Concomitant use of sodium-glucose co-transporter 2 inhibitors and metformin and the risk of osteomyelitis reporting: a disproportionality analysis based on FAERS database.

Background: Recent clinical case reports have generated controversy concerning the adverse events (AEs) of amputation linked to sodium-glucose co-transporter 2 inhibitors (SGLT2i). We assessed the risk of osteomyelitis AE reporting linked to SGLT2i or SGLT2i-metformin co-medication.

Research Design And Methods: Investigated the FDA Adverse Event Reporting System for osteomyelitis-related AEs associated with SGLT2i or SGLT2i-metformin co-medication from 2013q2 to 2023q1.

Sesquiterpene lactones from Seriphidium transiliense and their anti-inflammation activity.

Six undescribed sesquiterpene lactones (1-6) and fifteen known compounds (7-21) were isolated from Seriphidium transiliense. The chemical structures were determined by extensive NMR spectroscopic data, HRESIMS, ECD and X-ray diffraction. Among the known compounds, twelve known compounds were isolated for the first time from this plant, including taurine (9), 11-epitaurin (10), α-santonin (11), artesin (13), 11-epiartesin (14), 1α-hydroxy-3β-acetoxyeudesm-4-en-6β, 7α, 11βH-12, 6-olide (15), 1α-hydroxy-3β-acetoxyeudesm-4-en-6β, 7α, 11αH-12, 6-olide (16), artegallin (17), 8α-hydroxytaurin (18), 8α-acetoxytaurine (19), methyl-4α-hydroxy-11(13)-eudesmen-12-oatesaniculamoid D (20), and saniculamoid D (21).

Chrysin modulates the BDNF/TrkB/AKT/Creb neuroplasticity signaling pathway: Acting in the improvement of cognitive flexibility and declarative, working and aversive memory deficits caused by hypothyroidism in C57BL/6 female mice.

Hypothyroidism is known to affect memory consolidation, and our prior research highlighted the potential of chrysin as a therapeutic agent to restore cognitive function. The present study aimed to investigate the action mechanism of chrysin on memory deficits in hypothyroid in C57BL/6 female mice. We assessed cognitive flexibility, declarative, working, and aversive memories while analyzing the BDNF/TrkB/AKT/Creb neuroplasticity signaling pathway and synaptic function in the hippocampus and prefrontal cortex.

Catalogue of inherited autosomal recessive disorders found amongst the Roma population of Europe.

Background: The Roma population are an endogamous, genetically isolated, minority population who migrated from North-Western India to Europe from the 10 Century throughout the Byzantine period and continues to the present day. Approximately 10-12 million Romani people reside in segregated settlements in Europe, and smaller populations live in North America and China. In addition to the endogamy, they also practice consanguinity.

Evaluating Efflux Pump Inhibition in Staphylococcus aureus 1199B Strain Using Thiadiazine-Derived Compounds: In Vitro and In Silico Approaches.

Thiadiazines are heterocyclic compounds known for some pharmacological activities. However, the ability of these compounds and their derivatives to act as antibacterial agents and inhibitors of the efflux system in resistant bacteria remains unknown. This study aims to evaluate the antibacterial and NorA efflux pump inhibitory activities of thiadiazine-derived compounds (IJ14, IJ15, IJ16, IJ17, IJ18, IJ19, and IJ20) against the Staphylococcus aureus 1199B strain.

Variants in EP400, encoding a chromatin remodeler, cause epilepsy with neurodevelopmental disorders.

EP400 encodes a core catalytic ATPase subunit of ATP-dependent chromatin remodeling complexes. The gene-disease association of EP400 is undetermined. In this study, we performed trio-based whole-exome sequencing in a cohort of 402 families with epilepsy and neurodevelopmental disorders (NDDs) and identified compound heterozygous EP400 variants in six unrelated individuals.

Dihydrofolate reductase inhibitory potential of 1H-indole-based-meldrum linked 1H-1,2,3-triazoles as new anticancer derivatives: In-vitro and in-silico studies.

In this present work, we describe the syntheses of a new series of 32 1H-indole-based-meldrum linked 1H-1,2,3-triazole derivatives (2-13, 15a-15f, 16a-16f, 17a-17f and 19a, 19b, 20a), which constitute a new class of 1H-1,2,3-triazoles. Compounds 15a-15f, 16a-16f, 17a-17f have been prepared by employing "click" reactions between substituted 1H-indole-based meldrum alkynes (11, 12 and 13) and substituted aromatic azides (14a-14f) in the presence of copper iodide (CuI) and Hünig's base. Then, the synthesis of compounds 19, 20 through decomposition of meldrum moiety.

