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5-Hydroxymethylcytosine modifications in circulating cell-free DNA: frontiers of cancer detection, monitoring, and prognostic evaluation.

Developing accurate, clinically convenient, and non-invasive methods for early cancer detection, monitoring, and prognosis assessment is essential for improving patient survival rates, enhancing quality of life, and reducing the socioeconomic burden associated with cancer. This goal is critical in precision oncology. Genetic and epigenetic alterations in circulating cell-free DNA (cfDNA) have emerged as transformative tools for advancing early cancer detection, monitoring, and improving patient outcomes. Among these, 5-hydroxymethylcytosine (5hmC) modifications in circulating cfDNA stand out a

High-throughput drug screening reveals Pyrvinium pamoate as effective candidate against pediatric MLL-rearranged acute myeloid leukemia.

Pediatric MLL-rearranged acute myeloid leukemia (AML) has a generally unfavorable outcome, primarily due to relapse and drug resistance. To overcome these difficulties, new therapeutic agents are urgently needed. Yet, implementing novel drugs for clinical use is a time-consuming, laborious, costly and high-risk process. Therefore, we applied a drug-repositioning strategy by screening drug libraries, comprised of >4000 compounds that are mostly FDA-approved, in a high-throughput format on primary MLL-rearranged AML cells. Here we identified pyrvinium pamoate (pyrvinium) as a novel candidate dru

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… Mycoplasma testing and DNA fingerprinting were regularly performed as quality control. …

Роль NLRP3 испарения в нейродегенеративных и метаболических заболеваниях и в соответствующих перспективных терапевтических вмешательствах.

Инфламасомы представляют собой внутриклеточные мультипротеиновые комплексы в цитоплазме, которые регулируют воспаление во врожденной иммунной системе в ответ на патогены и на прием самопроизводственных молекул. Последние достижения значительно улучшили наше понимание активации нуклеотидно-обязательного олигомеризации домена-подобный рецептору (NLR) семейный пирин, содержащий 3 (NLRP3) воспаление на молекулярном уровне. NLRP3 принадлежит подсемейству NLRP, которая активирует Caspase 1, что приводит к производству провоспалительных цитокинов (interleukin) 1β и интерлейкин 18) и пироптоз. Это вос

Epigenetic reprogramming in multiple myeloma-Challenges and opportunities.

In cancer, mutational processes act in concert with epigenetic reprogramming to endow malignant cells with hallmark properties that underpin tumorigenesis. Compared with the relatively rigid and slow processes of genetic evolution, the plastic nature of chromatin enables cells to adapt to a changing environment more rapidly. Multiple myeloma is characterised by high levels of inter- and intra-patient heterogeneity at both the genetic and epigenetic levels. Understanding the many layers of genetic and non-genetic evolution and their interplay is crucial to improve patient outcomes. In this shor

Интеграция нанотехнологий в онкологию для передовых стратегий наночастиц в целевую диагностику и лечение рака.

Рак остается одной из основных глобальных проблем в области здравоохранения. Обычная терапия часто ограничивается низкой избирательностью опухолей, системной токсичностью, резистентностью к многочисленным лекарствам и неоптимальными фармакокинетиками. Нанотехнология предлагает преобразующий подход в онкологии. Она позволяет осуществлять целенаправленные поставки наркотиков, контролировать или стимулировать их высвобождение и использовать многофункциональные платформы, сочетающие в себе терапию и диагностику. Нанопчасти повышают растворимость наркотиков, продлевают циркуляцию и повышают внутрик

The Relevance of Mass Spectrometry Analysis for Personalized Medicine through Its Successful Application in Cancer "Omics".

Mass spectrometry (MS) is an essential analytical technology on which the emerging omics domains; such as genomics; transcriptomics; proteomics and metabolomics; are based. This quantifiable technique allows for the identification of thousands of proteins from cell culture; bodily fluids or tissue using either global or targeted strategies; or detection of biologically active metabolites in ultra amounts. The routine performance of MS technology in the oncological field provides a better understanding of human diseases in terms of pathophysiology; prevention; diagnosis and treatment; as well a

Euchromatic Histone Lysine Methyltransferase 2 Inhibition Enhances Carfilzomib Sensitivity and Overcomes Drug Resistance in Multiple Myeloma Cell Lines.

