The objective of the current study was to achieve a sustained release profile of capecitabine (CAP), an anticancer agent frequently administered in conventional dosage form due to its short plasma half-life. A drug-loaded smart pH responsive chitosan/fenugreek-g-poly (MAA) hydrogel was synthesized by an aqueous free radical polymerization technique. The developed network was evaluated for capecitabine loading %, swelling response, morphology, structural and compositional characteristics, and drug release behavior. Significantly higher swelling and in vitro drug release rate were exhibited by formulations at pH 7.4 than at pH 1.2, demonstrating the pH responsive character of hydrogels. Swelling percentage and CAP loading ranged within 74.45–83.54% and 50.13–72.43%, respectively. Maximum release, up to 93%, was demonstrated over 30 h, evidencing the controlled release pattern of CAP from hydrogels. The optimized formulation was further screened for acute oral toxicity studies. No signs of oral, dermal, or ocular toxicities were noticed, confirming safety evidence of the network. Furthermore, pharmacokinetic analysis demonstrated the sustained release response of CAP from hydrogels as confirmed by a significant increase in plasma half-life (t_1/2) (13 h) and AUC (42.88 µg h/mL) of CAP. Based on these findings, fabricated hydrogels are strongly recommended as a biocompatible carrier for colorectal delivery of active agents.

Isoquinoline alkaloids constitute one of the most common classes of alkaloids that have shown a pronounced role in curing various diseases. Finding ways to reduce the toxicity of these molecules and to increase their therapeutic margin is an urgent matter. Here, a one-step method for the synthesis of a series of 1-aryl-6,7-dimethoxy-1,2,3,4-tetrahydroisoquinolines was performed in 85–98% yield by the Pictet–Spengler reaction. This was accomplished using the reaction between 3,4-dimethoxyphenylethylamine and substituted benzaldehydes boiling in trifluoroacetic acid. Furthermore, 1-(3′-amino-, 4′-aminophenyl)-6,7-dimethoxy-1,2,3,4-tetrahydroisoquinolines were obtained in 94% and 97% yield by reduction in 1-(3′-nitro-, 4′-nitrophenyl)-6,7-dimethoxy-1,2,3,4-tetrahydroisoquinolines with SnCl₂ × 2H₂O. The structures of the substances obtained were confirmed by infrared (IR) and nuclear magnetic resonance (¹H and ¹³C NMR) spectra. ADMET/TOPKAT in silico study concluded that the synthesized compounds exhibited acceptable pharmacodynamic and pharmacokinetic properties without carcinogenic or mutagenic potential but with variable hepatotoxicity. The acute toxicity and structure–toxicity relationship (STR) in the series of 20 derivatives of 1-aryl-6,7-dimethoxy-1,2,3,4-tetrahydroisoquinolines (3a–r, 4a, b) was studied via determination of acute toxicity and resorptive action in white mice employing intragastric step-by-step administration. The first compound, 1-phenyl-6,7-dimethoxy-1,2,3,4-tetrahydroisoquinoline hydrochloride (3a), showed the highest toxicity with LD₅₀ of 280 mg/kg in contrast to 1-(3′-bromo -4′-hydroxyphenyl)-6,7-methylenedioxy-1,2,3,4-tetrahydroisoquinoline hydrochloride (3e) which proved to be the safest of the compounds studied. Its toxicity was 13.75 times lower than that of the parent compound 3a. All compounds investigated showed high local anesthetic activity on rabbit eyes in the concentrations studied. Only 3r, 3n, and 4a caused eye irritation and redness. All investigated derivatives (except 4b) in 1% concentration were more active than lidocaine, providing longer duration of complete anesthesia. Therefore, based on the obtained results of in silico tests, local anesthesia, and acute toxicity, a conclusion can be drawn that the experimental compounds need further extensive future investigations and possible modifications so that they can act as promising drug candidates.

In this study, a series of coumarin derivatives, either alone or as hybrids with cinnamic acid, were synthesized and evaluated for their cytotoxicity against a panel of cancer cells using the MTT assay. Then, the most active compounds were inspected for their mechanism of cytotoxicity by cell-cycle analysis, RT-PCR, DNA fragmentation, and Western blotting techniques. Cytotoxic results showed that compound (4) had a significant cytotoxic effect against HL60 cells (IC₅₀ = 8.09 µM), while compound (8b) had a noticeable activity against HepG2 cells (IC₅₀ = 13.14 µM). Compounds (4) and (8b) mediated their cytotoxicity via PI3K/AKT pathway inhibition. These results were assured by molecular docking studies. These results support further exploratory research focusing on the therapeutic activity of coumarin derivatives as cytotoxic agents.

