Targeting unique ligand binding domain structural features downregulates DKK1 in Y537S ESR1 mutant breast cancer cells.

Resistance to endocrine therapies remains a major clinical hurdle in breast cancer. Mutations to estrogen receptor alpha (ERα) arise after continued therapeutic pressure. Next generation selective estrogen receptor modulators and degraders/downregulators (SERMs and SERDs) show clinical efficacy, but responses are often non-durable.

First generation vanadium-based PTEN inhibitors: Comparative study in vitro and in vivo and identification of a novel mechanism of action.

PTEN, a tumor suppressor phosphatase, regulates cellular functions by antagonizing the growth promoting PI3K/Akt/mTOR pathway through the dephosphorylation of the second messenger PIP. Many preclinical cellular and animal studies have used PTEN inhibitors to highlight specific disease contexts where acute activation of PI3K/Akt/mTOR pathway might offer therapeutic advantages. In the present study we have re-evaluated first-generation PTEN inhibitors, including established bisperoxo-vanadium complexes (bpVs).

Enhanced thermogenesis in PAS Kinase-deficient male mice.

PAS domain-containing serine/threonine-protein kinase (PASK) is a nutrient and energy sensor regulated by fasting/refeeding conditions in hypothalamic areas involved in controlling energy balance. In this sense, PASK plays a role in coordinating the activation/inactivation of AMP-activated protein kinase (AMPK) and mechanistic target of rapamycin (mTOR) in response to fasting. PASK deficiency protects against the development of diet-induced obesity.

PSMC2 promotes resistance against temozolomide in glioblastoma via suppressing JNK-mediated autophagic cell death.

Temozolomide is universally used to treat glioblastoma due to its unique ability to cross the blood-brain barrier and inhibit tumor growth through DNA alkylation. However, over time, the inevitable emergence of resistance to temozolomide impedes successful treatment of this cancer. As a result, there is an urgent need to identify new therapeutic targets to improve treatment outcomes for this malignancy.

Blended ƙ-carrageenan and xanthan gum hydrogel containing ketoprofen-loaded nanoemulsions: Design, characterization, and evaluation in an animal model of rheumatoid arthritis.

This study reports the preparation of hydrogels (HG) made with xanthan gum (XG) and ƙ-carrageenan (KC) polysaccharides containing ketoprofen (KET)-loaded nanoemulsions (NK) and their evaluation in a rheumatoid arthritis (RA) model. The nano-based HGs exhibited nanometric-sized droplets (~ 100 nm), an acidic pH (5.10-6.

Dietary deacetylated chitin nanoparticles confer protection against diazinon toxicity in male African catfish: evaluation of immune-biochemical, antioxidant, and reproductive profiles.

Currently, deacetylated chitin (chitosan) nanoparticles (CNPs) are successfully utilized in aquaculture practices. This trial demonstrates the efficacy of CNPs in combating diazinon (DZN) toxicity in African catfish, Clarias gariepinus, via monitoring hepato-renal function, serum immune trait, hormonal function, and hepato-renal antioxidant activity. Four groups were allocated as follows: a control group, a CNPs group (0.

A Novel Facile and Efficient Prophylaxis Avenue of Chitosan Oligosaccharide/PLGA Based Polydatin Loaded Nanoparticles Against Bleomycin-Induced Lung Inflammation in Experimental Rat Model.

Lung inflammation is a hallmark of several respiratory diseases. Despite the great effectiveness of the synthetic antiinflammatory agents, they cause potential side effects. Polydatin (PD), a natural phytomedicine, has antioxidant and antiinflammatory effects.

Liraglutide mitigates dexamethasone-induced fatty acid synthase (FASN) and the cluster of differentiation36 (CD36) expression: a potential treatment for glucocorticoid-induced non-alcoholic fatty liver disease (NAFLD).

The clinical use of dexamethasone (DXM) is associated with the development of non-alcoholic fatty liver disease (NAFLD). However, the mechanisms by which DXM-induced NAFLD is still incompletely known. Therefore, the current study aims to test the hypothesis that DXM-induced NAFLD is mediated by dysregulation of key genes involved in lipid metabolism and liraglutide (LG) can ameliorate these effects.

Brivaracitam Ameliorates Increased Inflammation, Oxidative Stress, and Acetylcholinesterase Activity in Ischemic Mice.

Objective: Cerebral ischemia is a medical condition that occurs due to poor supply of blood in the brain. Reperfusion being savage further exaggerates the tissue injury causing cerebral ischemia/reperfusion injury (CI/R). CI/R is marked by an impairment in release of neurotransmitter, excitotoxicity, oxidative stress, inflammation, and neuronal apoptosis.

