Pyridinethiolate-Capped CdSe Quantum Dots for Red-Light-Driven H2 Production in Water.

The utilization of low-energy sunlight to produce renewable fuels is a subject of great interest. Here we report the first example of metal chalcogenide quantum dots (QDs) capped with a pyridinethiolate carboxylic acid (pyS-COOH) for red-light-driven H2 production in water. The precious-metal-free system is robust over 240 h, and achieves a turnover number (TON) of 43910 ± 305 (vs Ni) with a rate of 31570 ± 1690 mmol g-1 h-1 for hydrogen production. In contrast to the inactive QDs capped with other thiolate ligands, the CdSe-pyS-COOH QDs give a significantly higher singlet oxygen quantum yield [ΦΔ (1O2)] in solution.

Molecular Nickel Thiolate Complexes for Electrochemical Reduction of CO2 to C1-3 Hydrocarbons.

We report the unprecedented electrocatalytic activity of a series of molecular nickel thiolate complexes (1-5) in reducing CO2 to C1-3 hydrocarbons on carbon paper in pH-neutral aqueous solutions. Ni(mpo)2 (3, mpo=2-mercaptopyridyl-N-oxide), Ni(pyS)3 - (4, pyS=2-mercaptopyridine), and Ni(mp)2 - (5, mp=2-mercaptophenolate) were found to generate C3 products from CO2 for the first time in molecular complex. Compound 5 exhibits Faradaic efficiencies (FEs) of 10.6 %, 7.2 %, 8.2 % for C1 , C2 , C3 hydrocarbons respectively at -1.0 V versus the reversible hydrogen electrode. Addition of CO to the system significantly promotes the FEC1-C3 to 41.1 %, suggesting that a key Ni-CO intermediate is associated with catalysis. A variety of spectroscopies have been performed to show that the structures of nickel complexes remain intact during CO2 reduction.

Combination of Organic Dye and Iron for CO2 Reduction with Pentanuclear Fe2Na3 Purpurin Photocatalysts.

Molecular photocatalysts designed with earth-abundant elements are rare and challenging in artificial photosynthesis study. Herein, we report a multimetallic Fe2Na3 purpurin (1) complex for the reduction of CO2 in DMF under visible-light irradiation. The photocatalytic system achieves 91% selectivity and 2625 ± 334 turnovers of CO in 120 h, which is among the highest reported for a noble-metal-free catalyst without an additional photosensitizer. UV-vis and electrochemical studies suggest that the mechanism involves subsequent reductions and protonations of 1 to generate [FeII2Na3((H)2PP)6]5- and [FeIII2Na3((H)2PP)6]3- as the active photocatalysts in CO2 reduction.

Efficient Red-Light-Driven Hydrogen Evolution with an Anthraquinone Organic Dye.

The direct utilization of the full solar spectrum to obtain renewable fuels remains a challenge because the conversion of the low-energy light (red and near-infrared) is difficult. Current light-driven systems show activity for hydrogen generation with the high-energy part of sunlight. Here we report the use of a simple anthraquinone organic dye in an artificial photosynthetic system that promotes efficient red-light-driven production of hydrogen. The system contains no noble metal and exhibits a turnover number greater than 0.78 million and a quantum yield of 30.6% at 630 nm. A mechanistic study revealed that the excited-state and redox properties of the chromophore are critical to achieving high activity and stability.

Red blood cell distribution width: A severity indicator in patients with COVID-19.

