GC-MS and HPTLC Fingerprinting Analysis and Evaluation of Antimicrobial Activity of Naga Chilli: An In Vitro and In Silico Approach.

Naga chilli (Capsicum chinense Jacq.) have garnered significant attention due to the plant's possible health benefits and variety of phytochemical components. Utilizing cutting-edge analytical techniques such as gas chromatography-mass spectrometry (GC-MS) and high-performance thin layer chromatography (HPTLC) in conjunction with bioautography, this study conducts a thorough phytochemical profiling and biological activity assessment of the Naga chilli plant.

Trait responsiveness to verbal suggestions predicts nocebo responding: A meta-analysis.

Background: Nocebo responding involves the experience of adverse health outcomes in response to contextual cues. These deleterious responses impact numerous features of mental and physical health but are characterized by pronounced heterogeneity. Suggestion is widely recognized as a contributing factor to nocebo responding but the moderating role of trait responsiveness to verbal suggestions (suggestibility) in nocebo responding remains poorly understood.

TNIK: A redox sensor in endothelial cell permeability.

Dysregulation of endothelial barrier integrity can lead to vascular leak and potentially fatal oedema. TNF-α controls endothelial permeability during inflammation and requires the actin organizing Ezrin-Radixin-Moesin (ERM) proteins. We identified TRAF2 and NCK-interacting kinase (TNIK) as a kinase directly phosphorylating and activating ERM, specifically at the plasma membrane of primary human endothelial cells.

Release-modulating mechanism and comparative pharmacokinetics in beagle dogs of bethanechol-loaded oral dosage forms.

Bethanechol chloride (BTC), a quaternary ammonium compound used in bladder dysfunction treatment, requires challenges in developing optimal oral dosage forms due to its high water-solubility, short half-life, rapid elimination and four times a day administration. The aim of this study was to develop optimal BTC-loaded oral dosage forms that could provide both rapid onset and sustained therapeutic effects while reducing the frequency of conventional four-times-daily dosing (Mytonin® tablets). Four different BTC-loaded oral dosage forms were designed including gastro-retentive tablet (GRT), controlled-release tablet (CRT), bilayer tablet (BLT), and tablet-in-tablet (TIT).

Nitazene opioids and the heart: Identification of a cardiac ion channel target for illicit nitazene opioids.

The growing use of nitazene synthetic opioids heralds a new phase of the opioid crisis. However, limited information exists on the toxic effects of these drugs, aside from a propensity for respiratory depression. With restricted research availability of nitazenes, we used machine-learning-based tools to evaluate five nitazene compounds' interaction potential with the hERG potassium channel, a key drug antitarget in the heart.

Antitumor activity of selenopsammaplin A analog (SPA-10091-HCl) via histone methyltransferase DOT1L degradation and apoptosis induction in castration-resistant prostate cancer cells.

Castrate-resistant prostate cancer (CRPC) is one of the most difficult cancers in men and is characterized by a poor prognosis and a high risk of metastasis. The overexpression of the disruptor of telomeric silencing 1-like (DOT1L), which is a specific methyltransferase for histone H3 at lysine residue 79 (H3K79), has been related to poor outcomes in patients with CRPC. Therefore, targeting DOT1L is considered a potential therapeutic approach to overcome the significant medical challenges of CRPC.

Non-, a Treatable Provocateur of Parkinson's Disease: Hypothesis, Evidence and Species Specificity.

Epidemiological and eradication trial evidence indicates that , a major causative factor in peptic ulcer and gastric cancer, is a driver of the hypokinesia of Parkinson's disease (PD). Psychological (cognitive impairment, depression and anxiety) and gastrointestinal (peptic ulceration and constipation) PD features can precede the symptomatic onset of motor features by decades. We hypothesise that the non- (NHPH), which have farm, companion and wild animals as their main hosts, can have a role in PD aetiopathogenesis.

Exploring the DPP IV inhibitory potential: molecular docking and dynamic simulations of pyridine-3-carboxylic acid and pyrrolidine-2-carboxylic acid analogs.

