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New genomic and proteomic biomarker discovery in cancer: revolutionizing diagnosis and prognostication.

Cancer remains a major global health challenge, with substantial morbidity and mortality worldwide. Advances in genomic and proteomic biomarker discovery have transformed cancer diagnosis, prognosis, and treatment selection. The evolution from early serological markers such as carcinoembryonic antigen (CEA) and prostate-specific antigen (PSA) to modern multi-omics approaches enabled by next-generation sequencing (NGS), mass spectrometry (MS), and advanced bioinformatics has revolutionized personalized medicine and targeted therapy, leading to improved outcomes. This review highlights the histo

Artificial Intelligence and Machine Learning Technology Driven Modern Drug Discovery and Development.

The discovery and advances of medicines may be considered as the ultimate relevant translational science effort that adds to human invulnerability and happiness. But advancing a fresh medication is a quite convoluted, costly, and protracted operation, normally costing USD ~2.6 billion and consuming a mean time span of 12 years. Methods to cut back expenditure and hasten new drug discovery have prompted an arduous and compelling brainstorming exercise in the pharmaceutical industry. The engagement of Artificial Intelligence (AI), including the deep-learning (DL) component in particular, has bee

Adult-Onset Hyperammonemia: Case Report and Review of Literature.

INTRODUCTION: Hyperammonemia is a life-threatening condition most associated with liver disease, though non-cirrhotic causes are increasingly recognized. CASE PRESENTATION: We report an 18-year-old female presenting with 1 week of progressive confusion, abdominal pain, and nausea. Initial evaluation showed normal routine laboratories but markedly elevated ammonia and respiratory alkalosis. She rapidly deteriorated, requiring intubation and intensive care. Ammonia peaked at 795 µg/dL and improved rapidly after urgent venous hemofiltration and medical therapy, with full neurological recovery by

Leveraging the bacteria for enhanced cancer immunotherapy: from a perspective of synthetic biology.

In recent years, synthetic biology has been widely applied to engineer and program cellular behaviors. Using this approach, bacteria can be designed to express immunotherapeutic agents, improve tumor targeting, and deliver therapeutic payloads directly to tumor sites. To further improve efficacy, strategies such as hypoxia-responsive promoters, bacterial swarming, and extracellular vesicles (EVs) have been investigated, along with the synergistic effects of combining bacterial therapy with other treatments (e.g., photodynamic therapy, chemotherapy, immune checkpoint inhibitors). This review su

Triple MAPK inhibition salvaged a relapsed post-BCMA CAR-T cell therapy multiple myeloma patient with a BRAF V600E subclonal mutation.

BACKGROUND: Multiple Myeloma (MM) is a progressive plasma cell neoplasm characterized by heterogeneous clonal expansion. Despite promising response rates achieved with anti-BCMA CAR-T cell therapy, patients may still relapse and there are currently no clear therapeutic options in post-CAR-T settings. In this report, we present a case of a post-BCMA CAR-T relapsed/refractory (RR) MM patient with skin extramedullary disease (EMD) in which a novel MAPK inhibition combinatorial strategy was implemented based on next-generation sequencing and in vitro experiments. CASE PRESENTATION: A 61-year-old

Следующие биомаркеры в нескольких миеломах: расширение диагностики, стратификация рисков и достоверная терапия за пределами нынешних руководящих принципов.

Множественная миелома (ММ) — онкогематологическая неоплазма, характеризующаяся аномальным распространением неопластических плазменных клеток в костном мозге и чрезмерным сечением моноклонных антител в кровоток. Примерно 3 в адрес 5% :: пациенты, имеющие разновидность болезни, в которой нет секреции моноклонных белков, характеризующие несекретарскую картину MM. Она имеет весьма сложную и разнородную генетическую сигнатуру, позволяющую классифицировать болезнь в предмалярные организмы и симптомные формы. В этом контексте был проведен комплексный обзор описательной части, охватывающий геномные, э

Совпадение в полном тексте источника
… Liquid Biopsy by Analysis of Circulating Myeloma Cells and Cell-Free Nucleic Acids: A Novel Noninvasive Approach of Disease Evaluation in Multiple Myeloma. Biomark. Res. 2023;11:27. doi: 10.1186/s40364-023-00469-6. 10. …

BCL-2 and BCL-xL in Cancer: Regulation, Function, and Therapeutic Targeting.

