查看更多>>摘要：Ovary plays an important role in the female reproductive system.The maintenance and regulation of ovarian function are affected by various physical and chemical factors.With the development of industrialization,environmental pollutants have caused great harm to public health.Phthalates,as a class of endocrine-disrupting chemicals (EDCs),are synthesized and used in large quantities as plasticizers due to their chemical properties.They are easily released into environment because of their noncovalent interactions with substances,causing human exposure and possibly impairing ovary.In recent years,more and more attention has been paid to the role of epigenetics in the occurrence and development of diseases.And it is urgent to study the role of methylation,gene imprinting,miRNA,and other epigenetic mechanisms in reproductive toxicology.
查看更多>>摘要：Tumorigenicity-inhibiting compounds have been identified in our daily diet.For example,isothiocyanates (ITCs) found in cruciferous vegetables were reported to have potent cancer-prevention activities.The best characterized ITC is sulforaphane (SF).SF can simultaneously modulate multiple cellular targets involved in carcinogenesis,including (1) modulating carcinogen-metabolizing enzymes and blocking the action of mutagens;(2) inhibition of cell proliferation and induction of apoptosis;and (3) inhibition of neo-angiogenesis and metastasis.SF targets cancer stem cells through modulation of nuclear factor kappa B (NF-κB),Sonic hedgehog (SHH),epithelial-mesenchymal transition,and Wnt/β-catenin pathways.Conventional chemotherapy/SF combination was tested in several studies and resulted in favorable outcomes.With its favorable toxicological profile,SF is a promising agent in cancer prevention and/or therapy.In this article,we discuss the human metabolism of SF and its effects on cancer prevention,treatment,and targeting cancer stem cells,as well as providing a brief review of recent human clinical trials on SF.
查看更多>>摘要：Tumorigenicity-inhibiting compounds have been identified in our daily diet.For example,isothiocyanates (ITCs) found in cruciferous vegetables were reported to have potent cancer-prevention activities.The best characterized ITC is sulforaphane (SF).SF can simultaneously modulate multiple cellular targets involved in carcinogenesis,including (1) modulating carcinogen-metabolizing enzymes and blocking the action of mutagens;(2) inhibition of cell proliferation and induction of apoptosis;and (3) inhibition of neo-angiogenesis and metastasis.SF targets cancer stem cells through modulation of nuclear factor kappa B (NF-κB),Sonic hedgehog (SHH),epithelial-mesenchymal transition,and Wnt/β-catenin pathways.Conventional chemotherapy/SF combination was tested in several studies and resulted in favorable outcomes.With its favorable toxicological profile,SF is a promising agent in cancer prevention and/or therapy.In this article,we discuss the human metabolism of SF and its effects on cancer prevention,treatment,and targeting cancer stem cells,as well as providing a brief review of recent human clinical trials on SF.
查看更多>>摘要：This study investigated the association of a tobacco-specific nitrosamine carcinogen,4-(methylnitrosamino)-l-(3-pyridyl)-l-butanol (NNAL) with urinary cotinine (uCot),urinary sodium (uNa) excretion,systolic blood pressure (sBP),and total energy intake in adolescents and children in relation to the subjects' age.A total of 790 subjects aged 6-19 years were evaluated.NNAL,uCot,corrected NNAL (cNNAL),the NNAL/uCot ratio,uNa,sBP,and nutrient intake were measured.A strong association between uCot and cNNAL was observed in children who were 11 years of age (r=0.881,P＜0.001);however,no significant association was noted in adolescents who were 19 years of age.The uNa level was significantly higher (133.9 mmol/L vs.107.8 mmol/L,P＜0.001) and sBP was significantly lower (105.3 mmHg vs.110.6 mmHg,P=0.012) in adolescents with elevated NNAL than in those without elevated NNAL.NNAL was significantly higher in subjects with increased uNa excretion than in those without increased uNa excretion.NNAL was positively correlated with uNa (r=0.183,P＜0.001) and negatively correlated with sBP (r=-0.142,P＜0.001).Non-smokers with elevated NNAL/uCot ratios had significantly lower total energy intake than those without elevated NNAL/uCot ratios (1729.0 kcal/day vs.1911.0 kcal/day,P=0.008).The relationship between NNAL and uCot varied according to the subjects' age.NNAL seems to play a role in decreasing sBP by enhancing uNa excretion.Insufficient nutrient intake may contribute to endogenous formation of NNAL in non-smoking adolescents and children.
