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Всеобъемлющий анализ two Китайские геномы огурцов и мутантов как ресурсы для точного размножения.

Cumuis sativus L., известный как огурец, является важным овощным растениеводством во всем мире, крупнейшим производителем которого является Китай, в особенности северный и южно-китайский типы. В то время как обширные геномные исследования были сосредоточены на Северном Китае, особенно на китайском Лонге. 9930, исследования по Южно-Китайскому типу остаются ограниченными. В этом исследовании мы собрали высококачественные геномы two широко культивируемые и репрезентативные родные разновидности: S36 (тип Северной Китая) и H19 (тип Южной Китая) и провели анализ мутагенезов. Сравнительный анализ ген

Epigenetic and Genetic Keys to Fight HPV-Related Cancers.

Cervical cancer ranks as the fourth most prevalent cancer among women globally, with approximately 600,000 new cases being diagnosed each year. The principal driver of cervical cancer is the human papillomavirus (HPV), where viral oncoproteins E6 and E7 undertake the role of driving its carcinogenic potential. Despite extensive investigative efforts, numerous facets concerning HPV infection, replication, and pathogenesis remain shrouded in uncertainty. The virus operates through a variety of epigenetic mechanisms, and the epigenetic signature of HPV-related tumors is a major bottleneck in our

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… This epigenetic landscape becomes favorable for the recruitment of RNA polymerase II, which, in turn, initiates the transcription of the HPV16 oncogenes from the early promoter [ 139 ]. …

LncRNA RHPN1-AS1 Targeting miR-625/REG3A Promotes Cell Proliferation And Invasion Of Glioma Cells.

IntroductionGlioma arises from the proliferation of neuroglial cells differentiated from the ectoderm. Evidence has confirmed that differentially expressed long non-coding RNAs (lncRNAs) may be involved in the development and progression of various tumors. The present study aimed to explore the biological function of lncRNA RHPN1-AS1 in glioma.Materials and methodsThe expressions of RHPN1-AS1 in glioma tissues and cells were examined using RT-PCR. Colony formation assay, MTT assay, wound healing assay and transwell assay were performed to detect cell cloning efficiency, proliferation, migratio

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… polymerase II transcription, was initially considered to have no biological function. 19 However, recent studies have confirmed that lncRNA has many biological functions, including chromatin modification, 20 chromosome silencing, 21 transcriptional regulation and other biological processes, 22 affecting … Inhibition of RNA polymerase II transcription in human cells by synthetic DNA-binding ligands . Proc Natl Acad Sci U S A . 1998 ; 95 ( 22 ): 12890 – 12895 . doi: 10.1073/pnas.95.22.12890 9789010 PMC23643 20. Sun M , Nie F , Wang Y , et al. …

NDP52 и его новая роль в патогенезе.

Автофагика - это процесс, способствующий выживанию, который регулирует деградацию и обновление клеточных компонентов, что делает его важнейшим механизмом для клеточного гомеостазиза. Существуют выборочные формы автофагии, характерные для ряда субстратов, таких, как патогены (бактерии или вирусы), белковые агрегаты или излишние/поврежденные органеллы. Эти процессы включают в себя в качестве ключевых игроков автофагичные рецепторы, которые связывают груз, подлежащий деградации, с автофагическим оборудованием. Среди них NDP52 (известный также как КАКПО2) был охарактеризован как «бридж» между авто

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… Authors demonstrated that NDP52 clusters with RNA polymerase II (RNAP II) within the nucleus and binds specifically and with high affinity to double-stranded DNA (dsDNA) [ 20 ]. … Finally, NDP52 has a nuclear function as it is able to cluster with RNA polymerase II (RNAPII) at transcription initiation sites and bind double-stranded DNA to induce changes in DNA structure. …

Mechanisms of IFNalpha-1a-Induced Apoptosis in a Laryngeal Cancer Cell Line.

BACKGROUND Interferon alpha (IFNalpha) exerts its anti-proliferative effect on many human cancers. Among the 13 subtypes of human IFNalpha, IFNalpha-1 subtype has 2 variants, named IFNalpha-1a and IFNalpha-1b, that differ from each other in only 1 amino acid, at residue 114. However, the mechanism by which IFNalpha-1a mediates growth inhibition is still unclear. MATERIAL AND METHODS Human laryngeal carcinoma HEp2 cells were treated with IFNalpha-1a by either transient transfection or exogenous delivery. Western blot and RT-PCR analysis were carried out to assess apoptotic pathways active in IF

A dual-mechanism model of Selinexor in DLBCL: p53 reactivation and metabolic reprogramming.