Muscle-derived myostatin is a major endocrine driver of follicle-stimulating hormone synthesis.

Myostatin is a paracrine myokine that regulates muscle mass in a variety of species, including humans. In this work, we report a functional role for myostatin as an endocrine hormone that directly promotes pituitary follicle-stimulating hormone (FSH) synthesis and thereby ovarian function in mice. Previously, this FSH-stimulating role was attributed to other members of the transforming growth factor-β family, the activins.

Ultrasound-activated erythrocyte membrane-camouflaged Pt (II) layered double hydroxide enhances PD-1 inhibitor efficacy in triple-negative breast cancer through cGAS-STING pathway-mediated immunogenic cell death.

Immunogenic cell death (ICD) offers a promising avenue for the treatment of triple-negative breast cancer (TNBC). However, optimizing immune responses remains a formidable challenge. This study presents the design of RBCm@Pt-CoNi layered double hydroxide (RmPLH), an innovative sonosensitizer for sonodynamic therapy (SDT), aimed at enhancing the efficacy of programmed cell death protein 1 (PD-1) inhibitors by inducing robust ICD responses.

Lipid-encapsulated gold nanoparticles: an advanced strategy for attenuating the inflammatory response in SARS-CoV-2 infection.

Background: Nanodrugs play a crucial role in biomedical applications by enhancing drug delivery. To address safety and toxicity concerns associated with nanoparticles, lipid-nanocarrier-based drug delivery systems have emerged as a promising approach for developing next-generation smart nanomedicines. Ginseng has traditionally been used for various therapeutic purposes, including antiviral activity.

Antibacterial and antioxidant potentials, detection of host origin compounds, and metabolic profiling of endophytic Bacillus spp. isolated from Rauvolfia serpentina (L.) Benth. ex Kurz.

The research highlights the importance of exploring endophytic microbiomes of medicinal plants to uncover their potential for secondary metabolite production and their role in the biosynthesis of host-derived compounds. This study was aimed to isolate leaf endophytic bacteria of Rauvolfia serpentina, investigate their antibacterial, antioxidant potentials and detect host-origin compound reserpine using Reverse Phase High-Performance Liquid Chromatography (RPHPLC). Untargeted analysis via Ultra High-Performance Liquid Chromatography-High-Resolution Mass Spectrometry (UHPLC-HRMS/MS) was conducted for profiling main phytochemicals in the leaves and to explore potential bioactive compounds in bacterial extracts.

Can we diagnose noninvasive follicular thyroid neoplasm with papillary-like nuclear features before surgery?

Noninvasive follicular thyroid neoplasm with papillary-like nuclear features (NIFTP) can be differentiated from invasive encapsulated follicular variant of papillary thyroid carcinoma (eFV-PTC) by the presence of a tumor capsule or blood vessel invasion in histological examination. The objective of this study was to investigate whether it is possible to distinguish between NIFTP and invasive eFV-PTC before surgery. Patients diagnosed with NIFTP and invasive eFV-PTC from 2017 to 2023 were analyzed for biochemical, ultrasonographic, and cytological features.

Assessment of the impact of VDR polymorphisms on selected hormonal, metabolic and mineral balance markers in young women with hyperandrogenism.

Objectives: Hyperandrogenism is a frequently recognized endocrine imbalance in which there is excessive production of androgens. The purpose of the study was to investigate the impact of vitamin D receptor (VDR) gene polymorphisms on chosen bone metabolism and biochemical parameters in women with hyperandrogenism.

Material And Methods: Eighty young females with hyperandrogenism were enrolled in the study, in whom selected parameters of bone turnover, endocrine and metabolic parameters were determined.

Assessment of salicylic acid and potassium nitrate to mitigate frost stress in autumn-sown potato crop cv. Sutlej.

Potato is cultivated all the year round in Pakistan. However, the major crop is the autumn crop which is planted in mid-October and contributes 80-85% of the total production. The abrupt climate change has affected the weather patterns all over the world, resulting in the reduction of the mean air temperature in autumn by almost 1.

A Bifunctional Peptide with Penetration Ability for Treating Retinal Angiogenesis via Eye Drops.

Numerous diseases, such as diabetic retinopathy and age-related macular degeneration, can lead to retinal neovascularization, which can seriously impair the visual function and potentially result in blindness. The presence of the blood-retina barrier makes it challenging for ocularly administered drugs to penetrate physiological barriers and reach the ocular posterior segments, including the retina and choroid. Herein, we developed an innovative bifunctional peptide, Tat-C-RP7, which exhibits excellent penetration capabilities and antiangiogenic properties aimed at treating retinal neovascularization diseases.

