Biota Pharmaceuticals (United States)

ABSTRACT Psidium guineense (Myrtaceae) is traditionally used for various medicinal purposes, although its stem remains underexplored. This study provides the first integrated phytochemical, pharmacological and computational evaluation of the stem extracts to elucidate their antioxidant, antidiabetic and antibacterial potential. The crude methanolic extract was fractionated with petroleum ether, dichloromethane, ethyl acetate and water. Preliminary phytochemical screening confirmed the presence of flavonoids, tannins, saponins, steroids, alkaloids, terpenoids and glycosides. Total phenolic and flavonoid contents were measured spectrophotometrically using the Folin–Ciocalteu reagent and the aluminium chloride colorimetric method, respectively. Antioxidant capacity was measured via 2,2‐diphenyl‐1‐picrylhydrazyl (DPPH) assay, antidiabetic potential via α‐amylase and α‐glucosidase inhibition, and antibacterial activity via disc diffusion method. Gas Chromatography‐Mass Spectrometry (GC‐MS) profiling of the methanolic extract led to the identification of 28 phytoconstituents. Among all fractions, the dichloromethane fraction (DPG) exhibited the highest phenolic (247.94 ± 15.38 mg gallic acid equivalents/g) and flavonoid levels (510.27 ± 16.71 mg quercetin equivalents/g), along with superior DPPH radical scavenging capacity. DPG demonstrated scavenging activity (IC 50 = 7.45 ± 0.87 µg/mL) comparable to ascorbic acid. In enzyme inhibition assays, DPG showed remarkable α‐amylase and α‐glucosidase inhibitory effects (IC 50 = 22.28 ± 0.97 and 25.00 ± 2.01 µg/mL, respectively)—activities that surpass those reported for leaf extracts of related species. All fractions exhibited moderate, selective antibacterial activity against B. subtilis with zones of inhibition 7–16 mm. GC‐MS profiling enabled tentative identification of compounds with reported antioxidant, antidiabetic and antimicrobial activities, supported by in silico docking showing strong predicted binding of selected tentatively identified constituents. These findings provide the first scientific investigation for the traditional use of P. guineense stem and highlight it as a previously unrecognized source of bioactive compounds warranting further isolation and characterization.

Abstract Description Background Senescent cells contribute to tumor growth, immune suppression and resistance to therapy. We investigated anticancer efficacy of SenoVax™, a dendritic cell (DC) based senescent cell targeting immunotherapy. Materials and Methods SenoVax was prepared from syngeneic bone marrow derived DC pulsed with lysates of senescent fibroblasts in vitro. Fibroblasts were rendered senescent using doxorubicin and confirmed by expression of p16, beta-galactosidase, and HMGB1. Mice were implanted with 4T1 breast cancer, GL261 glioma, LLC lung carcinoma, PAN 02 pancreatic adenocarcinoma, and B16 melanoma cells and treated with SenoVax. Assessment of tumor growth and immunity was performed. Results and Discussion: SenoVax administration resulted in growth inhibition and regression of the 4T1, GL261, LLC, PAN 02, and B16 tumors in vivo. In vitro analysis of lymphocytes from SenoVax-treated mice demonstrated induction of immunity to senescence-associated p16 and p21 protein antigens. Tumor regressions were associated with immunological cell infiltration and reduction of the SASP protein IL-6 and augmentation of the natural killer cell-promoting cytokine IL-12. These data support filed IND 30745 representing a proposed clinical trial for SenoVax in lung cancer. Topic Categories Tumor Immunology: Checkpoints, Prevention, and Treatment (TIPT)

Porcine epidemic diarrhea virus (PEDV) causes varying degrees of diarrhea, vomiting, dehydration, and emaciation in pigs, and severe cases can result in the death of suckling piglets. PEDV is one of the significant viruses affecting the global swine industry. In this study, we investigated the prevalence of PEDV infection in 2,346 pig samples collected from 20 provinces in China, with an overall positive rate of 43.3% (1,015/2,346). Phylogenetic analysis of 15 newly sequenced PEDV strains revealed that 1 strain belonged to the G1c (S-INDEL) genotype, 4 strains to G2b, and the remaining 10 strains to G2c, indicating that G2c is currently the dominant subtype. Compared with the classical CV777 strain, the nucleotide and amino acid sequence identities of the S gene of these 15 PEDV strains ranged from 92.71 to 94.83% and 92.89 to 94.99%, respectively. Amino acid alignment identified mutations of varying degrees within key neutralizing epitopes, including COE, SS2, SS6, and 2C10. Using the server, a new potential N-glycosylation site at position 302 (NKTI) in the S protein of the PEDV/XinJiang/2 strain was identified. Furthermore, linear and discontinuous antigenic epitopes of resolved PEDV proteins were predicted using ElliPro, revealing conserved potential antigenic regions at amino acid 31–54, 90–103, 1,170–1,177, 1,179–1,197, 1,201–1,211, 1,221–1,236, and 1,243–1,254. These findings provide new epidemiological data on PEDV circulating in China and offer valuable insights for the development of future vaccines and molecular diagnostics based on these antigenic epitopes, thereby contributing to improved PED control strategies.

