Search Results (22,509)

Background: Bayesian model-informed precision dosing (MIPD) is increasingly used to individualize drug therapy; therefore, this review aimed to identify and characterize its implementation in routine clinical practice. Methods: A focused systematic review was conducted. Web of Science Core Collection and PubMed were searched from inception to February 2026. Eligible studies were original research articles evaluating Bayesian MIPD in routine clinical practice using software platforms that supported dosing decisions. Data were synthesized descriptively. No formal risk-of-bias assessment was performed due to heterogeneity in study design. Results: Fifteen studies met the inclusion criteria. Anti-infective therapy predominated, particularly vancomycin (n = 11), with additional studies involving busulfan, mycophenolate mofetil, amikacin, and tobramycin. Commonly reported software platforms included InsightRx (n = 6) and DoseMeRx (n = 4), along with Abbottbase, NextDose, and ISBA. MIPD was mainly applied with therapeutic drug monitoring, reflecting predominant a posteriori use in routine care. Across studies, implementation was associated with improved pharmacokinetic target attainment, while a subset reported clinical benefits, including reduced nephrotoxicity and favorable effectiveness-related outcomes. Pharmacist involvement was commonly described. Conclusions: Published evidence indicates that Bayesian MIPD is being implemented in routine clinical settings, but current published experience is dominated by vancomycin-focused studies. Although the evidence base remains limited, it has grown since 2020 and suggests that software-supported Bayesian dosing can improve pharmacokinetic target attainment and may support better clinical outcomes. Full article

Pediatric sepsis is a life-threatening systemic infectious response syndrome. Its core pathophysiological process involves a systemic imbalance between oxygen delivery and demand, coupled with cellular energy metabolism dysfunction, which collectively contribute to high mortality rates. Parameters of oxygen metabolism serve as critical indicators reflecting tissue perfusion and cellular oxygen utilization. Consequently, these parameters hold significant value for the early identification, severity stratification, therapeutic guidance, and prognostic evaluation of pediatric sepsis. This review systematically elucidates the pathophysiological mechanisms underlying oxygen metabolism disorders in pediatric sepsis. Furthermore, it highlights the current clinical applications and significance of key monitoring indices, including blood lactate, central venous oxygen saturation, oxygen delivery, and oxygen consumption. By integrating recent research advancements, this paper also explores therapeutic strategies aimed at optimizing oxygen metabolism, such as blood purification, microcirculation-targeted therapies, and extracorporeal membrane oxygenation. Finally, we provide future perspectives on emerging biomarkers and metabolomic approaches, aiming to establish a theoretical foundation for the optimized clinical management of pediatric sepsis. Full article

Natural killer (NK) cells are increasingly recognized as a complementary platform to T-cell-based cancer immunotherapies. Their innate, MHC-unrestricted recognition, capacity to mediate antibody-dependent cellular cytotoxicity (ADCC) and comparatively favorable toxicity profile have given rise to a broad therapeutic pipeline that includes cytokine-supported regimens, adoptive NK products, bispecific and trispecific NK engagers, and chimeric antigen receptor (CAR)-engineered NK cells. Clinical data, particularly in hematologic malignancies, show that NK-cell-based strategies can be safe and biologically active, although limited persistence, suboptimal trafficking and immune escape remain key challenges. Nasopharyngeal carcinoma (NPC), an Epstein–Barr virus (EBV)-driven epithelial cancer, illustrates how a tumor microenvironment (TME) can simultaneously impair NK function and create specific vulnerabilities that NK-focused therapies can exploit. This review summarizes NK biology and current therapeutic platforms, analyzes major limitations, highlights the specific context of NK-cell-based strategies in NPC and compares NK- and T-cell-based therapies with an emphasis on clinical translation. Full article