查看更多>>摘要：This study investigated the association of a tobacco-specific nitrosamine carcinogen,4-(methylnitrosamino)-l-(3-pyridyl)-l-butanol (NNAL) with urinary cotinine (uCot),urinary sodium (uNa) excretion,systolic blood pressure (sBP),and total energy intake in adolescents and children in relation to the subjects' age.A total of 790 subjects aged 6-19 years were evaluated.NNAL,uCot,corrected NNAL (cNNAL),the NNAL/uCot ratio,uNa,sBP,and nutrient intake were measured.A strong association between uCot and cNNAL was observed in children who were 11 years of age (r=0.881,P＜0.001);however,no significant association was noted in adolescents who were 19 years of age.The uNa level was significantly higher (133.9 mmol/L vs.107.8 mmol/L,P＜0.001) and sBP was significantly lower (105.3 mmHg vs.110.6 mmHg,P=0.012) in adolescents with elevated NNAL than in those without elevated NNAL.NNAL was significantly higher in subjects with increased uNa excretion than in those without increased uNa excretion.NNAL was positively correlated with uNa (r=0.183,P＜0.001) and negatively correlated with sBP (r=-0.142,P＜0.001).Non-smokers with elevated NNAL/uCot ratios had significantly lower total energy intake than those without elevated NNAL/uCot ratios (1729.0 kcal/day vs.1911.0 kcal/day,P=0.008).The relationship between NNAL and uCot varied according to the subjects' age.NNAL seems to play a role in decreasing sBP by enhancing uNa excretion.Insufficient nutrient intake may contribute to endogenous formation of NNAL in non-smoking adolescents and children.
查看更多>>摘要：Cognitive impairment is the main clinical manifestation of Alzheimer's disease (AD),and amyloid-β (Aβ) deposition and senile plaques are the characteristic neuropathological hallmarks in AD brains.This study aimed to explore the effect and mechanism of tetrahydroxy stilbene glucoside (TSG) on cognitive function in APP/PS1 mice during long-term administration.Here,we treated APP/PS1 model mice of AD with different doses of TSG (50 mg/kg and 100 mg/kg) for 5 to 17 months by gavage,and we further observed whether TSG could ameliorate the cognitive decline in APP/PS1 mice using behavioral tests,and investigated the possible mechanisms by immunohistochemistry and Western blotting.Our results showed that TSG treatment rescued the spatial and non-spatial learning and memory impairments of APP/PS1 mice at Morris water maze test and novel object recognition test.Furthermore,Aβ40/42 deposition in the cortex andhippocampus of APP/PS1 mice treated with TSG was significantly reduced compared to the wild type mice using the immunohistochemical technique.Finally,Western blotting showed that TSG primarily decreased the APP expression to avoid the Aβ plaque deposition in the cortex and hippocampus of mice.These results reveal the beneficial effects of TSG in APP/PS 1-AD mice,which may be associated with the reduction of Aβ deposits in the brain.
查看更多>>摘要：Cognitive impairment is the main clinical manifestation of Alzheimer's disease (AD),and amyloid-β (Aβ) deposition and senile plaques are the characteristic neuropathological hallmarks in AD brains.This study aimed to explore the effect and mechanism of tetrahydroxy stilbene glucoside (TSG) on cognitive function in APP/PS1 mice during long-term administration.Here,we treated APP/PS1 model mice of AD with different doses of TSG (50 mg/kg and 100 mg/kg) for 5 to 17 months by gavage,and we further observed whether TSG could ameliorate the cognitive decline in APP/PS1 mice using behavioral tests,and investigated the possible mechanisms by immunohistochemistry and Western blotting.Our results showed that TSG treatment rescued the spatial and non-spatial learning and memory impairments of APP/PS1 mice at Morris water maze test and novel object recognition test.Furthermore,Aβ40/42 deposition in the cortex andhippocampus of APP/PS1 mice treated with TSG was significantly reduced compared to the wild type mice using the immunohistochemical technique.Finally,Western blotting showed that TSG primarily decreased the APP expression to avoid the Aβ plaque deposition in the cortex and hippocampus of mice.These results reveal the beneficial effects of TSG in APP/PS 1-AD mice,which may be associated with the reduction of Aβ deposits in the brain.
