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The Proliferative and Apoptotic Landscape of Basal-like Breast Cancer.

Basal-like breast cancer (BLBC) is an aggressive molecular subtype that represents up to 15% of breast cancers. It occurs in younger patients, and typically shows rapid development of locoregional and distant metastasis, resulting in a relatively high mortality rate. Its defining features are that it is positive for basal cytokeratins and, epidermal growth factor receptor and/or c-Kit. Problematically, it is typically negative for the estrogen receptor and human epidermal growth factor receptor 2 (HER2), which means that it is unsuitable for either hormone therapy or targeted HER2 therapy. As

Animal models of chemotherapy-induced cognitive decline in preclinical drug development.

RationaleChemotherapy-induced cognitive impairment (CICI), chemobrain, and chemofog are the common terms for mental dysfunction in a cancer patient/survivor under the influence of chemotherapeutics. CICI is manifested as short/long term memory problems and delayed mental processing, which interferes with a person's day-to-day activities. Understanding CICI mechanisms help in developing therapeutic interventions that may alleviate the disease condition. Animal models facilitate critical evaluation to elucidate the underlying mechanisms and form an integral part of verifying different treatment

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… It may lead to the opening of mitochondrial permeability transition pores (PTP), causing uncontrolled leakage of cellular constituents and resulting in mitochondrial damage (Javadov and Kuznetsov 2013 ). …

Natural products targeting ferroptosis in cancer: molecular mechanisms and applications.

Ferroptosis is a novel class of programmed cell death that is mainly dependent on intracellular iron accumulation and lipid peroxidation. Ferroptosis is closely related to a variety of human diseases, especially different kinds of cancer. Several small molecule inducers have been developed to induce ferroptosis in tumor cells, some of which have been used in clinical studies. However, these chemical small molecules have toxic effects that limit its wide application. Natural products, however, have a natural advantage in cancer therapy due to their low toxicity and side effects. Some natural pr

Applications of nanotechnologies for miRNA-based cancer therapeutics: current advances and future perspectives.

MicroRNAs (miRNAs) are short (18-25 nt), non-coding, widely conserved RNA molecules responsible for regulating gene expression via sequence-specific post-transcriptional mechanisms. Since the human miRNA transcriptome regulates the expression of a number of tumor suppressors and oncogenes, its dysregulation is associated with the clinical onset of different types of cancer. Despite the fact that numerous therapeutic approaches have been designed in recent years to treat cancer, the complexity of the disease manifested by each patient has prevented the development of a highly effective disease

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… Consequently, once the ARC restraint effect has been suppressed, the pro-apoptotic protein BAX enters the mitochondria, decreasing mitochondrial membrane potentials, activating ROS production, and promoting mitochondrial permeability transition pores opening ( Chen et al., 2021 ). …

An integrative review of nonobvious puzzles of cellular and molecular cardiooncology.

Oncologic patients are subjected to four major treatment types: surgery, radiotherapy, chemotherapy, and immunotherapy. All nonsurgical forms of cancer management are known to potentially violate the structural and functional integrity of the cardiovascular system. The prevalence and severity of cardiotoxicity and vascular abnormalities led to the emergence of a clinical subdiscipline, called cardiooncology. This relatively new, but rapidly expanding area of knowledge, primarily focuses on clinical observations linking the adverse effects of cancer therapy with deteriorated quality of life of

Resveratrol: Molecular Mechanisms, Health Benefits, and Potential Adverse Effects.

Resveratrol (RES), a naturally occurring polyphenolic compound, has garnered significant attention due to its diverse biological activities, which include anti-inflammatory, antioxidant, and antiaging properties. This review synthesizes current evidence concerning the molecular mechanisms, therapeutic efficacy, and safety profile of RES across a variety of pathologies, with an emphasis on the latest research conducted in recent years. Mechanistically, RES is known to modulate critical signaling pathways such as the activation of sirtuin 1. These actions collectively contribute to the attenuati

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… RES also protects the heart by downregulating glucose metabolism enzymes or increasing the expression of SIRT3, which facilitates the deacetylation of cyclophilin D in myocytes affected by pulmonary arterial hypertension, thereby regulating the openness of the mitochondrial permeability transition pore …

Emerging Nanotherapeutic Approaches to Overcome Drug Resistance in Cancers with Update on Clinical Trials.

