Результаты поиска

Роль кишечника микробиота-митохондрия в нейродегенерации: основополагающие механизмы и потенциальные методы лечения.

Появляющиеся данные свидетельствуют о том, что микробиота кишечника тесно связана с патологическими проявлениями множественных нейродегенеративных заболеваний через ось кишечника, которая относится к перекрестку между кишечником и центральной нервной системой. Еще важнее то, что митохондрия считается выдающимся посредником взаимодействия между кишечной микробиотой и мозгом. Кишечные микробы могут модифицировать функцию митохондриала в центральной нервной системе, чтобы повлиять на развитие нейродегенеративных заболеваний. Митохондрия необходима для удовлетворения значительных потребностей носи

Совпадение в полном тексте источника
… A significant influx of calcium, and the overproduction of reactive oxygen species (ROS) and active nitrogen by impaired mitochondria can lead to the formation of mitochondrial permeability transition pores which are known to be associated with neurodegenerative diseases (Li et al., 2017). … For example, high concentrations of glutamate have been shown to impair mitochondrial function in human neuroblastoma SHSY5Y cells by increasing the production of ROS and intra-mitochondrial calcium, thus promoting the opening of mitochondrial permeability transition pores, and dissipating the MMP (Dubey …

From Innate Immunity to Cancer Therapy: Antimicrobial Peptides as Emerging Anticancer Agents.

The potential for the use of antimicrobial peptides (AMPs) as anticancer agents has garnered much interest because of their selective cytotoxicity to tumor cells and ability to evade multidrug resistance mechanisms. AMPs are shorter cationic amphiphilic molecules, part of our innate immune system, with direct membrane-disruptive activity and immunomodulatory effects. Anticancer peptides (ACPs) can be derived from natural biophysical sources or synthetically engineered, taking advantage of the unique biophysical properties of cancer cell membranes to exert their anti-tumor activities rapidly an

α2-3-sialylated Гликосфинголипиды при нейроинфламмации, иммунитете и запрограммированной смерти клеток: механистические доказательства и регулирование в зависимости от контекста: всеобъемлющий обзор.

α2-3-sialylated glycosphingolids (α2)3-GSLs) являются основными составляющими нейронных мембран и липидных плотов, где они формируют сепарацию рецепторов, комплекс сигналов и связь с клетками. Однако их биологическое воздействие варьируется в зависимости от молекулярного подтипа, типа клеток, стадии заболевания, концентрации и местной микроокружающей среды. В настоящем обзоре обобщены данные о перепончатых изменениях в α2-3-GSL профили и их связи с нейроинфламмацией, иммунной реакцией, протеостазом и запрограммированной клеточной смертностью через болезнь Паркинсона, болезнь Альцгеймера, болез

Совпадение в полном тексте источника
… permeability transition pore ( 60 ). … Concurrently, disrupted calcium homeostasis may impair mitochondrial membrane potential and promote opening of the mitochondrial permeability transition pore (mPTP), followed by cytochrome c release and activation of caspase-9/3-associated apoptotic signaling ( 160 , 161 ). …

Retrospective Analysis of Clinicopathological Characteristics of Lacrimal Gland Pleomorphic Adenoma and Mechanism of Tumorigenesis by the Imbalance Between Apoptosis and Proliferation.

BACKGROUND Lacrimal gland pleomorphic adenoma (LGPA) is the most common clinically benign epithelial tumor of the lacrimal gland and is predominantly comprised of epithelial cells and interstitial components. At present, the exact pathogenesis of LGPA remains unclear. Previous research has indicated that the occurrence of LGPA may be related to excessive cell proliferation. MATERIAL AND METHODS This study observed the clinicopathological characteristics of LGPA and investigated the tumorigenesis mechanism of cell over-proliferation caused by the imbalance between apoptosis and proliferation. A

Совпадение в полном тексте источника
… When the expression of bcl-2 was upregulated and the bcl-2/bax ratio increased, bcl-2 formed a heterodimer with bax that decreased the sensitivity of lacrimal gland histiocytes to apoptosis-stimulating factors, and mitochondrial permeability transition pore opening was prolonged or remained in an “off …

Resveratrol Nanoformulations for Cancer Management: A Comprehensive Review of Disease-Specific Strategies and Clinical Translational Barriers.