Boswellic acid synergizes with low-dose ionizing radiation to mitigate thioacetamide-induced hepatic encephalopathy in rats.

Hepatic encephalopathy (HE) is a syndrome that arises from acute or chronic liver failure. This study was devised to assess the impact of a combination of boswellic acid (BA) and low doses of gamma radiation (LDR) on thioacetamide (TAA)-induced HE in an animal model. The effect of daily BA treatment (175 mg/kg body weight, for four weeks) and/or fractionated low-dose γ-radiation (LDR; 0.

Extended spectrum betalactamase and Carbapenemase producing gram negative bacteria from healthcare workers gowns at Debre Berhan Comprehensive Specialized Hospital, Ethiopia.

Extended-spectrum beta-lactamase (ESBL) and carbapenemase-producing (CP) gram-negative bacteria are the major public health concerns. Gowns used by healthcare workers (HCWs) in daily practice are a source of hospital-acquired infections in hospital settings. The study aimed to determine the prevalence of extended-spectrum beta-lactamase and carbapenemase-producing gram-negative bacteria from gowns of healthcare workers at Debre Berhan Comprehensive Specialized Hospital, Amhara Regional State, Ethiopia.

Role of AIM2 and cGAS-STING signaling in high fat high carbohydrate diet-induced gut dysbiosis associated neurodegeneration.

Aims: Gut dysbiosis modulates CNS complications and cognitive decline through the gut-brain axis. The study aims to investigate the molecular mechanisms involved in gut dysbiosis-associated cognitive changes and the potential effects of probiotics in high fat-high carbohydrate diet-induced gut dysbiosis-associated neurodegeneration.

Materials And Methods: We used high fat, high-carbohydrate diet (HFHCD) and high-fat diet (HFD) to induce gut dysbiosis-associated neurodegeneration in C57BL/6 mice.

Hydrogen-Rich Saline Combined With Vacuum Sealing Drainage Promotes Wound Healing by Altering Biotin Metabolism.

Impaired wound healing affects the life quality of patients and causes a substantial financial burden. Hydrogen-rich medium is reported to have antioxidant and anti-inflammatory effects. However, the role of hydrogen-rich saline (HRS) in cutaneous wound healing remains largely unexplored, especially by metabolomics.

5,7-Dihydroxy-4-Methylcoumarin enhances osteogenesis and ameliorates osteoporosis via the AKT1 pathway.

Osteoporosis is a chronic disease distinguished by decreased bone density and degradation of bone microstructure, frequently linked with inflammation and oxidative stress, both of which contribute to the acceleration of bone resorption. The compound 5,7-Dihydroxy-4-methylcoumarin (D4M) present in Artemisia dracunculus exhibits significant antioxidant and anti-inflammatory properties. Nonetheless, the potential anti-osteoporotic effects of D4M, along with the molecular targets and mechanisms responsible for these effects, have not been studied.

Pym-18a, a novel pyrimidine derivative ameliorates glucocorticoid induced osteoblast apoptosis and promotes osteogenesis via autophagy and PINK 1/Parkin mediated mitophagy induction.

Glucocorticoid-induced osteoporosis (GIOP) is the most common type of secondary osteoporosis, marked by reduced bone density and impaired osteoblast function. Current treatments have serious side effects, highlighting the need for new drug candidates. Pyrimidine derivatives have been noted for their potential in suppressing osteoclastogenesis, but their effects on osteogenesis and GIOP remain underexplored.

Dissecting the mechanisms of velvet antler extract against diabetic osteoporosis via network pharmacology and proteomics.

Ethnopharmacological Relevance: Velvet antler (VAE) is a famous traditional Chinese medicine (TCM), which has been used for thousands of years to treat bone-related diseases. Nonetheless, whether VAE has anti-diabetic osteoporosis (DOP) properties remains to be elucidated.

Aim Of The Study: The therapeutic mechanism of VAE on DOP is based on integrated proteomics of network pharmacology strategies to study related targets and pathways.

Clinical and molecular analysis of ESBL, carbapenemase, and colistin-resistant bacteria in UTI patients.

Uropathogens, particularly bacteria, can infect any part of the urinary tract and cause bacteriuria. Our study aimed to examine the antibiotic-resistant profile, associated risk factors, and phenotypic and genotypic features of ESBL, carbapenemase, and mcr resistance genes in multidrug-resistant bacteria. Samples were inoculated on culture media, identified using standard biochemical tests, and species confirmation was performed via 16S rRNA gene amplification.