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Targeting Metabolic Reprogramming in Acute Myeloid Leukemia.

The cancer metabolic reprogramming allows the maintenance of tumor proliferation, expansion and survival by altering key bioenergetics, biosynthetic and redox functions to meet the higher demands of tumor cells. In addition, several metabolites are also needed to perform signaling functions that further promote tumor growth and progression. These metabolic alterations have been exploited in different cancers, including acute myeloid leukemia, as novel therapeutic strategies both in preclinical models and clinical trials. Here, we review the complexity of acute myeloid leukemia (AML) metabolism

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Computational proteomics to enhance personalized treatment of COVID-19 and Long COVID.

The coronavirus disease 2019 (COVID-19) pandemic, caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), has led to significant global health burden, including both acute infections and persistent post-acute sequelae, also known as Long COVID (LC) in survivors. While clinical management has reduced case-fatality rates, a substantial proportion of patients develop LC, a heterogeneous syndrome with long-term symptoms. This complex continuum requires therapeutic strategies for both the acute and chronic phases. Plasma proteomics has emerged as a powerful tool in precision medicin

Decoding IL-23 Signaling Cascade for New Therapeutic Opportunities.

The interleukin 23 (IL-23) is a key pro-inflammatory cytokine in the development of chronic inflammatory diseases, such as psoriasis, inflammatory bowel diseases, multiple sclerosis, or rheumatoid arthritis. The pathological consequences of excessive IL-23 signaling have been linked to its ability to promote the production of inflammatory mediators, such as IL-17, IL-22, granulocyte-macrophage colony-stimulating (GM-CSF), or the tumor necrosis factor (TNFα) by target populations, mainly Th17 and IL-17-secreting TCRγδ cells (Tγδ17). Due to their pivotal role in inflammatory diseases, IL-23 and

Targeting Intercellular Communication in the Bone Microenvironment to Prevent Disseminated Tumor Cell Escape from Dormancy and Bone Metastatic Tumor Growth.

Metastasis to the bone is a common feature of many cancers including those of the breast, prostate, lung, thyroid and kidney. Once tumors metastasize to the bone, they are essentially incurable. Bone metastasis is a complex process involving not only intravasation of tumor cells from the primary tumor into circulation, but extravasation from circulation into the bone where they meet an environment that is generally suppressive of their growth. The bone microenvironment can inhibit the growth of disseminated tumor cells (DTC) by inducing dormancy of the DTC directly and later on following forma

Molecular mechanisms of the preventable causes of cancer in the United States.

Annually, there are 1.6 million new cases of cancer and nearly 600,000 cancer deaths in the United States alone. The public health burden associated with these numbers has motivated enormous research efforts into understanding the root causes of cancer. These efforts have led to the recognition that between 40% and 45% of cancers are associated with preventable risk factors and, importantly, have identified specific molecular mechanisms by which these exposures modify human physiology to induce or promote cancer. The increasingly refined knowledge of these mechanisms, which we summarize here,

Anticancer Role of PPARgamma Agonists in Hematological Malignancies Found in the Vasculature, Marrow, and Eyes.

The use of targeted cancer therapies in combination with conventional chemotherapeutic agents and/or radiation treatment has increased overall survival of cancer patients. However, longer survival is accompanied by increased incidence of comorbidities due, in part, to drug side effects and toxicities. It is well accepted that inflammation and tumorigenesis are linked. Because peroxisome proliferator-activated receptor (PPAR)-gamma agonists are potent mediators of anti-inflammatory responses, it was a logical extension to examine the role of PPARgamma agonists in the treatment and prevention of

Multidisciplinary supportive care in systemic light chain amyloidosis.

The immunoglobulin light-chain amyloidosis is a multisystemic disease which manifests by damage to the vital organs by light chain-derived amyloid fibril. Traditionally, the treatment has been directed to the underlying plasma cell clone with or without high dose chemotherapy followed by autologous stem cell transplantation using melphalan based conditioning. Now with the approval of highly tolerable anti-CD38 monoclonal antibody daratumumab based anti-plasma cell therapy in 2021, high rates of hematologic complete responses are possible even in patients who are otherwise deemed not a candidat

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… In general, cardiac amyloidosis involves the expansion of the extracellular space of the myocardial tissues which later contributes to chamber stiffening and thickening without compensatory dilation [ 11 , 12 ]. …

Ongoing clinical trials and treatment options for patients with systemic sclerosis-associated interstitial lung disease.

SSc is a rare CTD that affects multiple organ systems, resulting in substantial morbidity and mortality. Evidence of interstitial lung disease (ILD) is seen in ∼80% of patients with SSc. Currently there is no approved disease-modifying treatment for ILD and few effective treatment options are available. CYC is included in treatment guidelines, but it has limited efficacy and is associated with toxicity. MMF is becoming the most commonly used medication in clinical practice in North America and the UK, but its use is not universal. Newer agents targeting the pathogenic mechanisms underlying SSc

Anticancer potential of decursin, decursinol angelate, and decursinol from Angelica gigas Nakai: A comprehensive review and future therapeutic prospects.

Many naturally derived compounds are currently used in oncotherapy. Besides official medicine, complementary and alternative medicine practices, including old herbal remedies, are widely used and accepted as additional tools in cancer treatment. Angelica gigas Nakai (AGN), a medicinal herb in Asia, has roots historically used in medicine. This review focuses on key bioactive compounds from AGN roots - decursin, decursinol angelate (DA), and decursinol (DOH). Exploring their source, biosynthesis, and therapeutic mechanisms, the review highlights their role in cancer treatment. Biotechnological

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

The Role of Purported Mucoprotectants in Dealing with Irritable Bowel Syndrome, Functional Diarrhea, and Other Chronic Diarrheal Disorders in Adults.