Resistance to chemotherapy and subsequent relapse remain the primary challenge in pediatric acute myeloid leukemia (pAML), particularly in CBFA2T3-GLIS2 (C/G) fusion-positive acute megakaryoblastic leukemia. Here we demonstrate that the C/G fusion drives extensive DNA methylation changes and oncogenic enhancer activation at cis-regulatory elements (CREs), reshaping gene expression. This multi-omics analysis reveals a distinct hypermethylation pattern at promoters of up-regulated genes in C/G+ pAML across patient samples (n = 24) and representative cell lines, notably enriched in adhesion-related, TGFβ, or Wnt signaling pathways. Hypermethylated regions adjacent to transcription start sites (TSS) maintain open chromatin with H3K27ac enrichment, supporting a mechanism of de novo chromatin looping and active transcription in a non-canonical manner. Additionally, C/G fusion binding near the DNA methyltransferase 3B (DNMT3B) promoter correlates with elevated DNMT3B expression, implicating its role in aberrant DNA methylation changes at CREs. This study elucidates the epigenetic mechanisms driving C/G+ pAML, showing how the fusion reshapes chromatin and DNA methylation landscapes by impacting the expression (and likely activity) of epigenetic modifiers like DNMT3B. Functionally, DNMT3B inhibition enhances apoptotic sensitivity to BCL2 blockade, indicating that targeting DNMT3B may overcome apoptotic resistance in C/G+ leukemic cells and offer a therapeutic strategy for this high-risk subtype.

IntroductionAcne pathogenesis is multifactorial, involving systemic factors including gut dysbiosis, hormones, and chronic inflammation. Probiotics, myoinositol, and plant-derived molecules may modulate acne by targeting these factors. The objective is to compare a synbiotic containing herbs against a myoinositol-based herbal supplement on how they influence acne, the gut microbiome, short chain fatty acids (SCFAs), and hormonal profiles.MethodsThis was an 8-week, randomized study involving 36 male and female patients aged 12 to 45 years with non-cystic acne. Subjects received either a synbiotic or a myoinositol-based herbal supplement (MBHS). Acne lesions were counted, stool samples were collected for gut microbiome and SCFA analyses, and hormone collections were performed at baseline, 4, and 8 weeks.ResultsSeveral gut bacteria increased by at least threefold at both week 4 and 8 in the synbiotic (Erysipelatoclostridium merdavium, Blautia argi, Faecalibacterium prausnitzii, Prevotella copri, Streptococcus sp001556435, Blautia sp900541955) and MBHS group (Megamonas funiformis, Ligilactobacillus ruminis, Prevotella ssp015074785, Prevotella copri, Gca-900199835 sp900176495). Acne lesion counts decreased significantly in both groups at week 4 (p < 0.0001) and week 8 (synbiotic, p < 0.0001; MBHS, p < 0.0001). There were significant and trending increases in stool and plasma SCFAs in both cohorts at week 4 and 8. After 8 weeks of MBHS, 17-OHP and androstenedione significantly decreased from 27.3 to 11.3 pg/ml (p = 0.001) and 94.9 to 68.0 pg/ml (p = 0.04), respectively.ConclusionBoth the synbiotic and MBHS improved gut health, augmented SCFAs, and reduced lesion counts in those with non-cystic acne. The MBHS may act by reducing hormone levels of 17-OHP and androstenedione.Clinical Trial Registrationwww.clinicaltrials.gov (NCT05919810).

An important pathogenic role for neutrophils in systemic lupus erythematosus (SLE) has been proposed. Neutrophils that lack brain and muscle aryl hydrocarbon receptor nuclear translocator-like 1 (Bmal1), one of the clock genes, are defective in aging and proinflammatory responses. We assessed the role of Bmal1 in clinical and immunologic manifestations of murine lupus and in human SLE neutrophils. Myeloid-conditional Bmal1 knockout mice (Bmal1Mye-/- ) and wild type (WT) were treated with epicutaneous TLR7/8 agonist (imiquimod; IMQ) for 6 weeks to induce a lupus phenotype. Upon euthanasia, immune responses, autoantibodies and renal manifestations were evaluated. NET formation and gene expression of bone marrow (BM)-derived murine neutrophils were evaluated. BMAL1 expression was quantified in SLE neutrophils and compared with clinical disease. IMQ-treated Bmal1Mye-/- and WT displayed comparable systemic inflammation. While renal function did not differ, serum anti-dsDNA levels and renal immune complex deposition were significantly increased in Bmal1Mye-/- . While no differences were observed in NET formation, expression levels of April in BM neutrophils were significantly higher in Bmal1Mye-/- . Bulk RNA-sequence data showed that BM neutrophils in IMQ-treated Bmal1Mye-/- were relatively immature when compared with IMQ-treated WT. BM showed an enhanced April protein expression in Bmal1Mye-/- mice. BMAL1 levels in human SLE peripheral blood neutrophils correlated positively with serum C3 and negatively with serum anti-dsDNA levels. Bmal1 is associated with lower disease activity in SLE. These results indicate that perturbation in the circadian rhythm of neutrophils can have pathogenic consequences in SLE.

Abstract Background Periodontal disease (PD) is a common oral disease in dogs and humans. Dogs have distinctly different oral environments from humans. Although common bacteria are observed in both species, profiling of the causative bacteria for the progression of PD in dogs is limited compared to humans. Our study examined the shifts in the bacterial community within canine plaque as PD intensifies, analyzing plaque samples from 48 dogs at various PD stages. Additionally, we examined the impact of a tooth-brushing regimen using a dental gel on twelve dogs. Results We revealed a correlation between the age of the dogs and the severity of PD. As PD advanced, we noted a marked increase in Porphyromonas abundance, a key pathogenic genus. Conversely, Conchiformibius prevalence diminished in higher PD levels. Furthermore, a regimen of two week brushing with a dental gel resulted in a notable decrease in Porphyromonas levels and five of the twelve dogs improve severity. Conclusions Our findings suggest the potential efficacy of daily brushing with dental gels, incorporating compounds proven effective in humans, for managing PD in dogs. This study demonstrate a distinct disease progression in dogs compared to humans, underscoring the need for continued research and innovation in veterinary oral healthcare.