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BACKGROUND: Both sodium-glucose cotransporter-2 (SGLT2) inhibitors and glucagon-like peptide-1 receptor agonists (GLP-1 RAs) may have neuroprotective effects in patients with type 2 diabetes (T2D). However, their comparative effectiveness in preventing dementia remains uncertain. OBJECTIVE: To compare the risk for dementia between SGLT2 inhibitors and dulaglutide (a GLP-1 RA). DESIGN: Target trial emulation study. SETTING: Nationwide health care data of South Korea obtained from the National Health Insurance Service between 2010 and 2022. PATIENTS: Patients aged 60 years or older who have T2D and are initiating treatment with SGLT2 inhibitors or dulaglutide. MEASUREMENTS: The primary outcome was the presumed clinical onset of dementia. The date of onset was defined as the year before the date of dementia diagnosis, assuming that the time between the onset of dementia and diagnosis was 1 year. The 5-year risk ratios and risk differences comparing SGLT2 inhibitors with dulaglutide were estimated in a 1:2 propensity score-matched cohort adjusted for confounders. RESULTS: Overall, 12 489 patients initiating SGLT2 inhibitor treatment (51.9% dapagliflozin and 48.1% empagliflozin) and 1075 patients initiating dulaglutide treatment were included. In the matched cohort, over a median follow-up of 4.4 years, the primary outcome event occurred in 69 participants in the SGLT2 inhibitor group and 43 in the dulaglutide group. The estimated risk difference was -0.91 percentage point (95% CI, -2.45 to 0.63 percentage point), and the estimated risk ratio was 0.81 (CI, 0.56 to 1.16). LIMITATION: Residual confounding is possible; there was no adjustment for hemoglobin A1c levels or duration of diabetes; the study is not representative of newer drugs, including more effective GLP-1 RAs; and the onset of dementia was not measured directly. CONCLUSION: Under conventional statistical criteria, a risk for dementia between 2.5 percentage points lower and 0.6 percentage point greater for SGLT2 inhibitors than for dulaglutide was estimated to be highly compatible with the data from this study. However, whether these findings generalize to newer GLP-1 RAs is uncertain. Thus, further studies incorporating newer drugs within these drug classes and better addressing residual confounding are required. PRIMARY FUNDING SOURCE: Ministry of Food and Drug Safety of South Korea.
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Iron and myelin are primary susceptibility sources in the human brain. These substances are essential for a healthy brain, and their abnormalities are often related to various neurological disorders. Recently, an advanced susceptibility mapping technique, which is referred to as χ-separation (pronounced as "chi"-separation), has been proposed, successfully disentangling paramagnetic iron from diamagnetic myelin. This method provided a new opportunity for generating high-resolution iron and myelin maps of the brain. Utilizing this technique, this study constructs a normative χ-separation atlas from 106 healthy human brains. The resulting atlas provides detailed anatomical structures associated with the distributions of iron and myelin, clearly delineating subcortical nuclei, thalamic nuclei, and white matter fiber bundles. Additionally, susceptibility values in a number of regions of interest are reported along with age-dependent changes. This atlas may have direct applications such as localization of subcortical structures for deep brain stimulation or high-intensity focused ultrasound and also serve as a valuable resource for future research.
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OBJECTIVE: Subjective cognitive decline (SCD) refers to self-reported memory loss despite normal cognitive function and is considered a preclinical stage of Alzheimer's disease. This study aimed to examine the mediating effects of depression and Instrumental Activities of Daily Living (IADL) on the association between the scoring of Clinical Dementia Rating Scale-Sum of Boxes (CDR-SB) and Subjective Cognitive Decline Questionnaire (SCD-Q). METHODS: A sample of 139 community-dwelling older adults aged 65-79 with normal cognitive function completed the SCD-Q, a comprehensive neuropsychological battery, and functional/psychiatric scales. We conducted 1) a correlation analysis between SCD-Q scores and other variables and 2) a path analysis to examine the mediating effects of depression and IADL on the relationship between CDR-SB and SCD-Q. RESULTS: CDR-SB was found to be indirectly associated with SCD-Q, with depressive symptoms mediating this relationship. However, no direct association was observed between SCD-Q and CDR-SB. Additionally, IADL was not associated with SCD-Q and did not mediate the relationship between CDR-SB and SCD-Q. The model fit was acceptable (minimum discrepancy function by degrees of freedom divided [CMIN/DF]=1.585, root mean square error of approximation [RMSEA]=0.065, comparative fit index [CFI]=0.955, Tucker-Lewis index [TLI]=0.939). CONCLUSION: Our results suggest that SCD-Q is influenced by depressive symptoms, but not by IADL. The role of depressive symptoms as a mediator between CDR-SB and SCD-Q indicates that psychological factors may contribute to the perception of SCD. Therefore, interventions targeting depression may mitigate the concerns associated with SCD and reduce feelings of worse performance compared to others of the same age group.
