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The Future of Oncology in Psychiatric Medications.

Recent years have provided numerous reports on the mechanisms of action of psychiatric medications (antidepressants, antipsychotics, mood stabilizers, and antidementia drugs) that directly inhibit the growth of cancer cells, as well as on their indirect effects on the psyche and immune system, and their supportive effects on chemotherapeutic agents. The mechanisms of the anticancer activity of psychiatric drugs include inhibition of dopamine and N-methyl-D-aspartate receptors that work via signaling pathways (PI3K/AKT/mTOR/NF-κB, ERK, Wnt/ß-catenin, and bcl2), metabolic pathways (ornithine dec

Epigenetic Dysregulation in Neurodegeneration: The Role of Histone Deacetylases and Emerging Inhibitor Strategies.

Neurodegenerative diseases such as Alzheimer's disease (AD), Parkinson's disease (PD), and Huntington's disease (HD) are characterized by complex pathologies with progressive neurodegeneration, protein misfolding, oxidative stress, and persistent inflammation. Recent findings indicate the pivotal involvement of epigenetic disruption, particularly aberrant histone deacetylase (HDAC) activity, in disease initiation and progression. In the current review, we systematically discuss the mechanistic function of HDACs across all classes (I, IIa, IIb, III, and IV) in neurodegenerative disease mechanis

Metformin and Its Benefits for Various Diseases.

Metformin is a widely used biguanide drug due to its safety and low cost. It has been used for over 60 years to treat type 2 diabetes at the early stages because of its outstanding ability to decrease plasma glucose levels. Over time, different uses of metformin were discovered, and the benefits of metformin for various diseases and even aging were verified. These diseases include cancers (e.g., breast cancer, endometrial cancer, bone cancer, colorectal cancer, and melanoma), obesity, liver diseases, cardiovascular disease, and renal diseases. Metformin exerts different effects through differe

Роли глюкагонового пептида 1 Агонисты-рецепторы в биологии иммунных клеток и аутоиммунных/аутоинфлампмидативных заболеваниях.

Глукагон-подобный peptide-1 (В тыс.GLP-1) — гормон, полученный кишечником, необходимый для поддержания глюкозы гомеостаза через многочисленные физиологические пути: инсулина, ингибирующего секрецию глюкагонов, замедляющего опустошение желудочков, усиливающего чувство полноты и подавляющего аппетит. С тех пор GLP-1 может разлагаться при помощи дипептидила пептидаза 4, GLP-1 рецепторные агонисты (GLP-1RAs) были разработаны для решения этой проблемы деградации. В настоящее время GLP-1RAs стали высокоэффективными методами лечения для управления типом 2 сахарный диабет и ожирение. Помимо их хорошо

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

Exploiting the potential of the ubiquitin-proteasome system in overcoming tyrosine kinase inhibitor resistance in chronic myeloid leukemia.

The advent of tyrosine kinase inhibitors (TKI) targeting BCR-ABL has drastically changed the treatment approach of chronic myeloid leukemia (CML), greatly prolonged the life of CML patients, and improved their prognosis. However, TKI resistance is still a major problem with CML patients, reducing the efficacy of treatment and their quality of life. TKI resistance is mainly divided into BCR-ABL-dependent and BCR-ABL-independent resistance. Now, the main clinical strategy addressing TKI resistance is to switch to newly developed TKIs. However, data have shown that these new drugs may cause serio

МикроРНК-219 в центральной нервной системе: потенциальный тераностический подход.

Несмотря на недавние терапевтические достижения в области неврологических расстройств, лечебная терапия во многих случаях остается серьезной проблемой. Несмотря на то, что в последние годы мы стали свидетелями развития генной терапии из различных терапевтических подходов, влияющих на патофизиологические механизмы, существуют интригующие аспекты, касающиеся эффективности, безопасности и механизма действий генной терапии. Микрорибонуклеиновая кислота (микроRNA-miRNA) в качестве основного генного регулятора регулирует рибонуклеиновую кислоту курьера (mRNA) путем прямого соединения через 3'неперев

Разъяснение роли GRK2: от иммунного регулирования к терапии рака.