The BCL-2 family of proteins plays a central role in the regulation of apoptosis, with BCL-2 and BCL-xL representing two of its most prominent antiapoptotic members. This review explores the molecular regulation of BCL-2 and BCL-xL genes, emphasizing the structural domains that define the functions of the broader BCL-2 family. Beyond their canonical roles in preventing mitochondrial outer membrane permeabilization, both proteins contribute significantly to cancer development. Their overexpression enhances invasiveness and tumor progression, supports angiogenesis, and critically modulates cellu

Окисляющий стресс и воспаление в патогенезе неврологических расстройств: механизмы и последствия.

Нейрозащита — это активный подход к защите нервной системы, включая мозг, спинной мозг и периферийные нервы, путем предотвращения или ограничения повреждения нервных клеток и других компонентов. Она защищает центральную нервную систему от повреждений от острых и прогрессивных нейродегенеративных расстройств. Окисляющий стресс, дисбаланс между естественными механизмами защиты тела и образованием реактивных видов кислорода, имеет решающее значение для развития неврологических расстройств. Из-за высокой скорости метаболизма и потребления кислорода мозг особенно уязвим к окисляющему стрессу. Чрезм

Babesia microti-induced fulminant sepsis in an immunocompromised host: A case report and the case-specific literature review.

Babesia microti is an obligate intra-erythrocytic parasite transmitted by infected ticks. B. microti is a eukaryote much larger than prokaryotic microbes and more similar to human hosts in their biochemistry and metabolism. Moreover, Babesia spp. possess various immune evasion mechanisms leading to persistent and sometimes life-threatening diseases in immunocompromised hosts. Chronic lymphocytic leukemia (CLL) is the most prevalent adult B-cell malignancy, and a small percentage of CLL transforms into aggressive lymphomas. CLL also causes immune dysfunction due to the over-expansion of immatur

Molecular Mechanisms of Bortezomib Action: Novel Evidence for the miRNA-mRNA Interaction Involvement.

Bortezomib is an anti-tumor agent, which inhibits 26S proteasome degrading ubiquitinated proteins. While apoptotic transcription-associated activation in response to bortezomib has been suggested, mechanisms related to its influence on post-transcriptional gene silencing mediated regulation by non-coding RNAs remain not fully elucidated. In the present study, we examined changes in global gene and miRNA expression and analyzed the identified miRNA-mRNA interactions after bortezomib exposure in human neuroblastoma cells to define pathways affected by this agent in this type of cells. Cell viabi

Poly(ethylene glycol)-Prodrug Conjugates: Concept, Design, and Applications.

Poly(ethylene glycol) (PEG) is the most widely used polymer in delivering anticancer drugs clinically. PEGylation (i.e., the covalent attachment of PEG) of peptides proteins, drugs, and bioactives is known to enhance the aqueous solubility of hydrophobic drugs, prolong circulation time, minimize nonspecific uptake, and achieve specific tumor targetability through the enhanced permeability and retention effect. Numerous PEG-based therapeutics have been developed, and several have received market approval. A vast amount of clinical experience has been gained which has helped to design PEG prodru

Targeting Histone Deacetylases: Opportunities for Cancer Treatment and Chemoprevention.

The dysregulation of gene expression is a critical event involved in all steps of tumorigenesis. Aberrant histone and non-histone acetylation modifications of gene expression due to the abnormal activation of histone deacetylases (HDAC) have been reported in hematologic and solid types of cancer. In this sense, the cancer-associated epigenetic alterations are promising targets for anticancer therapy and chemoprevention. HDAC inhibitors (HDACi) induce histone hyperacetylation within target proteins, altering cell cycle and proliferation, cell differentiation, and the regulation of cell death pr

The PATHFINDER Study: Assessment of the Implementation of an Investigational Multi-Cancer Early Detection Test into Clinical Practice.

To examine the extent of the evaluation required to achieve diagnostic resolution and the test performance characteristics of a targeted methylation cell-free DNA (cfDNA)-based multi-cancer early detection (MCED) test, ~6200 participants ≥50 years with (cohort A) or without (cohort B) ≥1 of 3 additional specific cancer risk factors will be enrolled in PATHFINDER (NCT04241796), a prospective, longitudinal, interventional, multi-center study. Plasma cfDNA from blood samples will be analyzed to detect abnormally methylated DNA associated with cancer (i.e., cancer "signal") and a cancer signal ori

Krill oil extract suppresses the proliferation of colorectal cancer cells through activation of caspase 3/9.