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BACKGROUND: Despite the notable pharmacological potential of natural ginsenosides, their industrial application is hindered by low oral bioavailability. Recent research centers on the production of less-glycosylated minor ginsenosides. PURPOSE: This study aimed to explore the effect of a biologically synthesized ginsenoside CK-rich minor ginsenoside complex (AceCK40), on ameliorating colitis using DSS-induced colitis models in vitro and in vivo. METHODS: The ginsenoside composition of AceCK40 was determined by HPLC-ELSD and UHPLC-MS/MS analyses. In vitro colitis model was established using dextran sodium sulfate (DSS)-induced Caco-2 intestinal epithelial model. For in vivo experiments, DSS-induced severe colitis mouse model was established. RESULTS: In DSS-stimulated Caco-2 cells, AceCK40 downregulated mitogen-activated protein kinase (MAPK) activation (p < 0.05), inhibited monocyte chemoattractant protein-1 (MCP-1) production (p < 0.05), and enhanced MUC2 expression (p < 0.05), mediated via signaling pathway regulation. Daily AceCK40 administration at doses of 10 and 30 mg/kg/day was well tolerated by DSS-induced severe colitis mice. These doses led to significant alleviation of disease activity index score (> 36.0% decrease, p < 0.05), increased luminal immunoglobulin (Ig)G (> 37.6% increase, p < 0.001) and IgA (> 33.8% increase, p < 0.001), lowered interleukin (IL)-6 (> 65.7% decrease, p < 0.01) and MCP-1 (> 116.2% decrease, p < 0.05), as well as elevated serum IgA (> 51.4% increase, p < 0.001) and lowered serum IL-6 (112.3% decrease at 30 mg/kg, p < 0.001). Hematoxylin and eosin (H&E) and periodic acid-Schiff (PAS) staining revealed that DSS-mediated thickening of the muscular externa, extensive submucosal edema, crypt distortion, and decreased mucin droplets were significantly alleviated by AceCK40 administration. Additionally, daily administration of AceCK40 led to significant recovery of colonic tight junctions damaged by DSS through the elevation in the expression of adhesion molecules, including occludin, E-cadherin, and N-cadherin. CONCLUSION: This study presents the initial evidence elucidating the anti-colitis effects of AceCK40 and its underlying mechanism of action through sequential in vitro and in vivo systems employing DSS stimulation. Our findings provide valuable fundamental data for the utilization of AceCK40 in the development of novel anti-colitis candidates.
Subject(s)
Colitis , Ginsenosides , Humans , Mice , Animals , Ginsenosides/metabolism , Caco-2 Cells , Mice, Inbred C57BL , Tandem Mass Spectrometry , Colitis/chemically induced , Colitis/drug therapy , Colitis/metabolism , Colon , Immunoglobulin A/metabolism , Immunoglobulin A/pharmacology , Immunoglobulin A/therapeutic use , Dextran Sulfate/adverse effects , Disease Models, Animal , Intestinal Mucosa/metabolismABSTRACT
Cellular energy is primarily produced from glucose and fat through glycolysis and fatty acid oxidation (FAO) followed by the tricarboxylic acid cycle in mitochondria; energy homeostasis is carefully maintained via numerous feedback pathways. In this report, we uncovered a new master regulator of carbohydrate and lipid metabolism. When ubiquitin E3 ligase ß-TrCP2 was inducibly knocked out in ß-TrCP1 knockout adult mice, the resulting double knockout mice (DKO) lost fat mass rapidly. Biochemical analyses of the tissues and cells from ß-TrCP2 KO and DKO mice revealed that glycolysis, FAO, and lipolysis were dramatically upregulated. The absence of ß-TrCP2 increased the protein stability of metabolic rate-limiting enzymes including 6-phosphofructo-2-kinase/fructose-2,6-bisphosphatase (PFKFB3), adipose triglyceride lipase (ATGL), carnitine palmitoyltransferase 1A (CPT1A), and carnitine/acylcarnitine translocase (CACT). Our data suggest that ß-TrCP is a potential regulator for total energy homeostasis by simultaneously controlling glucose and fatty acid metabolism and that targeting ß-TrCP could be an effective strategy to treat obesity and other metabolic disorders.