Diabetes mellitus remains a global challenge, with Type 2 Diabetes Mellitus (T2DM) prevalence increasing from 4% to 6.4% in the past 30 years. Presently oral hypoglycaemic agents like GLP-1 agonists, biguanides, sulphonylureas, glinides, and thiazolidinediones are employed in clinical practice.

QbD-guided phospholipid-tagged nanonized boswellic acid naturosomal delivery for effective rheumatoid arthritis treatment.

Studies have reported the potential role of Boswellic acids (BAs), bioactive pentacyclic triterpenes from (BS), in treating rheumatoid arthritis (RA). However, poor water solubility and limited oral absorption are restricting factors for its better therapeutic efficacy. Based on these assumptions, the current study aimed to develop naturosomal delivery of BAs to boost their extremely low bioavailability, colloidal stability, and water solubility.

Hepatoprotective Effects of Resveratrol on Acetaminophen-Induced Acute Liver Injury and Its Implications for Tofacitinib Disposition in Rats.

Tofacitinib, which is used to treat rheumatoid arthritis (RA), is primarily metabolized by the hepatic cytochrome P450 (CYP) enzymes, CYP3A1/2 and CYP2C11. Acetaminophen (APAP), which is frequently used for pain relief in patients with RA, can induce acute liver injury (ALI) when taken in excess, profoundly affecting drug metabolism. Resveratrol (RVT) is a polyphenolic compound with hepatoprotective properties.

Polystyrene nanoplastics promote the blood-brain barrier dysfunction through autophagy pathway and excessive erythrophagocytosis.

There is increasing concern regarding the risks posed by plastics to human health. Nano-sized plastics enter the body through various exposure routes. Although nano-sized particles circulate through the bloodstream and access the blood-brain barrier (BBB), the harmful impacts of nano-sized plastics on BBB function including endothelial cells are not well known.

Cascade Reaction of Enyne-Amides with Sulfur-Ylides for the Synthesis of Indole-Tethered 5-Oxaspiro[2.4]hept-6-ene Derivatives.

An unexpected cascade reaction of enyne-amides with sulfur-ylides has been developed. This cascade reaction involves cycloisomerization, dearomatic cyclopropanation, ring-opening rearomatization, and subsequent cyclopropanation, differing from the common [2 + n] cyclization of enyne-amides. A variety of (spirocyclopropane)dihydrofuran derivatives have been efficiently and conveniently synthesized in a single vessel, exhibiting excellent diastereoselectivity and good functional group tolerance.

Controllable Phosphine-Catalyzed Three-Component Domino Reaction of Activated Alkenes with Morita-Baylis-Hillman (MBH) Carbonates: Divergent Synthesis of Densely Functionalized Cyclopentanes and Diquinanes.

An unexpected phosphine-catalyzed controllable three-component domino reaction involving [1 + 2 + 2] annulation and [1 + 2 + 2]/[3 + 2] sequential annulation reaction of 2-arylmethylidene cyanoacetates/malononitriles with Morita-Baylis-Hillman (MBH) carbonates has been developed. A broad range of densely functionalized cyclopentanes and diquinanes bearing five or four consecutive stereogenic centers, including two all-carbon quaternary stereocenters, were smoothly acquired in moderate to excellent yields under mild reaction conditions from readily available materials. Moreover, this divergent transformation enables the simultaneous generation of three or four new C-C bonds and one or two carbocyclic rings in only one step.

Bi-modal confirmation of liposome delivery to the brain after focused ultrasound-induced blood-brain barrier opening.

Focused ultrasound-mediated opening of the blood-brain barrier offers a great opportunity to deliver therapeutics into hard-to-treat brain tumors such as glioblastoma multiforme or diffuse midline glioma. However, the potential of the technique to offer a time window for efficient nanomedicine delivery has not been thoroughly studied. Non-invasive and targeted delivery of large drug-loaded nanocarriers, such as liposomes, could offer a safe and scalable method of personalized therapy for the treatment of brain pathologies.