Red blood cell distribution width (RDW) was frequently assessed in COVID-19 infection and reported to be associated with adverse outcomes. However, there was no consensus regarding the optimal cutoff value for RDW. Records of 98 patients with COVID-19 from the First People's Hospital of Jingzhou were reviewed. They were divided into two groups according to the cutoff value for RDW on admission by receiver operator characteristic curve analysis: ≤11.5% (n = 50) and >11.5% (n = 48). The association of RDW with the severity and outcomes of COVID-19 was analyzed. The receiver operating characteristic curve indicated that the RDW was a good discrimination factor for identifying COVID-19 severity (area under the curve = 0.728, 95% CI: 0.626-0.830, p < 0.001). Patients with RDW > 11.5% more frequently suffered from critical COVID-19 than those with RDW ≤ 11.5% (62.5% vs. 26.0%, p < 0.001). Multivariate logistic regression analysis showed RDW to be an independent predictor for critical illness due to COVID-19 (OR = 2.40, 95% CI: 1.27-4.55, p = 0.007). A similar result was obtained when we included RDW > 11.5% into another model instead of RDW as a continuous variable (OR = 5.41, 95% CI: 1.53-19.10, p = 0.009). RDW, as an inexpensive and routinely measured parameter, showed promise as a predictor for critical illness in patients with COVID-19 infection. RDW > 11.5% could be the optimal cutoff to discriminate critical COVID-19 infection.

Improving Photocatalytic Hydrogen Production through Incorporating Copper to Organic Photosensitizers.

Organic dyes have been investigated extensively as promising photosensitizers in noble-metal-free photocatalytic systems for hydrogen production. However, other than functional group optimization, there are very few methods reported to be effective in improving their photocatalytic activity. Herein, we report the incorporation of Cu2+ into purpurin and gallein dyes for visible-light-driven hydrogen production. These Cu-dye chromophores significantly promote the photocatalytic activity of homogeneous systems when paired with a series of molecular Ni or Fe catalysts. Under optimal conditions, the Cu-purpurin and Cu-gallein photosensitizers exhibit more than 20-fold increases in turnover frequencies for hydrogen evolution when compared with purpurin and gallein. Catalytic systems with the Cu-purpurin chromophore show no decrease in activity over 120 h. Based on electrochemical and fluorescence quenching experiments, the enhancement of photocatalytic activity is likely due to the fact that Cu2+ can facilitate the transfer of electrons from the photosensitizers to the catalysts through creating highly reducing centers.

Epidemiological characteristics and risk factors of obstetric infection after the Universal Two-Child Policy in North China: a 5-year retrospective study based on 268,311 cases.

BACKGROUND: Obstetrical infection is one of the causes of maternal death and a difficult problem for many clinicians. Changes in the demographic and obstetric background of pregnant women following the Universal Two-Child Policy may have an impact on some fertility phenomena. And with the increase in the number of deliveries, the limited medical resources become more scarce. How will China's health system quickly adapt to the growing needs and expectations for maternal health and ensure the provision of qualified and accessible medical services? In addition, what social support measures should be provided to reduce preventable obstetric complications? Given the relatively low per capita share of medical resources in China, how should China deal with the impact of the Universal Two-Child Policy? Therefore, more studies based on the change of fertility policy are needed. We try to analyze the epidemiological characteristics and risk factors of obstetric infection before and after the Universal Two-Child Policy, with a view to providing reference for the prevention and control of obstetric infection in regions after the change of fertility policy, and also hope to make corresponding contributions to the solution of the above problems through relevant studies. METHODS: The subjects of the survey were 268,311 pregnant women from Hebei Province Maternal Near Miss Surveillance System (HBMNMSS) of Hebei Women and Children's Health Center from January 1, 2013 to December 31, 2017. We analyzed the region, time and population distribution characteristics of obstetric infection, compared the epidemiological factors of obstetric infection before and after the Universal Two-Child Policy, and analyzed the relevant risk factors of obstetric infection. RESULTS: The incidence of obstetric infection increased nearly twice after the Universal Two-Child Policy. The incidence of obstetric infection was highest in Chengde (1.9%), a city with a northward geographical distribution, Baoding (1.6%), Cangzhou (1.5%) followed; The higher the hospital grade, the higher the incidence; The incidence of obstetric infections in hospitals at all levels has increased; The age of onset before the Universal Two-Child Policy was (27.82 ± 5.047) years old, and the age after the Universal Two-Child Policy was (28.97 ± 4.880) years old; The incidence of obstetric infections is higher in winter. The rate of abortion-related infection (increased from 0.61 to 1.65%) and the rate of pregnant women with high school education (increased from 0.35 to 0.74%) increased significantly. The results of multivariate Logistic regression analysis after the Universal Two-Child Policy showed that anemia (OR = 1.249, 95%CI: 1.071-1.458), chronic hypertension (OR = 1.934, 95%CI: 1.375-2.722), mild preeclampsia (OR = 2.103, 95%CI: 1.323-3.344) and severe preeclampsia (OR = 2.228, 95%CI: 1.703-2.916) were independent risk factors for obstetric infection. Gestational age ≥ 37 weeks was a protective factor. CONCLUSION: After the Universal Two-Child Policy, the prevention and control of obstetric infections should be strengthened, especially for abortion-related infections and elderly maternal with obstetric complications and complication in high-grade hospitals in winter. Educational background is also one of the factors that should be considered in the prevention of obstetric sensation. Prolonging gestational age is helpful to reduce the incidence of obstetric infection.

