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Facing CAR T Cell Challenges on the Deadliest Paediatric Brain Tumours.

Central nervous system (CNS) tumours comprise 25% of the paediatric cancer diagnoses and are the leading cause of cancer-related death in children. Current treatments for paediatric CNS tumours are far from optimal and fail for those that relapsed or are refractory to treatment. Besides, long-term sequelae in the developing brain make it mandatory to find new innovative approaches. Chimeric antigen receptor T cell (CAR T) therapy has increased survival in patients with B-cell malignancies, but the intrinsic biological characteristics of CNS tumours hamper their success. The location, heterogen

Associations between type 1 diabetes and autoimmune skin diseases: Mendelian randomization analysis.

BACKGROUND: Type 1 diabetes mellitus (T1DM) may be associated with various autoimmune diseases, but the causal relationship between T1DM and autoimmune skin diseases is not yet clear. METHODS: The summary statistical data on T1DM and nine autoimmune skin diseases in European populations were extracted for mendelian randomization (MR) analysis. Subsequently, the analysis was replicated in East Asian populations. In the MR estimation, inverse variance-weighted (IVW), MR-Egger, weighted median, simple mode, and weighted mode methods were utilized. Outliers were excluded using MR-PRESSO, and horiz

Advancing gene editing therapeutics: Clinical trials and innovative delivery systems across diverse diseases.

Gene editing is a groundbreaking therapeutic approach that can potentially treat a broad spectrum of genetic and acquired diseases. This review highlights recent clinical trials employing advanced gene editing technologies such as CRISPR-Cas9, zinc-finger nucleases (ZFNs), and base editors across multiple disease areas including metabolic disorders, autoimmune diseases, muscular dystrophies, and inherited eye disorders. Central to the success of these therapies is the development of efficient and safe delivery systems, including lipid nanoparticles (LNPs), viral vectors (adenoviral and lentivi

Кристальная структура и каталитический механизм дрименоловой синтазы, необычная двухфункциональная терпеновая киклаза-фосфатаза.

Дрименол синтаза из Aquimarina pongiae (ASDMS) — очень необычная химера, интегрирующая two - отдельные, последовательные операции по переработке изопреноидов в рамках единой полипептидной цепи. ASDMS катализирует циклизацию фарнесилового дифосфата (FPP) класса II для образования дрименилового дифосфата, который затем подвергается гидролизу энзим-катализу для получения дрименинола, биоактивного сескитерпенового спирта с антифунгальными и антираковыми свойствами. Здесь мы сообщаем рентгеновские кристаллы ASDMS и его комплекс с сескитерпен тиол. Структура ASDMS имеет дидомаиновую архитектуру, сос

Bispecific antibodies as powerful immunotherapeutic agents for urological cancers: Recent innovations based on preclinical and clinical evidence.

Conventional immunotherapy has emerged as a key option for cancer treatment. However, its efficacy has been limited in urological cancers, especially prostate cancer, because of the immunosuppressive tumor microenvironment (TME), difficulty in drug delivery, aberrant immune response, and damage to normal cells. Bispecific antibodies (BsAbs) are engineered proteins with two different antigen-binding domains, designed using different technologies and in various formats. BsAb-based tumor immunotherapy has yielded optimistic results in preclinical and clinical investigations of many tumor types, i

Регулирование на основе Virobiome микробиота-гут-мозговой оси сигнализирует и нейроиммунный гомеостаз.

Ось человеческого кишечника все чаще признается как сложная двунаправленная коммуникационная система, объединяющая микробные, нейронные, эндокринные и иммунные сети, формирующие неврологическое здоровье. Хотя бактериальный вклад в этот диалог получил широкую окраску, вирусный компонент кишечной экосистемы, виром, стал важным компонентом, связанным с физиологическим регулированием принимающей стороны. В этом обзоре обобщены данные, свидетельствующие о том, что бактериофаги и эукариотические вирусы могут способствовать микробному и иммунальному гомеостазу и оказывать влияние на сигнализацию вдол

Exposures to IARC Carcinogenic Agents in Work Settings Not Traditionally Associated with Sinonasal Cancer Risk: The Experience of the Italian National Sinonasal Cancer Registry.

