搜索结果：Biomedical reports

Chitosan, a derivative of the abundant biopolymer chitin, holds significant biotechnological potential but is limited by its poor solubility. Its oligomeric forms, chitooligosaccharides (COSs), exhibit superior bioactivity and solubility, driving demand for efficient enzymatic production methods. This study reports the biochemical and functional characterization of a novel chitosanase, SlCsn46A, identified from Streptomyces lydicus M01 and classified into the glycoside hydrolase family 46 (GH46). The enzyme was successfully heterologously expressed in Escherichia coli and purified. SlCsn46A demonstrated high catalytic efficiency, with an optimal activity at 60°C and pH 6.0 and a maximum specific activity of 957.80 U·mg- 1. It exhibited broad pH stability and significantly enhanced activity in the presence of Mn2 + and Tween 80. Kinetic analysis revealed a low Michaelis constant (Km = 0.61 mg·mL- 1), indicating strong substrate affinity. Product analysis confirmed its endo-type action mode, specifically hydrolyzing chitosan to yield chitobiose [(GlcN)2] and chitotriose [(GlcN)3] as the predominant end products. These properties collectively establish SlCsn46A as an efficient and specific biocatalyst, demonstrating great potential for the targeted and efficient synthesis of low-degree-of-polymerization COS for applications in the food, agricultural, and biomedical industries.

Drug-induced obsessive-compulsive (OC) symptoms have been described for clozapine and several second-generation antipsychotics, whereas reports involving cariprazine remain scarce. The present report describes the case of a 28-year-old Thai female patient with bipolar II disorder who had premorbid, subclinical counting compulsion, which had remained stable since its onset in adolescence. After 3 days of cariprazine treatment during a regimen switch for bipolar disorder, the pre-existing counting compulsion worsened and additional patterns of OC symptoms emerged. At seven days after discontinuation of cariprazine, the newly emerged symptoms were fully resolved, while the counting compulsion returned to its baseline subclinical severity. The present report highlights the need for clinical vigilance regarding OC symptom exacerbation with cariprazine treatment as a part of comprehensive follow-up of the mental health and wellbeing of psychiatric patients. Potential mechanistic considerations involving serotonergic and dopaminergic systems are discussed. The literature review of drug-induced OC symptomatology in the present study also identified limited documentation of premorbid OC symptomatology and age-at-onset phenotypes. Future reports incorporating detailed phenotypic characterization may improve the identification of patients at risk of symptom exacerbation.

Healthcare litigation is increasing globally and imposes significant emotional, financial and reputation and trust-related costs. Orthopaedic and spine surgery carry particularly high medico-legal risk because of technical complexity, uncertain outcomes and heightened patient expectations. Alternative dispute resolution (ADR), especially mediation, offers confidential and collaborative means to both prevent and resolve conflict. To (i) examine litigation-prevention strategies and ADR modalities applicable to orthopaedic and spine practice; (ii) synthesise common sources of conflict, the advantages of ADR over litigation and implementation challenges within the Nigerian health system and (iii) propose recommendations for hospital governance, professional regulation and incorporation of ADR training in medical education. A narrative review of English-language literature was conducted across biomedical databases and grey sources using predefined keywords ADR, ADR processes with outcome and barriers in low- and middle-income countries, and patient safety. Eligible studies included empirical research and programme reports. Thematic synthesis focused on conflict drivers, mediation, on medical litigation, orthopaedics, policy and legal analyses, preventive mechanisms and spine surgery. One hundred and fifty-two sources met the inclusion criteria. Major conflict drivers were consent and communication failures, poor documentation, expectation-outcome mismatch, disputes over surgical indication, peri-operative complications, implant and device issues, financial hardship and delayed presentation. ADR consistently showed advantages in cost, timeliness, confidentiality, therapeutic relationship preservation and learning potential. Barriers included weak institutional ADR frameworks, limited mediator clinical literacy, fragmented regulation, low insurance penetration and poor quality-improvement data. ADR provides an effective, confidential approach to reducing litigation in orthopaedic and spine practice by addressing communication failures early and preserving therapeutic relationships. Strengthening consent, documentation, institutional ADR pathways and mediator clinical skills, supported by policy reforms and ADR education, can reduce preventable conflicts and promote safer, more accountable surgical care in Nigeria.

