Abstract
Aging is accompanied by impaired mitochondrial function and accumulation of senescent cells. Mitochondrial dysfunction contributes to senescence by increasing the levels of reactive oxygen ...species and compromising energy metabolism. Senescent cells secrete a senescence‐associated secretory phenotype (SASP) and stimulate chronic low‐grade inflammation, ultimately inducing inflammaging. Mitochondrial dysfunction and cellular senescence are two closely related hallmarks of aging; however, the key driver genes that link mitochondrial dysfunction and cellular senescence remain unclear. Here, we aimed to elucidate a novel role of carnitine acetyltransferase (CRAT) in the development of mitochondrial dysfunction and cellular senescence in dermal fibroblasts. Transcriptomic analysis of skin tissues from young and aged participants showed significantly decreased CRAT expression in intrinsically aged skin. CRAT downregulation in human dermal fibroblasts recapitulated mitochondrial changes in senescent cells and induced SASP secretion. Specifically, CRAT knockdown caused mitochondrial dysfunction, as indicated by increased oxidative stress, disruption of mitochondrial morphology, and a metabolic shift from oxidative phosphorylation to glycolysis. Mitochondrial damage induced the release of mitochondrial DNA into the cytosol, which activated the cyclic GMP‐AMP synthase (cGAS)‐stimulator of interferon genes (STING) and NF‐ĸB pathways to induce SASPs. Consistently, fibroblast‐specific CRAT‐knockout mice showed increased skin aging phenotypes in vivo, including decreased cell proliferation, increased SASP expression, increased inflammation, and decreased collagen density. Our results suggest that CRAT deficiency contributes to aging by mediating mitochondrial dysfunction‐induced senescence.
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•The flexible antibacterial ZnO nanopiilar arrays were sucessfully fabricated by assistance of sonochemical reaction.•The ZnO formation mechanism is also proposed and investigated ...using FT-IR and XRD.•Antibacterial efficiency was depthly investigated using realistic pathogetnic bacteria model of E. coli O157:H7 and S. aureus.•ZnO nanopiilar arrays have improved antibacterial behavior because of nanotopological effects and electrostatic interaction.
Antibacterial activity is essential and highly demanded in worldwide to prevent potential bacterial infection. Here in this work, we report a new approch for the fabrication of flexible zinc oxide nanopillar arrays (ZG-NPA) film with an efficient antibacterial activity. A flexible NPA film served as a substrate for the rapid formation of ZnO by using ultrasound-assisted method. The enhancement of antibacterial activity were induced by cellular damages because of nano topological effects and electrostatic interaction between bacteria and ZG-NPA. Owing to the benefits of combination with flexibility, high surface areas from nano-features and excellent antibacterial efficiency (>80%) of ZG-NPA, the film can show great potential for use as novel biomaterials for preventing bacterial infections.
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Photoaging mainly occurs due to ultraviolet (UV) radiation, and is accompanied by increased secretion of matrix metalloproteinases (MMPs) and degradation of collagen. UV radiation ...induces cell senescence in the skin; however, the role of senescent cells in photoaging remains unclear. Therefore, to elucidate the role of senescent cells in photoaging, we evaluated the effect of senolytics in a photoaging mouse model and investigated the underlying mechanism of their antiaging effect. Both UV-induced senescent human dermal fibroblasts and a photoaging mouse model, ABT-263 and ABT-737, demonstrated senolytic effects on senescent fibroblasts. Moreover, we found that several senescence-associated secretory phenotype factors, such as IL-6, CCL5, CCL7, CXCL12, and SCF, induced MMP-1 expression in dermal fibroblasts, which decreased after treatment with ABT-263 and ABT-737 in vivo and in vitro. Both senolytic drugs attenuated the induction of MMPs and decreased collagen density in the photoaging mouse model. Our data suggest that senolytic agents reduce UV-induced photoaging, making strategies for targeting senescent dermal fibroblasts promising options for the treatment of photoaging.
•Secretory phenotypes from UV-induced senescent fibroblasts induced MMP-1 expression.•Treatment with senolytic drugs attenuated collagen degradation in photoaged mice.•Elimination of senescent cells in photoaged skin exhibited an antiaging effect.
•A natural compound harmine decreased melanin synthesis and tyrosinase expression in human MNT-1 melanoma cells and human primary melanocytes.•Melanin synthesis was reduced by inhibition of DYRK1A, a ...harmine target, and enhanced by knockdown of NFATC3, a potential DYRK1A target.•Harmine decreases melanin synthesis through regulation of the DYRK1A/NFATC3 pathway.
Melanin plays important roles in determining human skin color and protecting human skin cells against harmful ultraviolet light. However, abnormal hyperpigmentation in some areas of the skin may become aesthetically unpleasing, resulting in the need for effective agents or methods to regulate undesirable hyperpigmentation.
