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A new taxonomy was developed for overlap across 'overviews of systematic reviews': A meta-research study of research waste.

Multiple 'overviews of reviews' conducted on the same topic ("overlapping overviews") represent a waste of research resources and can confuse clinicians making decisions amongst competing treatments. We aimed to assess the frequency and characteristics of overlapping overviews. MEDLINE, Epistemonikos and Cochrane Database of Systematic Reviews were searched for overviews that: synthesized reviews of health interventions and conducted systematic searches. Overlap was defined as: duplication of PICO eligibility criteria, and not reported as an update nor a replication. We categorized overview to

A Possible Role of Remdesivir and Plasma Therapy in the Selective Sweep and Emergence of New SARS-CoV-2 Variants.

Since summer 2020, SARS-CoV-2 strains at the origin of the COVID-19 pandemic have suddenly been replaced by new SARS-CoV-2 variants, some of which are highly transmissible and spread at a high rate. These variants include the Marseille-4 lineage (Nextclade 20A.EU2) in Europe, the 20I/501Y.V1 variant first detected in the UK, the 20H/501Y.V2 variant first detected in South Africa, and the 20J/501Y.V3 variant first detected in Brazil. These variants are characterized by multiple mutations in the viral spike protein that is targeted by neutralizing antibodies elicited in response to infection or

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

Role of Telomeres and Telomeric Proteins in Human Malignancies and Their Therapeutic Potential.

Telomeres are the ends of linear chromosomes comprised of repetitive nucleotide sequences in humans. Telomeres preserve chromosomal stability and genomic integrity. Telomere length shortens with every cell division in somatic cells, eventually resulting in replicative senescence once telomere length becomes critically short. Telomere shortening can be overcome by telomerase enzyme activity that is undetectable in somatic cells, while being active in germline cells, stem cells, and immune cells. Telomeres are bound by a shelterin complex that regulates telomere lengthening as well as protects t

APOBEC3B reporter myeloma cell lines identify DNA damage response pathways leading to APOBEC3B expression.

Apolipoprotein B mRNA-editing enzyme catalytic polypeptide-like (APOBEC) DNA cytosine deaminase 3B (A3B) is a DNA editing enzyme which induces genomic DNA mutations in multiple myeloma and in various other cancers. APOBEC family proteins are highly homologous so it is especially difficult to investigate the biology of specifically A3B in cancer cells. To easily and comprehensively investigate A3B function in myeloma cells, we used CRISPR/Cas9 to generate A3B reporter cells that contain 3×FLAG tag and IRES-EGFP sequences integrated at the end of the A3B gene. These reporter cells stably express

Synthetic lethality and DNA damage response targeting in cancer stem cells: a comprehensive review.

This comprehensive review explores the critical intersection of Synthetic Lethality (SL) and DNA Damage Response (DDR) targeting within Cancer Stem Cells (CSCs), a subpopulation central to tumor initiation, metastasis, and therapeutic resistance. CSCs exhibit unique biological properties, including enhanced DNA repair mechanisms and metabolic plasticity, rendering them intrinsically resistant to conventional therapies. The fundamental mechanisms of DDR pathways and their dysregulation in cancer are delineated, highlighting how these vulnerabilities can be exploited through SL. The review synth

Targeting MDM2, RAS, and PCNA for cancer targeted therapy: pan-cancer approaches vs. cancer-specific strategies.

Cancer therapy and cancer drug discovery and development have been historically focused on specific cancers (tissue/organ of origin). However, with advances in molecular biology and multi-omics of cancer, there is a trend to develop pan-cancer therapeutic modalities. In targeted therapy, pan-cancer strategies target common molecular alterations across different cancer types and specific cancer strategies are tailored to the unique biological characteristics of individual tumor types. Each approach offers distinct advantages and limitations, and understanding these differences is critical in th

Drug repurposing approach to fight COVID-19.

