Nuclear Genome-Encoded Mitochondrial OXPHOS Complex I Genes in Female Buffalo Show Tissue-Specific Differences.

Buffalo physiology intricately balances energy, profoundly influencing health, productivity, and reproduction. This study explores nuclear-mitochondrial crosstalk, revealing OXPHOS Complex I gene expression variations in buffalo tissues through high-throughput RNA sequencing. Unveiling tissue-specific disparities, the research elucidates the genomic landscape of crucial energy production genes, with broader implications for veterinary and agricultural progress. Post-slaughter, tissues from post-pubertal female buffaloes underwent meticulous processing and RNA extraction using the TRIzol method. RNA-Seq library preparation and IlluminaHiSeq 2500 sequencing were performed on QC-passed samples. Data underwent stringent filtration, mapping to the Bubalus bubalis genome using HISAT2. DESeq2 facilitated differential expression gene (DEG) analysis focusing on 57 Mitocarta 3-derived genes associated with OXPHOS complex I. Nuclear-encoded mitochondrial protein transcripts of OXPHOS complex 1 exhibited tissue-specific variations, with 51 genes expressing significantly across tissues. DEG analysis emphasized tissue-specific expression patterns, highlighting a balanced OXPHOS complex I subunit expression in the kidney vs. brain. Gene Ontology (GO) enrichment showcased mitochondria-centric terms, revealing distinct proton motive force-driven mitochondrial ATP synthesis regulation. Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway analyses emphasized Thermogenesis and OXPHOS pathways, enriching our understanding of tissue-specific energy metabolism. Noteworthy up-regulation of NDUFB10 in the heart and kidney aligned with heightened metabolic activity. Brain-specific up-regulation of NDUFAF6 indicated a focus on mitochondrial function, while variations in NDUFA11 and ACAD9 underscored pivotal roles in the heart and kidney. GO and KEGG analyses highlighted tissue-specific mitochondrial ATP synthesis and NADH dehydrogenase processes, providing molecular insights into organ-specific metabolic demands and regulatory mechanisms. Our study unveils conserved and tissue-specific nuances in nuclear-encoded mitochondrial OXPHOS complex I genes, laying a foundation for understanding diverse energy demands and potential health implications.

Differential Expression of Nuclear-Encoded Mitochondrial Protein Genes of ATP Synthase Across Different Tissues of Female Buffalo.

The physiological well-being of buffaloes, encompassing phenotypic traits, reproductive health, and productivity, depends on their energy status. Mitochondria, the architects of energy production, orchestrate a nuanced interplay between nuclear and mitochondrial domains. Oxidative phosphorylation complexes and associated proteins wield significant influence over metabolic functions, energy synthesis, and organelle dynamics, often linked to tissue-specific pathologies. The unexplored role of ATP synthase in buffalo tissues prompted a hypothesis: in-depth exploration of nuclear-derived mitochondrial genes, notably ATP synthase, reveals distinctive tissue-specific diversity. RNA extraction and sequencing of buffalo tissues (kidney, heart, brain, and ovary) enabled precise quantification of nuclear-derived mitochondrial protein gene expression. The analysis unveiled 24 ATP synthase transcript variants, each with unique tissue-specific patterns. Kidney, brain, and heart exhibited elevated gene expression compared to ovaries, with 10, 8, and 19 up-regulated genes, respectively. The kidney showed 3 and 12 down-regulated genes compared to the brain and heart. The heart-brain comparison highlighted ten highly expressed genes in ATP synthase functions. Gene ontology and pathway analyses revealed enriched functions linked to ATP synthesis and oxidative phosphorylation, offering a comprehensive understanding of energy production in buffalo tissues. This analysis enhances understanding of tissue-specific gene expression, emphasizing the influence of energy demands. Revealing intricate links between mitochondrial gene expression and tissue specialization in buffaloes, it provides nuanced insights into tissue-specific expression of nuclear-encoded mitochondrial protein genes, notably ATP synthase, advancing the comprehension of buffalo tissue biology.

Supersaturation Behavior: Investigation of Polymers Impact on Nucleation Kinetic Profile for Rationalizing the Polymeric Precipitation Inhibitors.

