Результаты поиска

Role of growth differentiation factor 15 in cancer cachexia (Review).

Growth differentiation factor 15 (GDF15), a member of the transforming growth factor-β family, is a stress-induced cytokine. Under normal circumstances, the expression of GDF15 is low in most tissues. It is highly expressed during tissue injury, inflammation, oxidative stress and cancer. GDF15 has been established as a biomarker in patients with cancer, and is associated with cancer cachexia (CC) and poor survival. CC is a multifactorial metabolic disorder characterized by severe muscle and adipose tissue atrophy, loss of appetite, anemia and bone loss. Cachexia leads to reductions in quality

CCN proteins in the musculoskeletal system: current understanding and challenges in physiology and pathology.

The acronym for the CCN family was recently revised to represent "cellular communication network". These six, small, cysteine-enriched and evolutionarily conserved proteins are secreted matricellular proteins, that convey and modulate intercellular communication by interacting with structural proteins, signalling factors and cell surface receptors. Their role in the development and physiology of musculoskeletal system, constituted by connective tissues where cells are interspersed in the cellular matrix, has been broadly studied. Previous research has highlighted a crucial balance of CCN prote

Management of Myeloma Bone Lesions.

Multiple myeloma (MM) is a B-cell neoplasm characterized by clonal plasma-cell proliferation. The survival and prognosis of this condition have been significantly improved by treatment with active anti-MM drugs such as bortezomib or lenalidomide. Further, the discovery of novel agents has recently paved the way for new areas of investigation. However, MM, including myeloma-related bone diseases, remains fatal. Bone disease or bone destruction in MM is a consequence of skeletal involvement with bone pain, spinal cord compression, and bone fracture resulting from osteolytic lesions. These conseq

Совпадение в полном тексте источника
… TNF-α increases the BMSC production of OC-activating factors, such as RANKL and IL-6, by increasing the transcription factor spliced X-box binding protein 1, thereby increasing osteoclastogenesis. …

Targeting Glutathione Metabolism: Partner in Crime in Anticancer Therapy.

Glutathione (GSH) is the predominant low-molecular-weight antioxidant with a ubiquitous distribution inside the cell. The steady-state level of cellular GSH is dependent on the balance between synthesis, hydrolysis, recycling of glutathione disulphide (GSSG) as well as cellular extrusion of reduced, oxidized, or conjugated-forms. The augmented oxidative stress typical of cancer cells is accompanied by an increase of glutathione levels that confers them growth advantage and resistance to a number of chemotherapeutic agents. Targeting glutathione metabolism has been widely investigated for cance

miRNA-seq identification and clinical validation of CD138+ and circulating miR-25 in treatment response of multiple myeloma.

BackgroundDespite significant advancements in multiple myeloma (MM) therapy, the highly heterogenous treatment response hinders reliable prognosis and tailored therapeutics. Herein, we have studied the clinical utility of miRNAs in ameliorating patients' management.MethodsmiRNA-seq was performed in bone marrow CD138+ plasma cells (PCs) of 24 MM and smoldering MM (sMM) patients to analyze miRNAs profile. CD138+ and circulating miR-25 levels were quantified using in house RT-qPCR assays in our screening MM/sMM cohort (CD138+ plasma cells n = 167; subcohort of MM peripheral plasma samples n = 69)

Recent advances in CAR-MSCs: the new engine of cellular immunotherapy evolution.

In recent years, the development of chimeric antigen receptor (CAR) technology has greatly promoted the progress of cellular immunotherapy. Among them, CAR-T cell therapy has shown remarkable clinical effects in the treatment of hematological malignancies. However, this therapy still faces a series of challenges, including immunogenicity, toxic side effects, and insufficient maintenance of long-term efficacy. The latest research progress has extended CAR technology to mesenchymal stem cells (MSCs), and the resulting CAR-MSCs combine the precise targeting ability of CAR molecules with the inher

Role of bone-anabolic agents in the treatment of breast cancer bone metastases.

Skeletal metastases are an incurable complication afflicting the majority of patients who die from advanced breast cancer. They are most often osteolytic, characterized by net bone destruction and suppressed new bone formation. Life expectancy from first diagnosis of breast cancer bone metastases is several years, during which time skeletal-related events - including pain, fracture, hypercalcemia, and spinal cord compression - significantly degrade quality of life. The bone marrow niche can also confer hormonal and chemo-resistance. Most treatments for skeletal metastases target bone-destroyin

Lost in transcription: molecular mechanisms that control HIV latency.

