Isatin-indoloquinoxaline click adducts with a potential to overcome platinum-based drug-resistance in ovarian cancer.

Herein, a series of isatin tethered indolo[2,3-b]quinoxaline hybrids was synthesized by considering the pharmacophoric features of known DNA intercalators and topoisomerase II inhibitors. The anti-proliferative properties of the synthesized compounds were evaluated against ovarian cancer cell lines (SKOV-3 and Hey A8). Four of the compounds exhibited promising anti-proliferative activities, with one of them being 10-fold more potent than cisplatin against drug-resistant Hey A8 cells.

mutations are associated with a response to alvocidib and 5-azacytidine combination in myelodysplastic neoplasms.

Inhibitors of anti-apoptotic BCL-2 family proteins in combination with chemotherapy and hypomethylating agents (HMA) are promising therapeutic approaches in acute myeloid leukemia (AML) and high-risk myelodysplastic syndromes (MDS). Alvocidib, a cyclin-dependent kinase 9 (CDK9) inhibitor and indirect transcriptional repressor of the anti-apoptotic factor MCL-1, has previously shown clinical activity in AML. Availability of biomarkers for response to the alvocidib + 5-azacytidine (5-AZA) could also extend the rationale of this treatment concept to high-risk MDS.

Novel echocardiographic markers for left ventricular filling pressure prediction in heart failure with preserved ejection fraction (ECHO-PREDICT): a prospective cross-sectional study.

Heart failure with preserved ejection fraction is a complex clinical syndrome associated with a high level of morbidity and mortality, constituting 56% of heart failure cases and showing an increasing prevalence. The E/Ea ratio, used for echocardiographic assessment of left ventricular (LV) filling pressure, has been commonly recommended as a noninvasive measure. However, its validity lacks robust prospective validation in patients with preserved LV ejection fraction, and its accuracy has been questioned in comparison to patients with reduced LV ejection fraction.

AIPs-SnTCN: Predicting Anti-Inflammatory Peptides Using fastText and Transformer Encoder-Based Hybrid Word Embedding with Self-Normalized Temporal Convolutional Networks.

Inflammation is a biologically resistant response to harmful stimuli, such as infection, damaged cells, toxic chemicals, or tissue injuries. Its purpose is to eradicate pathogenic micro-organisms or irritants and facilitate tissue repair. Prolonged inflammation can result in chronic inflammatory diseases.

Comparative Analysis of the GNAI Family Genes in Glioblastoma through Transcriptomics and Single-Cell Technologies.

Glioblastoma multiforme (GBM) is one of the most aggressive cancers with a low overall survival rate. The treatment of GBM is challenging due to the presence of the blood-brain barrier (BBB), which hinders drug delivery. Invasive procedures alone are not effective at completely removing such tumors.

Prophylactic Use Of Levofloxacin During Induction Of Acute Lymphoblastic Leukaemia In Children-Experience From Pakistan.

To assess whether prophylactic use of Levofloxacin would reduce the number of febrile neutropenia episodes during the induction phase, a single-centre, case-control study was carried out. Data was collected prospectively of patients who received Levofloxacin prophylaxis during the induction chemotherapy from September 2019 till October 2020. The cases were compared with historical controls who did not receive antibiotics prophylaxis.

Polymersome Membrane Engineering with Active Targeting or Controlled Permeability for Responsive Drug Delivery.

Polymersomes have been extensively investigated for drug delivery as nanocarriers for two decades due to a series of advantages including high stability under physiological conditions, simultaneous encapsulation of hydrophilic and hydrophobic drugs inside inner cavities and membranes, respectively, and facile adjustment of membrane and surface properties, as well as controlled drug release through incorporation of stimuli-responsive components. Despite these features, polymersome nanocarriers frequently suffer from nontargeting delivery and poor membrane permeability. In recent years, polymersomes have been functionalized for more efficient drug delivery.

Is Greenfield investment improving welfare: A quantitative analysis for Latin American and Caribbean developing countries.

