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гинекологическое здоровье: недостающее звено во всеобъемлющем мониторинге лечения множественных склерозов.

Мониторинг безопасности методов лечения болезней (ДМТ), используемых для лечения множественных склерозов (МС), в значительной степени не учитывает область гинекологического здоровья. Цель этого тематического обзора состоит в том, чтобы предоставить врачам по НР обзор трех категорий осложнений, описанных на сегодняшний день, а также стратегий уменьшения рисков. К ним относятся повышенный риск позитивности вируса папилломы человека (ВПВ) и связанных с ним шейных дисплазий/канцеров; подстрекательский и инфекционный вагинит и подверженность бактериальному вагинозу (ВВ); и герпесвирусные инфекции,

European guidance for the diagnosis and management of osteoporosis in postmenopausal women.

UnlabelledGuidance is provided in a European setting on the assessment and treatment of postmenopausal women with or at risk from osteoporosis.IntroductionThe European Foundation for Osteoporosis and Bone disease (subsequently the International Osteoporosis Foundation) published guidelines for the diagnosis and management of osteoporosis in 1997. This manuscript updates these in a European setting.MethodsThe following areas are reviewed: the role of bone mineral density measurement for the diagnosis of osteoporosis and assessment of fracture risk; general and pharmacological management of oste

From undruggable to degradable: A deep learning-enabled framework for precision orthopaedic protein degradation.

BACKGROUND/OBJECTIVE: A fundamental translational impasse in musculoskeletal disorders-from osteoarthritis to bone metastases-is the "undruggability" of critical pathological drivers sequestered within anatomically restricted and avascular skeletal niches. While Targeted Protein Degradation (TPD) offers a revolutionary event-driven modality to eradicate these refractory targets, its clinical translation to orthopaedics is severely hindered by the physicochemical incompatibility of large degraders with dense extracellular matrices and the scarcity of bone-specific E3 ligases. METHODS: In this

Proceedings of the Canadian Society of Allergy and Clinical Immunology Annual Scientific Meeting 2018

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Hypercalcemia From Trenbolone Use: A Case Report.

In this case, a patient presented to the emergency department (ED) with fatigue after CareNow noted abnormal laboratory results. The patient reported using trenbolone, an anabolic-androgenic steroid (AAS) often used for athletic performance enhancement or cosmetic purposes. In the ED, the patient was noted to have significant hypercalcemia (15 mg/dL) and acute kidney injury (AKI) (creatinine 6.02 mg/dL). The workup ruled out malignancy, hyperparathyroidism, and vitamin D toxicity. The patient was admitted and received intravenous fluids and pamidronate, which improved the patient's hypercalcem

Targeting the AMP-Activated Protein Kinase for Cancer Prevention and Therapy.

Despite the advances in biomedical research and clinical applications, cancer remains a leading cause of death worldwide. Given the limitations of conventional chemotherapeutics, including serious toxicities and reduced quality of life for patients, the development of safe and efficacious alternatives with known mechanism of action is much needed. Prevention of cancer through dietary intervention may hold promise and has been investigated extensively in the recent years. AMP-activated protein kinase (AMPK) is an energy sensor that plays a key role in the regulation of protein and lipid metabol

Targeting SREBP-2-Regulated Mevalonate Metabolism for Cancer Therapy.

Recently, targeting metabolic reprogramming has emerged as a potential therapeutic approach for fighting cancer. Sterol regulatory element binding protein-2 (SREBP-2), a basic helix-loop-helix leucine zipper transcription factor, mainly regulates genes involved in cholesterol biosynthesis and homeostasis. SREBP-2 binds to the sterol regulatory elements (SREs) in the promoters of its target genes and activates the transcription of mevalonate pathway genes, such as HMG-CoA reductase (HMGCR), mevalonate kinase and other key enzymes. In this review, we first summarized the structure of SREBP-2 and

RANK/RANK-L/OPG in patients with bone metastases treated with anticancer agents and zoledronic acid: a prospective study.

