Chiral coordination complexes continue to attract interest as potential therapeutic agents, yet their stereochemical properties are rarely examined with the rigor now standard in organic drug discovery. Here we investigate whether the Δ and Λ enantiomers of the highly potent Ru(II) oligothienyl photosensitizer ML19G01 exhibit intrinsic differences in photobiological activity. Five independently synthesized batches of rac-ML19G01 were separated by direct chiral chromatography on a functionalized cyclofructan-6 (CF6-RN) stationary phase using both LC and sub/supercritical fluid chromatography. Enantiomeric excess was established by analytical chiral HPLC, absolute configuration was assigned by vibrational circular dichroism (VCD)/DFT comparison, and removal of trifluoroacetic acid (TFA), triethylamine (TEA), and counterion impurities was verified by 1H and 19F NMR. Enantiomeric integrity under illumination was confirmed to exclude photoracemization. Across 24 independent photobiological assays performed over several years in SK-MEL-28 melanoma cells, Δ- and Λ-ML19G01 displayed statistically indistinguishable dark and light EC50 values and phototherapeutic indices. Although individual experiments occasionally suggested enhanced potency of one enantiomer, these differences were not reproducible and were not supported by ANOVA/Tukey analysis. Small deviations observed for the racemate arose from non-stereochemical factors, including polymorphism, differential purification histories, and statistical averaging. These results demonstrate that ML19G01 does not exhibit meaningful enantiospecific photobiological behavior and provide practical recommendations for the preparation, characterization, and biological evaluation of chiral coordination complexes.

Cyclodextrin glucanotransferase (CGTase, EC 2.4.1.9) is an enzyme with its unique capability to transform starch and related substrates into cyclodextrins (CDs). Cyclodextrins are widely used in various industries (food, pharmaceuticals, textiles, and cosmetics). The present study focuses on the purification method of native CGTase from Alkalihalobacillus trypoxylicola KRM and enzyme characterization. The CGTase was purified to homogeneity by ammonium sulfate precipitation followed by starch adsorption and gel filtration. The purified CGTase demonstrated a specific activity of 2733.46 U/mg, corresponding to a 33.2-fold purification. Optimal activity was found at pH 8.0 (Tris HCl buffer) and at 50 °C temperature. CGTase was strongly inhibited by Fe3 +, Zn2+, Pb2+ and Al3+, while some metal ions (Ca2+, Na+, K+ and Mg2+) exerted stimulating effect. A metal chelating agent had a strong inhibitory effect, suggesting that metal ions may contribute to enzyme activity or structural stability. The detergent Triton X-100 was found to be lethal to the CGTase. CGTase showed temperature-dependent loss of activity with increasing first-order deactivation rates and Arrhenius analysis indicated an activation energy of ∼78.7 kJ/mol. The Km (1.83 mg/ml), and Vmax (833.33 μmol/min/ml) values were measured using a Lineweaver-Burk plot. To the best of our knowledge, this is the first report of a CGTase purified from Alkalihalobacillus trypoxylicola KRM. The enzyme exhibited moderate thermal stability and favorable catalytic properties under alkaline conditions.

Doxorubicin (DOX) is a highly effective anthracycline chemotherapeutic agent whose clinical utility is limited by dose-dependent cardiotoxicity. Although oxidative stress and mitochondrial injury are established mechanisms, the contribution of regulated metal-dependent cell death (MCD) pathways remains incompletely defined. This study investigated the ferroptosis and cuproptosis role in doxorubicin-induced cardiotoxicity (DIC) and evaluated the protective effects of luteolin (LUT) and nanoliposomal LUT using an integrated network pharmacology and experimental validation approach in rats. Network pharmacology identified multitarget interactions linking LUT with oxidative stress, metal homeostasis, and cell death signaling pathways. In vivo, DOX administration induced marked cardiac dysfunction, elevated serum cardiac injury biomarkers, myocardial histopathological damage, and ultrastructural abnormalities. These changes were accompanied by significant cardiac iron and copper accumulation, increased malondialdehyde (MDA), depleted superoxide dismutase (SOD) and glutathione (GSH), reduced glutathione peroxidase-4 (GPX4) activity, and increased tumor protein p53 (TP53) expression. At the molecular level, DOX downregulated the ferroptosis-protective genes, SLC7A11 and SLC3A2, while upregulating the iron transport genes, transferrin receptor 1 (TFR1) and SLC39A14, together with the cuproptosis-related genes ferredoxin-1 (FDX1) and SLC31A1, while suppressing ATP7A. These changes were further supported by altered protein expression of SLC7A11, ATP7A, and TP53. LUT significantly ameliorated these functional, biochemical, molecular, and structural alterations, indicating suppression of both ferroptotic and cuproptotic signaling. Nanoliposomal LUT showed superior efficacy to free LUT across most assessed parameters. Collectively, these findings support the involvement of ferroptosis and cuproptosis related signaling in DIC and highlight LUT, particularly in nanoliposomal form, as a promising cardioprotective strategy against anthracycline toxicity.