Postoperative nausea and vomiting (PONV) remain a leading preventable perioperative complication despite advances in anesthetic and surgical care, significantly affecting recovery within Enhanced Recovery After Surgery (ERAS) pathways. ERAS protocols provide a structured, multidisciplinary framework for perioperative optimization; however, variability in the implementation of PONV prevention strategies persists. This narrative review synthesizes current evidence on perioperative strategies for PONV prevention within ERAS pathways, focusing on patient risk stratification, multimodal pharmacologic prophylaxis, anesthetic techniques, and adjunctive non-pharmacologic interventions. We evaluate validated risk prediction tools, including the Apfel score, and highlight the importance of individualized prophylactic strategies based on patient, surgical, and anesthetic risk factors. Multimodal antiemetic regimens, opioid-sparing anesthesia, total intravenous anesthesia (TIVA), and regional techniques are discussed as key components of perioperative management. In addition, non-pharmacologic interventions such as optimized fluid therapy, early mobilization, and supportive perioperative care are reviewed as integral elements of ERAS-based recovery pathways. Complementing existing consensus guidelines, this review provides a practical, workflow-based framework spanning preoperative risk assessment, intraoperative decision-making, and postoperative monitoring for direct application within ERAS protocols. Full article

Cancer stem cells (CSCs) are a distinct subpopulation within a tumor that play an important role in tumor initiation, metastasis, therapeutic resistance, and cancer relapse. Their persistence is strongly influenced by the tumor microenvironment (TME), which provides a range of biological signals that maintain stemness, promote immune evasion, and resistance to cancer treatment. Therefore, effective targeting of CSCs is essential to improve therapeutic efficacy. In this review, we summarize the key characteristics of CSCs and their niche within the TME, emphasizing their interactions with immune cells, stromal components, and secreted factors. We also discuss the major challenges in targeting CSCs, including immune evasion, metabolic constraints, and intratumoral heterogeneity. We further highlight current and emerging immunotherapeutic strategies targeting CSCs, including immune checkpoint inhibitors, cancer vaccines, monoclonal antibodies, nanobodies, bispecific antibodies, antibody-drug conjugates (ADCs), CAR-T and CAR-NK cell therapies, oncolytic viruses, as well as innovative approaches such as targeted protein degradation. Finally, we emphasize the importance of a combinatorial approach that integrates CSCs targeting with modulation of the TME. Together, these strategies may lead to more durable responses, enhance therapy efficacy and reduce the risk of tumor recurrence. Full article

Background/Objective: Psoriasis is a systemic inflammatory disease often associated with metabolic comorbidities, including hyperuricemia. While biological therapies effectively target inflammatory pathways, their specific impact on serum uric acid (SUA) levels remains debated. This study aimed to evaluate whether biological therapy, while reducing systemic inflammation, influences SUA levels in patients with moderate-to-severe plaque psoriasis. Methods: A prospective longitudinal cohort study was conducted involving 30 patients with moderate-to-severe plaque psoriasis. Patients received biological treatment (adalimumab, secukinumab or ustekinumab) and tsDMARDS (apremilast). Clinical severity was assessed using the Psoriasis Area and Severity Index (PASI). C-reactive protein (CRP), erythrocyte sedimentation rate (ESR), SUA levels and other laboratory markers were measured at baseline and after 48 weeks of therapy. Results: Biological therapy led to a significant reduction in PASI scores (from 21.6 ± 10.7 at baseline to 0.4 ± 0.86 after 48 weeks of therapy, p < 0.001), and CRP decreased from a median of 5.75 mg/L at baseline to 3.55 mg/L, p < 0.001. ESR also declined from 26.2 ± 11.4 mm/h to 19.0 ± 8.06 mm/h, p < 0.001. However, no statistically significant change was observed in mean SUA levels 5.49 ± 1.55 vs. 5.55 ± 1.60 mg/dL; p = 0.758. Subgroup analysis revealed that SUA levels remained stable regardless of the specific biological agent used or the degree of clinical improvement. Conclusions: Our findings suggest that while biological therapy is highly effective in controlling skin and systemic inflammation in psoriasis, it does not modify SUA levels. These results imply that hyperuricemia in psoriasis may be driven by metabolic factors independent of the primary inflammatory pathways targeted by current biologics. Full article

