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Терапия клеток CAR-T и модуляция микробиоты в мультислерозе: новые терапевтические стратегии и текущие ограничения.

Множественный склероз (MS) — хроническое аутоиммунное воспалительное заболевание центральной нервной системы (CNS), характеризующееся разрушением миелиновой оболочки вокруг нервных клеток. Широкое распространение и серьезные последствия НР свидетельствуют о недостатках существующих методов лечения и о важности разработки новаторских терапевтических подходов. На основе успешных экспериментальных исследований среди пациентов и экспериментальной модели мышью аутоиммунного энцефаломиелита (EAE) клетки CAR-T предлагают новый терапевтический механизм путем непосредственной адресации и ликвидации кле

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… These lesions exhibit elevated innate immune activity, which is linked to endoplasmic reticulum (ER) stress and the unfolded protein response (UPR) [ 67 ]. …

Drug Repurposing Opportunities in Pancreatic Ductal Adenocarcinoma.

Pancreatic ductal adenocarcinoma (PDAC) is considered one of the deadliest tumors worldwide. The diagnosis is often possible only in the latter stages of the disease, with patients already presenting an advanced or metastatic tumor. It is also one of the cancers with poorest prognosis, presenting a five-year survival rate of around 5%. Treatment of PDAC is still a major challenge, with cytotoxic chemotherapy remaining the basis of systemic therapy. However, no major advances have been made recently, and therapeutic options are limited and highly toxic. Thus, novel therapeutic options are urgen

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… Moreover, a DRD2 blockage led to ER stress in pancreatic tumor cells, inducing cell cycle arrest, apoptosis and activation of the Unfolded Protein Response (UPR) [ 80 ]. …

Abstracts from the 11th International Conference for Healthcare and Medical Students (ICHAMS) : Virtual. 10-12 February 2022.

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… Transient activation of the unfolded protein response (UPR) stimulates adaptations which include increased β-cell proliferation. Phosphorylated eIF2α (p-eIF2α) signals activation of the PERK pathway of the UPR. …

A review of chemotherapeutic drugs-induced arrhythmia and potential intervention with traditional Chinese medicines.

Significant advances in chemotherapy drugs have reduced mortality in patients with malignant tumors. However, chemotherapy-related cardiotoxicity increases the morbidity and mortality of patients, and has become the second leading cause of death after tumor recurrence, which has received more and more attention in recent years. Arrhythmia is one of the common types of chemotherapy-induced cardiotoxicity, and has become a new risk related to chemotherapy treatment, which seriously affects the therapeutic outcome in patients. Traditional Chinese medicine has experienced thousands of years of cli

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… Endoplasmic reticulum stress and unfolded protein response in cardiovascular diseases. Nat. Rev. Cardiol. 18 (7), 499–521. 10.1038/s41569-021-00511-w Richards W. G., Zellos L., Bueno R., Jaklitsch M. T., Jänne P. A., Chirieac L. R., et al. (2006). …

Insulin Resistance at the Crossroads of Metabolic Inflammation, Cardiovascular Disease, Organ Failure and Cancer.

Insulin resistance (IR) describes impaired hormone signaling that triggers compensatory homeostatic responses resulting in hyperinsulinemia, increased accumulation of fatty substrates, lipotoxicity, oxidative stress, inflammation, cell death and fibrosis in target tissues. These processes ultimately lead to organ dysfunction and predispose certain individuals to various types of cancer. In this context, we will review the molecular pathogenesis and clinical significance of IR, its role in 'metaflammation', and the damage caused by IR in the pancreas, cardiovascular system, liver, and kidneys.

A Review of Gaucher Disease Pathophysiology, Clinical Presentation and Treatments.

Gaucher disease (GD, ORPHA355) is a rare, autosomal recessive genetic disorder. It is caused by a deficiency of the lysosomal enzyme, glucocerebrosidase, which leads to an accumulation of its substrate, glucosylceramide, in macrophages. In the general population, its incidence is approximately 1/40,000 to 1/60,000 births, rising to 1/800 in Ashkenazi Jews. The main cause of the cytopenia, splenomegaly, hepatomegaly, and bone lesions associated with the disease is considered to be the infiltration of the bone marrow, spleen, and liver by Gaucher cells. Type-1 Gaucher disease, which affects the

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… Mutant GCase is retained in the Endoplasmic reticulum, which causes ER stress and evokes the ER stress response (Unfolded Protein Response) [ 57 ]. Saposin C can have a modulating effect on this by binding to GCase and thus maintaining its activity [ 51 , 58 ]. 4.6. …

The role of Rhizoma Paridis saponins on anti-cancer: The potential mechanism and molecular targets.