Highly active antiretroviral therapy (HAART) has limited the replication and spread of the human immunodeficiency virus (HIV). However, despite treatment, HIV infection persists in latently infected reservoirs, and once therapy is interrupted, viral replication rebounds quickly. Extensive efforts are being directed at eliminating these cell reservoirs. This feat can be achieved by reactivating latent HIV while administering drugs that prevent new rounds of infection and allow the immune system to clear the virus. However, current approaches to HIV eradication have not been effective. Moreover,

PIWI-interacting RNAs (PiRNAs) as emerging biomarkers and therapeutic targets in biliary tract cancers: A comprehensive review.

Cancers affecting the biliary tract, such as gallbladder cancer and cholangiocarcinoma, make up a small percentage of adult gastrointestinal malignancies, but their incidence is on the rise. Due to the lack of dependable molecular biomarkers for diagnosis and prognosis, these cancers are often not detected until later stages and have limited treatment options. Piwi-interacting RNAs (piRNAs) are a type of small noncoding RNA that interacts with Piwi proteins and has been linked to various diseases, especially cancer. Manipulation of piRNA expression has the potential to serve as an important bi

Challenges and strategies in clinical applications of CAR-T therapy for autoimmune diseases.

Chimeric antigen receptor (CAR) T-cell therapy has demonstrated substantial efficacy against various hematological malignancies. The remarkable success of CAR-T cell therapy in targeting B-cell malignancies has generated significant interest in its potential application for treating autoimmune diseases (ADs). By engineering T cells to express CARs that specifically recognize B-cell antigens, researchers aim to selectively eliminate or modulate the dysregulated autoimmune responses underlying disease pathology. Early clinical trials targeting the B-cell marker CD19 have shown promising results,

Бенефициарное воздействие Омега-3 Жировых кислот на ожирение и связанные с ним метаболические и хронические воспаленные заболевания.

Известно, что омега-3 полинунасыщенные жирные кислоты (N-3 PUFA) помогают решить проблему воспаления посредством создания антивоспалительных эйкосаноидов и специализированных посредников по восстановлению, включая резолвинов, защитных сооружений и мареинов. Благодаря привязке к рецептору GPR120/FFAR4 они оказывают благоприятное воздействие в результате фосфолипидной реконструкции мембраны, повреждения воспалительных сигнальных молекул, последующего ингибирования NF-ИВ и воспаления активации, а также уменьшения окислительного стресса. Ожирение, хроническое воспалительное заболевание, которое пр

Circadian rhythm-guided cellular therapy in hematologic malignancies: mechanisms, clinical evidence, and optimization strategies.

Circadian rhythms are endogenous 24-hour timing systems that coordinate hematopoiesis and immune function through central and peripheral clocks. Increasing evidence indicates that the initiation and progression of hematologic malignancies are frequently accompanied by circadian disruption, which not only contributes to malignant transformation and disease progression but also anti-tumor immunity and variable treatment responses. Cellular therapies, particularly hematopoietic stem cell transplantation (HSCT) and chimeric antigen receptor T-cell therapy (CAR-T), have emerged as transformative mo

Нацеливание экспорта эндоплазмического ретикулума нарушает метаболическую устойчивость в множестве миэломы.

Множественная миелома (ММ) характеризуется производством и секрецией большого количества иммуноглобулинов, в результате чего эта злонамеренность в значительной степени зависит от механизмов, которые поддерживают клеточный протеостаз. Несмотря на значительный клинический прогресс, достигнутый в области деградативной ветки протеостаза, гораздо меньше внимания уделяется биосинтетической ветке. В этом исследовании мы продемонстрировали, что сдерживание экспорта эндоплазмического ретикулума (ER), зависящего от COPII, приводит к смерти клеток в нескольких линиях ММ и основных клеток, созданных пацие

Liposomal Nanoparticle Delivery of Ginkgo Flavone Glycosides Enhances SIRT1 Activation and Improves Diabetic Cardiomyopathy.

