The overprescribing and misuse of antibiotics have led to the rapid development of multidrug-resistant bacteria, such as those that cause UTIs. UTIs are the most common outpatient infections and are mainly caused by Escherichia coli and Klebsiella spp., although some Gram-positive bacteria, such as Pseudomonas aeruginosa, have been isolated in many cases. The rise of antimicrobial-resistant bacteria is a major public health concern, as it is predicted to lead to increased healthcare costs and poor patient outcomes and is expected to be the leading cause of global mortality by 2050. Antibiotic resistance among bacterial species can arise from a myriad of factors, including intrinsic and acquired resistance mechanisms, as well as mobile genetic elements, such as transposons, integrons, and plasmids. Plasmid-mediated resistance is of major concern as drug-resistance genes can quickly and efficiently spread across bacterial species via horizontal gene transfer. The emergence of extended-spectrum β-lactamases (ESBLs) such as NDM-1, OXA, KPC, and CTX-M family members has conferred resistance to many commonly used antibiotics in the treatment of UTIs, including penicillins, carbapenems, cephalosporins, and sulfamethoxazole. This review will focus on plasmid-mediated bacterial genes, especially those that encode ESBLs, and how they contribute to antibiotic resistance. Early clinical detection of these genes in patient samples will provide better treatment options and reduce the threat of antibiotic resistance.

This critical review investigates the impact of SWI/SNF-related, matrix-associated, actin-dependent regulator of chromatin, subfamily A, member 4 (SMARCA4) mutations on survival outcomes in non-small cell lung cancer (NSCLC) through an analysis of 21 peer-reviewed articles. Survival analyses across this review demonstrated consistently worse outcomes for SMARCA4-mutated vs. SMARCA4 wild-type NSCLC patients, specifically emphasizing class 1 truncating mutations as an independent factor for poor overall survival. In addition, this review explores the clinicopathologic characteristics of SMARCA4 mutations and their impact on various treatment modalities, including immune checkpoint inhibitors (ICIs) both with and without Kirsten rat sarcoma viral oncogene homolog (KRAS) co-mutations. The potential ineffectiveness of ICI treatment in NSCLC is explored through the impact of SMARCA4/KRAS co-mutations on the tumor microenvironment. Moreover, this NSCLC review consistently reported statistically worse overall survival outcomes for SMARCA4/KRAS co-mutations than SMARCA4 wild-type/KRAS-mutated cohorts, extending across ICIs, chemo-immunotherapy (CIT), and KRAS G12C inhibitors. Designing prospective clinical SMARCA4-mutated or SMARCA4/KRAS co-mutated NSCLC trials to evaluate targeted therapies and immunotherapy may lead to a better understanding of how to improve cancer patients’ outcomes and survival rates.

Identification of antimicrobial resistance markers in urinary tract infections could provide a more targeted approach in the diagnosis and treatment of UTIs while reducing overall public health burdens. We describe a molecular assay as a diagnostic tool for antibiotic resistance characterization to promote faster diagnosis of antibiotic regimens compared to standard microbiology techniques. Targeted antibiotic usage for pathogenic infections remains a main goal for effective antibiotic treatment protocols and reducing the overall public health burden. Rapid identification of the pathogen(s) causing the infection and harboring the antibiotic resistance gene is also a main area of exploration for antibiotic appropriation and stewardship. Urinary tract infections are a common clinical disease and reservoir for pathogenic infection and the development of antibiotic resistance, especially in hospital- and community-acquired settings. Standard methods require urine culture, which is time consuming and relies on phenotypic characterization. A genetic diagnostic method is warranted for the rapid molecular characterization of antibiotic resistance genes to reduce inappropriate exposure to antibiotics while improving the overall treatment model for urinary tract infections. The purpose of this study is to demonstrate logical viability for real-time molecular diagnostics for early identification, active surveillance and overall targeted antibiotic stratification that is proposed as an in vitro rapid and comprehensive tool for assessing proper antibiotic stewardship in UTIs. Here, we describe a multiplex real-time fluorescence polymerase chain reaction (PCR) for probe-based detection of the top 24 antibiotic resistance genes with targeted relationships to target molecular drug classes and administered antibiotics. Multiplexed analysis based on molecular features enables rapid testing while shifting the diagnostic detection paradigm from monocentric infections towards polymicrobial infections. We utilized 366 samples from the FDA-CDC Antimicrobial Resistance Isolate Bank to test the efficacy of the assay and propose a model to infer the identity of bacterial isolates. We found that, in addition to a high level of accuracy in predicting bacterial genus classification, the assay was mostly in agreement with CDC-tested genotypic and phenotypic results. This study provides evidence for using genetic diagnostic methods, such as multiplex qPCR, in the rapid identification of antibiotic resistance (ABR) genes for the characterization and treatment of urinary tract infections.

