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Immune reprogramming in the bone marrow microenvironment: a new perspective on the bone immune microenvironment of postmenopausal osteoporosis.

Research on postmenopausal osteoporosis (PMOP), a common bone metabolic disease, has traditionally focused on bone loss and imbalance in bone remodeling. However, with the development of bone immunology, the complex interactions between immune cells and bone cells in the bone marrow microenvironment have gradually been revealed, and "immune reprogramming" is considered a key factor driving the persistent bone loss in PMOP. Current evidence indicates that the postmenopausal bone marrow microenvironment undergoes significant structural and functional changes. These changes are characterized by a

Emerging role of low-frequency somatic mutations in cancer relapse: from early detection to precision oncology.

Somatic mutations with low variant allele frequencies offer a highly sensitive lens for detecting cancer relapse driven by diverse causes, including clonal evolution and therapy resistance. Advances in next-generation sequencing have enabled robust subclonal variant identification that typically fall below conventional detection limits, supporting a comprehensive understanding of individual molecular profiles that can lead to relapse. These low-level alterations frequently emerge before clinical or radiological relapse and can inform response-adaptive treatment decisions. This review integrate

Потенциальная роль TNFRSF12A в установлении связи между глиобластомой и болезнью Альцгеймера через общие пути подавления опухолей.

Гены, подавляющие опухоль, являются критическими регуляторами клеточного гомеостаза и широко изучаются в области онкологической биологии. Однако их роль в нейродегенеративных заболеваниях, особенно в болезни Альцгеймера, остается слабой. Недавние данные об обратной связи между раком и АД указывают на существование общих молекулярных механизмов. Мы провели комплексный анализ для выявления ТГС, которые могут участвовать как в AD, так и в глиобластоме (GBM), с использованием менделийской случайности, транскриптомного профилирования (булка и одноклеточная RNA-seq), вывода в отношении связи между к

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… Epigenomics 10.2217/epi-2023-0373 (2023). 9. Hassin-Baer, S. et al. The leucine rich repeat kinase 2 (LRRK2) G2019S substitution mutation. Association with Parkinson disease, malignant melanoma and prevalence in ethnic groups in Israel. J. …

Механистические понимания и достижения биконкретной T-клетки, использующей антителную терапию в мультимиеломе.

Множественная миелома (ММ) — клональная порча неизмеримо дифференцированных плазменных клеток, характеризующаяся инфильтрацией костного мозга и чрезмерным производством моноклонных иммуноглобулинов, что приводит к повреждению конечной формы, например остеолитических повреждений костей. Несмотря на значительный терапевтический прогресс, достигнутый с протеаозными ингибиторами, иммуномодуляционными препаратами и anti-CD38 Моноклональные антитела, множественная миелома остаются неизлечимыми, а результаты для трехклассных пациентов-восстановителей остаются мрачными, при этом медиана выживаемости н

Challenges in Implementing Comprehensive Precision Medicine Screening for Ovarian Cancer.

Precision medicine has revolutionised targeted cancer treatments; however, its implementation in ovarian cancer remains challenging. Diverse tumour biology and extensive heterogeneity in ovarian cancer can limit the translatability of genetic profiling and contribute to a lack of biomarkers of treatment response. This review addresses the barriers in precision medicine for ovarian cancer, including obtaining adequate and representative tissue samples for analysis, developing functional and standardised screening methods, and navigating data infrastructure and management. Ethical concerns relat

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… Multi-omics integration combining genomics, transcriptomics, proteomics, metabolomics, and epigenomics could offer a holistic understanding of ovarian cancer biology, uncovering novel actionable pathways and biomarkers for use in downstream precision medicine approaches. …

The potential of FCRL genes as targets for cancer treatment: insights from bioinformatics and immunology.

Cancer is a prevalent and dangerous disease that requires a multifaceted approach to treatment. The FCRL family gene has been linked to immune function and tumor progression. Bioinformatics may help unravel their role in cancer treatment. We conducted a comprehensive analysis of the FCRL family genes in pan-cancer using publicly available databases and online tools. Specifically, we examined gene expression, prognostic significance, mutation profiles, drug resistance, as well as biological and immunomodulatory roles. Our data were sourced from The Cancer Genome Atlas, Genotype-Tissue Expressio

Immune therapy: a new therapy for acute myeloid leukemia.

