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Twenty-five years of type I interferon-based treatment: a critical analysis of its therapeutic use.

The clinical exploitation of type I interferon (IFN) as an antiviral and antineoplastic agent is based on the properties originally attributed to this cytokine family, with schedules reflecting only their antiviral and antiproliferative activities. Nevertheless, type I IFN has emerged as a central activator of the innate immunity. As current schedules of treatment for chronic hepatitis C and for hematological and solid tumors, based on the continuous administration of recombinant type I IFN or pegylated formulations, disregard viral resistance, host genetic variants predicting treatment outcom

Selegiline induces neuroprotection via PGC-1α/Nrf2 gene upregulation in H2O2 -treated hippocampal-derived neural stem/progenitor cells.

Oxidative stress mediated by reactive oxygen species (ROS) is a major contributor to the pathogenesis of neurodegenerative diseases, including Alzheimer's, Parkinson's, Huntington's, multiple sclerosis, and amyotrophic lateral sclerosis. Selegiline, a monoamine oxidase B inhibitor, has been reported to exert neuroprotective effects, although its precise cytoprotective mechanisms remain unclear. In this study, we investigated the effects of selegiline on apoptosis, necrosis, and cell survival in hydrogen peroxide (H₂O₂)-treated hippocampal-derived neural stem/progenitor cells (HD-NSPCs) in vitr

An Updated Review on Marine Anticancer Compounds: The Use of Virtual Screening for the Discovery of Small-Molecule Cancer Drugs.

Marine secondary metabolites are a promising source of unexploited drugs that have a wide structural diversity and have shown a variety of biological activities. These compounds are produced in response to the harsh and competitive conditions that occur in the marine environment. Invertebrates are considered to be among the groups with the richest biodiversity. To date, a significant number of marine natural products (MNPs) have been established as antineoplastic drugs. This review gives an overview of MNPs, both in research or clinical stages, from diverse organisms that were reported as bein

The Cancer Antioxidant Regulation System in Therapeutic Resistance.

Antioxidants play a pivotal role in neutralizing reactive oxygen species (ROS), which are known to induce oxidative stress. In the context of cancer development, cancer cells adeptly maintain elevated levels of both ROS and antioxidants through a process termed "redox reprogramming". This balance optimizes the proliferative influence of ROS while simultaneously reducing the potential for ROS to cause damage to the cell. In some cases, the adapted antioxidant machinery can hamper the efficacy of treatments for neoplastic diseases, representing a significant facet of the resistance mechanisms ob

Advancing CRISPR genome editing into gene therapy clinical trials: progress and future prospects.

Genome editing has recently evolved from a theoretical concept to a powerful and versatile set of tools. The discovery and implementation of CRISPR-Cas9 technology have propelled the field further into a new era. This RNA-guided system allows for specific modification of target genes, offering high accuracy and efficiency. Encouraging results are being announced in clinical trials employed in conditions like sickle cell disease (SCD) and transfusion-dependent beta-thalassaemia (TDT). The path finally led the way to the recent FDA approval of the first gene therapy drug utilising the CRISPR/Cas

IDH Mutations in Glioma: Molecular, Cellular, Diagnostic, and Clinical Implications.

In 2021, the World Health Organization classified isocitrate dehydrogenase (IDH) mutant gliomas as a distinct subgroup of tumors with genetic changes sufficient to enable a complete diagnosis. Patients with an IDH mutant glioma have improved survival which has been further enhanced by the advent of targeted therapies. IDH enzymes contribute to cellular metabolism, and mutations to specific catalytic residues result in the neomorphic production of D-2-hydroxyglutarate (D-2-HG). The accumulation of D-2-HG results in epigenetic alterations, oncogenesis and impacts the tumor microenvironment via i

Epigenetic and Transcriptomic Regulation Landscape in HPV+ Cancers: Biological and Clinical Implications.

Human Papillomavirus (HPV) is an oncogenic virus that causes the highest number of viral-associated cancer cases and deaths worldwide, with more than 690,000 new cases per year and 342,000 deaths only for cervical cancer (CC). Although the incidence and mortality rates for CC are declining in countries where screening and vaccination programs have been implemented, other types of cancer in which HPV is involved, such as oropharyngeal cancer, are increasing, particularly in men. Mutational and transcriptional profiles of various HPV-associated neoplasms have been described, and accumulated evid

Looking for the Holy Grail-Drug Candidates for Glioblastoma Multiforme Chemotherapy.

