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Aberration of miRNAs Expression in Leukocytes from Sporadic Amyotrophic Lateral Sclerosis.

BACKGROUND: Accumulating evidence indicates that miRNAs play an important role in the development of amyotrophic lateral sclerosis (ALS). Most of previous studies on miRNA dysregulation in ALS focused on the alterative expression in ALS animal model or in limited samples from European patients with ALS. In the present study, the miRNA expression profiles were investigated in Chinese ALS patients to explore leukocytes miRNAs as a potential biomarker for the diagnosis of ALS. METHODS: We analyzed the expression profiles of 1733 human mature miRNAs using microarray technology in leukocytes obtai

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… Unlike other biomarkers, miRNAs can be easily secreted into the extracellular space from neurons and other CNS cells. Also, miRNAs are isolated and quantified from a variety of biofluids, allowing miRNAs as ideal potential biomarkers for ALS. …

Длинная и извилистая дорога: гомеостатические и беспорядочные микроэкологические ниши: обзор описательной части.

Микроэкологические ниши Haematopoiet были охарактеризованы как "приемники" крови и иммунной системы. Эти ниши меняются во время онтгении, при этом костный мозг становится доминирующим местом гематопоисиса в послеродовой жизни в стабильных условиях. Для определения структуры и функции различных микроэкологических ниш гематопоиета необходимо четко определить конкретные подмножества гематопоиетических стеблей и потомковых клеток во время офгении и понять их временной внешний вид и анатомическое позиционирование. Различные гематопоиетические и негематопоиетические клетки способствуют появлению гем

Cytotoxic CD4+ T cells: origin, biological functions, diseases and therapeutic targets.

Cytotoxic CD4+ T lymphocytes are a unique subset of CD4+ T cells characterized by their cytokine secretion and cytolytic activity. Unlike traditional CD4+ helper T cells, cytotoxic CD4+ T lymphocytes exhibit similar cytotoxicity to that of CD8+ T cells, revealing unexpected plasticity in CD4+ T-cell functions. This flexibility suggests that CD4+ T cells can transform and acquire effector functions beyond their conventional functions, emphasizing their importance in various immune responses. Despite the identification of cytotoxic CD4+ T lymphocytes decades ago, recent advancements have broaden

Integrating CRISPR/Cas technology with clinical trials: Principles, progress and challenges.

CRISPR represent a groundbreaking genome-editing technology that has revolutionized genetic modification. This innovative tool offers an unparalleled revolution in the future treatment of genetic disorders, neurological diseases, infectious diseases and cancer. Despite the rapid expansion of CRISPR applications, its clinical use in humans is still relatively limited, with only 69 active clinical trials and 6 completed studies reported so far. This review examined current clinical trials and their processes in addressing various diseases via the CRISPR/Cas system. While earlier literatures have

Applications of Aggregation-Induced Emission Materials in Immunology: From Diagnostics to Immunotherapy.

Aggregation-induced emission (AIE) materials, due to their unique ability to significantly enhance optical emission in aggregated states, have demonstrated vast potential in immunology, particularly in early disease diagnosis and immunotherapy. AIE materials can serve as highly efficient fluorescent probes for biomarker detection, providing critical insights for early diagnosis. Additionally, they can act as cancer vaccines, enhancing the effectiveness of immunotherapy through photodynamic therapy, photothermal therapy, or activation of immune cells. This review highlights the applications of

Proteasome Inhibitors and Their Potential Applicability in Osteosarcoma Treatment.

Osteosarcoma (OS) is the most common type of bone cancer, with ~30% of patients developing secondary/metastatic tumors. The molecular complexity of tumor metastasis and the lack of effective therapies for OS has cultivated interest in exploiting the proteasome as a molecular target for anti-cancer therapy. As our understanding towards the behavior of malignant cells expands, it is evident that cancerous cells display a greater reliance on the proteasome to maintain homeostasis and sustain efficient biological activities. This led to the development and approval of first- and second-generation

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

Molecular mechanisms and clinical management of cancer bone metastasis.

