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Scientific Reports Jul 2023Inflammation is a key factor in the pathogenesis of dry eye disease (DED). We aimed to investigate the role of microRNA-146a (miR-146a) in regulating corneal...
Inflammation is a key factor in the pathogenesis of dry eye disease (DED). We aimed to investigate the role of microRNA-146a (miR-146a) in regulating corneal inflammation in a mouse model of benzalkonium chloride (BAC)-induced dry eye and the TNF-α-induced NF-κB signaling pathway in human corneal epithelial cells (HCECs). A mouse model of dry eye was established by administering with BAC to BALB/c mice, and the expression of TNF-α, IL-1β, IL-6, IL-8, cyclooxygenase 2 (COX2), interleukin-1 receptor-associated kinase 1 (IRAK1) and TNF receptor-associated factor 6 (TRAF6) in the corneas of dry eye model mice was significantly increased; this was accompanied by the upregulation of miR-146a and activation of the NF-κB pathway. In vitro, TNF-α induced miR-146a expression in HCECs, while the NF-κB inhibitor SC-514 reduced the expression of miR-146a. Overexpression of miR-146a decreased the expression of IRAK1 and TRAF6, which have been identified as targets of miR-146a. Furthermore, overexpression of miR-146a suppressed NF-κB p65 translocation from the cytoplasm to the nucleus. Moreover, overexpression of miR-146a attenuated the TNF-α-induced expression of IL-6, IL-8, COX2 and intercellular adhesion molecule 1 (ICAM1), while inhibition of miR-146a exerted the opposite effect. Our results suggest that miR-146a mediates the inflammatory response in DED. MiR-146a negatively regulates inflammation in HCECs through the IRAK1/TRAF6/NF-κB pathway, and this may serve as a potential therapeutic approach for the treatment of DED.
Topics: Animals; Humans; Mice; Benzalkonium Compounds; Cyclooxygenase 2; Disease Models, Animal; Dry Eye Syndromes; Inflammation; Interleukin-1 Receptor-Associated Kinases; Interleukin-6; Interleukin-8; MicroRNAs; NF-kappa B; Signal Transduction; TNF Receptor-Associated Factor 6; Tumor Necrosis Factor-alpha
PubMed: 37433841
DOI: 10.1038/s41598-023-38367-4 -
Advanced Drug Delivery Reviews Nov 2023Surfactants are a diverse group of compounds that share the capacity to adsorb at the boundary between distinct phases of matter. They are used as pharmaceutical... (Review)
Review
Surfactants are a diverse group of compounds that share the capacity to adsorb at the boundary between distinct phases of matter. They are used as pharmaceutical excipients, food additives, emulsifiers in cosmetics, and as household/industrial detergents. This review outlines the interaction of surfactant-type excipients present in oral pharmaceutical dosage forms with the intestinal epithelium of the gastrointestinal (GI) tract. Many surfactants permitted for human consumption in oral products reduce intestinal epithelial cell viability in vitro and alter barrier integrity in epithelial cell monolayers, isolated GI tissue mucosae, and in animal models. This suggests a degree of mis-match for predicting safety issues in humans from such models. Recent controversial preclinical research also infers that some widely used emulsifiers used in oral products may be linked to ulcerative colitis, some metabolic disorders, and cancers. We review a wide range of surfactant excipients in oral dosage forms regarding their interactions with the GI tract. Safety data is reviewed across in vitro, ex vivo, pre-clinical animal, and human studies. The factors that may mitigate against some of the potentially abrasive effects of surfactants on GI epithelia observed in pre-clinical studies are summarised. We conclude with a perspective on the overall safety of surfactants in oral pharmaceutical dosage forms, which has relevance for delivery system development.
Topics: Animals; Humans; Excipients; Drug Compounding; Pharmaceutical Preparations; Intestines; Surface-Active Agents
PubMed: 37739041
DOI: 10.1016/j.addr.2023.115086 -
Food Science & Nutrition Jul 2023Dietary exposure was introduced as the primary way Bisphenol A (BPA) enters the human body. Although significant efforts have been made to analyze BPA's presence in... (Review)
Review
Dietary exposure was introduced as the primary way Bisphenol A (BPA) enters the human body. Although significant efforts have been made to analyze BPA's presence in different foodstuffs, less attention has been given to introducing the conditions that facilitate BPA release. This review aimed to mention possible factors affecting BPA release into foods and beverages. According to the results, the critical factors in BPA release are temperature, manufacturing process, food and packaging type, pH, mineral elements, repeated use, irradiation, washing, contact time, and using detergents. It showed that using PC containers, high temperature and pH, storage under solar irradiation, alkaline detergents, water hardness, and repeated use could increase the BPA release from containers into foodstuff. During various conditions, hydrolysis of the carbonate linkage and -spacing will increase. Considering these parameters and limiting the use of PC containers, the potential risk of BPA exposure could be eliminated.