Conformation Influences Biological Fates of Peptide-Based Nanofilaments by Modulating Protein Adsorption and Interfilament Entanglement.

Filamentous structures exert biological functions mediated by multivalent interactions with their counterparts in sharp contrast with spherical ones. The physicochemical properties and unique behaviors of nanofilaments that are associated with multivalent interaction with protein are poorly understood. Here, peptide-based nanofilaments containing different homotetrapeptidic inserts are reported and their protein adsorption and biological fates are tested.

Impact of 'street' benzodiazepines on drug-related deaths in England, Wales and Northern Ireland.

Introduction: 'Street' benzodiazepines (BZD) are structurally and pharmacologically related to BZDs licensed for human use. In this study we investigated how street BZDs contribute to overall BZD use and death prevalences in England, Wales and Northern Ireland.

Methods: Data were analysed from deaths reported to the National Programme on Substance Use Mortality with post-mortem BZD detections (1999-2021), BZDs seized from music festivals (2017-2021) and drug samples with BZD detections submitted to Welsh Emerging Drugs and Identification of Novel Substances (WEDINOS) (2017-2021).

Non-invasive in vivo sensing of bacterial implant infection using catalytically-optimised gold nanocluster-loaded liposomes for urinary readout.

Staphylococcus aureus is a leading cause of nosocomial implant-associated infections, causing significant morbidity and mortality, underscoring the need for rapid, non-invasive, and cost-effective diagnostics. Here, we optimise the synthesis of renal-clearable gold nanoclusters (AuNCs) for enhanced catalytic activity with the aim of developing a sensitive colourimetric diagnostic for bacterial infection. All-atom molecular dynamics (MD) simulations confirm the stability of glutathione-coated AuNCs and surface access for peroxidase-like activity in complex physiological environments.

Efficacy and safety of everolimus for patients with focal cortical dysplasia type 2.

Objective: This study aimed to evaluate the effectiveness and safety of everolimus in treating seizures associated with focal cortical dysplasia type 2 (FCD 2).

Methods: A prospective, crossover, placebo-controlled clinical trial (ClinicalTrials.gov: NCT03198949) enrolled patients aged 4-40 years with pathologically confirmed FCD 2 and a history of ≥3 seizures per month for two out of the 3 months prior to screening.

cGAS/STING pathway modulation in polyhexamethyleneguanidine phosphate-induced immune dysregulation and pulmonary fibrosis using human monocytic cells (THP-1) and male C57BL/6 mice.

Polyhexamethyleneguanidine phosphate (PHMG), a widely used antimicrobial agent, has been implicated in humidifier disinfectant-associated lung injuries (HDLI). PHMG exposure suppressed interferon regulatory factor 3 (IRF3) activation and interferon-β (IFN-β) expression induced by a cGAS agonist or a STING agonist in human monocytic cells (THP-1), which are known to transition to alveolar macrophages during pulmonary fibrosis development. However, the mechanisms underlying PHMG-induced pulmonary toxicity in lung remain unclear.

Sodium alginate based fast swelling nanogels for solubility enhancement of chlorthalidone; synthesis, characterization and biosafety evaluation.

Purpose of the study was to enhance the solubility of chlorthalidone, poorly soluble diuretic that has been the used for lowering high blood pressure for the past half-century. Solubility is a challenge for approximately 90% of drug candidates. Chlorthalidone is BCS Class IV drug whose poor solubility needs to be improved in order to optimize its efficacy.

Antibiotic Prescribing Decisions for Upper Respiratory Tract Infections Among Primary Healthcare Physicians in China: A Mixed-Methods Approach Based on the Theory of Planned Behavior.

In China, primary healthcare (PHC) facilities have high antibiotic prescribing rates for upper respiratory tract infections (URTIs), which are primarily viral and self-limited. This study aimed to identify the main factors influencing PHC physicians' antibiotic decisions for URITs based on the theory of planned behavior. A convergent mixed-methods study was conducted at 30 PHC facilities across Shaanxi Province, China.