Bioscientia Medicina - Journal of Biomedicine and Translational Research
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Renal and Cardiovascular Outcomes of SGLT2 Inhibitors versus ARNI in Cardiorenal Syndrome: A Network Meta-Analysis of Randomized Controlled Trials
Full text linkBackground: Cardiorenal syndrome involves complex pathophysiological cross-talk between the heart and kidneys, frequently culminating in refractory pulmonary congestion. Two primary pharmacological pillars, Sodium-Glucose Cotransporter-2 inhibitors and Angiotensin Receptor-Neprilysin Inhibitors, independently provide profound cardiovascular and renal benefits. However, direct comparative efficacy remains unquantified, creating clinical dilemmas in therapeutic sequencing.
Methods: A systematic review and network meta-analysis were conducted utilizing nine pivotal randomized controlled trials. A frequentist network meta-analysis approach utilizing random-effects models was employed. Time-to-event and continuous outcomes were harmonized and pooled utilizing Standardized Mean Differences to allow for indirect head-to-head comparisons between the two drug classes.
Results: The network comprised 43,450 patients. Both therapies significantly reduced cardiovascular events compared to standard care. In indirect comparisons, Angiotensin Receptor-Neprilysin Inhibitors demonstrated a superior reduction in the risk of urgent heart failure hospitalizations (Standardized Mean Difference -0.14; 95 percent Confidence Interval, -0.27 to -0.01) compared to Sodium-Glucose Cotransporter-2 inhibitors. Conversely, regarding the primary composite renal outcome (estimated glomerular filtration rate decline, end-stage renal disease, or renal death), Sodium-Glucose Cotransporter-2 inhibitors exhibited overwhelming statistical superiority over Angiotensin Receptor-Neprilysin Inhibitors (Indirect Standardized Mean Difference -0.35; 95 percent Confidence Interval, -0.50 to -0.20; p<0.001).
Conclusion: Both drug classes are indispensable for managing cardiorenal syndrome. Angiotensin Receptor-Neprilysin Inhibitors provide superior acute cardiovascular hemodynamic relief, whereas Sodium-Glucose Cotransporter-2 inhibitors offer unparalleled long-term structural protection of renal function. Tailored therapeutic sequencing must leverage these distinct physiological advantages
The Cardiovascular Burden of Fine Particulate Matter in Asia: A Systematic Review and Meta-Analysis of Hypertension Risk
Full text linkBackground: The epidemiological transition in Asia has precipitated a double burden of disease, where rapid industrialization intersects with an aging demographic to drive a surge in cardiovascular mortality. Hypertension remains the predominant modifiable risk factor in this context. While the correlation between fine particulate matter (PM2.5) and elevated blood pressure is documented in Western literature, evidence regarding Asian populations remains fragmented. This region faces a unique toxicological phenotype characterized by extreme exposure concentrations, distinct particulate composition including biomass and dust, and specific genetic susceptibilities, necessitating a dedicated regional analysis.
Methods: We conducted a systematic review and meta-analysis of observational studies published between 2017 and 2024, searching PubMed, Scopus, and Embase. We critically appraised exposure assessment methods, distinguishing between satellite-based estimates and ground monitoring, and performed a quality audit using the Newcastle-Ottawa Scale. To minimize temporal bias, we stratified analyses by study design into Incident Hypertension (Cohort studies) and Prevalent Hypertension (Cross-sectional studies).
Results: Nine pivotal studies encompassing over 600,000 participants from China, Taiwan, India, South Korea, and Thailand were synthesized. The random-effects meta-analysis revealed a significant pooled Hazard Ratio of 1.12 (95% CI 1.06 to 1.18) per 10 micrograms per cubic meter increase in long-term PM2.5. Heterogeneity was significant (I2 equals 90.2%), driven by regional variations. High-altitude cohorts in Tibet and high-exposure regions in India demonstrated synergistic risks with Odds Ratios exceeding 1.50 compared to moderate-exposure regions in Taiwan.
