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Exosomes for angiogenesis induction in ischemic disorders.

Ischaemic disorders are leading causes of morbidity and mortality worldwide. While the current therapeutic approaches have improved life expectancy and quality of life, they are unable to "cure" ischemic diseases and instate regeneration of damaged tissues. Exosomes are a class of extracellular vesicles with an average size of 100-150 nm, secreted by many cell types and considered a potent factor of cells for paracrine effects. Since exosomes contain multiple bioactive components such as growth factors, molecular intermediates of different intracellular pathways, microRNAs and nucleic acids, t

Juvenile-onset Systemic Lupus Erythematosus: Recent Advances in Pathogenesis and Treatment.

PURPOSE OF REVIEW: This review summarizes recent advances in understanding the pathogenesis and therapeutic landscape of juvenile-onset systemic lupus erythematosus (jSLE), with a focus on how emerging genetic and immunologic insights inform patient stratification, targeted treatments, and Treat-to-Target (T2T) approaches in pediatric care. RECENT FINDINGS: Studies of (ultra-)rare gene variants (e.g., affecting TLR7, UNC93B1, PLD4, PTPN2, BACH2) aided in understanding key pathogenic pathways, and allowed linking these to associated clinical phenotypes. Multi-ancestral genomic studies and cumu

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… PBMCs analyses did not reveal pathological type I IFN signature. [ 17 ] ADAR encodes for adenosine deaminases that edit double-stranded RNA by converting adenosine to inosine, thereby regulating RNA stability, splicing, and innate immune responses. … Family history included malformation syndromes and unexplained early deaths. | PBMCs analyses did not reveal pathological type I IFN signature. | [ 17 ] | ADAR encodes for adenosine deaminases that edit double-stranded RNA by converting adenosine to inosine, thereby regulating RNA stability, splicing …

How histone modifications influence cellular radiosensitivity: Pharmaceutically targeting epigenetic regulators as a promising avenue to overcome radioresistance.

Cancer remains the leading cause of mortality worldwide. Radiotherapy (RT), a cornerstone of oncological treatment for over a century, has achieved great success in various cancers. However, radioresistance remains the primary factor leading to the failure of radiotherapy. Histone modifications in cancer cells are known to play a pivotal role in regulating radiosensitivity by modulating chromatin structure, either by loosening or tightening it. Here, we provide a comprehensive summary of the link between aberrant histone modifications and radiation resistance across various cancer and normal t

A New Generation of Vaccines in the Age of Immunotherapy.

Purpose of reviewCancer vaccines are one of the most extensively studied immunotherapy type in solid tumors. Despite favorable presuppositions, so far, the use of cancer vaccines has been associated with disappointing results. However, a new generation of vaccines has been developed, promising to revolutionize the immunotherapy field.Recent findingsIn this review, we aim to highlight the advances in cancer vaccines and the remaining hurdles to overcome. Cancer vaccination has experienced tremendous progress in the last decade, with myriad promising developments. Future efforts should focus on

Osteoporosis: Current and Emerging Therapies Targeted to Immunological Checkpoints.

Osteoporosis is a skeletal pathology characterized by compromised bone strength leading to increased risk of fracture, mainly the spine and hip fractures. Osteoporosis affects more than 200 million people worldwide and because of the skeletal fractures it causes, represents a major cause of morbidity, disability and mortality in older people. Recently, the new discoveries of osteoimmunology have clarified many of the pathogenetic mechanisms of osteoporosis, helping to identify new immunological targets for its treatment opening the way for new and effective therapies with biological drugs. Cur

Картирование молекулярных путей множественного склероза: генная приоритизация и сетевой анализ патологии белой материи.

ЦЕЛИ: Быстрое развитие транскриптомики стимулировало усилия по выявлению дерегулированных путей в многочисленных склерозовых (МС) тканях, хотя многие обнаруженные дифференциально выраженные гены, вероятно, являются ложными положительными, при этом лишь небольшая доля отражает фактические патологические явления. Для точного понимания молекулярных механизмов, лежащих в основе патологии MS, необходимы надежные, комплексные методы. Мы провели анализ приоритезации генов MS патологических исследований патологии белых материй. Статьи искали в Scopus и PubMed до июля 31, 2024. К числу потенциально при

NDP52 и его новая роль в патогенезе.