Glioblastoma multiforme (GBM) is the deadliest and the most heterogeneous brain cancer. The median survival time of GBM patients is approximately 8 to 15 months after initial diagnosis. GBM development is determined by numerous signaling pathways and is considered one of the most challenging and complicated-to-treat cancer types. Standard GBM therapy consist of surgery followed by radiotherapy or chemotherapy, and combined treatment. Current standard of care (SOC) does not offer a significant chance for GBM patients to combat cancer, and the selection of available drugs is limited. For almost

The role and mechanisms of action of microRNAs in cancer drug resistance.

MicroRNAs (miRNAs) are small non-coding RNAs with a length of about 19-25 nt, which can regulate various target genes and are thus involved in the regulation of a variety of biological and pathological processes, including the formation and development of cancer. Drug resistance in cancer chemotherapy is one of the main obstacles to curing this malignant disease. Statistical data indicate that over 90% of the mortality of patients with cancer is related to drug resistance. Drug resistance of cancer chemotherapy can be caused by many mechanisms, such as decreased antitumor drug uptake, modified

TMED2/9/10 Serve as Biomarkers for Poor Prognosis in Head and Neck Squamous Carcinoma.

Background: Head and neck squamous carcinoma (HNSC) is one of the most common malignant tumors with high incidence and poor prognosis. Transmembrane emp24 structural domain (TMED) proteins are involved in protein transport and vesicle budding processes, which have implicated various malignancies' progression. However, the roles of TMEDs in HNSC, especially in terms of development and prognosis, have not been fully elucidated. Methods: We applied TIMER 2.0, UALCAN, GEPIA 2, Kaplan-Meier plotter, GEO, The Human Protein Atlas (HPA), cBioPortal, Linkedomics, Metascape, GRNdb, STRING, and Cytoscape

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… The potential upstream transcriptional regulators predicted by TMED2 were XBP1, cAMP-responsive element-binding protein 3 (CREB3), cAMP-responsive element-binding protein three like 2 (CREB3L2), ETS transcription factor ELK3 (ELK3), ETS variant transcription factor 6 (ETV6), and RNA polymerase II subunit …

Клетки T-бет+CXCR3+B вызывают гиперреактивное взаимодействие клеток B-T в множестве склерозов.

Множественный склероз (MS) — аутоиммунное заболевание центральной нервной системы (CNS). Одним из ключевых механизмов в НР является автораспространение (АП) ячеек В и Т, основанное на самопропитании. Здесь мы показываем, что про-воспаление B-T-обогащенные клетки клеток (BTEC) формируются во время AP и зеркальные особенности реакции микроцентра. T-bet+CXCR3+B — основной подмножество клеток, усиливающих и поддерживающих свои параллельные клетки TH1 с помощью интерферона (IFN)-__, и присутствуют в сильно воспламенённой менингетной ткани. Фундаментальная сигнатура активации клеток В находит свое о

Selective molecular inhibition of the HDAC6 ZnF-UBP binding domain impairs multiple myeloma cell function.

Multiple myeloma is a plasma cell malignancy with a poor prognosis despite the recent development of new therapeutic options. Histone deacetylase 6 (HDAC6) is overexpressed in multiple myeloma cells and may be involved in the acquisition of resistance to conventional anti-proteasome treatments. In addition to displaying a deacetylase catalytic activity, HDAC6 plays an essential role in the regulation of autophagy and cell death by recognizing ubiquitinated motifs from misfolded proteins through its C-terminal ZnF-UBP binding domain. These defective proteins are sent to the aggresome to facilit

Spatiotemperal Dynamics of Osteoarthritis: Преобразование значений от стенда до Бедсайда.

Остеоартрит (OA) представляет собой многогранное дегенеративное совместное расстройство, вызванное различными факторами риска, такими, как возраст, механический стресс, воспаление и метаболическое воздействие. Эти элементы способствуют его разнообразным фенотипам и эндотипам, что подчеркивает имманентную сложность болезни. Участие нескольких тканей и их взаимодействие еще больше осложняет расследование ОА. Нынешние ограничения в области технологий пространственного фенотификации в сочетании со сложной сетью многофакторных взаимодействий препятствуют обнаружению надежных ранних диагностических

Многоступенчатые ассоциации патогенеза и болезней Mycobacterium avium подраздел паратуберкулез.