Cold Atmospheric Plasma (CAP) has garnered significant attention in biomedical science, owing to its wide therapeutic applications in wound healing, disinfection, dentistry, cancer care and inflammation. Although, anti-inflammatory effects of CAP are studied, there are no reports investigating its effect on T cell hyperactivation associated pathologies. This study examines CAP's impact on antigen driven and homeostatic T cell proliferation and its potential to prevent acute graft-versus-host disease (aGvHD). CAP treatment significantly attenuated GvHD-associated mortality and morbidity in mice. CAP inhibited stimulation-induced T cell activation, surface marker expression, cytokine secretion, and proliferation without inducing cell death, indicating non-cytotoxic immunomodulation. CAP modulated cellular redox and pre-treatment with N-acetylcysteine (NAC) or PEG-catalase (PEG-CAT) abrogated CAP-mediated suppression of mitogen-induced T cell responses. Moreover, CAP-mediated inhibition of stimulation-induced T-cell responses was associated with suppression of immune-regulatory, redox-sensitive transcription factors, NF-κB and Nrf2. These findings underscore immunotherapeutic potential of CAP in treatment of disorders linked to T cell hyperactivation.

Peripartum cardiomyopathy (PPCM) is a rare disease that causes heart failure during pregnancy or in the early postpartum period, and there were no reports on the trend of clinical condition and treatment in Japan. This explanatory retrospective study aimed to investigate the changes in clinical conditions and treatment in patients with PPCM. Twenty-three patients (aged 22-43 years; mean age, 32 years) with PPCM from four hospitals in Nagasaki Prefecture were included. We compared the heart failure status and treatments of PPCM between the 10 years from January 2002 to December 2011 (first era) (N = 10) and the 11 years from January 2012 to December 2022 (second era) (N = 13). Left ventricular ejection fraction (LVEF) on admission was higher (first era 20% (interquartile range (IQR) 17-34) vs. second era 34% (IQR 25-37), p = 0.0213), and less patients treated with inotropes in patients in second era than those in first era (first era 6/10 (60%) vs. second era 2/13 (15%), p = 0.0393). Hospitalization period was shorter in second era than those in first era (first era 38 days (IQR 22-45) vs. second era 19 days (IQR 16-22), p = 0.0159). In recent years, patients with PPCM have been admitted before progression of LV dysfunction, and that may be related to a decrease in use of inotropes and hospitalization period in Japan.

Hidradenitis suppurativa (HS) is a painful inflammatory skin disease within the pilosebaceous unit associated with numerous comorbidities, including obesity type-2-diabetes (T2DM), and a general meta-inflammatory state. This narrative review explores the therapeutic potential of GLP-1-receptor-agonists (GLP-1RAs) in treating HS by analyzing mechanisms of action and clinical outcomes. Based on a literature search, encompassing 12 cohorts and 4 case-based reports, current evidence demonstrates significant improvements in both clinical and patient-reported outcomes in patients with HS treated with GLP-1RAs. Treatment consistently resulted in reduced body mass index (BMI) and disease activity, measured by Hurley-staging and the number of nodules and abscesses. Patients across studies experienced fewer flares and less pain, supporting improvements in dermatology quality of life (DLQI) scores. Studies observed reductions in systemic inflammatory markers and improved glycemic control. The beneficial effects of GLP-1RAs in HS are attributed to the reduction in mechanical friction and metabolic improvements from weight loss. Suggestively, concurrent and direct anti-inflammatory mechanisms, including inhibition of the nuclear factor kappa-light-chain-enhancer of activated B cells (NF-κB) signaling pathway and modulation of cytokines, occur independently of weight-reduction. Results from cohorts and cases supported this theory, showing significant improvements in HS and metabolic markers independent of weight-related outcomes. Four supplementary cohorts found GLP-1RAs beneficial for cardiovascular comorbidities in patients with HS. Additionally, studies suggest that GLP-1RAs enhance the efficacy of biologic therapies used for HS and reduce the need for adjunctive treatment. In conclusion, GLP-1RAs represent a promising pleiotropic treatment within a multimodal therapy strategy for HS and comorbidities.

