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Рецепт 1 в диабете и его хронические осложнения: механизмы сигнализации и новые терапевтические достижения.

Диабет моллюсков (DM) — системное метаболическое расстройство, характеризующееся хронической гипергликемией, которая может оказывать воздействие на почки, сетчатку, периферийные нервы и сердечно-сосудистую систему, что в конечном счете приводит к многочисленным хроническим осложнениям. 1 (PAR1) — G-белковый рецептор, приводимый в действие через каноническое декольте, например тромбинированный декольте и неканоническое декольте, например, декольте с помощью активированного белка C или матрицы Metalloproteinase-1. Эти режимы активации инициируют различные каналы подачи сигналов вниз по течению,

Свойства антиракера ВИЧ-ингибатора Нелфинавира.

Традиционные методы лечения рака могут потерять свою эффективность после появления новых мутации или развития химиотерапии. Несвоевременная диагностика, высокая стоимость лечения и потребность в высокоэффективной инфраструктуре для лечения раковых заболеваний затрудняют доступ к надлежащему лечению в условиях с низким уровнем доходов и ограниченными ресурсами. Переориентация утвержденных лекарственных средств на лечение рака может привести к снижению стоимости и сокращению сроков разработки новых лекарственных средств и к ускорению появления новых и эффективных вариантов лечения для нуждающихс

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… Besse et al. showed nelfinavir and lopinavir-mediated ROS production in carfilzomib-resistant MM cells, which was rescued by the addition of mitochondrial permeability transition pore antagonist decylubiqinone [ 87 ]. 2.8. …

Targeting Metal Ion Homeostasis for Regulated Cell Death-Amplified Tumor Nanomedicine.

Amidst escalating global health challenges, neoplastic diseases remain a predominant cause of morbidity and mortality, exerting complex and far-reaching effects on human health and societal well-being. The advent of precision medicine has ushered in an era of tailored therapeutic strategies, leveraging individual genetic profiles, tumor microenvironmental features, and exogenous factors to redefine oncology care. Central to these advances is the understanding of cell death, a fundamental biological process encompassing both programmed and non-programmed forms. Programmed cell death is orchestr

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… When inside of cells Ca 2+ concentrations rise abnormally, the mitochondrial permeability transition pore (mPTP) opens irreversibly, causing the collapse of the membrane potential of mitochondrial cells,impaired the production of ATP, and the dissolution of cytochrome c. …

Pathobiology of cancer chemotherapy-induced peripheral neuropathy (CIPN).

Chemotherapy induced peripheral neuropathy (CIPN) is a type of neuropathic pain that is a major dose-limiting side-effect of potentially curative cancer chemotherapy treatment regimens that develops in a "stocking and glove" distribution. When pain is severe, a change to less effective chemotherapy agents may be required, or patients may choose to discontinue treatment. Medications used to alleviate CIPN often lack efficacy and/or have unacceptable side-effects. Hence the unmet medical need for novel analgesics for relief of this painful condition has driven establishment of rodent models of C

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… Opening of the mPTP and dysregulation of calcium homoeostasis Paclitaxel opens the mitochondrial permeability transition pore (mPTP), a multi-molecular complex containing a voltage-dependent anion channel that induces mitochondrial calcium release (Kidd et al., 2002 ; Flatters and Bennett, 2006 ). … Paclitaxel affects cytosolic calcium signals by opening the mitochondrial permeability transition pore . J. Biol. Chem . 277 , 6504 – 6510 10.1074/jbc.M106802200 11724773 Kim H. K. Zhang Y. P. Gwak Y. S. Abdi S. ( 2010 ). …

Updates in Anthracycline-Mediated Cardiotoxicity.

Cardiotoxicity is one of the main adverse effects of chemotheraphy, affecting the completion of cancer therapies and the short- and long-term quality of life. Anthracyclines are currently used to treat many cancers, including the various forms of leukemia, lymphoma, melanoma, uterine, breast, and gastric cancers. World Health Organization registered anthracyclines in the list of essential medicines. However, anthracyclines display a major cardiotoxicity that can ultimately culminate in congestive heart failure. Taking into account the growing rate of cancer survivorship, the clinical significa

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… Cardiolipin peroxidation leads to (i) detachment of cytochrome c from mitochondrial membrane, leading to caspase-depending apoptosis, (ii) uncouples respiratory chain complexes I, III, and IV in the mitochondria, (ii) forms a mitochondrial permeability transition pore (mPTP). …

Calcium Signalling in Breast Cancer Associated Bone Pain.

Calcium (Ca2+) is involved as a signalling mediator in a broad variety of physiological processes. Some of the fastest responses in human body like neuronal action potential firing, to the slowest gene transcriptional regulation processes are controlled by pathways involving calcium signalling. Under pathological conditions these mechanisms are also involved in tumoral cells reprogramming, resulting in the altered expression of genes associated with cell proliferation, metastatisation and homing to the secondary metastatic site. On the other hand, calcium exerts a central function in nocicepti

Mechanisms of Chemotherapy-Induced Peripheral Neuropathy.

