The missing link between cancer stem cells and immunotherapy.

Cancer stem cells (CSCs) are cancer cells that can self-renew and give rise to tumors. The multipotency of CSCs enables the generation of diverse cancer cell types and their potential for differentiation and resilience against chemotherapy and radiation. Additionally, specific biomarkers have been identified for them, such as CD24, CD34, CD44, CD47, CD90, and CD133. The CSC model suggests that a subset of CSCs within tumors is responsible for tumor growth. The tumor microenvironment (TME), including fibroblasts, immune cells, adipocytes, endothelial cells, neuroendocrine (NE) cells, extracellular matrix (ECM), and extracellular vesicles, has a part in shielding CSCs from the host immune response as well as protecting them against anticancer drugs. The regulation of cancer stem cell plasticity by cancer-associated fibroblasts (CAFs) occurs through specific signaling pathways that differ among various types of cancer, utilizing the IGF-II/IGF1R, FAK, and c-Met/FRA1/HEY1 signaling pathways. Due to the intricate dynamics of CSC proliferation, controlling their growth necessitates innovative approaches and much more research. Our current review speculates an outline of how the TME safeguards stem cells, their interaction with CSCs, and the involvement of the immune and inflammatory systems in CSC differentiation and maintenance. Several technologies have the ability to identify CSCs; however, each approach has limitations. We discuss how these methods can aid in recognizing CSCs in several cancer types, comprising brain, breast, liver, stomach, and colon cancer. Furthermore, we explore different immunotherapeutic strategies targeting CSCs, including stimulating cancer-specific T cells, modifying immunosuppressive TMEs, and antibody-mediated therapy targeting CSC markers.

Synaptic modulation by coffee compounds: Insights into neural plasticity.

The physiological structure and functioning of the brain are determined by activity-dependent processes and affected by "synapse plasticity." Because chemical transmitters target and regulate synapses, exogenous chemical stimulants and transmitters can alter their physiological functions by interacting with synaptic surface receptors or chemical modulators. Caffeine, a commonly used pharmacologic substance, can target and alter synapses. It impact various biological, chemical, and metabolic processes related to synaptic function. This chapter investigates how caffeine affects fluctuations in structure and function in the hippocampus formation and neocortical structure, regions known for their high synaptic plasticity profile. Specifically, caffeine modulates various synaptic receptors and channel activities by mobilizing intracellular calcium, inhibiting phosphodiesterase, and blocking adenosine and GABA cellular receptors. These caffeine-induced pathways and functions allow neurons to generate plastic modulations in synaptic actions such as efficient and morphological transmission. Moreover, at a network level, caffeine can stimulate neural oscillators in the cortex, resulting in repetitive signals that strengthen long-range communication between cortical areas reliant on N-methyl-d-aspartate receptors. This suggests that caffeine could facilitate the reorganization of cortical network functions through its effects on synaptic mobilization.

Beneficial effects of physical exercise on cognitive-behavioral impairments and brain-derived neurotrophic factor alteration in the limbic system induced by neurodegeneration.

Neurodegenerative diseases (NDDs) are a class of neurological disorders marked by the progressive loss of neurons that afflict millions of people worldwide. These illnesses affect brain connection, impairing memory, cognition, behavior, sensory perception, and motor function. Alzheimer's, Parkinson's, and Huntington's diseases are examples of common NDDs, which frequently include the buildup of misfolded proteins. Cognitive-behavioral impairments are early markers of neurodevelopmental disorders, emphasizing the importance of early detection and intervention. Neurotrophins such as brain-derived neurotrophic factor (BDNF) are critical for neuron survival and synaptic plasticity, which is required for learning and memory. NDDs have been associated with decreased BDNF levels. Physical exercise, a non-pharmacological intervention, benefits brain health by increasing BDNF levels, lowering cognitive deficits, and slowing brain degradation. Exercise advantages include increased well-being, reduced depression, improved cognitive skills, and neuroprotection by lowering amyloid accumulation, oxidative stress, and neuroinflammation. This study examines the effects of physical exercise on cognitive-behavioral deficits and BDNF levels in the limbic system impacted by neurodegeneration. The findings highlight the necessity of including exercise into NDD treatment to improve brain structure, function, and total BDNF levels. As research advances, exercise is becoming increasingly acknowledged as an important technique for treating cognitive decline and neurodegenerative disorders.

Molecular functions of microRNAs in colorectal cancer: recent roles in proliferation, angiogenesis, apoptosis, and chemoresistance.

