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Нанотехнология в области гематологии: усиление терапевтической эффективности с помощью нанопчастей.

Фон и цели Гематологические заболевания, такие, как лейкемия, лимфома и множественная миелома, вносят значительный вклад в глобальный диагноз рака. Несмотря на прогресс в традиционных методах лечения, таких, как химиотерапия и иммунотерапия, эти методы лечения сталкиваются с ограничениями, включая неконкретную адресность, побочные эффекты и резистентность к лекарствам. Цель этого обзора заключается в изучении потенциала нанотехнологии, в частности наночастиц (НФ), для улучшения терапевтических последствий для этих раковых заболеваний путем расширения поставок наркотиков и снижения токсичности.

Mechanisms of ferroptotic and non-ferroptotic organ toxicity of chemotherapy: protective and therapeutic effects of ginger, 6-gingerol and zingerone in preclinical studies.

Chemotherapy (CT) is one of the flagship options for the treatment of cancers worldwide. It involves the use of cytotoxic anticancer agents to kill or inhibit the proliferation of cancer cells. However, despite its clinical efficacy, CT triggers side effect toxicities in several organs, which may impact cancer patient's quality of life and treatment outcomes. While the side effect toxicity is consistent with non-ferroptotic mechanisms involving oxidative stress, inflammation, mitochondrial impairment and other aberrant signalling leading to apoptosis and necroptosis, recent studies show that f

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… Mitochondrial apoptosis is characterized by the loss of Δψm, which opens the mitochondrial permeability transition pore (mPTP) and releases pro-apoptotic substances such as cytochrome c and apoptosis-inducing factor (AIF) (Rocca et al. 2022 ). …

Current Advances of Nanomedicines Delivering Arsenic Trioxide for Enhanced Tumor Therapy.

Arsenic trioxide (ATO) is one of the first-line chemotherapeutic drugs for acute promyelocytic leukemia. Its anti-cancer activities against various human neoplastic diseases have been extensively studied. However, the clinical use of ATO for solid tumors is limited, and these limitations are because of severe systemic toxicity, low bioavailability, and quick renal elimination before it reaches the target site. Although without much success, several efforts have been made to boost ATO bioavailability toward solid tumors without raising its dose. It has been found that nanomedicines have various

Phosphodiesterase 7: a potential novel therapeutic target in ovarian cancer.

INTRODUCTION: Chemoresistance and disease relapses in epithelial ovarian cancer (EOC) highlight the need for novel therapeutic strategies. Here, we investigated phosphodiesterase 7A (PDE7A) as a potential target in ovarian cancer treatment. METHODS: Gene expression was performed by RNA sequencing data comparing high-grade serous ovarian carcinoma (HGSOC) and fallopian tube samples. The PDE7 inhibitor BRL 50481, alone or combined with paclitaxel (PTX), was tested in drug-sensitive A2780 and multi-resistant OVCAR3 cells by Diphenyltetrazolium bromide (MTT) assay. To validate data from the high

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… Also, during necrosis, the mitochondria become dysfunctional, in part through the opening of the mitochondrial permeability transition pore ( Karch and Molkentin, 2015 ). Our TEM results showed alterations in mitochondrial morphology as well as the enlargement of the mitochondrial ridge. …

Возможная роль метаформы и фибробластного роста Factor-21 В Multical Sclerosis Neuropathology: Birds of a Feather Flock Common.

Множественный склероз (MS) — прогрессивное демиелинизирующее заболевание CNS, характеризующееся воспалением, образованием CNS-клеров и повреждением нейронной миелинской оболочки (graphical abstract). Фактор роста фибробласта 21 (FGF21) занимается различными метаболическими расстройствами и нейродегенеративными заболеваниями. FFF21 и его корецептор β-Kloth имеют существенно важное значение для процесса ремиелиции MS. Метформин, инсулин-сенсибилизирующее лекарство, которое является первой линией лечения для типа 2 Мэлитус диабета (T2DM) может оказывать потенциальное нейрозащитное воздействие, ре

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… Findings from preclinical study observed that imeglimin by inhibiting of mitochondrial permeability transition pore (mPTP) and microglial activation attenuates ischemia‐induced brain damage in rats (Zemgulyte et al.  2022 ). …

Crosstalk of the Wnt/β-Catenin Signaling Pathway in the Induction of Apoptosis on Cancer Cells.

The Wnt/β-catenin signaling pathway plays a major role in cell survival and proliferation, as well as in angiogenesis, migration, invasion, metastasis, and stem cell renewal in various cancer types. However, the modulation (either up- or downregulation) of this pathway can inhibit cell proliferation and apoptosis both through β-catenin-dependent and independent mechanisms, and by crosstalk with other signaling pathways in a wide range of malignant tumors. Existing studies have reported conflicting results, indicating that the Wnt signaling can have both oncogenic and tumor-suppressing roles, d

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… An excessive mitochondrial division promotes the depolarization of mitochondrial membrane, triggering the opening of mitochondrial permeability transition pores (mPTP), the release of cyt c into the nucleus, and finally the activation of caspase-3 and -9, inducing apoptosis [ 244 ]. …

Renaissance of Traditional Mineral Drugs in Cancer: Advanced Delivery Strategies and Bioengineering Approaches.

