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Gene expression signatures that predict radiation exposure in mice and humans.

BackgroundThe capacity to assess environmental inputs to biological phenotypes is limited by methods that can accurately and quantitatively measure these contributions. One such example can be seen in the context of exposure to ionizing radiation.Methods and findingsWe have made use of gene expression analysis of peripheral blood (PB) mononuclear cells to develop expression profiles that accurately reflect prior radiation exposure. We demonstrate that expression profiles can be developed that not only predict radiation exposure in mice but also distinguish the level of radiation exposure, rang

Processes and therapeutic perspectives of acylation modifications of lysine and cysteine in tumors.

Acylation modification plays a crucial role in tumor progression through altering protein homeostasis and localization. However, a comprehensive summary of these processes is lacking. Protein acylation modifications are comprehensively summarized and categorized based on the amino acids that are modified. This review focuses on modifications of the lysine (acetylation, succinylation, crotonylation, malonylation, and glutarylation) and cysteine (myristoylation and palmitoylation) groups. The key enzymes involved in the occurrence and erasure of different modifications, as well as their effects

An Extensive Review on Preclinical and Clinical Trials of Oncolytic Viruses Therapy for Pancreatic Cancer.

Chemotherapy resistance and peculiar tumor microenvironment, which diminish or mitigate the effects of therapies, make pancreatic cancer one of the deadliest malignancies to manage and treat. Advanced immunotherapies are under consideration intending to ameliorate the overall patient survival rate in pancreatic cancer. Oncolytic viruses therapy is a new type of immunotherapy in which a virus after infecting and lysis the cancer cell induces/activates patients' immune response by releasing tumor antigen in the blood. The current review covers the pathways and molecular ablation that take place

Upregulation of TTK expression is associated with poor prognosis and immune infiltration in endometrial cancer patients.

BackgroundThreonine and tyrosine kinase (TTK) is associated with invasion and metastasis in various tumors. However, the prognostic importance of TTK and its correlation with immune infiltration in endometrial cancer (EC) remain unclear.MethodsThe expression profile of TTK was analyzed using data from The Cancer Genome Atlas (TCGA) and the Clinical Proteome Cancer Analysis Consortium (CPTAC). TTK protein and mRNA levels were verified in EC cell lines. Receiver operating characteristic (ROC) curve analysis was used to evaluate the ability of TTK to distinguish between normal and EC tissues. K-M

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… Chandler BC TTK inhibition radiosensitizes basal-like Breast cancer through impaired homologous recombination J Clin Invest 2020 130 2 958 73 10.1172/JCI130435 31961339 PMC6994133 28. …

Targeting Glutathione Metabolism: Partner in Crime in Anticancer Therapy.

Glutathione (GSH) is the predominant low-molecular-weight antioxidant with a ubiquitous distribution inside the cell. The steady-state level of cellular GSH is dependent on the balance between synthesis, hydrolysis, recycling of glutathione disulphide (GSSG) as well as cellular extrusion of reduced, oxidized, or conjugated-forms. The augmented oxidative stress typical of cancer cells is accompanied by an increase of glutathione levels that confers them growth advantage and resistance to a number of chemotherapeutic agents. Targeting glutathione metabolism has been widely investigated for cance

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… Several examples of synthetic lethal approaches involve DNA damage response pathways including non-homologous end joining (NHEJ) and homologous recombination (HR) for double-strand break (DSB) repair or base excision repair (BER) for single-strand break (SSB) damages. …

Parasites revive hope for cancer therapy.

Parasites have attained a life-long stigma of being detrimental organisms with deleterious outcomes. Yet, recently, a creditable twist was verified that can dramatically change our perception of those parasites from being a source of misery to millions of people to a useful anti-cancerous tool. Various parasites have shown promise to combat cancer in different experimental models, including colorectal, lung, and breast cancers, among others. Helminths and protozoan parasites, as well as their derivatives such as Echinococcus granulosus protein KI-1, Toxoplasma gondii GRA15II, and Trypanosoma c

Advancements in antibody-drug conjugates as cancer therapeutics.

