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Targeting endoplasmic reticulum stress-induced lymphatic dysfunction for mitigating bisphosphonate-related osteonecrosis.

BACKGROUND: Bisphosphonates (BPs) are the first-line treatment to stop bone resorption in diseases, including osteoporosis, Paget's disease, multiple myeloma and bone metastases of cancer. However, BPs-related osteonecrosis of the jaw (BRONJ), characterized by local inflammation and jawbone necrosis, is a severe intractable complication. The cumulative inflammatory burden often accompanies impaired lymphatic drainage, but its specific impact on BRONJ and the underlying mechanisms remain unclear. METHODS: The mouse BRONJ model was established to assess the integrity and drainage function of ly

Nanoscale insights into hematology: super-resolved imaging on blood cell structure, function, and pathology.

Fluorescence nanoscopy, also known as super-resolution microscopy, has transcended the conventional resolution barriers and enabled visualization of biological samples at nanometric resolutions. A series of super-resolution techniques have been developed and applied to investigate the molecular distribution, organization, and interactions in blood cells, as well as the underlying mechanisms of blood-cell-associated diseases. In this review, we provide an overview of various fluorescence nanoscopy technologies, outlining their current development stage and the challenges they are facing in term

Interventional Radiology in the Management of Metastases and Bone Tumors.

Interventional Radiology (IR) has experienced an exponential growth in recent years. Technological advances of the last decades have made it possible to use new treatments on a larger scale, with good results in terms of safety and effectiveness. In musculoskeletal field, painful bone metastases are the most common target of IR palliative treatments; however, in selected cases of bone metastases, IR may play a curative role, also in combination with other techniques (surgery, radiation and oncology therapies, etc.). Primary malignant bone tumors are extremely rare compared with secondary bone

Integrative analysis of bulk and single-cell gene expression profiles to identify bone marrow mesenchymal cell heterogeneity and prognostic significance in multiple myeloma.

BackgroundMultiple myeloma is a hematologic malignancy characterized by complex interactions within the tumor microenvironment, where mesenchymal stem cells (MSCs) contribute significantly to disease progression, immune suppression, and drug resistance.MethodsThis study investigated the heterogeneity of MSCs in multiple myeloma using single-cell RNA sequencing (10X) and bulk transcriptomic data. Further analysis was performed by Seurat, SCENIC, CellChat. GSE4581 and GSE136337 were used as training set and validation set to construct a newly described prognostic model through COX and LASSO.Resu

Цифровой дистанционный мониторинг людей с множественным склерозом.

ВВЕДЕНИЕ: Множественный склероз (MS) является хроническим нейродегенеративным заболеванием, которое затрагивает более 2,8 млн. человек во всем мире и приводит к значительным симптомам моторного и немоторного происхождения. Эффективный мониторинг заболеваний имеет решающее значение для улучшения результатов лечения пациентов, но часто затрудняется ограниченностью редких клинических оценок. Цифровые средства дистанционного мониторинга с использованием больших данных, и МА открывает новые возможности для отслеживания симптомов в режиме реального времени и выявления развития заболеваний. МЕТОДЫ: В

Ось miR4261/PAMM в множестве миэломы стимулирует ресорбцию костей.

В рамках этого исследования изучаются механизмы, лежащие в основе заболевания костями миэломы (МБД) в множестве миеломы (МММ), с уделением особого внимания экзосомам миеломы и жидким биопсическим биомаркерам в целях выявления терапевтических целей для снижения остеокластной активности и усиления гомеостазиза костей. Совместная культурная деятельность ОПМ2, РПМ 8226, и NCI-H929 линии миэломы THP-1 Клетки использовались для оценки miR4261 и перокса ироксина, активированного в M-CSF-стимулированных моноцитах (PAMM) через RT-qPCR. Двухлюсиферазы подтвердили, что miR4261 связывает 3Непереведенная о

Current Trends and Challenges in the Clinical Translation of Nanoparticulate Nanomedicines: Pathways for Translational Development and Commercialization.

The use of nanotechnology in medicine has the potential to have a major impact on human health for the prevention, diagnosis, and treatment of diseases. One particular aspect of the nanomedicine field which has received a great deal of attention is the design and development of nanoparticulate nanomedicines (NNMs) for drug delivery (i.e., drug-containing nanoparticles). NNMs are intended to deliver drugs via various mechanisms: solubilization, passive targeting, active targeting, and triggered release. The NNM approach aims to increase therapeutic efficacy, decrease the therapeutically effecti

Natural extract-derived compounds for the treatment of hematological diseases through modulation of the bone marrow microenvironment.