As one of the most common metastatic sites of malignancies, bone has a unique microenvironment that allows metastatic tumor cells to grow and flourish. The fenestrated capillaries in the bone, bone matrix, and bone cells, including osteoblasts and osteoclasts, together maintain the homeostasis of the bone microenvironment. In contrast, tumor-derived factors act on bone components, leading to subsequent bone resorption or excessive bone formation. The various pathways involved also provide multiple targets for therapeutic strategies against bone metastases. In this review, we summarize the curr

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Novel Investigations of Flavonoids as Chemopreventive Agents for Hepatocellular Carcinoma.

We would like to highlight the application of natural products to hepatocellular carcinoma (HCC). We will focus on the natural products known as flavonoids, which target this disease at different stages of hepatocarcinogenesis. In spite of the use of chemotherapy and radiotherapy in treating HCC, patients with HCC still face poor prognosis because of the nature of multidrug resistance and toxicity derived from chemotherapy and radiotherapy. Flavonoids can be found in many vegetables, fruits, and herbal medicines that exert their different anticancer effects via different intracellular signalin

DNA Methylation Cancer Biomarkers: Translation to the Clinic.

Carcinogenesis is accompanied by widespread DNA methylation changes within the cell. These changes are characterized by a globally hypomethylated genome with focal hypermethylation of numerous 5'-cytosine-phosphate-guanine-3' (CpG) islands, often spanning gene promoters and first exons. Many of these epigenetic changes occur early in tumorigenesis and are highly pervasive across a tumor type. This allows DNA methylation cancer biomarkers to be suitable for early detection and also to have utility across a range of areas relevant to cancer detection and treatment. Such tests are also simple in

Clinical Applications and Anticancer Effects of Antimicrobial Peptides: From Bench to Bedside.

Cancer is a multifaceted global health issue and one of the leading causes of death worldwide. In recent years, medical science has achieved great advances in the diagnosis and treatment of cancer. Despite the numerous advantages of conventional cancer therapies, there are major drawbacks including severe side effects, toxicities, and drug resistance. Therefore, the urgency of developing new drugs with low cytotoxicity and treatment resistance is increasing. Antimicrobial peptides (AMPs) have attracted attention as a novel therapeutic strategy for the treatment of various cancers, targeting tu

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… The first is that cell lysis and following release of the intracellular content to the extracellular space could increase the amount of tumor-associated antigen that stimulated T cells through antigen-presenting cells (APCs) ( 170 ). …

Oxidative Stress: Signaling Pathways, Biological Functions, and Disease.

The dysregulated accumulation of reactive oxygen species (ROS) and reactive nitrogen species disrupts redox homeostasis, triggering oxidative stress (OS) and driving pathophysiological changes across multiple organ systems. OS modulates critical signaling pathways, induces inflammation, impairs mitochondrial function, alters metabolic homeostasis, and dysregulates autophagy, contributing to disease progression. While prior research has largely focused on OS within single-organ diseases (e.g., neurodegenerative, cardiovascular, and oncological disorders), the systemic role of OS in pan-organ di

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… Ultimately, through transcriptional activation and chromatin decondensation, NETs are released into the extracellular space. In cases of NOX‐independent NETosis, the primary driver for NET formation is the increase in mitochondrial ROS (mtROS) production. … In conclusion, similar to NOX‐dependent NETosis, NETs are released into the extracellular space. …

NRF2: A crucial regulator for mitochondrial metabolic shift and prostate cancer progression.

Metabolic alterations are a common survival mechanism for prostate cancer progression and therapy resistance. Oxidative stress in the cellular and tumor microenvironment dictates metabolic switching in the cancer cells to adopt, prosper and escape therapeutic stress. Therefore, regulation of oxidative stress in tumor cells and in the tumor-microenvironment may enhance the action of conventional anticancer therapies. NRF2 is the master regulator for oxidative stress management. However, the overall oxidative stress varies with PCa clinical stage, metabolic state and therapy used for the cancer.

