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How histone modifications influence cellular radiosensitivity: Pharmaceutically targeting epigenetic regulators as a promising avenue to overcome radioresistance.

Cancer remains the leading cause of mortality worldwide. Radiotherapy (RT), a cornerstone of oncological treatment for over a century, has achieved great success in various cancers. However, radioresistance remains the primary factor leading to the failure of radiotherapy. Histone modifications in cancer cells are known to play a pivotal role in regulating radiosensitivity by modulating chromatin structure, either by loosening or tightening it. Here, we provide a comprehensive summary of the link between aberrant histone modifications and radiation resistance across various cancer and normal t

Disappearance of femoral head shortly after femoral neck fracture: a case report and literature review.

This case report describes a woman in her 70s who presented with a 3-month history of hip pain and inability to walk. Upon admission, she was diagnosed with the extremely rare condition of complete femoral head disappearance. A comprehensive examination was conducted to determine the cause and devise an effective treatment strategy, taking the patient's medical history into account. Through interdisciplinary discussions, occult infection and other potential causes were ruled out. The femoral head disappearance was ultimately determined to be due to wear, ischemia, and absorption following a fr

Inflammatory Microenvironment and Specific T Cells in Myeloproliferative Neoplasms: Immunopathogenesis and Novel Immunotherapies.

The Philadelphia-negative myeloproliferative neoplasms (MPNs) are malignancies of the hematopoietic stem cell (HSC) arising as a consequence of clonal proliferation driven by somatically acquired driver mutations in discrete genes (JAK2, CALR, MPL). In recent years, along with the advances in molecular characterization, the role of immune dysregulation has been achieving increasing relevance in the pathogenesis and evolution of MPNs. In particular, a growing number of studies have shown that MPNs are often associated with detrimental cytokine milieu, expansion of the monocyte/macrophage compar

Primary Osteoporosis Induced by Androgen and Estrogen Deficiency: The Molecular and Cellular Perspective on Pathophysiological Mechanisms and Treatments.

Primary osteoporosis is closely linked to hormone deficiency, which disrupts the balance of bone remodeling. It affects postmenopausal women but also significantly impacts older men. Estrogen can promote the production of osteoprotegerin, a decoy receptor for RANKL, thereby preventing RANKL from activating osteoclasts. Furthermore, estrogen promotes osteoblast survival and function via activation of the Wnt signaling pathway. Likewise, androgens play a critical role in bone metabolism, primarily through their conversion to estrogen in men. Estrogen deficiency accelerates bone resorption throug

LncRNA NORAD promotes bone marrow stem cell differentiation and proliferation by targeting miR-26a-5p in steroid-induced osteonecrosis of the femoral head.

BACKGROUND: Steroid-induced osteonecrosis of the femoral head (SONFH) is a devastating orthopedic disease, which seriously affects the quality of life of patients. The study aims to investigate the effects of LncRNA NORAD on SONFH. METHODS: Human bone marrow-derived mesenchymal stem cells (hBMSCs) were isolated from the proximal femur of patients during routine orthopedic surgery and then cultured with dexamethasone (Dex) and transfected with NORAD overexpression vector, siRNA-NORAD and miR-26a-5p mimics. The mRNA expression of NORAD, miR-26a-5p, OPG, RANK, and RANKL was detected by RT-qPCR.

Future Options of Molecular-Targeted Therapy in Small Cell Lung Cancer.

Lung cancer is the leading cause of cancer-related deaths worldwide. With a focus on histology, there are two major subtypes: Non-small cell lung cancer (NSCLC) (the more frequent subtype), and small cell lung cancer (SCLC) (the more aggressive one). Even though SCLC, in general, is a chemosensitive malignancy, relapses following induction therapy are frequent. The standard of care treatment of SCLC consists of platinum-based chemotherapy in combination with etoposide that is subsequently enhanced by PD-L1-inhibiting atezolizumab in the extensive-stage disease, as the addition of immune-checkp

New players in the landscape of renal cell carcinoma bone metastasis and therapeutic opportunities.