BackgroundCurrently available treatments for colorectal cancer (CRC) associate with numerous side-effects that reduce patients' quality of life. The effective nutraceuticals with high anti-proliferative efficacy and low side-effects are desirable. Our previous study has reported that free fatty acids extract (FFAE) of krill oil induced apoptosis of CRC cells, possibly associated with changes in mitochondrial membrane potential (MMP). The aims of this study were to compare the anti-proliferative efficacy of FFAE from krill oil on CRC cells with commonly used chemotherapeutic drug, Oxaliplatin,

Modulation of miR-204 and miR-375 Expression by Flavonoid Chrysin Treatment During Melphalan-Induced Histopathological Damage in Adult Rat Skin and Hair Tissue.

Chemotherapy-induced skin and hair follicle damage, driven in part by miRNAs such as miR-204 and miR-375 that regulate apoptosis and autophagy after alkylating agent exposure, significantly impacts patient quality of life. While chrysin-a common food-derived flavonoid and nutritional bioactive with antioxidant and cytoprotective properties-has shown potential to modulate miRNA activity, its role in melphalan-induced injury and associated miRNA expression remains unclear. This study investigated the effects of melphalan on skin and hair follicle integrity in rats, focusing on miR-204 and miR-37

Micronutrient Status and Breast Cancer: A Narrative Review.

Breast cancer is one of the most common cancers worldwide, at the same time being one of the most prevalent causes of women's death. Many factors such as alcohol, weight fluctuations, or hormonal replacement therapy can potentially contribute to breast cancer development and progression. Another important factor in breast cancer onset includes micronutrient status. In this narrative review, we analyzed 23 micronutrients and their possible influence on breast cancer onset and progression. Further, the aim of this study was to investigate the impact of micronutrient status on the prevention of b

JunB is a key regulator of multiple myeloma bone marrow angiogenesis.

Bone marrow (BM) angiogenesis significantly influences disease progression in multiple myeloma (MM) patients and correlates with adverse prognosis. The present study shows a statistically significant correlation of the AP-1 family member JunB with VEGF, VEGFB, and IGF1 expression levels in MM. In contrast to the angiogenic master regulator Hif-1α, JunB protein levels were independent of hypoxia. Results in tumor-cell models that allow the induction of JunB knockdown or JunB activation, respectively, corroborated the functional role of JunB in the production and secretion of these angiogenic fa

A dual-mechanism model of Selinexor in DLBCL: p53 reactivation and metabolic reprogramming.

BACKGROUND: Diffuse large B-cell lymphoma (DLBCL) is an aggressive malignancy with limited therapeutic options in the relapsed or refractory setting. Selinexor, a selective inhibitor of nuclear export targeting XPO1, has demonstrated clinical activity in DLBCL. However, the molecular mechanisms underlying its antitumor effects remain incompletely defined. METHODS: We evaluated the clinical efficacy of Selinexor in a real-world cohort of lymphoma patients and performed integrative transcriptomic and proteomic analyses in DLBCL cell models representing germinal center B-cell–like (GCB) and non-G

Сопутствующая реанимация острого миелоида лейкемии, связанного с терапией, и ИгГ-МГС во время устного децитабина-седазуридина: доклад по делу.

Фон и клиническая значимость: связь между острой миэлоидной лейкемией (АМЛ) и моноклонной гаммопатией неопределенного значения (МГУС) является редкой и, вероятно, случайной из-за аналогичной эпидемиологии этих двух кровеносных расстройств у пожилых пациентов, которые не имеют права на интенсивную химиотерапию или агрессивное лечение, поскольку они могут быть чрезмерно миэлоспрессивными. Такие методы лечения включают в себя те, которые содержат венетоклакс, легкую для использования разнородную форму децитабина-цедазуридина (DEC-C), которая в настоящее время доступна и утверждена для целей борьб

Novel Insights into the Links between N6-Methyladenosine and Regulated Cell Death in Musculoskeletal Diseases.

Musculoskeletal diseases (MSDs), including osteoarthritis (OA), osteosarcoma (OS), multiple myeloma (MM), intervertebral disc degeneration (IDD), osteoporosis (OP), and rheumatoid arthritis (RA), present noteworthy obstacles associated with pain, disability, and impaired quality of life on a global scale. In recent years, it has become increasingly apparent that N6-methyladenosine (m6A) is a key regulator in the expression of genes in a multitude of biological processes. m6A is composed of 0.1-0.4% adenylate residues, especially at the beginning of 3'-UTR near the translation stop codon. The m