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931.
RaiHua Lai ChihCheng Hsu BenHui Yu YuRu Lo YuehYing Hsu MeiHsin Chen JyhLyh Juang 《Aging cell》2022,21(8)
Vitamin D deficiency has been epidemiologically linked to Alzheimer''s disease (AD) and other dementias, but no interventional studies have proved causality. Our previous work revealed that the genomic vitamin D receptor (VDR) is already converted into a non‐genomic signaling pathway by forming a complex with p53 in the AD brain. Here, we extend our previous work to assess whether it is beneficial to supplement AD mice and humans with vitamin D. Intriguingly, we first observed that APP/PS1 mice fed a vitamin D‐sufficient diet showed significantly lower levels of serum vitamin D, suggesting its deficiency may be a consequence not a cause of AD. Moreover, supplementation of vitamin D led to increased Aβ deposition and exacerbated AD. Mechanistically, vitamin D supplementation did not rescue the genomic VDR/RXR complex but instead enhanced the non‐genomic VDR/p53 complex in AD brains. Consistently, our population‐based longitudinal study also showed that dementia‐free older adults (n = 14,648) taking vitamin D3 supplements for over 146 days/year were 1.8 times more likely to develop dementia than those not taking the supplements. Among those with pre‐existing dementia (n = 980), those taking vitamin D3 supplements for over 146 days/year had 2.17 times the risk of mortality than those not taking the supplements. Collectively, these animal model and human cohort studies caution against prolonged use of vitamin D by AD patients. 相似文献
932.
ErhHsuan Lin JhenWei Hsu TingFang Lee ChiungFang Hsu TsungHsien Lin YiHua Jan HsiangYi Chang ChunMing Cheng HuiJan Hsu WeiWei Chen BoHung Chen HsingFang Tsai JungJung Li ChiYing Huang ShihHsien Chuang JiaMing Chang Michael Hsiao ChengWen Wu 《Journal of cellular and molecular medicine》2022,26(15):4305
Lung cancer is the leading cause of cancer‐associated death, with a global 5‐year survival rate <20%. Early metastasis and recurrence remain major challenges for lung cancer treatment. The stemness property of cancer cells has been suggested to play a key role in cancer plasticity, metastasis and drug‐resistance, and is a potential target for drug development. In this study, we found that in non‐small cell lung cancer (NSCLC), BMI1 and MCL1 play crucial roles of cancer stemness including invasion, chemo‐resistance and tumour initiation. JNK signalling serves as a link between oncogenic pathway or genotoxicity to cancer stemness. The activation of JNK, either by mutant EGFR or chemotherapy agent, stabilized BMI1 and MCL1 proteins through suppressing the expression of E3‐ubiquitin ligase HUWE1. In lung cancer patient samples, high level of BMI1 is correlated with poor survival, and the expression of BMI1 is positively correlated with MCL1. A novel small‐molecule, BI‐44, was developed, which effectively suppressed BMI1/MCL1 expressions and inhibited tumour formation and progression in preclinical models. Targeting cancer stemness mediated by BMI1/MCL1 with BI‐44 provides the basis for a new therapeutic approach in NSCLC treatment. 相似文献
933.
Rhinogobius candidianus is a freshwater goby distributed in north, northwest, west, and south Taiwan, but this species has been introduced to east Taiwan and became dominant. To investigate its native population genetic diversity and structure and evaluate the sources and diversity of translocated populations, the mitochondrial DNA control region and cytochrome b gene (1981 bp) from 220 specimens were analyzed. These results indicated that (1) the east populations originated from two sources in west Taiwan; (2) translocated populations exist in east Taiwan and south Taiwan; (3) many populations have likely been moved secondarily by human intervention; (4) the effective size of the populations had declined greatly; (5) within the native populations, the ancestral populations colonized Taiwan during the land bridge phase in the Pleistocene through north Taiwan; (6) the landform changes in Taiwan shaped the population structure; and (7) the landforms of the coastline during glaciation also shaped the native range. The low‐level genetic diversity, high population differentiation, and population decline greatly suggest the need for resource management and conservation interventions. Four clades (α–δ) should be managed as four distinct evolutionarily significant units, while the translocated populations should be managed as separate management units. Moreover, the translocated populations in east Taiwan should be evaluated and monitored carefully. 相似文献
934.