Patients with solid cancer frequently develop bone metastases (BM). Zoledronic acid (Zometa®, ZA), routinely used to treat patients with BM, acts on osteoclasts and also has antitumor properties. We aimed to assess the effect of ZA over time in novel bone turnover markers (RANK/receptor activator of nuclear factor-k B ligand (RANK-L)/ Osteoprotegerin (OPG)) and to correlate these with serum N-terminal telopeptide (NTX). The study prospectively evaluated levels of RANK, RANK-L and OPG transcripts by real-time PCR and NTX expression by ELISA in the peripheral blood of 49 consecutive patients wit

Triple-Negative Breast Cancer: Basic Biology and Immuno-Oncolytic Viruses.

Triple-negative breast cancer (TNBC) is the most lethal subtype of breast cancer. TNBC diagnoses account for approximately one-fifth of all breast cancer cases globally. The lack of receptors for estrogen, progesterone, and human epidermal growth factor 2 (HER-2, CD340) results in a lack of available molecular-based therapeutics. This increases the difficulty of treatment and leaves more traditional as well as toxic therapies as the only available standards of care in many cases. Recurrence is an additional serious problem, contributing substantially to its higher mortality rate as compared to

The interrelationship between prostate cancer and osteoporosis: new perspectives on shared molecular pathways and treatment strategies.

Osteoporosis is frequently regarded as a complication associated with androgen deprivation therapy (ADT) in patients with prostate cancer. Nevertheless, a notably higher incidence of osteoporosis has been observed in prostate cancer patients even in the absence of ADT, when compared to age-matched healthy individuals. This phenomenon is likely attributable to the synergistic effects of aging, chronic inflammation, and tumor-related factors, which collectively contribute to accelerated bone loss in this population. Accumulating evidence has demonstrated that signaling pathways such as RANKL/RAN

Medicinal chemistry perspectives on anticancer drug design based on clinical applications (2015-2025).

Cancer therapy has undergone a remarkable evolution over the past few decades, driven largely by innovations in medicinal chemistry. This review explores the pivotal role of medicinal chemistry in designing, optimizing, and classifying anticancer agents, from traditional cytotoxics to modern targeted therapies, immunotherapies, and radiotheranostics. The article categorizes FDA-approved anticancer drugs (2015-2025), evaluates their mechanisms of action, structural features, and structure-activity relationships (SAR), and highlights both success stories and challenges in clinical translation. A

Generic Anticancer Drugs of the Jan Aushadhi Scheme in India and Their Branded Counterparts: The First Cost Comparison Study.

Introduction In India, the costs of cancer drugs are exorbitant and cause significant financial toxicity to the affected patient and their family members. Considering this, Jan Aushadhi pharmacy stores were established across the country by the government of India with the objective of providing cheap generic medicines to patients. The objective of this study was to perform a cost comparison study of generic chemotherapeutic drugs provided through Jan Aushadhi pharmacies versus their branded counterparts. This will help patients and physicians get first-hand information on the cost variation b

Effects of exosomes from different origins on osteoclasts.

Abnormal osteoclast function is closely related to the development of osteolytic diseases such as osteoporosis and tumor bone metastasis, which seriously affects patients' quality of life. The cellular microenvironment is complex and variable, and exosomes, as an important pathway mediating intercellular communication, can be secreted by a variety of cells in the human body, which carry "cargo" that can affect the biological function of recipient cells. Osteoclasts receive a variety of cellular exosomes to regulate and influence the body's bone homeostasis. In this narrative review, we summari

Recognition and management of persistent chylomicronemia: A joint expert clinical consensus by the National Lipid Association and the American Society for Preventive Cardiology.

Extreme hypertriglyceridemia, defined as triglyceride (TG) levels ≥1000 mg/dL, is almost always indicative of chylomicronemia. The current diagnostic approach categorizes individuals with chylomicronemia into familial chylomicronemia syndrome (FCS; prevalence 1-10 per million), caused by the biallelic combination of pathogenic variants that impair the lipolytic action of lipoprotein lipase (LPL), or multifactorial chylomicronemia syndrome (MCS, 1 in 500). A pragmatic framework should emphasize the severity of the phenotype and the risk of complications. Therefore, we endorse the term "persiste

Targeting Sphingosine 1-Phosphate Metabolism as a Therapeutic Avenue for Prostate Cancer.

