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Progress on the Application of Bortezomib and Bortezomib-Based Nanoformulations.

Bortezomib (BTZ) is the first proteasome inhibitor approved by the Food and Drug Administration. It can bind to the amino acid residues of the 26S proteasome, thereby causing the death of tumor cells. BTZ plays an irreplaceable role in the treatment of mantle cell lymphoma and multiple myeloma. Moreover, its use in the treatment of other hematological cancers and solid tumors has been investigated in numerous clinical trials and preclinical studies. Nevertheless, the applications of BTZ are limited due to its insufficient specificity, poor permeability, and low bioavailability. Therefore, in r

Influence of the TGF-β Superfamily on Osteoclasts/Osteoblasts Balance in Physiological and Pathological Bone Conditions.

The balance between bone forming cells (osteoblasts/osteocytes) and bone resorbing cells (osteoclasts) plays a crucial role in tissue homeostasis and bone repair. Several hormones, cytokines, and growth factors-in particular the members of the TGF-β superfamily such as the bone morphogenetic proteins-not only regulate the proliferation, differentiation, and functioning of these cells, but also coordinate the communication between them to ensure an appropriate response. Therefore, this review focuses on TGF-β superfamily and its influence on bone formation and repair, through the regulation of

Role of Dietary Antioxidants in p53-Mediated Cancer Chemoprevention and Tumor Suppression.

Cancer arises through a complex interplay between genetic, behavioral, metabolic, and environmental factors that combined trigger cellular changes that over time promote malignancy. In terms of cancer prevention, behavioral interventions such as diet can promote genetic programs that may facilitate tumor suppression; and one of the key tumor suppressors responsible for initiating such programs is p53. The p53 protein is activated by various cellular events such as DNA damage, hypoxia, heat shock, and overexpression of oncogenes. Due to its role in cell fate decisions after DNA damage, regulato

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… Targeting 3-phosphoinositide-dependent protein kinase 1 by N-acetyl-cysteine through activation of peroxisome proliferators activated receptor alpha in human lung cancer cells, the role of p53 and p65. …

Targeting super enhancers for liver disease: a review.

BackgroundSuper enhancers (SEs) refer to the ultralong regions of a gene accompanied by multiple transcription factors and cofactors and strongly drive the expression of cell-type-related genes. Recent studies have demonstrated that SEs play crucial roles in regulating gene expression related to cell cycle progression and transcription. Aberrant activation of SEs is closely related to the occurrence and development of liver disease. Liver disease, especially liver failure and hepatocellular carcinoma (HCC), constitutes a major class of diseases that seriously endanger human health. Currently,

The interplay of mitochondrial dysfunction and altered metabolic pathways in glioblastoma.

Glioblastoma (GBM) is the most aggressive and lethal primary brain tumor, characterized by rapid progression, treatment resistance, and poor prognosis, with a survival rate of less than five years despite advances in medical interventions. A hallmark of GBM is metabolic reprogramming, which supports tumor growth and progression. Mitochondrial dysfunction plays a critical role in this metabolic shift by altering energy production and disrupting key cellular pathways. However, the precise molecular mecha-nisms underlying these alterations remain inadequately understood. This review highlights th

Pathogenesis and Treatment of Myeloma-Related Bone Disease.

Multiple myeloma is a hematologic malignancy of plasma cells that causes bone-destructive lesions and associated skeletal-related events (SREs). The pathogenesis of myeloma-related bone disease (MBD) is the imbalance of the bone-remodeling process, which results from osteoclast activation, osteoblast suppression, and the immunosuppressed bone marrow microenvironment. Many important signaling cascades, including the RANKL/RANK/OPG axis, Notch signaling, the Wnt/β-Catenin signaling pathways, and signaling molecules, such as DKK-1, sclerostin, osteopontin, activin A, chemokines, and interleukins

Myelin Displacement and Revention in the Central Nervous System: Молекулярные механизмы, болезни и перспективные терапевтические цели.

