Baicalein analogues as prospective SARS-CoV-2 main protease (Mpro) inhibitors: A dataset of molecular docking-based virtual screening hits.

The global coronavirus disease 2019 (COVID-19) pandemic originating from severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) has exerted profound damage to millions of lives. Baicalein is a flavonoid that has gotten a lot of attention as a possible SARS-CoV-2 main protease (Mpro) inhibitor because it can fight off many different viruses. We prepared and screened three sets of databases, each containing 2563 baicalein analogues, against Mpro using molecular docking simulation. The data showed that several baicalein analogues exhibited stable binding energies relative to standard baicalein, indicating that they have some selectivity against Mpro. The binding properties of the top three stable analogues from each database were further analyzed with respect to their binding properties, such as binding mode, binding energy, and binding interaction of putative stable ligand confirmations at the target binding site region.

Device-assisted continuous ambulatory peritoneal dialysis: A single-centre experience.

BACKGROUND: Peritoneal dialysis (PD) patients with impaired hand-eye function require helper assistance. Our centre developed a connection device that assists patients with impaired hand-eye function to perform PD exchange themselves, but the clinical outcomes in these patients have not been investigated. METHODS: We retrospectively reviewed patients who had device-assisted continuous ambulatory peritoneal dialysis (CAPD) during 2007-2016 and compared their clinical outcomes with age- and sex-matched patients receiving helper-assisted CAPD. RESULTS: One hundred seventy-two patients (86 each in the device- and helper-assisted CAPD groups) were followed for 29.9 (19.4-43.3) months. The device- and helper-assisted groups had comparable peritonitis rates (0.489 and 0.504 episode per patient-year, respectively, p = 0.814), with no difference in the distribution of causative organisms and the organism-specific peritonitis rates. The device-assisted group showed similar peritonitis-free survival compared with the helper-assisted group (2.58 (1.85-3.31) vs. 1.78 (0.68-2.88) years, p = 0.363) and time-to-PD discontinuation (6.27 (3.65-8.90) vs. 4.35 (3.48-5.22) years, p = 0.677). The median patient survival was similar between the two groups (3.89 (2.22-5.55) vs. 3.81 (3.27-4.36) years in the device- and helper-assisted groups, respectively, p = 0.505). CONCLUSION: Device-assisted CAPD confers comparable outcomes as helper-assisted CAPD and is a viable option in PD patients with impaired hand-eye function.

Resolution of severe eosinophilic peritonitis in a patient on continuous ambulatory peritoneal dialysis by changing from Dianeal peritoneal dialysis solution to Stay-Safe Balance solution: a case report.

BACKGROUND: Eosinophilic peritonitis is a well-known complication at the initiation of peritoneal dialysis. It is often due to an allergic reaction to peritoneal dialysis solution or sometimes to the peritoneal dialysis catheter itself. Most cases are self-limiting with expected spontaneous resolution within a few weeks. Treatment is necessary for severe or persistent cases. However, the optimal treatment has not yet been defined. There have been only a few case reports on the use of anti-histamines and/or steroids for the treatment of eosinophilic peritonitis. We reported a case of severe eosinophilic peritonitis successfully treated by switching the brand of peritoneal dialysis fluid (same glucose concentration). To the best of our knowledge, this is the first reported case employing such a treatment strategy. CASE PRESENTATION: An eighty-two-year-old man with end-stage renal failure was started on continuous ambulatory peritoneal dialysis with Dianeal® (Baxter) peritoneal dialysis solution. He developed eosinophilic peritonitis 19 days after initiation of peritoneal dialysis. Infectious causes were ruled out by bacterial, fungal and tuberculosis smears and cultures. In view of the persistent and severe symptoms, we intervened by switching from Dianeal® (Baxter) peritoneal dialysis solution to Stay-Safe Balance® (Fresenius) solution with the same glucose concentration. His eosinophilic peritonitis resolved 5 days after switching the peritoneal dialysis solution. CONCLUSION: In severe or persistent cases of eosinophilic peritonitis requiring treatment, other than the use of steroids and anti-histamines, switching to a different brand of peritoneal dialysis solution can be considered.

Monomeric, Dimeric, and Trimeric Tropane Alkaloids from Pellacalyx saccardianus.

Seven new tropane alkaloids, including five monomeric (1-5), one dimeric (6), and one trimeric (7) 3α-nortropane ester, along with two known monomeric nortropane alkaloids (8 and 9), were isolated from the leaves and bark of Pellacalyx saccardianus. Their structures, including the absolute configuration of the enantiomeric pair of (±)-6, were elucidated by comprehensive spectroscopic analyses. Alkaloids 6 and 7 showed cytotoxicity toward human pancreatic cancer cell lines (AsPC-1, BxPC3, PANC-1, and SW1990). Alkaloids 1, 4, and 9 induced a smooth muscle relaxation effect comparable to that of atropine (Emax 106.1 ± 7.5%, 97.0 ± 5.2%, 100.9 ± 1.4%, 111.7 ± 1.7%, respectively) on isolated rat tracheal rings.

