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Endothelial TFEB signaling-mediated autophagic disturbance initiates microglial activation and cognitive dysfunction.

Cognitive impairment caused by systemic chemotherapy is a critical question that perplexes the effective implementation of clinical treatment, but related molecular events are poorly understood. Herein, we show that bortezomib exposure leads to microglia activation and cognitive impairment, this occurs along with decreased nuclear translocation of TFEB (transcription factor EB), which is linked to macroautophagy/autophagy disorder, STAT3 (signal transducer and activator of transcription 3) phosphorylation and IL23A (interleukin 23 subunit alpha) expression. Pharmacological enhancement of TFEB

Next-generation antibody-based therapeutics in cancer: antibody-drug conjugates bispecific antibodies across hematologic malignancies and solid tumors.

The therapeutic paradigm in oncology is undergoing a profound transformation driven by antibody-drug conjugates (ADCs) and bispecific antibodies (bsAbs). This review comprehensively summarizes recent clinical advances of these platforms across both hematologic malignancies and solid tumors. ADCs such as trastuzumab deruxtecan have expanded the concept of targetable HER2 expression, demonstrating meaningful intracranial activity and redefining standards of care in HER2-low breast cancer and beyond. The landscape continues to broaden with novel ADC targets (TROP2, CLDN18.2, B7-H3, HER3) and bisp

"Complimenting the Complement": Mechanistic Insights and Opportunities for Therapeutics in Hepatocellular Carcinoma.

Hepatocellular carcinoma (HCC) is the most common primary malignancy of the liver and a leading cause of death in the US and worldwide. HCC remains a global health problem and is highly aggressive with unfavorable prognosis. Even with surgical interventions and newer medical treatment regimens, patients with HCC have poor survival rates. These limited therapeutic strategies and mechanistic understandings of HCC immunopathogenesis urgently warrant non-palliative treatment measures. Irrespective of the multitude etiologies, the liver microenvironment in HCC is intricately associated with chronic

Case Report: Acute kidney injury due to minimal dilated obstructive nephropathy in the context of gastric cancer.

Postrenal obstruction is a rare but reversible cause of acute kidney injury (AKI), often underrecognized when hydronephrosis is mild or absent. We present a 55-year-old woman with gastric cancer who developed severe AKI requiring hemodialysis. Initial non-contrast abdominal CT revealed only mild bilateral hydronephrosis without obvious ureteral obstruction. Given these subtle radiologic findings and a history of chemotherapy and NSAID exposure. Initially, a multidisciplinary team attributed the AKI to intrinsic renal causes. Subsequent renal biopsy revealed only minimal glomerular changes, ins

Микроглии/Макропатии в области аутоиммунной демьелинизации энцефаломелита (многообразный склероз/нейромиелит Оптика).

Микроглии и макрофаги являются важнейшими посредниками иммунной реакции в центральной нервной системе. Их функции варьируются от гомеостатического обслуживания до патогенеза аутоиммунных демиелинизирующих заболеваний, таких, как множественный склероз и оптический спектр нейромелита. В рамках этого обзора изучаются источники микроглии и макрофаги, а также механизмы их активации, взаимодействие с другими нейронными клетками и вклад в развитие и восстановление заболеваний. В нем также подчеркивается актуальность перевода знаний, полученных с помощью моделей животных, и терапевтический потенциал,

Biopharmaceuticals for Cancer Treatment: An Update.

Cancer is one of the most debilitating diseases, causing profound physical and psychological impacts on patients. The global number of cancer patients has been steadily rising over the last few decades. The development of effective cancer therapies remains the primary focus in life science research, requiring a precise understanding of specific pathways and the regulation of tumor markers. The approved cancer therapies demonstrate effectiveness by acting on specific regulatory enzymes, components required for cell division, hormones, and cell-specific receptors, etc. While small-molecule drugs

Epigenetic modification in diabetic kidney disease.

Diabetic kidney disease (DKD) is a common microangiopathy in diabetic patients and the main cause of death in diabetic patients. The main manifestations of DKD are proteinuria and decreased renal filtration capacity. The glomerular filtration rate and urinary albumin level are two of the most important hallmarks of the progression of DKD. The classical treatment of DKD is controlling blood glucose and blood pressure. However, the commonly used clinical therapeutic strategies and the existing biomarkers only partially slow the progression of DKD and roughly predict disease progression. Therefor

New developments in immunotherapy for SCLC.

