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Nucleic acid aptamers in orthopedic diseases: promising therapeutic agents for bone disorders.

Precision medicine has become a cornerstone in modern therapeutic strategies, with nucleic acid aptamers emerging as pivotal tools due to their unique properties. These oligonucleotide fragments, selected through the Systematic Evolution of Ligands by Exponential Enrichment process, exhibit high affinity and specificity toward their targets, such as DNA, RNA, proteins, and other biomolecules. Nucleic acid aptamers offer significant advantages over traditional therapeutic agents, including superior biological stability, minimal immunogenicity, and the capacity for universal chemical modificatio

Immune mediated inflammatory diseases: moving from targeted biologic therapy, stem cell therapy to targeted cell therapy.

Despite the advancements in targeted biologic therapy for immune-mediated inflammatory diseases (IMIDs), significant challenges persist, including challenges in drug maintenance, primary and secondary non-responses, and adverse effects. Recent data have strengthened the evidence supporting stem cell therapy as an experimental salvage therapy into a standard treatment option. Recent preclinical and clinical studies suggested that chimeric antigen receptor T cell (CAR-T) therapy, which depleting tissue and bone marrow B cells, may lead to improvement, even inducing long-lasting remissions for pa

Tumor heterogeneity as a driver of drug resistance and its implications for personalized therapy.

Tumors are highly dynamic diseases characterized by significant heterogeneity. They consist of multiple cellular populations with distinct properties that respond differently to therapeutic pressure. This heterogeneity may arise from spatial variation across tumor regions (spatial heterogeneity) as well as from temporal changes during tumor evolution and treatment (temporal heterogeneity). As a consequence, drug-resistant subclones often emerge under therapy and contribute to treatment failure. Advances in single-cell and spatial multi-omics technologies enable precise quantification of tumor

Immunological Targets in Generalized Myasthenia Gravis Treatment: Where Are We Going Now?

BackgroundGeneralized myasthenia gravis (gMG) is a heterogeneous autoimmune disorder marked by antibody-mediated disruption of neuromuscular transmission. Despite advancements in immunosuppressive therapies and biologics, a subset of patients remains refractory, necessitating more targeted and personalized treatment strategies.ObjectiveThis review aims to synthesize current knowledge of the immunopathological mechanisms across gMG subtypes and to explore emerging therapeutic targets tailored to these diverse disease phenotypes.MethodsA narrative review was conducted, integrating recent finding

Cytokine-Engineered Chimeric Antigen Receptor-T Cell Therapy: How to Balance the Efficacy and Toxicity.

Chimeric antigen receptor (CAR)-T cell immunotherapy has revolutionized the paradigm in hematological malignancies. However, its efficacy in treating solid tumors remains limited because the immunosuppressive tumor microenvironment (ITME) seriously blocks T cell activation, infiltration, and proliferation. Cytokines, driving potent assisted function by enhanced T cell expansion, persistence, and direct tumor cell killing, have long been acknowledged as promising candidates combined with CAR-T cells to improve treatment outcomes. Despite their preclinical success, significant toxicity occurs in

Identification of Potentially Pathogenic Variants Associated with Recurrence in Medication-Related Osteonecrosis of the Jaw (MRONJ) Patients Using Whole-Exome Sequencing.

Background: Bisphosphonates are antiresorptive and antiangiogenic drugs that prevent and treat bone loss and mineralization in women with postmenopausal osteoporosis and cancer patients. Medication-related osteonecrosis of the jaw (MRONJ) is commonly caused by tooth extraction and dental trauma. Although genetic and pathological studies about MRONJ have been conducted, the pathogenesis of MRONJ still remains unclear. Methods: We aimed to identify genetic variants associated with MRONJ, using whole-exome sequencing (WES). Ten MRONJ patients prescribed bisphosphonates were recruited for WES, and

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… In addition, three substitutions (A181T, L207F, and K231E) are located in the RNA recognition motifs (RRMs) of PABPC3 that bind the poly(A)tail of single-stranded RNAs ( Figure 4 A). …

Gene and cell therapy of human genetic diseases: Recent advances and future directions.