Substandard and falsified (SF) systemic anti-infective medications (SAMs) detected by the National Health Authority of Peru between 2015 and 2023 were quantified and characterized. An observational, descriptive, and retrospective design was applied, based on test reports issued by the National Quality Control Center on the quality of SAIs, complemented with national evidence of antimicrobial resistance (AMR). Of 9799 pharmaceutical products evaluated, 1247 (12.7%) were SF; of these, 189 (15.2%) corresponded to SF-SAM, with falsified ones predominating (11.0%). The main groups were β-lactams (27.5%), sulfonamides/tri-methoprim (26.5%), and quinolones (12.7%). 59.8% had informal origin, mostly from Lima (72%). The circulation of SF-SAM could promote selective pressure, the spread of AMR, and therapeutic failure.

We conducted a descriptive cross-sectional study in the neonatology service of the Hospital Nacional Guillermo Almenara Irigoyen (2020-2024) to characterize the clinical and microbiological profile of neonates with carbapenemase-producing Klebsiella pneumoniae bacteremia. Nineteen neonates were included; most were preterm and low birth weight, and approximately half presented bacteremia secondary to a respiratory focus. All strains carried the blaNDM gene. In vitro, 84.2% (16/19) were susceptible to amikacin and 40% (6/15) to tigecycline. All isolates had intermediate susceptibility to colistin and resistance to multiple antimicrobials. Empirical therapy was appropriate in 7/16 (43.8%) and about a fifth of the patients died. The identification of blaNDM reinforces the importance of local genomic surveillance to guide empirical therapy. The type of carbapenemase and its impact on mortality is a future research gap.

The HTR2A polymorphisms rs6311 (A-1438G) and rs6313 (T102C) have been thoroughly studied for their impact on atypical antipsychotics (AAPs) responsiveness in schizophrenia. However, the results remain inconsistent owing to the complex genetic and pharmacodynamic interactions. The Joanna Briggs Institute and Preferred Reporting Items for Systematic reviews and Meta-Analyses Extension for Scoping Reviews criteria were followed in this scoping review to map the available data on the association between HTR2A polymorphisms and outcomes. We identified 28 studies published before May 2025. Several studies reported that the rs6311 A allele was more frequently associated with improved treatment response, whereas the G allele was linked to poorer or absent response. In contrast, rs6313 exhibited heterogeneous patterns, with some studies reporting poorer response associated with the C allele and others reporting improved response associated with the T allele. This variability across studies likely reflects differences related to specific AAPs, as well as variations in study design and outcome definitions, rather than population or ethnicity-specific biological effects. Overall, HTR2A variants may contribute to interindividual variability in response to AAPs in schizophrenia. However, the current evidence remains insufficient for clinical application and requires further validation in well-designed and adequately powered studies.

Lignans constitute a diverse family of plant metabolites with therapeutic potential. Among them, podophyllotoxin-type aryltetralin lignans serve as precursors for etoposide and teniposide. Etoposide is an essential anticancer medicine approved for first-line treatment of small cell lung cancer, whereas teniposide is used for treatment of leukemia and some brain tumors. Currently, these drugs depend on extraction of precursors from the endangered plant Sinopodophyllum hexandrum, followed by chemical transformations. By identifying key glycosyltransferases and executing more than 60 genetic edits involving 45 heterologous enzymes, the complex biosynthetic pathway of podophyllotoxin-type lignans was reconstructed in yeast. In this study, we established a chemoenzymatic route that streamlines the synthesis of etoposide and teniposide through a single chemical step from biosynthetic precursor 4'-demethyl-epipodophyllotoxin-4-O-glucoside, which enables a secure supply chain of these essential medicines.

