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Osteonecrosis of the Jaw and Antiresorptive Agents in Benign and Malignant Diseases: A Critical Review Organized by the ECTS.

CONTEXT: Antiresorptive therapy significantly reduces fracture risk in patients with benign bone disease and skeletal-related events (SREs) in patients with bone metastases (BM). Osteonecrosis of the jaw (ONJ) is a rare but severe condition manifested as necrotic bone lesion or lesions of the jaws. ONJ has been linked to the use of potent antiresorptive agents, termed medication-related ONJ (MRONJ). OBJECTIVE: We aimed to identify the differences various aspects of MRONJ among distinct patient categories and provide recommendations on how to mitigate the risk and optimally manage MRONJ in eac

Targeting SREBP-2-Regulated Mevalonate Metabolism for Cancer Therapy.

Recently, targeting metabolic reprogramming has emerged as a potential therapeutic approach for fighting cancer. Sterol regulatory element binding protein-2 (SREBP-2), a basic helix-loop-helix leucine zipper transcription factor, mainly regulates genes involved in cholesterol biosynthesis and homeostasis. SREBP-2 binds to the sterol regulatory elements (SREs) in the promoters of its target genes and activates the transcription of mevalonate pathway genes, such as HMG-CoA reductase (HMGCR), mevalonate kinase and other key enzymes. In this review, we first summarized the structure of SREBP-2 and

Recent Insights in Multi-Target Drugs in Pharmacology and Medicinal Chemistry.

Many of the drugs used in treatment today have been designed based on the "specificity paradigm". Resistance has developed against drugs designed using this approach, leading to a decrease in their effectiveness. In addition, it is well-documented in the literature that diseases with complex etiologies, such as Alzheimer's, Parkinson's, and cancer are influenced by multiple genetic and/or environmental factors. As a result, specificity paradigm is often insufficient for treating these diseases. Therefore, there is a need to develop drugs that interact with multiple targets simultaneously throu

Postbiotics as Emerging Strategy Targeting Obesity- and Aging-Related Breast Cancer-Prospects in Prophylaxis and Therapy.

Aging and obesity accompanied with hormonal disequilibrium represent critical, inter-related risk factors for breast cancer, significantly influencing disease incidence, progression, and therapeutic outcomes. This review aims to elucidate the multifaceted biological mechanisms linking obesity and aging to breast carcinogenesis, with a particular focus on the emerging therapeutic and preventive potential of postbiotics as molecules targeting cellular events important for cancer growth and responsiveness. Despite continuous advancement, breast cancer therapy still poses several challenges, such

Insights into Endothelial Progenitor Cells: Origin, Classification, Potentials, and Prospects.

With the discovery of endothelial progenitor cells (EPCs) in the late 1990s, a paradigm shift in the concept of neoangiogenesis occurred. The identification of circulating EPCs in peripheral blood marked the beginning of a new era with enormous potential in the rapidly transforming regenerative field. Overwhelmed with the revelation, researchers across the globe focused on isolating, defining, and interpreting the role of EPCs in various physiological and pathological conditions. Consequently, controversies emerged regarding the isolation techniques and classification of EPCs. Nevertheless, th

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.

Therapeutic Potential of Autophagy Modulation in Cholangiocarcinoma.

Autophagy is a multistep catabolic process through which misfolded, aggregated or mutated proteins and damaged organelles are internalized in membrane vesicles called autophagosomes and ultimately fused to lysosomes for degradation of sequestered components. The multistep nature of the process offers multiple regulation points prone to be deregulated and cause different human diseases but also offers multiple targetable points for designing therapeutic strategies. Cancer cells have evolved to use autophagy as an adaptive mechanism to survive under extremely stressful conditions within the tumo

Post-Translational Modifications in Atopic Dermatitis: Current Research and Clinical Relevance.