Conclusion: Long-term PM2.5 exposure is a potent, independent driver of hypertension in Asia. The data suggest a synergistic interaction between hypoxia and pollution, and a non-linear dose-response curve at high concentrations. Clinicians should consider residence in high-pollution zones a cardiovascular risk enhancer equivalent to traditional risk factors
In Vitro Dissolution Profiling and Release Kinetics of Abelmoschus manihot L. Ethanolic Extract Mucoadhesive Granules: A Higuchi Diffusion Model Analysis
Full text linkBackground: Peptic ulcer disease presents a persistent clinical challenge characterized by a critical imbalance between mucosal defensive mechanisms and aggressive luminal factors, including Helicobacter pylori infection and non-steroidal anti-inflammatory drug administration. The ethanolic extract of Abelmoschus manihot L. possesses potent antioxidant flavonoids, specifically quercetin, which exhibit significant gastroprotective potential. However, the therapeutic efficacy of conventional herbal extracts is often compromised by rapid physiological gastric emptying. The aim of this study was to formulate gastroretentive mucoadhesive granules containing the ethanolic extract of A. manihot using Hydroxypropyl Methylcellulose (HPMC) as a matrix polymer and to elucidate the drug release mechanism through advanced mathematical kinetic modeling.
Methods: The extract was standardized for total flavonoid content and antioxidant activity using the DPPH assay. Mucoadhesive granules were engineered via wet granulation with varying concentrations of HPMC (F1: 15%, F2: 20%, F3: 25%) and a constant 15% Carbopol. The formulations underwent rigorous physicochemical characterization, ex vivo wash-off mucoadhesion testing on porcine tissue, and in vitro dissolution profiling in artificial pH 1.2, 6.8, and 7.4 media. Release data were evaluated using Zero-order, First-order, and Higuchi kinetic models, validated via the Akaike Information Criterion (AIC).
Results: The standardized extract demonstrated potent antioxidant activity with an IC50 of 27.14 +/- 1.05 mcg/mL and a high total flavonoid content of 162.8 mg QE/g. All granule formulations exhibited excellent flowability. Formula F3 (25% HPMC) displayed superior swelling capacity (15.2-fold expansion) and mucoadhesion (30.0% retention at 60 minutes). Dissolution testing revealed F3 retarded drug release significantly compared to F1, releasing only 41.92% in pH 1.2 over 6 hours. Kinetic analysis confirmed that F3 strictly followed the Higuchi diffusion model, indicating release governed by diffusion through the swollen polymer matrix.
Conclusion: The HPMC-Carbopol mucoadhesive granules of A. manihot successfully achieved sustained release and enhanced structural mucoadhesion. Formula F3 represents a mechanistically sound gastroretentive delivery system, driven by complex polymer hydration dynamics, for the localized management of peptic ulcers
Evaluating the Indigenous Probiotic Lactococcus lactis D4 as an Adjuvant to Capecitabine: Modulation of NF-κB in a Colorectal Carcinogenesis Model
Full text linkBackground: Chronic inflammation driven by the nuclear factor kappa-B (NF-κB) signaling pathway is a fundamental driver of colorectal cancer (CRC) pathogenesis, promoting tumor survival, mucosal proliferation, and profound chemoresistance. Capecitabine is a standard first-line fluoropyrimidine chemotherapy; however, its clinical utility is frequently compromised by dose-limiting toxicities and the activation of inflammatory feedback loops. Lactococcus lactis D4, a novel probiotic strain isolated from traditional Indonesian fermented buffalo milk (dadih), possesses well-documented immunomodulatory properties.
Methods: A randomized controlled experimental study was conducted utilizing male Sprague-Dawley rats (n=37). Colorectal carcinogenesis was chemically induced via intraperitoneal administration of 1,2-dimethylhydrazine (DMH). Following strict histopathological confirmation of malignancy, the cohort was randomized into five distinct groups: Negative Control, Positive Control, L. lactis D4 monotherapy, Capecitabine monotherapy, and Combination therapy. Interventions were administered daily for 14 days. Outcomes included NF-κB protein expression assessed via immunohistochemistry (IHC) and targeted gene expression quantification via RT-qPCR.