Group B Streptococcus (GBS) colonization in pregnant women is a major risk factor for neonatal diseases; however, molecular epidemiological studies on GBS in Japan remain limited. We characterized 219 GBS isolates recovered from vaginal screening cultures at a general hospital in Osaka Prefecture, Japan between 2021 and 2023. Capsular type, clonal complex/sequence type (CC/ST), virulence factors (pilus islands, Alp family, Srr1/Srr2, and HvgA), and antimicrobial resistance determinants were analyzed using whole-genome sequencing. The predominant lineages were CC19 (27.9%), CC23 (21.9%), and CC1 (21.0%), whereas the hypervirulent CC17 lineage accounted for only 5.5% of isolates. Capsular type Ia, III, and V comprised >60% of the isolates. PI-1/PI-2a (58.0%) was the predominant pilus profile, and rib (35.2%) was the most frequent Alp family gene. The hypervirulence-associated markers hvgA and srr2 were confined to capsular types III/CC17 and IV/CC452. All isolates were susceptible to β-lactams and vancomycin, whereas resistance to macrolides, clindamycin, and levofloxacin was observed at varying frequencies. These findings provide a pre-vaccine molecular baseline for maternal GBS carriage in Japan and highlight srr2-positive CC452 as a potential emerging lineage of concern.

Aleuritopteris bicolor, a fern species known locally as "Raani Sinkaa" in Nepal, has traditionally been used to treat wounds, diarrhea, dysentery, and gastritis. Despite its widespread use, scientific data on its bioactive compounds and bioactivities remain limited. To address this gap, this study aimed to isolate bioactive compounds from A. bicolor and evaluate their antioxidant, antibacterial, and antidiabetic properties using both in vitro and in silico methods. The 70% methanol extract of A. bicolor afforded three compounds: 20-hydroxyecdysone (1), and a mixture of quercetin 3-O-β-D-glucopyranoside (2) and quercetin 3-O-β-D-galactopyranoside (3), isolated via column chromatography. The structures of the isolated compounds were elucidated based on spectroscopic (NMR) and spectrometric (LC-MS) analyses. Compound 1 exhibited weak antioxidant activity, with an IC50 of 38.38 ± 3.41 µg/mL in the DPPH free radical scavenging assay. In contrast, the mixture of compounds 2 and 3 demonstrated significant antioxidant activity, with an IC50 of 1.56 ± 0.3 µg/mL, surpassing the standard ascorbic acid (IC50: 4.15 ± 0.3 µg/mL). Compounds 2 and 3 also showed moderate antibacterial activity against Staphylococcus aureus and Klebsiella pneumoniae. Furthermore, these compounds exhibited notable inhibition of α-amylase and α-glucosidase enzymes in in vitro assays, with EC50 values of 99.48 ± 3.2 µg/mL and 68.53 ± 1.7 µg/mL, respectively. In silico molecular docking analyses supported these enzyme inhibitions by revealing favorable interactions between compound 2 and key catalytic residues of the target enzymes, with binding energies of -7.2 kcal/mol for α-amylase and -7.1 kcal/mol for α-glucosidase. Additionally, ADMET analysis suggests further lead optimization of compounds 2 and 3. This study successfully isolated three bioactive compounds from A. bicolor and recommends further medicinal chemistry and in vivo investigations to establish their therapeutic potential as antidiabetic phytomedicine.