Майлин пластичность имеет основополагающее значение для формирования нейронных сетей и оптимизации нейронных функций, формирования схем, регулирующих эмоции, сознание, сенсацию и управление двигателем. Подкомбинированный олигодендроцитами, миелин подвергается пожизненной реконструкции, которая требует высокой метаболической активности; это делает миелин-олигодендроцитную единицу весьма восприимчивой к метаболическому стрессу, старению и патологическим оскорблениям. Хотя обезвоживание является основной характеристикой различных хронических неврологических расстройств, в настоящем обзоре особо п

Combination Therapy With Histone Deacetylase Inhibitors (HDACi) for the Treatment of Cancer: Achieving the Full Therapeutic Potential of HDACi.

Genetic and epigenetic changes in DNA are involved in cancer development and tumor progression. Histone deacetylases (HDACs) are key regulators of gene expression that act as transcriptional repressors by removing acetyl groups from histones. HDACs are dysregulated in many cancers, making them a therapeutic target for the treatment of cancer. Histone deacetylase inhibitors (HDACi), a novel class of small-molecular therapeutics, are now approved by the Food and Drug Administration as anticancer agents. While they have shown great promise, resistance to HDACi is often observed and furthermore, H

Evaluation of the Effect of Loratadine versus Diosmin/Hesperidin Combination on Vinca Alkaloids-Induced Neuropathy: A Randomized Controlled Clinical Trial.

Neurological injury is a crucial problem that interferes with the therapeutic use of vinca alkaloids as well as the quality of patient life. This study was conducted to assess the impact of using loratadine or diosmin/hesperidin on neuropathy induced by vinca alkaloids. Patients were randomized into one of three groups as follows: group 1 was the control group, group 2 received 450 mg diosmin and 50 mg hesperidin combination orally twice daily, and group 3 received loratadine 10 mg orally once daily. Subjective scores (numeric pain rating scale, douleur neuropathique 4, and functional assessme

Reprogramming of nitrogen metabolism in tumors: mechanisms and therapeutic implications.

Nitrogen metabolism plays a key role in maintaining normal physiological functions of the organism and cell proliferation and differentiation. Nitrogen metabolism in normal human body maintains a dynamic balance to meet the body's demand for synthesis of biological macromolecules such as proteins and nucleic acids. However, in the process of tumor development, the nitrogen metabolism of tumor cells is reprogrammed to meet the demand of rapid proliferation, showing significantly different metabolic characteristics from normal cells. Key enzymes in the tumor microenvironment affect nitrogen meta

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… Spermine directly activates peroxisome proliferators-activated receptors(PPARγ), systemically enhancing Tregs’ mitochondrial oxidative phosphorylation capacity, thereby substantially boosting their immunosuppressive function(Gu et al. 2025 ). …

Protein breakdown in muscle wasting: role of autophagy-lysosome and ubiquitin-proteasome.

Skeletal muscle adapts its mass as consequence of physical activity, metabolism and hormones. Catabolic conditions or inactivity induce signaling pathways that regulate the process of muscle loss. Muscle atrophy in adult tissue occurs when protein degradation rates exceed protein synthesis. Two major protein degradation pathways, the ubiquitin-proteasome and the autophagy-lysosome systems, are activated during muscle atrophy and variably contribute to the loss of muscle mass. These degradation systems are controlled by a transcription dependent program that modulates the expression of rate-lim

A Narrative Review on the Antitumoral Effects of Selected Mediterranean Plant Products from Southern Italy.

Natural products are a valuable source of bioactive compounds with established roles in oncology. Their structural diversity and ability to target multiple cancer-related pathways make them promising candidates for anticancer drug development. Increasing preclinical and clinical data highlight their potential not only to exert direct antitumor effects but also to enhance patient tolerance to conventional therapies by reducing side effects and improving treatment adherence. The Mediterranean region, known for its biodiversity and traditional dietary habits, provides a rich array of natural comp

The Role of Irisin and Physical Activity in Breast Cancer.

BACKGROUND/AIM: Irisin, a myokine released during physical activity, has been proposed as a mediator of exercise's protective effects against breast cancer (BC). This review underscores the critical role of irisin in mediating the anticancer effects of exercise and its potential application in BC prevention and prognosis. MATERIALS AND METHODS: Studies published up to 2025 were identified in PubMed, Scopus, and Web of Science databases. Data from experimental models, clinical trials, and observational studies were analyzed with emphasis on exercise-induced irisin secretion and its effects on

The potential role of cannabidiol (CBD) in lung cancer therapy: a systematic review of preclinical and clinical evidence.

