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The Role of Cullin-RING Ligases in Striated Muscle Development, Function, and Disease.

The well-orchestrated turnover of proteins in cross-striated muscles is one of the fundamental processes required for muscle cell function and survival. Dysfunction of the intricate protein degradation machinery is often associated with development of cardiac and skeletal muscle myopathies. Most muscle proteins are degraded by the ubiquitin-proteasome system (UPS). The UPS involves a number of enzymes, including E3-ligases, which tightly control which protein substrates are marked for degradation by the proteasome. Recent data reveal that E3-ligases of the cullin family play more diverse and c

Extraskeletal benefits and risks of calcium, vitamin D and anti-osteoporosis medications.

UnlabelledDrugs used for the prevention and the treatment of osteoporosis exert various favourable and unfavourable extra-skeletal effects whose importance is increasingly recognized notably for treatment selection.IntroductionThe therapeutic armamentarium for the prevention and the treatment of osteoporosis is increasingly large, and possible extra-skeletal effects of available drugs could influence the choice of a particular compound.MethodsThe present document is the result of a national consensus, based on a systematic and critical review of the literature.ResultsObservational research has

The effectiveness of exercise-based interventions on muscle mass, muscle strength, functional performance, aerobic capacity, and health-related quality of life in adults with malignant lymphoma undergoing chemotherapy: a systematic review of randomized controlled trials.

PurposeThis study aims to identify and summarize evidence on the effectiveness of exercise-based interventions on muscle mass, muscle strength, functional performance, aerobic capacity, health-related quality of life (HRQoL), feasibility of the interventions, in patients with malignant lymphoma undergoing chemotherapy.MethodsA systematic search was conducted in six electronic databases and trials registers on November 15, 2023. Peer-reviewed randomized controlled trials (RCTs) comparing exercise intervention with controls/usual care in adults (≥18 years) diagnosed with Hodgkin's lymphoma and n

Molecular and cellular mechanisms of skeletal muscle atrophy: an update.

Skeletal muscle atrophy is defined as a decrease in muscle mass and it occurs when protein degradation exceeds protein synthesis. Potential triggers of muscle wasting are long-term immobilization, malnutrition, severe burns, aging as well as various serious and often chronic diseases, such as chronic heart failure, obstructive lung disease, renal failure, AIDS, sepsis, immune disorders, cancer, and dystrophies. Interestingly, a cooperation between several pathophysiological factors, including inappropriately adapted anabolic (e.g., growth hormone, insulin-like growth factor 1) and catabolic pr

T-Type Calcium Channels: A Mixed Blessing.

The role of T-type calcium channels is well established in excitable cells, where they preside over action potential generation, automaticity, and firing. They also contribute to intracellular calcium signaling, cell cycle progression, and cell fate; and, in this sense, they emerge as key regulators also in non-excitable cells. In particular, their expression may be considered a prognostic factor in cancer. Almost all cancer cells express T-type calcium channels to the point that it has been considered a pharmacological target; but, as the drugs used to reduce their expression are not complete

A Comprehensive Review on the Therapeutic Potential of Curcuma longa Linn. in Relation to its Major Active Constituent Curcumin.

Curcuma longa Linn. (C. longa), popularly known as turmeric, belongs to the Zingiberaceae family and has a long historical background of having healing properties against many diseases. In Unani and Ayurveda medicine, C. longa has been used for liver obstruction and jaundice, and has been applied externally for ulcers and inflammation. Additionally, it is employed in several other ailments such as cough, cold, dental issues, indigestion, skin infections, blood purification, asthma, piles, bronchitis, tumor, wounds, and hepatic disorders, and is used as an antiseptic. Curcumin, a major constitu

Clinical evaluation and outcome in heart failure patients receiving chemotherapy with different anti-cancer agents.

BACKGROUND: The optimal strategy for modern chemotherapy should be based on a comprehensive approach for cancer patients with cardiovascular diseases. Therefore, cardio-oncology has received increasing attention owing to the cardiotoxic effects of anti-cancer therapies. OBJECTIVES: We aimed to evaluate the clinical characteristics and outcomes of patients with heart failure (HF) who received chemotherapy compared with those of a matched cohort with HF who did not receive chemotherapy, using real-world HF data. METHODS: This study was based on the Diagnosis Procedure Combination (DPC) databas

Chemokines in COPD: From Implication to Therapeutic Use.

