Rhabdomyosarcoma: Current Therapy, Challenges, and Future Approaches to Treatment Strategies.

Rhabdomyosarcoma is a rare cancer arising in skeletal muscle that typically impacts children and young adults. It is a worldwide challenge in child health as treatment outcomes for metastatic and recurrent disease still pose a major concern for both basic and clinical scientists. The treatment strategies for rhabdomyosarcoma include multi-agent chemotherapies after surgical resection with or without ionization radiotherapy.

Analytical sensitivity of a method is critical in detection of low-level BRCA1 constitutional epimutation.

Recent reports based on a substantial number of cases, warrant need for population-based research to determine implications of constitutional methylation of tumor suppressor genes such as BRCA1 occurring in healthy tissue in the prediction of cancer. However, the detection of the constitutional methylation in DNA extracted from blood has already been shown to be technologically challenging, mainly because epimutations appear to be present in blood at a very low level. The analytical sensitivity required for low-level methylation detection can be provided by NGS, but this technique is still labor and cost-intensive.

Nuclear expression of Ku70/80 is associated with CHEK2 germline mutations in breast cancer.

Ku70/80 protein inhibitors reduce the repair of DNA double-strand breaks via the Ku70/80 pathway, so they can be used to treat cancers with Ku70/80 overexpression. Since the association of Ku70/80 with germline CHEK2 mutations in breast cancer is unknown, in this study we evaluated the expression of Ku70/80 in breast cancers with germline CHEK2 mutations. Immunohistochemistry with a Ku70/80 antibody on tissue microarrays from 225 CHEK2-associated breast cancers was used and automatically assessed with computerized image analysis.

Improving mitochondrial function in preclinical models of heart failure: therapeutic targets for future clinical therapies?

Introduction: Heart failure is a complex clinical syndrome resulting from the unsuccessful compensation of symptoms of myocardial damage. Mitochondrial dysfunction is a process that occurs because of an attempt to adapt to the disruption of metabolic and energetic pathways occurring in the myocardium. This, in turn, leads to further dysfunction in cardiomyocyte processes.

The association between CYB5A gene rs1790834 polymorphism and clinical improvement after 6 months of leflunomide treatment in women with rheumatoid arthritis.

Introduction/objectives: Rheumatoid arthritis (RA) is a disease affecting around 1% of the population in developed countries and can be treated with leflunomide. The higher prevalence of RA among women and numerous previous studies suggested the crucial role of sex hormones. Cytochrome CYB5A regulates the synthesis of androgens.

The Role of the Human Microbiome in the Pathogenesis of Pain.

Understanding of the gut microbiome's role in human physiology developed rapidly in recent years. Moreover, any alteration of this microenvironment could lead to a pathophysiological reaction of numerous organs. It results from the bidirectional communication of the gastrointestinal tract with the central nervous system, called the gut-brain axis.

An update on drugs with therapeutic potential for SARS-CoV-2 (COVID-19) treatment.

The COVID-19 pandemic is one of the greatest threats to human health in the 21st century with more than 257 million cases and over 5.17 million deaths reported worldwide (as of November 23, 2021. Various agents were initially proclaimed to be effective against SARS-CoV-2, the etiological agent of COVID-19.

The Role of CTLA4 and Its Polymorphisms in Solid Organ and Haematopoietic Stem Cell Transplantation.

HLA matching, transplantation technique, or underlying disease greatly influences the probability of long-term transplantation success. It has been hypothesised that genetic variation affecting antigen presentation also contributes to the outcomes of both solid organ transplantation and allogeneic haematopoietic stem cell transplantation (AHSCT). Those genes, along with those responsible for innate and adaptive immunity, have become targets of investigation.

Role of PFKFB3 and PFKFB4 in Cancer: Genetic Basis, Impact on Disease Development/Progression, and Potential as Therapeutic Targets.

Glycolysis is a crucial metabolic process in rapidly proliferating cells such as cancer cells. Phosphofructokinase-1 (PFK-1) is a key rate-limiting enzyme of glycolysis. Its efficiency is allosterically regulated by numerous substances occurring in the cytoplasm.

Pleiotropic effects of statins: A focus on cancer.

The statin drugs ('statins') potently inhibit hydroxymethylglutaryl-coenzyme A (HMG-CoA) reductase by competitively blocking the active site of the enzyme. Statins decrease de novo cholesterol biosynthesis and thereby reduce plasma cholesterol levels. Statins exhibit "pleiotropic" properties that are independent of their lipid-lowering effects.

FDA approved drugs with pharmacotherapeutic potential for SARS-CoV-2 (COVID-19) therapy.

In December 2019, a novel SARS-CoV-2 coronavirus emerged, causing an outbreak of life-threatening pneumonia in the Hubei province, China, and has now spread worldwide, causing a pandemic. The urgent need to control the disease, combined with the lack of specific and effective treatment modalities, call for the use of FDA-approved agents that have shown efficacy against similar pathogens. Chloroquine, remdesivir, lopinavir/ritonavir or ribavirin have all been successful in inhibiting SARS-CoV-2 in vitro.

COVID-19: Pain Management in Patients with SARS-CoV-2 Infection-Molecular Mechanisms, Challenges, and Perspectives.