The aim of this study is to highlight tasks and jobs not commonly considered at high risk for sinonasal cancer (SNC) identified by Regional Operating Centers currently active in the Italian National Sinonasal Cancer Registry (ReNaTuNS), which retrieve occupational histories through a standardized questionnaire. Data on exposures to IARC carcinogenic agents in work settings unknown to be associated with SNC risk were collected and analyzed. Out of 2,208 SNC cases recorded in the ReNaTuNS database, 216 cases and their worked exposure periods were analyzed. Unsuspected jobs with exposure to wood

Anticancer natural products from the Middle East and North Africa: biodiversity, mechanisms, and translational challenges.

Cancer remains one of the leading causes of morbidity and mortality worldwide, imposing substantial clinical, societal, and economic burdens. Despite major advances in surgical oncology, systemic chemotherapy, radiation therapy, molecularly targeted therapeutics, and immune checkpoint inhibition, contemporary cancer treatment remains constrained by dose-limiting toxicities, intratumoral and intertumoral heterogeneity, and the inexorable emergence of multifaceted drug resistance mechanisms. These persistent therapeutic challenges have reinstated interest in natural products (NPs) as evolutionar

Vertebral fracture and splenomegaly in a head and neck cancer producing granulocyte colony-stimulating factor: A case report of systemic complications associated with a cytokine-producing solid tumor.

Granulocyte colony-stimulating factor (G-CSF)-producing tumors are rare and are associated with a poor prognosis when they occur in the lungs and the head and neck region. Positron emission tomography/computed tomography has been reported to show systemic specific accumulation of fluorodeoxyglucose in these cases, but the systemic complications associated with the cytokines produced are not well known. We herein present the case of a G-CSF-producing maxillary sinus squamous cell carcinoma in a 73-year-old Japanese woman with a vertebral fracture and splenomegaly. These findings are known sever

Oncologic Emergencies: Immune-Based Cancer Therapies and Complications.

Cancer therapies have undergone several recent advancements. Current cancer treatments include immune-based therapies comprised of checkpoint inhibitors, and adoptive immunotherapy; each treatment has the potential for complications that differ from chemotherapy and radiation. This review evaluates immune-based therapies and their complications for emergency clinicians. Therapy complications include immune-related adverse events (irAE), cytokine release syndrome (CRS), autoimmune toxicity, and chimeric antigen receptor (CAR) T-cell-related encephalopathy syndrome (CRES). Immune-related adverse

Nanotechnology in Prostate Cancer: PSMA-Targeted Nanoplatforms, TME-Responsive Therapy, Immunomodulation, and Clinical Translation Challenges.

The field of nanotechnology has demonstrated considerable potential in the diagnosis and treatment of prostate cancer, particularly through the use of prostate-specific membrane antigen (PSMA)-targeted platforms and tumor microenvironment (TME)-responsive systems. In the context of diagnosis, nanoparticle-based molecular imaging probes have been shown to enhance detection sensitivity and specificity. These probes include superparamagnetic iron oxide, which is utilized in magnetic resonance imaging, and near-infrared fluorescent nanomicelles. Additionally, nanostructured liquid biopsy systems h

Organoids as Innovative Models for Bone and Joint Diseases.

Bone is one of the key components of the musculoskeletal system. Bone and joint disease are the fourth most widespread disease, in addition to cardiovascular disease, cancer, and diabetes, which seriously affect people's quality of life. Bone organoids seem to be a great model by which to promote the research method, which further could improve the treatment of bone and joint disease in the future. Here, we introduce the various bone and joint diseases and their biology, and the conditions of organoid culture, comparing the in vitro models among 2D, 3D, and organoids. We summarize the differin

The microbiota-gut-brain-axis theory: role of gut microbiota modulators (GMMs) in gastrointestinal, neurological, and mental health disorders.

The modulation of gut microbiota presents promising therapeutic possibilities for various health conditions, ranging from gastrointestinal infections to neurodegenerative and mental health disorders. Among the available interventions, gut microbiota modulators (GMMs) such as probiotics and prebiotics have demonstrated significant potential in infection prevention and neuroprotection. Despite these encouraging findings, the clinical application of GMMs remains challenging due to safety concerns and inconsistent effectiveness across diverse patient populations. These factors create substantial b

Opinion: more mouse models and more translation needed for ALS.