Cancer is a disease characterized by uncontrolled cell proliferation, leading to excessive growth and invasion that can spread to other parts of the body. Traditional Chinese medicine has made new advancements in the treatment of cancer, providing new perspectives and directions for cancer treatment. Rhizoma Paridis is a widely used Chinese herbal medicine with documented anti-cancer effects dating back to ancient times. Modern research has shown that Rhizoma Paridis saponins (RPS) have various pharmacological activities. RPS can inhibit cancer in multiple ways, such as suppressing tumor growt

Exploration of Site-Specific Drug Targeting-A Review on EPR-, Stimuli-, Chemical-, and Receptor-Based Approaches as Potential Drug Targeting Methods in Cancer Treatment.

Cancer has been one of the most dominant causes of mortality globally over the last few decades. In cancer treatment, the selective targeting of tumor cells is indispensable, making it a better replacement for conventional chemotherapies by diminishing their adverse side effects. While designing a drug to be delivered selectively in the target organ, the drug development scientists should focus on various factors such as the type of cancer they are dealing with according to which drug, targeting moieties, and pharmaceutical carriers should be targeted. All published articles have been collecte

Усовершенствованные методы МРТ: диагностика и последующая деятельность в связи с множественным склерозом

Снимки мозга и спинного мозга играют ключевую роль в оказании помощи врачам в диагностике и мониторинге множественных склерозов. Тем не менее значение магнитного резонансного изображения в MS выходит за рамки его клинической полезности. Усовершенствованные методы визуализации способствовали обнаружению в vivo различных компонентов MS патогенеза, и в последние годы для оценки реакции пациентов с повторной эмиссией MS на имеющиеся методы лечения использовались биомаркеры MRI. Аналогичным образом, показатели МРТ, характеризующие нейродегенерацию, демонстрируют потенциал в качестве первичных и вто

Uncommon Factors Leading to Nephrotic Syndrome.

Nephrotic syndrome (NS) is characterized by proteinuria, hypoalbuminemia, edema, and hyperlipidemia. Apart from the traditional causes of NS, such as minimal change disease, focal segmental glomerulosclerosis, diabetes, infections, malignancies, autoimmune conditions, and nephrotoxic agents, there are also rare causes of NS, whose knowledge is of the utmost importance. The aim of this article was to highlight the less well-known causes that have a significant impact on diagnosis and treatment. Genetic syndromes such as Schimke immuno-osseous dysplasia, familial lecithin-cholesterol acyltransfe

Omega-3 Fatty Acids and Cancer Cell Cytotoxicity: Implications for Multi-Targeted Cancer Therapy.

Cancer is a major disease worldwide. Despite progress in cancer therapy, conventional cytotoxic therapies lead to unsatisfactory long-term survival, mainly related to development of drug resistance by tumor cells and toxicity towards normal cells. n-3 polyunsaturated fatty acids (PUFAs), eicosapentaenoic acid (EPA) and docosahexaenoic acid (DHA), can exert anti-neoplastic activity by inducing apoptotic cell death in human cancer cells either alone or in combination with conventional therapies. Indeed, n-3 PUFAs potentially increase the sensitivity of tumor cells to conventional therapies, poss

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… Disruption of any of these processes causes ER stress and activates the unfolded protein response (UPR). However, following prolonged ER stress, imbalanced calcium storage will activate calpain, which can inactivate Bcl-Xl and also activate the executioner caspases, leading to apoptosis. …

Biologics for bone regeneration: advances in cell, protein, gene, and mRNA therapies.

Bone fractures represent a significant global healthcare burden. Although fractures typically heal on their own, some fail to regenerate properly, leading to nonunion, a condition that causes prolonged disability, morbidity, and mortality. The challenge of treating nonunion fractures is further complicated in patients with underlying bone disorders where systemic and local factors impair bone healing. Traditional treatment approaches, including autografts, allografts, xenografts, and synthetic biomaterials, face limitations such as donor site pain, immune rejection, and insufficient mechanical

Relapsed/Refractory Multiple Myeloma: A Review of Available Therapies and Clinical Scenarios Encountered in Myeloma Relapse.

Multiple myeloma remains an incurable disease with the usual disease course requiring induction therapy, autologous stem cell transplantation for eligible patients, and long-term maintenance. Risk stratification tools and cytogenetic alterations help inform individualized therapeutic choices for patients in hopes of achieving long-term remissions with preserved quality of life. Unfortunately, relapses occur at different stages of the course of the disease owing to the biological heterogeneity of the disease. Addressing relapse can be complex and challenging as there are both therapy- and patie

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… This accumulation yields an apoptotic response via endoplasmic reticulum stress termed the terminal unfolded protein response [ 32 , 33 ]. 2.3. …

Molecular and cellular mechanisms of aging in hematopoietic stem cells and their niches.

