Unravelling molecular mechanisms in atherosclerosis using cellular models and omics technologies.

Despite the discovery and prevalent clinical use of potent lipid-lowering therapies, including statins and PCSK9 inhibitors, cardiovascular diseases (CVD) caused by atherosclerosis remain a large unmet clinical need, accounting for frequent deaths worldwide. The pathogenesis of atherosclerosis is a complex process underlying the presence of modifiable and non-modifiable risk factors affecting several cell types including endothelial cells (ECs), monocytes/macrophages, smooth muscle cells (SMCs) and T cells. Heterogeneous composition of the plaque and its morphology could lead to rupture or erosion causing thrombosis, even a sudden death.

Perfluorooctane sulfonate causes DNA damage and apoptosis via oxidative stress in umbilical cord fibroblast cells of Yangtze finless porpoise.

Yangtze finless porpoise (YFP) is a critically endangered species in China. It has been found that YFP is constantly exposed to perfluorooctane sulfonate (PFOS) in aquatic environments, leading to significant bioaccumulation. However, the impacts of PFOS on YFP health and survival are still unknown.

The clinical phenotype of isolated ocular or oral dryness in Sjögren's disease.

Objectives: To assess if isolated mouth or eye dryness constitutes distinct clinical phenotypes in Sjögren's disease (SjD).

Methods: We analysed 1765 patients meeting the 2016 ACR-EULAR SjD criteria, followed up at four centres in Greece and Italy (Universities of Pisa, Italy, and Athens, Harokopion, and Ioannina, Greece). Patients with isolated mouth or eye dryness were identified and matched 1:2 with those experiencing both symptoms, according to age at SjD diagnosis, gender, and disease duration.

Local changes in potassium ions regulate input integration in active dendrites.

During neuronal activity, the extracellular concentration of potassium ions ([K+]o) increases substantially above resting levels, yet it remains unclear what role these [K+]o changes play in the dendritic integration of synaptic inputs. We here used mathematical formulations and biophysical modeling to explore the role of synaptic activity-dependent K+ changes in dendritic segments of a visual cortex pyramidal neuron, receiving inputs tuned to stimulus orientation. We found that the spatial arrangement of inputs dictates the magnitude of [K+]o changes in the dendrites: Dendritic segments receiving similarly tuned inputs can attain substantially higher [K+]o increases than segments receiving diversely tuned inputs.

The molecular underpinnings of female predominance in lupus.

Most people affected by systemic lupus erythematosus (SLE) are women. Although the role of sex hormones has been appreciated, we discuss emerging evidence that links X-linked genes escaping from dosage compensation to female predisposition to lupus. This is exemplified by TLR7 and CXorf21 whose female-biased expression may converge to enhance interferon responses and promote autoantibody-producing B cells, which are hallmarks of SLE.

Advanced aspects of acetogens.

Acetogens are a diverse group of anaerobic bacteria that are capable of carbon dioxide fixation and have for long fascinated scientists due to their unique metabolic prowess. Historically, acetogens have been recognized for their remarkable ability to grow and to produce acetate from different one-carbon sources, including carbon dioxide, carbon monoxide, formate, methanol, and methylated organic compounds. The key metabolic pathway in acetogens responsible for converting these one-carbon sources is ́the Wood-Ljungdahl pathway.

Improving macromolecular structure refinement with metal-coordination restraints.

Metals are essential components for the structure and function of many proteins. However, accurate modelling of their coordination environments remains a challenge due to the complexity and diversity of metal-coordination geometries. To address this, a method is presented for extracting and analysing coordination information, including bond lengths and angles, from the Crystallography Open Database.

Exploring plant-microbe interactions in adapting to abiotic stress under climate change: a review.

Climatic change and extreme weather events have become a major threat to global agricultural productivity. Plants coexist with microorganisms, which play a significant role in influencing their growth and functional traits. The rhizosphere serves as an ecological niche encompassing plant roots and is a chemically complex environment that supports the growth and development of diverse plant-interactive microbes.

Bioinformatics and Experimental Insights Into miR-182, hsa_circ_0070269, and circ-102,166 as Therapeutic Targets for HCV-Associated HCC.

Aims: Hepatocellular carcinoma (HCC) is a type of malignant tumor and the sixth leading cause of death worldwide. It is caused by HBV, HCV infection, and alcohol consumption. MicroRNAs are typically small, non-coding RNAs that are involved in the regulation of mRNA expression.

Decoding T cell senescence in cancer: Is revisiting required?

Senescence is an inherent cellular mechanism triggered as a response to stressful insults. It associates with several aspects of cancer progression and therapy. Senescent cells constitute a highly heterogeneous cellular population and their identification can be very challenging.

BIOTECH 1766 Attenuates Oxidative Stress and Histopathological Changes following Aluminum Poisoning in ICR Mice.