Atopic dermatitis (AD) is a chronic and relapsing cutaneous disorder characterized by compromised immune system, excessive inflammation, and skin barrier disruption. Post-translational modifications (PTMs) are covalent and enzymatic modifications of proteins after their translation, which have been reported to play roles in inflammatory and allergic diseases. However, less attention has been paid to the effect of PTMs on AD. This review summarized the knowledge of six major classes (including phosphorylation, acetylation, ubiquitination, SUMOylation, glycosylation, o-glycosylation, and glycati

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… Loss of Sirtuin 1 (SIRT1) Disrupts Skin Barrier Integrity and Sensitizes Mice to Epicutaneous Allergen Challenge. J. Allergy Clin. Immunol. 135, 936–945. e4. 10.1016/j.jaci.2014.09.035 Mohapatra B., Ahmad G., Nadeau S., Zutshi N., An W., Scheffe S., et al. (2013a). …

Research progress on the anti-cancer mechanisms of edible salty-flavored Chinese materia medica.

Edible salty-flavored Chinese materia medica (ESCM) refers to a category of traditional Chinese medicine (TCM) that also serve as food, characterized by their salty flavor. According to the TCM theory, ESCM can soften and disperse knots, thus potentially offering benefits for cancer prevention and treatment. With cancer remaining a major global health challenge, its primary prevention strategies, especially through dietary modification, are crucial. ESCM have recently garnered substantial attention, due to their remarkable clinical efficacy and low side-effect profile. Researches on ESCM demon

A new era of cancer immunotherapy: vaccines and miRNAs.

Cancer immunotherapy has transformed the treatment landscape, introducing new strategies to fight various types of cancer. This review examines the important role of vaccines in cancer therapy, focusing on recent advancements such as dendritic cell vaccines, mRNA vaccines, and viral vector-based approaches. The relationship between cancer and the immune system highlights the importance of vaccines as therapeutic tools. The discussion covers tumor cell and dendritic cell vaccines, protein/peptide vaccines, and nucleic acid vaccines (including DNA, RNA, or viral vector-based), with a focus on th

Drug resistance and tumor immune microenvironment: An overview of current understandings (Review).

The use of antitumor drugs represents a reliable strategy for cancer therapy. Unfortunately, drug resistance has become increasingly common and contributes to tumor metastasis and local recurrence. The tumor immune microenvironment (TME) consists of immune cells, cytokines and immunomodulators, and collectively they influence the response to treatment. Epigenetic changes including DNA methylation and histone modification, as well as increased drug exportation have been reported to contribute to the development of drug resistance in cancers. In the past few years, the majority of studies on tum

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… In a study on prostate cancer, lactate released by CAF glycolysis reduced Th1 through sirtuin 1 (SIRT1)-mediated deacetylation of T-bet, and activated NF-κB to upregulate the expression of FoxP3, thereby stimulating the polarization of CD4 + T cells to Tregs ( 171 ). …

Drug-induced oxidative stress in cancer treatments: Angel or devil?

Oxidative stress (OS), defined as redox imbalance in favor of oxidant burden, is one of the most significant biological events in cancer progression. Cancer cells generally represent a higher oxidant level, which suggests a dual therapeutic strategy by regulating redox status (i.e., pro-oxidant therapy and/or antioxidant therapy). Indeed, pro-oxidant therapy exhibits a great anti-cancer capability, attributing to a higher oxidant accumulation within cancer cells, whereas antioxidant therapy to restore redox homeostasis has been claimed to fail in several clinical practices. Targeting the redox

Crosstalk between Circadian Rhythm Dysregulation and Tumorigenesis, Tumor Metabolism and Tumor Immune Response.

Circadian rhythm is a self-regulating 24-hour system that synchronizes with the day and night cycle in organisms. The regulation of this system is controlled by clock genes, which function to harmoniously express molecular levels that facilitate the orderly coordination of various cellular processes, such as sleep, metabolism, endocrine function, cell proliferation and immunity. The root cause of tumorigenesis is that the body loses its normal regulation of cell growth at the genetic level. Long-term disruptions in circadian rhythms caused by factors such as shift work, jet lag, and unstable s

Bortezomib-induced peripheral neuropathy: from molecular mechanisms to clinical management.

Bortezomib (BTZ) is a first-generation proteasome inhibitor that has shown significant efficacy in the treatment of multiple myeloma (MM), providing significant therapeutic benefits without severely compromising overall patient health. However, one of the most common and debilitating side effects associated with BTZ therapy is bortezomib-induced peripheral neuropathy (BIPN). This condition is the leading complication observed in patients undergoing BTZ treatment and has a profound impact on treatment regimens, often necessitating dose reductions or alterations in the dosing schedule. Despite t

Redefining Chemoresistance: Natural Bioactives as Molecular Modulators at the Cancer-Tumor Microenvironment Interface.

