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marzo 29, 2021, Page 2

Clinical Relevance of Gain- and Loss-of-Function Germline Mutations in STAT1: A Systematic Review

Background: Germline mutations in signal transducer and activator of transcription 1 (STAT1), which lead to primary immunodeficiency, are classified as defects in intrinsic and innate immunity. To date, no comprehensive overview comparing GOF with LOF in early-onset immunodeficiency has been compiled. Objective: To collect and systematically review all studies reporting STAT1 GOF and LOF cases, and to describe the clinical, diagnostic, molecular, and therapeutic characteristics of all the…

Unique para-aminobenzenesulfonyl oxadiazoles as novel structural potential membrane active antibacterial agents towards drug-resistant methicillin resistant Staphylococcus aureus

A class of structurally unique para-aminobenzenesulfonyl oxadiazoles as new potential antimicrobial agents was designed and synthesized from acetanilide. Some target para-aminobenzenesulfonyl oxadiazoles showed antibacterial potency. Noticeably, hexyl derivative8b (MIC = 1 μg/mL) was more active than norfloxacin against drug resistant MRSA. Compound8bwas able to disturb the membrane effectively and intercalate into deoxyribonucleic acid (DNA) to form a steady8b-DNA complex, which might be…

Sublancin protects against methicillin-resistant Staphylococcus aureus infection by the combined modulation of innate immune response and microbiota

Methicillin-resistant Staphylococcus aureus (MRSA) is a major pathogen responsible for community and hospital bacterial infections. In the present study, the protective role of sublancin, an antimicrobial peptides, was explored in MRSA infection model. We report that sublancin directly induce macrophage migration through the chemotactic receptors. We further show that sublancin exhibits protection in a mouse MRSA infection model. This protection involved an immunomodulatory activity, but was…

PRIMER FOR DEVELOPMENT OF GUIDELINES FOR HELICOBACTER PYLORI THERAPY USING ANTIBIOTIC STEWARDSHIP

We provide a primer to assist in the difficult transition of Helicobacter pylori therapy guidelines to those that adhere to the principles of antimicrobial stewardship. This transition will entail abandonment of many of the principles that heretofore formed the basis of treatment guidelines and recommendations. The goals of antimicrobial stewardship include optimization of the use of antibiotics while reducing antimicrobial resistance. The critical outcome measure is absolute cure rate which…

Molecular analysis of clinical isolates of ceftazidime-avibactam-resistant Klebsiella pneumoniae

CONCLUSIONS: Different mutations including single amino-acid substitutions, insertions or deletions within the bla(KPC) gene were found in 26/31 CZA -resistant KPC-Kp strains belonging to high-risk clones circulating in Italy. Of note, in 14/31 cases the isolates displayed resistance to both CZA and carbapenems, raising the alarm for the possible selection of a multi-drug-resistant phenotype.

Chloroquine and hydroxychloroquine in antitumor therapies based on related-autophagy mechanisms

Chloroquine (CQ) and hydroxychloroquine (HCQ) are the most common drugs used to relieve acute and chronic inflammatory diseases, In this article, we present a review about the use of CQ and HCQ in antitumor therapies based on related-autophagy mechanisms. These molecules break/discontinue autophagosome-lysosome fusions in initial phases and enhance antiproliferative action of chemotherapeutics. Their sensitizing effects of chemotherapy when used as an adjuvant option in clinical trials against…

Nuclear factor-κB signaling inhibitors revert multidrug-resistance in breast cancer cells

The emergence of multidrug resistance (MDR) is among the crucial obstacles to breast cancer therapy success. The transcription factor nuclear factor (NF)-κB is correlated in the pathogenesis of breast cancer and resistance to therapy. NF-κB augments the expression of MDR1 gene, which encodes for the membrane transporter P-glycoprotein (P-gp) in cancer cells. Since NF-κB activity is considered to be relatively high in particular when it comes to breast cancer, in the present work, we proposed…

Extracellular Vesicles in Chemoresistance

Chemotherapy represents the current mainstay therapeutic approach for most types of cancer. Despite the development of targeted chemotherapeutic strategies, the efficacy of anti-cancer drugs is severely limited by the development of drug resistance. Multidrug resistance (MDR) consists of the simultaneous resistance to various unrelated cytotoxic drugs and is one of the main causes of anticancer treatment failure. One of the principal mechanisms by which cancer cells become MDR involves the…

Understanding the binding conformation of ceftolozane/tazobactam with Metallo-beta-lactamases VIM-5 and IMP-7 of Pseudomonas aeruginosa: A molecular docking and virtual screening process

Pseudomonas aeruginosa (P. aeruginosa) is one of the community-acquired and healthcare-associated infections causing organisms. It has become resistant to most of the available antibiotics and is termed multi-drug resistance (MDR). There are a limited number of antibiotics are available to treat such MDR organism causing infections. The ceftolozane/tazobactam is one among the combination drug therapy (CDT) prescribed for the treatment of MDR causing infections. The resistance for the same CDT…