Greenfield investment is considered the backbone of emerging economies and developing countries. This research is carried out to investigate the causal impact of Greenfield investment as a target variable and some other controlled variables for the sample of 23 Latin American and Caribbean (LA&C) developing countries. The period is 1998-2017, and Levin, Lin and Chu (LLC) and System-Generalized Method of Moment (Sys-GMM) techniques are employed for analytical analysis.

Chromosome-level genome assembly and population genomic analysis provide novel insights into the immunity and evolution of Sogatella furcifera.

Sogatella furcifera is a destructive agricultural pest causing large threats to rice production in China and Southeast Asian countries. Despite recent breakthroughs in long-read sequencing, high quality genomic data are very limited in S. furcifera.

Corrigendum: Curcumin-mediated degradation of S-phase kinase protein 2 induces cytotoxic effects in human papillomavirus-positive and negative squamous carcinoma cells.

[This corrects the article DOI: 10.3389/fonc.2018.

Natural Alternatives to Non-biodegradable Polymers in 3D Printing of Pharmaceuticals.

Background: Due to potential toxicity, non-biodegradable polymers used in 3D (3-dimensional) printing of drugs could be dangerous for patient safety and the environment.

Objective: This review aims to investigate the toxicity of non-biodegradable polymers and investigate the use of natural materials as an alternative in 3D printing medicines. The study evaluates the dangers connected to 3D printing.

Credentials That Matter While Selecting a Surgeon for Major Surgical Treatment.

Purpose: The credentials of surgeons, which include elements such as medical degree and length of practice, are vital information that forms a perception of their expertise in the patients' minds. The specific credentials that matter to patients and how important they are have not been sufficiently studied. The objective of this study was to assess the relative importance that patients assign to the specific credentials of a surgeon while selecting one for surgical treatment.

Unveiling the obstacles encountered by women doctors in the Pakistani healthcare system: A qualitative investigation.

In Pakistan, women outnumber men in medical colleges with 80 percent enrollment, yet many fail to practice medicine following graduation. Pakistan Medical Council (PMC) states 50 percent of graduated women doctors either did not practice or left employment in a short period. Thus, the non-servicing women doctors are assumed as the one of the major causes for the overall doctors' shortage in the country.

Organic amendment-mediated reclamation and build-up of soil microbial diversity in salt-affected soils: fostering soil biota for shaping rhizosphere to enhance soil health and crop productivity.

Soil salinization is a serious environmental problem that affects agricultural productivity and sustainability worldwide. Organic amendments have been considered a practical approach for reclaiming salt-affected soils. In addition to improving soil physical and chemical properties, organic amendments have been found to promote the build-up of new halotolerant bacterial species and microbial diversity, which plays a critical role in maintaining soil health, carbon dynamics, crop productivity, and ecosystem functioning.

Multifaceted role of mTOR (mammalian target of rapamycin) signaling pathway in human health and disease.

The mammalian target of rapamycin (mTOR) is a protein kinase that controls cellular metabolism, catabolism, immune responses, autophagy, survival, proliferation, and migration, to maintain cellular homeostasis. The mTOR signaling cascade consists of two distinct multi-subunit complexes named mTOR complex 1/2 (mTORC1/2). mTOR catalyzes the phosphorylation of several critical proteins like AKT, protein kinase C, insulin growth factor receptor (IGF-1R), 4E binding protein 1 (4E-BP1), ribosomal protein S6 kinase (S6K), transcription factor EB (TFEB), sterol-responsive element-binding proteins (SREBPs), Lipin-1, and Unc-51-like autophagy-activating kinases.

A systematic review of quantitative studies exploring staff views on antipsychotic use in residents with dementia in care homes.

Background: Despite significant warnings of adverse effects, antipsychotics continue to be prescribed for managing the behavioural and psychological symptoms of dementia (BPSD) in care homes. Information provided by staff working within care homes is a factor that can influence prescribing decisions in residents with BPSD.