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… Therefore, in normal prostate epithelial cells, the TCA cycle is truncated, and the unused citrate is released to the extracellular space. Excess extracellular citrate and intracellular zinc levels result in the dependency of normal prostate epithelial cells on glycolysis. …

Overview of Ayurveda and Ashwagandha: Bioactive Phytochemicals and Potential Applications to Gliomas.

Ayurveda is the traditional medical system of India and has been in use for more than 5000 years. The focus of Ayurveda is to maintain harmony and balance of the three Doshas (Vata, Pitta, Kapha), or life forces, that govern the physiology and health of each individual. Ashwagandha is considered one of the most useful plants in the Ayurvedic system for various illnesses, including cancer. Ethnopharmacological and phytochemical analyses have been elucidating the bioactive compounds in ashwagandha that mediate the anti-cancer effects. The most bioactive compounds appear to be the withanolides, i

Abscopal Effects in Metastatic Cancer: Is a Predictive Approach Possible to Improve Individual Outcomes?

Patients with metastatic cancers often require radiotherapy (RT) as a palliative therapy for cancer pain. RT can, however, also induce systemic antitumor effects outside of the irradiated field (abscopal effects) in various cancer entities. The occurrence of the abscopal effect is associated with a specific immunological activation in response to RT-induced cell death, which is mainly seen under concomitant immune checkpoint blockade. Even if the number of reported apscopal effects has increased since the introduction of immune checkpoint inhibition, its occurrence is still considered rare and

Therapeutic Advances in Oncology.

Around 77 new oncology drugs were approved by the FDA in the past five years; however, most cancers remain untreated. Small molecules and antibodies are dominant therapeutic modalities in oncology. Antibody-drug conjugates, bispecific antibodies, peptides, cell, and gene-therapies are emerging to address the unmet patient need. Advancement in the discovery and development platforms, identification of novel targets, and emergence of new technologies have greatly expanded the treatment options for patients. Here, we provide an overview of various therapeutic modalities and the current treatment

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… A cleavable linker was designed to promote drug release to extracellular space to cause a stronger bystander effect. In addition, higher drug to antibody ratio (DAR) was implemented in the design of ADC to deliver a higher payload to tumor cells that have lower HER2 expression [ 61 ]. …

Targeting dorsal root ganglia for chemotherapy-induced peripheral neuropathy: from bench to bedside.

Chemotherapy-induced peripheral neuropathy (CIPN) is a debilitating condition affecting an increasing number of cancer survivors worldwide. However, insights into its pathophysiology and availability of effective therapies remain lacking. Dorsal root ganglia (DRG) have been studied as a key component of chemotherapeutic drug toxicity and a potential therapeutic target for CIPN treatment. This comprehensive review aims to synthesize, summarize, and correlate the results of both preclinical and clinical studies relevant to the pathophysiology and management of CIPN in relation to the DRG. Design

CRISPR/Cas9: A revolutionary genome editing tool for human cancers treatment.

Cancer is a genetic disease stemming from genetic and epigenetic mutations and is the second most common cause of death across the globe. Clustered regularly interspaced short palindromic repeats (CRISPR) is an emerging gene-editing tool, acting as a defense system in bacteria and archaea. CRISPR/Cas9 technology holds immense potential in cancer diagnosis and treatment and has been utilized to develop cancer disease models such as medulloblastoma and glioblastoma mice models. In diagnostics, CRISPR can be used to quickly and efficiently detect genes involved in various cancer development, prol

Cancer Immune Therapy for Philadelphia Chromosome-Negative Chronic Myeloproliferative Neoplasms.

Philadelphia chromosome-negative chronic myeloproliferative neoplasms (MPN) are neoplastic diseases of the hematopoietic stem cells in the bone marrow. MPN are characterized by chronic inflammation and immune dysregulation. Of interest, the potent immunostimulatory cytokine interferon-α has been used to treat MPN for decades. A deeper understanding of the anti-cancer immune response and of the different immune regulatory mechanisms in patients with MPN has paved the way for an increased perception of the potential of cancer immunotherapy in MPN. Therapeutic vaccination targeting the driver mut

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… Additionally, it has been demonstrated that mutant CALR protein is not retained within the mutant cell but released into the extracellular space [ 80 ]. …