G белковые рецепторы (GPCR) представляют собой наиболее заметное семейство мембранных белков. В противоположность этому, G-белковые рецепторы (GRKs) играют ключевую роль в быстрой десенсибилизации ГПКР. GRK2 является особенно важным членом семьи GRK. Недавние исследования показали, что GRK2 в первую очередь регулирует функции иммунных клеток и гомеостаз через десенсибилизацию рецептора. За последнее десятилетие был достигнут существенный прогресс в разъяснении роли GRK2 в различных заболеваниях человека. В частности, GRK2 имеет отношение к целому ряду аутоиммунных расстройств, включая ревматуи

Ущерб от белой материи при нарушении центральной нервной системы.

По мере ускорения процесса старения и улучшения условий жизни болезни центральной нервной системы (СНС) стали одной из основных проблем здравоохранения. Болезни CNS вызывают не только повреждения серых веществ, которые в первую очередь характеризуются потерей нейронов, но и повреждения белых веществ. Однако в большинстве предыдущих исследований основное внимание уделялось травматизму серого вещества (ГМИ), при этом было проведено меньше исследований травматизма белого вещества (ВМИ). В этой статье мы кратко опишем структуру и функцию белого вещества, подытожим патологические изменения ВМИ и со

Sorcin: a novel potential target in therapies of cancers.

Soluble resistance-related calcium-binding protein (sorcin) is a member of the penta-EF-hand protein family. Sorcin is widely distributed in normal human tissues, such as the brain, heart, lymphocytes, kidneys, breast and skin. Findings suggest that sorcin is associated with the regulation of calcium homeostasis, cell cycle and vesicle trafficking. It has been reported that many types of non-neoplastic diseases such as diabetes, viral infection, infertility, and nervous system diseases were affected by the expression of sorcin. One of the main issues is the role of sorcin in neoplastic disease

Постройте мышцы и защитите миелина.

Множественный склероз (MS) представляет собой хроническое и изнуряющее аутоиммунное заболевание центральной нервной системы (СНС), при котором иммунная реакция, основанная на CNS, разрушает миелин, что приводит к широкому спектру симптомов, включая онемение и покалывание, проблемы зрения, нарушение подвижности и т.д. Oligodendrocytes — это миелионирующие клетки в CNS, которые образуются из олигодендроголовых потомков (OPC) посредством дифференциации. Однако по целому ряду причин ОЗК не проводят различия с олигодендроцитами в РС, и в результате, стимулирование дифференциации ОЗК с олигодендроци

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… Although there are two prominent histone acetyl transferases (p300 and CREB-binding protein or CBP) 63 ], [ 64 ], [ 65 , HMB retains CBP, but not p300, to the PPRE of myelin gene promoter in OPCs [ 57 ]. … Saha RN Ghosh A Palencia CA Fung YK Dudek SM Pahan K TNF-alpha preconditioning protects neurons via neuron-specific up-regulation of CREB-binding protein J Immunol 2009 183 2068 78 10.4049/jimmunol.0801892 19596989 PMC2724010 64. …

Microbiota-derived metabolites as modulators of cancer immunotherapy response.

The microbiome is a key regulator of host homeostasis and immune activity, in part through the production of metabolites. These microbiota-derived metabolites can modulate both the innate and adaptive immune system, as well as directly target tumour cells, thereby regulating anti-tumour immunity and response to immunotherapy. Here, we describe the current mechanistic knowledge on how these metabolites exert their effects and outline the methodologies used to detect and assess these metabolites. Finally, we summarize microbiota-targeted therapies capable of improving microbial functionality to

Cyclic nucleotide phosphodiesterases as drug targets.

Cyclic nucleotides are synthesized by adenylyl and/or guanylyl cyclase, and downstream of this synthesis, the cyclic nucleotide phosphodiesterase families (PDEs) specifically hydrolyze cyclic nucleotides. PDEs control cyclic adenosine-3',5'monophosphate (cAMP) and cyclic guanosine-3',5'-monophosphate (cGMP) intracellular levels by mediating their quick return to the basal steady state levels. This often takes place in subcellular nanodomains. Thus, PDEs govern short-term protein phosphorylation, long-term protein expression, and even epigenetic mechanisms by modulating cyclic nucleotide levels

Potential Adverse Effects of Dexamethasone Therapy on COVID-19 Patients: Review and Recommendations.

In the context of the coronavirus disease 2019 (COVID-19) pandemic, the global healthcare community has raced to find effective therapeutic agents against severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2). To date, dexamethasone is the first and an important therapeutic to significantly reduce the risk of death in COVID-19 patients with severe disease. Due to powerful anti-inflammatory and immunosuppressive effects, dexamethasone could attenuate SARS-CoV-2-induced uncontrolled cytokine storm, severe acute respiratory distress syndrome and lung injury. Nevertheless, dexamethasone tre

BCL-2 and BCL-xL in Cancer: Regulation, Function, and Therapeutic Targeting.