Subject(s)
Carbohydrate Metabolism , Fatty Acids , beta-Transducin Repeat-Containing Proteins , Animals , Mice , beta-Transducin Repeat-Containing Proteins/genetics , beta-Transducin Repeat-Containing Proteins/metabolism , Fatty Acids/metabolism , Glucose/metabolism , Glycolysis , Mice, Knockout , Ubiquitin-Protein Ligases/metabolismABSTRACT
Objectives: Diffusion tensor image analysis along the perivascular space (DTI-ALPS) is a recently introduced method for the assessment of the glymphatic system without the need for contrast injection. The purpose of our study was to assess the glymphatic system in cognitively normal older adults with or without subjective cognitive decline (SCD) using DTI-ALPS, and correlating with amyloid PET. Design and participants: To evaluate the glymphatic system in cognitively normal older adults using DTI-ALPS, we built a prospective cohort including a total of 123 objectively cognitively normal older adults with or without SCD. The ALPS index was calculated from DTI MRI and was assessed by correlating it with standardized uptake value ratios (SUVRs) from amyloid PET and clinically relevant variables. The study subjects were also divided into amyloid "positive" and "negative" groups based on the result of amyloid PET, and the ALPS indices between those two groups were compared. Results: The ALPS index was not significantly different between the normal and SCD groups (P = 0.897). The mean ALPS index from the amyloid positive and amyloid negative group was 1.31 and 1.35, respectively, which showed no significant difference (P = 0.308). Among the SUVRs from variable cortices, that of the paracentral cortex was negatively correlated with the ALPS index (r = -0.218, P = 0.016). Multivariate linear regression revealed that older age (coefficient, -0.007) and higher SUVR from the paracentral cortex (coefficient, -0.101) were two independent variables with a significant association with a lower ALPS index (P = 0.015 and 0.045, respectively). Conclusion: DTI-ALPS may not be useful for evaluation of the glymphatic system in subjects with SCD. Older age was significantly associated with lower ALPS index. Greater amyloid deposition in the paracentral cortex was significantly associated with lower glymphatic activity in cognitively normal older adults. These results should be validated in future studies on the relationships between ALPS index and other fundamental compartments in glymphatic system, such as perivenous space and the meningeal lymphatic vessels.
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The present study aimed to investigate the effect of oral administration of snail-derived mucin extract (SM) on ameliorating constipation symptoms of loperamide-induced constipated rats (n = 6). The analytical results indicated that SM mainly contains a glucan-rich snail mucin heteropolysaccharide with high molecular weights (108.5-267.9 kDa), comprising primarily of glucose (64.9 %) and galactose (22.4 %) with some deoxyhexoses (5.0 %) and hexosamines (4.9 %). Daily SM administration at doses of 10-40 mg/kg/day to the loperamide-induced constipated rats significantly (p < 0.05) ameliorated the deterioration in fecal parameters, such as numbers and weight of feces, fecal water contents, and gastrointestinal transit ratio. The histomorphometric results showed that the loperamide-induced decreases in the thickness of mucosal and muscularis mucosae layers as well as the distribution of mucin and c-KIT-positive areas were significantly (p < 0.05) improved via SM consumption at all doses tested. SM administration at all doses significantly increased the expression of genes encoding tryptophan hydroxylases (TPH1 and TPH2; p < 0.05), tight junction molecules (OCLN, CLDN1, and TJP1; p < 0.05), and mucin (MUC2 and MUC4; p < 0.05), but significantly decreased the aquaporin-encoding genes (AQP3 and AQP8; p < 0.05). Gut microbial community analysis indicated that SM administration could modulate loperamide-induced dysbiosis by increasing the phyla Actinobacteria (11.72-12.64 % at 10-40 mg/kg doses; p < 0.05) and Firmicutes (79.33 % and 74.24 % at 20 and 40 mg/kg doses; p < 0.05) and decreasing the phyla Bacteroidetes (5.98-12.47 % at 10-40 mg/kg doses; p < 0.05) and Verrucomicrobia (2.21 % and 2.78 % at 20 and 40 mg/kg doses; p < 0.05), suggesting that SM administration is effective in ameliorating constipation by controlling gut microbial communities. These findings can be utilized as fundamental data for developing novel functional materials using SM to prevent or treat constipation.
