Cannabidiol Suppresses Metastatic Castration-Resistant Prostate Cancer Progression and Recurrence through Modulating Tryptophan Catabolism.

Metastatic castration-resistant prostate cancer (mCRPC) is an aggressive phenotype of prostate cancer (PC). Tryptophan oxidative catabolism by indoleamine 2,3-dioxygenase-1 (IDO1) cleaves the indole ring to kynurenine (Kyn), an endogenous ligand for the aryl hydrocarbon receptor (AhR), which activates multiple tumorigenesis pathways. The IDO1-Kyn-AhR axis is aberrantly dysregulated in mCRPC.

Statin Consumption and Appealing Colors: Exploring Statin-Related Injuries for Children Under the Age of Three Years.

Introduction: Statins are frequently prescribed to lower the risk of atherosclerosis and cardiovascular-related diseases. While statins are considered safe, there are occasional accidental overdoses in children that warrant concern for how to protect children from unintended consumption. We aimed to determine which statins were more prone to injury, characterize the injury types commonly seen for each statin, assess the age at which statin-related injuries were most frequent, and compare statin-related injuries among genders.

The Usnic Acid Analogue 4-FPBUA Enhances the Blood-Brain Barrier Function and Induces Autophagy in Alzheimer's Disease Mouse Models.

Preclinical and clinical studies have indicated that compromised blood-brain barrier (BBB) function contributes to Alzheimer's disease (AD) pathology. BBB breakdown ranged from mild disruption of tight junctions (TJs) with increased BBB permeability to chronic integrity loss, affecting transport across the BBB, reducing brain perfusion, and triggering inflammatory responses. We recently developed a high-throughput screening (HTS) assay to identify hit compounds that enhance the function of a cell-based BBB model.

Decoding the secrets of small extracellular vesicle communications: exploring the inhibition of vesicle-associated pathways and interception strategies for cancer treatment.

Cancer disease is the second leading cause of death worldwide. In 2023, about 2 million new cancer cases and 609,820 cancer deaths are projected to occur in the United States. The driving forces of cancer progression and metastasis are widely varied and comprise multifactorial events.

Bioactive metabolites identified from Aspergillus terreus derived from soil.

Aspergillus terreus has been reported to produce many bioactive metabolites that possess potential activities including anti-inflammatory, cytotoxic, and antimicrobial activities. In the present study, we report the isolation and identification of A. terreus from a collected soil sample.

Antimicrobial, antiproliferative activities and molecular docking of metabolites from Alternaria alternata.

Endophytic fungi allied to plants have sparked substantial promise in discovering new bioactive compounds. In this study, propagation of the endophytic fungus Alternaria alternata HE11 obtained from Colocasia esculanta leaves led to the isolation of Ergosterol (1), β-Sitosterol (2), Ergosterol peroxide (3), in addition to three dimeric naphtho-γ-pyrones, namely Fonsecinone A (4), Asperpyrone C (5), and Asperpyrone B (6), which were isolated from genus Alternaria for the first time. Structures of the isolated compounds were established on the basis of extensive 1D and 2D NMR and, MS measurements.

Pseurotin A Validation as a Metastatic Castration-Resistant Prostate Cancer Recurrence-Suppressing Lead via PCSK9-LDLR Axis Modulation.

Metastatic castration-resistant prostate cancer (mCRPC) cells can de novo biosynthesize their own cholesterol and overexpress proprotein convertase subtilisin/kexin type 9 (PCSK9). PCSK9 proved to contribute to mCRPC cell motility since PCSK9 knockdown (KD) in mCRPC CWR-R1ca cells led to notable reductions in cell migration and colony formation. Human tissue microarray results proved a higher immunohistoscore in patients ≥ 65 years old, and PCSK9 proved to be expressed higher at an early Gleason score of ≤7.

Towards Developing Novel Prostate Cancer Recurrence Suppressors: Acute Toxicity of Pseurotin A, an Orally Active PCSK9 Axis-Targeting Small-Molecule in Swiss Albino Mice.

The proprotein convertase subtilisin kexin type 9 (PCSK9) emerged as a molecular target of great interest for the management of cardiovascular disorders due to its ability to reduce low density lipoprotein (LDL) cholesterol by binding and targeting at LDLR for lysosomal degradation in cells. Preliminary studies revealed that pseurotin A (PsA), a spiro-heterocyclic γ-lactam alkaloid from several marine and terrestrial and species, has the ability to dually suppress the PCSK9 expression and protein-protein interaction (PPI) with LDLR, resulting in an anti-hypercholesterolemic effect and modulating the oncogenic role of PCSK9 axis in breast and prostate cancers progression and recurrence. Thus, a preliminary assessment of the PsA acute toxicity represents the steppingstone to develop PsA as a novel orally active PCSK9 axis modulating cancer recurrence inhibitor.