: Chronic Obstructive Pulmonary Disease (COPD) represents the 3rd leading cause of death in the world. The underlying pathophysiological mechanisms have been the focus of extensive research in the past. The lung has a complex architecture, where structural cells interact continuously with immune cells that infiltrate into the pulmonary tissue. Both types of cells express chemokines and chemokine receptors, making them sensitive to modifications of concentration gradients. Cigarette smoke exposure and recurrent exacerbations, directly and indirectly, impact the expression of chemokines and chem

Burden of illness among patients with relapsed or refractory multiple myeloma, and eligible for B-cell maturation antigen-targeted therapies.

BACKGROUND: B-cell maturation antigen (BCMA)-targeted therapies were approved for triple-class exposed relapsed/refractory multiple myeloma (RRMM) after ≥4 lines of therapy. METHODS: This claims-based retrospective analysis examined clinical and economic burden among United States patients who met eligibility for BCMA-targeted therapies and started a new therapy between 1 January 2016 and 30 September 2022. RESULTS: Of 228 eligible patients (median age: 64, 52.6% male, 68.7% White), clinical burden was characterized by prevalent MM-related conditions and complications, and high treatment fai

Cyclic nucleotide phosphodiesterases as drug targets.

Cyclic nucleotides are synthesized by adenylyl and/or guanylyl cyclase, and downstream of this synthesis, the cyclic nucleotide phosphodiesterase families (PDEs) specifically hydrolyze cyclic nucleotides. PDEs control cyclic adenosine-3',5'monophosphate (cAMP) and cyclic guanosine-3',5'-monophosphate (cGMP) intracellular levels by mediating their quick return to the basal steady state levels. This often takes place in subcellular nanodomains. Thus, PDEs govern short-term protein phosphorylation, long-term protein expression, and even epigenetic mechanisms by modulating cyclic nucleotide levels

Совпадение в полном тексте источника
… Milrinone (IC 50 = 2.1 μ M) was the first PDE3 inhibitor developed to improve myocardial contraction in heart failure and safe for short-term use, avoiding death by arrhythmia after chronic use ( Lanfear et al, 2009 ). …

The clinical effectiveness and safety of traditional Chinese medicine uremic clearance granule combined with high-flux hemodialysis in the treatment of uremic pruritus: A protocol for systematic review and meta analysis.

BackgroundSkin pruritus is a common complication in patients with uremia. When the hemodialysis time of patients is extended, and the probability of skin pruritus is greater. Patients often have the symptoms of skin pruritus intolerable, affecting the normal sleep and normal life of patients. The patients with uremic pruritus often constant scratching and pruritus skin, resulting in broken skin, and further symptoms such as infection, and subsequent skin shedding, prurigo nodularis, and other adverse complications, aggravating the patient's condition. Some patients will experience symptoms suc

Clinical Efficacy of Ruxolitinib in Patients with Myelofibrosis: A Nationwide Population-Based Study in Korea.

Previous studies have reported the survival benefit after ruxolitinib treatment in patients with myelofibrosis (MF). However, population-based data of its efficacy are limited. We analyzed the effects of ruxolitinib in MF patients with data from the Korean National Health Insurance Database. In total, 1199 patients diagnosed with MF from January 2011 to December 2017 were identified, of which 731 were included in this study. Patients who received ruxolitinib (n = 224) were matched with those who did not receive the drug (n = 507) using the 1:1 greedy algorithm. Propensity scores were formulate

Treatment Inertia and Symptom Burden in Anemia of CKD: Insights from the SATISFY Survey in the Middle East, South Africa, and Türkiye.