Traditional mineral drugs represent an underexploited reservoir of natural antitumor agents; however, their clinical translation has historically been hindered by poor bioavailability, non-specific biodistribution, and dose-limiting toxicity. This review comprehensively examines the pharmacological mechanisms and modern formulation strategies driving the renaissance of mineral-based oncology therapeutics. We highlight how mineral drugs exert potent anticancer effects through interconnected pathways, including regulated cell death (e.g., apoptosis, ferroptosis), cell-cycle arrest, and immunomod

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… ATO similarly induces membrane potential loss and mitochondrial permeability transition pore (mPTP) opening [ 125 ]. Sustained mPTP opening disrupts mitochondrial homeostasis, leading to swelling, outer membrane permeabilization, and release of cytochrome c into the cytosol [ 126 ]. … Permeability Transition Pore MRI | Magnetic Resonance Imaging N/A | Not Applicable NDs | Nanodiamonds NR | Nanodiamonds Not Reported NRA | Nano-realgar PEG | Polyethylene glycol PK | Pharmacokinetics PLGA | Poly (lactic-co-glycolic acid) PML | Promyelocytic Leukemia rhG-CSF | Recombinant Human Granulocyte …

ER-mitochondria tethering and its signaling: A novel therapeutic target in breast cancer.

Communication between the endoplasmic reticulum (ER) and mitochondria through mitochondria-associated ER membranes (MAMs) is assisted by tethering proteins and signaling pathways, manifesting the dynamic exchange of lipids, calcium, and signaling molecules. However, dysregulation of tethering and signaling proteins contributes to the progression of breast cancer (BC). Abnormal MAM structures and altered ER-mitochondrial tethering impair mitochondrial functions and thereby drive BC progression. Altered mitochondrial dynamics, often characterized by dysregulated dynamin-related protein 1 (Drp1)

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… A recent study demonstrated that Cdk5 found in MAMs promotes BC by regulating calcium homeostasis in mitochondria via negatively controlling the opening of mitochondrial permeability transition pore and facilitating the uptake of calcium by mitochondria. 109 Abnormal ER stress, ER-mitochondrial tethering …

Терапевтический потенциал кетогенного диета в лечении прогрессивного множественного склероза

До недавнего времени множественный склероз рассматривался как полностью подстрекательское заболевание без признания значительного нейродегенеративного компонента, ответственного за прогрессирование заболеваний и инвалидность. Этому аспекту мешают наблюдения о диссоциации между воспалением и нейродегенерацией, когда нейродегенеративный компонент может играть более важную роль в прогрессии заболеваний. В этом обзоре мы изучаем взаимосвязь между митохондриальной дисфункцией и нейродегенерацией при множественном склерозе. Мы анализируем доказательства того, что кетогенная диета может улучшить функ

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… The “open state” of K ATP channels located on the inner mitochondrial membrane prevents the formation of mitochondrial permeability transition pores (MPTPs) that can lead to mitochondrial swelling and cell death. …

Novel roles of PIWI proteins and PIWI-interacting RNAs in human health and diseases.

Non-coding RNA has aroused great research interest recently, they play a wide range of biological functions, such as regulating cell cycle, cell proliferation, and intracellular substance metabolism. Piwi-interacting RNAs (piRNAs) are emerging small non-coding RNAs that are 24-31 nucleotides in length. Previous studies on piRNAs were mainly limited to evaluating the binding to the PIWI protein family to play the biological role. However, recent studies have shed more lights on piRNA functions; aberrant piRNAs play unique roles in many human diseases, including diverse lethal cancers. Therefore

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

Circulating Tumour Cells (CTCs) in NSCLC: From Prognosis to Therapy Design.

Designing optimal (neo)adjuvant therapy is a crucial aspect of the treatment of non-small-cell lung carcinoma (NSCLC). Standard methods of chemotherapy, radiotherapy, and immunotherapy represent effective strategies for treatment. However, in some cases with high metastatic activity and high levels of circulating tumour cells (CTCs), the efficacy of standard treatment methods is insufficient and results in treatment failure and reduced patient survival. CTCs are seen not only as an isolated phenomenon but also a key inherent part of the formation of metastasis and a key factor in cancer death.

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… It causes opening of the mitochondrial permeability transition pore, mitochondrial swelling, loss of mitochondrial membrane potential, and inhibition of ATP synthesis [ 355 , 356 ]. …

A Recent Review on Cancer Nanomedicine.

Cancer is one of the most prevalent diseases globally and is the second major cause of death in the United States. Despite the continuous efforts to understand tumor mechanisms and various approaches taken for treatment over decades, no significant improvements have been observed in cancer therapy. Lack of tumor specificity, dose-related toxicity, low bioavailability, and lack of stability of chemotherapeutics are major hindrances to cancer treatment. Nanomedicine has drawn the attention of many researchers due to its potential for tumor-specific delivery while minimizing unwanted side effects

Navigating the landscape of protein folding and proteostasis: from molecular chaperones to therapeutic innovations.

