Bioscientia Medicina - Journal of Biomedicine and Translational Research
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Cell-Free Regenerative Therapy for Pulmonary Hypertension: Human Breastmilk Stem Cell Secretome Restores Endothelial Barrier Integrity and BMPR2 Signaling Under Hypoxic Stress
Full text linkBackground: Pulmonary hypertension (PH) is a severe vascular disorder characterized by chronic hypoxia-induced endothelial dysfunction, leading to aberrant remodeling and right ventricular failure. The human breastmilk-derived stem cell (hBSC) secretome contains bioactive factors that may promote endothelial regeneration. However, the temporal dynamics of secretome-mediated repair on critical structural and signaling molecules remain poorly understood.
Methods: An in vitro experimental study was conducted using human umbilical vein endothelial cells (HUVECs) exposed to severe hypoxia (1% O₂, 10% CO₂, 37°C) to replicate PH-associated endothelial dysfunction. Cells were divided into four groups: normoxia control, hypoxia control, and hypoxia treated with hBSC secretome for 24 and 72 hours. Expression of bone morphogenetic protein receptor type 2 (BMPR2) and vascular endothelial cadherin (VE-cadherin) was quantified via ELISA. CCK-8 assays evaluated cellular viability. Data were analyzed using one-way ANOVA and least significant difference (LSD) post-hoc tests.
Results: Hypoxia significantly diminished cell viability and reduced BMPR2 and VE-cadherin expression compared to normoxia (p<0.001). Administration of hBSC secretome significantly restored BMPR2 and VE-cadherin levels at both 24 and 72 hours (p<0.001), surpassing normoxic baselines. BMPR2 expression plateaued between 24 and 72 hours, while VE-cadherin expression demonstrated sustained functional recovery.
Conclusion: The hBSC secretome actively reverses hypoxia-induced endothelial injury through rapid, time-dependent modulation of BMPR2 signaling and VE-cadherin junctional integrity, presenting a viable cell-free therapeutic target for PH. 
Therapeutic Efficacy of Thymoquinone in Attenuating Obstructive Renal Fibrosis: A Dose-Response Analysis of Tumor Necrosis Factor-Alpha Suppression and Histopathological Remodeling
Full text linkBackground: Chronic kidney disease is characterized by progressive renal fibrosis, a maladaptive process driven by chronic inflammation and extracellular matrix accumulation. Tumor necrosis factor-alpha (TNF-α) plays a central role in this fibrogenic cascade. Thymoquinone (TQ), the primary bioactive compound of Nigella sativa, exhibits potent anti-inflammatory properties.
Methods: In this therapeutic intervention model, 107 male Wistar rats were subjected to Unilateral Ureteral Obstruction (UUO). To test TQ's ability to halt established fibrogenesis, treatment was delayed until day 7 post-obstruction. Rats were randomized to receive TQ intraperitoneally at 5, 10, or 20 mg/kg body weight for 14 days. Outcomes included renal function (urea/creatinine), tubulointerstitial injury (PAS staining), fibrosis area (Sirius Red staining), and localized TNF-α mRNA expression (reverse transcriptase PCR normalized to GAPDH). Data were analyzed using ANOVA followed by Tukey’s Honestly Significant Difference (HSD) test.
Results: UUO induced significant structural injury and upregulated TNF-α expression compared to sham controls (p < 0.001). TQ intervention significantly reduced the tubulointerstitial injury score, with the greatest reduction at 20 mg/kg (p < 0.01). The positively stained fibrotic area exhibited a U-shaped response, maximally decreased at the 10 mg/kg dose (p < 0.01). Similarly, TNF-α mRNA relative expression was significantly suppressed by TQ, exhibiting a pharmacological ceiling effect at 10 mg/kg (p < 0.01).
Conclusion: Thymoquinone administered therapeutically mitigates established structural renal fibrosis and tubulointerstitial injury by downregulating TNF-α-mediated inflammation. A 10 mg/kg dose represents the optimal therapeutic threshold for anti-fibrotic efficacy in obstructive nephropathy. 