Mycobacterium avium subsp. паратуберкулез (MAP) является основным агентом причинно-следственной связи болезни Джона (JD) в румынках и имеет потенциальные последствия для здоровья населения. Совокупные эпидемиологические и молекулярные данные предполагают, что MAP может способствовать болезни Крона (CD), в то время как его связь с множественным склерозом (MS), тип 1 Болелезный диабет (T1DM) и амиотропический боковой склероз (ALS) остаются ассоциативными без подтвержденной причинно-следственной связи. В настоящем описательном обзоре синтезируются данные о распределении по окружающей среде, генот

Новое применение XPO1 для лечения миэлофиброза.

Myelofibrosis (MF) — новообразование, характеризующееся конституционными симптомами, прогрессивными цитопентиями и селеногамели. В основе патобологии MF лежит активация мутации на пути JAK/STAT и регулирование цитокинового костного мозга. Хотя многие ингибиторы JAK в настоящее время официально утверждены и обеспечивают значительное улучшение симптомов, эти агенты не имеют курса на изменение потенциала. Кроме того, результаты являются неудовлетворительными для пациентов, которые не справляются с ингибиторами JAK, что подчеркивает необходимость применения новых методов лечения, основанных на исп

Liquid biopsies in myeloid malignancies.

Hematologic malignancies are the most common type of cancer affecting children and young adults, and encompass diseases, such as leukemia, lymphoma, and myeloma, all of which impact blood associated tissues such as the bone marrow, lymphatic system, and blood cells. Clinical diagnostics of these malignancies relies heavily on the use of bone marrow samples, which is painful, debilitating, and not free from risks for leukemia patients. Liquid biopsies are based on minimally invasive assessment of markers in the blood (and other fluids) and have the potential to improve the efficacy of diagnosti

Cold atmospheric plasma sensitizes head and neck cancer to chemotherapy and immune checkpoint blockade therapy.

Head and neck cancer (HNC) is the seventh most prevalent cancer globally, often characterized by chemo-resistance and immunosuppression, which significantly hampers treatment efficacy. Cold atmospheric plasma (CAP) has recently emerged as a promising adjuvant oncotherapy with substantial potential and advantages. In this study, Piezobrush® PZ2, a handheld CAP unit based on the piezoelectric direct discharge technology, was used to generate and deliver non-thermal plasma. We aimed to investigate the effects of CAPPZ2 on various types of HNC cells and elucidate the underlying mechanisms. In addi

Temsirolimus in the treatment of relapsed and/or refractory mantle cell lymphoma.

Patients with mantle cell lymphoma (MCL) have a poor prognosis; consequently, new therapeutic approaches, such as rapamycin and its derivates, mammalian target of rapamycin (mTOR) inhibitors, are warranted. Temsirolimus (also known as CCI-779), a dihydroester of rapamycin, in MCL cell lines inhibited mTOR, downregulated p21 and v-Raf, and induced autophagy. The first clinical trial in MCL patients was performed using 250 mg of temsirolimus weekly for 6-12 cycles. The overall response rate was 38%; the median time to progression was 6.5 months, median overall survival was 12 months, and the med

Androgen Receptor-CaMKK2 Axis in Prostate Cancer and Bone Microenvironment.

The skeletal system is of paramount importance in advanced stage prostate cancer (PCa) as it is the preferred site of metastasis. Complex mechanisms are employed sequentially by PCa cells to home to and colonize the bone. Bone-resident PCa cells then recruit osteoblasts (OBs), osteoclasts (OCs), and macrophages within the niche into entities that promote cancer cell growth and survival. Since PCa is heavily reliant on androgens for growth and survival, androgen-deprivation therapy (ADT) is the standard of care for advanced disease. Although it significantly improves survival rates, ADT detrime

Advances in the assessment of minimal residual disease in mantle cell lymphoma.

The clinical impact of minimal residual disease detection at early time points or during follow-ups has been shown to accurately predict relapses among patients with lymphomas, mainly in follicular and diffuse large B cell lymphoma. The field of minimal residual disease testing in mantle cell lymphoma is still evolving but has great impact in determining the prognosis. Flow cytometry and polymerase chain reaction-based testing are most commonly used methods in practice; however, these methods are not sensitive enough to detect the dynamic changes that underline lymphoma progression. Newer meth