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Artificial Intelligence and Machine Learning Technology Driven Modern Drug Discovery and Development.

The discovery and advances of medicines may be considered as the ultimate relevant translational science effort that adds to human invulnerability and happiness. But advancing a fresh medication is a quite convoluted, costly, and protracted operation, normally costing USD ~2.6 billion and consuming a mean time span of 12 years. Methods to cut back expenditure and hasten new drug discovery have prompted an arduous and compelling brainstorming exercise in the pharmaceutical industry. The engagement of Artificial Intelligence (AI), including the deep-learning (DL) component in particular, has bee

" Interleukin-27 " и " Аутоиммунные расстройства: компрессивный обзор иммунных функций " .

Аутоиммунные расстройства (АД) создают значительное бремя для здоровья и экономики во всем мире, характеризующееся ошибочной атакой иммунной системы организма на его собственные ткани. Хотя конкретные механизмы, лежащие в основе их развития, по-прежнему остаются неясными, речь идет о сочетании генетической предрасположенности (генетических предрасположений) и экологических факторов. Interleukin-27 (IL-27), среди многочисленных участвующих цитокинов, стал ключевым регулятором, выполняющим двойную роль в иммунной модуляции. Этот обзор погружается в молекулярную структуру и механизмы сигнализации

The reporting quality and transparency of orthopaedic studies using Bayesian analysis requires improvement: A systematic review.

BackgroundBayesian methods are being used more frequently in orthopaedics. To advance the use and transparent reporting of Bayesian studies, reporting guidelines have been recommended. There is currently little known about the use or applications of Bayesian analysis in orthopedics including adherence to recommended reporting guidelines. The objective is to investigate the reporting of Bayesian analysis in orthopedic surgery studies; specifically, to evaluate if these papers adhere to reporting guidelines.MethodsWe searched PUBMED to December 2nd, 2020. Two reviewers independently identified s

Терапевтическое применение иммунобиологии в аутоиммунных и воспаленных заболеваниях.

Иммунобиологика или биологическая экспертиза революционизировали терапевтическую парадигму аутоиммунных и подстрекательских заболеваний путем выборочного целеопределения и модуляции дисрегулированных иммунных путей. По сравнению с обычными широкоспектральными иммунопрепрессантами биологика обеспечивает более конкретный и основанный на механизмах рациональный подход, зачастую связанный с повышением эффективности и сокращением неблагоприятных явлений. В этом обзоре содержится всеобъемлющий обзор репертуара терапевтической биологики, механизмов их действий, важнейших клинических испытаний и клини

Tumor Biology Hides Novel Therapeutic Approaches to Diffuse Large B-Cell Lymphoma: A Narrative Review.

Diffuse large B-cell lymphoma (DLBCL) is a malignancy of immense biological and clinical heterogeneity. Based on the transcriptomic or genomic approach, several different classification schemes have evolved over the years to subdivide DLBCL into clinically (prognostically) relevant subsets, but each leaves unclassified samples. Herein, we outline the DLBCL tumor biology behind the actual and potential drug targets and address the challenges and drawbacks coupled with their (potential) use. Therapeutic modalities are discussed, including small-molecule inhibitors, naked antibodies, antibody-dru

Myelin-реактивные CD8+T клетки оказывают влияние на обычные дендритные поднаборы клеток в направлении зрелого и регулируемого фенотипа в экспериментальном аутоиммунном энцефаломиэлите.

Множественный склероз (MS) — аутоиммунное демиелинизирующее заболевание центральной нервной системы, моделируемое в мышах как экспериментальный аутоиммунный энцефаломиелит (EAE). В то время как CD4+T клетки, в первую очередь TH1 и TH17, движут патогенезом болезней, точная функция CD8+T клеток остается неясной. Ранее мы продемонстрировали, что переносимые миелином-реактивные CD8+T клетки (PLP-CD8) предотвращают индукцию EAE и подавляют текущие заболевания путем вовлечения MHC класса I в мышей-реципиента. Здесь мы показываем, что PLP-CD8 вызывает регулятивные изменения в обоих подмножествах обыч

High Serum miR-361-3p Predicts Early Postdischarge Infections after Autologous Stem Cell Transplantation.