Circulating Syndecan-1 as a Biomarker of Endothelial Injury and Survival in Hemodialysis: A Systematic Review and Meta-Analysis of Hemodynamic and Prognostic Associations
Full text linkBackground: Cardiovascular disease remains the primary cause of mortality in patients with end-stage renal disease (ESRD) undergoing hemodialysis (HD). Conventional risk factors fail to fully explain the high prevalence of resistant hypertension and intradialytic hemodynamic instability in this population. Emerging evidence points to the degradation of the endothelial glycocalyx (eGC), a protective luminal layer regulating vascular tone and permeability. Syndecan-1 (SDC-1), a core component of the eGC, sheds into the circulation during vascular stress. This study aimed to synthesize evidence regarding the magnitude of dialysis-induced SDC-1 shedding and its validity as a prognostic biomarker for survival and vascular stiffness. M
ethods: We conducted a systematic review and associative meta-analysis of observational studies and clinical trials. We searched Scopus, PubMed, and Web of Science for studies quantifying serum SDC-1 in HD patients and relevant physiologic comparators. Data were stratified to analyze three domains: the second hit phenomenon (acute pre- vs. post-dialysis shedding), diagnostic correlations with pulse wave velocity (PWV) and fluid status, and prognostic hazard ratios (HR) for all-cause mortality. A random-effects model was employed to account for population heterogeneity, specifically stratifying hemodialysis cohorts from heart failure comparators.
Results: Ten pivotal studies involving over 1,500 patients were included. The analysis confirmed a substantial acute surge in serum SDC-1 post-hemodialysis (Standardized Mean Difference = 1.24, p < 0.001), indicating that the dialysis procedure actively injures the endothelium. Elevated baseline SDC-1 correlated significantly with arterial stiffness (PWV) and sodium overload, supporting a mechanism of salt-induced vascular stiffening. In prognostic analysis, high SDC-1 was a robust independent predictor of mortality (Pooled HR = 1.65, 95% CI: 1.12–2.43).
Conclusion: Hemodialysis acts as a vascular stressor, triggering acute shedding of the endothelial glycocalyx. This shedding is mechanistically linked to sodium dysregulation and vascular stiffness, independent of traditional uremic toxins. SDC-1 serves as a valuable prognostic marker for endothelial health and survival, suggesting a need for endothelium-protective dialysis strategies
Immediate Reconstruction of Massive Gluteal Defects Following Giant Malignant Peripheral Nerve Sheath Tumors Excision: Application of the Fasciocutaneous Rotational Flap in a Resource-Stratified Setting
Full text linkBackground: Malignant peripheral nerve sheath tumors (MPNSTs) are aggressive soft tissue sarcomas often requiring radical excision. In the gluteal region, achieving oncological clearance for giant tumors creates massive defects characterized by dead space and tension. This study evaluates the utility of the fasciocutaneous rotational flap for immediate closure when free tissue transfer is unavailable.
Case presentation: A 56-year-old female presented with a rapidly enlarging, Grade III MPNST on the right buttock measuring 18 cm in diameter. Wide local excision resulted in a defect measuring 18 cm by 16 cm by 10 cm, exposing the gluteus maximus. Due to resource limitations preventing intraoperative frozen section analysis, wide anatomical clearance was prioritized. Immediate reconstruction was performed using a random-pattern fasciocutaneous rotational flap based on inferior gluteal artery perforators. The flap arc length measured 52 cm with a 1:3.25 defect-to-arc ratio. Postoperative histopathology confirmed Grade III MPNST with positive deep margins (R1), necessitating adjuvant radiotherapy. The flap healed completely by day 14 without necrosis, and the patient was discharged on day 5. At the 3-month follow-up, the wound remained stable with no dehiscence during radiation.