Currently, there are no treatment options available for the deadly contagious disease, coronavirus disease 2019 (COVID-19). Drug repurposing is a process of identifying new uses for approved or investigational drugs and it is considered as a very effective strategy for drug discovery as it involves less time and cost to find a therapeutic agent in comparison to the de novo drug discovery process. The present review will focus on the repurposing efficacy of the currently used drugs against COVID-19 and their mechanisms of action, pharmacokinetics, dosing, safety, and their future perspective. R

USP33 Promotes Lung Adenocarcinoma Brain Metastasis by Inhibiting the K48-Linked Ubiquitination and Degradation of S100A9 and Facilitating Vimentin Secretion.

Brain metastasis has a deterministic influence on the evolutionary trajectory of lung adenocarcinoma (LUAD). Given the profound clinical importance of LUAD brain metastases and the formidable obstacles that hinder their precise prediction, novel therapeutic targets are urgently needed. Notably, a substantial fraction of lung carcinoma cells in brain metastatic foci demonstrates marked S100A9 overexpression. However, whether these cells represent the primary drivers of brain metastasis requires further elucidation. Coculture of S100A9-overexpressing LUAD cells with human brain microvascular end

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

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… In addition, E2 is very important for the recruitment of E1 to the replication origin. … Studies using C33a cells infected with HPV16 have revealed that the histone deacetylase sirtuin 1 (SIRT1) is recruited to the HPV replication origin to become part of the functional E1-E2 complex. …

Re-Cellularised Kidney Scaffold for Chikungunya Virus Propagation: A Novel Approach.

BACKGROUND: Re-emerging viral attacks are catastrophic for health and economy. It is crucial to grasp the viral life cycle, replication and mutation policies and attack strategies. It is also absolute to fathom the cost-efficient antiviral remedies earliest possible. METHODS: We propose to use a lab-grown organ (re-cellularized scaffold of sheep kidney) for viral culture and understand its interaction with extra-cellular matrices of the host tissue. RESULTS: Our findings showed that the chikungunya virus (CHIKV) could be better replicated in tissue-engineered bio models than cell culture. A

Beyond Vaccines: Clinical Status of Prospective COVID-19 Therapeutics.

Since November 2019 the SARS-CoV-2 pandemic has caused nearly 200 million infection and more than 4 million deaths globally (Updated information from the World Health Organization, as on 2nd Aug 2021). Within only one year into the pandemic, several vaccines were designed and reached approval for the immunization of the world population. The remarkable protective effects of the manufactured vaccines are demonstrated in countries with high vaccination rates, such as Israel and UK. However, limited production capacities, poor distribution infrastructures and political hesitations still hamper th

Ancient genes establish stress-induced mutation as a hallmark of cancer.

Cancer is sometimes depicted as a reversion to single cell behavior in cells adapted to live in a multicellular assembly. If this is the case, one would expect that mutation in cancer disrupts functional mechanisms that suppress cell-level traits detrimental to multicellularity. Such mechanisms should have evolved with or after the emergence of multicellularity. This leads to two related, but distinct hypotheses: 1) Somatic mutations in cancer will occur in genes that are younger than the emergence of multicellularity (1000 million years [MY]); and 2) genes that are frequently mutated in cance

Определение стабильных и высокоурожайных генотипов кукурузы с использованием показателей стабильности на основе БЛУП и многопробегового отбора в различных средах.

Мейз (Zea Mays L.) one Наиболее важные зерновые культуры во всем мире служат основным источником продовольствия, корма и промышленного сырья; однако выявление высокоурожайных и стабильных генотипов кукурузы в различных средах является одной из ключевых целей программ улучшения кукурузы. Всего 60 Проведена оценка генотипов кукурузы four среды [лето] 2023 (E1), зима 2023 (E2), лето 2024 (Е3) и зима 2024 (Е4)] в конструкции альфа-латице с two тиражирование, включая six неполные блоки с 10 данные в блоке. Впоследствии 15 Для выявления более совершенных и стабильных генотипов кукурузы в различных с

CD38 Is Robustly Induced in Human Macrophages and Monocytes in Inflammatory Conditions.