Автофагика - это процесс, способствующий выживанию, который регулирует деградацию и обновление клеточных компонентов, что делает его важнейшим механизмом для клеточного гомеостазиза. Существуют выборочные формы автофагии, характерные для ряда субстратов, таких, как патогены (бактерии или вирусы), белковые агрегаты или излишние/поврежденные органеллы. Эти процессы включают в себя в качестве ключевых игроков автофагичные рецепторы, которые связывают груз, подлежащий деградации, с автофагическим оборудованием. Среди них NDP52 (известный также как КАКПО2) был охарактеризован как «бридж» между авто

Синергический потенциал стволовых клеток костного мозга и miR181-a комбинированная терапия против множественных склерозов.

Множественный склероз (MS) — прогрессивное аутоиммунное заболевание, характеризующееся массовой воспламенительной инфильтрацией, демиелинацией и последующими повреждениями аксона и нейронными повреждениями в центральной нервной системе (КНС). Этиология MS остается неясной, и пока еще нет окончательного графика лечения этого заболевания. Месенхимальные стволовые клетки костного мозга (МСЦ), демонстрирующие функции нейроиммунной модуляции в целях смягчения различных аутоиммунных заболеваний, демонстрируют большой потенциал в лечении MS. Вместе с тем нестабильность иммуноусилительного воздействия

Venetoclax enhances DNA damage induced by XPO1 inhibitors: A novel mechanism underlying the synergistic antileukaemic effect in acute myeloid leukaemia.

Acute myeloid leukaemia (AML) is a highly heterogeneous haematologic malignancy with poor prognosis. We previously showed synergistic antileukaemic interaction between exportin 1 (XPO1) inhibitor KPT-330 (Selinexor) and Bcl-2 inhibitor venetoclax (ABT-199) in preclinical models of AML, which was partially meditated by Mcl-1, although the full mechanism of action remains unknown. In this study, using real-time RT-PCR and Western blot analysis, we show that inhibition of XPO1 via KPT-330 or KPT-8602 (Eltanexor) decreases the mRNA and protein levels of c-Myc, CHK1, WEE1, RAD51 and RRM2. KPT-330 a

Meibomian Gland Dysfunction Is Associated with Low Levels of Immunoglobulin Chains and Cystatin-SN.

Meibomian gland dysfunction (MGD) is a highly prevalent condition and the most common cause of evaporative dry eye disease. Studying the proteome of MGD can result in important advances in the management of the condition. Here, we collected tear film samples from treatment naïve patients with MGD (n = 10) and age-matched controls (n = 11) with Schirmer filtration paper. The samples were analyzed with label-free quantification nano liquid chromatography-tandem mass spectrometry. The proteins were considered differentially expressed if p < 0.05. A total of 88 proteins were significantly regulate

Alu-dependent RNA editing of GLI1 promotes malignant regeneration in multiple myeloma.

Despite novel therapies, relapse of multiple myeloma (MM) is virtually inevitable. Amplification of chromosome 1q, which harbors the inflammation-responsive RNA editase adenosine deaminase acting on RNA (ADAR)1 gene, occurs in 30-50% of MM patients and portends a poor prognosis. Since adenosine-to-inosine RNA editing has recently emerged as a driver of cancer progression, genomic amplification combined with inflammatory cytokine activation of ADAR1 could stimulate MM progression and therapeutic resistance. Here, we report that high ADAR1 RNA expression correlates with reduced patient survival

Tumor Biology Hides Novel Therapeutic Approaches to Diffuse Large B-Cell Lymphoma: A Narrative Review.

Diffuse large B-cell lymphoma (DLBCL) is a malignancy of immense biological and clinical heterogeneity. Based on the transcriptomic or genomic approach, several different classification schemes have evolved over the years to subdivide DLBCL into clinically (prognostically) relevant subsets, but each leaves unclassified samples. Herein, we outline the DLBCL tumor biology behind the actual and potential drug targets and address the challenges and drawbacks coupled with their (potential) use. Therapeutic modalities are discussed, including small-molecule inhibitors, naked antibodies, antibody-dru

Reactive oxygen species (ROS) in cancer: from mechanism to therapeutic implications.

Reactive oxygen species (ROS) act as critical secondary messengers in various intracellular signaling pathways that regulate cellular proliferation, differentiation, and survival under normal physiological conditions. However, dysregulation of redox signaling-driven by genetic mutations, epigenetic alterations, and posttranscriptional or posttranslational modifications-plays a central role in malignant transformation and cancer progression. Cancer cells typically exhibit elevated basal ROS levels due to increased metabolic activity, mitochondrial dysfunction, and oncogene activation. This mode

Cyclic Peptides in Modern Drug Discovery: Trends and Therapeutic Directions.

