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Transcription and Translation Inhibitors in Cancer Treatment.

Transcription and translation are fundamental cellular processes that govern the protein production of cells. These processes are generally up regulated in cancer cells, to maintain the enhanced metabolism and proliferative state of these cells. As such cancerous cells can be susceptible to transcription and translation inhibitors. There are numerous druggable proteins involved in transcription and translation which make lucrative targets for cancer drug development. In addition to proteins, recent years have shown that the "undruggable" transcription factors and RNA molecules can also be targ

COVID-19 Therapeutic Options Under Investigation.

Since its emergence in China in December 2019, COVID-19 has quickly spread around the globe causing a pandemic. Vaccination or the development of herd immunity seems the only way to slow down the spread of the virus; however, both are not achievable in the near future. Therefore, effective treatments to mitigate the burden of this pandemic and reduce mortality rates are urgently needed. Preclinical and clinical studies of potential antiviral and immunomodulatory compounds and molecules to identify safe and efficacious therapeutics for COVID-19 are ongoing. Two compounds, remdesivir, and dexame

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… The active favipiravir-RTP act as a terminator of nascent RNA strand elongation by competing with purine nucleosides for RdRp binding ( Sangawa et al., 2013 ). Other studies revealed that favipiravir induces its antiviral activity by acting as a lethal mutagen ( Baranovich et al., 2013 ). …

CRISPR-Cas9-Based Gene Knockout of Immune Checkpoints in Expanded NK Cells.

Natural killer (NK) cell immunotherapy has emerged as a novel treatment modality for various cancer types, including leukemia. The modulation of inhibitory signaling pathways in T cells and NK cells has been the subject of extensive investigation in both preclinical and clinical settings in recent years. Nonetheless, further research is imperative to optimize antileukemic activities, especially regarding NK-cell-based immunotherapies. The central scientific question of this study pertains to the potential for boosting cytotoxicity in expanded and activated NK cells through the inhibition of in

Pneumonia in Transplant Recipients: A Comprehensive Review of Diagnosis and Management.

Transplant recipients have an increased risk of complications, including graft dysfunction and infections, which can be life-threatening if not recognized early. Pneumonia ranks as one of the most frequent complications in both solid organ and hematopoietic stem cell transplants. Clinical symptoms manifest late during infections in immunocompromised patients. An aggressive approach centered on early confirmatory diagnosis and a low threshold for empiric therapy is often the most effective strategy. The isolation of a pathogen in an upper airway sample does not necessarily mean the same organis

Molecular factors associated with lung cancer in people living with HIV.

Lung cancer is the most common Non-AIDS-Defining Cancer (NADC) and a leading cause of cancer-related death in People Living With HIV (PLWH). Despite antiretroviral therapy, PLWH are at higher risk of developing cancer compared to the general population. This increased susceptibility reflects a combination of immunosuppression, chronic inflammation, smoking, and direct oncogenic effects of HIV proteins. Tat, gp120, and Nef modulate cell cycle control, apoptosis, epithelial-mesenchymal transition, angiogenesis, and immune evasion. Persistent HIV reservoirs in lung tissue (mainly effector memory

Viruses

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Drugs and Epigenetic Molecular Functions. A Pharmacological Data Scientometric Analysis.

Interactions of drugs with the classical epigenetic mechanism of DNA methylation or histone modification are increasingly being elucidated mechanistically and used to develop novel classes of epigenetic therapeutics. A data science approach is used to synthesize current knowledge on the pharmacological implications of epigenetic regulation of gene expression. Computer-aided knowledge discovery for epigenetic implications of current approved or investigational drugs was performed by querying information from multiple publicly available gold-standard sources to (i) identify enzymes involved in c

Amino acid metabolism in primary bone sarcomas.

Primary bone sarcomas, including osteosarcoma (OS) and Ewing sarcoma (ES), are aggressive tumors with peak incidence in childhood and adolescence. The intense standard treatment for these patients consists of combined surgery and/or radiation and maximal doses of chemotherapy; a regimen that has not seen improvement in decades. Like other tumor types, ES and OS are characterized by dysregulated cellular metabolism and a rewiring of metabolic pathways to support the biosynthetic demands of malignant growth. Not only are cancer cells characterized by Warburg metabolism, or aerobic glycolysis, bu

Integrating Single-Cell Transcriptome and Network Analysis to Characterize the Therapeutic Response of Chronic Myeloid Leukemia.

Chronic myeloid leukemia (CML) is a myeloproliferative disease characterized by a unique BCR-ABL fusion gene. Tyrosine kinase inhibitors (TKIs) were developed to target the BCR-ABL oncoprotein, inhibiting its abnormal kinase activity. TKI treatments have significantly improved CML patient outcomes. However, the patients can develop drug resistance and relapse after therapy discontinues largely due to intratumor heterogeneity. It is critical to understand the differences in therapeutic responses among subpopulations of cells. Single-cell RNA sequencing measures the transcriptome of individual c

What Has Been Learned from Postmortem Studies?

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Herpes Simplex Virus and Varicella Zoster Virus Infections in Cancer Patients.

Herpes simplex virus (HSV) and varicella zoster virus (VZV) are alpha herpesviruses that establish life-long latent infection in neuronal ganglia after primary infection. Periodic reactivation of these viruses results in recurrent infections that can have significant impact on patients' quality of life. HSV commonly causes oral and genital mucocutaneous infections whereas VZV is responsible for varicella/chickenpox and herpes zoster/shingles, but cancer patients are at particularly higher risk of complications including disseminated and visceral infections due to impaired cell-mediated immunit

Novel Molecular Therapies and Genetic Landscape in Selected Rare Diseases with Hematologic Manifestations: A Review of the Literature.