PurposeThis study aims to explore the therapeutic mechanisms of Ginkgo Flavone Glycosides (GFGs) delivered via liposomal nanoparticles in treating Diabetic Cardiomyopathy (DCM) by upregulating Sirtuin 1 (SIRT1) to restore energy metabolism and autophagy homeostasis.MethodsA DCM mouse model was employed, with groups treated with different doses of GFGs. Various evaluations, including body weight, blood glucose levels, and cardiac function, were performed. Network pharmacology, transcriptomic analysis, and molecular docking studies were conducted to elucidate the key role of SIRT1 in inhibiting

CAR T cell therapy in solid tumors: A review of current clinical trials.

Chimeric antigen receptor (CAR) T cell therapy has made tremendous strides in the arena of hematological malignancies with approved therapies in certain leukemias, lymphomas, and recently myeloma with overall highly favorable response rates. While numerous clinical studies are still ongoing for hematological malignancies, research is developing to translate the feasibility of CAR T therapy in solid organ malignancies. Unfortunately, the majority of diagnosed cancers are primarily solid tumors. Thus, a highly unmet clinical need for further research and development exists in this field. This re

Tumor heterogeneity as a driver of drug resistance and its implications for personalized therapy.

Tumors are highly dynamic diseases characterized by significant heterogeneity. They consist of multiple cellular populations with distinct properties that respond differently to therapeutic pressure. This heterogeneity may arise from spatial variation across tumor regions (spatial heterogeneity) as well as from temporal changes during tumor evolution and treatment (temporal heterogeneity). As a consequence, drug-resistant subclones often emerge under therapy and contribute to treatment failure. Advances in single-cell and spatial multi-omics technologies enable precise quantification of tumor

Последствия применения обеспеченных предписаний для амбулаторного использования прегабалина во Франции: региональная оценка во Французском Нувеле-Аквитане.

AIM: Французские власти разрешили использовать в мае безопасные рецепты на догабалин. 2021. Цель этого исследования заключалась в оценке воздействия этой меры на использование и неправильное использование догабалинов в Нувеле-Акитане, юго-западном французском регионе, расположенном вокруг six million Жители. МЕТОДЫ: Это исследование было проведено на основе региональных баз данных французской системы медицинского страхования " Нувел-Аквитейн " . В нее входят все лица, которые получают по крайней мере one Возмещение расходов на догабалин между 24 Май 2020 и 24 Май 2022. Мы проанализир

Pilot study of lithium to restore intestinal barrier function in severe graft-versus-host disease.

UNLABELLED: Severe intestinal graft-vs-host disease (GVHD) after allogeneic hematopoietic cell transplantation (HCT) causes mucosal ulceration and induces innate and adaptive immune responses that amplify and perpetuate GVHD and the associated barrier dysfunction. Pharmacological agents to target mucosal barrier dysfunction in GVHD are needed. We hypothesized that induction of Wnt signaling by lithium, an inhibitor of glycogen synthase kinase (GSK3), would potentiate intestinal crypt proliferation and mucosal repair and that inhibition of GSK3 in inflammatory cells would attenuate the deregula

Pro-inflammatory cytokine-mediated anemia: regarding molecular mechanisms of erythropoiesis.

Anemia of cancer and chronic inflammatory diseases is a frequent complication affecting quality of life. For cancer patients it represents a particularly bad prognostic. Low level of erythropoietin is considered as one of the causes of anemia in these pathologies. The deficiency in erythropoietin production results from pro-inflammatory cytokines effect. However, few data is available concerning molecular mechanisms involved in cytokine-mediated anemia. Some recent publications have demonstrated the direct effect of pro-inflammatory cytokines on cell differentiation towards erythroid pathway,

Osteoarthritis of the knee - biochemical aspect of applied therapies: a review.

The most prevalent form of arthritis is osteoarthritis (OA) of the knee, which is characterized by a degeneration of articular cartilage resulting in the development of osteophytes, or bone spurs. Main goals of OA treatment are to reduce pain, slow the disease progression, and improve joint function and the quality of life. The purpose of this study was to verify all the therapies recommended by the European Society for Clinical and Economic Aspects of Osteoporosis and Osteoarthritis (ESCEO) from the biochemical point of view. Non-steroidal anti-inflammatory drugs (NSAIDs) inhibit the synthesi