Modulating Amyloid-β Toxicity: In Vitro Analysis of Aβ42(G37V) Variant Impact on Aβ42 Aggregation and Cytotoxicity.

Alzheimer's disease (AD) is primarily driven by the formation of toxic amyloid-β (Aβ) aggregates, with Aβ42 being a pivotal contributor to disease pathology. This study investigates a novel agent to mitigate Aβ42-induced toxicity by co-assembling Aβ42 with its G37V variant (Aβ42(G37V)), where Gly at position 37 is substituted with valine. Using a combination of Thioflavin-T (Th-T) fluorescence assays, Western blot analysis, atomic force microscopy (AFM)/transmission electron microscopy (TEM), and biochemical assays, we demonstrated that adding Aβ42(G37V) significantly accelerates Aβ42 aggregation rate and mass while altering the morphology of the resulting aggregates.

Natural phytochemicals as small-molecule proprotein convertase subtilisin/kexin type 9 inhibitors.

A decrease in the levels of low-density lipoprotein receptors (LDLRs) leads to the accumulation of LDL cholesterol (LDL-C) in the bloodstream, resulting in hypercholesterolemia and atherosclerotic cardiovascular diseases. Increasing the expression level or inducing the activity of LDLR in hepatocytes can effectively control hypercholesterolemia. Proprotein convertase subtilisin/kexin type 9 (PCSK9) protein, primarily produced in the liver, promotes the degradation of LDLR.

Overview of clinical status, treatment, and long-term outcomes of pediatric autosomal-dominant polycystic kidney disease: a nationwide survey in Taiwan.

This retrospective study investigated the incidence, medication use, and outcomes in pediatric autosomal-dominant polycystic kidney disease (ADPKD) using Taiwan's National Health Insurance Research Database (NHIRD). A 1:4 matched control group of individuals included in the NHIRD during the same period was used for comparative analyses. A total of 621 pediatric patients were identified from 2009 to 2019 (mean age, 9.

C-X-C motif chemokine ligand 12-C-X-C chemokine receptor type 4 signaling axis in cancer and the development of chemotherapeutic molecules.

Chemokines are small, secreted cytokines crucial in the regulation of a variety of cell functions. The binding of chemokine C-X-C motif chemokine ligand 12 (CXCL12) (stromal cell-derived factor 1) to a G-protein-coupled receptor C-X-C chemokine receptor type 4 (CXCR4) triggers downstream signaling pathways with effects on cell survival, proliferation, chemotaxis, migration, and gene expression. Intensive and extensive investigations have provided evidence suggesting that the CXCL12-CXCR4 axis plays a pivotal role in tumor development, survival, angiogenesis, metastasis, as well as in creating tumor microenvironment, thus implying that this axis is a potential target for the development of cancer therapies.

Xanthohumol, a prenylated chalcone, regulates lipid metabolism by modulating the LXRα/RXR-ANGPTL3-LPL axis in hepatic cell lines and high-fat diet-fed zebrafish models.

Angiopoietin-like 3 (ANGPTL3) acts as an inhibitor of lipoprotein lipase (LPL), impeding the breakdown of triglyceride-rich lipoproteins (TGRLs) in circulation. Targeting ANGPTL3 is considered a novel strategy for improving dyslipidemia and atherosclerotic cardiovascular diseases (ASCVD). Hops (Humulus lupulus L.

Sequential rearrangement and stereochemical reorganization to design an antimicrobial peptide with enhanced stability.

Antimicrobial peptides (AMPs) are natural molecules that function within the innate immune system to counteract pathogenic invasion and minimize the detrimental consequences of infection. However, utilizing these molecules for medical applications has been challenging. In this study, we selected a model AMP with poor stability, Tilapia Piscidin 4 (TP4), and modified its sequence and chirality (TP4-γ) to improve its potential for clinical application.

Optimization of sequence and chiral content enhances therapeutic potential of tilapia piscidin peptides.