Conclusion: The gluteal fasciocutaneous rotational flap is a robust technique for closing massive defects where primary closure is impossible. While it provides excellent durable coverage for adjuvant therapy, the inability to confirm negative margins intraoperatively poses significant oncological risks. Immediate flap coverage should be weighed carefully against staged reconstruction in resource-stratified settings
The Ocular Toll of Drug Tourism: A Systematic Review and Meta-Analysis of Cannabis and Methamphetamine Impact on Retinal Architecture and Pupillary Dynamics
Full text linkBackground: Drug tourism involves individuals traveling across international borders to access recreational illicit substances. While psychiatric and cardiovascular toxicities of substances like cannabis and methamphetamine are established, quantitative data regarding their impact on ocular microstructures and functional dynamics remain scarce. This study aims to systematically review and meta-analyze the structural and functional ocular alterations induced by these substances.
Methods: A systematic review and meta-analysis complying with Preferred Reporting Items for Systematic Reviews and Meta-Analyses guidelines were conducted. Electronic databases (PubMed, Scopus, Web of Science, Cochrane Library) were searched from inception to January 2026. Data extraction targeted pupillary dynamics and structural optical coherence tomography measurements. Methodological quality was assessed using the Newcastle-Ottawa Scale and Cochrane Risk of Bias tools. A DerSimonian-Laird random-effects model was utilized in Review Manager 5.4 to pool continuous data, calculating Standardized Mean Differences and 95% Confidence Intervals. Heterogeneity was evaluated via the I-squared statistic.
Results: Nine primary research articles were included. The mean Newcastle-Ottawa Scale score was 8.1, indicating a low risk of bias. Chronic cannabis users exhibited significantly reduced pupillary constriction velocity (Standardized Mean Difference -0.85, 95% Confidence Interval -1.20 to -0.50, p < 0.001), prolonged reaction latency (Standardized Mean Difference 0.65, 95% Confidence Interval 0.30 to 1.00, p < 0.01), and decreased corneal endothelial cell density (Standardized Mean Difference -0.78, 95% Confidence Interval -1.15 to -0.41, p < 0.001). Methamphetamine abuse was associated with profound global retinal nerve fiber layer thinning (Standardized Mean Difference -1.12, 95% Confidence Interval -1.55 to -0.69, p < 0.001) and reduced minimum rim width (Standardized Mean Difference -0.95, p < 0.001).
Conclusion: Recreational cannabis and methamphetamine abuse cause significant, quantifiable ocular morbidity. Methamphetamine induces ischemic neurodegenerative retinal loss, while cannabis disrupts autonomic pupillary pathways and corneal integrity. Comprehensive ophthalmological screening is critical for individuals with substance abuse histories
Metabolic and Hematologic Synergism in Idiopathic Intracranial Hypertension: Reversal of Bilateral Papilledema via Multidisciplinary Gynecological and Systemic Interventions
Full text linkBackground: Idiopathic Intracranial Hypertension (IIH) conventionally presents with elevated intracranial pressure without structural etiologies, heavily associating with central adiposity. Emerging clinical frameworks recognize the intersecting roles of hematologic and metabolic abnormalities, notably iron deficiency anemia and hypovitaminosis D.
Case presentation: A 41-year-old obese female (Body Mass Index 30.04 kg/m2) presented with progressive, painless bilateral visual blurring. Initial evaluation revealed a right eye visual acuity of 6/7.5 and a severely reduced left eye visual acuity of 1/60, alongside prominent bilateral papilledema and flame-shaped hemorrhages. The patient was incorrectly diagnosed with optic neuritis externally. Upon referral, rigorous evaluation successfully dismantled the misdiagnosis; intact pupillary reflexes, absence of a relative afferent pupillary defect, and an enlarged blind spot pointed definitively to papilledema. A lumbar puncture confirmed an elevated opening pressure of 340 mmH2O with normal cerebrospinal fluid composition. Targeted systemic profiling uncovered severe iron deficiency anemia (Hemoglobin 7.90 g/dL) driven by chronic menorrhagia from a uterine myoma, compounded by marked hypovitaminosis D. A tailored multidisciplinary intervention was initiated. A conservative acetazolamide dosage (500 mg/day) was utilized to minimize systemic stress, combined with cholecalciferol supplementation, ferrous sulfate, and a laparotomic myomectomy. One month post-operatively, hemoglobin normalized to 11.70 g/dL, visual acuity was fully restored to 6/6 bilaterally, and papilledema completely resolved.