BACKGROUND: Diffuse large B-cell lymphoma (DLBCL) is an aggressive malignancy with limited therapeutic options in the relapsed or refractory setting. Selinexor, a selective inhibitor of nuclear export targeting XPO1, has demonstrated clinical activity in DLBCL. However, the molecular mechanisms underlying its antitumor effects remain incompletely defined. METHODS: We evaluated the clinical efficacy of Selinexor in a real-world cohort of lymphoma patients and performed integrative transcriptomic and proteomic analyses in DLBCL cell models representing germinal center B-cell–like (GCB) and non-G

Targeting the DNA Damage Response for Cancer Therapy.

Over the course of long-term evolution, cells have developed intricate defense mechanisms in response to DNA damage; these mechanisms play a pivotal role in maintaining genomic stability. Defects in the DNA damage response pathways can give rise to various diseases, including cancer. The DNA damage response (DDR) system is instrumental in safeguarding genomic stability. The accumulation of DNA damage and the weakening of DDR function both promote the initiation and progression of tumors. Simultaneously, they offer opportunities and targets for cancer therapeutics. This article primarily elucid

Протекционный субъект PSMD1 является ключевой терапевтической целью в множестве миеломы.

Мы пришли к выводу, что PSMD1 - ключевой субъект протеиновой регуляционной частицы 19S - был чрезмерно экспрессирован и коррелировал с плохим прогнозом в множестве миеломы (ММ). Генетическое истощение PSMD1 снизило жизнеспособность раковых клеток, вызвало поликутилизированное накопление белка и способствовало апоптозу. Протеомический анализ показал активацию иммунных путей, что свидетельствует о потенциале иммунной модуляции. Нацеливание PSMD1 на незначительную поражающую РНК (SIRNA), доставляемую через липидные наночастицы (LNPs), уменьшило рост опухоли в линиях клеток MM и первичных проб пац

Aminoquinolines as Translational Models for Drug Repurposing: Anticancer Adjuvant Properties and Toxicokinetic-Related Features.

The indiscriminate consumption of antimalarials against coronavirus disease-2019 emphasizes the longstanding clinical weapons of medicines. In this work, we conducted a review on the antitumor mechanisms of aminoquinolines, focusing on the responses and differences of tumor histological tissues and toxicity related to pharmacokinetics. This well-defined analysis shows similar mechanistic forms triggered by aminoquinolines in different histological tumor tissues and under coexposure conditions, although different pharmacological potencies also occur. These molecules are lysosomotropic amines th

Translational Advances in Oncogene and Tumor-Suppressor Gene Research.

Cancer, characterized by the uncontrolled proliferation of cells, is one of the leading causes of death globally, with approximately one in five people developing the disease in their lifetime. While many driver genes were identified decades ago, and most cancers can be classified based on morphology and progression, there is still a significant gap in knowledge about genetic aberrations and nuclear DNA damage. The study of two critical groups of genes-tumor suppressors, which inhibit proliferation and promote apoptosis, and oncogenes, which regulate proliferation and survival-can help to unde

Advances of DNA Damage Repair-Related Drugs and Combination With Immunotherapy in Tumor Treatment.

Cancer therapy has been an important and popular area in cancer research. With medical technology developing, the appearance of various targeted drugs and immunotherapy offer more choices to cancer treatment. With the increase in drug use, people have found more and more cases in which tumors are resistant to DNA damage repair (DDR)-based drugs. Recently, the concept of combination therapy has been brought up in cancer research. It takes advantages of combining two or more therapies with different mechanisms, aiming to benefit from the synergistic effects and finally rescue patients irresponsi

Enzimatic Paradox of Yeast Arginil-tRNA Synthetase: Исключительная передача Аргинина, контролируемая гибким механизмом признания tRNA.

Детерминанты идентичности необходимы для точного признания переноса РНК синтетиками аминоачил-тРНА. На сегодняшний день аргининские детерминанты в дрожжах сачаромице были выявлены исключительно in vitro и только на ограниченном числе изоприятцев trNA Arginin. В нынешнем исследовании мы выступаем за полный клеточный подход и расширяем исследования аргининских детерминант до всех four TRNA Arg изо-приемники. В более конкретном плане эта работа позволяет проанализировать актуальность нуклеотидов ТРНА на месте. 20, 35 и 36 в реакции дрожжей на аргинилацию. Мы построили 21 мутантов мутагенезом, упр

Revisiting potential value of antitumor drugs in the treatment of COVID-19.

Since an outbreak started in China in 2019, coronavirus disease 2019 (COVID-19) has rapidly become a worldwide epidemic with high contagiousness and caused mass mortalities of infected cases around the world. Currently, available treatments for COVID-19, including supportive care, respiratory support and antiviral therapy, have shown limited efficacy. Thus, more effective therapeutic modalities are highly warranted. Drug repurposing, as an efficient strategy to explore a potential broader scope of the application of approved drugs beyond their original indications, accelerates the process of d

Current landscape of gene-editing technology in biomedicine: Applications, advantages, challenges, and perspectives.