Subject(s)
Gastrointestinal Microbiome , Loperamide , Rats , Animals , Loperamide/adverse effects , Mucins , Glucans/therapeutic use , Ecosystem , Constipation/chemically induced , Constipation/drug therapyABSTRACT
Mild cognitive impairment is a typical symptom of early Alzheimer's disease (AD). Glehnia littoralis (G. littoralis), a medicinal halophyte plant commonly used to treat strokes, has been shown to possess some therapeutic qualities. In this study, we investigated the neuroprotective and anti-neuroinflammatory effects of a 50% ethanol extract of G. littoralis (GLE) on lipopolysccharide (LPS)-stimulated BV-2 cells and scopolamine-induced amnesic mice. In the in vitro study, GLE treatment (100, 200, and 400 µg/mL) markedly attenuated the translocation of NF-κB to the nucleus concomitantly with the significant mitigation of the LPS-induced production of inflammatory mediators, including NO, iNOS, COX-2, IL-6, and TNF-α. In addition, the GLE treatment suppressed the phosphorylation of MAPK signaling in the LPS-stimulated BV-2 cells. In the in vivo study, mice were orally administered with the GLE (50, 100, and 200 mg/kg) for 14 days, and cognitive loss was induced via the intraperitoneal injection of scopolamine (1 mg/kg) from 8 to 14 days. We found that GLE treatment ameliorated memory impairment and simultaneously improved memory function in the scopolamine-induced amnesic mice. Correspondingly, GLE treatment significantly decreased the AChE level and upregulated the protein expression of neuroprotective markers, such as BDNF and CREB, as well as Nrf2/HO-1 and decreased the levels of iNOS and COX-2 in the hippocampus and cortex. Furthermore, GLE treatment attenuated the increased phosphorylation of NF-κB/MAPK signaling in the hippocampus and cortex. These results suggest that GLE has a potential neuroprotective activity that may ameliorate learning and memory impairment by regulating AChE activity, promoting CREB/BDNF signaling, and inhibiting NF-κB/MAPK signaling and neuroinflammation.
Subject(s)
Apiaceae , NF-kappa B , Mice , Animals , NF-kappa B/metabolism , Scopolamine/pharmacology , Brain-Derived Neurotrophic Factor/metabolism , Neuroinflammatory Diseases , Lipopolysaccharides/adverse effects , Cyclooxygenase 2/metabolism , Memory Disorders/chemically induced , Memory Disorders/drug therapy , Memory Disorders/metabolism , MicrogliaABSTRACT
BACKGROUND: Prostate cancer is the second most common cause of cancer death worldwide in men. The development of novel and highly efficient therapeutic strategies is strongly recommended to treat prostate cancer. Cyperaceae are an ecologically and economically important family of plants with several pharmacological effects. However, the biological efficacy of Cyperus exaltatus var. iwasakii (CE) is unknown. PURPOSE: This study aimed to investigate the antitumor effect of the ethanol extract of CE against prostate cancer. METHODS: In vitro antitumor efficacy of CE was explored by the MTT assay, cell counting assay, FACS analysis, immunoblot, wound-healing migration, invasion assay, zymographic assay, and EMSA in prostate cancer cells, DU145 and LNCaP. For in vivo experiments, xenograft mice were injected with LNCaP cells. Histology (H&E and Ki-67) and biochemical enzyme assay were then performed. The toxicity test was evaluated by an acute toxicity assay. The phytochemical constituents of CE were identified by spectrometric and chromatographic analyses. RESULTS: CE exerted a significant antiproliferative effect against prostate cancer cells. CE-induced antiproliferative cells were associated with cell cycle arrest at G0/G1 (cyclin D1/CDK4, cyclin E/CDK2, p21Waf1) in DU145 cells, but G2/M (ATR, CHK1, Cdc2, Cdc25c, p21Waf1, and p53) in LNCaP cells. CE stimulated the phosphorylation of ERK1/2, p38 MAPK, and AKT in DU145 cells, but only p38 MAPK phosphorylation was increased in LNCaP cells. CE treatment suppressed migration and invasion in the two types of prostate cancer cells by inhibiting MMP-9 activity through the regulation of transcription factors, such as AP-1 and NF-κB. In vivo experiments showed a reduction in tumor weight and size following oral CE administration. Histochemistry confirmed that CE inhibited tumor growth in the mouse LNCaP xenograft model. The administration of CE had no adverse effects on body weight, behavioral patterns, blood biochemistry, and histopathology findings of vital organs in mice. Finally, a total of 13 phytochemical constituents were identified and quantified in CE. The most abundant secondary metabolites in CE were astragalin, tricin, and p-coumaric acid. CONCLUSION: Our results demonstrated the antitumor efficacy of CE against prostate cancer. These findings suggest that CE might be a potential candidate for prostate cancer prevention or treatment.