We investigated the effect of harmine, a natural harmala alkaloid belonging to the beta-carboline family, on melanin synthesis and further explored the signaling pathways involved in its mechanism of action.
Human MNT-1 melanoma cells and human primary melanocytes were treated with harmine, chemical inhibitors, small interfering RNAs, or mammalian expression vectors. Cell viability, melanin content, and expression of various target molecules were assessed.
Harmine decreased melanin synthesis and tyrosinase expression in human MNT-1 melanoma cells. Inhibition of DYRK1A, a harmine target, decreased melanin synthesis and tyrosinase expression. Further studies revealed that nuclear translocation of NFATC3, a potential DYRK1A substrate, was induced via the harmine/DYRK1A pathway and that NFATC3 knockdown increased melanin synthesis and tyrosinase expression. Suppression of melanin synthesis and tyrosinase expression via the harmine/DYRK1A pathway was significantly attenuated by NFATC3 knockdown. Furthermore, harmine also decreased melanin synthesis and tyrosinase expression through regulation of NFATC3 in human primary melanocytes.
Our results indicate that harmine decreases melanin synthesis through regulation of the DYRK1A/NFATC3 pathway and suggest that the DYRK1A/NFATC3 pathway may be a potential target for the development of depigmenting agents.
Abstract Agaricus bisporus (white button mushroom; WBM) contains high levels of dietary fibers and antioxidants including vitamin C, D, and B12 ; folates; and polyphenols that may provide beneficial ...effects on cardiovascular and diabetic diseases. The objective of this study was to examine the hypothesis that intake of the fruiting bodies of WBM regulates anticholesterolemic and antiglycemic responses in rats fed a hypercholesterolemic diet (0.5% cholesterol; 14% fat) and rats with type 2 diabetes induced by injection of streptozotocin (STZ) (50 mg/kg body weight), respectively. The STZ-induced diabetic male Sprague-Dawley rats fed the Agaricus bisporus powder (ABP; 200 mg/kg of body weight) for 3 weeks had significantly reduced plasma glucose and triglyceride (TG) concentrations (24.7% and 39.1%, respectively), liver enzyme activities, alanine aminotransferase and aspartate aminotransferase (11.7% and 15.7%, respectively), and liver weight gain ( P < .05). In hypercholesterolemic rats, oral feeding of ABP for 4 weeks resulted in a significant decrease in plasma total cholesterol (TC) and low-density lipoprotein (LDL) (22.8% and 33.1%, respectively) ( P < .05). A similar significant decrease in hepatic cholesterol and TG concentrations was observed (36.2% and 20.8%, respectively) ( P < .05). Decrease in TC, LDL, and TG concentrations was accompanied by a significant increase in plasma high-density lipoprotein concentrations. It was concluded that A bisporus mushroom had both hypoglycemic and hypolipidemic activity in rats.
The stigma associated with coronavirus disease (COVID-19) is relatively neglected in policies for handling the disease. Stigmatization occurs only within specific social contexts in local societies.
...This study aims to examine COVID-19 survivors' experiences of social stigma and discrimination in South Korea in the first 2 years of the pandemic.
Semi-structured interviews were conducted.
Of 52 participants, 45 reported that they had to cope with stigma and discrimination in their intimate social relationships, workplaces, and children's schools, ranging from subtle actions to job loss. Sexual minorities who were involved in mass disease transmission in the early part of the pandemic experienced a higher level of stigmatization. The stigmatization dealt with in this study was related to two themes: survivors' sense of causing trouble and possibility of transmission.
By intertwining this stigma with the experiences of public health measures through the voices of survivors, this study reveals the local context of East Asia in terms of culture-specific aspects of COVID-19-related stigma.