The expanding genome editing toolbox has revolutionized life science research ranging from the bench to the bedside. These "molecular scissors" have offered us unprecedented abilities to manipulate nucleic acid sequences precisely in living cells from diverse species. Continued advances in genome editing exponentially broaden our knowledge of human genetics, epigenetics, molecular biology, and pathology. Currently, gene editing-mediated therapies have led to impressive responses in patients with hematological diseases, including sickle cell disease and thalassemia. With the discovery of more e

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… GG‐NER used the heterotrimeric lesion recognition factor (consisting of XPC, RAD23, and CETN2) to detect DNA lesions, but TC‐NER used RNA polymerase II (RNAPII), Cockayne syndrome A (CSA) and CSB protein. The BER pathway is responsible for resolving nonbulky single‐base lesions. …

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. The initial results of a number of clinical trials involving various protocols of administr

Aptamers and Antisense Oligonucleotides for Diagnosis and Treatment of Hematological Diseases.

Aptamers or chemical antibodies are single-stranded DNA or RNA oligonucleotides that bind proteins and small molecules with high affinity and specificity by recognizing tertiary or quaternary structures as antibodies. Aptamers can be easily produced in vitro through a process known as systemic evolution of ligands by exponential enrichment (SELEX) or a cell-based SELEX procedure. Aptamers and modified aptamers, such as slow, off-rate, modified aptamers (SOMAmers), can bind to target molecules with less polar and more hydrophobic interactions showing slower dissociation rates, higher stability,

tRNA Derivatives in Multiple Myeloma: Investigation of the Potential Value of a tRNA-Derived Molecular Signature.

Multiple myeloma (MM) is a hematologic malignancy arising from the clonal proliferation of malignant plasma cells. tRNA-derived RNA fragments (tRFs) constitute a class of small non-coding RNAs, deriving from specific enzymatic cleavage of tRNAs. To the best of our knowledge, this is one of few studies to uncover the potential clinical significance of tRFs in MM. Total RNA was extracted from CD138+ plasma cells of MM and smoldering MM patients, and in vitro polyadenylated. First-strand cDNA synthesis was performed, priming from an oligo-dT-adaptor sequence. Next, real-time quantitative PCR (qPC

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… Most of the highly enriched molecular functions, combined with the also highly enriched biological process “mRNA transcription by RNA polymerase II”, could be explained by the regulatory role imputed to 3′tRFs, regarding gene expression. …

Biotechnological Innovations from Ocean: Transpiring Role of Marine Drugs in Management of Chronic Disorders.

Marine drugs are abundant in number, comprise of a diverse range of structures with corresponding mechanisms of action, and hold promise for the discovery of new and better treatment approaches for the management of several chronic diseases. There are huge reserves of natural marine biological compounds, as 70 percent of the Earth is covered with oceans, indicating a diversity of chemical entities on the planet. The marine ecosystems are a rich source of bioactive products and have been explored for lead drug molecules that have proven to be novel therapeutic targets. Over the last 70 years, m

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… These trabectedin abducts arrest the activity of RNA polymerase II and prevent the transcription of DNA, thereby preventing abnormal cellular growth. … The action of RNA polymerase II is arrested with simultaneous DNA transcription prohibition, hence preventing the abnormal growth of the cells. …

Overcoming temozolomide resistance in glioma: recent advances and mechanistic insights.

Temozolomide (TMZ) remains the cornerstone chemotherapy for glioma, yet intrinsic and acquired resistance mechanisms significantly limit its clinical effectiveness. This review summarizes the multifaceted molecular pathways contributing to TMZ resistance, including enhanced DNA repair mechanisms such as O6-methylguanine-DNA methyltransferase (MGMT), mismatch repair (MMR), and base excision repair (BER). Additional resistance factors include genetic mutations that affect the drug response, dysregulated non-coding RNAs (miRNAs, lncRNAs, and circRNAs), glioma stem cells (GSCs), cytoprotective aut

Application of Next Generation Sequencing in Laboratory Medicine.

The rapid development of next-generation sequencing (NGS) technology, including advances in sequencing chemistry, sequencing technologies, bioinformatics, and data interpretation, has facilitated its wide clinical application in precision medicine. This review describes current sequencing technologies, including short- and long-read sequencing technologies, and highlights the clinical application of NGS in inherited diseases, oncology, and infectious diseases. We review NGS approaches and clinical diagnosis for constitutional disorders; summarize the application of U.S. Food and Drug Administr