Chemotherapy-induced peripheral neuropathy (CIPN) is one of the most frequent side effects caused by antineoplastic agents, with a prevalence from 19% to over 85%. Clinically, CIPN is a mostly sensory neuropathy that may be accompanied by motor and autonomic changes of varying intensity and duration. Due to its high prevalence among cancer patients, CIPN constitutes a major problem for both cancer patients and survivors as well as for their health care providers, especially because, at the moment, there is no single effective method of preventing CIPN; moreover, the possibilities of treating t

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… Paclitaxel can cause the release of Ca 2+ from mitochondria, and the process is probably mediated by the activation of the mitochondrial permeability transition pore (mPTP), leading to rapid mitochondria depolarization [ 172 , 173 ]. …

Engineering precision nanoparticles for drug delivery.

In recent years, the development of nanoparticles has expanded into a broad range of clinical applications. Nanoparticles have been developed to overcome the limitations of free therapeutics and navigate biological barriers - systemic, microenvironmental and cellular - that are heterogeneous across patient populations and diseases. Overcoming this patient heterogeneity has also been accomplished through precision therapeutics, in which personalized interventions have enhanced therapeutic efficacy. However, nanoparticle development continues to focus on optimizing delivery platforms with a one-

Clinical Applications and Anticancer Effects of Antimicrobial Peptides: From Bench to Bedside.

Cancer is a multifaceted global health issue and one of the leading causes of death worldwide. In recent years, medical science has achieved great advances in the diagnosis and treatment of cancer. Despite the numerous advantages of conventional cancer therapies, there are major drawbacks including severe side effects, toxicities, and drug resistance. Therefore, the urgency of developing new drugs with low cytotoxicity and treatment resistance is increasing. Antimicrobial peptides (AMPs) have attracted attention as a novel therapeutic strategy for the treatment of various cancers, targeting tu

Oxidative Stress: Signaling Pathways, Biological Functions, and Disease.

The dysregulated accumulation of reactive oxygen species (ROS) and reactive nitrogen species disrupts redox homeostasis, triggering oxidative stress (OS) and driving pathophysiological changes across multiple organ systems. OS modulates critical signaling pathways, induces inflammation, impairs mitochondrial function, alters metabolic homeostasis, and dysregulates autophagy, contributing to disease progression. While prior research has largely focused on OS within single-organ diseases (e.g., neurodegenerative, cardiovascular, and oncological disorders), the systemic role of OS in pan-organ di

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… permeability transition pore (mPTP)‐derived mtROS/p38‐calcium synergy. … The increase in calcium levels is associated with mtROS production, which depends on the opening of the mitochondrial permeability transition pore (mPTP), facilitating NETosis [ 48 ]. …

Invited Lectures : Overviews Purinergic signalling: past, present and future.

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Anti-cancer mechanisms of action of therapeutic alternating electric fields (tumor treating fields [TTFields]).

Despite improved survival outcomes across many cancer types, the prognosis remains grim for certain solid organ cancers including glioblastoma and pancreatic cancer. Invariably in these cancers, the control achieved by time-limited interventions such as traditional surgical resection, radiation therapy, and chemotherapy is short-lived. A new form of anti-cancer therapy called therapeutic alternating electric fields (AEFs) or tumor treating fields (TTFields) has been shown, either by itself or in combination with chemotherapy, to have anti-cancer effects that translate to improved survival outc

The anti-inflammatory effects of mesenchymal stem cells and their research progress in hematopoietic stem cell transplantation: A comprehensive review.

Hematopoietic stem cell transplantation (HSCT) is frequently accompanied by severe inflammation-related complications, among which graft-versus-host disease (GVHD) stands out as one of the most common and life-threatening. As a systemic inflammatory disorder, GVHD arises when donor T cells recognize the recipient's alloantigens and initiate an immune attack. Currently, effective second-line treatment options remain scarce for patients with antibiotic-resistant or steroid-refractory GVHD. Mesenchymal stem cells (MSCs) are non-hematopoietic cells widely distributed in fetal and adult tissues and

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… In models of acute pancreatitis, mitochondrial transfer by MSCs protects cells from damage caused by the abnormal opening of mitochondrial permeability transition pores (mPTPs) 38 . …

Harnessing the Therapeutic Potential of Capsaicin and Its Analogues in Pain and Other Diseases.

Capsaicin is the most predominant and naturally occurring alkamide found in Capsicum fruits. Since its discovery in the 19th century, the therapeutic roles of capsaicin have been well characterized. The potential applications of capsaicin range from food flavorings to therapeutics. Indeed, capsaicin and few of its analogues have featured in clinical research covered by more than a thousand patents. Previous records suggest pleiotropic pharmacological activities of capsaicin such as an analgesic, anti-obesity, anti-pruritic, anti-inflammatory, anti-apoptotic, anti-cancer, anti-oxidant, and neur

Apoptosis and (in) Pain-Potential Clinical Implications.

