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Comprehensive analysis of mRNA-microRNA-lncRNA expression profiles in post-traumatic elbow heterotopic ossification using RNA sequencing and experimental validation.

BackgroundThis study aimed to profile the molecular signatures of post-traumatic elbow heterotopic ossification (HO) to identify key regulators and potential therapeutic targets.MethodsTotal RNA from post-traumatic elbow HO tissues (n=4) and normal bone tissues (n=6) was subjected to high-throughput sequencing to identify differentially expressed mRNAs (DEGs), microRNAs (DEMs), and lncRNAs (DELs). Bioinformatics analyses included Gene Ontology (GO), Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway enrichment, protein-protein interaction network construction, and transcription factor (TF)

Overcoming resistance to anabolic SARM therapy in experimental cancer cachexia with an HDAC inhibitor.

No approved therapy exists for cancer-associated cachexia. The colon-26 mouse model of cancer cachexia mimics recent late-stage clinical failures of anabolic anti-cachexia therapy and was unresponsive to anabolic doses of diverse androgens, including the selective androgen receptor modulator (SARM) GTx-024. The histone deacetylase inhibitor (HDACi) AR-42 exhibited anti-cachectic activity in this model. We explored combined SARM/AR-42 therapy as an improved anti-cachectic treatment paradigm. A reduced dose of AR-42 provided limited anti-cachectic benefits, but, in combination with GTx-024, sign

Killing me softly--future challenges in apoptosis research.

The induction of apoptosis, a highly regulated and clearly defined mode of cell dying, is a vital tenet of modern cancer therapy. In this review we focus on three aspects of apoptosis research which we believe are the most crucial and most exciting areas currently investigated and that will need to be better understood in order to enhance the efficacy of therapeutic measures. First, we discuss which target to select for cancer therapy and argue that not the cancer cell as such, but its interaction with the microenvironment is a more promising and genetically stable site of attack. Second, the

Advanced Technologies for Large Scale Supply of Marine Drugs.

Marine organisms represent a source of unique chemical entities with valuable biomedical potentialities, broad diversity, and complexity. It is essential to ensure a reliable and sustainable supply of marine natural products (MNPs) for their translation into commercial drugs and other valuable products. From a structural point of view and with few exceptions, MNPs of pharmaceutical importance derive from the so-called secondary metabolism of marine organisms. When production strategies rely on marine macroorganisms, harvesting or culturing coupled with extraction procedures frequently remain t

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

Integrating Nature Into Oncology: Enhancing Hematological Malignancies Therapies With Natural Medicine.

Hematological malignancies are complex clonal disorders that pose a significant threat to human health. Current treatment modalities, including radiotherapy, chemotherapy, immunotherapy, and bone marrow transplantation, have demonstrated efficacy but are often limited by side effects, drug resistance, and suboptimal cure rates. Natural medicines, as key elements of complementary and alternative medicine, exhibit considerable potential in combating hematological cancers. Particularly when used in combination with conventional therapies, they can enhance treatment efficacy and reverse drug resis

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

Ten tips for an onco-nephrology clinic.

An increasing number of cancer patients are benefiting from long term cancer-directed therapy with an ever-expanding arsenal of novel agents from monoclonal antibodies to small molecules and cellular therapies in addition to the mainstay cytotoxic chemotherapy. All these therapies are accompanied by a unique array of adverse events, which include kidney toxicity. In this context, the need for onco-nephrology expertise continues to grow. Oncologists and hematologists collaborate closely with onco-nephrologists to determine: (i) treatment options for special populations based on accurate assessm

Metabolic Rewiring in Radiation Oncology Toward Improving the Therapeutic Ratio.

To meet the anabolic demands of the proliferative potential of tumor cells, malignant cells tend to rewire their metabolic pathways. Although different types of malignant cells share this phenomenon, there is a large intracellular variability how these metabolic patterns are altered. Fortunately, differences in metabolic patterns between normal tissue and malignant cells can be exploited to increase the therapeutic ratio. Modulation of cellular metabolism to improve treatment outcome is an emerging field proposing a variety of promising strategies in primary tumor and metastatic lesion treatme

Companion Diagnostics in Clinical Therapy: Current Applications and Future Directions.

Companion diagnostics (CDx) plays a pivotal role in precision medicine by enabling personalized treatment plans based on individual biomarker profiles. This approach can enhance therapeutic efficacy in selected indications and may reduce healthcare expenditures. Particularly in oncology, precision targeted therapies targeting pathways such as EGFR, HER2, and programmed death-1/programmed death-ligand 1 have established robust models for biomarker-driven treatment. However, rapid advancements in diagnostic technologies, expanding application scopes, and increasingly complex mechanisms of biomar

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

Haematological and Oncological Training Therapy With Stationary Strength and Cardio Machines (HOT) in Routine Cancer Care: A 3-Year Real-World Evaluation of Acceptance, Feasibility, Safety, and Effects.