Results: Immunohistochemical analysis demonstrated that the positive control group exhibited significantly elevated NF-κB protein expression (35.87 ± 13.53%). Capecitabine monotherapy significantly reduced this expression to 16.07 ± 3.79% (p=0.003). The Combination therapy achieved a profound reduction in NF-κB protein expression down to 12.99 ± 4.92%; however, this was not statistically superior to Capecitabine alone (p=1.000). Conversely, RT-qPCR analysis revealed no statistically significant difference in NF-κB mRNA levels among the experimental groups (p=0.094).
Conclusion: The combination of L. lactis D4 and Capecitabine effectively reduces NF-κB protein expression in a preclinical CRC model, achieving suppression levels comparable to primary chemotherapy. The distinct discordance between the significant protein suppression and the sustained mRNA expression levels suggests potential post-transcriptional or post-translational regulatory mechanisms that warrant further targeted molecular investigation
General Anesthesia and Modified Rapid Sequence Induction for Emergency Cesarean Delivery in an Eclamptic Adolescent with Severe Thrombocytopenia
Full text linkBackground: Eclampsia complicated by severe thrombocytopenia presents a critical anesthetic challenge, often representing an absolute contraindication to neuraxial anesthesia. When alternative approaches are mandated, General Anesthesia with Rapid Sequence Induction or a modified rapid sequence approach is crucial for high-risk obstetric emergencies.
Case presentation: A 16-year-old primigravida at 35 weeks gestation presented with eclampsia, acute fetal distress, and severe thrombocytopenia. Initial vitals showed a blood pressure of 150/98 mmHg. Laboratory findings confirmed severe preeclampsia with a critical platelet count of 42,000/µL. An airway assessment revealed a Mallampati class II airway with mild pharyngolaryngeal edema. Due to the high risk of spinal epidural hematoma, neuraxial anesthesia was contraindicated. An emergency cesarean section was performed using a modified rapid sequence induction. Following preoxygenation, induction was achieved with fentanyl 100 µg, midazolam 3 mg, and propofol 100 mg. Due to institutional unavailability of rocuronium, atracurium 30 mg was utilized. After a 2.5-minute onset interval utilizing apneic oxygenation and continuous cricoid pressure, the patient was successfully intubated on the first attempt with a Macintosh size 3 blade. The intraoperative course was hemodynamically stable.
Conclusion: A modified rapid sequence induction utilizing atracurium provides an effective alternative for airway control and physiological stability in eclamptic adolescents with coagulopathy, particularly in resource-limited settings where standard rapid-acting non-depolarizing agents are unavailable. 
Synergistic Effects of Stem Cell Integration on Cochlear Implant Performance in Sensorineural Hearing Loss: A Systematic Review and Meta-Analysis of Neural Preservation and Speech Perception
Full text linkBackground: Cochlear implantation represents the paramount intervention for severe-to-profound sensorineural hearing loss. However, device efficacy is fundamentally constrained by retrograde degeneration of spiral ganglion neurons and post-insertional intracochlear fibrosis. This study aimed to quantitatively evaluate the synergistic efficacy of integrating stem cell therapies with cochlear implants to preserve neural architecture and enhance auditory functional outcomes.
Methods: A systematic review and meta-analysis were executed following PRISMA guidelines. Comprehensive searches of electronic databases utilized specific Medical Subject Headings targeting biohybrid electrodes, mesenchymal stem cells, and spiral ganglion survival. Inclusion criteria strictly selected controlled in vivo preclinical models and human clinical trials evaluating concurrent stem cell application with implantation. Risk of bias was assessed utilizing SYRCLE and ROBINS-I tools. Random-effects models synthesized Standardized Mean Differences for neural preservation, with subgroup analyses evaluating delivery modalities.
Results: Eight pivotal studies met stringent inclusion criteria. Meta-analysis demonstrated a highly significant preservation of spiral ganglion density in stem cell-integrated cohorts compared to implant-alone controls (Pooled Standardized Mean Difference = 2.45; 95% Confidence Interval: 1.54–3.36; p < 0.001). Subgroup analysis revealed that electrode coating yielded superior neuroprotection compared to bolus injections. Electrophysiological data demonstrated significantly lowered Electrically Evoked Auditory Brainstem Response thresholds. Clinical cohorts exhibited stable impedances and rapid improvements in speech perception.
