Natural products as inhibitors of human immunodeficiency virus reverse transcriptases.

Natural products as inhibitors of human immunodeficiency virus reverse transcriptases

Comparative analysis of post crisis recovery in Southeast Asia.

This report focuses on the comparative analysis of post crisis recovery within three most affected countries, namely Thailand, Indonesia and Malaysia, whereby each with different economic and political fundamentals undertakes different reforms and responses to the crisis and presents different recovery trajectionaries

Bioactive Compounds from <i>Vitex leptobotrys</i>

A new lignan, vitexkarinol (<b>1</b>), as well as a known lignan, neopaulownin (<b>2</b>), a known chalcone, 3-(4-hydroxyphenyl)-1-(2,4,6-trimethoxyphenyl)-2-propen-1-one (<b>3</b>), two known dehydroflavones, tsugafolin (<b>4</b>) and alpinetin (<b>5</b>), two known dipeptides, aurantiamide and aurantiamide acetate, a known sesquiterpene, vemopolyanthofuran, and five known carotenoid metabolites, vomifoliol, dihydrovomifoliol, dehydrovomifoliol, loliolide, and isololiolide, were isolated from the leaves and twigs of <i>Vitex leptobotrys</i> through bioassay-guided fractionation. The chalcone (<b>3</b>) was found to inhibit HIV-1 replication by 77% at 15.9 μM, and the two dehydroflavones (<b>4</b> and <b>5</b>) showed weak anti-HIV activity with IC₅₀ values of 118 and 130 μM, respectively, while being devoid of cytotoxicity at 150 μM. A chlorophyll-enriched fraction of <i>V. leptobotrys</i>, containing pheophorbide <i>a</i>, was found to inhibit the replication of HIV-1 by 80% at a concentration of 10 μg/mL. Compounds <b>1</b> and <b>3</b> were further selected to be evaluated against 21 viral targets available at NIAID (National Institute of Allergy and Infectious Diseases, National Institutes of Health, Bethesda, MD, USA)

Integrative Profiling of T790M-Negative EGFR-Mutated NSCLC Reveals Pervasive Lineage Transition and Therapeutic Opportunities

Purpose: Despite the established role of EGFR tyrosine kinase inhibitors (TKIs) in EGFR-mutated NSCLC, drug resistance inevitably ensues, with a paucity of treatment options especially in EGFRT790M-negative resistance. Experimental Design: We performed whole-exome and transcriptome analysis of 59 patients with first- and second-generation EGFR TKI-resistant metastatic EGFR-mutated NSCLC to characterize and compare molecular alterations mediating resistance in T790M-positive (T790M(+)) and -negative (T790M(-)) disease. Results: Transcriptomic analysis revealed ubiquitous loss of adenocarcinoma lineage gene expression in T790M(-) tumors, orthogonally validated using multiplex IHC. There was enrichment of genomic features such as TP53 alterations, 3q chromosomal amplifications, whole-genome doubling and nonaging mutational signatures in T790M(-) tumors. Almost half of resistant tumors were further classified as immune(hot), with clinical outcomes conditional on immune cell-infiltration state and T790M status. Finally, using a Bayesian statistical approach, we explored how T790M(-) and T790M(+) disease might be predicted using comprehensive genomic and transcriptomic profiles of treatment-naive patients. Conclusions: Our results illustrate the interplay between genetic alterations, cell lineage plasticity, and immune microenvironment in shaping divergent TKI resistance and outcome trajectories in EGFR-mutated NSCLC. Genomic and transcriptomic profiling may facilitate the design of bespoke therapeutic approaches tailored to a tumor's adaptive potential