The 4-variable kidney failure risk equation (KFRE) allows for the prediction of chronic kidney disease (CKD) progression using age, sex, estimated glomerular filtration rate, and urine albumin/creatinine ratio. Electronic health records enable KFRE auto-calculation, and registries allow population-level application. We assessed whether 2-year KFRE score categories are associated with CKD care metrics. Cross-sectional cohort. This study included individuals with CKD in March 2020 who were receiving care within the Partners HealthCare system in Massachusetts. The presence of sufficient data to calculate the KFRE and, among those with a KFRE score, performance on CKD clinical care metrics, including (1) prescription of angiotensin-converting enzyme inhibitor or angiotensin receptor blocker; (2) blood pressure at goal (<140/90 mm Hg) based on clinic measurements; (3) composite metric of hepatitis B virus immunity; (4) composite metric of referral, evaluation, or waitlist status for kidney transplantation; (5) advance directive documentation; (6) yearly influenza vaccination; and (7) pneumonia vaccination. Multivariable logistic regression analysis was used to analyze the association of KFRE score category with CKD care metrics. Of 61,546 patients, 18,272 (30%) had auto-calculated 2-year KFRE scores; the remaining patients lacked KFRE scores because of absent albuminuria assessment. Individuals with a KFRE score were more likely to have a primary care provider or nephrologist. Among patients with 2-year KFRE scores, high-risk patients had increased odds of completing advance directives (OR, 1.52; 95% CI, 1.07-2.17), while low-risk patients had decreased odds of influenza vaccination (OR, 0.85; 95% CI, 0.75-0.97). Patients with moderate- and high-risk KFRE scores had lower odds of having blood pressure at goal (OR, 0.77; 95% CI, 0.61-0.96 and OR, 0.63; 95% CI, 0.44-0.88, respectively). Albuminuria data may have been assessed outside of the Partners system. A higher-risk KFRE score is associated with the delivery of some but not all CKD care measures. An opportunity exists to improve albuminuria measurement.

Euclea divinorum Hiern is a medicinal plant widely distributed in the northeast parts of South Africa. This plant has been used to treat miscarriage and to alleviate gastrointestinal problems. It can also be used externally for the treatment of ulcers and gonorrhea. In this study, we investigated the phytochemical composition of E. divinorum leaf extract using LC-MS and explored its antioxidant properties in vitro and in vivo. The total polyphenolic content of the extract was determined by the Folin–Ciocalteu method. DPPH and FRAP assays were employed to confirm the plant’s antioxidant potential in vitro. A survival assay in the Caenorhabditis elegans model was used to evaluate the extract’s ability to counteract juglone-induced oxidative stress. Moreover, a docking study was performed for the extract’s metabolites, in order to predict possible molecular targets that could explain the antioxidant effect of the plant on a molecular level. This in silico approach was accomplished on three different proteins; xanthine oxidase enzyme, heat shock protein 90 (Hsp90), and induced nitric oxide synthase (iNOS). Docking scores of the resulting poses and their interactions with binding sites’ residues were explored for each protein and were compared to those of simultaneously docked respective co-crystallized and reference substrates. The extract furnished promising antioxidant activities in vitro and in vivo in the C. elegans model that might be attributed to the presence of 46 compounds, which showed several interactions and low binding scores with the tested enzymes. In conclusion, E. divinorum is a promising, safe, and effective antioxidant candidate that could be used to ameliorate oxidative stress-related disorders.

Rhizomes of ginger are commonly used as a spice and for home remedies in either fresh or dry form. This study aimed to assess the effect of sun drying on the volatile constituents, total phenolic and flavonoid content, and the antiviral activity of ginger against low-pathogenic human coronavirus. The antiviral effect of the major volatile compounds was predicted through molecular docking. GC/MS was employed for profiling the volatile constituents of both fresh and dry ginger oils. Moreover, chemometric analysis was applied to discriminate between fresh and dry ginger and to investigate the correlation between their volatile constituents and the antiviral activity using principal component analysis (PCA) and partial least-squares regression (PLS-R). GC/MS analysis revealed that the major effects of the drying process were an increase in α-curcumene and β-sesquiphellandrene. Moreover, total phenolic and flavonoid contents of dried ginger decreased considerably. A PCA score plot revealed significant discrimination between fresh and dry ginger, with α-curcumene and 4-thujanol identified as the main discriminating markers. These findings were validated by in silico molecular docking studies, which revealed that the compounds under consideration had good drug-like characteristics. Thus, ginger is rich in valuable phytoconstituents which showed promising therapy in viral infections such as COVID-19.