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The Role of NLRP3, a Star of Excellence in Myeloproliferative Neoplasms.

Nucleotide-binding domain (NOD)-like receptor protein 3 (NLRP3) is the most widely investigated inflammasome member whose overactivation can be a driver of several carcinomas. It is activated in response to different signals and plays an important role in metabolic disorders and inflammatory and autoimmune diseases. NLRP3 belongs to the pattern recognition receptors (PRRs) family, expressed in numerous immune cells, and it plays its primary function in myeloid cells. NLRP3 has a crucial role in myeloproliferative neoplasms (MPNs), considered to be the diseases best studied in the inflammasome

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… Endothelial JAK2V617F Expression Drives Inflammation and Cellular Senescence; New Evidence for the Roles of Endothelial Cells in MPN-Related Clotting Abnormalities? Blood. 2016;128:3134. doi: 10.1182/blood.V128.22.3134.3134. 23. Geyer H.L., Dueck A.C., Scherber R.M., Mesa R.A. …

Идентификация генотипов теплотерпимых томатов на основе комплексного фенотипного, биохимического, молекулярного анализа и анализа бипло ГПЭ.

Высокотемпературный стресс является одним из основных факторов, влияющих на продуктивность помидоров и качество фруктов во всем мире. Настоящее исследование направлено на выявление генотипов помидоров, терпимых к воздействию тепла, с использованием интегрированных морфологических, биохимических, молекулярных и ГПЭ (генотип плюс генотип по окружающей среде) биплоанализов в условиях контролируемого высокого температурного стресса ()40 ± 2 °C, день) по сравнению с оптимальными условиями (26 ± 2 °С, день). Thirty-five Проведена оценка генотипов томатов по садоводству, репродуктивному, биохимическо

Exploring the evolving role of apolipoproteins in oncology: global trends and emerging frontiers.

BackgroundMetabolic reprogramming, especially lipid metabolism, is crucial in cancer progression and treatment resistance. Apolipoproteins are crucial targets for research as they regulate autophagy, oxidative stress, and chemoresistance. A systematic bibliometric and bioinformatics approach is necessary to identify trends and elucidate the molecular mechanisms linking apolipoproteins to cancer.MethodsA systematic bibliometric analysis was conducted using the Web of Science Core Collection and PubMed. VOSviewer, CiteSpace, and the Bibliometrix R package were employed to analyze and visualize c

Tumor Microenvironment Onmyoji: Cytokines with Dual Protumor and Antitumor Roles.

Cytokines are essential components of the tumor microenvironment (TME) and play crucial roles in tumor initiation and progression. As key mediators of interactions between immune cells and tumor cells within the TME, many cytokines exhibit both protumor and antitumor properties. This complex duality, reminiscent of the balance philosophy pursued by "Onmyoji" in traditional Eastern philosophy, which involves observing and regulating opposing forces to achieve harmony, poses marked challenges in translating cytokine therapies from animal studies to clinical applications. More than 20 key cytokin

Innovation in Oncology Drug Development.

Significant progress has been made in our understanding of the molecular lesions responsible for tumor cells to exhibit uncontrolled growth while circumventing normal mechanisms of apoptosis and their ability to migrate and invade normal tissues while evading recognition and destruction by the immune system. This understanding has enabled the development of therapies specifically targeted to these lesions coupled to innovative treatment regimens to most effectively use these new targeted therapies with precision in selected subpopulations of patients. Innovation at the scientific and clinical

Immune Checkpoint Inhibitors and Immunomodulators for Cancer Immunotherapy: Insights Into Resistance and Therapeutic Strategies.

Cancer immunotherapy has redefined cancer treatment. However, the molecular and cellular basis of immune evasion and therapeutic resistance remains incompletely understood. Early immune checkpoint inhibitors have delivered significant clinical benefit, but their efficacy and durability remain limited in many patients. These limitations have driven the exploration of next-generation immune checkpoints and additional regulatory pathways that shape tumor-immune interactions. Recent advances have broadened the immune checkpoint landscape and revealed new targets. These targets operate within inter

The Role of Radiosensitizing Drugs in Osteosarcoma Treatment: Mechanisms and Clinical Perspectives.

Osteosarcoma is a highly malignant bone tumor that is resistant to radiotherapy and is associated with poor treatment outcomes and prognoses. Understanding the mechanisms of radioresistance and finding strategies to enhance the radiosensitivity is crucial for improving clinical efficacy. The aim of this review was to address the approaches for enhancing the efficacy of radiotherapy in osteosarcoma, thereby improving patient outcomes. Specifically, we have focused on the mechanisms of radiosensitization and the relationship between drugs that enhance radiosensitivity and cancer. These mechanism

Замена иммуноглобулина: Понятия управления несколькими миеломами.