After many years of stagnation in the treatment of acute myeloid leukemia (AML), there is currently a rapid move towards personalized medicine. Improvements in molecular diagnostics, risk assessment tools, targeted therapies, overall patient fitness assessments, and quality-of-life assessments have significantly changed how patients are treated. Genetic and molecular analyses, risk and health assessments, and measurable residual disease (MRD) monitoring are now integral to the treatment plan for evaluating patient responses and recurrence. In this regard, lower-intensity treatments are provided to older or unfit individuals. On the other hand, younger patients are usually subjected to curative therapies such as intensive chemotherapy to induce remission. Depending on their fitness and disease risk, they can be considered for hematopoietic cell transplantation, which is done after close observation for MRD. In addition, newer therapeutic drugs and immunotherapy techniques are being applied for patient management. Tremendous strides have been made in improving the efficiency of treatment programs in the relatively new area of personalized AML therapy, with a focus on functionality. Full article

Background/Objectives: Boron neutron capture therapy (BNCT) relies on the selective delivery of boron-10 to tumor cells. Although 4-[¹⁰B]borono-L-phenylalanine (BPA) is currently the only clinically approved BNCT agent, it is limited by poor L-type amino acid transporter 1 (LAT1)/LAT2 selectivity and aqueous solubility. We previously developed 3-borono-5-fluoro-α-methyl-L-phenylalanine (5F-αMe-3BPA), a novel BPA derivative designed to be a LAT1-targeted BNCT/positron emission tomography theranostic agent. This study comprehensively characterizes its pharmacological profile and explores its pharmacokinetic optimization by modulating renal organic anion transporter 1 (OAT1). Methods: Transport kinetics of BPA, related analogs, and 5F-αMe-3BPA were analyzed in HEK293 cells stably expressing LAT1 or LAT2 using Michaelis–Menten analysis. Time-dependent cellular uptake and intracellular retention of BPA and 5F-αMe-3BPA were evaluated in T3M-4 pancreatic cancer cells with or without the LAT1 inhibitor JPH203. In vivo biodistribution was examined in T3M-4 tumor-bearing mice after intravenous administration of 5F-αMe-3BPA or BPA, with assessment of probenecid pretreatment. Results: 5F-αMe-3BPA retained LAT1 affinity comparable to that of BPA while showing markedly reduced LAT2-mediated transport, indicating improved LAT1/LAT2 selectivity. In T3M-4 cells, 5F-αMe-3BPA showed stronger LAT1 dependence, higher steady-state accumulation, and better intracellular retention than BPA under amino acid-containing conditions. Although 5F-αMe-3BPA achieved favorable tumor-to-plasma and tumor-to-muscle ratios in vivo, it was rapidly cleared from circulation. Probenecid pretreatment increased plasma exposure, reduced early renal accumulation, and significantly enhanced tumor boron accumulation, reaching approximately twofold higher levels than control. Conclusions: These findings establish 5F-αMe-3BPA as a highly LAT1-selective BNCT candidate and identify probenecid pretreatment as a clinically translatable pharmacokinetic strategy for maximizing therapeutic boron delivery. Full article

Cryopreservation integrates technologies that enable the long-term preservation of biological materials at extremely low temperatures. Since the serendipitous discovery by Audrey Smith and Christopher Polge that glycerol enhances the survival of frozen chicken sperm, the field has advanced rapidly and found applications across cell therapy, biobanking, and tissue engineering. This concise review provides an overview of cryopreservation principles and the current commercial landscape in cell freezing media, highlighting key players, challenges and recent developments in tissue and small-organ preservation. Full article