A key issue with modern cancer treatments is the emergence of resistance to conventional chemotherapy and molecularly targeted medicines. Cancer nanotherapeutics were created in order to overcome the inherent limitations of traditional chemotherapeutics. Over the last few decades, cancer nanotherapeutics provided unparalleled opportunities to understand and overcome drug resistance through clinical assessment of rationally designed nanoparticulate delivery systems. In this context, various design strategies such as passive targeting, active targeting, nano-drug, and multimodal nano-drug combin

Mechanisms, Mediators, and Moderators of the Effects of Exercise on Chemotherapy-Induced Peripheral Neuropathy.

Chemotherapy-induced peripheral neuropathy (CIPN) is an adverse effect of neurotoxic antineoplastic agents commonly used to treat cancer. Patients with CIPN experience debilitating signs and symptoms, such as combinations of tingling, numbness, pain, and cramping in the hands and feet that inhibit their daily function. Among the limited prevention and treatment options for CIPN, exercise has emerged as a promising new intervention that has been investigated in approximately two dozen clinical trials to date. As additional studies test and suggest the efficacy of exercise in treating CIPN, it i

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… In this same study, exercise protected against the doxorubicin-induced opening of the mitochondrial permeability transition pore, reduction in mitochondrial biogenesis, and accumulation of reactive oxygen species [ 52 ]. …

Conditioned Media-Derived Tumor Extracellular Vesicles: Bridging Molecular Insights and Therapeutic Applications in Oncology.

Tumor-derived extracellular vesicles (EVs) are major mediators of oncogenic intercellular communication. However, many studies using conditioned media (CM) recover operationally defined EV- or small EV-enriched fractions rather than biogenesis-proven exosomes. This review synthesizes evidence from CM-derived tumor EV studies and aligns their biological interpretation with current EV nomenclature, characterization, and reporting principles. We first discuss exosome biogenesis as a defined endosomal pathway and then examine how CM collection, serum handling, culture format, oxygen tension, condi

Ранние синапсовые изменения фоторецептора Mitochondria в модели мыши Множественного склероза EAE

Множественный склероз (MS) — воспалительное аутоиммунное заболевание центральной нервной системы (CNS), связанное со многими неврологическими нарушениями. Взгляд на систему часто нарушается в MS. В предыдущих исследованиях мы наблюдали ранние синусосы фоторецепторовых лент в модели мыши EAE MS, которые включали изменения в цикле синаптического везикла и нарушения предсинаптического ка2+ гомеостаза. Поскольку эти преднаптические события требуют очень много энергии, мы проанализировали, может ли синаптическая митохондрия, играющая важную роль в синаптическом энергетическом метаболизме, быть заде

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… Chronic mitochondrial Ca 2+ overload can also lead to the opening of the mitochondrial permeability transition pore (mPTP), depolarization of mitochondrial membrane potential, mitochondrial swelling, and finally cell death [ 158 , 159 , 160 , 161 ]. …

Methamphetamine induces transcriptional changes in cultured HIV-infected mature monocytes that may contribute to HIV neuropathogenesis.

HIV-associated neurocognitive impairment (HIV-NCI) persists in 15-40% of people with HIV (PWH) despite effective antiretroviral therapy. HIV-NCI significantly impacts quality of life, and there is currently no effective treatment for it. The development of HIV-NCI is complex and is mediated, in part, by the entry of HIV-infected mature monocytes into the central nervous system (CNS). Once in the CNS, these cells release inflammatory mediators that lead to neuroinflammation, and subsequent neuronal damage. Infected monocytes may infect other CNS cells as well as differentiate into macrophages,

Understanding DMG: current treatment options and prospective solutions using nanoparticles.

Diffuse Midline Gliomas (DMGs), which include the subset formerly known as Diffuse Intrinsic Pontine Glioma (DIPG), are associated with an extremely poor prognosis and a five-year survival rate below 2-3%. The devastating prognosis stems from an inherently invasive nature, a deep, anatomically restricted location, rapid cellular drug efflux mediated by transporters such as P-glycoprotein (ABCB1) and breast cancer resistance protein (BCRP/ABCG2), and an immunologically "cold" microenvironment. Coupled with limited Blood-Brain Barrier (BBB) permeability, these biological factors render conventio

Role of mitochondria in physiological activities, diseases, and therapy.

Mitochondria are generally considered essential for life in eukaryotic organisms because they produce most of the energy or adenosine triphosphate (ATP) needed by the cell. Beyond energy production, it is now widely accepted that mitochondria also play a pivotal role in maintaining cellular homeostasis and signaling. The two core processes of mitochondrial dynamics, fission and fusion, serve as crucial foundations for maintaining mitochondrial morphology, distribution, and quantity, thereby ensuring cellular homeostasis. Mitochondrial autophagy (mitophagy) ensures the selective degradation of

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… Neuronal death following stroke is exacerbated by calcium overload, the opening of the mitochondrial permeability transition pore (mPTP), and excessive production of ROS, all of which are consequences of impaired mitochondrial function. …

A Mechanistic Understanding of Axon Degeneration in Chemotherapy-Induced Peripheral Neuropathy.

