Health disparities among Burmese diaspora: an integrative review.

Tens of thousands of displaced Burmese ethnic minorities have endured various adversities for over six decades but are largely underserved. This study aimed to illuminate the health impacts of their misfortunes and unmet areas of concern. Using a holistic lens, we conducted an integrative review of 47 papers spanning the years 2004 to 2022 from diverse data sources. The results revealed widespread multimorbidity, triggered mainly by displacement. The diaspora's problematic health conditions were worse than their host country's general population. There was a strong indication that the diaspora's unfortunate health trajectory is determined early in life. Ongoing human rights violations and grossly inadequate health care interventions deepened pre-existing health conditions. Noteworthy emerging treatment initiatives, including integrative health care, were underutilized. The persisting health and intervention needs among the diaspora warrant advanced studies to facilitate much-needed resource mobilization and collaboration among stakeholders to promote health equity. Funding: There was no financial support for this manuscript.

Synthesis and in vitro antibacterial activity of novel 3-azabicyclo[3.3.0]octanyl oxazolidinones.

We synthesized a series of oxazolidinone-type antibacterials in which morpholine C-ring of linezolid has been modified by substituted 3-azabicyclo[3.3.0]octanyl rings. Acetamide or 1,2,3-triazole heterocycle was used as C-5 side chain of oxazolidinone. The resulting series of compounds was then screened in vitro against panel of susceptible and resistant Gram-positive, Gram-negative bacteria, and Mycobacterium tuberculosis (Mtb). Several analogs in this series exhibited potent in vitro antibacterial activity comparable or superior to linezolid against the tested bacteria. Compounds 10a, 10b, 11a, and 15a displayed highly potent activity against M. tuberculosis. Selected compound 10b showed good human microsomal stability and CYP-profile, and showed low activity against hERG channel.

Purification and characterization of human nucleolar phosphoprotein 140 expressed in Escherichia coli.

Human nucleolar phosphoprotein 140, hNopp140, is one of the most highly phosphorylated mammalian proteins, which is involved in the biogenesis of nucleolus. It regulates the transcription of rDNA and has a tendency to bind to doxorubicin, which is widely used as an anti-cancer drug. The biochemical and biophysical property of hNopp140 has not been reported due to the fact that it is rather difficult to obtain protein in large enough quantity. In this paper, we report the cloning and overexpression of the soluble form of hNopp140 in Escherichia coli. The protein was purified to more than 90% homogeneity using hydroxyapatite and ion exchange chromatography. The purified protein can be extensively phosphorylated by casein kinase II and oligomerized into an insoluble aggregate in the presence of magnesium, carbonate, and fluoride ions.

Efficacious and orally bioavailable thrombin inhibitors based on a 2,5-thienylamidine at the P1 position: discovery of N-carboxymethyl-d-diphenylalanyl-l-prolyl[(5-amidino-2-thienyl)methyl]amide.

Thrombin, a crucial enzyme in the blood coagulation, has been a target for antithrombotic therapy. Orally active thrombin inhibitors would provide effective and safe prophylaxis for venous and arterial thrombosis. We conducted optimization of a highly efficacious benzamidine-based thrombin inhibitor LB30812 (3, K(i) = 3 pM) to improve oral bioavailability. Of a variety of arylamidines investigated at the P1 position, 2,5-thienylamidine effectively replaced the benzamidine without compromising the thrombin inhibitory potency and oral absorption. The sulfamide and sulfonamide derivatization at the N-terminal position in general afforded highly potent thrombin inhibitors but with moderate oral absorption, while the well-absorbable N-carbamate derivatives exhibited limited metabolic stability in S9 fractions. The present work culminated in the discovery of the N-carboxymethyl- and 2,5-thienylamidine-containing compound 22 that exhibits the most favorable profiles of anticoagulant and antithrombotic activities as well as oral bioavilability (K(i) = 15 pM; F = 43%, 42%, and 15% in rats, dogs, and monkeys, respectively). This compound on a gravimetric basis was shown to be more effective than a low molecular weight heparin, enoxaparin, in the venous thrombosis models of rat and rabbit. Compound 22 (LB30870) was therefore selected for further preclinical and clinical development.

Expression of the active human and duck hepatitis B virus polymerases in heterologous system of Pichia methanolica.

We expressed the Hepatitis B virus polymerase (HBV P protein) using a recently introduced yeast system, Pichia methanolica. HBV (1-680 amino acids) and Duck Hepatitis B virus (DHBV, 1-780 amino acids) polymerase were expressed and showed DNA dependent DNA polymerase (DDDP). The DHBV polymerase had RNA dependent DNA polymerase (RDDP) and RNase H activities. We present a new simplified way of obtaining active viral P protein using the yeast expression system. The viral P proteins proved to be stable and were not aggregated in the yeast system.