Anti-prostate cancer metabolites from the soil-derived .

Prostate cancer (PCa) ranks as one of the most commonly diagnosed malignancies worldwide. Toxicity, lack of clinical efficacy, and development of resistance phenotypes are the main challenges in the control of prostate malignancies. Notably, castration-resistance prostate cancer (CRPCa) is a highly aggressive and metastatic phenotype of the disease with a poor prognosis and very limited therapeutic options.

Melaleuca rugulosa (Link) Craven Tannins: Appraisal of anti-inflammatory, radical scavenging activities, and molecular modeling studies.

Ethnopharmacological Relevance: Genus Melaleuca or tea tree species are well known to be an important source of biological active oils and extracts. The biological significance appears in their usage for treatment of several clinical disorder owing to their traditional uses as anti-inflammatory, antibacterial, antifungal, and cytotoxic activities.

Aim Of The Study: Our study aimed to investigate the metabolic profile of the M.

Oleocanthal Attenuates Metastatic Castration-Resistant Prostate Cancer Progression and Recurrence by Targeting SMYD2.

Metastatic castration-resistant prostate cancer (mCRPC) is the most aggressive prostate cancer (PC) phenotype. Cellular lysine methylation is driven by protein lysine methyltransferases (PKMTs), such as those in the SET- and MYND-containing protein (SMYD) family, including SMYD2 methylate, and several histone and non-histone proteins. SMYD2 is dysregulated in metastatic PC patients with high Gleason score and shorter survival.

The Tobacco β-Cembrenediol: A Prostate Cancer Recurrence Suppressor Lead and Prospective Scaffold via Modulation of Indoleamine 2,3-Dioxygenase and Tryptophan Dioxygenase.

Prostate cancer (PC) is the second leading cause of death in men in the US. PC has a high recurrence rate, and limited therapeutic options are available to prevent disease recurrence. The tryptophan-degrading enzymes 2,3-indoleamine dioxygenase (IDO1) and tryptophan dioxygenase (TDO2) are upregulated in invasive PC.

Ethnopharmacological impact of Melaleuca rugulosa (Link) Craven leaves extract on liver inflammation.

Ethnopharmacological Relevance: Melaleuca species have been used by many ethnic communities for the management and treatment of several ailments as hemorrhoids, cough, skin infections, rheumatism, sore throat, pain, inflammation, and digestive system malfunctions. However, the detailed mechanistic pharmacological effect of Melaleuca rugulosa (Link) Craven leaves in the management of liver inflammation has not been yet addressed.

Aim Of The Study: The present study aimed to evaluate the anti-inflammatory, antioxidant, and antiapoptotic capacities of the aqueous methanol extract of M.

Intermittent fasting and continuous energy restriction result in similar changes in body composition and muscle strength when combined with a 12 week resistance training program.

Purpose: The objective of this study was to compare the effects of 12 weeks of resistance training combined with either 5:2 intermittent fasting or continuous energy restriction on body composition, muscle size and quality, and upper and lower body strength.

Methods: Untrained individuals undertook 12 weeks of resistance training plus either continuous energy restriction [20% daily energy restriction (CERT)] or 5:2 intermittent fasting [~ 70% energy restriction 2 days/week, euenergetic consumption 5 days/week (IFT)], with both groups prescribed a mean of ≥ 1.4 g of protein per kilogram of body weight per day.

Growth Inhibition and Apoptotic Effect of Pine Extract and Abietic Acid on MCF-7 Breast Cancer Cells via Alteration of Multiple Gene Expressions Using In Vitro Approach.

In vitro anti-proliferative activity of extract and its purified abietic acid was assessed against different human cancer cell lines (HepG-2, MCF-7 and HCT-116) compared to normal WI-38 cell line. Abietic acid showed more promising IC values against MCF-7 cells than pine extract (0.06 µg/mL and 0.

Cytotoxicity, Antimicrobial, and Studies of Secondary Metabolites From . Isolated From (L.) Juss. Ex Kunth Leaves.

Endophytes are prolific producers of privileged secondary metabolites with diverse therapeutic potential, although their anticancer and antimicrobial potential still have a room for further investigation. Herein, seven known secondary metabolites namely, arugosin C (1), ergosterol (2), iso-emericellin (3), sterigmatocystin (4), dihydrosterigmatocystin (5), versicolorin B (6), and diorcinol (7) were isolated from the rice culture of retrieved from (L.) Juss.

Polyphenolic profile and ethno pharmacological activities of Callistemonsubulatus (Cheel) Craven leaves cultivated in Egypt.