Rare diseases affect less than 1 in 2000 people and are characterized by a serious, chronic, and progressive course. Among the described diseases, a mutation in a single gene caused mastocytosis, thrombotic thrombocytopenic purpura, Gaucher disease, and paroxysmal nocturnal hemoglobinuria (KIT, ADAMTS13, GBA1, and PIG-A genes, respectively). In Castleman disease, improper ETS1, PTPN6, TGFBR2, DNMT3A, and PDGFRB genes cause the appearance of symptoms. In histiocytosis, several mutation variants are described: BRAF, MAP2K1, MAP3K1, ARAF, ERBB3, NRAS, KRAS, PICK1, PIK3R2, and PIK3CA. Genes like H

Кристальная структура и каталитический механизм дрименоловой синтазы, необычная двухфункциональная терпеновая киклаза-фосфатаза.

Дрименол синтаза из Aquimarina pongiae (ASDMS) — очень необычная химера, интегрирующая two - отдельные, последовательные операции по переработке изопреноидов в рамках единой полипептидной цепи. ASDMS катализирует циклизацию фарнесилового дифосфата (FPP) класса II для образования дрименилового дифосфата, который затем подвергается гидролизу энзим-катализу для получения дрименинола, биоактивного сескитерпенового спирта с антифунгальными и антираковыми свойствами. Здесь мы сообщаем рентгеновские кристаллы ASDMS и его комплекс с сескитерпен тиол. Структура ASDMS имеет дидомаиновую архитектуру, сос

Defining neuroblastoma: From origin to precision medicine.

Neuroblastoma (NB), a heterogenous pediatric tumor of the sympathetic nervous system, is the most common and deadly extracranial solid malignancy diagnosed in infants. Numerous efforts have been invested in understanding its origin and in development of novel curative targeted therapies. Here, we summarize the recent advances in the identification of the cell of origin and the genetic alterations occurring during development that contribute to NB. We discuss current treatment regimens, present and future directions for the identification of novel therapeutic metabolic targets, differentiation

Targetable pathways for drug repurposing in gastric cancer.

Gastric cancer (GC) is both the fifth most common cancer worldwide and the fifth in mortality. Owing to a lack of symptoms in the early stages and unspecific clinical presentation in the later stages, GC is usually diagnosed at advanced stages. This means that only approximately 60% of patients are eligible for curative treatment, and overall, GC patients have a 5-year survival rate of only 28.3%, underscoring the importance of developing new treatment strategies. Drug repurposing involves identifying new therapeutic uses for approved drugs and is a promising strategy for cancer treatment beca

RNA modifications in cancer.

RNA modifications are emerging as critical cancer regulators that influence tumorigenesis and progression. Key modifications, such as N6-methyladenosine (m6A) and 5-methylcytosine (m5C), are implicated in various cellular processes. These modifications are regulated by proteins that write, erase, and read RNA and modulate RNA stability, splicing, translation, and degradation. Recent studies have highlighted their roles in metabolic reprogramming, signaling pathways, and cell cycle control, which are essential for tumor proliferation and survival. Despite these scientific advances, the precise

Infections in Hospitalized Cancer Patients.

Cancer patients are at an increased risk of developing infections that are primarily treatment-driven but may also be malignancy-driven. While cancer treatments such as chemotherapy, radiotherapy, and surgery have been known to improve malignancy morbidity and mortality, they also have the potential to weaken immune defenses and induce periods of severe cytopenia. These adverse effects pave the way for opportunistic infections to complicate a hospitalized cancer patient's clinical course. Understanding the risk each patient inherently has for developing a bacterial, fungal, or viral infection

Microbiome and pancreatic cancer: time to think about chemotherapy.

Pancreatic ductal adenocarcinoma (PDAC) is a highly aggressive cancer characterized by late diagnosis, rapid progression, and a high mortality rate. Its complex biology, characterized by a dense, stromal tumor environment with an immunosuppressive milieu, contributes to resistance against standard treatments like chemotherapy and radiation. This comprehensive review explores the dynamic role of the microbiome in modulating chemotherapy efficacy and outcomes in PDAC. It delves into the microbiome's impact on drug metabolism and resistance, and the interaction between microbial elements, drugs,

Potential drug development and therapeutic approaches for clinical intervention in COVID-19.

While the vaccination is now available to many countries and will slowly dissipate to others, effective therapeutics for COVID-19 is still illusive. The SARS-CoV-2 pandemic has posed an unprecedented challenge to researchers, scientists, and clinicians and affected the wellbeing of millions of people worldwide. Since the beginning of the pandemic, a multitude of existing anti-viral, antibiotic, antimalarial, and anticancer drugs have been tested, and some have shown potency in the treatment and management of COVID-19, albeit others failed to leave any positive impact and a few also became cont

Immunological Targets in Generalized Myasthenia Gravis Treatment: Where Are We Going Now?

BackgroundGeneralized myasthenia gravis (gMG) is a heterogeneous autoimmune disorder marked by antibody-mediated disruption of neuromuscular transmission. Despite advancements in immunosuppressive therapies and biologics, a subset of patients remains refractory, necessitating more targeted and personalized treatment strategies.ObjectiveThis review aims to synthesize current knowledge of the immunopathological mechanisms across gMG subtypes and to explore emerging therapeutic targets tailored to these diverse disease phenotypes.MethodsA narrative review was conducted, integrating recent finding