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Sepsis in multimorbidity: a domain-based framework for systemic vulnerability and precision care.

Sepsis is a leading cause of morbidity and mortality, amplified by multimorbidity. This narrative review synthesizes epidemiological, pathophysiological, and immunological evidence to show how prevalent conditions-type 2 diabetes and obesity, heart failure and cerebrovascular disease, COPD, chronic kidney disease, cancer/HIV, and severe mental illness-reshape sepsis biology and outcomes. Convergent mechanisms include low-grade inflammation, impaired innate and adaptive immunity, endothelial injury with immunothrombosis/NETosis, barrier disruption with dysbiosis, and neuroendocrine maladaptatio

Long non-coding RNAs in bone metastasis: progresses and perspectives as potential diagnostic and prognostic biomarkers.

In a precision medicine perspective, among the biomarkers potentially useful for early diagnosis of cancers, as well as to define their prognosis and eventually to identify novel and more effective therapeutic targets, there are the long non-coding RNAs (lncRNAs). The term lncRNA identifies a class of non-coding RNA molecules involved in the regulation of gene expression that intervene at the transcriptional, post-transcriptional, and epigenetic level. Metastasis is a natural evolution of some malignant tumours, frequently encountered in patients with advanced cancers. Onset and development of

Exploring microRNA targeting as a promising approach for solid tumor treatment.

The discovery of microRNAs (miRNAs) and their pivotal role in gene regulation has opened up new avenues for innovative cancer treatments. Recent years have witnessed extensive research into the intricate mechanisms of miRNAs and their impact on solid tumors. These small non-coding RNA molecules are central to gene regulation and are frequently dysregulated in various cancers, particularly solid tumors. Dysregulation of specific miRNAs can initiate, progress, and metastasize tumors, making them appealing targets in cancer therapy. This article explores recent studies on identifying specific miR

Deciphering the Potentials of Cardamom in Cancer Prevention and Therapy: From Kitchen to Clinic.

Cardamom (cardamum) is a spice produced from the seeds of several Elettaria and Amomum plants of the Zingiberaceae family. Cardamom has been demonstrated to offer numerous benefits, including its antioxidant, antimicrobial, anti-inflammatory, and other metabolic (anti-diabetic) properties, and its potential to reduce cancer risk. Recently, researchers have extracted and tested multiple phytochemicals from cardamom to assess their potential effectiveness against various types of human malignancy. These studies have indicated that cardamom can help overcome drug resistance to standard chemothera

Нацеливание moTOR сигнализирующих путей в нескольких миеломах: биология и последствия для терапии.

Множественная миелома (ММ), рак неизлечимо дифференцированных плазменных клеток, является вторым по распространенности гематологической злокачественности и неизлечимо из-за неизбежного развития лекарственной устойчивости. Интенсивный синтез белка является отличительной чертой клеток MM, поддерживающей массовое производство клональных иммуноглобулинов или свободных световых цепей. Млекопитающая цель рэпамицин (mTR) киназы ценится как главный регулятор жизненно важных клеточных процессов, включая регулирование метаболизма и синтеза белка, и может быть найдена в two Мультипротеиновые комплексы, M

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… Moreover, MYC can stimulate ribosomal RNA (rRNA) modifications by controlling the expression of ribonucleases, rRNA-modifying enzymes, and nucleolar proteins involved in ribosome biogenesis such as NPM, Nop52, Nop56, and DKC1. …

Renal dysfunction, malignant neoplasms, atherosclerotic cardiovascular diseases, and sarcopenia as key outcomes observed in a three-year follow-up study using the Werner Syndrome Registry.

Werner syndrome is an adult-onset progeria syndrome that results in various complications. This study aimed to clarify the profile and secular variation of the disease. Fifty-one patients were enrolled and registered in the Werner Syndrome Registry. Their data were collected annually following registration. A cross-sectional analysis at registration and a longitudinal analysis between the baseline and each subsequent year was performed. Pearson's chi-squared and Wilcoxon signed-rank tests were used. Malignant neoplasms were observed from the fifth decade of life (mean onset: 49.7 years) and we

Safety of Eosinophil-Depleting Therapy for Severe, Eosinophilic Asthma: Focus on Benralizumab.

Eosinophils play a pivotal role in the inflammatory pathology of asthma and have been the target of new biologic treatments for patients with eosinophilic asthma. Given the central role of interleukin (IL)-5 in the eosinophil lifecycle, several therapies directed against the IL-5 pathway have been developed, including the anti-IL-5 antibodies mepolizumab and reslizumab and the IL-5 receptor α (IL-5Rα)-directed cytolytic antibody benralizumab. Eosinophil-depleting therapies represent a relatively new class of asthma treatment, and it is important to understand their long-term efficacy and safet

Liquid biopsies in myeloid malignancies.