Phelan–McDermid syndrome (PMS), caused by pathogenic variants in the SHANK3 gene or 22q13 deletions, is characterized by intellectual disability, autistic features, developmental delays, and neonatal hypotonia. Insulin-like growth factor 1 (IGF-1) and human growth hormone (hGH) have been shown to reverse neurobehavioral deficits in PMS. We assessed the metabolic profiling of 48 individuals with PMS and 50 controls and determined subpopulations by taking the top and bottom 25% of responders to hGH and IGF-1. A distinct metabolic profile for individuals with PMS showed a reduced ability to metabolize major energy sources and a higher metabolism of alternative energy sources. The analysis of the metabolic response to hGH or IGF-1 highlighted a major overlap between both high and low responders, validating the model and suggesting that the two growth factors share many target pathways. When we investigated the effect of hGH and IGF-1 on the metabolism of glucose, the correlation between the high-responder subgroups showed less similarity, whereas the low-responders were still relatively similar. Classification of individuals with PMS into subgroups based on responses to a compound can allow an investigation into pathogenic mechanisms, the identification of molecular biomarkers, an exploration of in vitro responses to candidate drugs, and eventually the selection of better candidates for clinical trials.

Background/Objectives: Breast cancer is the most common cause of death in women worldwide and the most commonly diagnosed cancer. Although several therapeutic approaches are widely used against breast cancer, their adverse effects often lead to symptoms severely affecting the quality of life. Alternative methods have been explored to reduce these adverse effects, and nutraceuticals have yielded promising results. This review will discuss mechanisms of action and potential applications against breast cancer of some nutraceuticals, specifically marjoram, thyme, and persimmon leaves. Methods: A systematic search was conducted across the public databases of PubMed, PubChem, and Google Scholar, with a specific focus on the plant extracts and phytochemicals of interest, as well as the anticarcinogenic mechanisms. Results: Ethnopharmacological and biochemical evidence support the anticarcinogenic role of marjoram, thyme, and persimmon. Numerous phytochemicals contained in these herbs’ extracts, like terpenes and flavonoids, possess remarkable potential to effectively treat breast cancer. Discussion: The phytochemicals contained in the reviewed nutraceuticals target the main cellular pathways involved in cell growth and disrupted in carcinogenesis, such as Nf-κB, MAPK/p38, TNF-α/IL-1β, and PI3K/Akt. The mechanisms of action of these compounds can successfully limit the abnormal growth and proliferation of cancerous breast cells. Conclusions: The potential use of the phytochemicals discussed in this review, either alone or in combination, may offer a valid alternative to chemotherapy against breast cancer with virtually no adverse effects, and further research on these molecules may lead to the identification of additional chemo-preventative and chemotherapeutic candidates.

Background/Objectives: Breast cancer is a prevalent and heterogeneous disease with multiple subtypes, which are defined by characteristics such as molecular biomarkers and metastatic status. This study aimed to profile the metabolic activity of various breast cancer subtypes, both with and without chemotherapy (doxorubicin) application. Methods: Six human breast cell lines were evaluated, two non-tumorigenic controls and four cancerous lines. The cancer lines were clustered as primary-derived, metastasis-derived, triple-negative (TNBC), and strong hormone receptor-positive (ER+/PR+) and analyzed using the Biolog phenotype mammalian microarrays (PM-M1 to PM-M8) to assess metabolic activity via NADH production under a wide array of substrate parameters. Results: Unique metabolic profiles emerged across the subtypes and clusters; the TNBC and metastatic cells demonstrated enhanced utilization of glycolytic and anaerobic substrates consistent with the Warburg effect. The ER+/PR+ cells showed heightened glucose utilization and unique sensitivity to metabolic effectors and doxorubicin. Additionally, significant metabolic differences were observed in nucleoside and amino acid utilization between cancer and control cells, particularly in metastatic and TNBC lines. Conclusions: Our findings reveal the profound metabolic diversity among breast cancer subtypes and highlight distinct substrate dependencies for proliferation. The results additionally provide a framework for developing metabolic biomarkers and targeted therapies for chemotherapy resistance in breast cancer subtypes.