Direct injection UPLC-MS/MS method for analysing 77 compounds including human biomarkers, illicit drugs, new psychoactive substances and metabolites in wastewater.

Wastewater analysis technology has emerged as a promising tool for monitoring illicit drug consumption. However, the current reliance on the solid-phase extraction (SPE) pre-treatment method presents significant challenges for widespread adoption and high-throughput monitoring, as it consumes a large amount of time and labor as well as requires specialized instruments. This study has developed a direct injection (DI) technique for UPLC-MS/MS, enabling the detection of 77 compounds encompassing metabolites of human biomarkers, illicit drugs, and new psychoactive substances.

A versatile and automatic on-line screening method: Transverse diffusion of laminar flow profiles-based capillary electrophoresis for exploring PTP1B inhibitors in natural products.

Natural products (NPs) play an important role in drug discovery and drug development due to their diverse chemical properties and biological activities. In the present work, an on-line capillary electrophoresis (CE) method was developed and applied to screen protein tyrosine phosphatase 1B (PTP1B) inhibitors in NPs. As a generic technique, transverse diffusion of laminar flow profiles (TDLFP) was utilized to mix all reactants in the capillary for on-line enzymatic reaction.

Recent advances in green solvents-based liquid-phase microextraction techniques for chromatographic analysis of active components in traditional Chinese medicine.

Traditional Chinese medicine (TCM) is a treasure of China and a crucial part of traditional medicine in the world, particularly in many oriental countries. TCM is the core and basis of traditional medicine in clinical practice for numerous diseases, and performs important function in nutraceuticals and dietary supplements. However, it is extremely difficult to extract each active ingredient from TCM to elucidate the mechanism of TCM clinical efficacy due to numerous compounds in TCM, especially trace compounds.

Triple-mode sensing platform for acetylcholinesterase activity monitoring and anti-Alzheimer's drug screening based on a highly stable Cu (I) compound.

Acetylcholinesterase (AChE) and AChE inhibitors play critical roles in the early diagnosis and treatment of Alzheimer's disease (AD). Herein, a fluorescence/colorimetry/smartphone triple-mode sensing platform was constructed for both AChE activity monitoring and AChE inhibitor screening by exploring a Cu (I) compound, CuI (SR) (R = CHCHNH), as a fluorescent probe. In comparison of most other fluorescent probes, CuI (SR) presented exceptional stability against pH, temperature, UV irradiation, redox agents, and metal ions, as well as good recyclability due to its unique chemical structure.

Comprehensive pharmacokinetic profiling of twelve compounds from Phellinus Igniarius extract in rats by UHPLC-MS/MS.

The medicinal fungus Phellinus Igniarius (P. igniarius) has been demonstrated to possess a variety of pharmacological effects, including anti-oxidant, anti-tumor, blood circulation promotion, anti-diarrheal and sedative properties, etc. In order to gain a deeper understanding of the components in P.

Recent advances in the study of mercury biogeochemistry in Arctic permafrost ecosystems.

Permafrost predominates in polar and high mountain regions, encompassing nearly 15 % of the exposed land in the Northern Hemisphere. It denotes soil or rock that remains at or below 0 °C for the duration of at least two consecutive years. These frozen soils serve as a barrier to contaminants that are stored and accumulated in permafrost over extended periods of time.

Esterified Lignin Nanoparticles for Targeted Chemical Delivery in Plant Protection.

There is a growing demand for biobased functional materials that can ensure targeted pesticide delivery and minimize active ingredient loss in the agricultural sector. In this work, we demonstrated the use of esterified lignin nanoparticles (ELNPs) as carriers and controlled-release agents of hydrophobic compounds. Curcumin was selected as a hydrophobic model compound and was incorporated during ELNP fabrication with entrapment efficiencies exceeding 95%.

A patent review of mitogen-activated protein kinase-interacting kinases (MNKs) modulators (2019-present).

Introduction: The mitogen-activated protein kinase interacting kinases (MNKs) modulate protein translation through the phosphorylation of eukaryotic initiation factor 4E (eIF4E) at serine 209, which is crucial for tumorigenesis but dispensable for normal development. MNKs are implicated in various pathological processes, including inflammation, obesity, cancer, etc. Thus, MNKs are considered as potential drug targets and the development of potent and selective MNK inhibitors is a current research focus.

Obacunone regulates ferroptosis in ovarian cancer through the Akt/p53 pathway.