The bone marrow microenvironment comprises a complex network of hematopoietic stem cells, immune cells, stromal cells, and non-cellular components such as the extracellular matrix and soluble factors, collectively maintaining the homeostasis of hematopoietic stem and progenitor cells. It is highly vulnerable to pathological perturbations induced by hematologic malignancies, solid tumors, inflammatory stress, and therapeutic exposure, which collectively destabilize microenvironmental homeostasis and promote hematopoietic failure, malignant progression, and immune dysregulation. Natural products

Valve repair after infective endocarditis secondary to perforation caused by Streptococcus gordonii: A case report.

BackgroundWe report a case of infective endocarditis (IE) in a patient with congenital heart valve lesions accompanied by IE, which was diagnosed based on blood culture analysis that revealed the presence of a gram-negative bacterium, Streptococcus gordonii.Case summaryThe patient had a history of precordial valve disease diagnosed by cardiac ultrasound, as well as a 4-mo history of fever. He was subjected to comprehensive anti-infection and anti-heart failure treatment in the internal medicine department. Further examination revealed sudden dislodgement from and perforation through the aortic

Увязка патогенеза с падением риска при множественном склерозе.

Множественный склероз — это хроническое неврологическое расстройство, характеризующееся постепенной инвалидностью, при этом падение является значительным следствием его физических и когнитивных расстройств. В настоящем обзоре рассматриваются основные вкладчики, с тем чтобы снизить риск для лиц с множественным склерозом, и анализируются более широкие последствия этих факторов, такие, как боязнь падения. К основным факторам, связанным с падением риска, относятся аномалии, когнитивная дисфункция и усталость. Эти факторы часто взаимодействуют друг с другом, что приводит к ограничению мобильности и

System analysis based on the T cell exhaustion‑related genes identifies CD38 as a novel therapy target for ovarian cancer.

Ovarian cancer (OV) is highly heterogeneous tumor with a very poor prognosis. Studies increasingly show that T cell exhaustion is prognostically relevant in OV. The aim of this study was to dissect the heterogeneity of T cell subclusters in OV through single cell transcriptomic analysis. The single RNA-sequencing (scRNA-seq) data of five OV patients were analyzed, and six major cell clusters were identified after threshold screening. Further clustering of T cell-associated clusters revealed four subtypes. Pathways related to oxidative phosphorylation, G2M checkpoint, JAK-STAT and MAPK signalin

The Adiponectin-AdipoR1 Axis Mediates Tumor Progression and Tyrosine Kinase Inhibitor Resistance in Metastatic Renal Cell Carcinoma.

The survival of patients diagnosed with metastatic renal cell carcinoma (RCC) is still limited and the current targeted therapies are only partially effective. Herein, we investigated the clinical value and functions of adiponectin receptors (AdipoR1 and AdipoR2) in metastatic renal cell carcinoma (RCC) patients treated with tyrosine kinase inhibitors (TKIs). A total of 127 mRCC patients treated with first-line TKIs between 2008 and 2017 at a single institution were collected. AdipoR1 and AdipoR2 expression was assessed by immunohistochemistry. AdipoR1 was positively expressed in 87.4% (111/12

A Super-Enhancer-Driven Transcriptional Regulatory Circuit Underlying Abiraterone Resistance in Castration-Resistant Prostate Cancer.

Castration-resistant prostate cancer (CRPC) remains the leading cause of mortality among prostate cancer patients. While second-generation androgen receptor (AR) pathway-targeted therapies, such as Abiraterone, have significantly improved survival outcomes, resistance to these treatments ultimately emerges, posing a critical challenge. Understanding the mechanisms underlying Abiraterone resistance is essential for developing strategies to enhance patient outcomes. In this study, a super-enhancer (SE)-driven transcriptional regulatory circuit is identified involving BCL6, NFIB, and SMAD3 that f

7-day longitudinal proteomics of critically ill patients: a pilot study.