Cancer remains a leading cause of mortality worldwide, highlighting the need for therapeutic strategies that reduce systemic toxicity and drug resistance. Resveratrol (RES), a natural polyphenolic stilbenoid, possesses antioxidant, anti-inflammatory, pro-apoptotic, anti-metastatic, and chemosensitizing activities. However, its clinical translation is limited by poor aqueous solubility, chemical instability, rapid metabolic clearance, and consequently low systemic bioavailability. Nanotechnology-based drug delivery systems provide a promising strategy to address these limitations. This review s

Совпадение в полном тексте источника
… In parallel, RES can elevate intracellular Ca2+ and drive mitochondrial Ca2+ overload, which promotes opening of the mitochondrial permeability transition pore (mPTP) and thereby reinforces ΔΨm collapse, cytochrome c release, and caspase-9/caspase-3 activation. 29 Notably, the convergence of these two … Abbreviations : FRα, folate receptor alpha; mPTP, mitochondrial permeability transition pore; RES, resveratrol. Resveratrol nanocarrier in prostate cancer: uptake, release, cell-cycle arrest, apoptosis. …

The Glycocalyx and Its Role in Vascular Physiology and Vascular Related Diseases.

PurposeIn 2007 the two senior authors wrote a review on the structure and function of the endothelial glycocalyx layer (Weinbaum in Annu Rev Biomed Eng 9:121-167, 2007). Since then there has been an explosion of interest in this hydrated gel-like structure that coats the luminal surface of endothelial cells that line our vasculature due to its important functions in (A) basic vascular physiology and (B) vascular related diseases. This review will highlight the major advances that have occurred since our 2007 paper.MethodsA literature search mainly focusing on the role of the glycocalyx in the

Последствия злоупотребления наркотиками для путей ферроптоза: потенциальные терапевтические цели для расстройств, связанных с потреблением психоактивных веществ.

Серьезными проблемами в области здравоохранения во всем мире, особенно в развитых странах, по-прежнему являются расстройства, связанные с потреблением психоактивных веществ. Для ОСВ характерна устойчивая нейроинфламмация и синаптическая дисфункция мозга. Несмотря на десятилетия интенсивного расследования, детальные механизмы, лежащие в основе ВСГ, по-прежнему остаются иллюзорными. Ферроптоз — это высокорегулируемый процесс смерти клеток, на который сильно влияют метаболизм железа, пероксидация липидов, производство реактивных видов кислорода (РОС) и антиоксидантные системы. Он был связан с мно

Совпадение в полном тексте источника
… Dopamine oxidation has been shown to cause mitochondrial swelling and opening of the mitochondrial permeability transition pore ( mPTP ) leading to ETC inhibition ( Khan et al., 2005 ). …

Protective Effects of Flavonoids Against Mitochondriopathies and Associated Pathologies: Focus on the Predictive Approach and Personalized Prevention.

Multi-factorial mitochondrial damage exhibits a "vicious circle" that leads to a progression of mitochondrial dysfunction and multi-organ adverse effects. Mitochondrial impairments (mitochondriopathies) are associated with severe pathologies including but not restricted to cancers, cardiovascular diseases, and neurodegeneration. However, the type and level of cascading pathologies are highly individual. Consequently, patient stratification, risk assessment, and mitigating measures are instrumental for cost-effective individualized protection. Therefore, the paradigm shift from reactive to pred

Совпадение в полном тексте источника
… Quercetin attenuated cardiac hypertrophy by increasing sulfhydryl group availability and mitochondrial superoxide dismutase activity and reducing mitochondrial permeability transition pore opening in the same model [ 129 ]. … A recent in vivo study using male Sprague Dawley rats was designed to assess the protective effects of HSYA-mediated mitochondrial permeability transition pore (mPTP) on cerebral ischemia/reperfusion injury and its mechanism. …

Lifestyle and Pharmacological Interventions to Prevent Anthracycline-Related Cardiotoxicity in Cancer Patients.

Anthracyclines remain a cornerstone of cancer therapy but are associated with a significant risk of cardiotoxicity, which can lead to overt heart failure. The risk is modulated by cumulative dose, pre-existing cardiovascular disease, and patient-specific factors. As cancer survival improves, the long-term cardiovascular consequences of anthracycline exposure have become a growing concern, underscoring the need for effective preventive strategies. This narrative review examines lifestyle and pharmacological interventions aimed at mitigating anthracycline-induced cardiotoxicity. Evidence suggest

Совпадение в полном тексте источника
… Prolonged mitochondrial calcium accumulation can trigger the opening of the mitochondrial permeability transition pore (mPTP), causing a loss of membrane potential, energy collapse, and eventual cell death [ 27 ]. 3.3. … Doxorubicin induced myocardial injury is exacerbated following ischaemic stress via opening of the mitochondrial permeability transition pore Toxicol. Appl. Pharmacol. 2013 268 149 156 10.1016/j.taap.2012.12.003 23262186 31. An J. Li P. Li J. Dietz R. Donath S. …

Ligand-Gated Ion Channels as Targets for Treatment and Management of Cancers.