Disruptions in normal development and the emergence of health conditions often result from the malfunction of vital genes in the human body. Decades of scientific research have focused on techniques to modify or substitute defective genes with healthy alternatives, marking a new era in disease treatment, prevention and cure. Recent strides in science and technology have reshaped our understanding of disorders, medication development and treatment recommendations, with human gene and cell therapy at the forefront of this transformative shift. Its primary objective is the modification of genes o

Engineering Immunity: Current Progress and Future Directions of CAR-T Cell Therapy.

Chimeric antigen receptor (CAR)-T cell therapy has emerged as a transformative form of immunotherapy, enabling the precise engineering of T cells to recognize and eliminate pathogenic cells. In hematologic malignancies, CAR-T cells targeting CD19 or B cell maturation antigens have achieved remarkable remission rates and durable responses in patients with otherwise refractory disease. Despite these successes, extending CAR-T cell therapy to solid tumors remains challenging due to antigen heterogeneity, poor T cell infiltration, and the immunosuppressive tumor microenvironment (TME). Beyond onco

Polyphyllin I Inhibits the Metastasis of Cervical Cancer Through the Regulation of the β-Catenin Signaling Pathway.

Cervical cancer ranks as the fourth most prevalent cancer and cause of cancer-related mortality among women globally. It exhibits a recurrence/metastasis rate of approximately 30% and a dismal 5-year survival of only 17% in metastatic cases. Despite significant advancements in surgical techniques, chemoradiotherapy, and targeted therapies, effective treatment options for metastatic cervical cancer remain limited. This study explored Polyphyllin I (PPI), which is a monomeric compound derived from the Rhizoma of Paris Polyphyllin, as a potential inhibitor of cervical cancer metastasis. Mechanist

CRISPR/Cas9: A revolutionary genome editing tool for human cancers treatment.

Cancer is a genetic disease stemming from genetic and epigenetic mutations and is the second most common cause of death across the globe. Clustered regularly interspaced short palindromic repeats (CRISPR) is an emerging gene-editing tool, acting as a defense system in bacteria and archaea. CRISPR/Cas9 technology holds immense potential in cancer diagnosis and treatment and has been utilized to develop cancer disease models such as medulloblastoma and glioblastoma mice models. In diagnostics, CRISPR can be used to quickly and efficiently detect genes involved in various cancer development, prol

Checking NEKs: Overcoming a Bottleneck in Human Diseases.

In previous years, several kinases, such as phosphoinositide 3-kinase (PI3K), mammalian target of rapamycin (mTOR), and extracellular-signal-regulated kinase (ERK), have been linked to important human diseases, although some kinase families remain neglected in terms of research, hiding their relevance to therapeutic approaches. Here, a review regarding the NEK family is presented, shedding light on important information related to NEKs and human diseases. NEKs are a large group of homologous kinases with related functions and structures that participate in several cellular processes such as th

Multiple Facets of Autophagy and the Emerging Role of Alkylphosphocholines as Autophagy Modulators.

Autophagy is a highly conserved multistep process and functions as passage for degrading and recycling protein aggregates and defective organelles in eukaryotic cells. Based on the nature of these materials, their size and degradation rate, four types of autophagy have been described, i.e. chaperone mediated autophagy, microautophagy, macroautophagy, and selective autophagy. One of the major regulators of this process is mTOR, which inhibits the downstream pathway of autophagy following the activation of its complex 1 (mTORC1). Alkylphosphocholine (APC) derivatives represent a novel class of a

An Update in Drug-Induced Thrombotic Microangiopathy.

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In vitro расширила человека CD4+CD25+ регуляционные T клетки, подавляющие распространение Т клеток.

Регулирующие Т клетки (Tregs) оказались критически важными в балансе между автоиммунизацией и терпимостью и были связаны с несколькими аутоиммунными заболеваниями человека. Однако небольшое число трегов в периферии крови ограничивает их терапевтический потенциал. Поэтому мы разработали протокол, который позволит расширить "Трегз" при сохранении их подавляющей активности. Мы изолировали клетки CD4+CD25 hi от человеческой периферической крови и расширили их in vitro в присутствии anti-CD3 и anti-CD28 Магнитные кситы и высокие концентрации внешнего интерлейкина (IL) -2. Траги были эффективно расш

Harnessing the tumor microenvironment: targeted cancer therapies through modulation of epithelial-mesenchymal transition.