Protein folding is a fundamental process ensuring that polypeptide chains acquire the correct three-dimensional structures required for biological function. This complex journey from nascent polypeptides to mature proteins is tightly regulated by the cellular proteostasis network-an integrated system of molecular chaperones, folding enzymes, and degradation machineries. Disruptions in this network lead to dysproteostasis, a pathological state implicated in a growing list of human diseases, including neurodegenerative disorders, metabolic syndromes, and cancer. In this review, we provide a comp

Radioprotectors & mitigators in radiation therapy: Harnessing diverse pathways for optimizing clinical outcomes.

Radioprotectors are agents that protect normal tissues from the harmful effects of radiation during cancer treatment. Combining these protective agents with advanced radiotherapy techniques such as stereotactic body radiotherapy (SBRT) and proton therapy offers a promising strategy to enhance therapeutic efficacy while minimizing normal tissue toxicity. However, despite extensive research and the identification of numerous potential radioprotectors, only a few have made it into clinical practice. It is primarily because the transition from laboratory research to clinical application faces sign

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… Radiation damages mitochondria, opening the mitochondrial permeability transition pore (MPTP), disrupting membrane potential, and leading to cell death 15 . MPTP inhibitors like cyclosporin A and sanglifehrin A prevent mitochondrial destabilization. …

Обзор " Метформин " и " нейродегенерация: всеобъемлющий обзор " .

В рамках этого всеобъемлющего обзора изучается терапевтический потенциал метаформина, хорошо зарекомендовавшего себя лекарство от диабета, при лечении нейродегенеративных расстройств. Первоначально использованная в качестве первой линии обработки для типа 2 диабет, недавние исследования начали изучать эффекты метаформина, выходящие за рамки метаболических расстройств, особенно его нейрозащитные способности против таких заболеваний, как болезнь Паркинсона, болезнь Альцгеймера, болезнь Хантингтона и множественный склероз. Ключевые выводы показывают, что нейрозащитный эффект метформина действует

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… Additionally, mitochondrial calcium regulation becomes dysfunctional, leading to dangerous cytoplasmic calcium accumulation that triggers excitotoxicity and cell death pathways, particularly through the mitochondrial permeability transition pore [ 191 , 192 ]. …

Перекресток между диабетом и болезнью Альцгеймера: Молекулярная перспектива.

Общемировая распространенность видов 2 Заболевание сахарным диабетом (T2DM) и болезнью Альцгеймера (AD) значительно возрастает в зависимости от возраста. Растущие данные подтверждают концептуализацию АД как типа 3 диабет, термин, предлагаемый для описания метаболического заболевания, вызванного главным образом поврежденной инсулиновой сигнализацией и инсулиновой резистентностью в мозге. В рамках этого обзора изучаются общие молекулярные механизмы, лежащие в основе как T2DM, так и AD, включая хроническую нейроинфламму, окислительный стресс, митохондриальную дисфункцию и поврежденный метаболизм

Towards a New Dawn for Neuro-Oncology: Nanomedicine at the Service of Drug Delivery for Primary and Secondary Brain Tumours.

(1) Background/Objectives: Primary and secondary brain tumours often hold devastating prognoses and low survival rates despite the application of maximal neurosurgical resection, and state-of-the-art radiotherapy and chemotherapy. One limiting factor in their management is that several antineoplastic agents are unable to cross the blood-brain barrier (BBB) to reach the tumour microenvironment. Nanomedicine could hold the potential to become an effective means of drug delivery to overcome previous hurdles towards effective neuro-oncological treatments. (2) Methods: A scoping review following th

Oleocanthal as a Multifunctional Anti-Cancer Agent: Mechanistic Insights, Advanced Delivery Strategies, and Synergies for Precision Oncology.

Oleocanthal (OC), a secoiridoid phenolic compound exclusive to extra virgin olive oil (EVOO), has emerged as a promising nutraceutical with multifaceted anti-cancer properties. Despite its well-characterized anti-inflammatory and antioxidant effects, the mechanistic breadth and translational potential of OC in oncology remain underexplored and fragmented across the literature. This comprehensive review synthesizes and critically analyzes recent advances in the molecular, pharmacological, and translational landscape of OC's anti-cancer activities, providing an integrative framework to bridge pr

Nature-Inspired Strategies in Cancer Management: The Potential of Plant Extracts in Modulating Tumour Biology.

Cancer is a serious group of diseases that is a huge problem on a global scale and is the second most common cause of death. Commonly used therapies do not always lead to the complete elimination of diseased cells or tissues and are also burdened with side effects that reduce the quality of life of patients. Due to these difficulties, new therapeutic approaches are still being sought. In recent years, there has been a return to interest in natural methods of treating various diseases, among which phytochemicals are particularly interesting. This article reviews plant extracts with anticancer p