Current clinical treatment options for traumatic brain injury (TBI) to limit permanent tissue damage and secondary injury remain inadequate. Intraparenchymal transplantation of neural stem cells is a potentially powerful therapy for TBI, acting through replacement and/or protection of damaged cells. This approach could be augmented by entrapping the stem cells within a pro-regenerative hydrogel, designed to both retain the therapeutic cells at the transplant site and modulate the inflammatory response. This study reports a decellularized extracellular matrix hydrogel derived from porcine dura for this purpose and the assessment of its efficacy in vitro and in vivo. In vitro, the dural ECM hydrogel ameliorated oxidative stress in hypoxic astrocytes and influenced collagen remodeling in fibroblast-derived matrices. Proteomic characterization revealed a composition of 559 proteins within the dural ECM, alongside matrix-bound vesicles that were demonstrated to be distinct from traditional cell-derived exosomes. In vivo, mice subjected to a controlled cortical impact traumatic brain injury displayed improved motor recovery when treated with the hydrogel alone, neural stem cells in suspension, or their combination. This novel biomaterial shows promise as a new therapy for TBI treatment, both independently and as a vehicle for cell delivery.

This study reports a congenital heart disease, characterized by ventricular wall thinning and septal defects, caused by a heterozygous missense mutation (R755 W) in the glycolytic gene PFKP (platelet isoform of phosphofructokinase-1). The pathogenic mechanism involves the PFKP mutation impairing enzyme activity, which inhibits cardiomyocyte proliferation and leads to the thinning of the compact myocardium. In the mouse model, we found that administering the downstream metabolite, fructose-1,6-bisphosphate, reversed the myocardial hypoplasia in fetal mice, providing proof-of-concept for in utero intervention. Clinically, we successfully prevented the transmission of the disease using preimplantation genetic testing, resulting in the birth of a healthy infant.

Testicular germ cell tumours (TGCTs) are the most common malignancy in young adult males. After chemotherapy, the evaluation of residual masses is critical. However, the current standard imaging modality, [18F]-FDG PET, has limited specificity-particularly in distinguishing viable tumour from necrosis or mature teratoma. This limitation often leads to unnecessary surgery or misinterpretation of treatment response. This systematic review aims to explore and evaluate novel PET tracers that could improve diagnostic accuracy in TGCTs, especially in post-chemotherapy settings. A comprehensive literature search was conducted on PubMed and Scopus through December 2025, using terms including "testicular," "germ cell tumour," "PET scan," and "novel." Studies focusing solely on [18F]-FDG were excluded. Preclinical studies, case reports, and clinical trials investigating alternative PET tracers or relevant molecular targets (e.g., ghrelin, claudin-6) were included. The quality of selected articles was assessed by using CASP for the qualitative research. A total of 17 studies met the inclusion criteria. Emerging PET tracers evaluated include [18F]-FLT, FAPI, αvβ3-integrin-targeted agents, [18F]-fluciclovine, PSMA-targeted tracers, and those based on ghrelin and claudin-6. Among these, αvβ3-targeted imaging has shown promising preclinical results in differentiating mature teratoma from necrosis. Ghrelin receptor tracers appear promising due to their high expression in TGCTs, although they remain in preclinical development. Claudin-6, a tight-junction protein, is highly expressed in most TGCT histologies and may be a viable molecular target, as supported by early-phase clinical trials. Novel PET tracers represent a promising avenue to refine TGCT management. αvβ3-integrin and ghrelin-based tracers are particularly noteworthy for their potential to guide decision-making after chemotherapy. However, further clinical validation is required before routine implementation. These innovations could significantly reduce overtreatment and enhance personalized care in TGCT patients.