An adult's health, indicated by measurable parameters, is stable over time. With the exception of circadian rhythms, variability in these parameters typically does not exceed 20%. In this pilot study, we looked into the stability of proteome in intensive care unit (ICU) patients. This was a single-center, prospective, observational pilot study of blood plasma from adult ICU patients with statistically heterogeneous patterns of clinically observed parameters. Eight week-long batches from seven patients (one patient participated twice) were analyzed by means of bottom-up proteomics. The data wer

Targeting the ROCK2/UBA52/DRP1 axis enhances ferroptosis and overcomes pemigatinib resistance in Cholangiocarcinoma.

Cholangiocarcinoma (CCA) is a highly aggressive cancer that arises from the bile duct and has an extremely poor prognosis. Pemigatinib is the only Food and Drug Administration (FDA)-approved CCA-targeted drug. The CCA treatment options are insufficient considering its poor prognosis and increasing morbidity. Recently, Rho-associated coiled-coil containing protein kinase 2 (ROCK2) has been reported to promote resistance to chemotherapy. In this study, we investigated the role that ROCK2 plays in the development of resistance of CCA cells to Pemigatinib. Here, we developed Pemigatinib-resistant

Review of oncological emergencies in small animal patients.

Oncological emergencies can occur at any time during the course of a malignancy and need to be recognized promptly to maximize successful outcomes. Emergencies are characterized as chemotherapy-induced, paraneoplastic syndromes, or directly related to the neoplasm. Prompt identification with treatment of these emergencies can prolong survival and improve quality of life, even in the setting of terminal illness. This review aims to educate the reader on the pathophysiology, clinical presentation and treatment of some of these emergencies, and to review the current veterinary literature to help

Анатомические и морфологические вариации, связанные с микрографированием в оливках in vitro с использованием клональных корнеплодов.

Микрографтация является мощным биотехнологическим инструментом для микропродукции фруктовых деревьев и может применяться для клонального распространения непристойных видов, искоренения вирусов, управления патогенами, раннего выявления совместимости с скионом/кротовым скотом и размножения. Однако в оливках этот метод по-прежнему недостаточно изучен, особенно в том, что касается пересадки на полностью клональные корнеплоды. В этом исследовании мы разработали протокол in vitro микрографирования (IVM), основанный исключительно на клонально распространяемом материале. Two Культиваторы: "Galega" и "

A case of renal damage induced by cryoglobulinemia associated with Monoclonal Gammopathy of Renal Significance.

BACKGROUND: Cryoglobulins are abnormal immunoglobulins present in circulation, capable of precipitating at lower temperatures and redissolving upon rewarming to body temperature (37 °C). It is widely accepted that mixed cryoglobulinemia is more commonly seen in chronic infections and autoimmune diseases. Here, we present a case of cryoglobulinemic nephritis due to Monoclonal Gammopathy of Renal Significance. CASE PRESENTATION: The patient was a 60-year-old male who presented with “bilateral lower limb edema for one month.” Clinical features included purpura on the lower extremities, proteinuri

Network analysis of master regulators associated with invasive phenotypes in multiple myeloma.

To elucidate the role of transcriptional regulators (TRs) associated with invasiveness in multiple myeloma (MM), we conducted a systematic network analysis to identify key master regulators (MRs) that govern MM invasiveness. We employed a consensus clustering method based on a 24-gene signature to classify MM patients into high invasiveness (INV-H) and low invasiveness (INV-L) groups. Subsequently, we identified TRs specific to the INV-H and INV-L phenotypes as MRs using a network-based approach, and we validated the MR activities that correlated with the INV-H phenotype across multiple indepe

Role of Ceramide from Glycosphingolipids and Its Metabolites in Immunological and Inflammatory Responses in Humans.

Glycosphingolipids (GSLs) are composed of hydrophobic ceramide and hydrophilic sugar chains. GSLs cluster to form membrane microdomains (lipid rafts) on plasma membranes, along with several kinds of transducer molecules, including Src family kinases and small G proteins. However, GSL-mediated biological functions remain unclear. Lactosylceramide (LacCer, CDw17) is highly expressed on the plasma membranes of human phagocytes and mediates several immunological and inflammatory reactions, including phagocytosis, chemotaxis, and superoxide generation. LacCer forms membrane microdomains with the Sr

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… GSLs that contain saturated fatty acid chains with higher transition temperatures [ 13 ] show ordered, less fluid, liquid phase. Cholesterol is composed of a highly hydrophobic sterol-ring system and 3-hydroxy moiety, the only hydrophilic part of the molecule. …