The tumor microenvironment (TME) is a highly adaptive and heterogeneous niche in which cancer stem cells (CSCs) promote immune evasion, metastatic dissemination, and therapy resistance. Among the mechanisms that support this phenotype, mitochondrial hijacking has emerged as a central strategy through which CSCs reprogram immune and stromal cells to favor tumor progression. This review synthesizes current evidence on how CSCs exploit mitochondrial transfer, particularly via tunneling nanotubes (TNTs) and extracellular vesicles (EVs), to impair antitumor immunity and remodel the metastatic niche. CSCs display marked metabolic plasticity, shifting between glycolysis and oxidative phosphorylation (OXPHOS) in response to environmental stress. They exploit this adaptability by transferring mitochondria and mitochondrial components to recipient cells, including tumor-associated macrophages (TAMs) and cytotoxic T cells, thereby disrupting ATP production, increasing oxidative stress, and skewing immune polarization. This mitochondrial hijacking contributes to an immunosuppressive milieu, stabilizes HIF-1α, and enhances PD-L1 expression, ultimately weakening T-cell activity and reinforcing CSC survival. EVs add another layer of regulation by transporting bioactive cargo, including oncogenic microRNAs (miRNAs) and mitomiRs such as miR-21, miR-210, and miR-34a. These molecules modulate mitochondrial gene expression, reshape immune signaling, and reinforce CSC phenotypes through autocrine and paracrine loops. Single-cell and spatial transcriptomic approaches have further revealed metabolic heterogeneity within CSC–immune synapses, identifying “metabolic hotspots” associated with profound immune dysfunction. Therapeutic strategies targeting OXPHOS, EV biogenesis, and miRNA activity are therefore being explored. In parallel, mitochondria-associated proteins such as TSGA10 may also contribute to CSC-driven immunometabolism regulation and deserve further investigation. Targeting downstream heterogeneity is like cutting the branches of a weed. Targeting the upstream mechanisms of mitochondrial hijacking and miRNA crosstalk aims to destroy the root (CSC plasticity) that generates the heterogeneity and drives therapy resistance in the first place. This review highlights mitochondrial hijacking and miRNA-mediated reprogramming as central determinants of CSC-driven immune escape and proposes a framework for precision interventions targeting CSC–immune interactions in metastatic cancer. Full article

HIV-associated neurocognitive disorders (HAND) arise from HIV infection of the central nervous system, resulting in chronic neuroinflammation and progressive neuronal damage that impair cognitive, motor, and behavioral functions. Clinically, HAND encompasses a spectrum of neurological impairments ranging from asymptomatic neurocognitive impairment to severe HIV-associated dementia. Despite the widespread use of combination antiretroviral therapy (cART) and significant improvements in the life expectancy of people living with HIV, HAND remains prevalent and continues to pose a major clinical challenge. One of the primary limitations of cART is the limited penetration of many antiretroviral drugs across the blood–brain barrier (BBB), thereby allowing the persistence of viral reservoirs within the CNS and contributing to sustained neuroinflammation and neuronal damage. To address these challenges, novel nanotherapeutic strategies have been developed to enhance the delivery of antiretroviral agents to the brain. These approaches include targeted delivery systems and the co-delivery of therapeutics across the BBB through mechanisms such as receptor-mediated transcytosis and other transport pathways. In this review, we discuss the pathophysiological challenges associated with HAND and recent advances in nanotherapeutic approaches designed to improve treatment efficacy. We also discuss the current state of the art in vitro and in vivo models used to test the efficacy of these advanced therapeutics. Finally, we outline the remaining challenges and future prospects for the development of nanotherapeutics to improve the treatment of HAND. Full article