BackgroundAutologous hematopoietic stem cell transplantation (AHSCT) is currently the backbone of the treatment of multiple myeloma (MM) and relapsed and refractory lymphomas. Notably, infections contribute to over 25% of fatalities among AHSCT recipients within the initial 100 days following the procedure. In this study, we aimed to evaluate three selected miRNAs: hsa-miR-155-5p, hsa-miR-320c, and hsa-miR-361-3p, in identifying AHSCT recipients at high risk of infectious events up to 100 days post-transplantation after discharge.Materials and methodsThe study group consisted of 58 patients (4

Advances in Extracellular Matrix-Associated Diagnostics and Therapeutics.

The extracellular matrix (ECM) is the common denominator of more than 50 chronic diseases. Some of these chronic pathologies lead to enhanced tissue formation and deposition, whereas others are associated with increased tissue degradation, and some exhibit a combination of both, leading to severe tissue alterations. To develop effective therapies for diseases affecting the lung, liver, kidney, skin, intestine, musculoskeletal system, heart, and solid tumors, we need to modulate the ECM's composition to restore its organization and function. Across diverse organ diseases, there are common denom

Symptom burden and symptom clusters in patients with breast cancer undergoing endocrine therapy: a cross‐sectional survey

OBJECTIVE: In China, many breast cancer (BC) patients opt for traditional Chinese medicine (TCM) to manage unpleasant symptoms. This study aimed to investigate the symptom clusters among patients with BC who are undergoing endocrine therapy and actively seek TCM treatment in China. METHODS: Patients with BC who were undergoing endocrine therapy were recruited. Data on symptom burden were gathered using the M.D. Anderson Symptom Inventory-Traditional Chinese Medicine (MDASI-TCM) and a BC-specific symptom questionnaire. The patient's quality of life (QoL) over the previous week was assessed usi

Совпадение в полном тексте источника
… Gan L, Miao YM, Dong XJ, Zhang QR, Ren Q, Zhang N (2023) Investigation on sexual function in young breast cancer patients during endocrine therapy: a latent class analysis. Front Med (Lausanne). 10:1218369 40. …

Astragaloside II, природный садонин, облегчает ремимиэлирование в демиэлинговых неврологических заболеваниях с помощью рецептора P75NTR, опосредованного осью сигнала β-катенина/Id2/MBP в клетках-прекурсорах олигодендроцитов.

КОЛИЧЕСТВО: Демиелинация является отличительной чертой неврологических расстройств, таких, как множественный склероз и оптика нейромиелита, что приводит к неврологическим расстройствам. Существующая терапия в первую очередь модифицирует иммунную реакцию, но не позволяет напрямую содействовать ремонту миелина. Расширение дифференциации олигодендроцитов и производства олигодендроцитов (ООП) имеет решающее значение для восстановления целостности миелина.ЦЕЛИ: В рамках этого исследования изучался терапевтический потенциал астрагалосида II (AS-II), биоактивного садонина с нейрозащитными и продиффер

A gain-of-function p53 mutant synergizes with oncogenic NRAS to promote acute myeloid leukemia in mice.

We previously demonstrated that a subset of acute myeloid leukemia (AML) patients with concurrent RAS pathway and TP53 mutations have an extremely poor prognosis and that most of these TP53 mutations are missense mutations. Here, we report that, in contrast to the mixed AML and T cell malignancy that developed in NrasG12D/+ p53-/- (NP-/-) mice, NrasG12D/+ p53R172H/+ (NPmut) mice rapidly developed inflammation-associated AML. Under the inflammatory conditions, NPmut hematopoietic stem and progenitor cells (HSPCs) displayed imbalanced myelopoiesis and lymphopoiesis and mostly normal cell prolife

Emerging Targets in Non-Small Cell Lung Cancer.