Amyotrophic lateral sclerosis is a complex disorder most of which is 'sporadic' of unknown origin but approximately 10% is familial, arising from single mutations in any of more than 30 genes. Thus, there are more than 30 familial ALS subtypes, with different, often unknown, molecular pathologies leading to a complex constellation of clinical phenotypes. We have mouse models for many genetic forms of the disorder, but these do not, on their own, necessarily show us the key pathological pathways at work in human patients. To date, we have no models for the 90% of ALS that is 'sporadic'. Potenti

Core Patient-Centered Outcomes for Adolescents and Young Adults with Cancer: A Comprehensive Review of the Literature from the STRONG-AYA Project.

BackgroundIn adolescents and young adults (AYAs) with cancer, the importance of patient-centered research outcomes is increasingly acknowledged and there is a need for consensus on the most relevant outcomes. This review provides a comprehensive overview of outcomes relevant to AYAs with cancer in order to develop an AYA-specific core outcome set (COS) as part of the European project STRONG-AYA.MethodsA literature search was conducted to identify relevant articles in five databases. Each article was reviewed by two independent researchers, using Rayyan (an online tool) to screen articles by th

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… A literature search of the following databases was performed in October 2022 to identify relevant articles: Embase, MEDLINE ALL, Web of Science Core Collection, Cochrane Central Register of Controlled Trials, and additional search engines, including Google Scholar. …

Abstracts from the 11th International Conference for Healthcare and Medical Students (ICHAMS) : Virtual. 10-12 February 2022.

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… Methods Studies focusing on the correlation between NSAIDs and COVID-19 were selected with the help of the medical search engine PubMed and included in a meta-analysis, with the help of formulas: hazard ratios, odds ratios, confidence intervals. …

Global perspectives on lupus nephritis: a review of clinical trials and therapeutic innovations.

BACKGROUND AND OBJECTIVES: Lupus nephritis (LN) remains a leading cause of morbidity and mortality in systemic lupus erythematosus (SLE). Although recent years have witnessed the approval of several targeted therapies, achieving long-term, drug-free remission remains challenging. This commentary evaluates the global landscape of interventional LN clinical trials from 2001 to 2026 to identify emerging trends and strategic gaps in drug development. METHODS: We analyzed 200 interventional pharmacological trials retrieved from three major global registries: ClinicalTrials.gov, Chinadrugtrials.org

Новые границы для лечения множественных склерозов: от целесообразных молекулов до биконкретных антител.

Множественный склероз (MS) — аутоиммунное демиелинирующее заболевание центральной нервной системы. С 1990-х годов был достигнут значительный прогресс в развитии терапевтического ландшафта MS, в результате чего было разработано более 20 различных методов лечения заболеваний (ДМТ). Эта терапия эффективно решает проблемы рецидивов и воспаления, но большинство из них не смогли реально предотвратить прогрессирование заболеваний. В то время как классически понимается как состояние с Т-камерой, наиболее эффективные DMT в замедлении движения также нацелены на клетки B. Новые классы методов лечения MS

Reimagination in art and science: Seeing the familiar in a new light and creating new things that didn't exist before.

Many groundbreaking works in art and science owe their origins to the creative spark ignited by reimagination-the process whereby artists and scientists reinterpret and reframe past and existing knowledge, envisioning it in a new context that reveals new possibilities. Artistic and scientific innovation originating from reimagination brings to mind William Faulkner's famous line, "The past is never dead. It's not even past." [W. Faulkner, Requiem for a Nun (1)].

Breakthroughs in modern cancer therapy and elusive cardiotoxicity: Critical research-practice gaps, challenges, and insights.

To date, five cancer treatment modalities have been defined. The three traditional modalities of cancer treatment are surgery, radiotherapy, and conventional chemotherapy, and the two modern modalities include molecularly targeted therapy (the fourth modality) and immunotherapy (the fifth modality). The cardiotoxicity associated with conventional chemotherapy and radiotherapy is well known. Similar adverse cardiac events are resurging with the fourth modality. Aside from the conventional and newer targeted agents, even the most newly developed, immune-based therapeutic modalities of anticancer