Hematologic malignancies are the most common type of cancer affecting children and young adults, and encompass diseases, such as leukemia, lymphoma, and myeloma, all of which impact blood associated tissues such as the bone marrow, lymphatic system, and blood cells. Clinical diagnostics of these malignancies relies heavily on the use of bone marrow samples, which is painful, debilitating, and not free from risks for leukemia patients. Liquid biopsies are based on minimally invasive assessment of markers in the blood (and other fluids) and have the potential to improve the efficacy of diagnosti

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… In fact, miRNAs are extremely resilient to ribonucleases, which may be associated to their ability to bind plasma proteins, such as Argonaute 2 and high-density lipoprotein [ 131 , 132 ] . …

Cardiac amyloidosis: evolving pathogenesis, multimodal diagnostics, and principles of treatment.

Amyloidosis is a protein deposition disorder in which insoluble fibril structures accumulate in the bodily tissues damaging the organ function. Cardiac amyloidosis is a severe but under-reported medical condition characterized by the accumulation of amyloid in the extracellular area of the myocardium, which results in thickening and stiffening of ventricular walls. Cardiac amyloidosis has recently gained much attention with its slowly surging incidence. With this study, we seek to comprehensively compile the pathophysiology and clinical picture of cardiac amyloidosis subtypes, extending a clin

MicroRNAs in B-cells: from normal differentiation to treatment of malignancies.

MicroRNAs (miRNAs) are small non-coding RNAs that play important post-transcriptional regulatory roles in a wide range of biological processes. They are fundamental to the normal development of cells, and evidence suggests that the deregulation of specific miRNAs is involved in malignant transformation due to their function as oncogenes or tumor suppressors. We know that miRNAs are involved in the development of normal B-cells and that different B-cell subsets express specific miRNA profiles according to their degree of differentiation. B-cell-derived malignancies contain transcription signatu

Endoplasmic reticulum stress in disease pathogenesis: its implications for therapy.

Endoplasmic reticulum (ER) stress is a key cellular mechanism that is important in the development of many diseases, including cancer. Since the discovery of the unfolded protein response (UPR), research has greatly improved our understanding of how ER stress affects cellular functions, especially protein folding and adaptation to stress. The UPR consists of three main branches: IRE1, ATF6, and PERK, each of which is crucial for regulating stress responses, protein homeostasis, and apoptosis. These pathways normally help cells handle stress effectively; however, excessive or prolonged activati

Nanoparticles for Targeted Drug Delivery to Cancer Stem Cells: A Review of Recent Advances.

Cancer stem cells (CSCs) are a subpopulation of cells that can initiate, self-renew, and sustain tumor growth. CSCs are responsible for tumor metastasis, recurrence, and drug resistance in cancer therapy. CSCs reside within a niche maintained by multiple unique factors in the microenvironment. These factors include hypoxia, excessive levels of angiogenesis, a change of mitochondrial activity from aerobic aspiration to aerobic glycolysis, an upregulated expression of CSC biomarkers and stem cell signaling, and an elevated synthesis of the cytochromes P450 family of enzymes responsible for drug

The Genetics and Epigenetics of 22q11.2 Deletion Syndrome.

Chromosome 22q11.2 deletion syndrome (22q11.2del) is a complex, multi-organ disorder noted for its varying severity and penetrance among those affected. The clinical problems comprise congenital malformations; cardiac problems including outflow tract defects, hypoplasia of the thymus, hypoparathyroidism, and/or dysmorphic facial features. Additional clinical issues that can appear over time are autoimmunity, renal insufficiency, developmental delay, malignancy and neurological manifestations such as schizophrenia. The majority of individuals with 22q11.2del have a 3 Mb deletion of DNA on chrom

Current concepts of the crosstalk between lncRNA and E2F1: shedding light on the cancer therapy.

Long noncoding RNAs (lncRNAs) constitute a distinctive subset of RNA molecules with limited protein-coding potential, which exert crucial impacts on various biological activities. In the context of cancer, dysregulated lncRNAs function as essential regulators that affect tumor initiation and malignant progression. These lncRNAs serve as competitive endogenous RNAs (ceRNAs) through sponging microRNAs and regulating the expression of targeted genes. Moreover, they also directly bind to RNA-binding proteins, which can be integrated into a complex mechanistic network. E2F1, an extensively studied

Modulating epigenetic modifications for cancer therapy (Review).