Aging drives the genetic and epigenetic changes that result in a decline in hematopoietic stem cell (HSC) functioning. Such changes lead to aging-related hematopoietic/immune impairments and hematopoietic disorders. Understanding how such changes are initiated and how they progress will help in the development of medications that could improve the quality life for the elderly and to treat and possibly prevent aging-related hematopoietic diseases. Here, we review the most recent advances in research into HSC aging and discuss the role of HSC-intrinsic events, as well as those that relate to the

Targeting neuroinflammation: 3-monothiopomalidomide a new drug candidate to mitigate traumatic brain injury and neurodegeneration.

BACKGROUND: Traumatic Brain Injury (TBI) is a major risk factor for neurodegenerative disorders such as Parkinson's disease (PD) and Alzheimer's disease (AD), with neuroinflammation playing a critical role in the secondary cell death that exacerbates the initial injury. While targeting neuroinflammation holds significant therapeutic promise, clinical trials of available anti-inflammatory agents have fallen short. 3-Mono-thiopomalidomide (3-MP), a novel immunomodulatory imide drug (IMiD), was designed to curb inflammation without the adverse effects of traditional IMiDs and was evaluated across

Revolutionizing in vivo therapy with CRISPR/Cas genome editing: breakthroughs, opportunities and challenges.

Genome editing using the CRISPR/Cas system has revolutionized the field of genetic engineering, offering unprecedented opportunities for therapeutic applications in vivo. Despite the numerous ongoing clinical trials focusing on ex vivo genome editing, recent studies emphasize the therapeutic promise of in vivo gene editing using CRISPR/Cas technology. However, it is worth noting that the complete attainment of the inherent capabilities of in vivo therapy in humans is yet to be accomplished. Before the full realization of in vivo therapeutic potential, it is crucial to achieve enhanced specific

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… The study revealed that deletion of genes involved in multiple diverse pathways, including NF-κB signaling, antigen presentation, and the unfolded protein response, sensitized melanoma tumors to immunotherapy. …

Evolution of Molecular Targeted Cancer Therapy: Mechanisms of Drug Resistance and Novel Opportunities Identified by CRISPR-Cas9 Screening.

Molecular targeted therapy has revolutionized the landscape of cancer treatment due to better therapeutic responses and less systemic toxicity. However, therapeutic resistance is a major challenge in clinical settings that hinders continuous clinical benefits for cancer patients. In this regard, unraveling the mechanisms of drug resistance may identify new druggable genetic alterations for molecularly targeted therapies, thus contributing to improved therapeutic efficacies. The recent rapid development of novel methodologies including CRISPR-Cas9 screening technology and patient-derived models

Bortezomib-induced peripheral neuropathy: from molecular mechanisms to clinical management.

Bortezomib (BTZ) is a first-generation proteasome inhibitor that has shown significant efficacy in the treatment of multiple myeloma (MM), providing significant therapeutic benefits without severely compromising overall patient health. However, one of the most common and debilitating side effects associated with BTZ therapy is bortezomib-induced peripheral neuropathy (BIPN). This condition is the leading complication observed in patients undergoing BTZ treatment and has a profound impact on treatment regimens, often necessitating dose reductions or alterations in the dosing schedule. Despite t

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… Endoplasmic reticulum (ER) stress Defects in ER-associated degradation, unfolded protein responses, and ER stress have been implicated in various myelin disorders ( Volpi et al., 2016 ). Schwann cells (SCs) in the BIPN mouse model have been shown to exhibit acute and transient ER damage. …

Immunotherapy in chronic lymphocytic leukemia: advances and challenges.

Chronic lymphocytic leukemia (CLL) is characterized as a clonal proliferation of mature B lymphocytes with distinct immunophenotypic traits, predominantly affecting the middle-aged and elderly population. This condition is marked by an accumulation of lymphocytes within the peripheral blood, bone marrow, spleen, and lymph nodes. The associated immune dysregulation predisposes CLL patients to a higher risk of secondary malignancies and infections, which significantly contribute to morbidity and mortality rates. The advent of immunotherapy has revolutionized the prognosis of CLL, advancing treat

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… Proteasome inhibitors induce a terminal unfolded protein response in multiple myeloma cells. Blood. 2006;107:4907–16. 46. Ng AP, Worth L, Chen L, Seymour JF, Prince HM, Slavin M, et al. …

FDA-Approved Drugs for Hematological Malignancies-The Last Decade Review.

Hematological malignancies, also referred to as blood cancers, are a group of diseases involving abnormal cell growth and persisting in the blood, lymph nodes, or bone marrow. The development of new targeted therapies including small molecule inhibitors, monoclonal antibodies, bispecific T cell engagers, antibody-drug conjugates, recombinant immunotoxins, and, finally, Chimeric Antigen Receptor T (CAR-T) cells has improved the clinical outcomes for blood cancers. In this review, we summarized 52 drugs that were divided into small molecule and macromolecule agents, approved by the Food and Drug