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Emerging Mechanisms and Treatment Progress on Liver Metastasis of Colorectal Cancer.

Colorectal cancer is currently the third largest malignant tumor in the world, with high new cases and high mortality. Metastasis is one of the most common causes of death of colorectal cancer, of which liver metastasis is the most fatal. Since the beginning of the Human Genome Project in 2001, people have gradually recognized the 3 billion base pairs that make up the human genome, of which only about 1.5% of the nucleic acid sequences are used for protein coding, including proto-oncogenes and tumor suppressor genes. A large number of differences in the expression of proto-oncogenes and tumor

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… The lncRNA with this function is also known as ceRNA (Competing endogenous RNA). 87 At the same time, because the expression of most long non-coding genes is transcribed by RNA polymerase II (RNAP II), the specific expression of these genes in tissues and developmental stages indicates that the transcription …

Computational proteomics to enhance personalized treatment of COVID-19 and Long COVID.

The coronavirus disease 2019 (COVID-19) pandemic, caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), has led to significant global health burden, including both acute infections and persistent post-acute sequelae, also known as Long COVID (LC) in survivors. While clinical management has reduced case-fatality rates, a substantial proportion of patients develop LC, a heterogeneous syndrome with long-term symptoms. This complex continuum requires therapeutic strategies for both the acute and chronic phases. Plasma proteomics has emerged as a powerful tool in precision medicin

Ранняя реакция на рост Gene 1 Выгоды Аутоиммунная болезнь путем поощрения дифференциации ячеек в качестве регулятора Foxp3.

Foxp3+ Регулирующие T (Treg) клетки, как один из подтипов CD4+T клеток, являются важнейшим сторожем в патогенезе самоантигенных реактивных заболеваний. В этом контексте мы продемонстрировали, что выборочная абляция гена раннего реагирования роста 1 (Egr-1) в CD4+T клеток усугубила экспериментальный аутоиммунный энцефаломиелит (EAE) в мюриновых моделях. Отсутствие Egr-1 в клетках CD4+T, полученное из мышей EAE и наивных клеток CD4+T, препятствовало дифференциации и влиянию Treg. Важно то, что в CD4+T клеток нескольких склерозных пациентов как Egr-1, так и Foxp3 было обнаружено снижение. Дальней

Landscape of small nucleic acid therapeutics: moving from the bench to the clinic as next-generation medicines.

The ability of small nucleic acids to modulate gene expression via a range of processes has been widely explored. Compared with conventional treatments, small nucleic acid therapeutics have the potential to achieve long-lasting or even curative effects via gene editing. As a result of recent technological advances, efficient small nucleic acid delivery for therapeutic and biomedical applications has been achieved, accelerating their clinical translation. Here, we review the increasing number of small nucleic acid therapeutic classes and the most common chemical modifications and delivery platf

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… The piRNA clusters are transcribed to primary piRNAs (pri-piRNAs) by RNA polymerase II in the nucleus, similar to the process of miRNAs. … polymerase II, thus increasing the expression of target proteins. 111 The selection of genomic regions is vital in the sequence design of saRNAs. …

Histone modifications across cancers: mechanisms, therapy and clinical translation.

Cancer continues to be a major cause of death across the globe, and epigenetic dysregulation, including histone modifications, has been recognized as a major hallmark of cancer development, heterogeneity, and drug resistance. This review seeks to offer an overview of histone modifications in cancer, including the more studied histone modifications such as acetylation and methylation, as well as the less explored histone modifications such as phosphorylation, ubiquitination, and glycosylation. It also examines the role of histone modifications in the dysregulation of the three categories of enz

Clinical epigenetics settings for cancer and cardiovascular diseases: real-life applications of network medicine at the bedside.

Despite impressive efforts invested in epigenetic research in the last 50 years, clinical applications are still lacking. Only a few university hospital centers currently use epigenetic biomarkers at the bedside. Moreover, the overall concept of precision medicine is not widely recognized in routine medical practice and the reductionist approach remains predominant in treating patients affected by major diseases such as cancer and cardiovascular diseases. By its' very nature, epigenetics is integrative of genetic networks. The study of epigenetic biomarkers has led to the identification of num

New understanding of the damage of SARS-CoV-2 infection outside the respiratory system.

Since early December 2019, a number of pneumonia cases associated with unknown coronavirus infection were identified in Wuhan, China, and many additional cases were identified in other regions of China and in other countries within 3 months. Currently, more than 80,000 cases have been diagnosed in China, including more than 3000 deaths. The epidemic is spreading to the rest of the world, posing a grave challenge to prevention and control. On February 12, 2020, the International Committee on Taxonomy of Viruses and the World Health Organization officially named the novel coronavirus and associa

Экссосомные микроРНК в качестве ранних биомаркеров переходного периода от периодических до вторичных прогрессивных множественных склерозов.

