Transcriptional and Metabolic Changes Following Repeated Fasting and Refeeding of Adipose Stem Cells Highlight Adipose Tissue Resilience.

Background: Obesity and related metabolic disorders have reached epidemic levels, calling for diverse therapeutic strategies. Altering nutrient intake, timing and quantity by intermittent fasting seems to elicit beneficial health effects by modulating endocrine and cell signaling networks. This study explores the impact of cyclic nutrient availability in the form of every-other-day fasting (EODF) on human adipose stem cells (ASCs).

Management of Ventilator-Associated Pneumonia Caused by and Organisms in a Pediatric Center: A Randomized Controlled Study.

A dangerous infection contracted in hospitals, ventilator-associated pneumonia is frequently caused by bacteria that are resistant to several drugs. It is one of the main reasons why patients in intensive care units become ill or die. This research aimed to determine the most effective empirical therapy of antibiotics for better ventilator-associated pneumonia control and to improve patient outcomes by using the minimal inhibitory concentration method and the Ameri-Ziaei double antibiotic synergism test and by observing the clinical responses to both single and combination therapies.

Need for and update on clinical trials for uncomplicated type B aortic dissection.

The mainstay of management for uncomplicated type B aortic dissection is currently optimal medical therapy, targeting blood pressure and heart rate, along with serial imaging. There is a paucity of data that informs whether early intervention with thoracic endografting in this group of patients will promote aortic remodeling and better long-term outcomes. Investigations to date, including the Investigation of Stent Grafts in Aortic Dissection (INSTEAD), INSTEAD-XL, and Acute Dissection: Stent Graft or Best Medical Therapy (ADSORB) studies, have compared thoracic endovascular aortic repair (TEVAR) with optimal medical therapy in patients with uncomplicated type B aortic dissection but have not shown a benefit for TEVAR conclusively.

Transdermal Delivery of Tofacitinib Citrate via Mannose-Decorated Transferosomes Loaded with Tofacitinib Citrate in Arthritic Joints.

Transdermal drug delivery systems are a promising option for the treatment of rheumatoid arthritis (RA) because they can lower systemic adverse effects of immunosuppressants. Janus kinase (JAK) inhibitors were found to be effective for the treatment of RA by inhibiting the JAK-STAT pathway and preventing autoimmune joint destruction. The aim of this study is to deliver tofacitinib (a JAK 1 and 3 inhibitor) through mannose-decorated transferosomes (MDTs) directly to inflamed joints.

A novel phosphodiesterase 5 inhibitor, RF26, improves memory impairment and ameliorates tau aggregation and neuroinflammation in the P301S tauopathy mouse model of Alzheimer's disease.

Phosphodiesterase-5 (PDE5) inhibitors are primarily used in the treatment of erectile dysfunction and pulmonary hypertension, but have also been reported to have a potential therapeutic effect for the treatment of Alzheimer's disease (AD). This is likely to be through stimulation of nitric oxide (NO)/cyclic guanosine monophosphate (cGMP) signaling by elevating cGMP, a secondary messenger involved in processes of neuroplasticity. In the present study, we evaluated the efficacy of a novel PDE5 inhibitor, RF26, using P301S tauopathy mice model.

Discovery of 1,3-disubstituted prop-2-en-1-one derivatives as inhibitors of neutrophilic inflammation via modulation of MAPK and Akt pathways.

Targeting neutrophil function has gained attention as a propitious therapeutic strategy for diverse inflammatory diseases. Accordingly, a series of enone-based derivatives were developed to inhibit neutrophil-mediated inflammation, showing promise for treating inflammatory diseases. These compounds fall into two clusters with distinct effects: one inhibits neutrophilic superoxide (SO) anion production and elastase release triggered by N-formyl-Met-Leu-Phe (fMLF), with compound being most effective (IC values of 1.

Predictive Factors for Bowel Resection in Childhood Intussusception.

Background: Intestinal intussusception is the most common cause of intestinal obstruction in infants and children under 3 years of age. Any delay in diagnosis or management can lead to intestinal ischaemia and perforation. The aim of this study is to determine the sociodemographic and clinical risk factors associated with bowel resection in infants and children with intussusception.

Novel Celecoxib Derivative, RF26, Blocks Colon Cancer Cell Growth by Inhibiting PDE5, Activating cGMP/PKG Signaling, and Suppressing β-catenin-dependent Transcription.