Because antimicrobial peptides (AMPs) often exhibit broad-spectrum bactericidal potency, we sought to develop peptide-based antimicrobials for potential clinical use against drug-resistant pathogens. To accomplish this goal, we first optimized the amino acid sequence of a broad-spectrum AMP known as Tilapia Piscidin 4 (TP4). Then, we used the optimized sequence to create a pair of heterochiral variants (TP4-α and TP4-β) with different percentages of D-enantiomers, as poly-L peptides often exhibit poor pharmacokinetic profiles.

A peptide derived from interleukin-10 exhibits potential anticancer activity and can facilitate cell targeting of gold nanoparticles loaded with anticancer therapeutics.

Human interleukin-10 (IL-10) is an immunosuppressive and anti-inflammatory cytokine, and its expression is upregulated in tumor tissues and serum samples of patients with various cancers. Because of its immunosuppressive nature, IL-10 has also been suggested to be a factor leading to tumor cells' evasion of immune surveillance and clearance by the host immune system. In this study, we refined a peptide with 20 amino acids, named NK20a, derived from the binding region of IL-10 on the basis of in silico analysis of the complex structure of IL-10 with IL-10Ra, the ligand binding subunit of the IL-10 receptor.

The Neuroprotective Effects of Flavonoid Fisetin against Corticosterone-Induced Cell Death through Modulation of ERK, p38, and PI3K/Akt/FOXO3a-Dependent Pathways in PC12 Cells.

The overactive hypothalamic-pituitary-adrenal (HPA) axis is believed to trigger the overproduction of corticosterone, leading to neurotoxicity in the brain. Fisetin is a flavonoid commonly found in fruits and vegetables. It has been suggested to possess various biological activities, including antioxidant, anti-inflammatory, and neuroprotective effects.

Pinostrobin modulates FOXO3 expression, nuclear localization, and exerts antileukemic effects in AML cells and zebrafish xenografts.

Acute myeloid leukemia (AML) is a disease characterized by abnormal cell proliferation in the bone marrow and is the most common quickly progressive leukemia in adults. Pinostrobin, a flavonoid phytochemical, has been reported to exhibit antioxidant, anti-inflammatory, and anticancer properties. In this study, we aimed to investigate the antileukemic effects of pinostrobin and its molecular mechanisms in human AML cells.

Self-assembly of gelatin and collagen in the polyvinyl alcohol substrate and its influence on cell adhesion, proliferation, shape, spreading and differentiation.

Culture substrates display profound influence on biological and developmental characteristic of cells cultured . This study investigates the influence of polyvinyl alcohol (PVA) substrates blended with different concentration of collagen or/and gelatin on the cell adhesion, proliferation, shape, spreading, and differentiation of stem cells. The collagen/gelatin blended PVA substrates were prepared by air drying.

Electrochemically synthesized green fluorescent carbon dots for quantitation of hypochlorite and carbendazim.

Green emission carbon dots (CDs) electrochemically prepared from 2,6-pyridinedicarboxylic acid and o-phenyl-enediamine were applied separately for the quantitation of hypochlorite and carbendazim. The characteristic and optical properties of the CDs were studied through fluorescence, UV-vis absorption, X-ray photoelectron spectroscopy, and transmission electron microscopy. The synthesized CDs were mainly 0.

Computer-aided discovery, design, and investigation of COVID-19 therapeutics.

Coronavirus disease 2019 (COVID-19) pandemic is currently the most serious public health threat faced by mankind. Thus, the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), which causes COVID-19, is being intensively investigated. Several vaccines are now available for clinical use.

Hepatitis C virus core protein: Not just a nucleocapsid building block, but an immunity and inflammation modulator.

Coevolution occurs between viruses and their hosts. The hosts need to evolve means to eliminate pathogenic virus infections, and the viruses, for their own survival and multiplication, have to develop mechanisms to escape clearance by hosts. Hepatitis C virus (HCV) of is a pathogen which infects human liver and causes hepatitis, a condition of liver inflammation.

Viral Hepatitis, Cholesterol Metabolism, and Cholesterol-Lowering Natural Compounds.

Hepatitis is defined as inflammation of the liver; it can be acute or chronic. In chronic cases, the prolonged inflammation gradually damages the liver, resulting in liver fibrosis, cirrhosis, and sometimes liver failure or cancer. Hepatitis is often caused by viral infections.