Subject(s)
Cyperus , Prostatic Neoplasms , Male , Humans , Animals , Mice , Phosphorylation , Proto-Oncogene Proteins c-akt/metabolism , MAP Kinase Signaling System , Ethanol/pharmacology , Matrix Metalloproteinase 9/metabolism , p38 Mitogen-Activated Protein Kinases/metabolism , Cell Line, Tumor , Cell Cycle , Prostatic Neoplasms/drug therapy , Cell Proliferation , ApoptosisABSTRACT
Subjective cognitive decline (SCD) is a clinical condition in which performance on standardized cognitive tests does not indicate impairment like mild cognitive impairment (MCI), but self-experienced cognitive capacity persistently declines. We aimed to explore the functional connectivity (FC) characteristics of SCD subjects compared to healthy controls and MCI patients. Resting-state functional MRI was performed on 152 elderly subjects: 65 normal controls, 62 SCD subjects, and 25 MCI patients. A seed-based FC analysis was performed to compare groups. The major brain regions of the default mode network (DMN) and dorsal attention network (DAN), large-scale brain networks disrupted in patients with dementia, were selected as seed regions. As a result, the SCD group showed stronger FC than the MCI group between DMN seeds and the supramarginal gyrus. Both the SCD and MCI groups showed stronger FC between the left lateral parietal cortex and right dorsolateral prefrontal cortex. In the FC analysis centred on DAN seeds, both the SCD and MCI groups showed weaker FC of the right posterior intraparietal sulcus in the left anterior cingulate cortex and the left insula, compared to those in the control group. Within the SCD group, hyperconnectivity between the right lateral parietal cortex and left supramarginal gyrus was significantly correlated with better performance on the Controlled Oral Word Association Test. In conclusion, the SCD group showed several DMN- and DAN-related FC alterations, similar to the MCI group, but with distinct hyperconnectivity between DMN seeds and the supramarginal gyrus. In particular, SCD has DMN-related FC patterns distinct from those of MCI that are associated with verbal fluency retention.
Subject(s)
Brain Mapping , Cognitive Dysfunction , Humans , Aged , Magnetic Resonance Imaging , Brain , Parietal LobeABSTRACT
Cognitive frailty (CF) is a state of impairment in both cognitive and motor functions. The concept of CF has been developed in several ways. However, it is difficult to identify consistent neuroimaging findings according to the application of the operational definition of different frailty models within the same concept, as well as the diversity of the concept itself of CF. This study aimed to review neuroimaging studies of CF and to determine suitable imaging biomarkers of CF. White matter abnormalities (e.g., white matter hyperintensity and microbleeds) seem likely to be considered imaging biomarkers of CF. The volume of the cerebral/cerebellar cortex and that of the subcortical nuclei are also candidates of imaging biomarkers of CF. These imaging biomarkers are expected to be more useful in discriminating the need for screening CF in visitors of clinics or health examination centers than in detecting the presence of CF in community-dwelling older adults.
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The whitening effect of reducing skin pigmentation is one of the most important goals of cosmetics. The purpose of this study was to determine whether Catalpa ovata extract and its fractions have potential as natural skin-lightening agents. Initially, we screened various fractions of Catalpa ovata extract using an in vitro antioxidant assay. Then, the inhibitory effects of C. ovata extract and its fraction on melanogenesis and the related mechanisms were investigated in B16F1 melanoma cells. The results showed that the ethyl acetate fraction (EF) from C. ovata extract markedly inhibited melanin synthesis in a dose-dependent manner at non-toxic concentrations. Furthermore, EF downregulated both the protein and mRNA levels of tyrosinase, which is a specific enzyme that catalyzes the conversion of tyrosine into melanin. We also found that EF decreased the microphthalmia-associated transcription factor (MITF) at the protein and mRNA levels. EF increased the phosphorylation of ERK and suppressed the phosphorylation of JNK and p38 in É-MSH-induced B16F1 cells. These results indicate that EF can regulate the MAPK pathway. In addition, EF has an anti-melanogenic effect via the downregulation of intracellular cyclic-AMP (cAMP). Nineteen major compounds of EF were identified using LC-MS/MS. Taken together, these results suggest that EF may be a potential anti-melanogenic agent for use in skin-whitening cosmetics and in topical treatments for hyperpigmentation disorders.