Chronic diarrhea is a frequent presenting symptom, both in primary care medicine and in specialized gastroenterology units. It is estimated that more than 5% of the global population suffers from chronic diarrhea. and that about 40% of these subjects are older than 60 years. The clinician is frequently faced with the need to decide which is the best therapeutic approach for these patients. While the origin of chronic diarrhea is diverse, impairment of intestinal barrier function, dysbiosis. and mucosal micro-inflammation are being increasingly recognized as underlying phenomena characterizing

Nano-formulations in disease therapy: designs, advances, challenges, and future directions.

Nano-formulations, as an innovative drug delivery system, offer distinct advantages in enhancing drug administration methods, improving bioavailability, promoting biodegradability, and enabling targeted delivery. By exploiting the unique size advantages of nano-formulations, therapeutic agents, including drugs, genes, and proteins, can be precisely reorganized at the microscale level. This modification not only facilitates the precise release of these agents but also significantly enhances their efficacy while minimizing adverse effects, thereby creating novel opportunities for treatment of a

Guggulsterone Induces Apoptosis in Multiple Myeloma Cells by Targeting High Mobility Group Box 1 via Janus Activated Kinase/Signal Transducer and Activator of Transcription Pathway.

Multiple myeloma (MM) is a hematological disorder characterized by the abnormal expansion of plasma cells in the bone marrow. Despite great advances over the past three decades in discovering the efficacious therapies for MM, the disease remains incurable for most patients owing to emergence of drug-resistant cancerous cells. Guggulsterone (GS), a phytosteroid, extracted from the gum resin of guggul plant, has displayed various anticancer activities in vitro and in vivo; however, the molecular mechanisms of its anticancer activity have not been evaluated in MM cells. Therefore, in this study,

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… The activation of the JAK/STAT signaling pathway regulates the nuclear-to-cytoplasmic translocation of HMGB1 and its subsequent release in the extracellular space [ 9 ]. …

Multiplex Screening for Interacting Compounds in Paediatric Acute Myeloid Leukaemia.

Paediatric acute myeloid leukaemia (AML) is a heterogeneous disease characterised by the malignant transformation of myeloid precursor cells with impaired differentiation. Standard therapy for paediatric AML has remained largely unchanged for over four decades and, combined with inadequate understanding of the biology of paediatric AML, has limited the progress of targeted therapies in this cohort. In recent years, the search for novel targets for the treatment of paediatric AML has accelerated in parallel with advanced genomic technologies which explore the mutational and transcriptional land

Adoptive cell therapies in solid tumors: current clinical landscape, challenges, and future directions.

Adoptive cell therapy (ACT) has emerged as a transformative strategy in cancer immunotherapy, offering durable clinical benefit in hematologic malignancies and expanding therapeutic potential in solid tumors. However, the translation of ACT to solid malignancies remains constrained by biological, immunological, and logistical challenges. This narrative review provides an evidence based overview of the current clinical landscape of ACT in solid tumors, with a focus on chimeric antigen receptor T cell (CAR-T), tumor-infiltrating lymphocyte (TIL), and T cell receptor-engineered T cell (TCR-T) the

Osteoid cell-derived chemokines drive bone-metastatic prostate cancer.

One of the greatest challenges in improving prostate cancer (PCa) survival is in designing new therapies to effectively target bone metastases. PCa regulation of the bone environment has been well characterized; however, bone-targeted therapies have little impact on patient survival, demonstrating a need for understanding the complexities of the tumor-bone environment. Many factors contribute to creating a favorable microenvironment for prostate tumors in bone, including cell signaling proteins produced by osteoid cells. Specifically, there has been extensive evidence from both past and recent

Obesity definition, diagnosis, bias, standard operating procedures (SOPs), and telehealth: An Obesity Medicine Association (OMA) Clinical Practice Statement (CPS) 2022.

BackgroundThe Obesity Medicine Association (OMA) Clinical Practice Statement (CPS) regarding definition, diagnosis, bias, standard operating procedures (SOPs) and telehealth is intended to provide clinicians an overview of obesity medicine and provide basic organizational tools towards establishing, directing, managing, and maintaining an obesity medical practice.MethodsThis CPS is based upon published scientific citations, clinical perspectives of OMA authors, and peer review by Obesity Medicine Association leadership.ResultsOMA has defined obesity as: "A chronic, progressive, relapsing, and

Cardiotoxicity Induced by Anticancer Therapies: A Call for Integrated Cardio-Oncology Practice.

The introduction of novel oncologic therapies, including targeted agents, immunotherapies, and antibody-drug conjugates, has transformed the therapeutic landscape of cancer care. This evolution has resulted in a dual clinical scenario; while survival outcomes have markedly improved, leading to a growing population of long-term cancer survivors, an increasing incidence of previously unrecognized treatment-related toxicities has emerged. Among these, cardiovascular adverse events represent some of the most prevalent and clinically significant complications observed in both conventional chemother

Олептические рецепторы в нейронной регенерации в центральной нервной системе.

Олептические рецепторы имеют решающее значение для обнаружения запахов и играют жизненно важную роль в нашем чувстве запаха, оказывая влияние на поведение, начиная от выбора пищи и кончая эмоциональными воспоминаниями. Эти рецепторы также способствуют нашему восприятию вкуса и могут применяться в медицинской диагностике и экологическом мониторинге. Способность обонятельной системы регенерировать свои сенсорные нейроны обеспечивает уникальную модель для изучения нейронной регенерации — явления, которое в основном отсутствует в центральной нервной системе. Понимание, полученное благодаря тому, к