Ovarian cancer is characterized by a high rate of recurrence and a poor prognosis. Ferroptosis, a programmed cell death that is dependent on iron and lipid peroxidation, has emerged as a novel therapeutic target in recent years. This study investigated the effects of Obacunone, a naturally occurring compound present in citrus fruits, on the induction of ferroptosis in ovarian cancer via the Akt/p53 signaling pathway.

Exploring the role of pomalidomide in androgen-dependent prostate cancer: a computational analysis.

Prostate cancer (PC) is among the most prevalent cancers in males. It is the leading cause of death in men, in around 48 out of 185 countries. Increased androgen receptor (AR) activity is the key factor contributing to the development or progression of newly diagnosed cases of prostate cancer.

Bixa orellana (Bixaceae) seeds as a potential source of bioactive compounds for modulating postprandial hyperglycemia.

Background: α-Amylase (α-AMY) and α-glucosidase (α-GLU) inhibitors are important for controlling postprandial hyperglycemia (PHG). Bixa orellana (annatto) reported inhibitory activity against these enzymes because of its bioactive compound content. However, an understanding of its inhibitory mechanisms and metabolic profile is necessary to establish its therapeutic potential.

From physicochemical characteristics variability to purple passion fruit (Passiflora edulis f. edulis) powders nutritional value: on the path of zero-waste.

Background: Purple passion fruit (Passiflora edulis f. edulis) is a highly appreciated fruit typically consumed in fresh or processed into various food products. The peel and seeds, which are by-products of fruit processing, are rich in nutrients and bioactive compounds with potential to be valorised into food applications.

Prebiotics and iron fortification among women of reproductive age group - Is there an association with liver and renal function tests?

Iron fortification compounds are of special interest to treat iron deficiency anemia, however, the dose-response effects of these fortificants on liver and renal functions have not been extensively reported in human subjects. The present study determines the effects of prebiotics and iron fortificants on liver function tests (LFTs) and renal function tests (RFTs) among women of reproductive age (WRA). A double-blind randomized controlled trial was performed for the duration of 90 days.

A brief history of chlorfluazuron in termite bait in the Asia-Pacific.

Chlorfluazuron was discovered and developed in the Asia-Pacific region by Ishihara Sangyo Kaisha (ISK) Japan and launched in the 1980s. The compound is a benzoylphenyl urea and acts as an insect growth regulator by inhibiting chitin synthesis in insects. Subsequently, Ensystex developed chlorfluazuron for termite baits, with test results demonstrating that it met key criteria for good termite baits.

Exploring the Complex Mechanisms of Isoflavones: From Cell Bioavailability, to Cell Dynamics and Breast Cancer.

In Western countries, the increase in the consumption of soy-derived products raises the population's exposure to isoflavones. These molecules, present in many foods, have numerous effects on the body's cells, including regulation of the transcription and epigenetics, cell signaling, cell cycle, cell growth, apoptosis, and oxidative stress. However, despite the multitude of studies conducted, on these compounds, it remains difficult to draw definitive conclusions regarding their safety or dangerousness in the diet.

Azadirachtin disrupts ecdysone signaling and alters sand fly immunity.

Background: Leishmaniasis is a group of neglected vector-borne diseases transmitted by phlebotomine sand flies. Leishmania parasites must overcome various defenses in the sand fly midgut, including the insects's immune response. Insect immunity is regulated by the ecdysone hormone, which binds to its nuclear receptor (EcR) and activates the transcription of genes involved in insect immunity.

Targeting SARS-CoV-2 main protease: a comprehensive approach using advanced virtual screening, molecular dynamics, and in vitro validation.

The COVID-19 pandemic, driven by the SARS-CoV-2 virus, necessitates the development of effective therapeutics. The main protease of the virus, Mpro, is a key target due to its crucial role in viral replication. Our study presents a novel approach combining ligand-based pharmacophore modeling with structure-based advanced virtual screening to identify potential inhibitors of Mpro.

Amorphous Solid Dispersions of Glycyrrhetinic Acid: Using Soluplus, PVP, and PVPVA as the Polymer Matrix to Enhance Solubility, Bioavailability, and Stability.

Glycyrrhetinic acid (GA) possesses various pharmacological effects, including anti-inflammatory, anti-tumor, and anti-viral properties. However, its clinical application is limited by poor solubility and low oral bioavailability. Polymers play a crucial role in pharmaceutical formulations, particularly as matrices in excipients to enhance the solubility, bioavailability, and stability of active pharmaceutical ingredients.