Approximately one-third of advanced renal cell carcinoma (RCC) patients develop osteolytic bone metastases, leading to skeletal complications. In this review, we first provide a comprehensive perspective of seminal studies on bone metastasis of RCC describing the main molecular modulators and growth factor signaling pathways most important for the RCC-stimulated osteoclast-mediated bone destruction. We next focus on newer developments revealing with in-depth details, the bidirectional interplay between renal cancer cells and the immune and stromal microenvironment that can through epigenetic r

Decreased Plasma Level of Cytokeratin 20 (KRT20) Is Indicative of the Emergence and Severity of Acute GvHD Irrespective to the Type of Organ Involvement.

Accurate risk prediction of acute graft versus host disease (aGvHD) is currently an unmet clinical need. This study sought to analyze whether three plasma proteins expressed in a largely skin- and gut-restricted manner would be affected by the development of acute cutaneous and gastrointestinal aGvHD. The diagnostic sensitivity, specificity, and prognostic value of plasma cytokeratin-15 (KRT15) cytokeratin-20 (KRT20), and occludin (OCLN) were evaluated in a discovery and a validation cohort using ELISA in comparison with elafin (PI3) and regenerating family member 3 alpha (REG3A), two establis

A technical note on emerging combination approach involved in the onconanotherapeutics.

Cancer is the second cause of mortality worldwide, and the currently available conventional treatment approach is associated with serious side effects and poor clinical outcomes. Based on the outcome of the exploratory preclinical and clinical studies, it was found that therapeutic response increases multiple folds when anticancer drugs are used in combination. However, the conventional combination of anticancer drugs was associated with various limitations such as increased cost of treatment, systemic toxicity, drug resistance, and reduced pharmacokinetic attributes. Hence, attempts were made

Applications of synthetic biology in medical and pharmaceutical fields.

Synthetic biology aims to design or assemble existing bioparts or bio-components for useful bioproperties. During the past decades, progresses have been made to build delicate biocircuits, standardized biological building blocks and to develop various genomic/metabolic engineering tools and approaches. Medical and pharmaceutical demands have also pushed the development of synthetic biology, including integration of heterologous pathways into designer cells to efficiently produce medical agents, enhanced yields of natural products in cell growth media to equal or higher than that of the extract

Inflammatory Signaling Pathways in Preleukemic and Leukemic Stem Cells.

Hematopoietic stem cells (HSCs) are a rare subset of bone marrow cells that usually exist in a quiescent state, only entering the cell cycle to replenish the blood compartment, thereby limiting the potential for errors in replication. Inflammatory signals that are released in response to environmental stressors, such as infection, trigger active cycling of HSCs. These inflammatory signals can also directly induce HSCs to release cytokines into the bone marrow environment, promoting myeloid differentiation. After stress myelopoiesis is triggered, HSCs require intracellular signaling programs to

Advances in cancer immunotherapy and future directions in personalized medicine.

Cancer immunotherapy has revolutionized oncologic treatment by harnessing and reprogramming the immune system to target malignant cells. This review provides a comprehensive picture of modern approaches to immunotherapy-based treatment strategies, such as immune checkpoint inhibitors (ICIs), chimeric antigen receptor T cells, mRNA vaccines, and biomaterials-based platforms, with a focus on their translational value and application to precision medicine. Emerging insights into the tumor microenvironment, immune resistance mechanisms, and T-cell subpopulation dynamics (e.g., γδ T cells, exhauste

Совпадение в полном тексте источника
… Research teams have developed circulating tumor DNA (ctDNA)-based biomarkers to monitor tumors directly through the detection of real-time evolution and therapy response, as well as resistance mechanisms. …

British Association for Cancer Research 22nd Annual general meeting. 13-15 April 1981. Abstracts.

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Advances in Molecular Regulation of Prostate Cancer Cells by Top Natural Products of Malaysia.

Prostate cancer (PCa) remains both a global health burden and a scientific challenge. We present a review of the molecular targets driving current drug discovery to fight this disease. Moreover, the preventable nature of most PCa cases represents an opportunity for phytochemicals as chemopreventive when adequately integrated into nutritional interventions. With a renovated interest in natural remedies as a commodity and their essential role in cancer drug discovery, Malaysia is looking towards capitalizing on its mega biodiversity, which includes the oldest rainforest in the world and an estim

MRD в нескольких миеломах: клиническая перспектива.