Hong-Ming Hsu Yen-Yu Yang Yu-Hsin Huang Chien-Hsin Chu Ting-Jui Tu Yen-Ting Wu Chu-Jen Chiang Shi-Bing Yang Daniel K. Hsu Fu-Tong Liu Jung-Hsiang Tai 《PLoS neglected tropical diseases》2023,17(1)
Cytoadherence of Trichomonas vaginalis to human vaginal epithelial cells (hVECs) was previously shown to involve surface lipoglycans and several reputed adhesins on the parasite. Herein, we report some new observations on the host-parasite interactions of adherent versus nonadherent T. vaginalis isolates to hVECs. The binding of the TH17 adherent isolate to hVECs exhibited an initial discrete phase followed by an aggregation phase inhibited by lactose. T. vaginalis infection immediately induced surface expression of galectin-1 and -3, with extracellular amounts in the spent medium initially decreasing and then increasing thereafter over the next 60 min. Extracellular galectin-1 and -3 were detected on the parasite surface but only the TH17 adherent isolate could uptake galectin-3 via the lysosomes. Only the adherent isolate could morphologically transform from the round-up flagellate with numerous transient protrusions into a flat amoeboid form on contact with the solid surface. Cytochalasin D challenge revealed that actin organization was essential to parasite morphogenesis and cytoadherence. Real-time microscopy showed that parasite exploring and anchoring on hVECs via the axostyle may be required for initial cytoadherence. Together, the parasite cytoskeleton behaviors may collaborate with cell surface adhesion molecules for cytoadherence. The nonadherent isolate migrated faster than the adherent isolate, with motility transiently increasing in the presence of hVECs. Meanwhile, differential histone acetylation was detected between the two isolates. Also, TH17 without Mycoplasma symbiosis suggests that symbiont might not determine TH17 innate cytoadherence. Our findings regarding distinctive host-parasite interactions of the isolates may provide novel insights into T. vaginalis infection. 相似文献
935.
Chih-Ming Lu Yu-Jen Wu Cheng-Chi Chen Jue-Liang Hsu Jiing-Chuan Chen Jeff Yi-Fu Chen Chun-Hsiung Huang Ying-Chin Ko 《Proteome science》2011,9(1):17
Background
Low-abundance proteins are difficultly observed on the two-dimensional gel electrophoresis (2-DE) maps of urine proteome, because they are usually obscured by high-abundance proteins such as albumin and immunoglobulin. In this study, a novel fractionation method was developed for enriching low-abundance proteins by removing high-abundance proteins and progressive elution with salts of various concentrations. 相似文献936.
Chih-Yu Lo Lin-Chen Hsu Min-Shin Chen Yi-Jing Lin Lih-Geeng Chen Cheng-Deng Kuo Jin-Yi Wu 《Bioorganic & medicinal chemistry letters》2013,23(1):305-309
To alter its hydrophobicity, a series of compounds bearing 9-O-alkyl- or 9-O-terpenyl- substituted berberine were synthesized and evaluated for anticancer activity against human cancer HepG2 and HT29 cell lines. We found that the lipophilic substitute of 9-O-alkyl- and 9-O-terpenyl berberine derivatives plays a role in inhibiting the human cancer cell growth and its activity could be maximized with the optimized substitute type and chain length. Most strikingly, nonetheless, of the six compounds prepared, sample 8, a farnesyl 9-O-substituted berberine, showed either comparable or better cytotoxic activity against human cancer HepG2 cell line than that of berberine. Compound 8 had also shown a 104-fold antiproliferation activity in compare with berberine against human hepatoma HepG2 cell lines after 48 incubation hours. Further, in Hoechst 33258 and annexin V-FITC/PI staining analyses it induced apoptosis in HepG2 cells at lower concentration than that of berberine for 24 h. Take all; farnesyl 9-O-substituted berberine could be a potential candidate for new anticancer drug development. 相似文献
937.