AGR2-induced cholesterol synthesis drives lovastatin resistance that is overcome by combination therapy with allicin.

Anterior gradient 2 (AGR2), a protein disulfide isomerase (PDI), is a multifunctional protein under physiological and pathological conditions. In this study we investigated the roles of AGR2 in regulating cholesterol biogenesis, lipid-lowering efficiency of lovastatin as well as in protection against hypercholesterolemia/statin-induced liver injury. We showed that AGR2 knockout significantly decreased hepatic and serum total cholesterol (TC) and low-density lipoprotein cholesterol (LDL-C) in mice with whole-body or hepatocyte-specific Agr2-null mutant, compared with the levels in their wild-type littermates fed a normal chow diet (NCD) or high-fat diet (HFD). In contrast, mice with AGR2 overexpression (Agr2/Tg) exhibited an increased cholesterol level. Mechanistic studies revealed that AGR2 affected cholesterol biogenesis via activation of AKT/sterol regulatory element-binding protein-2 (SREBP2), to some extent, in a PDI motif-dependent manner. Moreover, elevated AGR2 led to a significant decrease in the lipid-lowering efficacy of lovastatin (10 mg· kg-1· d-1, ip, for 2 weeks) in mice with hypercholesterolemia (hyperCho), which was validated by results obtained from clinical samples in statin-treated patients. We showed that lovastatin had limited effect on AGR2 expression, but AGR2 was inducible in Agr2/Tg mice fed a HFD. Further investigations demonstrated that drug-induced liver toxicity and inflammatory reactions were alleviated in hypercholesterolemic Agr2/Tg mice, suggesting the dual functions of AGR2 in lipid management and hyperCho/statin-induced liver injury. Importantly, the AGR2-reduced lipid-lowering efficacy of lovastatin was attenuated, at least partially, by co-administration of a sulfhydryl-reactive compound allicin (20 mg· kg-1· d-1, ip, for 2 weeks). These results demonstrate a novel role of AGR2 in cholesterol metabolism, drug resistance and liver protection, suggesting AGR2 as a potential predictor for selection of lipid-lowering drugs in clinic.

Nutritional screening based on objective indices at admission predicts in-hospital mortality in patients with COVID-19.

BACKGROUND: Could nutritional status serve as prognostic factors for coronavirus disease 2019 (COVID-19)? The present study evaluated the clinical and nutritional characteristics of COVID-19 patients and explored the relationship between risk for malnutrition at admission and in-hospital mortality. METHODS: A retrospective, observational study was conducted in two hospitals in Hubei, China. Confirmed cases of COVID-19 were typed as mild/moderate, severe, or critically ill. Clinical data and in-hospital death were collected. The risk for malnutrition was assessed using the geriatric nutritional risk index (GNRI), the prognostic nutritional index (PNI), and the Controlling Nutritional Status (CONUT) via objective parameters at admission. RESULTS: Two hundred ninety-five patients were enrolled, including 66 severe patients and 41 critically ill patients. Twenty-five deaths were observed, making 8.47% in the whole population and 37.88% in the critically ill subgroup. Patients had significant differences in nutrition-related parameters and inflammatory biomarkers among three types of disease severity. Patients with lower GNRI and PNI, as well as higher CONUT scores, had a higher risk of in-hospital mortality. The receiver operating characteristic curves demonstrated the good prognostic implication of GNRI and CONUT score. The multivariate logistic regression showed that baseline nutritional status, assessed by GNRI, PNI, or CONUT score, was a prognostic indicator for in-hospital mortality. CONCLUSIONS: Despite variant screening tools, poor nutritional status was associated with in-hospital death in patients infected with COVID-19. This study highlighted the importance of nutritional screening at admission and the new insight of nutritional monitoring or therapy.

