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Exploring the Potential of MicroRNA Let-7c as a Therapeutic for Prostate Cancer.

Prostate cancer (PCa) is one of the leading causes of mortality worldwide and often presents with aberrant microRNA (miRNA) expression. Identifying and understanding the unique expression profiles could aid in the detection and treatment of this disease. This review aims to identify miRNAs as potential therapeutic targets for PCa. Three bio-informatic searches were conducted to identify miRNAs that are reportedly implicated in the pathogenesis of PCa. Only hsa-Lethal-7 (let-7c), recognized for its role in PCa pathogenesis, was common to all three databases. Three further database searches were

Screening the Active Phytochemicals From Eclipta prostrata and Unraveling Their Molecular Insight Into Human Malignancies.

Current drugs against multiple human malignancies are limited, and developing new treatment strategies is improbable within a short time. So, considering the current situation, phytochemicals could be a viable option for developing chemotherapeutic agents for managing numerous types of malignancies. Therefore, we aimed to locate all phytochemicals of Eclipta prostrata and unravel their chemotherapeutic mechanisms and strategies individually. We defined 25 active compounds based on their anticancer activities after filtering through IMPPAT and literature search, and these compounds have chemoth

Towards Precision Oncology: The Role of Smoothened and Its Variants in Cancer.

The G protein-coupled receptor Smoothened (Smo) is a central signal transducer of the Hedgehog (Hh) pathway which has been linked to diverse forms of tumours. Stimulated by advancements in structural and functional characterisation, the Smo receptor has been recognised as an important therapeutic target in Hh-driven cancers, and several Smo inhibitors have now been approved for cancer therapy. This receptor is also known to be an oncoprotein itself and its gain-of-function variants have been associated with skin, brain, and liver cancers. According to the COSMIC database, oncogenic mutations o

Amino acid metabolism in immune cells: essential regulators of the effector functions, and promising opportunities to enhance cancer immunotherapy.

Amino acids are basic nutrients for immune cells during organ development, tissue homeostasis, and the immune response. Regarding metabolic reprogramming in the tumor microenvironment, dysregulation of amino acid consumption in immune cells is an important underlying mechanism leading to impaired anti-tumor immunity. Emerging studies have revealed that altered amino acid metabolism is tightly linked to tumor outgrowth, metastasis, and therapeutic resistance through governing the fate of various immune cells. During these processes, the concentration of free amino acids, their membrane bound tr

Emerging treatment options for patients with p53-pathway-deficient CLL.

Over the past 40 years, p53 has been the most widely studied protein in cancer biology. Originally thought to be an oncogene due to its stabilization in many cancers, it is now considered to be one of the most critical tumor suppressors in a cell's ability to combat neoplastic transformation. Due to its critical roles in apoptosis, cell-cycle arrest, and senescence, TP53 deletions and mutations are commonly observed and are often a portent of treatment failures and poor clinical outcomes. This is particularly true in chronic lymphocytic leukemia (CLL), as patients with p53 alterations have his

HDAC Inhibitors: Therapeutic Potential in Fibrosis-Associated Human Diseases.

Fibrosis is characterized by excessive deposition of the extracellular matrix and develops because of fibroblast differentiation during the process of inflammation. Various cytokines stimulate resident fibroblasts, which differentiate into myofibroblasts. Myofibroblasts actively synthesize an excessive amount of extracellular matrix, which indicates pathologic fibrosis. Although initial fibrosis is a physiologic response, the accumulated fibrous material causes failure of normal organ function. Cardiac fibrosis interferes with proper diastole, whereas pulmonary fibrosis results in chronic hypo

Mechanisms to medicines: navigating drug repurposing strategies in Alzheimer's disease.

Alzheimer's disease (AD) represents a continuously advancing neurodegenerative condition distinguished by the unremitting deterioration of cognitive abilities and memory impairment, which significantly hampers daily functioning of life. In the absence of disease modifying treatments, it continues to pose a significant global challenge. Though symptomatic treatment exists, the inherent complexity involved with AD pathogenesis related to Aβ plaques, neurofibrillary tangles, neuroinflammation, oxidative stress, etc. poses a tremendous challenge to developing drugs. With the incidence of AD increa

An updated overview of the search for biomarkers of osteoporosis based on human proteomics.