Heart failure (HF), a major global health challenge, affects millions worldwide and poses substantial healthcare and economic burdens. It is estimated that a large proportion of those with early systolic dysfunction remain asymptomatic at a stage when guideline-directed medical therapies have been shown to prevent disease progression. To develop an artificial intelligence (AI) model capable of predicting abnormal left ventricular ejection fraction (EF) directly from static, non-gated, non-contrast chest computed tomography (CT) scans as a form of opportunistic screening. Using a multi-institutional dataset of 34 058 paired non- contrast CT images and echocardiogram reports from two academic centres, we trained our model of classification for predicting left-ventricle ejection fraction (LVEF) categories: abnormal EF (EF < 50%) vs. normal on 25 948 studies. We validated the model on 8110 paired chest CT and echocardiogram results from a separate institution. The model achieved an area under the receiver operating characteristic (AUROC) curve of 0.786 on the hold-out test set and 0.762 on external validation to detect an abnormal EF (<50%). Beyond strong predictive performance, the AI model surpassed expert radiologists in both accuracy and efficiency and provided interpretable visualizations highlighting imaging features linked to reduced LVEF. In this study, we developed and validated an AI model capable of predicting abnormal LVEF directly from static, non-gated, non-contrast chest CT scans, a novel application for an imaging modality typically used for unrelated indications as a form of opportunistic screening. This technology holds significant promise for early detection of systolic HF, reducing the diagnostic gap, and improving outcomes in asymptomatic HF patients.

Doxorubicin (DOX) is a potent chemotherapeutic drug used to treat a variety of cancer types, but its usage is limited due to major cardiovascular side effects. According to World Health Organization reports, by 2050, new cancer cases are projected to increase to >35 million, implying an enhanced risk of DOX-induced cardiomyopathy (DIC). Despite its cardiotoxic side effects, DOX has remained an effective therapeutic choice for cancer treatment. Current evidence suggests that multiple pathophysiological mechanisms are involved in DIC, including oxidative stress, mitochondrial dysfunction, endoplasmic reticulum (ER) stress, calcium dysregulation, and inflammation, all of which lead to cardiac cell death and disease progression. Recently, several oxidative stress and inflammation-mediated signaling pathways, including MAPK, HMGB1/TLR4, NF&#x3ba;B, NLRP3 inflammasome, JAK-STAT, and TNF&#x3b1;, have been identified as contributing factors to cardiac remodeling in DIC. Although significant progress has been made over the past two decades in understanding the pathophysiological mechanisms of DIC, the exact mechanism leading to DIC remains unclear. Hence, in this review, we discuss various types of immune cells, including neutrophils, monocytes, and macrophages, cellular and molecular pathological mechanisms of inflammation, and various types of cell death in DIC. Further we discussed how understanding the significance of inflammatory mechanisms may enhance therapeutic efficacy and inform future perspectives.

The recent publication of extension data from post-regulatory trials of amyloid-lowering antibody therapies, such as donanemab and lecanemab, requires clinicians to critically appraise trial designs and analyses in order to evaluate claims made by authors and sponsors of disease modification. This Perspective outlines the challenges with assessing claims of disease course modification, provides a framework for their evaluation, reviews the different trial designs and analytical approaches used to test or support them, and proposes a practical appraisal checklist for evaluating studies.

The European Group for Blood and Bone Marrow transplantation Practice Harmonization and Guidelines Committee together with the Lymphoma Working Party convened 23 experts in Hodgkin lymphoma, transplantation, and radiation oncology, to develop consensus recommendations on the use of autologous and allogeneic haematopoietic cell transplantation (HCT) in relapsed or refractory Hodgkin lymphoma. Through a structured literature review and a 2-day workshop in Berlin, Germany, on Sept 29 and 30, 2025, the panel established guidance across major clinical decision points. The outcome of this review and workshop include the following recommendations. Salvage therapy should include brentuximab vedotin or checkpoint inhibitors, or both, with metabolic complete response preferred before autologous HCT. BEAM (carmustine, etoposide, cytarabine and melphalan) remains the most commonly used conditioning regimen, and autologous HCT continues to be the standard for chemosensitive relapse. Peri-transplantation radiotherapy could be considered for PET-positive or residual disease. Brentuximab vedotin consolidation is recommended for patients at high-risk. Allogeneic HCT is advised for eligible patients who relapse after autologous HCT, ideally with reduced intensity conditioning and post-transplantation cyclophosphamide as graft-versus-host disease prophylaxis. Routine maintenance after allogeneic HCT is not recommended; relapse management should be tailored and can involve donor lymphocyte infusion, brentuximab vedotin, checkpoint inhibitors, chemotherapy, radiotherapy, or clinical trial enrolment.