Targeting the lysosome by an aminomethylated Riccardin D triggers DNA damage through cathepsin B-mediated degradation of BRCA1.

RD-N, an aminomethylated derivative of riccardin D, is a lysosomotropic agent that can trigger lysosomal membrane permeabilization followed by cathepsin B (CTSB)-dependent apoptosis in prostate cancer (PCa) cells, but the underlying mechanisms remain unknown. Here we show that RD-N treatment drives CTSB translocation from the lysosomes to the nucleus where it promotes DNA damage by suppression of the breast cancer 1 protein (BRCA1). Inhibition of CTSB activity with its specific inhibitors, or by CTSB-targeting siRNA or CTSB with enzyme-negative domain attenuated activation of BRCA1 and DNA damage induced by RD-N. Conversely, CTSB overexpression resulted in inhibition of BRCA1 and sensitized PCa cells to RD-N-induced cell death. Furthermore, RD-N-induced cell death was exacerbated in BRCA1-deficient cancer cells. We also demonstrated that CTSB/BRCA1-dependent DNA damage was critical for RD-N, but not for etoposide, reinforcing the importance of CTSB/BRCA1 in RD-N-mediated cell death. In addition, RD-N synergistically increased cell sensitivity to cisplatin, and this effect was more evidenced in BRCA1-deficient cancer cells. This study reveals a novel molecular mechanism that RD-N promotes CTSB-dependent DNA damage by the suppression of BRCA1 in PCa cells, leading to the identification of a potential compound that target lysosomes for cancer treatment.

Acetyl-11-keto-ß-boswellic acid suppresses docetaxel-resistant prostate cancer cells in vitro and in vivo by blocking Akt and Stat3 signaling, thus suppressing chemoresistant stem cell-like properties.

Acquired docetaxel-resistance of prostate cancer (PCa) remains a clinical obstacle due to the lack of effective therapies. Acetyl-11-keto-ß-boswellic acid (AKBA) is a pentacyclic triterpenic acid isolated from the fragrant gum resin of the Boswellia serrata tree, which has shown intriguing antitumor activity against human cell lines established from PCa, colon cancer, malignant glioma, and leukemia. In this study, we examined the effects of AKBA against docetaxel-resistant PCa in vitro and in vivo as well as its anticancer mechanisms. We showed that AKBA dose-dependently inhibited cell proliferation and induced cell apoptosis in docetaxel-resistant PC3/Doc cells; its IC50 value in anti-proliferation was ∼17 µM. Furthermore, AKBA dose-dependently suppressed the chemoresistant stem cell-like properties of PC3/Doc cells, evidenced by significant decrease in the ability of mammosphere formation and down-regulated expression of a number of stemness-associated genes. The activation of Akt and Stat3 signaling pathways was remarkably enhanced in PC3/Doc cells, which contributed to their chemoresistant stem-like phenotype. AKBA (10-30 µM) dose-dependently suppressed the activation of Akt and Stat3 signaling pathways in PC3/Doc cells. In contrast, overexpression of Akt and Stat3 significantly attenuated the inhibition of AKBA on PC3/Doc cell proliferation. In docetaxel-resistant PCa homograft mice, treatment with AKBA significantly suppresses the growth of homograft RM-1/Doc, equivalent to its human PC3/Doc, but did not decrease their body weight. In summary, we demonstrate that AKBA inhibits the growth inhibition of docetaxel-resistant PCa cells in vitro and in vivo via blocking Akt and Stat3 signaling, thus suppressing their cancer stem cell-like properties.

Hyper-acetylation contributes to the sensitivity of chemo-resistant prostate cancer cells to histone deacetylase inhibitor Trichostatin A.