Macrophages and their monocyte precursors mediate innate immune responses and can promote a spectrum of phenotypes from pro-inflammatory to pro-resolving. Currently, there are few markers that allow for robust dissection of macrophage phenotype. We recently identified CD38 as a marker of inflammatory macrophages in murine in vitro and in vivo models. However, it is unknown whether CD38 plays a similar marker and/or functional role in human macrophages and inflammatory diseases. Here, we establish that CD38 transcript and protein are robustly induced in human macrophages exposed to LPS (±IFN-γ)

Mechanism of Brucea javanica against multiple myeloma via TNF-NF-κB signaling.

This study aims to explore the pharmacological mechanism of Brucea javanica (BJ) in treating multiple myeloma (MM) through network pharmacology and validate this mechanism via in vitro experiments. Active pharmaceutical ingredients (APIs) of BJ and their potential targets were identified, along with MM-related targets. By plotting protein-protein interaction (PPI) networks, hub genes responsible for BJ in treating MM were identified and subjected to molecular docking. In MM cell lines H929 and U266, regulatory effects of BJ and luteolin (the major compound of BJ) on the behaviors of MM cells w

Тип 1 Диабет и многоразовый склероз делятся общей генной переменой автономного иммунитета.

Справочная информация/цели: тип 1 диабет (T1D) и множественный склероз (MS) являются аутоиммунными, многофакторными, специфическими для органов расстройствами, обусловленными иммунными клетками. Их соучастие отчасти объясняется общими генетическими и экологическими факторами. Мы стремились расчленить общую генетическую архитектуру между T1D и MS с использованием крупномасштабных исследований по общегеномной ассоциации (GWAS) и анализа совместной локализации. Методы: Мы применили Байесовскую систему совместной локализации к two Крупномасштабные наборы данных GWAS: исследование T1D, включающее 1

Сенсорность клеток в глиальных клетках: последствия для множественного склероза.

Старение является наиболее распространенным фактором риска для развития заболевания множественным склерозом (MS). Клеточная сенсация, необратимое состояние остановки клеточного цикла, является основным фактором старения и, как было установлено, накапливается преждевременно в нейродегенеративных заболеваниях, включая болезнь Альцгеймера и Паркинсона. В последнее время внимание привлекает клеточная сенсация в центральной нервной системе пациентов MS, при этом ряд исследований свидетельствуют о том, что демиелинация вызывает клеточную сенесценцию с общими признаками p16INK4A и p21 выражения, окис

Методологии изучения мозговых органоидов для изучения механизмов заболевания в прогрессивном множественном склерозе.

Множественный склероз (MS) — изнуряющее аутоиммунное расстройство, направленное против центральной нервной системы (CNS), отмечен непрерывным обезвоживанием и воспалением. В клинической форме она представляет в трех различных формах: повторные выбросы MS (RRMS), первичные прогрессивные MS (PPMS) и вторичные прогрессивные MS (SPMS). Несмотря на то, что лечение с целью изменения болезней (ДМР) оказывает определенное содействие людям, страдающим СВЗ, варианты лечения прогрессивных СЗМ (ПМС) по-прежнему являются крайне неадекватными. Этот пробел свидетельствует о настоятельной необходимости примен

Coronavirus Disease (COVID-19) Control between Drug Repurposing and Vaccination: A Comprehensive Overview.

Respiratory viruses represent a major public health concern, as they are highly mutated, resulting in new strains emerging with high pathogenicity. Currently, the world is suffering from the newly evolving severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2). This virus is the cause of coronavirus disease 2019 (COVID-19), a mild-to-severe respiratory tract infection with frequent ability to give rise to fatal pneumonia in humans. The overwhelming outbreak of SARS-CoV-2 continues to unfold all over the world, urging scientists to put an end to this global pandemic through biological and