BACKGROUND: Although nucleation kinetic data is quite important for the concept of supersaturation behavior, its part in rationalizing the crystallization inhibitor has not been well understood. OBJECTIVE: This study aimed to investigate the nucleation kinetic profile of Dextromethorphan HBr (as an ideal drug, BCS-II) by measuring liquid-liquid phase segregation, nucleation induction time, and Metastable Zone width. METHODS: Surfeit action was examined by a superfluity assay of the drug. The concentration was scrutinized by light scattering techniques (UV spectrum (novel method) and Fluorometer (CL 53)). RESULTS: The drug induction time was 20 min without polymer and 90 and 110 min with polymers, such as HPMC K15M and Xanthan Gum, respectively. Therefore, the order of the polymer's ability to inhibit nucleation was Xanthan Gum > HPMC K15M in the medium (7.4 pH). Similarly, the drug induction time was 30 min without polymer and 20, 110, and 90 min with polymers, such as Sodium CMC, HPMC K15M, and Xanthan Gum, respectively. Therefore, the order of the polymer's ability to inhibit nucleation was HPMC K15M > Xanthan Gum > Sodium CMC in SIFsp (6.8 pH), which synchronizes the polymer's potentiality to interdict the drug precipitation. CONCLUSION: The HPMC K15M and xanthan Gum showed the best crystallization inhibitor effect for the maintenance of superfluity conditions till the drug absorption time. The xanthan gum is based on the "glider" concept, and this shows the novelty of this preliminary research. The screening methodology used for rationalizing the best polymers used in the superfluity formulations development successfully.

Understanding the Phytoestrogen Genistein Actions on Breast Cancer: Insights on Estrogen Receptor Equivalence, Pleiotropic Essence and Emerging Paradigms in Bioavailability Modulation.

Prevalent as a major phenolic ingredient of soy and soy products, genistein is recognized as an eminent phytoestrogen owing to its interacting ability with estrogen receptors (ERs). The metabolic conversion of plant-derived genistin to genistein by gut microbes and intestinal enzymes enhances its absorption at intestinal pH of ~7.5-7.8. Genistein interferes in breast cancer (BC) development via pleiotropic actions on cell proliferation, survival, angiogenesis, and apoptosis. Though multiple investigations have demonstrated genistein intake-driven reduced BC risk, similar efficacy has not been replicated in clinical trials. Furthermore, multiple studies have structurally and functionally equated genistein extents with 17-ß-estradiol (E2), the most available physiological estrogen in females, culminating in aggravated BC growth. Of note, both genistein and E2 function via interacting with ERs (ERα and ERß). However, although E2 shows almost equal affinity towards both ERα and ERß, genistein shows more affinity towards ERß than ERα. Our cautious literature survey revealed typical intake mode, ER expression pattern and the ratio of ERα and ERß, transactivators/ regulators of ERα and ERß expression and activities, patient age, and menopausal status as decisive factors affecting genistein BC activities. Of further interest are the mechanisms by which genistein inhibits triple-negative breast cancers (TNBCs), which lack ERs, progesterone receptors (PRs), and human epidermal growth factor receptors (HER2). Herein, we attempt to understand the dosage-specific genistein actions in BC cells and patients with an insight into its better response via derivative development, nanocarrier-assisted, and combinatorial delivery with chemotherapeutic drugs.

Development and Validation of In Vitro Discriminatory Dissolution Testing Method for Fast Dispersible Tablets of BCS Class II Drug.

OBJECTIVES: Fast dispersible tablets (FDTs) get dispersed very fast due to which the discrimination of in vitro drug release and their evaluation is difficult. Hence in the present study a new in vitro discriminatory dissolution method was developed and validated for FDTs of domperidone of BCS class II. MATERIALS AND METHODS: FDTs of domperidone were prepared by direct compression method. The dissolution studies were performed in an eight-station Electrolab TDT-082 dissolution testing apparatus, analyzed by ultraviolet spectrophotometer and evaluated in different dissolution mediums i.e. sodium lauryl sulphate (0.5%, 1.0% and 1.5%) with fresh distilled water, simulated intestinal fluid pH 6.8, simulated gastric fluid pH 1.2 without enzymes, phosphate buffer solution (pH 6.8) and 0.1 N hydrochloric acid at different agitation speeds. RESULTS: The developed method was validated in terms of specificity, accuracy, precision, linearity and robustness. Amongst the different mediums, 0.5% sodium lauryl sulfate (SLS) with distilled water was found to be optimum with higher rate of discriminatory power. The percentage recovery was found to be 96 to 100.12 % and the % relative standard deviation value for precision (intraday and interday) was found to be less than 1%. Also a dissolution profile of prepared FDTs were compared in distilled water containing 0.5% SLS using similarity (f2) and dissimilarity (f1) factor calculation which showed dissimilarity in release profile and confirms the discriminatory nature of developed method. CONCLUSION: The discriminatory dissolution method for FDTs was developed and validated. All the obtained results were satisfactory, accurate and in range. The current method could be beneficial for formulation development and for assessment of quality of FDTs.

Chlorpheniramine maleate containing chitosan-based nanoparticle-loaded thermosensitive in situ gel for management in allergic rhinitis.