Primary ciliary dyskinesia (PCD) is a genetically heterogeneous disorder caused by defective motile cilia, resulting in impaired mucociliary clearance, chronic respiratory disease, laterality defects and subfertility. Currently, no disease-modifying treatments exist. Targeting PCD at its root cause requires emerging genetic therapies, such as small molecules, oligonucleotides, mRNA therapy, gene replacement and genome editing. With over 52 implicated genes and numerous patient-specific variants, there is a need for robust preclinical models to evaluate and accelerate these approaches. This review examines human preclinical models that recapitulate patient-specific genotypes and phenotypes while providing sufficient scalability for screening and detailed efficacy assessment. The models should also resolve knowledge gaps, including which cells need targeting and at what stage of differentiation. Air-liquid interface cultures of primary human airway epithelial cells or induced pluripotent stem cells (iPSCs) represent the current practice, alongside three-dimensional organoids, spheroids and lung-on-a-chip platforms. To overcome the limited proliferative capacity of primary cells, strategies include BMI-1 or hTERT transduction, conditional reprogramming with Rho-associated kinase (ROCK) inhibitors and feeder layers, and differentiation of iPSCs. Patient-derived and CRISPR-edited models have been developed for multiple PCD genes. Outcome measures to confirm efficacy of the therapy include high-speed video microscopy for quantifying ciliary beat pattern, transmission electron microscopy for ultrastructural assessment, mucociliary clearance assays and deep molecular phenotyping. There is a need for field-wide standardisation through consensus protocols, core outcome sets, minimum reporting criteria, quality benchmarks and regulatory alignment to facilitate accelerated translation of preclinical findings to clinical therapeutics.

Primary ciliary dyskinesia (PCD) comprises a group of rare genetic disorders that primarily affect the function of motile respiratory cilia, leading to progressive sinopulmonary disease. Disease models can be used to investigate potential therapies or responses to environmental exposures. We sought to identify and describe knowledge gaps in the modelling approaches and outcome measures used in applied in vitro or ex vivo human respiratory cellular models of PCD. We conducted a scoping review of Medline and Embase (2000-2024), screening studies of in vitro or ex vivo human respiratory cellular models of PCD and charted modelling approaches, applications and outcome measures. Of the 612 screened abstracts, 10 articles were included in the qualitative synthesis. The modelling approaches included primary cell culture at an air-liquid interface (ALI) (n=5), spheroid culture (n=2), organoid culture (n=2) and induced pluripotent stem cell-derived ALI culture (n=1). Modelling protocols were heterogenous. Applications included 1) therapeutic gene correction or replacement applications (n=4) and therapeutic drug screening (n=1), or 2) exposure to infection (n=4), drugs (n=3) and house dust mite allergen (n=1). Outcome measures used for both model characterisation and evaluation of therapeutic interventions were inconsistent. Certain outcome measures, such as ciliary function, were reported inconsistently, which limited interpretability of findings. A variety of PCD models exist but a lack of standardised characterisation hinders the reproducibility and comparability of findings. Consensus is needed on the minimum requirements for model characterisation and standardised reporting of outcome measures, which will facilitate model development for therapeutic and exposure applications.