Osteoporosis is a chronic metabolic disease that increases bone fragility and, leads to severe osteoporotic fractures. In recent years, the use of high-throughput omics to explore physiological and pathological biomarkers related to bone metabolism has gained popularity. In this review, we first briefly review the technical approaches of proteomics. Additionally, we summarize the relevant literature in the last decade to provide a comprehensive overview of advances in human proteomics related to osteoporosis. We describe the specific roles of various proteins related to human bone metabolism,

Enhancing the Bioavailability of Resveratrol: Combine It, Derivatize It, or Encapsulate It?

Overcoming the limited bioavailability and extensive metabolism of effective in vitro drugs remains a challenge that limits the translation of promising drugs into clinical trials. Resveratrol, despite its well-reported therapeutic benefits, is not metabolically stable and thus has not been utilized as an effective clinical drug. This is because it needs to be consumed in large amounts to overcome the burdens of bioavailability and conversion into less effective metabolites. Herein, we summarize the more relevant approaches to modify resveratrol, aiming to increase its biological and therapeut

Histone H3K18 Lactylation Promotes the Malignant Progression of Wilms Tumor via a PSRC1/AKT/HIF-1α Positive Feedback Loop.

Nephroblastoma, also known as Wilms tumor (WT), is the most common pediatric renal malignancy. Current treatment regimens exhibit limited efficacy in high-risk patients and are associated with long-term adverse effects. Through gene set enrichment analysis (GSEA) and validation using clinical specimens, we identified aberrant glycolytic activity in WT, which drives lactate accumulation. Lactate is not merely a metabolic byproduct but also a critical epigenetic regulator that mediates histone lactylation; however, its functional role in WT remains uncharacterized. In this study, we found that t

Lost in transcription: molecular mechanisms that control HIV latency.

Highly active antiretroviral therapy (HAART) has limited the replication and spread of the human immunodeficiency virus (HIV). However, despite treatment, HIV infection persists in latently infected reservoirs, and once therapy is interrupted, viral replication rebounds quickly. Extensive efforts are being directed at eliminating these cell reservoirs. This feat can be achieved by reactivating latent HIV while administering drugs that prevent new rounds of infection and allow the immune system to clear the virus. However, current approaches to HIV eradication have not been effective. Moreover,

Stabilization of DEPTOR sensitizes hypopharyngeal cancer to radiotherapy via targeting degradation.

The use of radiotherapy for hypopharyngeal cancer (HC) treatment is increasing, and it is currently the primary treatment option for this cancer. However, radioresistance occurs in a proportion of patients. Here, we found that radiation increased proteasomal gene expression and that proteasome assembly was dependent on the induction of transcription factor NRF1 in HC. Through screening assays, we identified a mechanism by which proteasome-mediated degradation of DEP domain-containing mTOR-interacting protein (DEPTOR) contributes to the elevation of mTORC1 signaling after radiation. Therefore,

Recent Advances in the Development and Utilization of Nanoparticles for the Management of Malignant Solid Tumors.

The purpose of nanotechnology-based drug delivery systems or novel drug delivery systems is to improve the effectiveness of therapy, and their promising properties have led to their increasing significance in the management of cancer. The researchers have primarily focused on designing novel nanocarriers, like nanoparticles (NPs), that can effectively deliver drugs to target cells and respond specifically to conditions particular to cancer. Whether passive or active targeting, these nanocarriers can deliver therapeutic cargoes to the tumor site to release the drug from the drug delivery system

The Hedgehog-GLI pathway in embryonic development and cancer: implications for pulmonary oncology therapy.

Transcriptional regulation and epigenetic mechanisms closely control gene expression through diverse physiological and pathophysiological processes. These include the development of germ layers and post-natal epithelial cell-tissue differentiation, as well as, involved with the induction, promotion and/or progression of human malignancies. Diverse studies have shed light on the molecular similarities and differences involved in the stages of embryological epithelial development and dedifferentiation processes in malignant tumors of epithelial origin, of which many focus on lung carcinomas. In

Eukaryotic initiation factors: central factor associating mRNA translational plasticity during neuropathic pain progression.