Current immunosuppressive treatment is used for autoimmune, inflammatory, malignant, transplant-related, and other chronic conditions that may carry elevated cerebrovascular burden. Nationally representative evidence on current immunosuppressive treatment status and self-reported lifetime stroke history remains limited. This cross-sectional study used pooled 2023-2024 National Health Interview Survey Adult Sample data. The analytic sample included adults aged 18 years or older with valid survey weights and complete data on exposure, outcome, and selected covariates. The exposure was current self-reported use of medications that weaken the immune system. The outcome was self-reported lifetime stroke history. Survey-weighted logistic regression estimated odds ratios and 95% confidence intervals, accounting for National Health Interview Survey stratification, clustering, and adjusted sampling weights. The final analytic sample included 60,026 adults, representing approximately 250 million United States adults. The weighted prevalence of current immunosuppressive treatment was 4.6%. Stroke history was more common among adults receiving immunosuppressive treatment than among those not receiving treatment (6.0% versus 2.8%). In unadjusted analysis, immunosuppressive treatment was associated with higher odds of stroke history (odds ratio 2.24, 95% confidence interval 1.86-2.70, p < 0.001). After full adjustment for age, sex, race/ethnicity, hypertension, diabetes, smoking status, coronary heart disease, and income-to-poverty category, the association persisted (adjusted odds ratio 1.71, 95% confidence interval 1.40-2.08, p < 0.001). Current immunosuppressive treatment status, likely reflecting both medication exposure and underlying disease burden, was associated with higher odds of self-reported lifetime stroke history among United States adults. Because of the cross-sectional design, broad exposure definition, self-reported outcome, and potential confounding by indication, these findings should be interpreted as an association rather than evidence of causation.

Clerodendrum thomsoniae Balf. f. (Lamiaceae) is commonly known as the bleeding-heart vine or glory tree and traditionally used for treating blood-related disorders. This research investigated the phytochemical constituents, antioxidant capacity, and thrombolytic potential of leaf extracts. Among the extracts, the ethanol extract exhibited the highest total phenolic content, which correlated with its strong antioxidant activity demonstrated through multiple assays including DPPH, hydrogen peroxide, nitric oxide (NO) scavenging, and ferrous ion chelation. The petroleum ether extract showed notable thrombolytic activity by effectively lysing blood clots, achieving 34.52% clot lysis, which was significantly higher than the negative control (7.89%) but lower than the standard drug streptokinase (60.23%). Through GC-MS analysis, identified several bioactive compounds including sterols and fatty acids, which likely contribute these health benefits. These results suggest that C. thomsoniae leaves are a promising natural alternative for managing cardiovascular disorder and oxidative stress. Further in vivo studies and isolation of active compounds are essential.

Gastric cancer (GC) remains a leading cause of cancer-related mortality worldwide, driven by late-stage diagnosis, metastatic progression, and therapeutic resistance. Src homology region 2 domain-containing phosphatase 2 (SHP2) has emerged as a critical regulator of oncogenic signaling in gastric tumorigenesis, yet its therapeutic targeting remains underexplored. In this study, we evaluated the anti-cancer efficacy of NSC 57774, a novel SHP2 inhibitor, using integrated bioinformatics and functional assays in AGS gastric cancer cells. Analysis of The Cancer Genome Atlas (TCGA) and UALCAN datasets revealed marked upregulation of SHP2 and multiple receptor tyrosine kinases in gastric cancer tissues. NSC 57774 potently inhibited cell proliferation and migration, demonstrating selective cytotoxicity towards cancer cells over non-cancerous fibroblasts. Mechanistically, NSC 57774 disrupted key oncogenic pathways including MAPK/ERK, AKT and STAT3 in a concentration- and time-dependent manner, with higher doses achieving more sustained pathway suppression. NSC 57774 suppressed NF-κB inflammatory signaling at early timepoints and induced cleaved caspase-3 across all treatment groups at 72 hours, indicative of pro-apoptotic activity. A paradoxical late-phase increase in phospho-p38 was observed at 72 hours, consistent with a compensatory pro-apoptotic stress response. Comparative analysis revealed that NSC 57774 outperformed the commercial SHP2 inhibitor NSC 87877 and doxorubicin in reducing viability and migration of gastric cancer cells. Collectively, these findings position NSC 57774 as a promising candidate for targeted gastric cancer therapy, capable of disrupting multiple signaling pathways involved in tumor progression, metastasis, and inflammation, warranting further preclinical and clinical investigation.