Garcinol, a benzenetriol compound extracted from Garcinia cambogia, has antitumor activity, however, its antitumor mechanism remains unclear. The aim of this study was to investigate the role and mechanism of garcinol as a novel potential proteasome inhibitor. We applied the drug affinity responsive target stability (DARTS) method coupled to mass spectrometry to determine the binding protein of garcinol; the proteasome activity assay was used to determine the effect of garcinol on its hydrolase activity; immunofluorescence and proximity ligation assay (PLA) were used to detect the effects of garcinol on ubiquitin and RPN6; and flow cytometry were used to determine the effects of garcinol on cell apoptosis; and the anti-cancer effect was studied in organoid models. The results showed that RPN6 was a direct binding protein of garcinol; garcinol inhibited the hydrolase activity of proteasome, and induced the accumulation and aggregation of ubiquitin protein, and its proteasomal inhibitory effect was dependent on RPN6; further studies showed that garcinol induced oligomerization of RPN6 and formation of granules in the nucleus; finally, it was verified that garcinol induced apoptosis of tumor cells, and inhibited the growth of organoids of Apc^min/+ small intestine mice. These results suggest that garcinol is a potential proteasome inhibitor, which inhibits proteasome activity by directly targeting RPN6 on proteasome 19S, which in turn induces cell apoptosis and inhibits tumor growth.

Objective To analyze the amount and allocation of pediatric healthcare resources in Chengdu,and to recommend on local pediatric healthcare resources shortages.Methods Pediatric healthcare resources data of Chengdu came from pediatric relevant data reported regularly at yearend by the counties and districts to healthcare administration of the city.Data from such reports were subject to statistics with various indexes and descriptive analysis.Analyzed in focus was the distribution in 2015 of pediatric healthcare resources of the city among medical institutions of various types,levels and properties,as well as causes for such shortage.Results Tertiary hospitals hold 62.3% of the pediatric beds and 64.2% of pediatricians,and provide around 70% of the medical workload for pediatric outpatients and inpatients,upon the majority of pediatricians with master degree and above,and senior ones of/above associate chief physician titles;Tertiary hospitals have 58.7% of the pediatric beds and 49.7% of pediatricians,yet the outpatients served by specialized hospitals were 5% above tertiary hospitals.Conclusions The imbalance and shortage in total of pediatric resources in Chengdu result from stable source of manpower supply,high professional risk exposure,low income,and long training duration among others.Such measures as a better pediatrician development system,greater incentives for pediatric development,and enhanced development pediatric service consortiums,as well as greater support for private specialized pediatric hospitals.Those measures combined can effectively alleviate the shortage of pediatric resources.

Cestode Infections ; parasitology ; Humans ; Infant ; Male

Abstract: Objective　To understand the pollution characteristics and sources of PM2.5 in the atmosphere during heating and non-heating periods in Urumqi City in 2021, and provide scientific basis for pollution control during different periods. Method A total of 188 air samples were collected from area A and area B of Urumqi City, and 12 metal elements and 5 water-soluble ions were quantitatively analyzed, and the pollution sources were analyzed by enrichment factor method and principal component analysis method. Results In 2021, the mass concentrations of PM2.5 in areas A and B of Urumqi were 45.0 (20.0, 158) µg/m3 and 28.0 (17.5, 66.0) µg/m3, respectively, with statistically significant difference (Z=-2.870, P<0.05). During the heating period, the concentrations were 110 (68.0, 250) µg/m3 and 61.0 (31.0, 88.0) µg/m3, respectively, with no statistically significant difference (Z=-3.822, P<0.01). During the non-heating period, the concentrations were 18.0 (13.0, 22.3) µg/m3 and 18.0 (12.8, 22.0) µg/m3, respectively, with no statistically significant difference (Z=-0.596, P>0.05). The SNA (the sum of SO42-, NO3-and NH4+) accounted for 71.7% and 23.4% of PM2.5 in A area during heating and non-heating periods, respectively, with statistically significant difference (Z=-8.057, P<0.01); the corresponding proportions in B area were 60.7% and 24.9%, with statistically significant difference (Z=-6.672, P<0.01). During the heating and non-heating periods, the ratios of NO3-/SO42-are 0.63 and 0.54 in A area were 0.63 and 0.54, respectively, with statistically significant difference (Z=-2.382, P<0.05); and the corresponding ratios in B area were 0.72 and 0.53, respectively, with statistically significant difference (Z=-3.182, P<0.05). The ratio of NO3- to SO42- was less than 1 in both heating and non-heating periods in the two areas. and the correlation between five water-soluble ions was significant (P<0.05). The correlation coefficient between NH4+ and SO42-, NO3-and Cl- in A and B areas during heating periods were all >0.9, indicating that NH4+and SO42-, NO3- and Cl- bind in (NH4)2SO4, NH4HSO4, NH4NO3, and NH4Cl. During non-heating periods, the correlation between NH4+ and each ion was slightly lower. During heating periods in area A, Sb, As, Cd, Pb, and Tl were severely enriched (EF>100). During non-heating periods in the same area, As, Cd, Pb, Tl, and Hg were severely enriched (EF>100). During heating periods in area B, Sb, As, Cd, Pb, and Hg were severely enriched (EF>100), and during non-heating periods in the same area, Sb, Cd, and Hg were severely enriched (EF>100). Coal emission, photochemical secondary pollution, motor vehicle exhaust, dust and industrial pollution were the main sources of PM2.5 pollution in the two areas, and the contribution rate of fixed sources was higher than that of mobile sources. Conclusion In 2021, the mass concentration of PM2.5, water-soluble ions and metal elements in Urumqi City were higher in area A than area B, the heating period was higher than the non-heating period, the excess rate of area A was higher than that in area B, and the contribution rate of fixed air pollution was greater than that of mobile sources.