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Natural products are used in the discovery of novel therapeutic agents. Ischemic stroke is a neurological disorder caused by the obstruction of cerebral blood vessels, sometimes leading to paralysis and potentially death. Despite the complexity of this condition, therapeutic options are limited and typically associated with severe side effects, including intracranial hemorrhage. The present study aimed to explore the toxicity and anti-ischemic stroke activity of aqueous extracts from the aerial parts of gotu kola (Centella asiatica; CA), moringa leaves (Moringa oleifera; MO), turmeric rhizomes (Curcuma longa; CL), black pepper seeds (Piper nigrum; PN), and snakehead fish fillets (Channa striata; CS) in zebrafish. Toxicity tests were conducted in zebrafish embryos for 96 h. Ischemic stroke was induced in zebrafish larvae incubated in ponatinib (Pon) solution. In total, three concentrations of each extract, namely &#xbc; of the 10% lethal concentration (LC10), &#xbd; LC10 and LC10, were derived from toxicity testing and applied in anti-ischemic stroke assays. All extracts were considered non-toxic as their LC50 values were >100 &#xb5;g/ml. At certain concentrations, the extracts decreased hatching (>625 &#xb5;g/ml CA and CL, >250 &#xb5;g/ml MO, and >125 &#xb5;g/ml CS) and survival rates (>625 &#xb5;g/ml CA, >250 &#xb5;g/ml MO, >156.25 &#xb5;g/ml, >125 &#xb5;g/ml PN and CS) and resulted in morphological deformity. Moreover, CA, MO, CL and CS, especially at their highest concentrations, significantly decreased the area of cerebral thrombosis compared with the Pon group. CA, MO, PN and CS ameliorated locomotor deficits following ischemia, as evidenced by significant improvements in average speed and total distance traveled. Among all extracts, CS at 29 &#xb5;g/ml showed the greatest potential for development as an ischemic stroke treatment, exhibiting the strongest effects in preventing blood vessel blockage and restoring locomotor function following ischemia.

Baicalin has protective effects against a range of cardiovascular conditions, such as myocardial ischemia-reperfusion injury, cardiac dysfunction, and apoptosis in cardiomyocytes. However, the underlying protective mechanisms in diabetic cardiomyopathy (DCM) remain unclear. The present study aimed to investigate the specific molecular mechanism activated by baicalin to ameliorate DCM. The effects of baicalin were investigated in vitro and its potential targets and pathways were identified using network pharmacology, molecular docking, echocardiography, reverse transcription PCR, ELISA, histopathology, immunofluorescence staining and western blotting. Baicalin significantly alleviated high-glucose (HG)-induced injury in H9c2 cells by inhibiting fibrotic markers, inflammatory factors and pyroptosis. Moreover, protein tyrosine phosphatase non-receptor type 22 (PTPN22) and tumor necrosis factor (TNF) were identified as crucial targets for baicalin. Molecular docking indicated that baicalin exhibited a strong binding affinity for PTPN22 and TNF. Baicalin successfully suppressed HG-induced pyroptosis, inflammation and fibrotic markers in addition to inhibiting the activation of TNF-&#x3b1; and PTPN22 signaling pathways. In addition, PTPN22-small interfering RNA treatment modulated pyroptosis in vitro. The present study offers insight into the key therapeutic mechanisms activated by baicalin, and its potential therapeutic targets, PTPN22 and TNF-&#x3b1;.

Systemic corticosteroids and immunosuppressants remain the standard first-line therapy for non-anterior, non-infectious uveitis (NIU), but prolonged use carries significant systemic and ocular adverse effects. Several intraocular agents have recently emerged as effective alternative or adjunctive options. Our meta-analysis included 9 randomized controlled trials and 1 retrospective case series, investigating the efficacy and safety profiles of intravitreal fluocinolone acetonide implant (FAi), intravitreal dexamethasone implant, intravitreal or suprachoroidal triamcinolone acetonide (SCTA), intravitreal methotrexate, intravitreal ranibizumab, and standard of care (SOC) for NIU. Our results demonstrated that all the studied intraocular agents excluding ranibizumab demonstrated a better best-corrected visual acuity gain compared to SOC at 6 months. The 4mg SCTA demonstrated the greatest central macular thickness reduction surpassing other intraocular steroid therapies and SOC at 6 months for uveitic macular edema. With regards to side effects, 0.59mg FAi was associated with a higher risk of 2-year and 3-year intraocular pressure elevation &#x2265;10 mmHg when compared to SOC. Understanding the advantages and limitations of intraocular therapies is essential for initiating personalized treatment strategies in NIU.