Prostate cancer (PC) is the second most common cancer in men worldwide. More than 65% of men diagnosed with PC are above 65. Patients with localized PC show high long-term survival, however with the disease progression into a metastatic form, it becomes incurable, even after strong radio- and/or chemotherapy. Sphingosine 1-phosphate (S1P) is a bioactive lipid that participates in all the steps of oncogenesis including tumor cell proliferation, survival, migration, invasion, and metastatic spread. The S1P-producing enzymes sphingosine kinases 1 and 2 (SK1 and SK2), and the S1P degrading enzyme

Targeting epigenetic methylation: emerging diagnosis and therapeutic strategies in cancer.

Epigenetics shapes all aspects of cancer occurrence and progression. Among them, chromatin methylation is a particularly important regulator of oncogenic processes. The dynamic shifts in methylation can influence the development or death of tumor cells. In the therapeutic context, effectively targeting and modulating DNA, RNA, and histone methylation brings promise for the early detection, prognostic assessment, and treatment of cancer. In particular, novel methylation inhibitors or modulators powerfully kill tumor cells or improve existing therapeutic strategies through different signaling pa

Molecular events in the jaw vascular unit: A traditional review of the mechanisms involved in inflammatory jaw bone diseases.

Inflammatory jaw bone diseases are common in stomatology, including periodontitis, peri-implantitis, medication-related osteonecrosis of the jaw, radiation osteomyelitis of the jaw, age-related osteoporosis, and other specific infections. These diseases may lead to tooth loss and maxillofacial deformities, severely affecting patients' quality of life. Over the years, the reconstruction of jaw bone deficiency caused by inflammatory diseases has emerged as a medical and socioeconomic challenge. Therefore, exploring the pathogenesis of inflammatory diseases associated with jaw bones is crucial fo

Эпидемиология, патология и патогенез MS: терапевтические последствия.

Множественный склероз (MS) является хроническим и потенциально деактивирующим воспалительным заболеванием центральной нервной системы (CNS). МS, как правило, характеризуется повторяющимися и самоограниченными эпизодами неврологической дисфункции, которые происходят непредсказуемо и часто приводят к множественным повреждениям тканей в рамках CNS. В настоящее время женщины страдают в два-три раза чаще, чем мужчины, хотя это, возможно, не произошло в предыдущие периоды времени. Известно, что патогенез MS связан как с критическими генетическими, так и с экологическими механизмами. Тем не менее, по

Cancer Therapy and Exercise Intolerance: The Heart Is But a Part: JACC: CardioOncology State-of-the-Art Review.

The landscape of cancer therapeutics is continually evolving, with successes in improved survivorship and reduced disease progression for many patients with cancer. Improved cancer outcomes expose competing comorbidities, some of which may be exacerbated by cancer therapies. The leading cause of disability and death for many early-stage cancers is cardiovascular disease (CVD), which is often attributed to direct or indirect cardiac injury from cancer therapy. In this review, the authors propose that toxicities related to conventional and novel cancer therapeutics should be considered beyond th

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… Although aromatase inhibitors are associated with significant myalgias and muscle weakness, there is no clear evidence that these symptoms are secondary to muscle atrophy or myosteatosis. 118 Similarly, selective estrogen receptor modulators (eg, tamoxifen) do not appear to induce adverse changes in …

Bone health in cancer: perspective on the use of osteoanabolic agents.

Cancer negatively impacts bone health through various mechanisms, including treatment-induced bone loss and malignant bone lesions, often leading to increased fracture risk and higher morbidity and mortality. Antiresorptive agents (bisphosphonates and denosumab) are the current standard of care to reduce the risk of skeletal-related events and prevent treatment-related fragility fractures in patients with cancer. While there is strong evidence to support their benefits in cancer, there is potential room for further reduction in the risk of pathologic and fragility fractures. This narrative rev