Therapeutic agents are urgently needed for treating metastatic castration-refractory prostate cancer (mCRPC) that is unresponsive to androgen deprivation and chemotherapy. Our screening assays demonstrated that chemotherapy-resistant prostate cancer (PCa) cells are more sensitive to HDAC inhibitors than paired sensitive PCa cells, as demonstrated by cell proliferation and apoptosis in vitro and in vivo. Kinetic study revealed that TSA-induced apoptosis was significantly dependent on enhanced transcription and protein synthesis in an early stage, which subsequently caused ER stress and apoptosis. ChIP analysis indicated that TSA increased H4K16 acetylation, promoting ER stress gene transcription. The changes in Ac-H4K16, ATF3 and ATF4 were also validated in TSA-treated animals. Further study revealed the higher enzyme activity of HDACs and an increase in acetylated proteins in resistant cells. The higher nucleocytoplasmic acetyl-CoA in resistant cells was responsible for elevated acetylation status of protein and a more vigorous growth state. These results strongly support the pre-clinical application of HDAC inhibitors for treating chemotherapy-resistant mCRPC.

Downregulation of reticulocalbin-1 differentially facilitates apoptosis and necroptosis in human prostate cancer cells.

Reticulocalbin 1 (RCN1), an endoplasmic reticulum (ER)-resident Ca2+ -binding protein, is dysregulated in cancers, but its pathophysiological roles are largely unclear. Here, we demonstrate that RCN1 is overexpressed in clinical prostate cancer (PCa) samples, associated with cyclin B, not cyclin D1 expression, compared to that of benign tissues in a Chinese Han population. Downregulation of endogenous RCN1 significantly suppresses PCa cell viability and arrests the cell cycles of DU145 and LNCaP cells at the S and G2/M phases, respectively. RCN1 depletion causes ER stress, which is evidenced by induction of GRP78, activation of PERK and phosphorylation of eIF2α in PCa cells. Remarkably, RCN1 loss triggers DU145 cell apoptosis in a caspase-dependent manner but mainly causes necroptosis in LNCaP cells. An animal-based analysis confirms that RCN1 depletion suppresses cell proliferation and promotes cell death. Further investigations reveal that RCN1 depletion leads to elevation of phosphatase and tensin homolog (PTEN) and inactivation of AKT in DU145 cells. Silencing of PTEN partially restores apoptotic cells upon RCN1 loss. In LNCaP cells, predominant activation of CaMKII is important for necroptosis in response to RCN1 depletion. Thus, RCN1 may promote cell survival and serve as a useful target for cancer therapy.

Pro-metastatic activity of AGR2 interrupts angiogenesis target bevacizumab efficiency via direct interaction with VEGFA and activation of NF-κB pathway.

Anterior gradient 2 (AGR2), an endoplasmic reticulum (ER)-resident protein-disulfide isomerase (PDI), is associated with cancer development and malignant progression. Here, we show that high level of AGR2 promotes the aggressive phenotype of prostate cancer (PCa) mouse models developed by either patient-derived xenografts or surgical intra-prostate implantation of PCa cells, associated with enrichment of the blood vessel network in tumor tissues. Angiogenesis markers VEGFR2 and CD34, accompanied with the invasive marker Vimentin, were predominantly stained in metastatic liver tissues. Secreted AGR2 was defined to enhance VEGFR2 activity as evidenced by physical interaction of purified recombinant human AGR2 (rhAGR2) with rhVEGFA through the formation of a disulfide bond. Mutant or deleted thioredoxin motif in rhAGR2 was also unable to bind to rhVEGFA that led to the significant abolishment in the vessel formation, but partially affecting the aggressive process, implicating alternative mechanisms are required for AGR2-conferring metastasis. Cytosolic AGR2 contributed to cell metastasis ascribed to its stabilizing effect on p65 protein, which subsequently activated the NF-κB and facilitated epithelial to mesenchymal transition (EMT). Importantly, GSH and cabozantinib, but not bevacizumab, effectively blocked the pro-angiogenic effect of rhAGR2 in vitro and in vivo, providing evidence that secreted AGR2 acts as a predictive biomarker for selection of angiogenesis-targeting therapeutic drugs based on its levels in the circular system.