Cardiac glycoside cerberin exerts anticancer activity through PI3K/AKT/mTOR signal transduction inhibition.

Natural products possess a significant role in anticancer therapy and many currently-used anticancer drugs are of natural origin. Cerberin (CR), a cardenolide isolated from the fruit kernel of Cerbera odollam, was found to potently inhibit cancer cell growth (GI50 values < 90 nM), colony formation and migration. Significant G2/M cell cycle arrest preceded time- and dose-dependent apoptosis-induction in human cancer cell lines corroborated by dose-and time-dependent PARP cleavage and caspase 3/7 activation, in addition to reduced Bcl-2 and Mcl-1 expression. CR potently inhibited PI3K/AKT/mTOR signalling depleting polo-like kinase 1 (PLK-1), c-Myc and STAT-3 expression. Additionally, CR significantly increased the generation of reactive oxygen species (ROS) producing DNA double strand breaks. Preliminary in silico biopharmaceutical assessment of CR predicted >60% bioavailability and rapid absorption; doses of 1-10 mg/kg CR were predicted to maintain efficacious unbound plasma concentrations (>GI50 value). CR's potent and selective anti-tumour activity, and its targeting of key signalling mechanisms pertinent to tumourigenesis support further preclinical evaluation of this cardiac glycoside.

Developing a comprehensive, culturally sensitive conceptual framework of health domains in Singapore.

The increasing focus of healthcare systems worldwide on long-term care highlights the need for culturally sensitive Health-Related Quality of Life instruments to accurately capture perceived health of various populations. Such instruments require a contextualized conceptual framework of health domains, which is lacking in some socio-cultural contexts. We developed a comprehensive and culturally sensitive conceptual framework of health domains relevant to the Singaporean population. We recruited Singaporeans/ permanent residents, English/ Chinese-speaking, with/ without chronic illnesses to participate in focus group discussions (FGDs) and in-depth interviews (IDIs). We elicited health areas participants perceived to be important for them to be happy and satisfied with life. To encourage spontaneous emergence of themes, we did not specify any aspect beyond the broad domains of Physical, Mental, and Social health so as not to limit the emergence of new themes. Themes from the transcripts were distilled through open coding (two independent coders), then classified into more abstract domains (each transcript coded independently by two coders from a pool of six coders). From October 2013 to August 2014, 121 members of the general public participated in 18 FGDs and 13 IDIs (44.6% males, mean age: 53.3 years 77% Chinese, 9% Malay, 12% Indian, 63% with chronic illness) while 13 healthcare workers participated as patient-proxies in three FGDs. Thematic analysis identified 27 domains. The 15 physical domains included physical appearance, energy, physical fitness, and health and resistance to illness. The nine mental domains included emotions, self-esteem, and personal freedom. The three social domains were social contact, social relationships, and social roles. This conceptual framework reflected physical, mental, and social dimensions of well-being, suggesting that the Singapore population's views on health support the World Health Organization's definition of health as "a state of complete physical, mental and social well-being and not merely the absence of disease or infirmity".

Solvothermal synthesis of four polyoxometalate-based coordination polymers including diverse Ag(I)···π interactions.

Four 3D POM-based silver coordination polymers, namely, [Ag17(ptz)11(PW12O40)2]n (1), [Ag17(ptz)11(PMo12O40)2]n (2), [Ag12(ptz)6(CN)2(SiW12O40)]n (3), and [Ag19(ptz)8(H2ptz)(H3ptz)(AgP5W30O110)·7H2O]n (4), have been obtained by solvothermal reaction of AgNO3 and 5-phenyl-1H-tetrazole (Hptz) ligand in the presence of four types of polyoxometalates. Structural analysis shows that four types of Ag(I)···π interactions, m-η(1), m/p-η(2), o/m-η(2), and o/m/p-η(3), were observed in compounds 1-4, depending on the polyoxometalates used. The in situ generated CN(-) ion in compound 3 shows unprecedented mixed σ and π bonding modes, similar to the C2(2-) ion in well-studied silver acetylides. For 4, the Na(+) ion in the Preyssler heteropolyoxoanion, [NaP5W30O110](14-), was exchanged by Ag(I) under solvothermal conditions, generating a novel [AgP5W30O110](14-) anion. In addition, the photoluminescence behavior of 1-4 was also investigated.

Two triazole-based metal-organic frameworks constructed from nanosized Cu20 and Cu30 wheels.

Two metal-organic frameworks constructed from nanosized Cu(20) and Cu(30) wheels have been obtained under hydrothermal conditions based on 1,2,3-triazole and 1-H-1,2,3-benzotriazole, respectively. Crystal structure analysis shows that their differences in the size and nuclearity of Cu(20) and Cu(30) wheels are attributed to the steric effect of ligands.