BackgroundExercise improves physical function and health-related quality of life (HRQoL) in patients with cancer; however, nationwide structured programmes remain limited. A hospital in Germany implemented a donation-funded Haematological and Oncological Training Therapy with Stationary Strength and Cardio Machines (HOT), and a 3-year real-world data analysis aimed to evaluate its acceptance, feasibility, safety, and effects.MethodsHOT comprised 24 sessions of combined resistance and aerobic training, complemented by a sensorimotor module for patients with chemotherapy-induced peripheral neuro

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… The Leisure Score Index (LSI) was calculated by multiplying the number of activity bouts at each intensity by metabolic equivalents (3, 5, and 9 for mild, moderate, and strenuous, respectively) and summing the results. …

The inflammatory and metabolic status of patients with sudden-onset sensorineural hearing loss.

IntroductionSudden sensorineural hearing loss (SSNHL) is a common emergency symptom in otolaryngology that requires immediate diagnosis and treatment. SSNHL has a multifactorial etiology, and its pathophysiologic mechanisms may be associated with inflammatory and metabolic changes that may affect the cochlear microenvironment or its nervous component, thus triggering the process or hindering hearing recovery. Therefore, the aim of this study was to assess metabolic and inflammatory changes to identify systemic parameters that could serve as prognostic factors for hearing recovery in patients w

АКНП 60th Ежегодное совещание: выдержки из плакатов P276 - P550.

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2023 updated MASCC/ESMO consensus recommendations: prevention of nausea and vomiting following multiple-day chemotherapy, high-dose chemotherapy, and breakthrough nausea and vomiting.

PURPOSE: This review is an update of the MASCC/ESMO 2015 recommendations for the prophylaxis of acute and delayed nausea and vomiting induced by multiple-day chemotherapy, high-dose chemotherapy, and breakthrough nausea and vomiting. METHODS: A systematic literature search was conducted using PubMed from June 1, 2015, through February 1, 2023. RESULTS: We identified 56 references (16 were duplications or invalid), leaving 40 manuscripts for this search. The panel classified level I evidence (three manuscripts) and level II evidence (14 manuscripts). High-dose chemotherapy and stem cell trans

Возможности и препятствия для глубокого изучения биологии и медицины.

Глубокое обучение описывает класс алгоритмов машинного обучения, которые способны объединять исходные ресурсы в слои промежуточных характеристик. Эти алгоритмы недавно продемонстрировали впечатляющие результаты в различных областях. Биология и медицина являются богатыми данными дисциплинами, однако данные являются сложными и зачастую недопонятными. Поэтому методы глубокого обучения могут быть особенно подходящими для решения проблем в этих областях. Мы изучаем возможности углубленного изучения различных биомедицинских проблем - стационарная классификация, фундаментальные биологические процессы

PET Molecular Imaging: A Holistic Review of Current Practice and Emerging Perspectives for Diagnosis, Therapeutic Evaluation and Prognosis in Clinical Oncology.

PET/CT molecular imaging has been imposed in clinical oncological practice over the past 20 years, driven by its two well-grounded foundations: quantification and radiolabeled molecular probe vectorization. From basic visual interpretation to more sophisticated full kinetic modeling, PET technology provides a unique opportunity to characterize various biological processes with different levels of analysis. In clinical practice, many efforts have been made during the last two decades to standardize image analyses at the international level, but advanced metrics are still under use in practice.

Cancer and Exercise: Warburg Hypothesis, Tumour Metabolism and High-Intensity Anaerobic Exercise.

There is ample evidence that regular moderate to vigorous aerobic physical activity is related to a reduced risk for various forms of cancer to suggest a causal relationship. Exercise is associated with positive changes in fitness, body composition, and physical functioning as well as in patient-reported outcomes such as fatigue, sleep quality, or health-related quality of life. Emerging evidence indicates that exercise may also be directly linked to the control of tumour biology through direct effects on tumour-intrinsic factors. Beside a multitude of effects of exercise on the human body, on

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… Regular moderate to vigorous physical activity (any PA of an intensity >3 metabolic equivalents (METs)) was shown to be associated with a lower risk for developing several cancers, including proximal (24%) and distal (23%) colon, endometrial (17%, albeit only in postmenopausal overweight/obese women) …

New insights into non-small cell lung cancer bone metastasis: mechanisms and therapies.

Bone metastasis is a common cause of death in patients with non-small cell lung cancer (NSCLC), with approximately 30-40% of NSCLC patients eventually developing bone metastases. Bone metastasis, especially the occurrence of skeletal-related events (SREs), significantly reduces overall survival (OS) and quality of life (QoL) in patients. Although bone-targeting agents (BTAs) have been shown to reduce SREs and improve QoL in NSCLC patients with bone metastases, the prognosis for these patients remains poor. Understanding the underlying molecular pathways of bone metastasis is crucial for the de

Diverse antitumor effects of ascorbic acid on cancer cells and the tumor microenvironment.

Ascorbic acid has attracted substantial attention for its potential antitumor effects by acting as an antioxidant in vivo and as a cofactor in diverse enzymatic reactions. However, solid proof of its clinical efficacy against cancer and the mechanism behind its effect have not been established. Moreover, cancer forms cancer-specific microenvironments and interacts with various cells, such as cancer-associated fibroblasts (CAFs), to maintain cancer growth and progression; however, the effect of ascorbic acid on the cancer microenvironment is unclear. This review discusses the effects and mechan