Proteasome inhibitors (PIs) are extensively used for the therapy of multiple myeloma. However, patients continuously relapse or are intrinsically resistant to this class of drugs. In addition, adverse toxic effects such as peripheral neuropathy and cardiotoxicity could arise. Here, to identify compounds that can increase the efficacy of PIs, we performed a functional screening using a library of small-molecule inhibitors covering key signaling pathways. Among the best synthetic lethal interactions, the euchromatic histone-lysine N-methyltransferase 2 (EHMT2) inhibitor UNC0642 displayed a coope

The Gut Microbiota in Hematologic Malignancies: Mechanisms, Clinical Associations, and Translational Opportunities.

Hematologic malignancies arise and progress within a systemic ecosystem in which the gut microbiota is an increasingly recognized, partially modifiable component. Across acute leukemias, chronic lymphocytic leukemia, plasma cell disorders, lymphomas, and clonal myeloid neoplasms, human studies consistently report reduced microbial diversity, depletion of barrier-supportive, short-chain fatty acid-producing commensals, and enrichment of Gram-negative, pro-inflammatory, or hospital-adapted taxa. These alterations are associated with pre-leukemic clonal expansion, adverse genetic and immunologica

Design and Rationale of Prolonged Nightly Fasting for Multiple Myeloma Prevention (PROFAST): Protocol for a Randomized Controlled Pilot Trial.

BACKGROUND: Obesity is an established, modifiable risk factor of multiple myeloma (MM); yet, no lifestyle interventions are routinely recommended for patients with overweight or obesity with MM precursor conditions. Prolonged nightly fasting is a simple, practical dietary regimen supported by research, suggesting that the synchronization of feeding-fasting timing with sleep-wake cycles favorably affects metabolic pathways implicated in MM. We describe the design and rationale of a randomized controlled pilot trial evaluating the efficacy of a regular, prolonged nighttime fasting schedule among

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

Оценка уровней мальондиальдегида, окисляющего стресса и взаимодействия между хостингом и бактерией: Эшерития коли и Салмонелла Дерби.

Для изучения бактериальных процессов пероксидации липидов используются либо экстракты, либо суспензии без клеток, либо бактериальные суспензии. Наряду с газовой хроматографией - спектрометрией массы, жидкой хроматографией - спектрометрией массы, а также рядом других стратегий для определения малондиалдегида (МДА) и колориметрического обнаружения пероксидации липидов используется испытание тиобарбитуричной кислоты. Цель нынешнего исследования заключалась в оценке уровней процессов пероксидации липидов в суспензиях, экстрактах и культурных супернатантах штаммов Escherichia coli и Salmonella Дерб

Genetic and Functional Evidence of Complement Dysregulation in Multiple Myeloma Patients with Carfilzomib-Induced Thrombotic Microangiopathy Compared to Controls.

BACKGROUND: Carfilzomib, an irreversible proteasome inhibitor approved for the treatment of relapsed/refractory Multiple Myeloma (MM) has been associated with Thrombotic Microangiopathy (TMA). Several pathogenetic mechanisms of carfilzomib-induced TMA have been proposed; however, recently, there has been a shift of focus on the potential contribution of complement dysregulation. Our aim was to explore whether patients with carfilzomib-induced TMA harbor germline variants of complement-related genes, which have been characterized as risk factors for TMA. METHODS: We retrospectively recruited c

Lung Cancer: Spectral and Numerical Differentiation among Benign and Malignant Pleural Effusions Based on the Surface-Enhanced Raman Spectroscopy.

We present here that the surface-enhanced Raman spectroscopy (SERS) technique in conjunction with the partial least squares analysis is as a potential tool for the differentiation of pleural effusion in the course of the cancerous disease and a tool for faster diagnosis of lung cancer. Pleural effusion occurs mainly in cancer patients due to the spread of the tumor, usually caused by lung cancer. Furthermore, it can also be initiated by non-neoplastic diseases, such as chronic inflammatory infection (the most common reason for histopathological examination of the exudate). The correlation betw

Инсило-исследования для понимания взаимодействий флавонового ингибитора с nsp12-РНК-зависимой РНК-полимеразой SARS-CoV-2 и его гомологами.

