Amr Ali Mohamed Abdelgawwad El-Sehrawy

Osteosarcoma is a highly aggressive primary bone malignancy characterized by rapid proliferation, chemoresistance, and early metastasis. Recent advances in CRISPR/Cas (clustered regularly interspaced short palindromic repeats/CRISPR‐associated proteins) genome editing have enabled precise targeting of oncogenes, tumor suppressors, and regulators of epigenetic, metabolic, and signaling pathways, providing new insights into osteosarcoma biology. CRISPR‐mediated knockout of cell‐cycle regulators, including CDK11, impairs proliferation, while restoration of TP53 and suppression of TERT promoter activity inhibits tumor growth. Other line of studies has revealed that chemoresistance mechanisms mediated by ABCB1/MDR1, CD44, ATR, RAD18, and autophagy‐related genes have been effectively reversed through CRISPR interventions, restoring sensitivity to cisplatin and doxorubicin. Furthermore, CRISPR applications in immune modulation, such as PD‐L1 knockout, may enhance antitumor immunity. Importantly, high‐throughput CRISPR screens also may identify essential genes, novel oncogenic drivers, and synthetic lethal targets, thus informing potential precision therapeutic strategies. This review aims to critically summarize CRISPR/Cas‐mediated studies in osteosarcoma, focusing on targeting oncogenes and tumor suppressors, overcoming chemoresistance, modulating immune responses, regulating metabolism and autophagy, and identifying essential genes and vulnerabilities, providing a translational framework for precision therapy.

Sepsis‐associated acute respiratory distress syndrome (ARDS) remains associated with substantial mortality despite decades of research, and the reasons why many disease‐modifying treatments have failed remain incompletely understood. This narrative review synthesizes emerging evidence implicating neutrophil extracellular traps (NETs) in the interaction between innate immunity, immunothrombosis, and microvascular failure in sepsis‐ARDS. NETs, extruded lattices of DNA, histones, and granular enzymes, serve as antimicrobial scaffolds but may contribute to tissue injury when excessive or persistent. Within the pulmonary microcirculation, experimental studies indicate that NETs can concentrate tissue factor and proteases, activate platelets, suppress fibrinolysis, and injure endothelium through histone cytotoxicity, supporting a self‐amplifying thrombo‐inflammatory loop. These processes may contribute to microvascular obstruction and barrier dysfunction, although their relative importance varies across experimental models and patient populations. We critically evaluate emerging NET‐directed interventions, including peptidylarginine deiminase 4 (PAD4) inhibition to prevent NET formation, recombinant deoxyribonuclease (DNase) to dismantle existing scaffolds, targeted neutralization of NET components (citrullinated histones), and selective anticoagulation targeting factor XII/XI. Challenges of timing, infection risk, and patient heterogeneity support further evaluation of biomarker‐guided “NET‐otyping” using plasma myeloperoxidase‐DNA, citrullinated histone H3, and experimental molecular imaging. Building on existing work in microvascular protection, we examine whether more effective and selective NET targeting could improve treatment of sepsis‐ARDS. Clinical benefit remains to be established.

Bariatric surgery induces profound metabolic changes; however, its impact on levothyroxine (LT4) requirements, hormone pharmacokinetics, and gut microbiome

Non-alcoholic fatty liver disease (NAFLD) is a common metabolic condition characterized by hepatic steatosis and chronic low-grade inflammation, with oxidative stress playing a pivotal role in its progression. The neutrophil-to-lymphocyte ratio (NLR) has been proposed as an accessible marker reflecting systemic inflammatory status. This study aimed to examine the relationship between NLR, metabolic risk factors, body composition indices, and dietary antioxidant quality in adults with NAFLD. In this cross-sectional study, 257 adults with ultrasound-confirmed NAFLD were enrolled. Anthropometric parameters and body composition were measured using standardized procedures and bioelectrical impedance analysis. Fasting biochemical markers were assessed via enzymatic colorimetric methods. NLR was calculated from complete blood count data. Dietary intake was evaluated using a validated semi-quantitative food frequency questionnaire, and the Dietary Antioxidant Quality Score (DAQS) was derived based on the adequacy of vitamins A, C, and E, selenium, and zinc intake. Comparisons across NLR tertiles were performed using one-way analysis of variance, followed by Tukey’s post hoc test, and multivariable multinomial logistic regression was used to assess associations. Participants in the highest NLR tertile had significantly higher FBS (93.33 ± 11.03 vs. 88.40 ± 9.65 mg/dL), TC (191.81 ± 38.78 vs. 169.58 ± 32.62 mg/dL), and LDL-cholesterol levels (115.26 ± 33.63 vs. 99.11 ± 28.57 mg/dL) compared with those in the lowest tertile (all P < 0.05). Higher NLR levels were significantly associated with lower DAQS values and reduced intake of antioxidant vitamins A and C (p < 0.05). In stratified multinomial logistic regression analyses by physical activity, higher NLR was associated with increased FBS in the low activity group (Third tertile: OR: 1.07, 95% CI: 1.03–1.13, P = 0.003) and with higher TC in the high activity group (second tertile: OR: 1.02, 95% CI: 1.00–1.04, P = 0.05; third tertile: OR:1.02, 95% CI: 1.005–1.04, P = 0.016). Elevated NLR is associated with an unfavorable metabolic profile and poorer dietary antioxidant quality among individuals with NAFLD. These findings support the potential role of NLR as a practical inflammatory marker linked to metabolic risk and highlight the relevance of antioxidant-rich dietary patterns in mitigating inflammation in NAFLD.

Background: Chronic kidney disease necessitates safer, more continuous kidney replacement therapies (KRT), yet current dialysis and transplantation are constrained by intermittent treatment, organ scarcity, and immunosuppression‐related complications. Methods: This conceptual narrative review examines the potential integration of synthetic biology and soft robotics within a biohybrid KRT framework. We define a cyborg nephron as an engineered functional unit coupling living renal/vascular cells with compliant mechanical and fluidic interfaces, organized as a Modular Renal Assist Device (MRAD) with separable filtration, tubular transport, endocrine support, and control modules. Technology readiness levels (TRL) were applied to distinguish established, preclinical, and conceptual components. Results: Available evidence supports several individual components including cell‐based renal bioreactors, microphysiological models, endothelialized blood‐contacting surfaces, passive membranes, soft micropumps, and wireless sensing (TRL 3–5). Conversely, autonomous renal gene circuits, active immunoisolation, durable vascular integration, and fully implanted closed‐loop control remain predominantly preclinical or conceptual (TRL 1–2). Major barriers include thrombosis, oxygen delivery, cell maturation, genetic stability, mechanical fatigue, power demands, cybersecurity, and regulation of combined living‐device products. Conclusions: The cyborg nephron represents a hypothesis‐generating research framework rather than a near‐term clinical solution. Staged validation through modular development, conservative safety design, and comparison with simpler alternatives is essential before integrated preclinical testing can be justified.