Ligand-gated ion channels are an ionotropic receptor subtype characterized by the binding of an extracellular ligand, followed by the transient passage of ions through a transmembrane pore. Ligand-gated ion channels are commonly subcategorized into three superfamilies: purinoreceptors, glutamate receptors, and Cys-loop receptors. This classification is based on the differing topographical morphology of the receptors, which in turn confers functional differences. Ligand-gated ion channels have a diverse spatial and temporal expression which implicate them in key cellular processes. Given that t

Novel Therapeutics for Anthracycline Induced Cardiotoxicity.

Anthracyclines remain an essential component of the treatment of many hematologic and solid organ malignancies, but has important implications on cardiovascular disease. Anthracycline induced cardiotoxicity (AIC) ranges from asymptomatic LV dysfunction to highly morbid end- stage heart failure. As cancer survivorship improves, the detection and treatment of AIC becomes more crucial to improve patient outcomes. Current treatment modalities for AIC have been largely extrapolated from treatment of conventional heart failure, but developing effective therapies specific to AIC is an area of growing

Совпадение в полном тексте источника
… ACEi, angiotensin converting enzyme inhibitor; ARB, angiotensin II receptor blocker; BAI1, BAX activation inhibitor 1; Bax, bcl-2-associated X protein; Ca, calcium; Fe2+/3+, iron; IL, interleukin; mPTP, mitochondrial permeability transition pore; mtDNA, mitochondrial DNA; NF-kB, nuclear factor kappa …

Insights into platinum-induced peripheral neuropathy-current perspective.

Cancer is a global health problem that is often successfully addressed by therapy, with cancer survivors increasing in numbers and living longer world around. Although new cancer treatment options are continuously explored, platinum based chemotherapy agents remain in use due to their efficiency and availability. Unfortunately, all cancer therapies affect normal tissues as well as cancer, and more than 40 specific side effects of platinum based drugs documented so far decrease the quality of life of cancer survivors. Chemotherapy-induced peripheral neuropathy is a frequent side effects of plat

Совпадение в полном тексте источника
… All of these events cause redox imbalance, opening of mitochondrial permeability transition pores, depolarization of mitochondrial membrane and release of cytochrome c, deregulation of calcium homeostasis and initiation of apoptosis. … Paclitaxel induces rapid mitochondria depolarization and Ca 2+ release by activation of the mitochondrial permeability transition pore (Tsubaki et al., 2015). Axonal degeneration may be triggered by activation of protein kinases and caspases. …

Аккумулирование опустошающих липидов в Arf1-Ablanted Neurorons способствует нейродегенерации с помощью mtDNA и активации воспаляющих путей в Микроглии.

В нейронах и глиальных клетках были обнаружены липидные метаболические расстройства у пациентов с нейродегенеративной (ND) и животных. Однако патологическая связь между липидными капельками и НУ остается слабой. Недавняя работа высветила полезность модели мыши Arf1-knockout с учетом особенностей нейронов и соответствующих клеток для разъяснения связи между расстройствами липидного метаболизма и амиотропическим боковым склерозом (ALS) и множественным склерозом (MS). В этом исследовании было установлено, что недостача арф1 вызвала первичный синтез избытка жирной кислоты через ось АКТ-mTORC1-SREB

Совпадение в полном тексте источника
… As a pivotal organelle for calcium sequestration, the endoplasmic reticulum (ER) plays a critical role in modulating mitochondrial calcium homeostasis, thereby influencing the transition of the mitochondrial permeability transition pore (mPTP). … The accumulation of lipids within the cell may disrupt the calcium homeostasis between the ER‐mitochondria, leading to the accumulation of calcium ions in the mitochondria and the subsequent opening of the mitochondrial permeability transition pore (mPTP), which results in mitochondrial damage. …

Cannabidiol on the Path from the Lab to the Cancer Patient: Opportunities and Challenges.

Cannabidiol (CBD), a major non-psychotropic component of cannabis, is receiving growing attention as a potential anticancer agent. CBD suppresses the development of cancer in both in vitro (cancer cell culture) and in vivo (xenografts in immunodeficient mice) models. For critical evaluation of the advances of CBD on its path from laboratory research to practical application, in this review, we wish to call the attention of scientists and clinicians to the following issues: (a) the biological effects of CBD in cancer and healthy cells; (b) the anticancer effects of CBD in animal models and clin

Совпадение в полном тексте источника
… For example, although apoptosis was triggered first by CBD in leukemic cells, severe mitochondria damage and oxidative stress caused the switch to the mitochondrial permeability transition pore (mPTP)-driven necrosis [ 25 ]. …

Targeting the NLRP3 inflammasome in kidney disease: molecular mechanisms, pathogenic roles, and emerging small-molecule therapeutics.