Ethnopharmacological Relevance: The genus Callistemon (syn. Melaleuca) of the myrtle family (Myrtaceae) has been documented as an integral part in the ethnobotanical system of the indigenous people of Australian mainland and many of its islands. Several Callistemons including the species subulatus were used by aboriginal Australians for making rafts, roofs for shelters, bandages, and food recipes, in addition to the management of wounds, infections, pain, cough, bronchitis, and gastrointestinal tract (GIT) disorders.

Frailty in Stroke-A Narrated Review.

This narrative review provides a summary introduction to the relationship between stroke and physical and cognitive frailty syndromes and the neuro-inflammatory similarities (including inflammaging) between the two. The review argues the potential effects of Post COVID-19 Neurological Syndrome (PCNS, also known as Long COVID) with similar pathophysiology. Many patients who have suffered from acute stroke experience long-lasting symptoms affecting several organs including fatigue, brain fog, reduced physical activity, loss of energy, and loss of cognitive reserve, culminating in the loss of independence and poor quality of life.

Experimental Methods to Study the Pathogenesis of Human Enteric RNA Viruses.

Every year, millions of children are infected with viruses that target the gastrointestinal tract, causing acute gastroenteritis and diarrheal illness. Indeed, approximately 700 million episodes of diarrhea occur in children under five annually, with RNA viruses norovirus, rotavirus, and astrovirus serving as major causative pathogens. Numerous methodological advancements in recent years, including the establishment of novel cultivation systems using enteroids as well as the development of murine and other animal models of infection, have helped provide insight into many features of viral pathogenesis.

Norovirus evolution in immunodeficient mice reveals potentiated pathogenicity via a single nucleotide change in the viral capsid.

Interferons (IFNs) are key controllers of viral replication, with intact IFN responses suppressing virus growth and spread. Using the murine norovirus (MNoV) system, we show that IFNs exert selective pressure to limit the pathogenic evolutionary potential of this enteric virus. In animals lacking type I IFN signaling, the nonlethal MNoV strain CR6 rapidly acquired enhanced virulence via conversion of a single nucleotide.

Murine astrovirus tropism for goblet cells and enterocytes facilitates an IFN-λ response in vivo and in enteroid cultures.

Although they globally cause viral gastroenteritis in children, astroviruses are understudied due to the lack of well-defined animal models. While murine astroviruses (muAstVs) chronically infect immunodeficient mice, a culture system and understanding of their pathogenesis is lacking. Here, we describe a platform to cultivate muAstV using air-liquid interface (ALI) cultures derived from mouse enteroids, which support apical infection and release.

Long-term outcomes of warfarin versus aspirin after Fontan surgery.

Objectives: Because of the nature of the Fontan physiology, patients are at an increased risk of thromboembolic complications. As such, warfarin or aspirin is generally prescribed lifelong for thromboprophylaxis. This study aimed to compare long-term rates of cerebrovascular injury, thrombosis, bleeding, bone mineral density, and quality of life in people living with Fontan circulation receiving warfarin compared with aspirin.

Impact of adiposity on clinical outcomes in people living with a Fontan circulation.

Background: To assess the association between body composition and the risk of adverse outcomes in Fontan patients.

Methods: Participants from the Australian and New Zealand Fontan Registry with dual-energy X-ray absorptiometry scans were included. Appendicular lean mass (ALM), appendicular lean mass index (ALM divided by height squared; ALMI) and total body fat mass percentage (%BF) were calculated.

CD300lf is the primary physiologic receptor of murine norovirus but not human norovirus.

Murine norovirus (MNoV) is an important model of human norovirus (HNoV) and mucosal virus infection more broadly. Viral receptor utilization is a major determinant of cell tropism, host range, and pathogenesis. The bona fide receptor for HNoV is unknown.

Synthesis, anticancer evaluation and molecular docking studies of new heterocycles linked to sulfonamide moiety as novel human topoisomerase types I and II poisons.

A series of heterocyclic compounds with a sulfonamide moiety were synthesized from reaction of enaminone 4 with active methylene compounds, glycine derivatives, 1,4-benzoquinone, hydroxylamine hydrochloride, hydrazonyl halides and dimethylacetylenedicarboxylate. The newly synthesized sulfonamide derivatives were characterized by FT-IR, H NMR, C NMR, mass spectroscopy, elemental analysis and alternative synthetic routes. The reactions products were evaluated for their antiproliferative activity against a panel of three different human cancerous cell lines, MCF-7 (breast), HepG-2 (liver) and HCT-116 (colon) and the results were deployed to derive the structure-activity relationships (SAR).