Immunoglobulin (Ig) - заместительная терапия (IGRT) - состоит из применения низкодозированных поликлонных иг человека для лечения первичной и вторичной гипогаммаглобулинемии, которая связана с периодическими инфекциями и иммунной дисфункцией. ИГРТ восстанавливает физиологические уровни антител и вызывает иммуномумудуляторный эффект путем укрепления клеток иммунного эффекта, тем самым уменьшая инфекцию. Здесь мы описываем фармакологию различных составов иг с уделением особого внимания их механизму действий как низкодозированный ИГРТ, включая прямой антимикробный эффект и иммунодуляторную функци

Spatiotemperal Dynamics of Osteoarthritis: Преобразование значений от стенда до Бедсайда.

Остеоартрит (OA) представляет собой многогранное дегенеративное совместное расстройство, вызванное различными факторами риска, такими, как возраст, механический стресс, воспаление и метаболическое воздействие. Эти элементы способствуют его разнообразным фенотипам и эндотипам, что подчеркивает имманентную сложность болезни. Участие нескольких тканей и их взаимодействие еще больше осложняет расследование ОА. Нынешние ограничения в области технологий пространственного фенотификации в сочетании со сложной сетью многофакторных взаимодействий препятствуют обнаружению надежных ранних диагностических

Combating Methotrexate Resistance in Cancer Treatment: A Review on Navigating Pathways and Enhancing Its Efficacy With Fat-Soluble Vitamins.

Methotrexate (MTX), a potent analogue and antagonist of folic acid, is a first-line treatment for rheumatoid arthritis, IBD and cancer. The development of MTX resistance contributes to the reduced efficacy and development of adverse reactions, forcing clinicians to withdraw treatment early. This drawback requires combinational approaches to combat the resistance and enhance the efficacy and safety of MTX. To provide a brief overview of MTX resistance and strategies to mitigate its aftereffects in cancer therapy, a literature-based search was conducted using keywords such as cancer pathology, M

Neutropenic sepsis is associated with distinct clinical and biological characteristics: a cohort study of severe sepsis.

BackgroundImmunocompromised patients who develop sepsis while neutropenic are at high risk for morbidity and mortality; however, it is unknown if neutropenic sepsis is associated with distinct clinical and biological characteristics.MethodsWe conducted a prospective cohort study of patients admitted to the medical intensive care unit of an academic medical center with severe sepsis. Patients were followed for the development of acute respiratory distress syndrome (ARDS), acute kidney injury (AKI), and mortality. Plasma proteins, representing the host inflammatory response, anti-inflammatory re

Исцеление литических повреждений и восстановление костного здоровья в множестве миеломы посредством ингибиции склеростинов.

Множественная миелома (ММ) связана с изнурительным заболеванием костей, которое создает серьезные терапевтические проблемы. Болезнь костей MM характеризуется повышенной ресорбцией костей и подавлением остеобластов, что препятствует ремонту поврежденных костей. Склеростин, антагонист Wnt сигнализатора, выше у пациентов MM, и его ингибиция с нейтрализующим антителом (Scl-ab) была продемонстрирована для восстановления остеобластной функции в мышиных моделях MM. Однако остается неясным, может ли Scl-ab способствовать ремонту скелета, обеспечивать эффективный контроль над опухолью в сочетании с ант

Epigenetics-targeted drugs: current paradigms and future challenges.

Epigenetics governs a chromatin state regulatory system through five key mechanisms: DNA modification, histone modification, RNA modification, chromatin remodeling, and non-coding RNA regulation. These mechanisms and their associated enzymes convey genetic information independently of DNA base sequences, playing essential roles in organismal development and homeostasis. Conversely, disruptions in epigenetic landscapes critically influence the pathogenesis of various human diseases. This understanding has laid a robust theoretical groundwork for developing drugs that target epigenetics-modifyin

Field-Deployable Treatments For Leishmaniasis: Intrinsic Challenges, Recent Developments and Next Steps.

Leishmaniasis is a neglected tropical disease endemic primarily to low- and middle-income countries, for which there has been inadequate development of affordable, safe, and efficacious therapies. Clinical manifestations of leishmaniasis range from self-healing skin lesions to lethal visceral infection with chances of relapse. Although treatments are available, secondary effects limit their use outside the clinic and negatively impact the quality of life of patients in endemic areas. Other non-medicinal treatments, such as thermotherapies, are limited to use in patients with cutaneous leishman

Chemokines and their receptors in oral squamous cell carcinoma: mechanisms, clinical significance, and therapeutic implications.