Small cell lung cancer (SCLC) is an aggressive form of neuroendocrine neoplasm known for its striking initial response to treatment, followed by fast relapse and refractoriness in response to additional lines of therapy. New advances in immunotherapy are paving the way for more effective treatment strategies and have promising results with early clinical trial data. While SCLC rarely harbors actionable mutations, the receptor DLL3 is extensively present in SCLC, making it a potential target for immunotherapy. Three emerging therapeutic options include bispecific T cell engagers targeting DLL3,

The Eph/Ephrin system in primary bone tumor and bone cancer pain.

The family of Eph receptor tyrosine kinases and their Ephrin ligands system constitutes a bidirectional signaling pathway. Eph/Ephrin system coordinate a wide spectrum of pathologic processes during development, metastasis, prognosis, drug resistance and angiogenesis in carcinogenesis. Chemotherapy, surgery and radiotherapy are the most commonly used clinical treatments for primary bone tumors. Therefore, surgical resection is often unable to completely eliminate the tumor, and this is the main cause of metastasis and postoperative recurrence. A growing body of literature has been published la

Decoding the mechanisms underlying breast cancer brain metastasis: paving the way for precision therapeutics.

The development of brain metastasis is a major cause of significantly reduced survival in breast cancer patients. The initiation and progression of breast cancer brain metastasis (BCBM) involve multiple distinct molecular pathways and reprogramming of the tumor microenvironment (TME). This review systematically summarizes key mechanisms underlying BCBM, including epithelial-mesenchymal transition (EMT), extracellular matrix (ECM) remodeling, and the spatiotemporal dynamics of metabolic reprogramming regulated by critical signaling pathways during brain colonization. In particular, we highlight

The Gut-Bone Marrow Axis: Deciphering the Mechanistic Impact of Microbial Metabolites on Hematopoietic Homeostasis and Disorders.

The gut microbiota is increasingly recognized as a dynamic endocrine-like microbial network that exerts systemic effects far beyond the gastrointestinal tract. Emerging evidence supports the existence of a "gut-bone marrow axis" through which gut-derived signals orchestrate hematopoietic homeostasis. However, shifting from correlative observations to causal mechanisms remains a major challenge in defining precise microbial impacts on hematopoietic outcomes. In this review, we systematically synthesize current knowledge on the molecular mechanisms by which microbial products-specifically short-

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… The intestinal barrier maintains its permeability by sustaining the intact expression of tight junction proteins such as Occludin and Claudin-1, thereby stabilizing the structure of the gut microbiota. … The probiotic strain Akkermansia muciniphila can improve intestinal barrier function through the modulation of tight junction proteins such as occludin and claudins. …

A roadmap for establishing institutional readiness for cellular therapies targeting solid tumours and autoimmune diseases.

Adoptive cellular therapies have revolutionised treatment of haematological malignancies and demonstrate potential in solid tumours and autoimmune disease. Real-world implementation remains limited by biological, logistical, and manufacturing barriers, restricting global uptake despite a rapidly expanding clinical trial portfolio. Effective implementation requires national and institutional readiness, multidisciplinary collaboration, scalable manufacturing, and robust infrastructure. Efforts should prioritise decentralised and "off the shelf" platforms, integrated referral networks, and AI-ass

Длиннокаменистые толстые кислоты как движущие факторы нейроинфламмации в нейродегенерации: механистические связи с липидом пероксидацией, Ферроптозом и митохондриальной дисфункцией.

Фон: Нейродегенеративные заболевания (НИ) рассматриваются главным образом как расстройства, характеризующиеся серьезным иммунометаболическим дисбалансом, характеризующимся текущей нейроинфламмацией и глиальной активацией. Хотя митохондриальная дисфункция и окислительный стресс являются хорошо известными особенностями, метаболические факторы в верхнем течении, связывающие эти патологические процессы, по-прежнему плохо понимаются. Методы: В ходе этого обзора мы изучили недавние доклинические и клинические исследования, в ходе которых были изучены связи между липидным метаболизмом, иммунометаболи

Langerhans dendritic cell vaccine bearing mRNA-encoded tumor antigens induces antimyeloma immunity after autotransplant.