Since the end of 2019, the whole world has been struggling with the pandemic of the new Severe Acute Respiratory Syndrome Coronavirus (SARS-CoV-2). Available evidence suggests that pain is a common symptom during Coronavirus Disease 2019 (COVID-19). According to the World Health Organization, many patients suffer from muscle pain (myalgia) and/or joint pain (arthralgia), sore throat and headache.

COVID-19: The Potential Treatment of Pulmonary Fibrosis Associated with SARS-CoV-2 Infection.

In December 2019, a novel coronavirus, SARS-CoV-2, appeared, causing a wide range of symptoms, mainly respiratory infection. In March 2020, the World Health Organization (WHO) declared Coronavirus Disease 2019 (COVID-19) a pandemic, therefore the efforts of scientists around the world are focused on finding the right treatment and vaccine for the novel disease. COVID-19 has spread rapidly over several months, affecting patients across all age groups and geographic areas.

Reprogramming and transdifferentiation - two key processes for regenerative medicine.

Regenerative medicine based on transplants obtained from donors or foetal and new-born mesenchymal stem cells, encounter important obstacles such as limited availability of organs, ethical issues and immune rejection. The growing demand for therapeutic methods for patients being treated after serious accidents, severe organ dysfunction and an increasing number of cancer surgeries, exceeds the possibilities of the therapies that are currently available. Reprogramming and transdifferentiation provide powerful bioengineering tools.

Using pharmacogenetics to predict methotrexate response in rheumatoid arthritis patients.

Introduction: Methotrexate (MTX) is a folate antagonist and a first-line drug for the treatment of rheumatoid arthritis (RA). However, in up to 30% of cases, MTX monotherapy is insufficient, while a further 30% of patients suffer with severe adverse effects. Despite extensive clinical evidence, it is not currently possible to predict therapy outcomes and drug toxicity for MTX.

Aspirin and its pleiotropic application.

Aspirin (acetylsalicylic acid), the oldest synthetic drug, was originally used as an anti-inflammatory medication. Being an irreversible inhibitor of COX (prostaglandin-endoperoxide synthase) enzymes that produce precursors for prostaglandins and thromboxanes, it has gradually found several other applications. Sometimes these applications are unrelated to its original purpose for example its use as an anticoagulant.

The evolution in our understanding of the genetics of rheumatoid arthritis and the impact on novel drug discovery.

: Rheumatoid arthritis (RA) is an autoimmune disease that is characterized by chronic inflammation of the joints and affects 1% of the population. Polymorphisms of genes that encode proteins that primarily participate in inflammation may influence RA occurrence or become useful biomarkers for certain types of anti-rheumatic treatment.: The authors summarize the recent progress in our understanding of the genetics of RA.

Umbilical cord blood transplantation and the impact of the CTLA4 genotype on outcomes.

: Umbilical cord blood transplantation is an effective method of curing multiple diseases when there is no donor available for allogeneic hematopoietic stem cell transplantation (AHSCT). It has been recently suggested that polymorphisms in genes affecting antigen presentation could potentially affect cord blood transplantation (CBT) outcomes.: In this review, we present the results of the latest studies investigating the link between gene variability and umbilical cord blood transplantation outcomes.

The role of genetics and epigenetics in the pathogenesis of gestational diabetes mellitus.

Diabetes mellitus (DM) is a heterogeneous group of disorders whose common trait is chronic hyperglycemia. Gestational diabetes mellitus (GDM) is one of the subtypes of DM that manifests during pregnancy. It is believed that 2%-5% of pregnancies worldwide are complicated with GDM, with the prevalence having significantly increased over the last decade.

Betulin and its derivatives as novel compounds with different pharmacological effects.

Betulin (B) and Betulinic acid (BA) are natural pentacyclic lupane-structure triterpenoids which possess a wide range of pharmacological activities. Recent evidence indicates that B and BA have several properties useful for the treatment of metabolic disorders, infectious diseases, cardiovascular disorders, and neurological disorders. In the current review, we discuss B and BA structures and derivatives and then comprehensively explain their pharmacological effects in relation to various diseases.

New therapies for the treatment of heart failure: a summary of recent accomplishments.

Despite continuous efforts to prevent cardiovascular diseases (CVDs), heart failure prevails as the number one cause of death in developed countries. To properly treat CVDs, scientists had to take a closer look at the factors that contribute to their pathogenesis and either modernize current pharmaceuticals or develop brand new treatments. Enhancement of current drugs, such as tolvaptan and omecamtiv mecarbil, sheds new light on already-known therapies.

CTLA4 antagonists in phase I and phase II clinical trials, current status and future perspectives for cancer therapy.

Introduction: In cancer, the immune response to tumor antigens is often suppressed by inhibitors and ligands. Checkpoint blockade, considered one of the most promising frontiers for anti-cancer therapy, aims to stimulate the immune anti-cancer response. Agents such as cytotoxic T lymphocyte-associated antigen 4 (CTLA-4) inhibitors offer prolonged survival with manageable side effects.

Potential targets of gene therapy in the treatment of heart failure.

Introduction: Heart failure (HF) is one of the most prevalent diseases; it affects millions of people every year. In addition to being one of the major causes of mortality, it generates a financial burden on healthcare systems. Despite progress in developing new pharmaceuticals intended to treat HF, even the newest therapies are not satisfactory.