查看更多>>摘要：Block of proliferation 1 (BOP1) is a key protein involved in ribosome maturation and affects cancer progression.However,its role in gastric cancer (GC) remains unknown.This study aimed to explore the expression of BOP1 in GC and its potential mechanisms in regulating GC growth,and the relationship between BOP1 level in cancer tissues and survival was also analyzed.The expression of BOP1 was examined by immunohistochemistry (IHC) in a cohort containing 387 patients with primary GC.Cultured GC cells were treated by siRNA to knock down the BOP 1 expression,and examined by CCK-8 assay and plate clone formation to assess cell proliferation in vitro.Apoptotic rate of cultured GC cells was detected by flow cytometry with double staining of AnnxinV/PI.The xenografted mouse model was used to assess GC cell proliferation in vivo.Western blot and IHC were also performed to detect the expression levels of BOP1,p53 and p21.Patients with higher level of BOP1 in cancer tissues had significantly poorer survival.BOP1 silencing significantly suppressed GC cell proliferation both in vitro and in vivo.It blocked cell cycle at G0/G1 phase and led to apoptosis of GC cells via upregulating p53 and p21.BOP1 silencing-induced suppression of cell proliferation was partly reversed by pifithrin-α (a p53 inhibitor).Our study demonstrated that BOP 1 up-regulation may be a hallmark of GC and it may regulate proliferation of GC cells by activating p53.BOP1 might be considered a novel biomarker of GC proliferation,and could be a potential indicator of prognosis of GC patients.BOP1 might also be a potential target for the treatment of GC patients if further researched.
查看更多>>摘要：Block of proliferation 1 (BOP1) is a key protein involved in ribosome maturation and affects cancer progression.However,its role in gastric cancer (GC) remains unknown.This study aimed to explore the expression of BOP1 in GC and its potential mechanisms in regulating GC growth,and the relationship between BOP1 level in cancer tissues and survival was also analyzed.The expression of BOP1 was examined by immunohistochemistry (IHC) in a cohort containing 387 patients with primary GC.Cultured GC cells were treated by siRNA to knock down the BOP 1 expression,and examined by CCK-8 assay and plate clone formation to assess cell proliferation in vitro.Apoptotic rate of cultured GC cells was detected by flow cytometry with double staining of AnnxinV/PI.The xenografted mouse model was used to assess GC cell proliferation in vivo.Western blot and IHC were also performed to detect the expression levels of BOP1,p53 and p21.Patients with higher level of BOP1 in cancer tissues had significantly poorer survival.BOP1 silencing significantly suppressed GC cell proliferation both in vitro and in vivo.It blocked cell cycle at G0/G1 phase and led to apoptosis of GC cells via upregulating p53 and p21.BOP1 silencing-induced suppression of cell proliferation was partly reversed by pifithrin-α (a p53 inhibitor).Our study demonstrated that BOP 1 up-regulation may be a hallmark of GC and it may regulate proliferation of GC cells by activating p53.BOP1 might be considered a novel biomarker of GC proliferation,and could be a potential indicator of prognosis of GC patients.BOP1 might also be a potential target for the treatment of GC patients if further researched.
查看更多>>摘要：Since the outbreak of the novel corona virus disease 2019 (COVID-19) at the end of 2019,specific antiviral drugs have been lacking.A Chinese patent medicine Toujiequwen granules has been promoted in the treatment of COVID-19.The present study was designed to reveal the molecular mechanism of Toujiequwen granules against COVID-19.A network pharmacological method was applied to screen the main active ingredients of Toujiequwen granules.Network analysis of 149 active ingredients and 330 drug targets showed the most active ingredient interacting with many drug targets is quercetin.Drug targets most affected by the active ingredients were PTGS2,PTGS 1,and DPP4.Drug target disease enrichment analysis showed drug targets were significantly enriched in cardiovascular diseases and digestive tract diseases.An "active ingredienttarget-disease" network showed that 57 active ingredients from Toujiequwen granules interacted with 15 key targets of COVID-19.There were 53 ingredients that could act on DPP4,suggesting that DPP4 may become a potential new key target for the treatment of COVID-19.GO analysis results showed that key targets were mainly enriched in the cellular response to lipopolysaccharide,cytokine activity and other functions.KEGG analysis showed they were mainly concentrated in viral protein interaction with cytokine and cytokine receptors and endocrine resistance pathway.The evidence suggests that Toujiequwen granules might play an effective role by improving the symptoms of underlying diseases in patients with COVID-19 and multi-target interventions against multiple signaling pathways related to the pathogenesis of COVID-19.
NETL
NSTL
万方数据
维普