Restoring cefepime activity against multidrug-resistant KPC-producing by combination with boronic acid inhibitors, MB076 and S02030.

Foremost in the design of new β-lactamase inhibitors (BLIs) are the boronic acid transition state inhibitors (BATSIs). Two highly potent BATSIs being developed are S02030 and MB076 strategically designed to be active against cephalosporinases and carbapenemases, especially KPC. When combined with cefepime, S02030 and MB076 demonstrated potent antimicrobial activity against laboratory and clinical strains of expressing a variety of class A and class C β-lactamases, including and .

Insulinotropic and anti-obesity properties of ethno-medicinal plants: pharmacology-based and predictions.

The herbal extracts of four traditional plants; namely leaves, fruits leaves, and seeds, were identified for their main constituents using UHPLC/QTOF-MS/MS. Then, a pharmacology-based analysis and molecular docking verification were established targeting the evaluation of each individual herbal extract for their antidiabetic/anti-obesity potential besides their safety. Streptozotocin-induced diabetic rats were used to evaluate antiobesity and insulinotropic effects against insulin (10 U/Kg, IP) and metformin (100 mg/Kg, per oral) as standard regimens.

Respiratory complex I-mediated NAD regeneration regulates cancer cell proliferation through the transcriptional and translational control of p21 expression by SIRT3 and SIRT7.

The role of the electron transport chain (ETC) in cell proliferation control beyond its crucial function in supporting ATP generation has recently emerged. In this study, we found that, among the four ETC complexes, the complex I (CI)-mediated NAD regeneration is important for cancer cell proliferation. In cancer cells, a decrease in CI activity by RNA interference (RNAi) against NADH:ubiquinone oxidoreductase core subunit V1 (NDUFV1) arrested the cell cycle at the G/S phase, accompanying upregulation of p21 cyclin-dependent kinase inhibitor expression.

Fluorescent nucleobase analogue for cellular visualisation and regulation of immunostimulatory CpG oligodeoxynucleotides.

In this study, we explored the chemical modification of toll-like receptor 9 (TLR9) agonist DNA using a highly fluorescent thymine analogue, ThexT, focusing on its structural and photophysical characteristics. ThexT-labelled CpG oligonucleotides effectively demonstrated intracellular localisation within macrophage cell lines. Notably, immunostimulatory activity varied depending on the site of ThexT incorporation within the TLR9 agonist sequence.

Delving Into lncRNA-Mediated Regulation of Autophagy-Associated Signaling Pathways in the Context of Breast Cancer.

Breast cancer is a multifaceted and prevalent malignancy, impacting a considerable proportion of women globally. Numerous signaling pathways intricately regulate cellular functions such as growth, proliferation, and survival. Among the various regulators, lncRNAs have emerged as significant players despite their inability to encode proteins.

Pharmacophore-based virtual screening of the chromone derivatives as potential therapeutic for Alzheimer's disease.

Alzheimer's disease is one of the most complex neurological disorders and millions of people are suffering from this disease all over the world. In the past two decades acetylcholinesterase (AChE) has been the most explored pathological hallmark. The generation of potent AChE inhibitors has grown as a rapid pathological tool for the efficacious treatment of the disease.

Spatial multi-omics characterizes GPR35-relevant lipid metabolism signatures across liver zonation in MASLD.

Metabolic dysfunction-associated steatotic liver disease (MASLD) is a metabolic disease that can progress to metabolic dysfunction-associated steatohepatitis (MASH), cirrhosis, and cancer. The zonal distribution of biomolecules in the liver is implicated in mediating the disease progression. Recently, G-protein-coupled receptor 35 (GPR35) has been highlighted to play a role in MASLD, but the precise mechanism is not fully understood, particularly, in a liver-zonal manner.

Synergistic inhibition of colorectal cancer progression by silencing Aurora A and the targeting protein for Xklp2.

Background: Unraveling the pathogenesis of colorectal cancer (CRC) can aid in developing prevention and treatment strategies. Aurora kinase A (AURKA) is a key participant in mitotic control and interacts with its co-activator, the targeting protein for Xklp2 (TPX2) microtubule nucleation factor. AURKA is associated with poor clinical outcomes and high risks of CRC recurrence.