Szu-Hsien Yu Chih-Yang Huang Shin-Da Lee Ming-Fen Hsu Ray-Yau Wang Chung-Lan Kao Chia-Hua Kuo 《PloS one》2014,9(12)
Dammarane steroids (DS) are a class of chemical compounds present in Panax ginseng. Here, we evaluated the effect of 10 weeks of DS supplementation on inflammatory modulation in the soleus muscle following eccentric exercise (EE)-induced muscle damage (downhill running). Eighty rats were randomized into 4 groups of DS supplementation (saline, 20, 60, 120 mg/kg body weight). Inflammatory markers were measured at rest and again 1 h after EE. At rest, NFκB signaling, TNF-alpha and IL-6 mRNAs, 3-nitrotyrosine, glutathione peroxidase, and GCS (glutamylcysteine synthetase) levels were significantly elevated in the skeletal muscle of DS-treated rats in a dose-dependent manner. Additionally, there were no detectable increases in the number of necrotic muscle fibers or CD68+ M1 macrophages. However, muscle strength, centronucleation, IL-10 mRNA expression, and the number of CD163+ M2 macrophages increased significantly over controls with DS treatment in rat soleus muscle. Under EE-challenged conditions, significant increases in muscle fiber necrosis, CD68+ M1 macrophage distribution, and 3-nitrotyrosine were absent in rats that received low and medium doses (20 and 60 mg/kg) of DS treatment, suggesting that DS possess anti-inflammatory action protecting against a muscle-damaging challenge. However, this protective activity was diminished when a high dose of DS (120 mg/kg) was administered, suggesting that DS possess hormetic properties. In conclusion, our study provides new evidence suggesting that DS is an ergogenic component of ginseng that potentiate inflammation at baseline but that produce anti-inflammatory effects on skeletal muscle following muscle-damaging exercise. Furthermore, high doses should be avoided in formulating ginseng-based products. 相似文献
938.
939.
940.
Hsin-Ling Yang Ruei-Wan Lin Peramaiyan Rajendran Dony Chacko Mathew Varadharajan Thigarajan Chuan-Chen Lee Chih-Jung Hsu You-Cheng Hseu 《Journal of cellular physiology》2019,234(3):3029-3042
Antrodia salmonea is well known in Taiwan as a traditional Chinese medicinal fungus and has demonstrated antioxidant, anti-inflammatory, and anticancer effects. However, the anticancer activity of A. salmonea against human ovarian cancer is still elusive. Therefore, we investigated the antiovarian tumor activity of a fermented culture broth of A. salmonea and exhibits its underlying molecular mechanism. A. salmonea shows a significant effect on cell viability in human ovarian carcinoma (SKOV-3 or A2780) cell lines with an 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide assay. Increased terminal deoxynucleotidyl transferase dUTP nick-end labeling-positive cells and annexin V–propidium iodide stained cells indicate that A. salmonea induces late apoptosis in SKOV-3 cells. Notably, treatment with A. salmonea induced the following events: Apoptosis; caspase-3, -8, -9 and poly(ADP-ribose) polymerase activation; first apoptosis signal (Fas) and Fas ligand activation; Bid cleavage; and Bax2–B-cell lymphoma 2 dysregulation. The results show that A. salmonea-induced apoptosis was mediated by both mitochondrial and death receptor pathways. An increase in intracellular reactive oxygen species (ROS) was also observed in A. salmonea-treated cells, whereas the antioxidant N-acetylcysteine (NAC) prevented A. salmonea-induced cell death and DNA fragmentation, indicating that A. salmonea-induced apoptosis was mediated by ROS generation. Interestingly, A. salmonea-induced apoptosis is associated with the suppression of human epidermal growth factor receptor-2 (HER-2/neu) and phosphoinositide 3-kinase (PI3K)–protein kinase B (AKT) expression in HER-2/neu overexpressing SKOV-3 cells. NAC significantly prevented A. salmonea-induced HER-2/neu depletion and PI3K/AKT inactivation, indicating that A. salmonea-triggered apoptosis is mediated by ROS-inhibited HER-2/neu signaling cascades. To our knowledge, this is the first report describing the anticancer activity of this potentially beneficial mushroom against human ovarian carcinoma. 相似文献