IntroductionLimited data exist regarding treatment patterns and symptom burden of patients with anemia of chronic kidney disease (CKD) in the Middle East, South Africa, and Türkiye.MethodsThis real-world study explored clinical characteristics, symptom burden, and treatment patterns of patients with anemia of CKD living in the Middle East, South Africa, and Türkiye. Physician and patient perceptions of treatment were captured via cross-sectional surveys; patients' clinical characteristics were recorded by retrospective review of medical records.ResultsData were collected from 1788 patients and

Cardiac Cachexia: Unaddressed Aspect in Cancer Patients.

Tumor-derived cachectic factors such as proinflammatory cytokines and neuromodulators not only affect skeletal muscle but also affect other organs, including the heart, in the form of cardiac muscle atrophy, fibrosis, and eventual cardiac dysfunction, resulting in poor quality of life and reduced survival. This article reviews the holistic approaches of existing diagnostic, pathophysiological, and multimodal therapeutic interventions targeting the molecular mechanisms that are responsible for cancer-induced cardiac cachexia. The major drivers of cardiac muscle wasting in cancer patients are au

The prince and the pauper. A tale of anticancer targeted agents.

Cancer rates are set to increase at an alarming rate, from 10 million new cases globally in 2000 to 15 million in 2020. Regarding the pharmacological treatment of cancer, we currently are in the interphase of two treatment eras. The so-called pregenomic therapy which names the traditional cancer drugs, mainly cytotoxic drug types, and post-genomic era-type drugs referring to rationally-based designed. Although there are successful examples of this newer drug discovery approach, most target-specific agents only provide small gains in symptom control and/or survival, whereas others have consiste

Risk Factors for Adverse Outcomes in Cancer Patients With Sepsis.

BACKGROUND: Cancer and its various treatment modalities increase susceptibility to the development of sepsis. Because of the complex relationship between sepsis and cancer, we aimed to study the differences in risk factors and outcomes of sepsis in patients with cancer (SCa) compared to patients without cancer (SnoCa). METHODS: A retrospective cohort analysis of all adult patients who received care for sepsis in an urban tertiary healthcare center was conducted. Risk factors and outcomes were compared between the SCa and SnoCa groups. RESULTS: SCa group (n = 310) was older than SnoCa group (

Seventeen-year reassessment of diagnostic transitions, biologic therapy initiation and mortality in spondyloarthritis: results from the REGISPON-3 study.

OBJECTIVES: To evaluate disease evolution, diagnostic transitions, time to biologic treatment initiation and mortality in patients with spondyloarthritis (SpA) after 17 years from the original Spanish Registry of Spondyloarthritis (REGISPONSER). METHODS: Spondyloarthritis Registry 3 (REGISPON-3) is a two-timepoint longitudinal study with patients fulfilling the European Spondyloarthropathy Study Group criteria participating in the REGISPONSER study and re-evaluated after 17 years. Clinical, laboratory, radiological and treatment data were collected and compared with baseline. Diagnostic chang

Воспаление и воспаление болезней, маркеры и посредники: роль КПИ в некоторых воспламенительных заболеваниях

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NF-κB in biology and targeted therapy: new insights and translational implications.

NF-κB signaling has been discovered for nearly 40 years. Initially, NF-κB signaling was identified as a pivotal pathway in mediating inflammatory responses. However, with extensive and in-depth investigations, researchers have discovered that its role can be expanded to a variety of signaling mechanisms, biological processes, human diseases, and treatment options. In this review, we first scrutinize the research process of NF-κB signaling, and summarize the composition, activation, and regulatory mechanism of NF-κB signaling. We investigate the interaction of NF-κB signaling with other importa

Prevalence, characteristics, and mortality of patients with transthyretin amyloid cardiomyopathy in the Nordic countries.

AimsTransthyretin amyloid cardiomyopathy (ATTR-CM) is a progressive condition caused by deposition of transthyretin amyloid fibrils in the heart and is associated with poor quality of life and a shortened lifespan. This study aimed to describe the prevalence, clinical characteristics, and mortality of patients with ATTR-CM, using multiple national health registers in Denmark, Finland, Norway, and Sweden.Methods and resultsTransthyretin amyloid cardiomyopathy patients were identified during 2008-2018 using a combination of diagnosis codes for amyloidosis and heart disease and were matched to pa