Although complete remission could be achieved in about 60%-70% of acute myeloid leukemia (AML) patients after conventional chemotherapy, relapse and the state of being refractory to treatment remain the main cause of death. In addition, there is a great need for less intensive regimens for all medically frail patients (both due to age/comorbidity and treatment-related). Immune therapy anticipates improved prognosis and reduced toxicities, which may offer novel therapeutic rationales. However, one of the major difficulties in developing immune therapies against AML is that the target antigens a

Finding genetically-supported drug targets for Parkinson's disease using Mendelian randomization of the druggable genome.

Parkinson's disease is a neurodegenerative movement disorder that currently has no disease-modifying treatment, partly owing to inefficiencies in drug target identification and validation. We use Mendelian randomization to investigate over 3,000 genes that encode druggable proteins and predict their efficacy as drug targets for Parkinson's disease. We use expression and protein quantitative trait loci to mimic exposure to medications, and we examine the causal effect on Parkinson's disease risk (in two large cohorts), age at onset and progression. We propose 23 drug-targeting mechanisms for Pa

The beginning of a new therapeutic era in acute myeloid leukemia.

In the field of AML, the early 2000s were shaped by the advent of novel molecular biology technologies including high-throughput sequencing that improved prognostic classification, response evaluation through the quantification of minimal residual disease, and the launch of research on targeted therapies. Our knowledge of leukemogenesis, AML genetic diversity, gene-gene interactions, clonal evolution, and treatment response assessment has also greatly improved. New classifications based on chromosomal abnormalities and gene mutations are now integrated on a routine basis. These considerable ef

MicroRNAs-Based Nano-Strategies as New Therapeutic Approach in Multiple Myeloma to Overcome Disease Progression and Drug Resistance.

MicroRNAs (miRNAs, or miRs) are single-strand short non-coding RNAs with a pivotal role in the regulation of physiological- or disease-associated cellular processes. They bind to target miRs modulating gene expression at post-transcriptional levels. Here, we present an overview of miRs deregulation in the pathogenesis of multiple myeloma (MM), and discuss the potential use of miRs/nanocarriers association in clinic. Since miRs can act as oncogenes or tumor suppressors, strategies based on their inhibition and/or replacement represent the new opportunities in cancer therapy. The miRs delivery s

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… Clinical development of TargomiRs, a miRNA mimic-based treatment for patients with recurrent thoracic cancer Epigenomics 2016 8 1079 1085 10.2217/epi-2016-0035 27185582 118. Zhu B. Ju S. Chu H. Shen X. Zhang Y. Luo X. Cong H. …

Using an integrated omics approach to uncover the mechanisms underlying chemotherapy-induced peripheral neuropathy (CIPN).

Chemotherapy-induced peripheral neuropathy (CIPN) is a debilitating side effect with limited treatment options. The primary challenge in developing therapies is the lack of identified neurotoxic mechanisms. To address this, an integrated omics approach, combining transcriptomics, proteomics, and metabolomics, is essential to map the biological changes underlying the condition. Here, we show how data from these complementary approaches converge on key mechanisms involved in CIPN through a critical summary of animal and human studies. Current research highlights several key drivers of CIPN, such

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… Using transcriptomics to identify cellular RNA contributing to CIPN In recent years, the rapid progress of next-generation sequencing-based technologies, such as genomics (i.e., whole genome sequencing or whole exome sequencing), epigenomics (i.e., DNA methylation analysis) and transcriptomics (i.e. …

Prognostic pan-cancer and single-cancer models: A large-scale analysis using a real-world clinico-genomic database.

Prognostic models in oncology have a profound impact on personalized cancer care and patient profiling, but tend to be heterogeneously developed and implemented in narrow patient cohorts. Here, we develop and benchmark multiple machine learning models to predict survival in pan-cancer and 16 single-cancer settings using a de-identified clinico-genomic database of 28,079 US patients with cancer. We identify key predictors of cancer prognosis, including 15 shared across seven or more cancer types, revealing strong consistency in cancer prognostic factors. We demonstrate that pan-cancer models ge

Кардиотоксичность, вызванная множественными миэломатерапиями: механистическая конвергенция между протеиновыми ингибиторами, CAR-T и биконкретными антителами.

Сердечно-сосудистая токсичность стала важным препятствием на пути реализации полного клинического потенциала современной терапии для множественных миэломы (ММ), включая протеазонные ингибиторы (ИП), химерика антигенного рецептора Т-клеток (CAR-T) и CD3-engaging Биотипные антитела. Здесь мы обсуждаем эпидемиологию, лежащую в основе механистических путей, и новые стратегии предотвращения кардиотоксичности, вызванной терапией, в MM. На основе данных, полученных в ходе исследований по изучению мультиомики, доклинических моделей и данных наблюдений в реальном мире, мы синтезируем вклад митохондриал

Advancing Cancer-Targeted Nanotherapies with Tumor Homing Peptides.