Agaricus bisporus mushrooms contain an abundance of ergosterol, which on exposure to UV irradiation is converted to vitamin D2. The present study evaluated the effects UV-C irradiation on vitamin D2 ...formation and its bioavailability in rats. Fresh button mushrooms were exposed to UV-C irradiation at mean intensities of 0.403, 0.316, and 0.256 mW/cm2 from respective distances of 30, 40, and 50 cm for periods ranging from 2.5 to 60 min. Vitamin D2 and ergosterol were measured by HPLC-MS/MS. The stability and retention of vitamin D2 were assessed including the extent of discoloration during storage at 4 °C or at room temperature. Exposure to UV-C irradiation at 0.403 mW/cm2 intensity from 30 cm distance resulted in a time-dependent increase in vitamin D2 concentrations that was significantly higher than those produced at intensities of 0.316 and 0.256 mW/cm2 from distances of 40 and 50 cm, respectively. Furthermore, the concentrations of vitamin D2 produced after exposure to UV-C irradiation doses of 0.125 and 0.25 J/cm2 for, 2.5, 5, and 10 min were 6.6, 15.6, and 23.1 μg/g solids, equivalent to 40.6, 95.4, and 141 μg/serving, respectively. The data showed a high rate of conversion from ergosterol to vitamin D2 at short treatment time, which is required by the mushroom industry. The stability of vitamin D2 remained unchanged during storage at 4 °C and at room temperature over 8 days (P = 0.36), indicating no degradation of vitamin D2. By visual assessment or using a chromometer, no significant discoloration of irradiated mushrooms, as measured by the degree of “whiteness”, was observed when stored at 4 °C compared to that observed with mushrooms stored at room temperature over an 8 day period (P < 0.007). Vitamin D2 was well absorbed and metabolized as evidenced by the serum response of 25-hydroxyvitamin D in rats fed the irradiated mushrooms. Taken together, the data suggest that commercial production of button mushrooms enriched with vitamin D2 for improving consumer health may be practical.
Agaricus bisporus white button mushroom (WBM) is widely consumed in most countries for its culinary properties. Recently, its dietary intake has been shown to protect against breast cancer. Mushroom ...polysaccharides are known for their immunomodulating and antitumor properties; however, little is known regarding the properties of A. bisporus polysaccharides. Using size-exclusion chromatography to fractionate the crude extract of A. bisporus, two polysaccharide fractions (designated as ABP-1 and ABP-2) were obtained. The estimated molecular masses of ABP-1 and ABP-2 were 2,000 kDa and 40-70 kDa, respectively, and their sugar compositions consisted mainly of glucose, mannose, xylose, and fructose. Analysis of the effects of the polysaccharides on murine macrophages demonstrated that both fractions stimulated the production of nitric oxide, interleukin-6, and tumor necrosis factor-α. Modulation of macrophage function by A. bisporus polysaccharides was mediated in part through activation of nuclear factor-κB with the production p50/105 heterodimers. Both ABP-1 and ABP-2 had the ability to inhibit the growth of human breast cancer MCF-7 cells but had little effect on the growth of human colon, prostate, gastric cancer, and murine Sarcoma 180 cells as assessed by a tetrazolium dye 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide-based assay. However, when murine Sarcoma 180 cells exposed to ABP-1 or ABP-2 were implanted subcutaneously into mice, a reduction in tumor growth was observed compared with that observed in control mice. Taken together, our data provide a molecular basis to explain in part the reported beneficial therapeutic effects of A. bisporus WBM intake and suggest that macrophages likely contribute to the antitumor effects of Agaricus polysaccharides.
A bacteria-capturing platform is a critical function of accurate, quantitative, and sensitive identification of bacterial pathogens for potential usage in the detection of foodborne diseases. Despite ...the development of various nanostructures and their surface chemical modification strategies, relative to the principal physical contact propagation of bacterial infections, mechanically robust and nanostructured platforms that are available to capture bacteria remain a significant problem. Here, a three-dimensional (3D) hierarchically structured polyaniline nanoweb film is developed for the efficient capture of bacterial pathogens by hand-touching. This unique nanostructure ensures sufficient mechanical resistance when exposed to compression and shear forces and facilitates the 3D interfacial interactions between bacterial extracellular organelles and polyaniline surfaces. The bacterial pathogens (
Escherichia coli
O157:H7,
Salmonella enteritidis
, and
Staphylococcus aureus
) are efficiently captured through finger-touching, as verified by the polymerase chain reaction (PCR) analysis. Moreover, the real-time PCR results of finger-touched cells on a 3D nanoweb film show a highly sensitive detection of bacteria, which is similar to those of the real-time PCR using cultured cells without the capturing step without any interfering of fluorescence signal and structural deformation during thermal cycling.
Graphic Abstract
The hypolipidemic effect of an exo-biopolymer produced from a submerged mycelial culture of Hericium erinaceus was investigated in dietary-induced hyperlipidemic rats. Hypolipidemic effects were ...proportionally increased with the increasing concentration of the exo-biopolymer for oral administration. The exo-biopolymer, at the dose of 200 mg/kg body weight, substantially reduced the plasma total cholesterol (32.9%), LDL cholesterol (45.4%), triglyceride (34.3%), phospholipid (18.9%), atherogenic index (58.7%), and hepatic HMG-CoA reductase activity (20.2%). It increased the plasma HDL cholesterol level (31.1%) as compared to the control group. The molecular mass of this exo-biopolymer measured by HPLC was under 40 kDa. Total sugar and protein contents were 91.2 and 8.8%, respectively. The sugar and amino acid compositions of the exo-biopolymer were analyzed in detail.
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