Множественный склероз (MS) — хроническая, иммунная болезнь, затрагивающая молодых людей, приводящая к неврологическим расстройствам. Независимо от исследований и разработок, связанных с разработкой эффективной терапии для борьбы с заболеваниями (ДМТ), повторное излучающее множественный склероз (РРМС) перейдет к прогрессивному множеству склероза фенотипа. Момент перехода от RRMS к вторичному прогрессивному множественному склерозу (SPMS) трудно предсказать, и диагностика основана на накоплении инвалидности в эволюции болезни. Исследования по вопросу о роли микроРНК (миРНК) в MS начались в начале

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… The first form primary miRNA (pri-miRNA) interacts with RNA polymerase II to form a stem–loop structure (pre-miRNA) under the action of ribonuclease III Drosha in the nucleus. This is transported with the aid of exportin-5 to the cytoplasm [ 26 ]. …

Tumor-derived systems as novel biomedical tools-turning the enemy into an ally.

Cancer is a complex illness that presents significant challenges in its understanding and treatment. The classic definition, "a group of diseases characterized by the uncontrolled growth and spread of abnormal cells in the body," fails to convey the intricate interaction between the many entities involved in cancer. Recent advancements in the field of cancer research have shed light on the role played by individual cancer cells and the tumor microenvironment as a whole in tumor development and progression. This breakthrough enables the utilization of the tumor and its components as biological

Кровавые экзотические коннексины и небольшие РНК были связаны с демиелинизирующими заболеваниями.

ЦЕЛИ: Оценка экзосомы крови (Ex)-коннексина (Cx)43 (кодируется GJA1) и ее усеченной изоформы при множественных склерозах (MS) и оптицическом расстройстве нейромиелита (NMOSD), которые демонстрируют явные изменения в астроглиальном Cx43. МЕТОДЫ: 48 пациентов с сером (34 пациента с релапсирующими реактивными выбросами, 14 - вторичными), 35 - с NMOSD, 20 - с другими воспалительными неврологическими заболеваниями (OIND) и 17 - с здоровыми средствами контроля (HC) были подвергнуты количественному плёту для Cx43, одномолекулярному массиву для нейрофильм-L и количественной цепной реакции полимеразы н

Unveiling the Role of HGF/c-Met Signaling in Non-Small Cell Lung Cancer Tumor Microenvironment.

Non-small cell lung cancer (NSCLC) is characterized by several molecular alterations that contribute to its development and progression. These alterations include the epidermal growth factor receptor (EGFR), anaplastic lymphoma kinase (ALK), human epidermal growth factor receptor 2 (HER2), and mesenchymal-epithelial transition factor (c-MET). Among these, the hepatocyte growth factor (HGF)/c-MET signaling pathway plays a crucial role in NSCLC. In spite of this, the involvement of the HGF/c-MET signaling axis in remodeling the tumor microenvironment (TME) remains relatively unexplored. This rev

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

Melanoma and immunotherapy bridge 2015 : Naples, Italy. 1-5 December 2015.

MELANOMA BRIDGE 2015 KEYNOTE SPEAKER PRESENTATIONS Molecular and immuno-advances K1 Immunologic and metabolic consequences of PI3K/AKT/mTOR activation in melanoma Vashisht G. Y. Nanda, Weiyi Peng, Patrick Hwu, Michael A. Davies K2 Non-mutational adaptive changes in melanoma cells exposed to BRAF and MEK inhibitors help the establishment of drug resistance Gennaro Ciliberto, Luigi Fattore, Debora Malpicci, Luigi Aurisicchio, Paolo Antonio Ascierto, Carlo M. Croce, Rita Mancini K3 Tumor-intrinsic beta-catenin signaling mediates tumor-immune avoidance Stefani Spranger, Thomas F. Gajewski K4 Intra

Изучение антивоспламенительных эффектов после экстраполяции в модели мыши R6/2 болезни Хантингтона.

Болезнь Хантингтона - это прогрессивное, неизлечимое нейродегенеративное расстройство, вызванное мутацией в гене Хантингтин. Помимо нейродегенерации, изменённая иммунная активация связана с развитием болезни. Поскольку воспаление центральной нервной системы и дисфункция иммунных клеток признаются в качестве движущей силы, иммуномодуляция может представлять собой дополнительную терапевтическую стратегию. Известно, что короткоцепные жирные кислоты оказывают иммуномодулятивное воздействие на нервно-воспалительные заболевания, такие, как множественный склероз. В этом исследовании R6/2 мышей ежедне

Translational progress on tumor biomarkers.