Subject(s)
Acetates , Bignoniaceae , Melanogenesis , alpha-MSH/pharmacology , Melanins , Chromatography, Liquid , Tandem Mass Spectrometry , Monophenol Monooxygenase , Cyclic AMP , RNA, Messenger , Plant Extracts/pharmacologyABSTRACT
BACKGROUND: Subjective cognitive decline (SCD) is a target for Alzheimer's disease prediction. Plasma amyloid-beta oligomer (AßO), the pathogenic form of Aß in blood, has recently been proposed as a novel blood-based biomarker of AD prediction by representing brain Aß deposition. The relationship between plasma AßO, brain Aß deposition, and SCD in individuals with normal objective cognition has not been investigated. METHODS: In this cross-sectional study, we analyzed 126 participants with normal objective cognition. More SCD symptoms were expressed as higher scores of the Subjective Cognitive Decline Questionnaire (SCDQ) and Memory Age-associated Complaint Questionnaire (MACQ). The plasma AßO level of each participant was measured twice for validation and expressed as a concentration (ng/mL) and a ratio relative to the mean value of two internal standards. Brain Aß deposition was assessed by [18F] flutemetamol positron emission tomography (PET) and expressed as standard uptake value ratio (SUVR). Associations of SCDQ and MACQ with plasma AßO levels or SUVR were analyzed in multiple linear regression models. The association between plasma AßO level and flutemetamol PET positivity was assessed in logistic regression and receiver operative characteristic analyses. RESULTS: Overall, participants were 73.3 years old with female predominance (69.0%). After adjustment for confounders, high SCDQ and MACQ scores were associated with the high plasma AßO levels as both concentrations and ratios (ratios: standardized coefficient = 0.246 and p = 0.023 for SCDQ, standardized coefficient = 0.209 and p = 0.029 for MACQ; concentrations: standardized coefficient = 0.257 and p = 0.015 for SCDQ, standardized coefficient = 0.217 and p = 0.021 for MACQ). In contrast, SCDQ and MACQ were not significantly associated with SUVRs (p = 0.134 for SCDQ, p = 0.079 for MACQ). High plasma AßO levels were associated with flutemetamol PET (+) with an area under the curve of 0.694 (ratio) or 0.662 (concentration). Combined with APOE e4, plasma AßO presented area under the curves of 0.789 (ratio) and 0.783 (concentration). CONCLUSIONS: Our findings indicate that the high plasma AßO level could serve as a potential surrogate biomarker of severe SCD and the presence of brain Aß deposition in individuals with normal objective cognition.
Subject(s)
Alzheimer Disease , Amyloidosis , Cognitive Dysfunction , Humans , Female , Aged , Male , Amyloid beta-Peptides/metabolism , Cross-Sectional Studies , Cognitive Dysfunction/diagnosis , Alzheimer Disease/diagnosis , Brain/metabolism , Amyloid , Positron-Emission Tomography , BiomarkersABSTRACT
Recently, green synthesis-based nanoformulations using plants or microorganisms have attracted great interest because of their several advantages. Nanotechnology-based biological macromolecules are emerging materials with potential applications in cosmetics and medications for ameliorating and treating inflammatory skin diseases (ISDs). Eupatorium japonicum (EJ), a native Korean medicinal plant belonging to the family Asteraceae, has been traditionally used to prepare prescriptions for the treatment of various inflammatory diseases. EJ-based gold nanoparticles (EJ-AuNPs) were biosynthesized under optimal conditions and characterized their physicochemical properties using various microscopic and spectrometric techniques. Additionally, the effects of EJ-AuNPs on ISDs as well as their underlying mechanisms were investigated in the tumor necrosis factor-α/interferon-γ (T+I)-induced skin HaCaT keratinocytes. The MTT and live/dead cell staining assays showed that EJ-AuNP treatment was considerably safer than EJ treatment alone in HaCaT cells. Moreover, EJ-AuNP treatment effectively suppressed the production of T+I-stimulated inflammatory cytokines (RANTES, TARC, CTACK, IL-6, and IL-8) and intracellular reactive oxygen species, and such EJ-driven anti-inflammatory effects were shown to be associated with the downregulation of intracellular mitogen-activated protein kinase and nuclear factor-κB signaling pathways. The present study provides preliminary results and a valuable strategy for developing novel anti-skin dermatitis drug candidates using plant extract-based gold nanoparticles.