Lung cancer is responsible for a high burden of disease globally. Over the last two decades, the discovery of targetable oncogenic genomic alterations has revolutionized the treatment landscape for early-stage and advanced non-small cell lung cancer (NSCLC). New molecular drivers continue to emerge as promising therapeutic targets, including KRAS non-G12C, RAF/MEK, HER3, Nectin-4, folate receptor alpha, ITGB6, and PRMT5. In this review, we summarize the emerging molecular targets with a potential clinical impact in advanced NSCLC, elaborating on their clinical characteristics and specific mech

Recommendations for the effective use of T-cell-redirecting therapies: a Canadian consensus statement.

BackgroundT-cell-redirecting therapies, such as bispecific antibodies and chimeric antigen receptor T-cells, exploit the cytotoxic capabilities of the immune system to destroy cells expressing specific surface antigens, including malignant cells. These therapies have demonstrated unprecedented rates, depth, and duration of responses in relapsed and refractory multiple myeloma. However, there are significant challenges in implementing these therapies into practice, which require multidisciplinary and multicenter coordination and significant healthcare resources to effectively manage these patie

Comprehensive Review of Cyclamen: Development, Bioactive Properties, and Therapeutic Applications.

Plants are being researched as potential sources of novel drugs, which has led to a recent acceleration in the discovery of new bioactive compounds. Research on tissue culture technology for the synthesis and processing of plant compounds has skyrocketed, surpassing all expectations. These plants can be bought either raw or as extracts, where some of the chemicals are extracted by mashing the plant in water, alcohol, or another solvent. The use of herbal medicine may open new chances for reducing the onset of infections and treating different diseases including cancer. A perennial plant that b

A review on machine learning approaches and trends in drug discovery.

Drug discovery aims at finding new compounds with specific chemical properties for the treatment of diseases. In the last years, the approach used in this search presents an important component in computer science with the skyrocketing of machine learning techniques due to its democratization. With the objectives set by the Precision Medicine initiative and the new challenges generated, it is necessary to establish robust, standard and reproducible computational methodologies to achieve the objectives set. Currently, predictive models based on Machine Learning have gained great importance in t

Checkpoint inhibition and beyond: Precision immune engineering for the immune-privileged landscape of ocular malignancies.

Ocular malignancies, particularly uveal and conjunctival melanoma, exemplify tumors that evolve within one of the body's most immunologically constrained ecosystems, the eye's immune-privileged microenvironment. The limited success of PD-1/PD-L1 and CTLA-4 blockade in these cancers underscores the need to move beyond linear checkpoint inhibition toward multidimensional immune engineering. Through the confluence of synthetic bio-nanotechnology, AI-guided immunogenomics, and spatial immunomics, this review reframes ocular immunotherapy and redefines how tolerance and immunity might be programmat

Autoimmune Hemolytic Anemias: Challenges in Diagnosis and Therapy.

BackgroundAutoimmune hemolytic anemia (AIHA) is a rare disease due to increased destruction of erythrocytes by autoantibodies, with or without complement activation.SummaryAIHA is usually classified in warm AIHA (wAIHA) and cold agglutinin disease (CAD), based on isotype and thermal amplitude of the autoantibody. The direct antiglobulin test (DAT) or Coombs test is the cornerstone of AIHA diagnosis, as it is positive with anti-IgG in wAIHA, and with anti-C3d/IgM antisera plus high titer cold agglutinins in CAD. Therapy is quite different, as steroids and rituximab are effective in the former,

Abstracts cont.

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Evaluation of Proteasome Inhibitors in the Treatment of Idiopathic Pulmonary Fibrosis.

Idiopathic pulmonary fibrosis (IPF) is the most common form of idiopathic interstitial pneumonia, and it has a worse prognosis than non-small cell lung cancer. The pathomechanism of IPF is not fully understood, but it has been suggested that repeated microinjuries of epithelial cells induce a wound healing response, during which fibroblasts differentiate into myofibroblasts. These activated myofibroblasts express α smooth muscle actin and release extracellular matrix to promote matrix deposition and tissue remodeling. Under physiological conditions, the remodeling process stops once wound heal

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