Aim: The review aimed to capture care home staff views towards antipsychotics for residents with BPSD and separately analyse tools utilized in the studies, mapping them onto the theory of planned behaviour (TPB).

Stereo/regio-selective access to substituted 3-hydroxy-oxindoles with anti-proliferative assessment and validation.

The manuscript focuses on a highly stereo-/regioselective approach for synthesizing a diverse array of substituted-3-hydroxy-2-oxindoles. The synthesized compounds were subsequently subjected to anti-proliferative assessment against various cell lines, including colorectal carcinoma, ovarian cancer, and human metastatic melanoma cancer. The structural characterization of the synthesized scaffolds was unambiguously confirmed using X-ray diffraction analysis.

Site-Directed Mutations at Phosphorylation Sites in PHO1 Reveal Modulation of Enzymatic Activity by Phosphorylation at S566 in the L80 Region.

Starch phosphorylase (PHO) is a pivotal enzyme within the GT35-glycogen-phosphorylase (GT; glycosyltransferases) superfamily. Despite the ongoing debate surrounding the precise role of PHO1, evidence points to its substantial influence on starch biosynthesis, supported by its gene expression profile and subcellular localization. Key to PHO1 function is the enzymatic regulation via phosphorylation; a myriad of such modification sites has been unveiled in model crops.

Enhanced Antidepressant Activity of Nanostructured Lipid Carriers Containing Levosulpiride in Behavioral Despair Tests in Mice.

The potential of levosulpiride-loaded nanostructured lipid carriers (LSP-NLCs) for enhanced antidepressant and anxiolytic effects was evaluated in the current study. A forced swim test (FST) and tail suspension test (TST) were carried out to determine the antidepressant effect whereas anxiolytic activity was investigated using light-dark box and open field tests. Behavioral changes were evaluated in lipopolysaccharide-induced depressed animals.

First Generation of Antioxidant Precursors for Bioisosteric Se-NSAIDs: Design, Synthesis, and In Vitro and In Vivo Anticancer Evaluation.

The introduction of selenium (Se) into organic scaffolds has been demonstrated to be a promising framework in the field of medicinal chemistry. A novel design of nonsteroidal anti-inflammatory drug (NSAID) derivatives based on a bioisosteric replacement via the incorporation of Se as diacyl diselenide is reported. The antioxidant activity was assessed using the DPPH radical scavenging assay.

A Case of Locally Advanced Fibrosarcoma in a Young Male.

Fibrosarcoma is a rare, highly malignant tumor that develops from uncontrolled overgrowth of fibroblastic cells. It may start as a painless lump or swelling under the skin. But as it grows, it can push surrounding structures - organs, muscles, nerves, or blood vessels - and lead to pain and tenderness.

Indicators for cochlear implantation in children with auditory neuropathy spectrum disorder: A systematic review.

Purpose: ANSD refers to a group of auditory diseases demonstrating intact outer hair cells and desynchronized neural firings of the auditory nerve. A cochlear implant is a promising intervention strategy for severe to profound sensorineural hearing loss (SNHL). However, due to its variable outcomes in children with ANSD, a consensus has yet to be reached on its performance.

Evolution of human kidney allograft pathology diagnostics through 30 years of the Banff classification process.

The second half of the previous century witnessed a tremendous rise in the number of clinical kidney transplants worldwide. This activity was, however, accompanied by many issues and challenges. An accurate diagnosis and appropriate management of causes of graft dysfunction were and still are, a big challenge.

A reliable numerical investigation of an SEIR model of measles disease dynamics with fuzzy criteria.

The terms susceptibility, exposure, infectiousness, and recovered all have some inherent ambiguity because different population members have different susceptibility levels, exposure levels, infectiousness levels, and recovery patterns. This uncertainty becomes more pronounced when examining population subgroups characterized by distinct behaviors, cultural norms, and varying degrees of resilience across different age brackets, thereby introducing the possibility of fluctuations. There is a need for more accurate models that take into account the various levels of susceptibility, exposure, infectiousness, and recovery of the individuals.