Objective: The aim of this study was to investigate the protective effects of BIOTECH 1766 against oxidative damage in the brain, liver, and kidneys induced by aluminum (Al) poisoning in ICR mice.

Methods: Twenty mice were divided into four groups (n = 5): (I) control, (II) Al, (III) citric acid (CA), and (IV) BIOTECH 1766 group. A 14-day treatment period was implemented, wherein groups I and II received sterile water, while groups III and IV received 10 mg/kg bw of CA and 1 x 10 cfu/kg bw of BIOTECH 1766, respectively.

Multimodal beneficial effects of BNN27, a nerve growth factor synthetic mimetic, in the 5xFAD mouse model of Alzheimer's disease.

Alzheimer's Disease (AD) is an incurable and debilitating progressive, neurodegenerative disorder which is the leading cause of dementia worldwide. Neuropathologically, AD is characterized by the accumulation of Aβ amyloid plaques in the microenvironment of brain cells and neurovascular walls, chronic neuroinflammation, resulting in neuronal and synaptic loss, myelin and axonal failure, as well as significant reduction in adult hippocampal neurogenesis. The hippocampal formation is particularly vulnerable to this degenerative process, due to early dysfunction of the cholinergic circuit.

Impact of water models on the structure and dynamics of enzyme tunnels.

Protein hydration plays a vital role in many biological functions, and molecular dynamics simulations are frequently used to study it. However, the accuracy of these simulations is often sensitive to the water model used, a phenomenon particularly evident in intrinsically disordered proteins. Here, we investigated the extent to which the choice of water model alters the behavior of complex networks of tunnels within proteins.

A Glimpse of Noncoding RNAs: Secondary Structure, Emerging Trends, and Potential Applications in Human Diseases.

An appealing strategy for the treatment of several diseases is the therapeutic targeting of noncoding RNAs (ncRNAs), such as microRNAs (miRNAs) and long noncoding RNAs (lncRNAs). Many antisense oligonucleotides and small interfering RNAs have been tested in clinical studies over the past 10 years, and several of these have received FDA approval. However, trial results have thus far been mixed, with some studies reporting strong effects and others showing low effectiveness or side effects, including toxicity.

Modulation of miR-205 expression using a phyto-nano hybrid as a potential therapeutic agent against breast cancer.

Breast cancer is the fifth major cause of fatalities associated with cancer worldwide and in Pakistan, 34 066 female breast cancer cases were recorded in 2018. This study was designed to understand extracts of () and to evaluate the epigenetic modulation of microRNA expression for breast cancer therapy using a selected phyto-nanohybrid treatment. The phytochemical screening revealed the presence of potential phytochemicals and antioxidant scavenging activity in the extracts with a DPPH (2-diphenyl-1-picryl-hydroxyl) assay giving an IC value of 20.

A polygenic risk score model for psoriasis based on the protein interactions of psoriasis susceptibility loci.

Introduction: Polygenic Risk Scores (PRS) are an emerging tool for predicting an individual's genetic risk to a complex trait. Several methods have been proposed to construct and calculate these scores. Here, we develop a biologically driven PRS using the UK BioBank cohort through validated protein interactions (PPI) and network construction for psoriasis, incorporating variants mapped to the interacting genes of 14 psoriasis susceptibility (PSORS) loci, as identified from previous genetic linkage studies.

Comparative analysis of polysaccharide and cell wall structure in Aspergillus nidulans and Aspergillus fumigatus by solid-state NMR.

Invasive aspergillosis poses a significant threat to immunocompromised patients, leading to high mortality rates associated with these infections. Targeting the biosynthesis of cell wall carbohydrates is a promising strategy for antifungal drug development and will be advanced by a molecular-level understanding of the native structures of polysaccharides within their cellular context. Solid-state NMR spectroscopy has recently provided detailed insights into the cell wall organization of Aspergillus fumigatus, but genetic and biochemical evidence highlights species-specific differences among Aspergillus species.

Sugar mimics and their probable binding sites: design and synthesis of thiazole linked coumarin-piperazine hybrids as galectin-1 inhibitors.

Sugar mimics are valuable tools in medicinal chemistry, offering the potential to overcome the limitations of carbohydrate inhibitors, such as poor pharmacokinetics and non-selectivity. In our continued efforts to develop heterocyclic galectin-1 inhibitors, we report the synthesis and characterization of thiazole-linked coumarin piperazine hybrids (10a-10i) as Gal-1 inhibitors. The compounds were characterized using H NMR, C NMR and HRMS.

Thapsigargin and its prodrug derivatives: exploring novel approaches for targeted cancer therapy through calcium signaling disruption.

Thapsigargin, a sesquiterpene lactone derived from Thapsia garganica L., has demonstrated mixed potential as an anticancer agent due to its potent ability to disrupt calcium signaling and induce apoptosis. This review evaluates the chemopreventive and chemotherapeutic potential of thapsigargin, focusing on its molecular mechanisms and toxicity.