Therapeutic resistance remains a critical barrier in effective cancer treatment, contributing to disease recurrence, progression, and reduced patient survival. In recent years, natural bioactive compounds have emerged as promising adjuncts in oncology due to their ability to modulate multiple biological processes involved in resistance. This review explores current evidence on the role of natural compounds in influencing cancer cell behavior and their interactions with the tumor microenvironment. By organizing these compounds into chemical families, we provide a structured overview of their po

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… On the epigenetic level, it activates Sirtuin 1 (SIRT1) gene, reshapes histone acetylation patterns, alters DNA methylation, and modulates microRNAs, collectively reprogramming gene expression linked to cell cycle control and apoptosis [ 158 , 159 ]. …

The microbiota-gut-brain-axis theory: role of gut microbiota modulators (GMMs) in gastrointestinal, neurological, and mental health disorders.

The modulation of gut microbiota presents promising therapeutic possibilities for various health conditions, ranging from gastrointestinal infections to neurodegenerative and mental health disorders. Among the available interventions, gut microbiota modulators (GMMs) such as probiotics and prebiotics have demonstrated significant potential in infection prevention and neuroprotection. Despite these encouraging findings, the clinical application of GMMs remains challenging due to safety concerns and inconsistent effectiveness across diverse patient populations. These factors create substantial b

Polydatin: Pharmacological Mechanisms, Therapeutic Targets, Biological Activities, and Health Benefits.

Polydatin is a natural potent stilbenoid polyphenol and a resveratrol derivative with improved bioavailability. Polydatin possesses potential biological activities predominantly through the modulation of pivotal signaling pathways involved in inflammation, oxidative stress, and apoptosis. Various imperative biological activities have been suggested for polydatin towards promising therapeutic effects, including anticancer, cardioprotective, anti-diabetic, gastroprotective, hepatoprotective, neuroprotective, anti-microbial, as well as health-promoting roles on the renal system, the respiratory s

2,4 Dinitrophenol as Medicine.

In the sanctity of pure drug discovery, objective reasoning can become clouded when pursuing ideas that appear unorthodox, but are spot on physiologically. To put this into historical perspective, it was an unorthodox idea in the 1950's to suggest that warfarin, a rat poison, could be repositioned into a breakthrough drug in humans to protect against strokes as a blood thinner. Yet it was approved in 1954 as Coumadin® and has been prescribed to billions of patients as a standard of care. Similarly, no one can forget the horrific effects of thalidomide, prescribed or available without a prescri

Tumour Cell Size Control and Its Impact on Tumour Cell Function.

Cell size is an important component of cell morphological characteristics. It reflects the characteristics of the cell type, nutritional status, growth stage and physiological function. The cell size of cells of the same type tends to be homogeneous and stable. However, in tumour cells, mutations in cell cycle genes and cytoskeletal genes and overexpression of the corresponding signalling pathways often lead to large variations in tumour cell size. Tumour cells regulate cell size and growth and proliferation through multiple signalling pathways, such as PI3K/Akt/mTOR, Myc and Hippo pathways, w

Xanthohumol: Mechanistic Actions and Emerging Evidence as a Multi-Target Natural Nutraceutical.

BACKGROUND: Xanthohumol (XN), a prenylated chalcone flavonoid derived from hops (Humulus lupulus), is increasingly recognized as a highly pleiotropic natural compound. OBJECTIVE: We aimed to structure XN's mechanistic hierarchy with emerging translational relevance across disease areas. METHODS: We performed a comprehensive and integrative literature review of XN for its biological and translational effects across cancer, metabolic, neurological, cardiovascular, hepatic, renal, and dermatological disorders. RESULTS: Mechanistically, XN exerts diverse bioactivities by inhibiting major pro-on

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… AMPK, AMP-activated protein kinase; SIRT1, sirtuin 1; GLUT4, glucose transporter type 4; PEPCK, phosphoenolpyruvate carboxykinase; G6Pase, glucose-6-phosphatase; NAFLD, non-alcoholic fatty liver disease; CPT-1, carnitine palmitoyltransferase-1; BAT, brown adipose tissue; ARE, antioxidant response element …