The aim of the present study was to fabricate a thermosensitive gel containing chlorpheniramine maleate (CPM)-loaded nanoparticles following intranasal administration for effective treatment of allergic rhinitis. Chitosan-based nanoparticles were prepared by a precipitation method followed by the addition of developed NPs within the poloxamer 407- and carbopol 934P-based mucoadhesive thermoreversible gel. Developed formulations were evaluated for particle size, PDI, % entrapment efficiency, and % cumulative drug permeation. NP3 formulation was found to be optimized on the basis of minimum particle size (143.9 nm), maximum entrapment efficiency (80.10 ± 0.414%), and highest drug permeation (90.92 ± 0.531%). The optimized formulation NP3 was then formulated into thermoreversible in situ gel. This intensifies the contact between the nasal mucosa and the drug and increases and facilitates the drug absorption which results in increased bioavailability. G4 formulation was selected as the optimized formulation on the basis of gelation ability and mucoadhesive strength. Histology was carried out to examine the damage caused by the optimized G4 formulation. Results revealed no visual signs of tissue damage thus indicated safe nasal delivery of nanoparticulate in situ gel formulation G4. Thus, intranasal CPM NP-loaded in situ gel was found to be a promising formulation for the management of allergic rhinitis.

Perianal Dermatitis, Its Incidence, and Patterns of Topical Therapies in a Level IV Neonatal Intensive Care Unit.

OBJECTIVE: To define the incidence of perianal dermatitis (PD) and determine the usage pattern and cost efficacy of diaper products among neonates admitted to a level IV neonatal intensive care unit (NICU) including those with a diagnosis of neonatal abstinence syndrome (NAS). METHODS: A retrospective cohort study to evaluate neonates with PD based on number of orders for Aquaphor, Bagbalm, Desitin, Flanders, or Nystatin. Various demographic and clinical parameters were recorded. Usage patterns of these five products were analyzed, and their costs estimated. Subgroup analysis was performed among infants with NAS. RESULTS: Of 1,241 admissions, 56.2% had at least one diaper product ordered during their NICU stay, while 52.6% had multiple products ordered. Only 23.0% of all neonates had appropriate documentation of PD. The most common product ordered first was Aquaphor (64.3%), followed by Desitin (19.2%). Note that 86% term NAS infants had PD compared with 28% term non-NAS infants. The estimated product cost was $14,139 over 2 years, averaging $20 per patient. CONCLUSION: Over half of NICU neonates were exposed to one or more diaper products, usually without documented PD diagnosis. Term NAS infants had three times higher incidence of PD than term non-NAS infants. The cost of diaper product use was significant, and possibly underestimated due to lack of documentation.

Neonatal Nasopharyngeal Colonization with Group B Streptococcus and its Association with Clinical Sepsis.

Objective This study aims to determine whether nasopharyngeal (NP) colonization with group B streptococcus (GBS) is associated with early-onset clinical sepsis within 72 hours of birth, prolonged antibiotic duration, longer neonatal intensive care unit (NICU) stay, and delay in tolerating full feeds among neonates ≥ 35 weeks gestation. Study Design A retrospective cohort study of 192 NICU neonates admitted for sepsis evaluation. Based on their GBS colonization status, the mother-neonate pairs were divided into four groups of mother-negative neonate (baby)-positive (MNBP), mother-positive neonate-positive (MPBP), mother-positive neonate-negative (MPBN), and a reference group of mother-negative neonate-negative (MNBN). Neonates with GBS-positive blood cultures were excluded. Results The colonized neonate groups of MNBP (odds ratio [OR]: 21.8, 95% confidence interval [CI]: 7.99, 59.44) and MPBP (OR: 35.5, 95% CI: 9.57, 131.70) were each associated with increased odds for clinical sepsis (p < 0.001). A similar pattern occurred for prolonged antibiotic use. MPBP group was associated with the increased NICU stay (adjusted ß: 0.1, standard error = 0.05, p < 0.01). None of the GBS groups were associated with increased days to full feeds. Conclusion Neonatal NP GBS colonization was found among a substantial proportion of GBS-negative mothers and was associated with an increased diagnosis of clinical sepsis.

Elevated pulmonary artery systolic pressures are associated with a lower risk of atrial fibrillation following lung transplantation.

BACKGROUND: Atrial fibrillation (AF) is common after open-chest procedures, but the etiology remains poorly understood. Lung transplant procedures allow for the study of novel contributing factors. METHODS: Records of lung transplant procedures performed at a single center between 2002 and 2009 were reviewed. RESULTS: Of 174 patients, 27 (16%) had AF a median 6 days post-surgery. Post-operative AF patients less often had right ventricular hypertrophy (RVH) by either electrocardiogram (0 versus 14%, P=.042) or echocardiography (19% versus 47%, P=.006), and had lower pulmonary artery systolic pressures (PASP) (39 ± 12 versus 51 ± 22, P=.005). After multivariable adjustment, every 10-mm Hg increase in PASP was associated with a 31% reduction in the odds of post-operative AF (OR 0.69, 95% CI 0.49-0.98, P=.035). A higher pulmonary pressure was the only predictor independently associated with less post-operative AF. CONCLUSIONS: Higher PASP was associated with a lower risk of AF after lung transplantation.