Monkey multi-organ cell atlas exposed to estrogen.

Awareness of estrogen's effects on health is broadening rapidly. The effects of long-term high levels of estrogen on the body involve multiple organs. Here, we used both single-cell chromatin accessibility and RNA sequencing data to analyze the potential effect of estrogen on major organs.

The immune landscape of fetal chorionic villous tissue in term placenta.

Introduction: The immune compartment within fetal chorionic villi is comprised of fetal Hofbauer cells (HBC) and invading placenta-associated maternal monocytes and macrophages (PAMM). Recent studies have characterized the transcriptional profile of the first trimester (T1) placenta; however, the phenotypic and functional diversity of chorionic villous immune cells at term (T3) remain poorly understood.

Methods: To address this knowledge gap, immune cells from human chorionic villous tissues obtained from full-term, uncomplicated pregnancies were deeply phenotyped using a combination of flow cytometry, single-cell RNA sequencing (scRNA-seq, CITE-seq) and chromatin accessibility profiling (snATAC-seq).

A biomarker framework for liver aging: the Aging Biomarker Consortium consensus statement.

In human aging, liver aging per se not only increases susceptibility to liver diseases but also increases vulnerability of other organs given its central role in regulating metabolism. Total liver function tends to be well maintained in the healthy elderly, so liver aging is generally difficult to identify early. In response to this critical challenge, the Aging Biomarker Consortium of China has formulated an expert consensus on biomarkers of liver aging by synthesizing the latest scientific literature, comprising insights from both scientists and clinicians.

Biochemical mechanisms and molecular interactions of vitamins in cancer therapy.

Recently, the potential role of vitamins in cancer therapy has attracted considerable research attention. However, the reported findings are inconsistent, with limited information on the biochemical and molecular interactions of different vitamins in various cancer cells. Importantly, the presence of vitamin receptors in tumor cells suggests that vitamins play a significant role in the molecular and biochemical interactions in cancers.

Despicable role of epithelial-mesenchymal transition in breast cancer metastasis: Exhibiting restorative regimens.

Breast cancer (BC) is the most prevalent cancer in women globally. Anti-cancer advancements have enabled the killing of BC cells through various therapies; however, cancer relapse is still a major limitation and decreases patient survival and quality of life. Epithelial-to-mesenchymal transition (EMT) is responsible for tumor relapse in several cancers.

Loss of phosphatase and tensin homolog () increases Lysyl oxidase-like 2 () expression enhancing the growth of fallopian tube epithelial cells as three-dimensional spheroids.

Background: High-grade serous ovarian cancer (HGSOC) accounts for 70-80% of all ovarian cancer-related deaths. Multiple studies have suggested that the fallopian tube epithelium (FTE) serves as the cell of origin of HGSOC. Phosphatase and tensin homolog () is a tumor suppressor and its loss is sufficient to induce numerous tumorigenic changes in FTE, including increased migration, formation of multicellular tumor spheroids (MTSs), and ovarian colonization.

DDO1002, an NRF2-KEAP1 inhibitor, improves hematopoietic stem cell aging and stress response.

Oxidative stress diminishes the functionality of hematopoietic stem cells (HSCs) as age advances, with heightened reactive oxygen species (ROS) levels exacerbating DNA damage, cellular senescence, and hematopoietic impairment. DDO1002, a potent inhibitor of the NRF2-KEAP1 pathway, modulates the expression of antioxidant genes. Yet, the extent to which it mitigates hematopoietic decline post-total body irradiation (TBI) or in the context of aging remains to be elucidated.

Danshen injection ameliorates unilateral ureteral obstruction-induced renal fibrosis by inhibiting ferroptosis via activating SIRT1/GPX4 pathway.

Introduction: The pathogenesis of renal fibrosis is related to blood stasis, and the method of promoting blood circulation and removing blood stasis is often used as the treatment principle. Danshen injection (DSI) is a commonly used drug for promoting blood circulation and removing blood stasis in clinic. However, whether DSI slows the progression of renal fibrosis or the potential mechanism is uncertain.

Recent advances in the role of neuroregulation in skin wound healing.