The tumor microenvironment (TME) is integral to cancer progression, impacting metastasis and treatment response. It consists of diverse cell types, extracellular matrix components, and signaling molecules that interact to promote tumor growth and therapeutic resistance. Elucidating the intricate interactions between cancer cells and the TME is crucial in understanding cancer progression and therapeutic challenges. A critical process induced by TME signaling is the epithelial-mesenchymal transition (EMT), wherein epithelial cells acquire mesenchymal traits, which enhance their motility and inva

Artificial intelligence in immunotherapy: revolutionizing diagnostic and therapeutic applications in cancer and autoimmune diseases.

Artificial intelligence (AI) is increasingly advancing precision immunotherapy by integrating high-dimensional biomedical data to support diagnosis, treatment selection, and longitudinal monitoring in both cancer and autoimmune diseases. This review summarizes AI applications in biomarker discovery, prediction of immune checkpoint inhibitor (ICI) response and toxicity, neoantigen prioritization, CAR-T cell optimization, and therapeutic antibody engineering. In oncology, multimodal models combining multi-omics, medical imaging, and clinical variables improve patient stratification and non-invas

Естественные и синтетические АМП из Латинской Америки по всему спектру технологий и приложений в области разнообразия.

Биоразнообразие в Латинской Америке примерно 60% в целом по миру, подпитывая научные исследования в области природных продуктов, весьма значимой области открытия наркотиков по сей день. Это сопровождается увеличением числа антимикробных пептидов (АМП), полученных из натуральных продуктов в регионе, которые за последнее десятилетие были переработаны путем модификации, усовершенствования и уточнения их физико-химических свойств и антимикробной эффективности с использованием подходов, которые варьируются от изучения рациональной конструкции и соотношения структуры-активности (САР) до методов иску

T Cell Based Immunotherapy for Cancer: Approaches and Strategies.

T cells are critical in destroying cancer cells by recognizing antigens presented by MHC molecules on cancer cells or antigen-presenting cells. Identifying and targeting cancer-specific or overexpressed self-antigens is essential for redirecting T cells against tumors, leading to tumor regression. This is achieved through the identification of mutated or overexpressed self-proteins in cancer cells, which guide the recognition of cancer cells by T-cell receptors. There are two main approaches to T cell-based immunotherapy: HLA-restricted and HLA-non-restricted Immunotherapy. Significant progres

HIV-1 matrix protein p17 misfolding forms toxic amyloidogenic assemblies that induce neurocognitive disorders.

Human immunodeficiency virus type-1 (HIV-1)-associated neurocognitive disorder (HAND) remains an important neurological manifestation that adversely affects a patient's quality of life. HIV-1 matrix protein p17 (p17) has been detected in autoptic brain tissue of HAND individuals who presented early with severe AIDS encephalopathy. We hypothesised that the ability of p17 to misfold may result in the generation of toxic assemblies in the brain and may be relevant for HAND pathogenesis. A multidisciplinary integrated approach has been applied to determine the ability of p17 to form soluble amyloi

Высокий уровень распространенности GALC Gene Options на взрослых с нейродегенеративными условиями.

ОКРУЖАЮЩАЯ СРЕДА И ЦЕЛЬ: Дефицит галактоцереброзидаза (ГАЛК) вызывает болезнь Краббе, тяжёлое лизосомальное нейродегенеративное состояние. Появляющиеся данные указывают на то, что гетерозиговые варианты GALC могут способствовать множеству склерозов, расстройству гиперактивности, отсутствию внимания, и синуклейнопатии. Мы намерены изучить потенциальную связь между гетероциговидными вариантами GALC и нейродегенеративными расстройствами, расширяя существующую литературу. МЕТОДЫ: Мы провели обследование 110 взрослых с симптомами, которые разделяются лизосомными расстройствами хранения (ЛСД) и расп