Peptide therapeutics are an important drug modality due to their high specificity, favorable safety, and expanding design potential. Among them, cyclic peptides occupy a space between small molecules and biologics, offering improved rigidity, stability, and target engagement. This report analyzes trends in cyclic peptide research using data from the CAS Content Collection over the past two decades. Results show a steady rise in academic publications and patents, reflecting growing interest across discovery and development. Notably, oral administration is gaining attention, indicating progress

Alternative Cancer Therapeutics: Unpatentable Compounds and Their Potential in Oncology.

Cancer remains a leading cause of death globally. Cancer patients often seek alternative therapies in addition to, or instead of, conventional treatments like chemotherapy, radiation, and surgery. The progress in medical advancements and early detection provides more treatment options; however, the development of cancer drugs requires a significant amount of time, demands substantial investments, and results in an overall low percent of regulatory approval. The complex relationship between patent protection and pharmaceutical innovation complicates cancer drug development and contributes to hi

Окисляющие молекулярные сигнатуры в неизлечимых заболеваниях: систематический обзор комплексных подходов к машинному обучению и системной биологии.

Окисляющий стресс является одним из основных факторов патогенеза иммунных заболеваний в результате его воздействия на клеточный метаболизм, митохондриальную функцию, иммунную сигнализацию и воспалительную травму тканей. Разрушение гомеостазиса способствует метаболическому перепрограммированию и постоянной активации врожденной и адаптивной иммунной реакции, что способствует прогрессированию заболеваний через многочисленные подстрекательские и аутоиммунные расстройства. Последние достижения в области высокопроизводительных молекулярных технологий привели к созданию крупномасштабных многомерных н

Molecular mechanisms of resveratrol as chemo and radiosensitizer in cancer.

One of the primary diseases that cause death worldwide is cancer. Cancer cells can be intrinsically resistant or acquire resistance to therapies and drugs used for cancer treatment through multiple mechanisms of action that favor cell survival and proliferation, becoming one of the leading causes of treatment failure against cancer. A promising strategy to overcome chemoresistance and radioresistance is the co-administration of anticancer agents and natural compounds with anticancer properties, such as the polyphenolic compound resveratrol (RSV). RSV has been reported to be able to sensitize c

Осколки периферальной крови, полученные в результате ТРНК, являются новыми неинвазивными биомаркерами для диагностики и прогнозируемой стратификации в множестве миеломы.

В последнее время в качестве критически важных регуляторов в области онкологической биологии появились небольшие РНК, полученные в результате передачи РНК; однако их профили экспрессии и клиническая значимость в нескольких миеломах (ММ) по-прежнему плохо определены. МЕТОДЫ: Секвенирование высокой производительности было проведено для всеобъемлющей характеристики профилей выражения ТСНК в периферийных моноядерных клетках крови (ПБМК) из 22 новые пациенты с диагнозом MM и 19 здоровый контроль. Общие целевые гены были предсказаны путем интеграции MiRanda и TookScan, и была создана сеть взаимодейс

Inhibition of Plk1 and Cyclin B1 expression results in panobinostat-induced G₂ delay and mitotic defects.

The development of clinically useful histone deacetylase inhibitors has expanded greatly. In a preclinical study, we showed that panobinostat (LBH589) inhibits cell cycle progression of human head and neck squamous cell carcinoma (HNSCC) cell lines at G₂/M and an associated decrease in expression of particular genes required for passage through G₂ and mitosis. In this study we sought to analyse the mechanistic underpinnings of panobinostat-induced growth arrest. HNSCC cell lines were synchronised and progression through mitosis monitored. We demonstrate that panobinostat causes a marked G₂ del

The Role of the Ubiquitin System in Eye Diseases.

The ubiquitin-proteasome system (UPS) is a fundamental process that regulates various biological functions, including immune response, cell cycle, oxidative stress, migration, and cellular proliferation. This system is responsible for the degradation of proteins, while proteasomes play a significant role in mechanisms involved in health and human diseases. The participation of the UPS in immune response is particularly relevant, leading to the involvement of immunoproteasomes. This specialized proteasome is involved in the processing and presentation of antigenic peptides, making it crucial fo