Discovery of New 4-Indolyl Quinazoline Derivatives as Highly Potent and Orally Bioavailable P-Glycoprotein Inhibitors

The major drawbacks of P-glycoprotein (P-gp) inhibitors at the clinical stage make the development of new P-gp inhibitors challenging and desirable. In this study, we reported our structure-activity relationship studies of 4-indolyl quinazoline, which led to the discovery of a highly effective and orally active P-gp inhibitor, YS-370. YS-370 effectively reversed multidrug resistance (MDR) to paclitaxel and colchicine in SW620/AD300 and HEK293T-ABCB1 cells. YS-370 bound directly to P-gp, did not…

Detection of extensively drug-resistant and hypervirulent Klebsiella pneumoniae ST15, ST147, ST377 and ST442 in Iran

In this study, we focused on the emergence of extensively drug-resistant (XDR), pandrug-resistant (PDR), and hypervirulent Klebsiella pneumoniae (hvKP) in Iran. During 2018 to 2020 a total of 52 K. pneumoniae isolates were collected from different clinical specimens. The hvKP isolates were identified by PCR amplification of virulence and capsular serotype-specific genes. Hypermucoviscous K. pneumoniae (hmKP) were identified by string test. Carbapenem-resistant hvKP (CR-hvKP), multidrug-resistant…

Cudraflavone C from <em>Artocarpus hirsutus</em> as a Promising Inhibitor of Pathogenic, Multidrug-Resistant <em>S. aureus</em>, Persisters, and Biofilms: A New Insight into a Rational Explanation of Traditional Wisdom

Artocarpus hirsutus Lam., or wild jack, a perennial tree of the Western Ghats of peninsular India, serves as a rich source of flavonoids. The indigenous knowledge of this multipurpose flora chronicles the efficient property of its bark as a natural treatment for various skin infections. Herein, we describe a rational explanation of this traditional knowledge via a broader evaluation of inhibitory activity of one of its phytoconstituents, cudraflavone C (Cud C), a prenyl flavone isolated from…

Preclinical Evaluation of Inhalational Spectinamide-1599 Therapy against Tuberculosis

The lengthy treatment time for tuberculosis (TB) is a primary cause for the emergence of multidrug resistant tuberculosis (MDR-TB). One approach to improve TB therapy is to develop an inhalational TB therapy that when administered in combination with oral TB drugs eases and shortens treatment. Spectinamides are new semisynthetic analogues of spectinomycin with excellent activity against Mycobacterium tuberculosis (Mtb), including MDR and XDR Mtb strains. Spectinamide-1599 was chosen as a…

Occurrence, Antibiotic Resistance, Virulence Factors, and Genetic Diversity of <em>Bacillus</em> spp. from Public Hospital Environments in South Africa

This study aimed to assess the molecular dissemination of Bacillus species in public hospitals in South Africa. The study conducted over 3 months during 2017 involved representative samples obtained from three wards (general ward, intensive care unit, and pediatric unit) from four public hospitals denoted as A (Central), B (Tertiary), C (Regional), and D (District). Swabs collected from 11 distinct hospital surfaces were screened using selective media, biochemical testing, and molecular methods….

Non-Operative Management of Appendicitis: Evolution, not Revolution

Background: The medical fascination with the appendix vermiformis dates from the clandestine prosectors of the fifteenth century. The surgical management of appendiceal inflammation dates from 1735, but acceptance that acute appendicitis (AA) should be treated primarily by resection with or without drainage would not follow for 150 years. Recent publication of several randomized clinical trials (RCTs) of non-operative management (NOM) of AA affords the opportunity to review the historical…

Non-Operative Management of Appendicitis: Evolution, not Revolution

Background: The medical fascination with the appendix vermiformis dates from the clandestine prosectors of the fifteenth century. The surgical management of appendiceal inflammation dates from 1735, but acceptance that acute appendicitis (AA) should be treated primarily by resection with or without drainage would not follow for 150 years. Recent publication of several randomized clinical trials (RCTs) of non-operative management (NOM) of AA affords the opportunity to review the historical…

Prospects for using low-dose radiation in the complex therapy for COVID-19

This review presents the literature data of new approaches for the treatment of COVID-19 with low doses of radiation (LDR). In addition, data on the use of LDR for the treatment of various disorders, in particular pneumonia, a number of inflammatory processes of various etiology, as well as Alzheimer’s disease are discussed. The mechanisms of LDR action are briefly described, associated with the activation of the immune system and antiinflammatory response due to the effect on the processes of…