There is an urgent need to apply basic research achievements to the clinic. In particular, mechanistic studies should be developed by bench researchers, depending upon clinical demands, in order to improve the survival and quality of life of cancer patients. To date, translational medicine has been addressed in cancer biology, particularly in the identification and characterization of novel tumor biomarkers. This review focuses on the recent achievements and clinical application prospects in tumor biomarkers based on translational medicine.

Доклиническая оценка клеток DC-CCK как потенциально эффективной иммунотерапии для лечения глиобластомы.

Несмотря на благоприятное воздействие иммунотерапии на различные виды раковых заболеваний, ее полный успех в борьбе с вредителями CNS по-прежнему сопряжен с трудностями. Недавно в результате успешного клинического испытания клеточной иммунотерапии, вызванной цитокинами, у пациентов с глиобластомой (ГБМ) открылась новая возможность для иммунотерапии с использованием клеточной селекции в малиньях CNS. На основе этих выводов мы изучили вопрос о том, могут ли дендритные клетки (DC) в сочетании с цитокиновыми клетками-убийцами (DC-CCK) также обеспечить альтернативный и более эффективный способ повы

Promotion of Bone Lesions Through the Myeloma Integrin α6-Mediated Osteolytic Signaling.

Osteolytic destruction is a hallmark of multiple myeloma and impairs myeloma patients' quality of life. However, the molecular mechanism underlying the pathogenesis of myeloma-associated bone disease remains unclear. In this study, we demonstrate the role of myeloma cell-expressed integrin α6 in bone. Integrin α6 binds to laminin 8 and epidermal growth factor receptor on mesenchymal stem cells (MSCs) to form a trimer complex and upregulates the secretion of osteolytic cytokines from both myeloma cells and MSCs, leading to enhanced bone resorption and reduced bone formation. Thus, this study el

Tuning epigenetics to enhance cancer virotherapy.

Cancer remains a major global health challenge, driving intensive research into novel therapeutic strategies. Oncolytic viruses (OVs) including herpesviruses, adenoviruses and echoviruses, have emerged as promising agents for cancer treatment, with several achieving regulatory approval. These viruses selectively lyse tumor cells and stimulate antitumor immunity. Nevertheless, their efficacy is constrained by limitations such as neutralization by serum factors and tumor cell resistance. Concurrently, epigenetic inhibitors modulate gene expression to suppress tumor proliferation and reshape immu

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… Additional mechanisms include RNA–DNA triplex formation to recruit DNMT3 or PRC2 205 , 206 , regulating transcription via RNA polymerase II 207 , and modulation of splicing and translation via RNA–RNA duplexes 208 . … OTX015 (MK-8628), an oral BETi, binds the acetyl-lysine pocket of BRD2/3/4, displacing them from chromatin and suppressing RNA polymerase II signaling. This downregulates c-Myc, induces cell cycle arrest, and reduces proliferation in myeloma and mesothelioma 55 , 56 . …

Реконструкция петли антикодона и форма D-стима приводят к конкретному распознаванию ANN-декодирования tRNA для модификации t6A.

N6-threonylcarbamoyladenosine (t6A) — универсальная трансфертная модификация RNA (tRNA), необходимая для перевода. Модификация устанавливается в положение 37 ANN-декодирование tRNAs (N is A, U, G или C) путем переноса треонилкарбамойла из промежуточного пути, катализированного в бактериях комплексом ЦаБД. Несмотря на строгое требование в отношении 36-UAA-38 Последовательность в субстрате tRNS, структурная основа этой специфичности остается неясной. Мы определили крио-эм-структуры "Термотога маритима Т6А" синтазы, связанные с немодифицированной и изначально модифицированной ТRNA с модификацией

Analysis of differential gene immune infiltration and clinical characteristics of skin cutaneous melanoma based on systems biology and drug repositioning methods to identify drug candidates for skin cutaneous melanoma.

Skin cutaneous melanoma (SKCM) has a low early detection rate and a high mortality rate. There are many problems such as side effects and drug resistance in existing therapeutic drugs. Current studies have confirmed that SKCM pathogenesis-related genes promote the invasion and metastasis of cutaneous melanoma, but their roles in the tumor microenvironment (TME) remain unclear. Network pharmacology provides new opportunities for drug repurposing and repositioning, and is a fast, safe, and inexpensive drug discovery method to find new drugs for the treatment of SKCM. In this study, based on 3 da