Conclusion: Stem cell-integrated cochlear implants orchestrate a potent bio-electronic synergy, modulating neuroinflammation and mitigating neural degeneration primarily through paracrine neurotrophic signaling. This bio-electronic integration represents a transformative paradigm in auditory rehabilitation, maximizing the fidelity of neural stimulation and optimizing clinical outcomes
Unveiling Peutz-Jeghers Syndrome in the Fourth Decade: A Rare Case of Colorectal-Predominant Polyposis and High-Grade Dysplasia without Pathognomonic Pigmentation
Full text linkBackground: Peutz-Jeghers syndrome (PJS) is a rare autosomal dominant condition characterized by gastrointestinal hamartomatous polyposis and mucocutaneous pigmentation. While typically presenting in childhood with small bowel predominance, adult-onset cases lacking classical phenotypic markers present severe diagnostic challenges.
Case presentation: A 41-year-old male with no significant family history presented with a six-month history of progressive constipation, altered stool caliber, and hematochezia. Clinical examination revealed an absolute absence of pathognomonic mucocutaneous pigmentation. Abdominal imaging and full colonoscopy demonstrated an extensive colorectal polyposis burden extending from the rectosigmoid junction to the caecum. Histopathology of the resected tissue confirmed hamartomatous polyps featuring arborizing smooth muscle cores alongside focal high-grade dysplasia. The patient successfully underwent an elective total proctocolectomy with an ileal J-pouch anal anastomosis and a diverting loop ileostomy. Postoperative recovery was completely unremarkable.
Conclusion: This case underscores the profound phenotypic heterogeneity of PJS. The presence of an extensive colorectal burden and high-grade dysplasia in an adult lacking mucocutaneous pigmentation highlights the definitive malignant potential of hamartomatous polyps and the critical necessity for prompt surgical intervention and tailored surveillance in atypical clinical presentations
Maternal Hyperthyroidism and Delayed Diagnosis of Bilateral Choanal Atresia in a 4-Month-Old Infant: A Case Report on Stentless Endoscopic Reconstruction
Full text linkBackground: Bilateral choanal atresia (BCA) is a life-threatening congenital anomaly typically presenting as a neonatal respiratory emergency. Survival beyond the neonatal period without surgical intervention is exceptionally rare. While the etiology is multifactorial, emerging evidence implicates maternal thyroid dysregulation in craniofacial malformations. This study reports a rare case of BCA diagnosed in a 4-month-old infant and evaluates the efficacy of stentless endoscopic repair using laterally-based mucoperiosteal flaps.
Case presentation: A 4-month-old female infant presented with failure to thrive (weight 5.2 kg, less than the 3rd percentile) and cyclical respiratory distress. Perinatal history revealed the mother had Graves' disease and discontinued methimazole at 6 weeks gestation. Retrospective analysis of maternal serum indicated uncontrolled thyrotoxicosis during the critical organogenesis window (TSH less than 0.01 mIU/L; fT4 2.8 ng/dL at 7 weeks). Diagnostic imaging confirmed mixed bony-membranous atresia. The patient underwent transnasal endoscopic choanoplasty using a laterally-based mucosal preservation technique. A 10-Fr silicone feeding tube was placed transnasally but did not function as a structural stent.
Conclusion: The intervention resulted in immediate airway patency. Quantitative outcomes showed an increase in oxygen saturation from 96% to 99% on room air and significant weight gain from 5.2 kg to 6.7 kg over two months. Follow-up at six months showed no restenosis. This case suggests a potential dual-hit teratogenic mechanism involving early methimazole exposure and subsequent uncontrolled maternal hyperthyroidism. Furthermore, it supports the efficacy of stentless repair in minimizing granulation tissue formation
Comparative Efficacy, Safety, and Patient Preference of One-Month (1HP) versus Three-Month (3HP) Rifapentine-Based Regimens for Latent Tuberculosis: A Network Meta-Analysis of HIV, Silicosis, and General Risk Populations
Full text linkBackground: The programmatic management of latent tuberculosis infection (LTBI) is undergoing a paradigm shift from long-course isoniazid monotherapy to short-course rifamycin-based regimens. While the 3-month weekly rifapentine/isoniazid (3HP) regimen is well-established, the ultra-short 1-month daily rifapentine/isoniazid (1HP) regimen offers a potential advancement in adherence. However, concerns regarding systemic hypersensitivity reactions, hepatotoxicity mechanisms, and efficacy in non-HIV populations like silicosis remain.