Neuropathic pain causes plasticity in the nervous system, which is often associated with altered protein synthesis. Proteins are the key executors of cellular functions, and their alteration is closely related to the occurrence of neuropathic pain. Protein synthesis is a finely regulated process involving the interaction of multiple biomolecules. Among them, the eukaryotic translation initiation factors (eIFs) are a group of key regulatory proteins that control the initiation phase of protein translation and thus influence the rate and type of protein synthesis. Recent studies have shown that

NF-κB in Cell Deaths, Therapeutic Resistance and Nanotherapy of Tumors: Recent Advances.

The transcription factor nuclear factor-κB (NF-κB) plays a complicated role in multiple tumors. Mounting evidence demonstrates that NF-κB activation supports tumorigenesis and development by enhancing cell proliferation, invasion, and metastasis, preventing cell death, facilitating angiogenesis, regulating tumor immune microenvironment and metabolism, and inducing therapeutic resistance. Notably, NF-κB functions as a double-edged sword exerting positive or negative influences on cancers. In this review, we summarize and discuss recent research on the regulation of NF-κB in cancer cell deaths,

The evolving roles of Wnt signaling in stem cell proliferation and differentiation, the development of human diseases, and therapeutic opportunities.

The evolutionarily conserved Wnt signaling pathway plays a central role in development and adult tissue homeostasis across species. Wnt proteins are secreted, lipid-modified signaling molecules that activate the canonical (β-catenin dependent) and non-canonical (β-catenin independent) Wnt signaling pathways. Cellular behaviors such as proliferation, differentiation, maturation, and proper body-axis specification are carried out by the canonical pathway, which is the best characterized of the known Wnt signaling paths. Wnt signaling has emerged as an important factor in stem cell biology and is

Иммуномодулирующий и противовоспалительный потенциал S-нитросглутатиона (GSNO) при множественной склерозе: обзор механизмов и терапевтических перспектив.

Многофакторная демиелинизация (МС) — это хроническое аутоиммунное заболевание центральной нервной системы (СНС), характеризующееся длительной нейроинфляминацией, окислительным стрессом, демиелинизацией и прогрессирующей нейродегенерацией. Несмотря на то, что МС остается неизлечимым, современные терапевтические средства (ТМС) помогают снизить частоту обострений и задерживать прогрессирование заболевания. Недавно разработанные инъекционные и инфузийные биологические ТМС обеспечивают целенаправленную иммуномодуляцию, но их клиническая полезность ограничена родственными методами введения и возможн

Mechanistic insights into bone destruction in multiple myeloma: Cellular and molecular perspectives.

Multiple myeloma (MM) is a hematological malignancy that leads to significant bone destruction, resulting in debilitating pain and skeletal-related events. The pathophysiology of osteolytic bone destruction in MM involves complex interactions between malignant plasma cells (PCs) and the bone marrow (BM) microenvironment. This review aims to provide a comprehensive synthesis of the cellular and molecular pathways underlying MM-associated bone disease. We discuss the role of osteoclast (OC), osteoblast (OB), osteocytes, along with the complex interactions between immune cells and the BM microenv

Pleiotropic Effects of Modified Citrus Pectin.

Modified citrus pectin (MCP) has a low-molecular-weight degree of esterification to allow absorption from the small intestinal epithelium into the circulation. MCP produces pleiotropic effects, including but not limited to its antagonism of galectin-3, which have shown benefit in preclinical and clinical models. Regarding cancer, MCP modulates several rate-limiting steps of the metastatic cascade. MCP can also affect cancer cell resistance to chemotherapy. Regarding fibrotic diseases, MCP modulates many of the steps involved in the pathogenesis of aortic stenosis. MCP also reduces fibrosis to

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… In the NTD, the serine 6 can be phosphorylated by casein kinases 1 and 2, contributing to nuclear translocation and a reduction of affinity to its ligands. …