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Nanotechnology-applied materials and related therapeutics have gained attention for treating inflammatory skin diseases. The beach rose (Rosa rugosa), belonging to the family Rosaceae, is a perennial, deciduous woody shrub endemic to northeastern Asia. In this study, R. rugosa-based gold nanoparticles (RR-AuNPs) were biologically synthesized under optimal conditions to explore their potential as anti-inflammatory agents for treating skin inflammation. The synthesized RR-AuNPs were analyzed using field emission-transmission electron microscopy, energy-dispersive X-ray spectrometry, selected-area electron diffraction, and X-ray diffraction. The uniformly well-structured AuNPs showed near-spherical and polygonal shapes. Cell viability evaluation and optical observation results showed that the RR-AuNPs were absorbed by human keratinocytes without causing cytotoxic effects. The effects of RR-AuNPs on the skin inflammatory response were investigated in human keratinocytes treated with tumor necrosis factor-α/interferon-γ (T + I). The results showed that T + I-stimulated increases in inflammatory mediators, including chemokines, interleukins, and reactive oxygen species, were significantly suppressed by RR-AuNP treatment in a concentration-dependent manner. The western blotting results indicated that the RR-AuNP-mediated anti-inflammatory effects were highly associated with the suppression of inflammatory signaling, mitogen-activated protein kinase, and nuclear factor-κB. These results demonstrate that plant extract-based AuNPs are novel anti-inflammatory candidates for topical application to treat skin inflammation.
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Particulate matters (PMs) from polluted air cause diverse pulmonary and cardiovascular diseases, including lung inflammation. While the fruits (Goji) of Lycium trees are commonly consumed as traditional medicine and functional food ingredients, the majority of their roots are discarded as by-products. To enhance the industrial applicability of Lycium roots, we prepared an ethanol extract (named GR30) of L. chinense Miller roots and evaluated its potential protective effects against particulate matter 10 (PM10)-induced inflammation and immune cell death. The GR30 treatment (0-500 µg/mL) significantly attenuated the PM10-induced cell cycle arrest, DNA fragmentation and mitochondria-dependent apoptosis in RBL-2H3 basophil cells. GR30 also significantly antagonized the PM10-induced expression of proinflammatory cytokines (IL-4, IL-13, and TNF-α) and COX2 expression through downregulation of MAPKs (ERK and JNK) signalling pathway. Oral administration of GR30 (200-400 mg/kg) to PM10 (20 mg/mL)-challenged mice significantly reduced the serum levels of IgE and the expression of TNF-α and Bax in lung tissues, which were elevated by PM10 exposure. These results revealed that the ethanolic extract (GR30) of L. chinense Miller roots exhibited anti-inflammatory and cyto-protective activity against PM10-induced inflammation and basophil cell death, and thus, it would be useful in functional food industries to ameliorate PM-mediated damage to respiratory and immune systems.
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The clinical benefits of nootropics in the treatment of cognitive decline has been either limited or controversial. This study aimed to observe the effectiveness of cholinesterase inhibitor (ChEI) and nootropics combination in the treatment of cognitive impairment in dementia. Data were based on electronic medical records in a university health system. Patients with mild-to-moderate dementia and no history of prior cognitive enhancer use were included (n = 583). The subjects were categorized into the ChEI only group and the ChEI and nootropics combination group. The primary outcome measure was the change in cognitive function, as assessed by the mini-mental state examination (MMSE) from baseline to 300-400 days after the first ChEI prescription. Subsequent analyses were conducted in consideration of the dementia type, medical adherence, and type of nootropics. The changes in MMSE scores from baseline to endpoint were not significantly different between the two groups. In Alzheimer's dementia, the combination group showed significantly less deterioration in MMSE language subscale scores compared to the ChEI only group (F = 6.86, p = 0.009), and the difference was consistent in the highly adherent subjects (F = 10.16, p = 0.002). The choline alfoscerate and the ginkgo biloba extract subgroups in Alzheimer's dementia showed more significant improvements in the MMSE language subscale scores compared to the other nootropics subgroup (F = 7.04, p = 0.001). The present study showed that the effectiveness of ChEI and nootropics combination on cognition may appear differently according to the dementia type. This emphasizes the need for well-controlled studies to generalize the effectiveness of nootropics across various clinical settings.
ABSTRACT
BACKGROUND: The purpose of this study was to investigate the effects of polycyclic aromatic hydrocarbons (PAHs) other than bisphenol A (BPA) and BPA substitutes on placental cells. METHODS: HTR-8/SVneo cells were treated with anthracene, benzo[k]fluoranthene, benzo[a]pyrene, and 4,4-(9-fluorenylidene)diphenol, which is used as a substitute for BPA-free products. After confirming the dose response for each reagent using the prepared cells, the cells were incubated for 24, 48, and 72 h. Cell viability was confirmed using the XTT assay. Each experiment was performed with the minimum number of samples (n = 3) required for statistical analysis. The results were analyzed using t-tests; p < 0.05 was considered statistically significant. RESULTS: After treatment with anthracene, benzo[k]fluoranthene, benzo[a]pyrene, and 4,4-(9-fluorenylidene)diphenol, the absorbance measured using the XTT assay decreased significantly with increasing concentration. The absorbance decreased significantly over time following treatment with each endocrine disruptor at the concentration confirmed by the dose-response analysis. CONCLUSIONS: This study showed that anthracene, benzo[k]fluoranthene, benzo[a]pyrene, and 4,4-(9-fluorenylidene)diphenol-a BPA substitute-affect cell viability and necrosis in the placental cell line. The study indicates the serious effects of PAHs that negatively affect pregnancy but were previously unknown. Further, this study would serve as a reference for the identification of harmful PAHs during pregnancy prognosis in women who are more susceptible to PAH exposure.