Cancer is a global public health concern. Alterations in epigenetic processes are among the earliest genomic aberrations occurring during cancer development and are closely related to progression. Unlike genetic mutations, aberrations in epigenetic processes are reversible, which opens the possibility for novel pharmacological treatments. Non‑coding RNAs (ncRNAs) represent an essential epigenetic mechanism, and emerging evidence links ncRNAs to carcinogenesis. Epigenetic drugs (epidrugs) are a group of promising target therapies for cancer treatment acting as coadjuvants to reverse drug resist

Восстановление ТРНС последнего универсального общего пастора (Общества) на пути к восстановлению системы перевода Древних.

Реконструирование ансестральной последовательности (АСР) было использовано для изучения эволюции переводческой системы путем определения последовательности tRNA в "Last Archaeal Common Ancestor" (LACA), "Last Bacterial Common Ancestor" (LBCA) и "Last Universal Common Ansancestor" (LUCA), которые в наших предыдущих исследованиях назывались "Общество". Составное филогенетическое дерево, взятое из реконструированных последовательности ТРНА, выявило топологию, отличную от ранее выведенных аминоачил-тРНА синтетазы (АРС). Такая непоследовательность может отражать изменения в структурных особенностях

Иммуномодулирующие свойства месенхимальных стволовых клеток и их внеклеточных везиков: потенциальные клинические применения в аутоиммунных заболеваниях.

Мезенхимальные стволовые клетки (МСЦ)/мезенхимические стромальные клетки и их внеклеточные везикли (ЭМ), в частности экзосомы, появились в качестве терапевтических кандидатов в регенеративной медицине в силу их многопотенции, низкой иммуногенности и обширных иммунодуляторных свойств. В настоящем описательном обзоре содержится сводная информация об иммуномодуляции МСЦ- и МСЦ-В и о ее потенциале в плане перевода на другие языки. four основные аутоиммунные заболевания: множественный склероз (МС), тип 1 - сахарный диабет (T1D), системный волшебный эриматоз (SLE) и ревматоидный артрит (RA).Механист

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… Among their bioactive components, MSC-Exos are particularly enriched in miRNAs and contain a complex molecular composition including lipids, enzymes, nucleic acids, proteins, and pro- and anti-inflammatory cytokines, which contributes to protecting miRNAs from degradation by ribonucleases in body fluids …

mRNA vaccine in cancer therapy: Current advance and future outlook.

Messenger ribonucleic acid (mRNA) vaccines are a relatively new class of vaccines that have shown great promise in the immunotherapy of a wide variety of infectious diseases and cancer. In the past 2 years, SARS-CoV-2 mRNA vaccines have contributed tremendously against SARS-CoV2, which has prompted the arrival of the mRNA vaccine research boom, especially in the research of cancer vaccines. Compared with conventional cancer vaccines, mRNA vaccines have significant advantages, including efficient production of protective immune responses, relatively low side effects and lower cost of acquisitio

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… This is challenging due to the negative charge of both the mRNA molecules and cell membrane, relatively large size of mRNA molecules and degradability by ribonucleases existing in skin and blood. 143 To overcome this, a number of mRNA delivery methods and mRNA delivery carriers have been explored and …

CRISPR-Cas: Converting A Bacterial Defence Mechanism into A State-of-the-Art Genetic Manipulation Tool.

Bacteriophages are pervasive viruses that infect bacteria, relying on their genetic machinery to replicate. In order to protect themselves from this kind of invader, bacteria developed an ingenious adaptive defence system, clustered regularly interspaced short palindromic repeats (CRISPR). Researchers soon realised that a specific type of CRISPR system, CRISPR-Cas9, could be modified into a simple and efficient genetic engineering technology, with several improvements over currently used systems. This discovery set in motion a revolution in genetics, with new and improved CRISPR systems being

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… In all types of CRISPR-Cas systems, the CRISPR locus is transcribed into a crRNA precursor (pre-crRNA), which is subsequently cleaved and processed by Cas proteins or cellular ribonucleases, yielding smaller units of mature crRNA [ 32 ]. …

Biochemical and Clinical Impact of Organic Uremic Retention Solutes: A Comprehensive Update.

In this narrative review, the biological/biochemical impact (toxicity) of a large array of known individual uremic retention solutes and groups of solutes is summarized. We classified these compounds along their physico-chemical characteristics as small water-soluble compounds or groups, protein bound compounds and middle molecules. All but one solute (glomerulopressin) affected at least one mechanism with the potential to contribute to the uremic syndrome. In general, several mechanisms were influenced for each individual solute or group of solutes, with some impacting up to 7 different biolo