Antibody-drug conjugates (ADCs) represent a promising approach in targeted cancer therapy, combining the targeted precision of antibodies with the potency of cytotoxic payloads to selectively target tumour cell whilst minimising off-target effects. This review provides a comprehensive analysis of ADCs, encompassing their structural components, mechanisms of action, and clinical applications. It also examines recent technological advancements, particularly in antibody engineering and linker design, aimed at enhancing therapeutic efficacy and safety. The current clinical landscape is outlined, h

Учебный протокол: Исследовательный эксперимент на базе осмотина в качестве адъютанта для лечения прогрессивного множественного склероза.

ЦЕЛЬ: Множественный склероз (MS) является первой причиной нетравматических неврологических расстройств у молодых людей. Первичные и вторичные прогрессивные MS по-прежнему не имеют эффективных методов лечения. Недавно был разработан новый продукт, изготовленный из листьев листьев биоинженерных киви (Actinidia deliciosa), перевыражающих осмотин. Осмотин — белок, связанный с адаптацией к стрессу в растительных клетках, и он обладает противовоспалительными и нейрозащитными свойствами с адипонектином млекопитающих. Цель этого исследования заключается в изучении вопроса о безопасности и эффективност

Долгосрочная стабильность и производительность генных движителей на основе Cas9/Guide RNA в анофелиновых комарах.

Разрабатываются стратегии изменения численности населения с целью борьбы с распространением анофелиных комаров паразитов, вызывающих человеческую малярию. Эти подходы направлены на сокращение заболеваемости и заболеваемости за счет распространения доминирующих генов антипаратионного эффекта среди переносчиков инфекции. Для того чтобы штаммы могли оказывать эпидемиологическое воздействие, они должны в течение продолжительного периода времени сохранять свойства привода и подавления паразитов. Three Gene-drive штаммы, AcTP13 и AcTP43 в Anopheles coluszii и AgTP13 в Anopheles gambiae, с автономным

Inflammation in cancer: therapeutic opportunities from new insights.

As one part of the innate immune response to external stimuli, chronic inflammation increases the risk of various cancers, and tumor-promoting inflammation is considered one of the enabling characteristics of cancer development. Recently, there has been growing evidence on the role of anti-inflammation therapy in cancer prevention and treatment. And researchers have already achieved several noteworthy outcomes. In the review, we explored the underlying mechanisms by which inflammation affects the occurrence and development of cancer. The pro- or anti-tumor effects of these inflammatory factors

Small molecules in targeted cancer therapy: advances, challenges, and future perspectives.

Due to the advantages in efficacy and safety compared with traditional chemotherapy drugs, targeted therapeutic drugs have become mainstream cancer treatments. Since the first tyrosine kinase inhibitor imatinib was approved to enter the market by the US Food and Drug Administration (FDA) in 2001, an increasing number of small-molecule targeted drugs have been developed for the treatment of malignancies. By December 2020, 89 small-molecule targeted antitumor drugs have been approved by the US FDA and the National Medical Products Administration (NMPA) of China. Despite great progress, small-mol

Osteoporosis: Current and Emerging Therapies Targeted to Immunological Checkpoints.

Osteoporosis is a skeletal pathology characterized by compromised bone strength leading to increased risk of fracture, mainly the spine and hip fractures. Osteoporosis affects more than 200 million people worldwide and because of the skeletal fractures it causes, represents a major cause of morbidity, disability and mortality in older people. Recently, the new discoveries of osteoimmunology have clarified many of the pathogenetic mechanisms of osteoporosis, helping to identify new immunological targets for its treatment opening the way for new and effective therapies with biological drugs. Cur

Review of Potential Barriers to Effective Hemostatic Management of Acquired Hemophilia A by Non-Hemophilia Experts in the United States.

Acquired hemophilia A (AHA) is an ultra-rare autoimmune disorder caused by autoantibodies against factor VIII. It often presents with life-threatening bleeding to non-hemophilia experts, who have limited awareness of this condition. This review evaluated hemostatic management and identified barriers to optimal management of AHA by non-hemophilia experts in the United States through a literature review. AHA case reports published by non-hemophilia experts from January 2016 through November 2021 in non-hematology journals were critically reviewed for a chronology of clinical course and managemen

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

Unlocking the potential: advancements and applications of gene therapy in severe disorders.