Минимальное остаточное заболевание (МРД) стало ключевым прогнозным фактором в случае множественной миэломы (ММ), что позволяет более точно оценивать эффективность лечения после обычной полной ремиссии. Технологии высокой чувствительности, включая цитометрию потока следующего поколения (СПГ), последовательность следующего поколения (СПГ) и количественную PCR для олигонуклеотида аллеля, позволяют обнаруживать остаточные заболевания при уровнях 10-5-10-6. Достижение негатива MRD последовательно ассоциируется с продолжительным безподвижным выживанием (PFS) и общим выживанием (OS) в различных услов

Совпадение в полном тексте источника
… Future perspectives Ongoing research aims to refine MRD detection techniques, explore non-invasive approaches such as circulating tumor DNA, and prospectively validate MRD-guided treatment strategies. …

Этап II - испытание параллельной химиорадиотерапии с использованием L-аспарагиназы и MIDLE химиотерапии для недавно диагностированной стадии I/II экстранодал NK/T-клеток лимфомы носового типа (CISL-1008).

Всего 372 Иксоды рицины тикают101 женщины, 122 мужского пола; и 149 Нимфы), собранные с помощью пометок 6 В зависимости от культуры были изучены смешанные лесные массивы восточной Польши на предмет наличия внутренних отрицательных бактерий, помимо бурдорфери Борелия. Галочка для взрослых была изучена в пулах 2 Каждый образец и каждый имфл были изучены в пулах 3-5 Каждый образец. Тики были дезинфицированы в 70 % этанол и гомогенизированный 0.85% NaCl. Разбавленный гомогенат был привит на 3 Виды агарной среды: буферная добыча дрожжей из древесного угля (BCYE-alpha) для изоляции стойко-отрицатель

Aberrant NSUN2-mediated m5C modification of exosomal LncRNA MALAT1 induced RANKL-mediated bone destruction in multiple myeloma.

The impact of exosome-mediated crosstalk between multiple myeloma (MM) cells and osteoclasts (OCs) on bone lesions remains to be investigated. Here, we identified NSUN2 and YBX1-mediated m5C modifications upregulated LncRNA MALAT1 expression in MM cells, which could be transported to OCs via exosomes and promote bone lesions. Methodologically, RNA-seq was carried out to detect the cargoes of exosomes. TRAP staining and WB were used to evaluate osteoclastogenesis in vitro. Micro-CT and bone histomorphometric analyses were performed to identify bone destruction in vivo. RNA pull-down, RIP, MeRIP

Assessment of evidence from teeth and the alveolar bone of skulls.

A notable lack of agreement on a standardised criterion for representing changes in alveolar bone persists, which limits its application in forensic dentistry. This study aimed to describe the data on loss of tooth substance and alveolar bone in skulls. Dental and trabecular bone information from 28 skulls from the German Helmer skull collection was collected through dental charting, intraoral photographs taken with a DSLR camera (Nikon D5600, Nikon Corporation, Japan), and small radiographs obtained using a handheld dental X-ray device (Nomad Pro 2, Kavo Kerr, Biberach, Germany). Adobe Photos

SOX9 Induces Orbital Fibroblast Activation in Thyroid Eye Disease Via MAPK/ERK1/2 Pathway.

PurposeTo evaluate the expression of sry-box transcription factor 9 (SOX9) in orbital fibroblasts (OFs) of thyroid eye disease (TED) and to find its potential role and underlying mechanism in orbital fibrosis.MethodsOFs were cultured from orbital connective tissues obtained from patients with TED (n = 10) and healthy controls (n = 6). SOX9 was depleted by small interfering RNA or overexpressed through lentivirus transduction in OFs. Fibroblast contractile activity was measured by collagen gel contraction assay and proliferation was examined by EdU assay. Transcriptomic changes were assessed by

Прогресс в развитии лекарственных средств на основе пептида: платформы для доставки, терапевтические средства и вакцины.

Успешное утверждение лекарств на основе пептида можно отнести на счет совместных усилий по целому ряду дисциплин. Интеграция новых методов разработки и синтеза лекарственных средств, отображение библиотечных технологий, систем доставки, достижений в области биоинженерии и искусственного интеллекта в значительной степени ускорила разработку новейших лекарств на основе пептида, эффективно устраняя препятствия, связанные с их характером, такие, как быстрое обезвреживание и деградация, необходимость субколичественной инъекции, ведущей к усилению дискомфорта пациентов, и в конечном итоге продвигая