PubMed: 37457148
DOI: 10.1002/fsn3.3398 -
Biological Chemistry Jun 2023Na/taurocholate cotransporting polypeptide (NTCP) is a member of the solute carrier (SLC) family 10 transporters (gene symbol ) and is responsible for the... (Review)
Review
Interactions of Na/taurocholate cotransporting polypeptide with host cellular proteins upon hepatitis B and D virus infection: novel potential targets for antiviral therapy.
Na/taurocholate cotransporting polypeptide (NTCP) is a member of the solute carrier (SLC) family 10 transporters (gene symbol ) and is responsible for the sodium-dependent uptake of bile salts across the basolateral membrane of hepatocytes. In addition to its primary transporter function, NTCP is the high-affinity hepatic receptor for hepatitis B (HBV) and hepatitis D (HDV) viruses and, therefore, is a prerequisite for HBV/HDV virus entry into hepatocytes. The inhibition of HBV/HDV binding to NTCP and internalization of the virus/NTCP receptor complex has become a major concept in the development of new antiviral drugs called HBV/HDV entry inhibitors. Hence, NTCP has emerged as a promising target for therapeutic interventions against HBV/HDV infections in the last decade. In this review, recent findings on protein-protein interactions (PPIs) between NTCP and cofactors relevant for entry of the virus/NTCP receptor complex are summarized. In addition, strategies aiming to block PPIs with NTCP to dampen virus tropism and HBV/HDV infection rates are discussed. Finally, this article suggests novel directions for future investigations evaluating the functional contribution of NTCP-mediated PPIs in the development and progression of HBV/HDV infection and subsequent chronic liver disorders.
Topics: Humans; Antiviral Agents; Hep G2 Cells; Hepatitis B; Hepatitis B virus; Hepatitis Delta Virus; Hepatocytes; Peptides; Symporters; Taurocholic Acid; Virus Internalization
PubMed: 37103224
DOI: 10.1515/hsz-2022-0345 -
Frontiers in Molecular Biosciences 2023Insoluble α-synuclein (αSyn) filaments in brain tissue are a hallmark of Parkinson's disease (PD) and Multiple system atrophy (MSA), and for structural studies, they...
Insoluble α-synuclein (αSyn) filaments in brain tissue are a hallmark of Parkinson's disease (PD) and Multiple system atrophy (MSA), and for structural studies, they have for decades been extracted using the detergent sarkosyl. We asked if PD and MSA patient-derived αSyn filament strains display different stability to sarkosyl extraction as this may confound our interpretation of the landscape of structural strains present in patients' tissue. We compared the stability of cerebrospinal fluid-derived strains from four PD and four MSA patients using sedimentation and immunoassays and tested the seeding competence and strain-specific characteristics of the sarkosyl-soluble fractions using a seed amplification assay (SAA) and Thioflavin T (ThT) fluorescence. We demonstrate that filaments from PD are less resistant to sarkosyl than from MSA after they have been subjected to freezing and sonication. An enhanced release of monomers from PD filaments was the major difference between PD and MSA, but the sarkosyl-soluble fraction released from both PD and MSA filaments contained aggregates that displayed aggregate-specific epitopes and seeding activity with preserved disease-specific strain characteristics. Our results demonstrate that sarkosyl differentially destabilizes patient derived αSyn filament strains, which may compromise our ability to fully appreciate the landscape of αSyn filament currently being uncovered by high resolution cryoEM analyses. This should motivate an effort to develop more gentle extraction protocols.
PubMed: 37621995
DOI: 10.3389/fmolb.2023.1177556 -
Physiological Research Oct 2023The rapid development of tissue engineering (TE) and regenerative medicine brings an acute need for biocompatible and bioactive biological scaffolds to regenerate or...
The rapid development of tissue engineering (TE) and regenerative medicine brings an acute need for biocompatible and bioactive biological scaffolds to regenerate or restore damaged tissue. Great attention is focused on the decellularization of tissues or even whole organs, and the subsequent colonization of such decellularized extracellular matrices by recipient cells. The foreskin is an integral, normal part of the external genitalia that forms the anatomical covering of the glans penis and the urinary meatus of all human and non-human primates. It is mucocutaneous tissue that marks the boundary between mucosa and skin. In this work, we compared two innovative decellularization techniques for human foreskins obtained from donors. We compared the efficacy and feasibility of these protocols and the biosafety of prepared acellular dermal matrixes that can serve as a suitable scaffold for TE. The present study confirms the feasibility of foreskin decellularization based on enzymatic or detergent methods. Both techniques conserved the ultrastructure and composition of natural ECM while being DNA-free and non-toxic, making it an excellent scaffold for follow-up research and TE applications.
Topics: Male; Animals; Humans; Tissue Engineering; Foreskin; Tissue Scaffolds; Extracellular Matrix; Regenerative Medicine
PubMed: 37888972
DOI: 10.33549/physiolres.935185 -
Advanced Science (Weinheim,... Nov 2023In this study, the potential of complex emulsions is investigated as transducers in sensing applications. Complex emulsions are stabilized without external detergents by...
