 5.75 % ± 0.10 % to 1.01 % ± 0.12 %, improving protein removal by 57.20 % compared with protein removal obtained by Bet/G alone. The crystallinity and deacetylation degrees of chitin remained unchanged after the treatment.

Traditional Scraping (Gua Sha) Combined with Copper-Curcumin Nanoparticle Oleogel for Accurate and Multi-Effective Therapy of Androgenic Alopecia.

Androgenetic alopecia (AGA) is a prevalent systemic disease caused by diverse factors, for which effective treatments are currently limited. Herein, the oleogel (OG) containing copper-curcumin (CuR) nanoparticles is developed, designated as CuRG, which is also combined with traditional naturopathic scraping (Gua Sha, SCR) as a multifunctional therapy for AGA. With the assistance of lipophilic OG and SCR, CuR can efficaciously penetrate the epidermal and dermal regions where most hair follicles (HFs) reside, thereby releasing curcumin (CR) and copper ions (Cu2+) subcutaneously to facilitate hair regeneration. Concomitantly, the mechanical stimulation induced by SCR promotes the formation of new blood vessels, which is conducive to reshaping the microenvironment of HFs. This study validates that the combination of CuRG and SCR is capable of systematically interfering with different pathological processes, ranging from improvement of perifollicular microenvironment (oxidative stress and insufficient vascularization), regulation of inflammatory responses to degradation of androgen receptor, thus potentiating hair growth. Compared with minoxidil, a widely used clinical drug for AGA therapy, the designed synergistic system displays augmented hair regeneration in the AGA mouse model.

Anemarrhena saponins attenuate insulin resistance in rats with high-fat diet-induced obesity via the IRS-1/PI3K/AKT pathway.

ETHNOPHARMACOLOGICAL RELEVANCE: Anemarrhena asphodeloides is the dry rhizome of Anemarrhena asphodeloides Bge. Anemarrhena Saponins isolated from Anemarrhena asphodeloides are one of the pharmacologically active components of this plant and have blood lipid reduction and blood glucose reduction properties. These facts suggest that these saponins might be helpful in the treatment of insulin resistance. AIM OF THE STUDY: To determine the therapeutic effect of anemarrhena saponins on insulin resistance and the probable underlying mechanism. MATERIALS AND METHODS: Insulin-resistant rats were used as the experimental subject, to observe the therapeutic effect of anemarrhena saponins. The blood glucose and blood lipid parameters were determined using the relevant kits. We used hematoxylin and eosin (H&E) staining to observe the protective effect of anemarrhena saponins on the livers of insulin-resistant rats and reverser transcripition polymerase chain reaction (RT-PCR) to analyze the mRNA expressions patterns of genes related to glucose metabolism and inflammatory factors. The toxicity of anemarrhena saponins to HepG2 cells was calculated using the MTT assay. Further, we conducted in vivo and in vitro experiments, and Western-blot analysis to study the effects of anemarrhena saponins on the IRS-1/PI3K/AKT pathway. RESULTS: Anemarrhena saponins were found to improve dyslipidemia, reduce obesity and inflammation, and alleviate liver injury in insulin-resistant rats. Anemarrhena saponins also reduced the mRNA expression of gluconeogenesis-related genes sunch as G6pase, PEPCK, and GSK3ß in the liver. Moreover, anemarrhena saponins up-regulated the phosphorylation levels of IRS-1, PI3K and AKT, promoted insulin signal transduction, and reduced liver injury induced by insulin resistance. CONCLUSIONS: These findings suggest that anemarrhena saponins could promote insulin signal transduction through the IRS-1/PI3K/AKT pathway, thereby reducing the damage caused by insulin resistance.

MiR-592 suppresses the development of glioma by regulating Rho-associated protein kinase.

MicroRNAs are a class of small noncoding RNAs that regulate the translation of target mRNA transcripts. MiR-592 has been considered to play important roles in the initiation and progression of cancer by targeting various molecules in several human cancers, but its role in glioma has not been explored. This study aims to explore the suppressive mechanism of miR-592 in the regulation of glioma development, an effect that is crucial for the further exploration of miR-592 as a novel therapeutic target for glioma. Our results proved that the expression of miR-592 was lower and the expression of Rho-associated protein kinase (ROCK1) was higher in glioma tissue than in adjacent tissue and that lower miR-592 expression was associated negatively with ROCK1 expression. Then, we showed that miR-592 was downregulated in glioma and could suppress the growth of the glioma cell lines U87 and U251. ROCK1, which is a known oncogene, was identified as a direct target of miR-592. A luciferase reporter assay indicated that miR-592 regulates ROCK1 expression through binding to its 3'-UTR. Furthermore, our results showed that miR-592 targets the ROCK1 transcript and suppresses glioma cell growth and invasive growth, thereby providing a potential therapeutic target for glioma treatment.