Angiopoietin-Like Protein 3 (ANGPTL3) Modulates Lipoprotein Metabolism and Dyslipidemia.

Dyslipidemia is characterized by increasing plasma levels of low-density lipoprotein-cholesterol (LDL-C), triglycerides (TGs) and TG-rich lipoproteins (TGRLs) and is a major risk factor for the development of atherosclerotic cardiovascular disorders (ASCVDs). It is important to understand the metabolic mechanisms underlying dyslipidemia to develop effective strategies against ASCVDs. Angiopoietin-like 3 (ANGPTL3), a member of the angiopoietin-like protein family exclusively synthesized in the liver, has been demonstrated to be a critical regulator of lipoprotein metabolism to inhibit lipoprotein lipase (LPL) activity.

Valine-279 Deletion-Mutation on Arginine Vasopressin Receptor 2 Causes Obstruction in G-Protein Binding Site: A Clinical Nephrogenic Diabetes Insipidus Case and Its Sub-Molecular Pathogenic Analysis.

Congenital nephrogenic diabetes insipidus (CNDI) is a genetic disorder caused by mutations in arginine vasopressin receptor 2 () or aquaporin 2 genes, rendering collecting duct cells insensitive to the peptide hormone arginine vasopressin stimulation for water reabsorption. This study reports a first identified mutation in Taiwan and demonstrates our effort to understand the pathogenesis caused by applying computational structural analysis tools. The CNDI condition of an 8-month-old male patient was confirmed according to symptoms, family history, and DNA sequence analysis.

Nanosized Particles Assembled by a Recombinant Virus Protein Are Able to Encapsulate Negatively Charged Molecules and Structured RNA.

RNA-based molecules have recently become hot candidates to be developed into therapeutic agents. However, successful applications of RNA-based therapeutics might require suitable carriers to protect the RNA from enzymatic degradation by ubiquitous RNases in vivo. Because of their better biocompatibility and biodegradability, protein-based nanoparticles are considered to be alternatives to their synthetic polymer-based counterparts for drug delivery.

Internal water channel formation in CXCR4 is crucial for G-protein coupling upon activation by CXCL12.

Chemokine receptor CXCR4 is a major drug target for numerous diseases because of its involvement in the regulation of cell migration and the developmental process. In this study, atomic-level molecular dynamics simulations were used to determine the activation mechanism and internal water formation of CXCR4 in complex with chemokine CXCL12 and G-protein. The results indicated that CXCL12-bound CXCR4 underwent transmembrane 6 (TM6) outward movement and a decrease in tyrosine toggle switch by eliciting the breakage of hydrophobic layer to form a continuous internal water channel.

Altered susceptibility to air sampling stress by filtration is related to colistin resistance development in Acinetobacter baumannii.

The accurate quantification of antibiotic-resistant bacteria in indoor air has recently attracted increasing attention. Here, we investigated whether the susceptibility of a nosocomial infection-related microbe, Acinetobacter baumannii, to strong sampling stress caused by Nuclepore filter changes as it develops resistance to a drug called colistin. Both colistin-sensitive A.

A Sequence in the loop domain of hepatitis C virus E2 protein identified in silico as crucial for the selective binding to human CD81.

Hepatitis C virus (HCV) is a species-specific pathogenic virus that infects only humans and chimpanzees. Previous studies have indicated that interactions between the HCV E2 protein and CD81 on host cells are required for HCV infection. To determine the crucial factors for species-specific interactions at the molecular level, this study employed in silico molecular docking involving molecular dynamic simulations of the binding of HCV E2 onto human and rat CD81s.

Impact of cuticle photoluminescence on the color morphism of a male damselfly Ischnura senegalensis (Rambur, 1842).

In this study the damselfly Ischnura senegalensis (Rambur, 1842) was first found to produce strong photoluminescence (PL) emissions from various colored-body portions, such as the eighth abdominal segment of the tail. The colors of the colored-body portions can be enhanced or modified by the PL emissions for assistance in reducing intrasexual and male harassment, and improving mature mating and conspecific identity. Therefore, the PL emissions that contribute to the color modification and coloration are involved in the cuticle evolution of the damselflies.