Цель. ВИРУС COVID-19 продолжает быть важной проблемой здравоохранения. РНК-зависимый РНК-полимераза (RdRp) SARS-CoV-2, которая критична для репликации, поэтому является потенциальным объектом для лекарственной терапии. Методология. На основе экспериментальных структур RdRp от SARS-CoV-2 были сгенерированы вычислительные модели его гомологов от SARS-CoV-1, MERS и летучих мышей. SARS-CoV-2 RdRp был использован для виртуального скрининга в нуклеотидном связывающем сайте с молекулами из базы данных COCONUT Natural Products с помощью Glide. Комплексы с верхней ингибиторной молекулой были смоделиров

A Comparative Oncology Drug Discovery Pipeline to Identify and Validate New Treatments for Osteosarcoma.

BackgroundOsteosarcoma is a rare but aggressive bone cancer that occurs primarily in children. Like other rare cancers, treatment advances for osteosarcoma have stagnated, with little improvement in survival for the past several decades. Developing new treatments has been hampered by extensive genomic heterogeneity and limited access to patient samples to study the biology of this complex disease.MethodsTo overcome these barriers, we combined the power of comparative oncology with patient-derived models of cancer and high-throughput chemical screens in a cross-species drug discovery pipeline.R

Oncogenic Roles and Inhibitors of DNMT1, DNMT3A, and DNMT3B in Acute Myeloid Leukaemia.

Epigenetic alteration has been proposed to give rise to numerous classic hallmarks of cancer. Impaired DNA methylation plays a central role in the onset and progression of several types of malignancies, and DNA methylation is mediated by DNA methyltransferases (DNMTs) consisting of DNMT1, DNMT3A, and DNMT3B. DNMTs are frequently implicated in the pathogenesis and aggressiveness of acute myeloid leukaemia (AML) patients. In this review, we describe and discuss the oncogenic roles of DNMT1, DNMT3A, and DNMT3B in AML. The clinical response predictive roles of DNMTs in clinical trials utilising hy

Transplantation Tolerance through Hematopoietic Chimerism: Progress and Challenges for Clinical Translation.

The perception that transplantation of hematopoietic stem cells can confer tolerance to any tissue or organ from the same donor is widely accepted but it has not yet become a treatment option in clinical routine. The reasons for this are multifaceted but can generally be classified into safety and efficacy concerns that also became evident from the results of the first clinical pilot trials. In comparison to standard immunosuppressive therapies, the infection risk associated with the cytotoxic pre-conditioning necessary to allow allogeneic bone marrow engraftment and the risk of developing gra

Clinical antitumor application and pharmacological mechanisms of Dahuang Zhechong Pill.

Cancer still has elevated morbidity and mortality, which undoubtedly impacts the life quality of affected individuals. Remarkable advances have been made in cancer therapy, although the toxicities of traditional therapies remain an obvious challenge. Dahuang Zhechong Pill (DHZCP), developed by Zhongjing Zhang in the Synopsis of the Golden Chamber, represents an effective anticancer traditional Chinese medicine (TCM). In this review, it was found that DHZCP is therapeutically utilized in liver, lung, gastric, pancreatic and other cancers in clinic. Pharmacological evidence showed that its anti-

Macrophage Activation Markers, CD163 and CD206, in Acute-on-Chronic Liver Failure.

Macrophages facilitate essential homeostatic functions e.g., endocytosis, phagocytosis, and signaling during inflammation, and express a variety of scavenger receptors including CD163 and CD206, which are upregulated in response to inflammation. In healthy individuals, soluble forms of CD163 and CD206 are constitutively shed from macrophages, however, during inflammation pathogen- and damage-associated stimuli induce this shedding. Activation of resident liver macrophages viz. Kupffer cells is part of the inflammatory cascade occurring in acute and chronic liver diseases. We here review the ex

Преобразование фотоэнергетики в наноматериалах для точной терапостики.

Быстро развивающаяся область тераностистики направлена на интеграцию терапевтических и диагностических функций в единую платформу для точной медицины, позволяющую одновременно лечить и контролировать болезни. Наноматериалы, основанные на преобразовании фотоэнергии, стали разносторонней платформой, использующей уникальные свойства света для активации тераностистики с высокой пространственной и временной точностью. В настоящем обзоре содержится всеобъемлющий обзор последних изменений в области преобразования фотоэнергетики с использованием наноматериалов с уделением особого внимания их применени