The deregulation of apoptosis is involved in the development of several pathologies, and recent evidence suggests that apoptosis may be involved in chronic pain, namely in neuropathic pain. Neuropathic pain is a chronic pain state caused by primary damage or dysfunction of the nervous system; however, the details of the molecular mechanisms have not yet been fully elucidated. Recently, it was found that nerve endings contain transient receptor potential (TRP) channels that sense and detect signals released by injured tissues and respond to these damage signals. TRP channels are similar to the

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… The five major mitochondrial functions (the mitochondrial energy generating system, ROS generation, mitochondrial permeability transition pore, apoptotic pathways, and intracellular calcium mobilization) may play critical roles in neuropathic and inflammatory pain [ 7 ]. …

XPO1: From basic research to clinical treatment (Review).

Exportin 1 (XPO1) is a key nuclear export receptor that mediates the nuclear export of tumor suppressor proteins and growth‑regulatory mRNAs from the nucleus to the cytoplasm. In several types of cancer, XPO1 is overexpressed or hyperactivated, leading to aberrant cytoplasmic sequestration of key tumor suppressors such as p53, p21, p73, FOXO and Rb. This mislocalization abrogates their nuclear transcriptional functions, disrupting cell cycle arrest, apoptosis and DNA repair, thereby promoting uncontrolled proliferation, survival and therapy resistance. Targeting XPO1 with selective inhibitors

New targets for the treatment of follicular lymphoma.

The last two decades have witnessed striking advances in our understanding of the biological factors underlying the development of Follicular lymphoma (FL). Development of newer treatment approaches have improved the outlook for many individuals with these disorders; however, with these advances come new questions. Given the long-term survival of patients with FL, drugs with favourable side-effect profile and minimal long-term risks are desired. FL is incurable with current treatment modalities. It often runs an indolent course with multiple relapses and progressively shorter intervals of remi

Breaking the Feedback Loop: A Model of Vicious Cycle for CIPN and Acupuncture-Medication Combination.

Chemotherapy-induced peripheral neuropathy (CIPN) is a prevalent and often debilitating complication of cancer therapy, whose chronicity and refractoriness cannot be adequately explained by traditional linear etiological models. This review proposes and organizes a "vicious cycle" model as a hypothesis: initial neuronal injury caused by chemotherapeutic agents initiates a self-sustaining positive feedback loop in which mitochondrial dysfunction and oxidative stress reciprocally amplify each other, thereby activating neuroinflammation and ion channel remodeling. These processes collectively dri

Длиннокаменистые толстые кислоты как движущие факторы нейроинфламмации в нейродегенерации: механистические связи с липидом пероксидацией, Ферроптозом и митохондриальной дисфункцией.

Фон: Нейродегенеративные заболевания (НИ) рассматриваются главным образом как расстройства, характеризующиеся серьезным иммунометаболическим дисбалансом, характеризующимся текущей нейроинфламмацией и глиальной активацией. Хотя митохондриальная дисфункция и окислительный стресс являются хорошо известными особенностями, метаболические факторы в верхнем течении, связывающие эти патологические процессы, по-прежнему плохо понимаются. Методы: В ходе этого обзора мы изучили недавние доклинические и клинические исследования, в ходе которых были изучены связи между липидным метаболизмом, иммунометаболи

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… This lipotoxic stress, in conjunction with elevated ROS and calcium dysregulation, triggers the opening of the mitochondrial permeability transition pore (mPTP), a complex inhibited by cyclosporine A. Persistent mPTP opening induces mitochondrial swelling, rupture, and profound oxidative stress. …

Peripheral Neuropathy under Oncologic Therapies: A Literature Review on Pathogenetic Mechanisms.

Peripheral neurologic complications are frequent adverse events during oncologic treatments and often lead to dose reduction, administration delays with time elongation of the therapeutic plan and, not least, worsening of patients' quality of life. Experience skills are required to recognize symptoms and clinical evidences and the collaboration between different health professionals, in particular oncologists and hospital pharmacists, grants a correct management of this undesirable occurrence. Some classes of drugs (platinates, vinca alkaloids, taxanes) typically develop this kind of side effe

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… This process includes mitotoxicity, in particular referring to the presence of swollen and vacuolated mitochondria in Aδ and C fibers which stimulates Ca 2+ release, opening mitochondrial permeability transition pore (mPTP) and leading to mitochondria depolarization [ 48 , 143 ] and neuronal excitability … Paclitaxel Affects Cytosolic Calcium Signals by Opening the Mitochondrial Permeability Transition Pore J. Biol. Chem. 2002 277 6504 6510 10.1074/jbc.M106802200 11724773 49. Duggett N.A. Griffiths L.A. McKenna O.E. De Santis V. Yongsanguanchai N. Mokori E.B. Flatters S.J.L. …