Inflammatory responses represent a core pathological process driving the progression of both acute and chronic kidney diseases. As a key effector of the innate immune system, the NLRP3 inflammasome is widely activated in renal resident cellsand infiltrating immune cells, positioning it as a critical nexus linking metabolic dysregulation, cellular stress, and tissue injury. Accumulating preclinical and clinical evidence in recent years demonstrates that aberrant activation of the NLRP3 inflammasome directly promotes glomerular damage, tubulointerstitial inflammation, fibrosis, and vascular dysf

Молекулярные модели, связанные с ущербом от митохондриала: нейроиммуномодуляторы в патофизиологии центральной нервной системы.

Нейроинфламмация способствует широкому спектру нейродегенеративных заболеваний, включая болезнь Альцгеймера, болезнь Паркинсона, болезнь Хантингтона и множественный склероз. Его движут неевропейские глиальные клетки, главным образом микроглии и астроциты. Микроглии являются постоянными иммунными клетками центральной нервной системы, в то время как астроциты являются основными элементами поддержки нейронных функций, но могут также участвовать в нейроиммунной реакции. Оба этих типа глиальных клеток могут стать реактивными при обнаружении определенных внутриклеточных молекул, которые появляются в

Липидированные мезофорные наночастицы, нагруженные тимокиноном, в качестве нового метода лечения аутоиммунного энцефаломиелита у крыс.

AIMS: Пересечение мозгового барьера (BBB) по-прежнему является серьезной проблемой для доставки терапевтических агентов в центральную нервную систему. Цель этого исследования состояла в том, чтобы оценить потенциал новых наноформуляционных силикатных силиканочастиц (MSN), покрытых липидным двуслойным слоем (LB), с тем чтобы повысить уровень доставки и потенциальное ремиелионирующее воздействие тимокинона (TQ). МЕТОДЫ: Составы характеризовались микроскопией передачи электронов и динамическим рассеиванием света для определения потенциала зета и размера частиц. Экспериментальная аутоиммунная энце

HDACs and Their Inhibitors on Post-Translational Modifications: The Regulation of Cardiovascular Disease.

Cardiovascular diseases (CVD), such as myocardial hypertrophy, heart failure, atherosclerosis, and myocardial ischemia/reperfusion (I/R) injury, are among the major threats to human health worldwide. Post-translational modifications alter the function of proteins through dynamic chemical modification after synthesis. This mechanism not only plays an important role in maintaining homeostasis and plays a crucial role in maintaining normal cardiovascular function, but is also closely related to the pathological state of various diseases. Histone deacetylases (HDACs) play an important role in the

Совпадение в полном тексте источника
… SIRT3 can inhibit reperfusion injury through the deacetylation of procyclin D, which prevents the opening of the mitochondrial permeability transition pore and subsequent cell death [ 158 ]. … Mitochondrial Hyperacetylation in the Failing Hearts of Obese Patients Mediated Partly by a Reduction in SIRT3: The Involvement of the Mitochondrial Permeability Transition Pore. Cell Physiol. Biochem. 2019;53:465–479. doi: 10.33594/000000151. 104. …

The role of necroptosis in disease and treatment.

Necroptosis, a distinctive type of programmed cell death different from apoptosis or necrosis, triggered by a series of death receptors such as tumor necrosis factor receptor 1 (TNFR1), TNFR2, and Fas. In case that apoptosis process is blocked, necroptosis pathway is initiated with the activation of three key downstream mediators which are receptor-interacting serine/threonine protein kinase 1 (RIPK1), RIPK3, and mixed lineage kinase domain-like protein (MLKL). The whole process eventually leads to destruction of the cell membrane integrity, swelling of organelles, and severe inflammation. Ove

Совпадение в полном тексте источника
… permeability transition pore Multiple sclerosis necrotizing enterocolitis Necrostatin‐1 Osteoarthritis Parkinson's disease pore‐forming toxin Rheumatoid arthritis retinal ganglion cells RIPK homeotype interaction motif Receptor‐interacting serine/threonine protein kinase 1 receptor‐interacting … RIPK3 can open the mitochondrial permeability transition pore (mPTP) by activating Ca2 + /calmodulin‐dependent protein kinase II (CaMK II). …

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

Совпадение в полном тексте источника
… . | [ 132 , 133 ] Targets F 0 F 1 -ATP synthase and depends on the mitochondrial proton gradient | Gboxin | Animal and cellular model of GBM | Resistance mechanism involving mitochondrial permeability transition pore causing Gboxin accumulation. | [ 134 ] Figure 2 illustrates the ETC complexes and promising … Salinomycin has the ability to stimulate p53, open the mitochondrial permeability transition pore, and promote mitochondrial ROS generation and accumulation. These processes ultimately lead to necrosis in U87 and U251 GBM cell lines [ 144 ]. …