Subject(s)
Cell Differentiation/drug effects , Cell Proliferation/drug effects , Polycyclic Aromatic Hydrocarbons/pharmacology , Anthracenes/pharmacology , Benzhydryl Compounds/pharmacology , Benzo(a)pyrene/pharmacology , Cell Line , Cell Survival/drug effects , Dose-Response Relationship, Drug , Female , Fluorenes/pharmacology , Humans , Phenols/pharmacology , Placenta/cytology , Pregnancy , Time FactorsABSTRACT
BACKGROUND: To isolate polysaccharides with enhanced immunostimulatory activity from Dendrobium officinale, which is used as a herbal medicine in China and Southeast Asia, D. officinale (DO) was pretreated with organic solvents (DOOS) or puffing at 7.5 and 9.0 kgf (7.5DO and 9DO). Hot-water extracts (DOOS-HW, 7.5DO-HW and 9DO-HW) were prepared from each pretreated DO, along with non-pretreated DO, and crude polysaccharides (DO-CP, DOOS-CP, 7.5DO-CP and 9DO-CP) were fractionated from each hot-water extract using ethanol (five volumes). RESULTS: When their immunostimulatory activities were compared by macrophage stimulation and intestinal immune system modulation via Peyer's patches, DOOS-CP showed more potent activity than DO-CP. However, crude polysaccharides fractionated from puffed DO showed significantly lower activity than non-puffed DO and DOOS. The most active polysaccharide contained 95% or more neutral sugar, and the composition ratio of mannose and glucose was 3.0, whereas the lowest polysaccharide content was 2.0 or less. In addition, DOOS-CP was a somewhat refined fraction containing a major peak, representing a molecular weight of 250 kDa, despite being a crude polysaccharide. CONCLUSION: These results suggest that pretreatment of D. officinale with organic solvents may enhance the immunostimulatory activity of polysaccharides and affect the mannose/glucose ratio of polysaccharides, which plays an important role in immunostimulation. © 2021 Society of Chemical Industry.
Subject(s)
Dendrobium , Dendrobium/chemistry , Glucose , Mannose , Plant Extracts/chemistry , Polysaccharides/chemistry , Solvents , Sugars , WaterABSTRACT
Objectives: As the significance of the early diagnosis of mild cognitive impairment (MCI) has emerged, it is necessary to develop corresponding screening tools with high ecological validity and feasible biomarkers. Virtual reality (VR)-based cognitive assessment program, which is close to the daily life of the older adults, can be suitable screening tools for MCI with ecological validity and accessibility. Meanwhile, dehydroepiandrosterone (DHEA) has been observed at a low concentration in the older adults with dementia or cognitive decline, indicating its potential as a biomarker of MCI. This study aimed to determine the efficacy and usability of a VR cognitive assessment program and salivary DHEA for screening MCI. Methods: The VR cognitive assessment program and the traditional Montreal Cognitive Assessment (MOCA) test were performed on 12 patients with MCI and 108 healthy older adults. The VR program operates in a situation of caring for a grandchild, and evaluates the memory, attention, visuospatial, and executive functions. An analysis of covariance (ANCOVA), a partial correlation analysis, and receiving operating characteristic (ROC) curve analysis were conducted for statistical analysis. Results: According to the ANCOVA, no significant difference in MOCA scores was found between the normal and MCI groups (F = 2.36, p = 0.127). However, the VR total score of the MCI group was significantly lower than that of the normal group (F = 8.674, p = 0.004). There was a significant correlation between the MOCA and VR scores in the total and matched subdomain scores. The ROC curve analysis also showed a larger area under the curve (AUC) for the VR test (0.765) than for the MOCA test (0.598), and the sensitivity and specificity of the VR program were 0.833 and 0.722, respectively. Salivary DHEA was correlated with VR total (R 2 = 0.082, p = 0.01) and attention scores (R 2 = 0.086, p = 0.009). Conclusion: The VR cognitive test was as effective as the traditional MOCA test in the MCI classification and safe enough for older adults to perform, indicating its potential as a diagnostic tool. It has also been shown that salivary DHEA can be used as a biomarker for MCI.