Posttransplant vaccination targeting residual disease is an immunotherapeutic strategy to improve antigen-specific immune responses and prolong disease-free survival after autologous stem cell transplantation (ASCT) for multiple myeloma (MM). We conducted a phase 1 vaccine trial to determine the safety, toxicity, and immunogenicity of autologous Langerhans-type dendritic cells (LCs) electroporated with CT7, MAGE-A3, and Wilms tumor 1 (WT1) messenger RNA (mRNA), after ASCT for MM. Ten patients received a priming immunization plus 2 boosters at 12, 30, and 90 days, respectively, after ASCT. Vacc

Integrative meta-analysis identifies microRNA-regulated networks in infantile hemangioma.

BackgroundHemangioma is a common benign tumor in the childhood; however our knowledge about the molecular mechanisms of hemangioma development and progression are still limited. Currently, microRNAs (miRNAs) have been shown as gene expression regulators with an important role in disease pathogenesis. Our goals were to identify miRNA-mRNA expression networks associated with infantile hemangioma.MethodsWe performed a meta-analysis of previously published gene expression datasets including 98 hemangioma samples. Deregulated genes were further used to identify microRNAs as potential regulators of

HMMR in human cancers: regulatory mechanism and biological function.

Hyaluronan-mediated motility receptor (HMMR), also referred to as RHAMM or CD168, has gained recognition as a multifunctional protein that mediates the transmission of extracellular matrix-derived hyaluronan (HA) signals to intracellular pathways regulating tumor growth, migration, and mitosis. Overexpression of HMMR is observed in various cancers, including head and neck squamous cell carcinoma, breast cancer, lung cancer, and prostate cancer, as well as several hematologic malignancies. This elevated expression correlates with poor prognosis, rendering it a valuable marker for survival predi

The current socioeconomic and regulatory landscape of immune effector cell therapies.

Immune cell effector therapies, including chimeric antigen receptor (CAR)-T cells, T-cell receptor (TCR) T cells, natural killer (NK) cells, and macrophage-based therapies, represent a transformative approach to cancer treatment, harnessing the immune system to target and eradicate malignant cells. CAR-T cell therapy, the most established among these, involves engineering T cells to express CARs specific to cancer cell antigens, showing remarkable efficacy in hematologic malignancies like leukemias, B-cell lymphomas, and multiple myeloma. Similarly, TCR-modified therapies, which reprogram T ce

Conditioned Media-Derived Tumor Extracellular Vesicles: Bridging Molecular Insights and Therapeutic Applications in Oncology.

Tumor-derived extracellular vesicles (EVs) are major mediators of oncogenic intercellular communication. However, many studies using conditioned media (CM) recover operationally defined EV- or small EV-enriched fractions rather than biogenesis-proven exosomes. This review synthesizes evidence from CM-derived tumor EV studies and aligns their biological interpretation with current EV nomenclature, characterization, and reporting principles. We first discuss exosome biogenesis as a defined endosomal pathway and then examine how CM collection, serum handling, culture format, oxygen tension, condi

Harnessing the potential of CAR-T cell therapy: progress, challenges, and future directions in hematological and solid tumor treatments.

Traditional cancer treatments use nonspecific drugs and monoclonal antibodies to target tumor cells. Chimeric antigen receptor (CAR)-T cell therapy, however, leverages the immune system's T-cells to recognize and attack tumor cells. T-cells are isolated from patients and modified to target tumor-associated antigens. CAR-T therapy has achieved FDA approval for treating blood cancers like B-cell acute lymphoblastic leukemia, large B-cell lymphoma, and multiple myeloma by targeting CD-19 and B-cell maturation antigens. Bi-specific chimeric antigen receptors may contribute to mitigating tumor anti

Current trends in theranostic applications of extracellular vesicles in cancer.

BackgroundExtracellular vesicles (EVs) play an integral role in cancer biology, influencing tumor progression, metastasis, and tumor microenvironment. Due to their distinctive molecular composition, including proteins, nucleic acids, and lipids, EVs present a promising candidate for cancer diagnostics and precision therapeutics.MethodsThis review was conducted by looking up recent studies obtained through PubMed, Scopus, and Web of Science databases using targeted keywords such as "Extracellular Vesicles," "Cancer Therapy," "Biomarkers," "Exosomes," "Tumor Microenvironment," and "Precision Med