Background: Previous studies have reported that the cGMP-specific PDE5 isozyme is overexpressed in colon adenomas and adenocarcinomas and essential for colon cancer cell proliferation, while PDE5 selective inhibitors (e.g., sildenafil) have been reported to have cancer chemopreventive activity.

Phytochemical Evaluation of , , , and , and Their Potential Effect on Monosodium Glutamate Induced Male Reproductive Dysfunction in Adult Wistar Rats.

Monosodium glutamate (MSG), a sodium salt derived from glutamic acid, is widely used in commercial food products to improve taste, quality, and preservation. However, its consumption may have detrimental effects on male reproductive function. Nevertheless, plant extracts, such as (Maca), (Fenugreek), (Spirulina), and (Tribulus), may ameliorate these adverse effects.

Seroprevalence and molecular detection of infection in livestock in the United Arab Emirates.

Small ruminants and camels are important livestock species in the United Arab Emirates (UAE), although infection can limit their productivity. This study aimed to investigate the seroprevalence of infection and its associated risk factors in small ruminants and camels in the Emirate of Abu Dhabi. Additionally, seropositive animals were tested for the DNA of .

Loose Intraperitoneal Spiral Tack Causing Small Bowel Obstruction Following Laparoscopic Intraperitoneal Onlay Mesh Repair of Ventral Incisional Hernia: A Case Report.

This case report discusses a rare complication of small bowel obstruction occurring in the early course following Intraperitoneal Onlay Mesh (IPOM) repair for an incisional hernia. The bowel obstruction, which failed to respond to conservative measures, was caused by band adhesions resulting from the presence of a loose intraperitoneal migrated surgical tack. This was successfully managed laparoscopically resulting in complete recovery.

Nanoparticles in liposomes: a platform for increased antibiotic selectivity in multidrug resistant bacteria in respiratory tract infections.

Antibiotic resistance is a cause of serious illness and death, originating often from insufficient permeability into gram-negative bacteria. Nanoparticles (NP) can increase antibiotic delivery in bacterial cells, however, may as well increase internalization in mammalian cells and toxicity. In this work, NP in liposome (NP-Lip) formulations were used to enhance the selectivity of the antibiotics (3C and tobramycin) and quorum sensing inhibitor (HIPS-1635) towards Pseudomonas aeruginosa by fusing with bacterial outer membranes and reducing uptake in mammalian cells due to their larger size.

Development of 5-hydroxybenzothiophene derivatives as multi-kinase inhibitors with potential anti-cancer activity.

Chemoresistance in cancer challenges the classical therapeutic strategy of 'one molecule-one target'. To combat this, multi-target therapies that inhibit various cancer-relevant targets simultaneously are proposed. We introduce 5-hydroxybenzothiophene derivatives as effective multi-target kinase inhibitors, showing notable growth inhibitory activity across different cancer cell lines.

Visual, ocular surface, and extraocular diagnostic criteria for determining the prevalence of computer vision syndrome: a cross-sectional smart-survey-based study.

Background: The American Optometric Association defines computer vision syndrome (CVS), also known as digital eye strain, as "a group of eye- and vision-related problems that result from prolonged computer, tablet, e-reader and cell phone use". We aimed to create a well-structured, valid, and reliable questionnaire to determine the prevalence of CVS, and to analyze the visual, ocular surface, and extraocular sequelae of CVS using a novel and smart self-assessment questionnaire.

Methods: This multicenter, observational, cross-sectional, descriptive, survey-based, online study included 6853 complete online responses of medical students from 15 universities.

Exploring chromone-2-carboxamide derivatives for triple-negative breast cancer targeting EGFR, FGFR3, and VEGF pathways: Design, synthesis, and preclinical insights.

Chromone-based compounds have established cytotoxic, antiproliferative, antimetastatic, and antiangiogenic effects on various cancer cell types via modulating different molecular targets. Herein, 17 novel chromone-2-carboxamide derivatives were synthesized and evaluated for their in vitro anticancer activity against 15 human cancer cell lines. Among the tested cell lines, MDA-MB-231, the triple-negative breast cancer cell line, was found to be the most sensitive, where the N-(2-furylmethylene) (15) and the α-methylated N-benzyl (17) derivatives demonstrated the highest growth inhibition with GI values of 14.

-Benzylated 5-Hydroxybenzothiophene-2-carboxamides as Multi-Targeted Clk/Dyrk Inhibitors and Potential Anticancer Agents.