INTRODUCTION: Several severe disorders, such as inherited diseases (e.g. cystic fibrosis and beta thalassemia), genetic diseases (e.g. malignant tumors and diabetes), and infectious diseases (e.g. HIV) are pose significant challenges to human health. BACKGROUND: Over the past few decades, researchers have been working on gene therapies, and currently, terrible dreams have come true. To date, the Food and Drug Administration (FDA) has approved multiple gene therapies such as Kynamro for familial hypercholesterolaemia, Exondys51 for duchenne muscular dystrophy, Spinraza for spinal muscular atro

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… Zinc finger nuclease (ZFN) The traditional in vivo gene targeting approach uses normal homologous recombination, which is a tedious, time-consuming, and inefficient process. … TALEN The foundation of TALENs is the in vivo homologous recombination method, which encourages extremely repetitive sequences. …

Toward fully exploiting the therapeutic potential of marketed pharmaceuticals: the use of octreotide and chloroquine in oncology.

Pleiotropy in biological systems and their targeting allows many pharmaceuticals to be used for multiple therapeutic purposes. Fully exploiting the therapeutic properties of drugs that are already marketed would be highly advantageous. This is especially the case in the field of oncology, where the ineffectiveness of typical anticancer agents is a common issue, while the development of novel anticancer agents is a costly and particularly time-consuming process. Octreotide and chloroquine are two pharmaceuticals that exhibit profound antitumorigenic activities. However, the current therapeutic

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… Importantly, chloroquine combined with carboplatin inhibited the homologous recombination-mediated repair of DNA double-strand breaks by selectively decreasing Rad50 and Rad51 levels in the CSC subpopulation. … Altogether, these data indicate the possible clinical exploitability of chloroquine combined with carboplatin in the treatment of TNBC, which would harness the anti-CSC properties of chloroquine and the ability of chloroquine in conjunction with carboplatin to prevent the homologous recombination-mediated …

SFRP5 inhibits melanin synthesis of melanocytes in vitiligo by suppressing the Wnt/β-catenin signaling.

Secreted frizzled-related protein 5 (SFRP5) plays a pivotal role in regulating the development of many tissues and organs, however, as an inhibitor of Wnt signaling, the role of SFRP5 in vitiligo remains unknown. Hence, we speculated that SFRP5 might be associated with melanogenesis in melanocytes by regulating Wnt signaling in vitiligo. In this study, we found that SFRP5 was overexpressed in the skin lesions of patients with vitiligo. Compared with that in normal epidermal melanocytes (PIG1), the expression of SFRP5 was increased in vitiligo melanocytes (PIG3V). To investigate the effect of S

Advances in the mechanism and therapies of achondroplasia.

Achondroplasia (ACH), is the prevailing type of genetic dwarfism in humans, caused by mutations in fibroblast growth factor receptor 3 (FGFR3) that are inherited in an autosomal dominant manner. FGFR3 is mainly expressed in condensed mesenchyme, chondrocytes, and mature osteoblasts and osteoclasts, in which it regulates the formation, development, growth, and remodeling of the skeletal system. Mutations in FGFR3 causing ACH result in enhanced FGFR3 signaling through combined mechanisms including enhancing FGF dimerization and tyrosine kinase activity and stabilizing FGF receptors. In ACH, supp

Recent Developments and Evolving Therapeutic Strategies in KMT2A-Rearranged Acute Leukemia.

BackgroundRearrangements of the histone-lysine-N-methyltransferase (KMT2A), previously referred to as mixed-lineage leukemia (MLL), are among the most common chromosomal abnormalities in patients with acute myeloid leukemia (AML) and acute lymphoblastic leukemia (ALL), involving numerous different fusion partners. KMT2A-rearranged (KMT2A-r) leukemia is characterized by a rapid onset, aggressive progression, and significantly worse prognosis compared to non-KMT2A-r leukemias. Even with contemporary chemotherapeutic treatments and hematopoietic stem cell transplantations (HSCT), patients with KM

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… This heightened sensitivity is attributed to their decreased production of critical homologous recombination (HR)‐related genes and their impaired response to damaged DNA (DDR). … recombination repair (HRR) | Selective induction of cytotoxicity in TCF3‐HLF–positive leukemic cells | [ 73 ] Clinical study in patients with KMT2A ‐r‐AML with solid tumor | Allo‐HSCT | Hematopoiesis | Eliminates the bad prognosis in KMT2A ‐r solid tumor therapy‐related AML | [ 74 ] Clinical study on …

Molecular Approaches To Target GPCRs in Cancer Therapy

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