MiRNAs (microRNAs) constitute a group of diminutive molecules of non-coding RNA intricately involved in regulating gene expression. This regulation is primarily accomplished through the binding of miRNAs to complementary sequences situated in the 3'-UTR of the messenger RNA (mRNA) target; as a result, they are degraded or repressed. The multifaceted biogenesis of miRNAs is characterized by a meticulously orchestrated sequence of events encompassing transcription, processing, transportation, and decay. Colorectal cancer stands as a pervasive and formidable ailment, afflicting millions across the globe. Colorectal cancer is not well diagnosed early, and metastasis rates are high, which results in low survival rates in advanced stages. The genesis and progression of colorectal cancer are subject to the influence of genetic and epigenetic factors, among which miRNAs play a pivotal role. When it comes to colorectal cancer, miRNAs have a dual character, depending on the genes they target, functioning as either tumor suppressors or oncogenes and the prevailing cellular milieu. Their impact extends to modulating critical facets of colorectal cancer pathogenesis, including proliferation, angiogenesis, apoptosis, chemoresistance, and radiotherapy response. The discernible potential of miRNAs which are used as biomarkers to diagnose colorectal cancer, prognosis, and treatment response has come to the forefront. Notably, miRNAs are easily found and detected readily in a variety of biological fluids, including saliva, blood, urine, and feces. This prominence is attributed to the inherent advantages of miRNAs over conventional biomarkers, including heightened stability, specificity, sensitivity, and accessibility. Various investigations have pinpointed miRNA signatures or panels capable of differentiating colorectal cancer patients from their healthy counterparts, predicting colorectal cancer stage and survival, and monitoring colorectal cancer recurrence and therapy response. Although there has been research on miRNAs in various diseases, there has been less research on miRNAs in cancer. Moreover, updated results of preclinical and clinical studies on miRNA biomarkers and drugs are required. Nevertheless, the integration of miRNAs as biomarkers for colorectal cancer is not devoid of challenges and limitations. These encompass the heterogeneity prevalent among colorectal cancer subtypes and stages, the variability in miRNA expression across different tissues and individuals, the absence of standardized methodologies for miRNA detection and quantification, and the imperative for validation through extensive clinical trials. Consequently, further research is imperative to conclusively establish the clinical utility and reliability of miRNAs as colorectal cancer biomarkers. MiR-21 demonstrates carcinogenic characteristics by targeting several tumor suppressor genes, which encourages cell division, invasion, and metastasis. On the other hand, by controlling the Wnt/ß-catenin pathway, the tumor suppressor miRNA miR-34a prevents CRC cell proliferation, migration, and invasion. Furthermore, in colorectal cancer, the miR-200 family increases chemotherapy sensitivity while suppressing epithelial-mesenchymal transition (EMT). As an oncogene, the miR-17-92 cluster targets elements of the TGF-ß signaling pathway to encourage the growth of CRC cells. Finally, miR-143/145, which is downregulated in CRC, influences apoptosis and the progression of the cell cycle. These miRNAs affect pathways like Wnt, TGF-ß, PI3K-AKT, MAPK, and EMT, making them potential clinical biomarkers and therapeutic targets. This review summarizes recent research related to miRNAs, their role in tumor progression and metastasis, and their potential as biomarkers and therapeutic targets in colorectal cancer. In addition, we combined miRNAs' roles in tumorigenesis and development with the therapy of CRC patients, leading to novel perspectives on colorectal cancer diagnosis and treatment.

Circulating tumor cells clusters and their role in Breast cancer metastasis; a review of literature.

Breast cancer is a significant and deadly threat to women globally. Moreover, Breast cancer metastasis is a complicated process involving multiple biological stages, which is considered a substantial cause of death, where cancer cells spread from the original tumor to other organs in the body-representing the primary mortality factor. Circulating tumor cells (CTCs) are cancer cells detached from the primary or metastatic tumor and enter the bloodstream, allowing them to establish new metastatic sites. CTCs can travel alone or in groups called CTC clusters. Studies have shown that CTC clusters have more potential for metastasis and a poorer prognosis than individual CTCs in breast cancer patients. However, our understanding of CTC clusters' formation, structure, function, and detection is still limited. This review summarizes the current knowledge of CTC clusters' biological properties, isolation, and prognostic significance in breast cancer. It also highlights the challenges and future directions for research and clinical application of CTC clusters.

Mitochondrial dysfunction and neurological disorders: A narrative review and treatment overview.

Mitochondria play a vital role in the nervous system, as they are responsible for generating energy in the form of ATP and regulating cellular processes such as calcium (Ca2+) signaling and apoptosis. However, mitochondrial dysfunction can lead to oxidative stress (OS), inflammation, and cell death, which have been implicated in the pathogenesis of various neurological disorders. In this article, we review the main functions of mitochondria in the nervous system and explore the mechanisms related to mitochondrial dysfunction. We discuss the role of mitochondrial dysfunction in the development and progression of some neurological disorders including Parkinson's disease (PD), multiple sclerosis (MS), Alzheimer's disease (AD), depression, and epilepsy. Finally, we provide an overview of various current treatment strategies that target mitochondrial dysfunction, including pharmacological treatments, phototherapy, gene therapy, and mitotherapy. This review emphasizes the importance of understanding the role of mitochondria in the nervous system and highlights the potential for mitochondrial-targeted therapies in the treatment of neurological disorders. Furthermore, it highlights some limitations and challenges encountered by the current therapeutic strategies and puts them in future perspective.

A promising RNA nanotechnology in clinical therapeutics: a future perspective narrative review.

Nanotechnology is the use of materials that have unique nanoscale properties. In recent years, nanotechnologies have shown promising results for human health, especially in cancer treatment. The self-assembly characteristic of RNA is a powerful bottom-up approach to the design and creation of nanostructures through interdisciplinary biological, chemical and physical techniques. The use of RNA nanotechnology in therapeutics is about to be realized. This review discusses different kinds of nano-based drug delivery systems and their characteristic features.

A branch of nanotechnology called RNA nanotechnology involves designing, studying, and utilizing synthetic structures based on RNA. This review discusses different kinds of nano-based drug delivery systems and their characteristic features. It aims to provide an overview of nanoparticles as a delivery system for gene therapy to treat diseases such as cancer. In order to enhance nanoparticle efficacy, these systems should be designed with this in mind in order to develop and test delivery systems rationally and scientifically.