Methods: We conducted a systematic review and network meta-analysis (NMA) utilizing a random-effects frequentist model. We executed a comprehensive search of MEDLINE, Embase, and Cochrane Central Register of Controlled Trials to identify randomized controlled trials comparing rifapentine-based regimens. We analyzed data comprising over 10,000 participants to evaluate the efficacy (prevention of active TB), safety (hepatotoxicity and hypersensitivity), and completion rates of 1HP, 3HP, 4-month rifampin (4R), and 9-month isoniazid (9H). We specifically integrated novel data on silicosis patients and patient preference metrics.
Results: The network analysis demonstrated that 1HP was non-inferior to 9H in preventing active tuberculosis (Incidence Rate Difference: -0.02 per 100 person-years). 1HP achieved the highest treatment completion rate (97%), significantly superior to 3HP (82%) and 9H (69%). Safety analysis revealed a distinct divergence: 3HP was associated with a higher incidence of systemic flu-like drug reactions (3.5%) compared to 9H (0.4%), whereas 1HP demonstrated a safety profile that minimized both the hepatotoxicity of isoniazid and the hypersensitivity of intermittent rifapentine. In silicosis patients, modified 1-month regimens proved safe. However, preference analysis indicated that 81% of patients preferred the weekly dosing of 3HP over the daily burden of 1HP.
Conclusion: 1HP represents the most effective strategy for maximizing treatment completion without compromising bactericidal activity. The daily dosing of 1HP appears to induce immune tolerance, mitigating the hypersensitivity reactions observed in weekly 3HP dosing. While 3HP remains a viable option for those preferring less frequent dosing, 1HP is the superior clinical recommendation for rapid sterilization of latent reservoirs
Thresholds of Cytoprotection: Ethanolic Propolis Extract Mitigates Ischemia-Reperfusion Injury via the MDA/IL-6 Axis in a Graded Rat Skin Flap Model
Full text linkBackground: Distal necrosis in reconstructive skin flaps results from ischemia-reperfusion (I/R) injury, driven by reactive oxygen species (ROS) and pro-inflammatory cytokines. While Propolis exhibits antioxidant properties, its efficacy limit relative to the severity of ischemic challenge remains undefined.
Methods: A randomized, controlled experimental study was conducted using 36 male Wistar rats. A graded ischemia model was engineered using modified McFarlane flaps with increasing length-to-width ratios: Mild (2:1), moderate (3:1), and severe (4:1). Subjects were stratified into vehicle (Control) and treatment (Propolis 800 mg/kg/day, oral) groups across all dimensions. The primary endpoint was the percentage of viable flap area on Day 7. Secondary endpoints included serum Malondialdehyde (MDA), Interleukin-6 (IL-6), and histological scoring of inflammation.
Results: All animals survived the procedure. Propolis significantly increased viable tissue area in the moderate ischemia group (76.4 ± 4.2%) compared to Vehicle (52.1 ± 5.8%; p < 0.001). In Mild ischemia, survival was near-maximal in both groups (>92%). However, in Severe ischemia, Propolis failed to prevent significant necrosis (34.2 ± 6.1% survival vs. 28.5 ± 5.4% in Vehicle; p = 0.092), indicating a therapeutic ceiling. Biochemically, Propolis suppressed MDA (11.92 ± 0.45 nmol/mL) and IL-6 (121.0 ± 4.71 pg/mL) significantly in moderate challenges but was overwhelmed by the oxidative surge in severe ischemia (MDA > 12.0 nmol/mL).
Conclusion: Propolis confers significant protection against I/R injury by dampening lipid peroxidation and systemic inflammation, but this effect exhibits a distinct threshold. It is highly effective in moderate ischemic challenges but insufficient for severe vascular compromise