Synthesis of Quinazolines via an Iron-Catalyzed Oxidative Amination of N-H Ketimines.

An efficient synthesis of quinazolines based on an iron-catalyzed C(sp3)-H oxidation and intramolecular C-N bond formation using tert-BuOOH as the terminal oxidant is described. The reaction of readily available 2-alkylamino benzonitriles with various organometallic reagents led to 2-alkylamino N-H ketimine species. The FeCl2-catalyzed C(sp3)-H oxidation of the alkyl group employing tert-BuOOH followed by intramolecular C-N bond formation and aromatization afforded a wide variety of 2,4-disubstituted quinazolines in good to excellent yields.

Terpenoids isolated from Chinese liverworts Lepidozia reptans and their anti-inflammatory activity.

Five new terpenoids (1-5) including two dollabellane-type, one ent-kaurane-type diterpenoids and two sesquiterpenoids were isolated from the Chinese liverwort Lepidozia reptans (L.) Dumort., together with nine known terpenoids (6-14). Their structures were determined on the basis of analysis of MS and NMR spectroscopic data, single-crystal X-ray diffraction and electronic circular dichroism calculations. The selected compounds 1, 2, 6, 7, 9 and 14 were screened for anti-inflammatory activities by the model of LPS-induced nitric oxide (NO) production with macrophage cells, and the mechanism of the active compounds 1 and 2 were further explored.

Anti-neuroinflammatory effects of grossamide from hemp seed via suppression of TLR-4-mediated NF-κB signaling pathways in lipopolysaccharide-stimulated BV2 microglia cells.

Grossamide, a representative lignanamide in hemp seed, has been reported to possess potential anti-inflammatory effects. However, the potential anti-neuroinflammatory effects and underlying mechanisms of action of grossamide are still unclear. Therefore, the present study investigated the possible effects and underlying mechanisms of grossamide against lipopolysaccharide (LPS)-induced inflammatory response in BV2 microglia cells. BV2 microglia cells were pre-treated with various concentrations of grossamide before being stimulated with LPS to induce inflammation. The levels of pro-inflammatory cytokines were determined using the enzyme-linked immunoassay (ELISA) and mRNA expression levels were measured by real-time PCR. The translocation of nuclear factor-kappa B (NF-κB) and contribution of TLR4-mediated NF-κB activation on inflammatory effects were evaluated by immunostaining and Western blot analysis. This study demonstrated that grossamide significantly inhibited the secretion of pro-inflammatory mediators such as interleukin 6 (IL-6) and tumor necrosis factor α (TNF-α), and decreased the level of LPS-mediated IL-6 and TNF-α mRNA. In addition, it significantly reduced the phosphorylation levels of NF-κB subunit p65 in a concentration-dependent manner and suppressed translocation of NF-κB p65 into the nucleus. Furthermore, grossamide markedly attenuated the LPS-induced expression of Toll-like receptor 4 (TLR4) and myeloid differentiation factor 88 (MyD88). Taken together, these data suggest that grossamide could be a potential therapeutic candidate for inhibiting neuroinflammation in neurodegenerative diseases.

Riccardin D-N induces lysosomal membrane permeabilization by inhibiting acid sphingomyelinase and interfering with sphingomyelin metabolism in vivo.

Lysosomes are important targets for anticancer drug discovery. Our previous study showed that Riccardin D-N (RD-N), a natural macrocylic bisbibenzyl derivative produced by Mannich reaction, induced cell death by accumulating in lysosomes. Experiments were performed on human lung squamous cell carcinoma tissue from left inferior lobar bronchus of patient xenografts and H460 cells. RD-N was administrated for 25days. The specimens of xenografts in Balb/c athymic (nu+/nu+) male mice were removed for immunohistochemistry, subcellular fractionation, enzyme activities and Western blotting analysis. mRFP-GFP-LC3 reporter was used to examine autophagy in H460 cells. Sphingomyelin assay was evaluated by thin-layer chromatography and assay kit. Lysosomal membrane permeabilization (LMP) caused by acid sphingomyelinase (ASM) inhibition and subsequent changes of sphingomyelin (SM) metabolism selectively destabilized the cancer cell lysosomes in RD-N-treated H460 cells in vitro and tumor xenograft model in vivo. The destabilized lysosomes induced the release of cathepsins from the lysosomes into the cytosol and further triggered cell death. These results explain the underlying mechanism of RD-N induced LMP. It can be concluded that a more lysosomotropic derivative was synthesized by introduction of an amine group, which could have more potential applications in cancer therapy.