Temperature/pH dual-responsive hydrogels are a class of smart materials capable of undergoing reversible structural or functional changes in response to temperature and pH stimuli. Owing to their remarkable dual-stimuli-responsive characteristics, these hydrogels have demonstrated significant potential in various biomedical applications, including drug delivery, tissue engineering, and diagnostics technologies, making them a prominent research focus. Although considerable progress has been made in recent years, a systematic summary of the preparation methods, structural design strategies and complex biomedical applications of these materials remains conspicuously absent. Consequently, this review aims to comprehensively examine the latest advancements in this field. First, the primary preparation methods of temperature/pH dual-responsive hydrogels, including chemical crosslinking, physical crosslinking, and hybrid crosslinking, are introduced and compared. Subsequently, the main structural design strategies, including microsphere, core–shell and layered structures, and their corresponding fabrication processes are systematically elucidated. Finally, the recent progress of temperature/pH dual-responsive hydrogels in biomedical applications is discussed, including drug delivery, cancer therapy, biosensing and diagnosis, tissue engineering and regenerative medicine, as well as wound healing. Based on the current research progress, this review also outlines the major challenges in the development of temperature/pH dual-responsive hydrogels, and presents perspectives on future research directions. Full article

Adoptive cell therapy (ACT) using tumor-infiltrating lymphocytes (TILs) has achieved clinically and biologically relevant responses in patients with solid cancer. Clinical efficacy has been increasingly linked to a specific T-cell phenotype, particularly CD8⁺ TILs exhibiting a progenitor stem-cell-like profile (CD39⁻ CD69⁻). This review explores the critical role of the sphingosine-1-phosphate (S1P) axis in orchestrating these responses. We detail the biological antagonism between the activation marker CD69 and S1P receptor 1 (S1PR1), where mutual exclusivity dictates thymic selection, if T-cells are retained in tissues or allowed to recirculate and maintain long-term immune surveillance. The S1PR1:S1P axis is further recognized as a critical regulator of mitochondrial fitness, sustaining the high energetic demands of precursor T-cells. We examine the “double-edged sword” nature of S1P in the tumor microenvironment (TME), where it can drive pro-tumorigenic processes like angiogenesis and vascular mimicry (VM), be hijacked by cancer cells to create immune-excluded environments, or S1P can increase T-cell fitness. We summarize the current landscape of clinical trials (as of January 2026) that target S1P production or signaling to modulate anti-tumor responses or use S1P as a biologically relevant marker of treatment outcome. Full article

Heart failure is a leading cause of global morbidity and mortality, often developing as a consequence of acute myocardial infarction. Current management focuses on timely reperfusion via percutaneous coronary intervention. Yet, this approach fails to prevent the molecular cascades that drive the death of viable yet stressed cardiomyocytes within the infarct and peri-infarct zone. Effective antifibrotic therapies remain limited, highlighting a critical gap in current management strategies. This review aims to integrate current understanding of the molecular mechanisms underpinning post-infarct fibrosis and potential interventions for therapeutic development. This emphasis on molecular death signal activation and cell elimination highlights the redundancy of interconnecting fibrosis pathways. Anti-inflammatory and cell-targeted therapies focussing on oxidative stress and haemodynamic load have demonstrated strong preclinical promise. Yet, these approaches have largely failed to translate into clinical benefit. Overall, these limitations emphasise a narrow therapeutic window for intervention. As such, current therapies often fail to preserve metabolically vulnerable myocardium that remains potentially salvageable. Therefore, emerging approaches including RNA-based therapies, cardiac reprogramming, and targeted delivery systems offer new opportunities to improve therapeutic precision. Collectively, these findings support a shift toward early, cell-targeted intervention strategies. This approach aims to prevent progression to heart failure and increases patient quality of life. Full article

Diabetes mellitus is a chronic and progressive metabolic disorder associated with abnormal blood glucose levels. The term involves several diseases with different pathophysiology mechanisms and treatment strategies. Stem cell-based treatments represent an emerging strategy for patients with diabetes mellitus with severe pancreatic insufficiency and poor glycemic control. Over the last 20 years, researchers have investigated mesenchymal stem cell infusion and the transplantation of stem cell-derived β cells and islet tissues. This review aims to comprehensively discuss the latest advances in the field of stem cell use in diabetes, including clinical studies and preclinical experiments aiming at improving the efficacy and safety of stem cell use. Full article