The development of smart nanoparticles for precision medicine in anticancer drug delivery and controlled release has the potential to revolutionize cancer treatment. This progress is driven by expanding body of preclinical and early clinical studies on anticancer nanoparticles. Despite these advancements, a critical challenge remains achieving a selective and efficient tumor accumulation, along with effective extravasation and deep tissue penetration of nanoparticles into the tumor parenchyma. Affinity targeting strategies using ligands such as homing peptides and antibodies leverage molecular

SLAMF7 regulates goblet cell mucus production and negatively impacts gut homeostasis and commensalism.

Crosstalk between the intestinal mucosal barrier and the gut microbiota contributes to maintaining intestinal homeostasis. Accumulating evidence suggests that diverse mechanisms are involved in maintaining intestinal homeostasis. Any disturbance in these pathways can compromise gut homeostasis and trigger chronic inflammatory diseases such as inflammatory bowel disease (IBD). However, how host factors regulate the intestinal mucosal barrier and change the gut microbiome has not been well defined. Here, we discovered that disruption of SLAMF7 protects against intestinal inflammation. SLAMF7 def

Изменения лакта и лактилации в неврологических расстройствах.

Значительное внимание стало уделяться изучению изменений в лактилации различных целевых органов как в области здравоохранения, так и в области болезней. Многие жизненно важные процессы и начало болезней связаны не только с избытком белков, но и в первую очередь регулируются различными посттрансляционными изменениями белков. Лактат, который раньше считался лишь побочным продуктом анаэробного метаболизма, превратился в важнейшую энергетическую субстрату и сигнализирующую молекулу, связанную как с физиологическими, так и патологическими процессами в нервной системе. Кроме того, в недавних исследо

Развитие микробиотерапии: роль синтетической биологии в инженерных микробных сообществах для точной медицины.

В последние годы исследования в области микробиотических исследований и синтетической биологии были посвящены изучению новых подходов к микробным манипуляциям в терапевтических целях. Тем не менее, по этому аспекту имеется фрагментированная информация с ключевыми идеями, разбросанными по различным дисциплинам, таким, как молекулярная биология, генетика, биоинженерия и медицина. Цель этого обзора заключается в создании преобразующего потенциала синтетической биологии в плане развития исследований и лечения микробиоме, что имеет значительные последствия для здравоохранения, сельского хозяйства и

Sex- and Gender-Related Differences in Obesity: From Pathophysiological Mechanisms to Clinical Implications.

Obesity, primarily characterized by excessive fat accumulation, is a multifactorial chronic disease with an increasing global prevalence. Despite the well-documented epidemiology and significant advances in understanding its pathophysiology and clinical implications, the impact of sex is typically overlooked in obesity research. Worldwide, women have a higher likelihood to become obese compared to men. Although women are offered weight loss interventions more often and at earlier stages than men, they are more vulnerable to psychopathology. Men, on the other hand, are less likely to pursue wei

Rejuvenation Strategy for Inducing and Enhancing Autoimmune Response to Eliminate Senescent Cells.

The process of aging, which involves progressive changes in the body over time, is closely associated with the development of age-related diseases. Cellular senescence is a pivotal hallmark and mechanism of the aging process. The accumulation of senescent cells can significantly contribute to the onset of age-related diseases, thereby compromising overall health. Conversely, the elimination of senescent cells enhances the body's regenerative and reparative capacity, thereby retarding the aging process. Here, we present a brief overview of 12 Hallmarks of aging and subsequently emphasize the po

Нацеливание moTOR сигнализирующих путей в нескольких миеломах: биология и последствия для терапии.

Множественная миелома (ММ), рак неизлечимо дифференцированных плазменных клеток, является вторым по распространенности гематологической злокачественности и неизлечимо из-за неизбежного развития лекарственной устойчивости. Интенсивный синтез белка является отличительной чертой клеток MM, поддерживающей массовое производство клональных иммуноглобулинов или свободных световых цепей. Млекопитающая цель рэпамицин (mTR) киназы ценится как главный регулятор жизненно важных клеточных процессов, включая регулирование метаболизма и синтеза белка, и может быть найдена в two Мультипротеиновые комплексы, M