Neuroregulation during skin wound healing involves complex interactions between the nervous system and intricate tissue repair processes. The skin, the largest organ, depends on a complex system of nerves to manage responses to injury. Recent research has emphasized the crucial role of neuroregulation in maximizing wound healing outcomes.

One-pot reaction of 3-vinylchromones, aromatic aldehydes, and ammonium acetate: an efficient approach to highly functionalized 1,6-dihydropyridine derivatives.

In this work, we present an efficient strategy for the straightforward synthesis of functionalized 1,6-dihydropyridine derivatives a three-component reaction of 3-vinylchromones, aromatic aldehydes, and ammonium acetate. A tandem procedure including NH aldimine formation/Michael-type addition/opening of the pyrone ring/isomerization/6π-electrocyclization/[1,5]-H shift allows rapid access to a series of dihydropyridines bearing an -hydroxybenzoyl and a benzoyl scaffold in good yields. Readily available precursors, simple heating conditions, and operational simplicity are some highlighted advantages of this transformation.

Correction: Design, synthesis, and studies of new quinazolinones tagged thiophene, thienopyrimidine, and thienopyridine scaffolds as antiproliferative agents with potential p38α MAPK kinase inhibitory effects.

[This corrects the article DOI: 10.1039/D4RA06744D.].

Hotspots and trends in stem cell therapy for liver fibrosis and cirrhosis: A bibliometric analysis.

Background: Liver fibrosis and cirrhosis are global medical challenges that require safe and effective treatments. In the past two decades, there has been a surge in research on stem cell therapy for liver fibrosis and cirrhosis. This study aimed to conduct a comprehensive analysis of the research hotspots and trends in this field through bibliometrics.

Integrating Machine Learning and Pharmacophore Features for Enhanced Prediction of H1 Receptor Blockers.

Introduction: Histamine Type I Receptor Antagonists (H1 blockers) are widely used to mitigate histamine-induced inflammation, particularly in allergic reactions. Histamine, a biogenic amine found in endothelial cells, vascular smooth muscle, bronchial smooth muscle, and the hypothalamus, is a key player in these responses. H1 blockers are essential in cough syrups and flu medications and are divided into two generations: first-generation H1 blockers, which are sedating and have numerous side effects, and second-generation blockers, which are non-sedating and generally less toxic but may still exhibit cross-reactivity with other receptors.

Natural Anticancer Drugs: Efficacy, Safety, and Future Challenges.

The investigation of naturally derived anticancer drugs has gained prominence in cancer therapy research. Within a broad context, this review seeks to elucidate the molecular foundations and diverse mechanisms underlying these compounds to understand their pivotal role in advancing effective interventions. Additionally by employing a systematic approach, this study examined the interplay between cellular components, signaling pathways, and genetic factors, providing valuable insights into the regulatory networks governing the efficacy of these drugs.

Synergizing CRISPR-Cas9 with Advanced Artificial Intelligence and Machine Learning for Precision Drug Delivery: Technological Nexus and Regulatory Insights.

The evolution of genetic exploration tools, from laborious methods like radiationinduced mutations to the transformative CRISPR-Cas9 system, has fundamentally reshaped genetic research and gene editing capabilities. This journey, initiated by foundational techniques such as ZFNs and TALENs and culminating in the groundbreaking work of Doudna and Charpentier in 2012, has ushered in an era of precise DNA alteration and profound insights into gene functions. The CRISPR/Cas9 system uses the Cas9 enzyme and guides RNA (gRNA) to precisely target and cleave DNA, with subsequent repair via error-prone NHEJ or precise HDR, enabling versatile gene editing.

Pattern of antibiotic dispensing at pharmacies according to access, watch, reserve (AWaRe) classification: multicenter study after COVID-19 waves in different districts of Pakistan.

Objective: The dispensing of non-prescription antibiotics is a worldwide concern, and antibiotics should only be dispensed with a legitimate prescription.

Methodology: A cross-sectional study was conducted using the simulated client methodology, with data collected, recorded, and analyzed using SPSS.

Results: The simulated client visited 210 pharmacies, of which 70 dispensed antibiotics without a prescription.