Conclusion: IIH is a multifactorial systemic syndrome. Prompt identification and aggressive correction of hematologic and metabolic drivers, including surgical eradication of hemorrhagic etiologies, are imperative for reversing intracranial hypertension and preventing permanent optic neuropathy
The Steel-Blue Peppering and Systemic Eosinophilia: Dermoscopic-Histopathological Correspondence of the Tyndall Effect in Generalized Fixed Drug Eruption
Full text linkBackground: Generalized fixed drug eruption (GFDE) represents a severe and distinctive variant of delayed-type hypersensitivity, characterized by widespread, recurrent pigmentary lesions involving at least three anatomical sites. Its clinical presentation often mimics extensive lichenoid dermatoses or infectious conditions such as Hansen’s disease, leading to significant diagnostic delays, particularly in geriatric populations with polypharmacy. While dermoscopy offers a non-invasive bridge to histopathology, specific correlative studies in generalized cases remain scarce.
Case presentation: We report the case of a 69-year-old male presenting with diffuse, well-demarcated, violaceous plaques affecting the face, trunk, extremities, and genitalia. The eruption demonstrated a pathognomonic acute latency, recurring at identical anatomical sites within six hours of re-exposure to an unprescribed analgesic cocktail. High-definition non-contact polarized dermoscopy identified two distinct morphological patterns: a brown starburst pattern with central clearing on the extremities and diffuse steel-blue peppering on femoral lesions. Notably, the patient exhibited a mixed immunophenotype characterized by marked eosinophilia (2,080 cells per microliter) and elevated total immunoglobulin E (2,295 IU per milliliter). Parasitic infection was rigorously excluded via negative stool examination and serology, and a Naranjo probability score of 10 confirmed a definite adverse drug reaction. Histopathological examination confirmed interface dermatitis with necrotic keratinocytes and marked pigment incontinence.
Conclusion: This study illustrates that steel-blue peppering is a reliable dermoscopic surrogate for deep dermal pigment incontinence via the Tyndall effect. The discrepancy between high systemic eosinophilia and low tissue eosinophilia suggests a complex, potentially mixed-hypersensitivity phenotype in generalized cases, distinct from classic localized fixed drug eruption
Utility of Tc-99m DTPA Hybrid SPECT/CT Cisternography in the Detection of Occult Postoperative CSF Fistula in an Infant with Lipomeningomyelocele: A Diagnostic Challenge and Technical Considerations
Full text linkBackground: Lipomeningomyelocele represents a complex spectrum of closed spinal dysraphism where surgical repair is frequently complicated by cerebrospinal fluid leakage. While overt fistulas are clinically apparent, occult or intermittent leaks in the pediatric population pose a severe diagnostic challenge. Magnetic resonance imaging, despite being the anatomical gold standard, frequently fails to distinguish active extravasation from postoperative seroma or edema due to overlapping signal intensities. This study evaluates the diagnostic superiority of Tc-99m DTPA Hybrid SPECT/CT cisternography in resolving this dilemma.
Case presentation: A 5-month-old female underwent resection of a large lumbosacral lipomeningomyelocele. Postoperatively, she developed persistent, clear fluid discharge from the incision, suggestive of a fistula, yet initial surgical re-exploration was inconclusive. The patient underwent radionuclide cisternography using 37 MBq of intrathecal Tc-99m DTPA. Standard planar scintigraphy at 1 hour and 3 hours was equivocal due to background renal activity. However, Hybrid SPECT/CT performed at 3 hours precisely localized an abnormal radiotracer tract extending from the thecal sac at L5 into the right multifidus muscle, a finding invisible on conventional imaging.