Chemotherapeutic agents cause many short and long term toxic side effects to peripheral nervous system (PNS) that drastically alter quality of life. Chemotherapy-induced peripheral neuropathy (CIPN) is a common and enduring disorder caused by several anti-neoplastic agents. CIPN typically presents with neuropathic pain, numbness of distal extremities, and/or oversensitivity to thermal or mechanical stimuli. This adverse side effect often requires a reduction in chemotherapy dosage or even discontinuation of treatment. Currently there are no effective treatment options for CIPN. While the under

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… Paclitaxel affects cytosolic calcium signals by opening the mitochondrial permeability transition pore. J. Biol. Chem. 277, 6504–6510. 10.1074/jbc.M106802200 Kroigard T., Schroder H. D., Qvortrup C., Eckhoff L., Pfeiffer P., Gaist D., et al. (2014). …

Advances in Molecular Regulation of Prostate Cancer Cells by Top Natural Products of Malaysia.

Prostate cancer (PCa) remains both a global health burden and a scientific challenge. We present a review of the molecular targets driving current drug discovery to fight this disease. Moreover, the preventable nature of most PCa cases represents an opportunity for phytochemicals as chemopreventive when adequately integrated into nutritional interventions. With a renovated interest in natural remedies as a commodity and their essential role in cancer drug discovery, Malaysia is looking towards capitalizing on its mega biodiversity, which includes the oldest rainforest in the world and an estim

Amino acids metabolism: a potential target for cancer treatment.

Metabolic reprogramming of amino acids has been recognized as a significant characteristic in various types of cancers. Numerous studies have indicated that the metabolic reprogramming of amino acids in tumors significantly supports certain malignant behaviors, including tumor proliferation, survival, invasion, and even immune escape. Amino acids can provide biomolecules such as nucleotides and glutathione (GSH) for tumors, and the bioavailability of amino acids influences tumor progression. Meanwhile, as essential metabolites, amino acids are closely associated with immune cell activation and

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Прогресс в развитии лекарственных средств на основе пептида: платформы для доставки, терапевтические средства и вакцины.

Успешное утверждение лекарств на основе пептида можно отнести на счет совместных усилий по целому ряду дисциплин. Интеграция новых методов разработки и синтеза лекарственных средств, отображение библиотечных технологий, систем доставки, достижений в области биоинженерии и искусственного интеллекта в значительной степени ускорила разработку новейших лекарств на основе пептида, эффективно устраняя препятствия, связанные с их характером, такие, как быстрое обезвреживание и деградация, необходимость субколичественной инъекции, ведущей к усилению дискомфорта пациентов, и в конечном итоге продвигая

Нейроинфламмация в нейродегенеративных заболеваниях: сосредоточение внимания на посредничестве лимфоцитов T.

Нейродегенеративные заболевания представляют собой группу заболеваний, характеризующихся постепенным ухудшением центральной нервной системы, что приводит к снижению когнитивных, моторных и эмоциональных способностей пациентов. Нейроинфламмация играет важную роль в развитии этих заболеваний. Вместе с тем исследования терапевтических подходов к целенаправленной борьбе с нейроинфламмацией носят ограниченный характер. Все шире признается роль лимфоцитов, которые являются важнейшими посредниками адаптивной иммунной реакции, в нейродегенеративных заболеваниях. В настоящем обзоре основное внимание уд

The Redox Paradox of Natural Supplements in Cancer: A Narrative Review to Guide Clinical Practice.

Supplements are widely perceived as safe and beneficial; yet in oncology, this assumption is questionable. Clinical trials over the past few decades have often produced disappointing results, raising a critical question: are these agents used correctly, or could they inadvertently cause harm? This review examines supplements frequently used in cancer care-such as oral vitamin C, berberine, N-acetylcysteine, vitamin D, vitamin E, melatonin, polyphenols, alpha-lipoic acid, selenium, and coenzyme Q10-which can act as tumor suppressors or promoters depending on dose, route, and disease stage. We e

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… CoQ10 also helps regulate the mitochondrial permeability transition pore (mPTP), reducing the release of ROS and Cyt-c, both of which are involved in apoptosis. …