Jungermannenone A and B induce ROS- and cell cycle-dependent apoptosis in prostate cancer cells in vitro.

AIM: Jungermannenone A and B (JA, JB) are new ent-kaurane diterpenoids isolated from Chinese liverwort Jungermannia fauriana, which show anti-proliferation activities in cancer cells. In this study we investigated the mechanisms underlying the anticancer action of JA and JB in PC3 human prostate cancer cells in vitro. METHODS: A panel of 9 human cancer cell lines was tested. Cell proliferation was assessed with a real-time cell analyzer and MTT assay. Cell apoptosis, cell cycle distribution and ROS levels were measured using cytometry. Mitochondrial damage was examined by transmission electron microscopy. DNA damage was detected with comet assay. Apoptotic, DNA damage- and cell cycle-related proteins were analyzed using Western blotting. The expression of DNA repair genes was measured with qRT-PCR. RESULTS: Both JA and JB exerted potent anti-proliferative action against the 9 cancer cell lines, and PC3 cells were more sensitive with IC50 values of 1.34±0.09 and 4.93±0.20 µmol/L, respectively. JA (1.5 µmol/L) and JB (5 µmol/L) induced PC3 cell apoptosis, which was attenuated by the caspase inhibitor Z-VAD. Furthermore, both JA and JB caused mitochondrial damage and ROS accumulation in PC3 cells, whereas vitamin C blocked the ROS accumulation and attenuated the cytotoxicity of JA and JB. Moreover, both JA and JB induced DNA damage, accompanied by downregulated DNA repair proteins Ku70/Ku80 and RDA51. JA induced marked cell cycle arrest at the G0/G1 phase, which was related to c-Myc suppression, whereas JB enforced the cell cycle blockade in the G2/M phase, which associated with activation of the JNK signaling. CONCLUSION: Both JA and JB induce prostate cancer apoptosis via ROS accumulation and induction of cell cycle arrest.

Changes in mast cell infiltration: a possible mechanism in detrusor overactivity induced by visceral hypersensitivity.

OBJECTIVE: To establish the detrusor overactivity (DO) model induced by visceral hypersensitivity (VH) and investigate the relationship between mast cell (MC) infiltration and DO. MATERIALS AND METHODS: Sixty rats are divided into 4 groups randomly: Group 1:Baseline group; Group 2: DO group; Group 3: CON group; Group 4: VH group. The colorectal distension (CRD) and abdominal withdral reflex (AWR) scores are performed to evaluate VH. The cystometric investigation and histological test of MC infiltration are assessed. RESULTS: The threshold pressure of CRD in the VH group is significantly lower than that in the CON group (P<0.001). At the distension pressure ≥20 mmHg, the AWR scores of the VH group are significantly higher than those of the CON group (10 mmHg: P=0.33; 20 mmHg: P=0.028; 40 mmHg: P<0.001; 60 mmHg: P<0.001; 80 mmHg: P<0.001). DO model is successfully established in the VH group (DO rate=100%). Compared with the CON group, the numbers of MC infiltration are significantly increased in the VH group, including submucosa of bladder (P<0.001), mucosa lamina propria/mesentery of small intestine (P<0.001), and mucosa lamina propria/mesentery of large intestine (P<0.001). Furthermore, more MC activation as well as degranulation are observed in the VH group. CONCLUSIONS: It is indicated that DO model can be established in the VH rats. The MC infiltration may play an important role in DO induced by VH, and may be helpful to understand the mechanisms of DO in VH patients.