Chemokines, a category of cytokines exhibiting chemotactic properties, have been thoroughly investigated as targets in cancer treatment in recent decades. In oral squamous cell carcinoma (OSCC), a prevalent and high-risk malignancy of the head and neck, chemokines interact with their specific receptors to initiate downstream signaling pathways. This signaling influences not only tumor cell proliferation, migration, invasion, and metastasis of oral cancer cells but also angiogenesis and vascular maturation. Furthermore, they modulate the tumor microenvironment (TME), which consists of diverse c

Case Report: longitudinal immunoglobulin abnormalities preceding IgA-λ MGUS and colonic DLBCL: a case suggesting immune-driven B-cell dysregulation.

Monoclonal gammopathy of undetermined significance (MGUS) is a common premalignant condition typically associated with progression to plasma cell disorders. Research suggests that MGUS may also coexist with or precede other lymphoid malignancies, potentially reflecting shared mechanisms involving chronic immune dysregulation. We report a 73-year-old man with more than 10 years of long-standing polyclonal immunoglobulin elevation, who subsequently developed IgA-λ MGUS and was later diagnosed with primary colonic diffuse large B-cell lymphoma (DLBCL). Molecular analysis identified mutations in T

Molecular Mechanism of Autophagy and Its Regulation by Cannabinoids in Cancer.

Autophagy is a "self-degradation" process whereby malfunctioned cytoplasmic constituents and protein aggregates are engulfed by a vesicle called the autophagosome, and subsequently degraded by the lysosome. Autophagy plays a crucial role in sustaining protein homeostasis and can be an alternative source of energy under detrimental circumstances. Studies have demonstrated a paradoxical function for autophagy in cancer, displaying both tumour suppressive and tumour promotive roles. In early phases of tumour development autophagy promotes cancer cell death. In later phases, autophagy enables canc

Herpes Zoster in Hematological Disorders: Pathogenesis, Risk Stratification, and Emerging Strategies for Prevention and Immunization.

BACKGROUND: Herpes zoster (HZ), resulting from reactivation of latent varicella-zoster virus (VZV), imposes a significant burden on immunocompromised patients, particularly those with hematological malignancies and recipients of hematopoietic stem cell transplants (HSCT). These populations face markedly increased risks of severe complications, including disseminated disease and postherpetic neuralgia. OBJECTIVE: This review examines the pathogenesis, epidemiology, risk factors, and evolving preventive strategies for HZ in patients with hematological disorders, with an emphasis on antiviral pr

Targeting BRD4: Potential therapeutic strategy for head and neck squamous cell carcinoma (Review).

As a member of BET (bromodomain and extra-terminal) protein family, BRD4 (bromodomain‑containing protein 4) is a chromatin‑associated protein that interacts with acetylated histones and actively recruits regulatory proteins, leading to the modulation of gene expression and chromatin remodeling. The cellular and epigenetic functions of BRD4 implicate normal development, fibrosis and inflammation. BRD4 has been suggested as a potential therapeutic target as it is often overexpressed and plays a critical role in regulating gene expression programs that drive tumor cell proliferation, survival, mi

The biogenesis and biological function of PIWI-interacting RNA in cancer.

Small non-coding RNAs (ncRNAs) are vital regulators of biological activities, and aberrant levels of small ncRNAs are commonly found in precancerous lesions and cancer. PIWI-interacting RNAs (piRNAs) are a novel type of small ncRNA initially discovered in germ cells that have a specific length (24-31 nucleotides), bind to PIWI proteins, and show 2'-O-methyl modification at the 3'-end. Numerous studies have revealed that piRNAs can play important roles in tumorigenesis via multiple biological regulatory mechanisms, including silencing transcriptional and posttranscriptional gene processes and a

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… A study showed that piR-39980 could induce neuroblastoma cellular senescence by changing the regulation of JAK3 expression through a route independent of classical apoptosis pathways [ 20 ]. … Banimohamad-Shotorbani B Kahroba H Sadeghzadeh H Wilson DM 3rd Maadi H Samadi N DNA damage repair response in mesenchymal stromal cells: From cellular senescence and aging to apoptosis and differentiation ability Ageing Res Rev 2020 62 101125 10.1016/j.arr.2020.101125 32683038 99. …