On June 8, 2018, an NS3/4A protease inhibitor called danoprevir was approved in China to treat the infections of HCV genotype (GT) 1b – the most common HCV genotype worldwide. Based on phase 2 and 3 clinical trials, the 12-week regimen of ritonavir-boosted danoprevir (danoprevir/r) plus peginterferon alpha-2a and ribavirin offered 97.1% (200/206) of sustained virologic response at post-treatment week 12 (SVR12) in treatment-naïve non-cirrhotic patients infected with HCV genotype 1b. Adverse events such as anemia, fatigue, fever, and headache were associated with the inclusion of peginterferon alpha-2a and ribavirin in the danoprevir-based regimen. Moreover, drug resistance to danoprevir could be traced to amino acid substitutions (Q80K/R, R155K, D168A/E/H/N/T/V) near the drug-binding pocket of HCV NS3 protease. Despite UNC2250 concentration , the clinical use of danoprevir is currently limited to its combination with peginterferon alpha-2a and ribavirin, thereby driving its development towards interferon-free, ribavirin-free regimens with improved tolerability and adherence. In the foreseeable future, pan-genotypic direct-acting antivirals with better clinical efficacy and less adverse events will be available to treat HCV infections worldwide.

Bupropion is an antidepressant drug that facilitates weight loss. It is a highly water-soluble drug that needs multiple dosing, so it is considered a potential candidate for oral controlled-release dosage form. The aim of this research was to formulate and evaluate satiety-inducing swellable floating bupropion tablets by direct compression targeting depression associated with eating disorders. Various combinations of natural and semi-synthetic hydrogels were selected to achieve maximum swelling and remaining buoyant in the stomach. This synergistically enhances weight loss by increasing satiety.

An I-optimal mixture design was conducted to establish the optimal quantitative composition of tablets. Friability, floating lag time, swelling index after 4 and 8 hours, along with the percent of bupropion released at 1 and 8 hours were selected as dependent variables. The optimized formulation was characterized by physicochemical properties, thermal stability, and chemical interaction. In vivo radiographic evaluation of gastric residence besides, the oral bioavailability relative to marketed Wellbutrin

sustained-release tablets were investigated using human volunteers.

The optimized formulation (73.3 mg xanthan, 120 mg glucomannan, 8.4 mg tamarind kernel powder, 78.3 mg HPMC K15M) was achieved with the overall desirability equals 0.782. In vivo radiographic study showed that formulation was retained for >8 hours in the stomach. Compared with the marketed BUP tablets, the C

was almost the same with a significant increase (p =0.004) for T

.

Using combinations of these hydrogels would be promising gastroretentive delivery systems in the control of bupropion rate release with enhanced floating and swelling features.

Using combinations of these hydrogels would be promising gastroretentive delivery systems in the control of bupropion rate release with enhanced floating and swelling features.

Zuojinwan (ZJW), a famous Chinese medicine formula, has been widely used to treat colorectal cancer (CRC). However, its bioactive compounds, potential targets, and molecular mechanism remain largely elusive.

A network pharmacology-based strategy combined with molecular docking studies and in vitro validation were employed to investigate bioactive compounds, potential targets, and molecular mechanism of ZJW against CRC.

Bioactive compounds and potential targets of ZJW, as well as related genes of CRC, were acquired from public databases. Important ingredients, potential targets, and signaling pathways were determined through bioinformatics analysis, including protein-protein interaction (PPI), the Gene Ontology (GO), and the Kyoto Encyclopedia of Genes and Genomes (KEGG). Subsequently, molecular docking and cell experiments were performed to further verify the findings.

A total of 36 bioactive ingredients of ZJW and 163 gene targets of ZJW were identified. The network analysis revealed that quercetin, m of ZJW against CRC. It also provided a promising approach to uncover the scientific basis and therapeutic mechanism of traditional Chinese medicine (TCM) formula treating for disease.

To investigate the neuroprotective effect of chrysophanol (CHR) on PC12 treated with Aβ

, and the involved mechanism.

After the establishment of an AD cell model induced by Aβ

, the cell survival rate was detected by MTT, cell apoptosis was assayed by Hoechst 33342 staining, mRNA expressions of calmodulin (CaM), calcium/calmodulin-dependent protein kinase kinase (CaMKK), calcium/calmodulin-dependent protein kinase IV (CaMKIV) and tau (MAPT; commonly known as tau) were determined by qRT-PCR, and protein levels of CaM, CaMKK, CaMKIV, phospho-CaMKIV (p-CaMKIV), tau and phospho-tau (p-tau) were detected by Western blot analysis.

When pretreated with CHR before exposure to Aβ

, PC12 cells showed that increased cell viability and reduced apoptosis. The qRT-PCR results indicated that the deposition of Aβ

triggers a decrease in levels of CaM, CaMKK, CaMKIV, and tau in PC12 cells. #link# In addition, Western blot results also suggested that Aβ

decreases the protein expression of CaM, CaMKK, CaMKIV, p-CaMKIV, and the ratio of p-tau to tau in PC12 cells. However, the above effects were significantly alleviated after the treatment of CHR.

CHR plays a neuroprotective role in AD though decreasing the protein level of CaM-CaMKK-CaMKIV and the expression of p-tau downstream.

CHR plays a neuroprotective role in AD though decreasing the protein level of CaM-CaMKK-CaMKIV and the expression of p-tau downstream.

Adhesive capsulitis of the shoulder results in pain and restricted movement of the glenohumeral joint. Hypothesis There would be a difference in active range of movement in the affected shoulder of patients with adhesive capsulitis after receiving a series of injections of collagenase

(CCH) compared to placebo.

This study reports the results from a single site that was part of a 321-participant, multicenter, double-blind, prospective parallel-group, randomized controlled clinical trial. Inclusion criteria over 18 years of age, unilateral idiopathic adhesive capsulitis for >3 months, but <12 months. Exclusion criteria recent physical therapy, injections, subacromial impingement, calcific tendonitis or glenohumeral joint arthritis in the affected shoulder. Subjects were randomized 31 to receive CCH 0.58 mg or placebo under ultrasound guidance. Injections were on days 1, 22, and 43. The primary outcome measure was a functional assessment of active range of movement.

Overall, 37 patients were screened, 26 subjects were excluded, and 11 subjects were randomly assigned to the treatment group (n=9) or the control group (n=2).