In this study, the potential of complex emulsions is investigated as transducers in sensing applications. Complex emulsions are stabilized without external detergents by developing a novel α-cyanostilbene substituted with PEG and semi-perfluoroalkyl chain (CNFCPEG). CNFCPEG exhibits unique variable emission properties depending on its aggregation state, allowing dual blue and green emissions in complex emulsions with hydrocarbon-in-fluorocarbon-in-water (H/F/W) morphology. The green excimer emissions result from the self-assembly of CNFCPEG at the fluorocarbon/water interface, while the blue emission observed is due to aggregation in the organic phase. A novel flow-injection method is developed by incorporating complex emulsions with CNFCPEG into multiple-well flow chips (MWFC). Iodine is successfully detected in a mobile aqueous solution by monitoring morphology changes. The findings demonstrate that self-stabilized complex emulsions with MWFC hold great promise for real-time sensing without costly instruments.
PubMed: 37702128
DOI: 10.1002/advs.202304108 -
Frontiers in Physiology 2023To date, the discussion concerning bile acids (BAs) during gestation is almost exclusively linked to pregnancy complications such as intrahepatic cholestasis of... (Review)
Review
To date, the discussion concerning bile acids (BAs) during gestation is almost exclusively linked to pregnancy complications such as intrahepatic cholestasis of pregnancy (ICP) when maternal serum BA levels reach very high concentrations (>100 μM). Generally, the placenta is believed to serve as a protective barrier avoiding exposure of the growing fetus to excessive amounts of maternal BAs that might cause detrimental effects (e.g., intrauterine growth restriction and/or increased vulnerability to metabolic diseases). However, little is known about the precise role of the placenta in BA biosynthesis, transport, and metabolism in healthy pregnancies when serum BAs are at physiological levels (i.e., low maternal and high fetal BA concentrations). It is well known that primary BAs are synthesized from cholesterol in the liver and are later modified to secondary BA species by colonic bacteria. Besides the liver, BA synthesis in extrahepatic sites such as the brain elicits neuroprotective actions through inhibition of apoptosis as well as oxidative and endoplasmic reticulum stress. Even though historically BAs were thought to be only "detergent molecules" required for intestinal absorption of dietary fats, they are nowadays acknowledged as full signaling molecules. They modulate a myriad of signaling pathways with functional consequences on essential processes such as gluconeogenesis -one of the principal energy sources of the fetus- and cellular proliferation. The current manuscript discusses the potential multipotent roles of physiologically circulating BAs on developmental processes during gestation and provides a novel perspective in terms of the importance of the placenta as a previously unknown source of BAs. Since the principle "not too much, not too little" applicable to other signaling molecules may be also true for BAs, the risks associated with fetal exposure to excessive levels of BAs are discussed.
PubMed: 37546542
DOI: 10.3389/fphys.2023.1213757 -
Gels (Basel, Switzerland) Aug 2023Hydrolases are enzymes that have found numerous applications in various industrial sectors spanning from pharmaceuticals to foodstuff and beverages, consumers' products... (Review)
Review
Hydrolases are enzymes that have found numerous applications in various industrial sectors spanning from pharmaceuticals to foodstuff and beverages, consumers' products such as detergents and personal care, textiles, and even for biodiesel production and environmental bioremediation. Self-assembling and gelling short peptides have been designed for their mimicry so that their supramolecular organization leads to the creation of hydrophobic pockets for catalysis to occur. Catalytic gels of this kind can also find numerous industrial applications to address important global challenges of our time. This concise review focuses on the last 5 years of progress in this fast-paced, popular field of research with an eye towards the future.
PubMed: 37754360
DOI: 10.3390/gels9090678 -
Molecules (Basel, Switzerland) Nov 2023Utilized for gaining structural insights, small-angle neutron and X-ray scattering techniques (SANS and SAXS, respectively) enable an examination of biomolecules,... (Review)
Review
Utilized for gaining structural insights, small-angle neutron and X-ray scattering techniques (SANS and SAXS, respectively) enable an examination of biomolecules, including photosynthetic pigment-protein complexes, in solution at physiological temperatures. These methods can be seen as instrumental bridges between the high-resolution structural information achieved by crystallography or cryo-electron microscopy and functional explorations conducted in a solution state. The review starts with a comprehensive overview about the fundamental principles and applications of SANS and SAXS, with a particular focus on the recent advancements permitting to enhance the efficiency of these techniques in photosynthesis research. Among the recent developments discussed are: (i) the advent of novel modeling tools whereby a direct connection between SANS and SAXS data and high-resolution structures is created; (ii) the employment of selective deuteration, which is utilized to enhance spatial selectivity and contrast matching; (iii) the potential symbioses with molecular dynamics simulations; and (iv) the amalgamations with functional studies that are conducted to unearth structure-function relationships. Finally, reference is made to time-resolved SANS/SAXS experiments, which enable the monitoring of large-scale structural transformations of proteins in a real-time framework.
Topics: Scattering, Small Angle; Cryoelectron Microscopy; X-Ray Diffraction; Proteins; Photosynthesis
PubMed: 37959833
DOI: 10.3390/molecules28217414