Numerous studies have reported that Dyrk1A, Dyrk1B, and Clk1 are overexpressed in multiple cancers, suggesting a role in malignant disease. Here, we introduce a novel class of group-selective kinase inhibitors targeting Dyrk1A, Dyrk1B, and Clk1. This was achieved by modifying our earlier selective Clk1 inhibitors, which were based on the 5-methoxybenzothiophene-2-carboxamide scaffold.

Alternative isoform expression of key thermogenic genes in human beige adipocytes.

Background: The beneficial effect of thermogenic adipocytes in maintaining body weight and protecting against metabolic disorders has raised interest in understanding the regulatory mechanisms defining white and beige adipocyte identity. Although alternative splicing has been shown to propagate adipose browning signals in mice, this has yet to be thoroughly investigated in human adipocytes.

Methods: We performed parallel white and beige adipogenic differentiation using primary adipose stem cells from 6 unrelated healthy subjects and assessed differential gene and isoform expression in mature adipocytes by RNA sequencing.

AI-based tool for early detection of Alzheimer's disease.

In the context of Alzheimer's disease (AD), timely identification is paramount for effective management, acknowledging its chronic and irreversible nature, where medications can only impede its progression. Our study introduces a holistic solution, leveraging the hippocampus and the VGG16 model with transfer learning for early AD detection. The hippocampus, a pivotal early affected region linked to memory, plays a central role in classifying patients into three categories: cognitively normal (CN), representing individuals without cognitive impairment; mild cognitive impairment (MCI), indicative of a subtle decline in cognitive abilities; and AD, denoting Alzheimer's disease.

Redirecting pantoprazole as a metallo-beta-lactamase inhibitor in carbapenem-resistant .

The development of resistance to carbapenems in due to the production of metallo-β-lactamases (MBLs) is a critical public health problem because carbapenems are the last-resort drugs used for treating severe infections of extended-spectrum β-lactamases (ESBLs) producing . Restoring the activity of carbapenems by the inhibition of metallo-β-lactamases is a valuable approach to combat carbapenem resistance. In this study, two well-characterized clinical multidrug and carbapenem-resistant isolates were used.

Novel 6-hydroxybenzothiazol-2-carboxamides as potent and selective monoamine oxidase B inhibitors endowed with neuroprotective activity.

In neurodegenerative diseases, using a single molecule that can exert multiple effects to modify the disease may have superior activity over the classical "one molecule-one target" approach. Herein, we describe the discovery of 6-hydroxybenzothiazol-2-carboxamides as highly potent and selective MAO-B inhibitors. Variation of the amide substituent led to several potent compounds having diverse side chains with cyclohexylamide 40 displaying the highest potency towards MAO-B (IC = 11 nM).

N-Benzoylated 5-(4-pyridinyl)indazole-based kinase inhibitors: Attaining haspin and Clk4 selectivity via modulation of the benzoyl substituents.

Haspin and Clk4 are both understudied protein kinases (PKs), offering potential targets for the development of new anticancer agents. Thus, the identification of new inhibitors targeting these PKs is of high interest. However, the inhibitors targeting haspin or Clk4 developed to date show a poor selectivity profile over other closely related PKs, increasing the risk of side effects.

Synthesis and evaluation of novel N1-acylated 5-(4-pyridinyl)indazole derivatives as potent and selective haspin inhibitors.

Protein kinase dysregulation was strongly linked to cancer pathogenesis. Moreover, histone alterations were found to be among the most important post-translational modifications that could contribute to cancer growth and development. In this context, haspin, an atypical serine/threonine kinase, phosphorylates histone H3 at threonine-3 and is notably overexpressed in various common cancer types.

Complicated anorectal sepsis: Validation of scoring system for predicting anorectal sepsis severity.

Anorectal sepsis is a common and potentially serious medical condition characterized by infection and inflammation of the anal canal and surrounding tissues. However, the lack of standardized and comprehensive scoring systems specifically tailored for predicting the severity of anorectal sepsis poses challenges in clinical practice. This study aimed to develop and validate a scoring system for predicting the severity of anorectal sepsis by incorporating relevant patient factors.

Phenotypic, molecular, and in silico characterization of coumarin as carbapenemase inhibitor to fight carbapenem-resistant Klebsiella pneumoniae.

Background: Carbapenems represent the first line treatment of serious infections caused by drug-resistant Klebsiella pneumoniae. Carbapenem-resistant K. pneumoniae (CRKP) is one of the urgent threats to human health worldwide.