Conclusion: The integration of physiological flow data from scintigraphy with the anatomical specificity of low-dose CT allows for the detection of slow-flow, occult leaks that evade MRI. In infants with distorted post-surgical anatomy, Hybrid SPECT/CT should be elevated from a problem-solving tool to a primary diagnostic modality when clinical suspicion persists. The technique facilitates targeted repair, minimizing morbidity in this vulnerable population
Delayed Right-Sided Traumatic Diaphragmatic Rupture Complicated by Hepatothorax and Visceral Herniation a Decade Post-Trauma: A Case Report
Full text linkBackground: Traumatic diaphragmatic rupture (TDR) is a rare consequence of high-energy blunt trauma, accounting for less than 1% of all traumatic injuries. Right-sided ruptures are particularly uncommon, representing only 5% to 20% of cases, largely due to the protective anatomical positioning of the liver. Consequently, right-sided injuries are notoriously difficult to detect, often leading to a delayed diagnosis.
Case presentation: We present the case of a 29-year-old female who presented with progressive dyspnea ten years after sustaining a motor vehicle collision. Her initial injury was managed as a right-sided hemothorax, with the diaphragmatic defect remaining undetected. A decade later, imaging revealed an elevated right hemidiaphragm with massive herniation of the liver, gallbladder, transverse colon, and omentum into the right thoracic cavity. The patient underwent a successful abdomino-thoracotomy with primary repair of a 10 cm x 4 cm defect, reinforced with a prosthetic mesh. She was discharged on postoperative day seven with an uneventful recovery.
Conclusion: This case emphatically highlights the persistent, lifelong risk of delayed visceral herniation following thoracoabdominal trauma. A high index of suspicion must be maintained for patients presenting with delayed respiratory symptoms, as prompt surgical intervention yields excellent outcomes
Dose-Dependent Amelioration of Ureteral Obstruction-Induced Kidney Fibrosis by Thymoquinone via GPx-Mediated Antioxidant Defense
Full text linkBackground: Chronic kidney disease inevitably progresses to renal fibrosis, driven heavily by oxidative stress and the depletion of endogenous antioxidants including Glutathione Peroxidase (GPx). Thymoquinone (TQ), a bioactive compound from Nigella sativa, exhibits potent antioxidant properties. This study investigates the dose-dependent efficacy of TQ in mitigating renal fibrosis via GPx modulation in a Unilateral Ureteral Obstruction (UUO) model.
Methods: Thirty male Rattus norvegicus were randomly assigned to six groups (n=5): Sham, UUO + olive oil (Negative Control), UUO without oil, and UUO treated with TQ at 5, 10, and 20 mg/kg body weight for 14 days. Renal function (ureum, creatinine) and oxidative stress (Malondialdehyde) were measured. GPx mRNA expression was quantified using Reverse Transcription-Polymerase Chain Reaction. Tubulointerstitial injury (TII) and Positively Stained Area (PSA) for fibrosis were assessed histopathologically.
Results: UUO induction significantly downregulated GPx expression (median 0.52 versus 1.40 in Sham, p=0.001) and exacerbated TII (score 3.58) and PSA (11.42%). TQ administration dose-dependently upregulated GPx expression, peaking at 20 mg/kg (median 0.62, p=0.009 versus Negative Control). Furthermore, TQ 20 mg/kg significantly reduced the TII score to 2.26 and decreased fibrotic PSA, ameliorating morphological damage.
Conclusion: Thymoquinone exerts potent, dose-dependent antifibrotic and renoprotective effects in obstructive nephropathy by restoring GPx-mediated antioxidant defenses and preventing tubulointerstitial remodeling