BackgroundLung cancer is one of the most prevalent and lethal cancers worldwide, with limited therapeutic options in advanced stages. Cannabinoids have recently attracted attention as potential anticancer agents; however, cannabidiol (CBD), a non-psychoactive compound derived from Cannabis sativa, has emerged as the most promising candidate. Unlike Δ9-tetrahydrocannabinol (THC), CBD lacks psychoactive properties, is generally well tolerated, and demonstrates a favorable safety profile. Moreover, CBD influences multiple cancer-relevant pathways-including apoptosis, epithelial-to-mesenchymal tra

Pharmacological Strategies for Mitigating Cytarabine-Induced Multi-Organ Toxicity: A Scoping Review on Mechanisms, Efficacy and Clinical Implications.

BACKGROUND: Cytarabine (Ara-C) remains the cornerstone of remission-induction and consolidation chemotherapy for acute myeloid leukemia (AML) and related hematological malignancies. Despite more than six decades of clinical use, its multi-organ toxicity continues to be managed almost exclusively through dose attenuation and supportive care, with no approved upstream pharmacological prevention strategy available. OBJECTIVES: This scoping review aimed to systematically map the breadth and nature of pharmacological agents tested in vivo for their capacity to mitigate cytarabine-induced multi-org

Изменения лакта и лактилации в неврологических расстройствах.

Значительное внимание стало уделяться изучению изменений в лактилации различных целевых органов как в области здравоохранения, так и в области болезней. Многие жизненно важные процессы и начало болезней связаны не только с избытком белков, но и в первую очередь регулируются различными посттрансляционными изменениями белков. Лактат, который раньше считался лишь побочным продуктом анаэробного метаболизма, превратился в важнейшую энергетическую субстрату и сигнализирующую молекулу, связанную как с физиологическими, так и патологическими процессами в нервной системе. Кроме того, в недавних исследо

Drug-Drug Interactions of Cannabidiol with Standard-of-Care Chemotherapeutics.

Cannabidiol (CBD) is an easily accessible and affordable Marijuana (Cannabis sativa L.) plant derivative with an extensive history of medical use spanning thousands of years. Interest in the therapeutic potential of CBD has increased in recent years, including its anti-tumour properties in various cancer models. In addition to the direct anticancer effects of CBD, preclinical research on numerous cannabinoids, including CBD, has highlighted their potential use in: (i) attenuating chemotherapy-induced adverse effects and (ii) enhancing the efficacy of some anticancer drugs. Therefore, CBD is ga

Osteoporosis and the Potential of Cell-Based Therapeutic Strategies.

Osteoporosis, the most common chronic metabolic bone disease, is characterized by low bone mass and increased bone fragility. Nowadays more than 200 million individuals are suffering from osteoporosis and still the number of affected people is dramatically increasing due to an aging population and longer life, representing a major public health problem. Current osteoporosis treatments are mainly designed to decrease bone resorption, presenting serious adverse effects that limit their safety for long-term use. Numerous studies with mesenchymal stem cells (MSCs) have helped to increase the knowl

Mechanisms of Chemotherapy-Induced Neurotoxicity.

Since the first clinical trials conducted after World War II, chemotherapeutic drugs have been extensively used in the clinic as the main cancer treatment either alone or as an adjuvant therapy before and after surgery. Although the use of chemotherapeutic drugs improved the survival of cancer patients, these drugs are notorious for causing many severe side effects that significantly reduce the efficacy of anti-cancer treatment and patients' quality of life. Many widely used chemotherapy drugs including platinum-based agents, taxanes, vinca alkaloids, proteasome inhibitors, and thalidomide ana

Metabolic crosstalk between stromal and malignant cells in the bone marrow niche.

Bone marrow is the primary site of blood cell production in adults and serves as the source of osteoblasts and osteoclasts that maintain bone homeostasis. The medullary microenvironment is also involved in malignancy, providing a fertile soil for the growth of blood cancers or solid tumors metastasizing to bone. The cellular composition of the bone marrow is highly complex, consisting of hematopoietic stem and progenitor cells, maturing blood cells, skeletal stem cells, osteoblasts, mesenchymal stromal cells, adipocytes, endothelial cells, lymphatic endothelial cells, perivascular cells, and n