The BCL-2 family of proteins plays a central role in the regulation of apoptosis, with BCL-2 and BCL-xL representing two of its most prominent antiapoptotic members. This review explores the molecular regulation of BCL-2 and BCL-xL genes, emphasizing the structural domains that define the functions of the broader BCL-2 family. Beyond their canonical roles in preventing mitochondrial outer membrane permeabilization, both proteins contribute significantly to cancer development. Their overexpression enhances invasiveness and tumor progression, supports angiogenesis, and critically modulates cellu

Mechanistic Insights into the Metabolic Pathways and Neuroprotective Potential of Pentacyclic Triterpenoids: In-Depth Analysis of Betulin, Betulinic, and Ursolic Acids.

Due to their complexity, both genotypic and phenotypic, neurodegenerative diseases are one of the main causes of death globally nowadays. Among phytochemicals of high scientific interest, based on experimental studies, pentacyclic triterpenoids (TTs), including mainly betulin, betulinic, and ursolic acid, became targets of scientific research in recent years, especially in terms of their biological activity and pharmacological potential. Due to their anti-inflammatory and antioxidant properties, as well as their involvement in cellular signal transductions, they have been observed to act as an

Воздействие и механизмы N-3 и n-6 политетрафицированных жировых кислот в центральной нервной системе.

Мозг богат жирными кислотами (FAs) и полинунасыщенными жирными кислотами (PUFAs), такими, как докоза гексаэноиновая кислота (C22:6n-3, DHA) и арахидоническая кислота (C20:4n-6, ARA), причем первые в основном хранятся в виде фосфатидилэтилена, фосфатидила этаноламина (PE, диачила и плазма фосфолипид проформы) и фосфатидилсерин (PS), в то время как последние встречаются главным образом в фосфоглицеридах этаноламина (EPG) и составляют большинство фосфоглицеридов. По требованию организма ПФФА освобождаются от мембранных фосфолипидов (либо непосредственно, либо через их метаболиты, генерируемые сер

Ferroptosis and its emerging role in esophageal cancer.

The occurrence and development of tumors involve a series of life activities of cells, among which cell death has always been a crucial part in the research of tumor mechanisms and treatment methods. Ferroptosis is a non-apoptotic form of cell death, which is characterized by lipid peroxidation accumulation and further cell membrane rupture caused by excessive production of intracellular oxygen free radicals dependent on iron ions. Esophageal cancer is one of the common digestive tract tumors. Patients in the early stage are mainly treated with surgery, and the curative effect is awe-inspiring

Modulation by Ozone Therapy of Oxidative Stress in Chemotherapy-Induced Peripheral Neuropathy: The Background for a Randomized Clinical Trial.

(1) Background: Chemotherapy-induced peripheral neuropathy (CIPN) decreases the quality of life of patients and can lead to a dose reduction and/or the interruption of chemotherapy treatment, limiting its effectiveness. Potential pathophysiological mechanisms involved in the pathogenesis of CIPN include chronic oxidative stress and subsequent increase in free radicals and proinflammatory cytokines. Approaches for the treatment of CIPN are highly limited in their number and efficacy, although several antioxidant-based therapies have been tried. On the other hand, ozone therapy can induce an ada

EP300 as a Molecular Integrator of Fibrotic Transcriptional Programs.

Fibrosis is a condition characterized by the excessive accumulation of extracellular matrix proteins in tissues, leading to organ dysfunction and failure. Recent studies have identified EP300, a histone acetyltransferase, as a crucial regulator of the epigenetic changes that contribute to fibrosis. In fact, EP300-mediated acetylation of histones alters global chromatin structure and gene expression, promoting the development and progression of fibrosis. Here, we review the role of EP300-mediated epigenetic regulation in multi-organ fibrosis and its potential as a therapeutic target. We discuss

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… EP300 and the CREB binding protein (CBP) are highly homologous proteins; given their functional redundancy, they are named CBP/EP300. However, in some specific circumstances, EP300 and CBP play distinct roles. … Role of Intrinsic Protein Disorder in the Function and Interactions of the Transcriptional Coactivators CREB-binding Protein (CBP) and p300. J. Biol. Chem. 2016;291:6714–6722. doi: 10.1074/jbc.R115.692020. 41. …