Maize seedlings were cultured in nickel or cadmium contaminated sand treated with α-naphthylacetic acid (NAA). The effects of NAA on nickel and cadmium uptake in roots, shoots, and subcellular fractions (cell wall, nuclei and remained parts of seedling cells) were determined. The data showed growth promotion when NAA was applied at low concentrations and inhibition at high concentrations. Uptake of nickel and cadmium content increased concurrently in roots and shoots. In the subcellular fraction, nickel and cadmium was greatest in the cell wall. The changes in growth had greatest correlation with nickel and cadmium content in the subcellular fraction.

OBJECTIVETo study the effect of electro-acupuncture (EA) at Neiguan (PC6) and Lieque (LU7) on the expression of protein kinases in cardiomyocytes of myocardial ischemia (MI) rats.

METHODSHealthy male SD rats were randomly divided into the control group, the model group, the Neiguan point group, the Lieque point group, and the non-meridian non-acupoint group, 10 in each group by random digit table. The MI rat model was established by injecting isoprenaline hydrochloride (85 mg/kg). EA at Neiguan (PC6), Lieque (LU7), and non-meridian non-acupoint were respectively performed. Changes of the expression of protein kinases [such as protein kinase A (PKA), protein kinase C (PKC), protein kinase G (PKG)] in rat cardiomyocytes were observed using Western blot.

RESULTSCompared with the control group, expression levels of PKA, PKC, and PKG increased obviously in the model group (P < 0.01). Compared with the model group, expression levels of PKA, PKC, and PKG decreased in the Neiguan point group and the Lieque point group (P < 0.01, P < 0.05). Expression levels of PKA decreased in the non-meridian non-acupoint group (P < 0.01). Compared with the Neiguan point group, expression levels of PKA, PKC, and PKG increased in the non-meridian non-acupoint group and the Lieque point group (P < 0.01, P < 0.05). Compared with the Lieque point group, expression levels of PKA, PKC, and PKG increased in the non-meridian non-acupoint group (P < 0.01, P < 0.05).

CONCLUSIONEA at Neiguan (PC6) and Lieque (LU7) could decrease protein expression levels of PKA, PKC and PKG in rat myocardial cells, and the effect of acupuncture at Neiguan (PC6) was better than that obtained by EA at Lieque (LU7).

Acupuncture Points ; Acupuncture Therapy ; Animals ; Coronary Artery Disease ; Cyclic AMP-Dependent Protein Kinases ; Electroacupuncture ; Male ; Meridians ; Myocardial Ischemia ; metabolism ; therapy ; Myocytes, Cardiac ; metabolism ; Plant Extracts ; Protein Kinases ; metabolism ; Rats ; Rats, Sprague-Dawley

Affinity chromatography is a chromatographic method for separating molecules using the binding characteristics of the stationary phase with potential drug molecules. This method can be performed as a high throughput screening method and a chromatographic separation method to screen a variety of active drugs. This paper summarizes the history of affinity chromatography, screening technology of affinity chromatography, and application of affinity chromatography in screening bio-active compounds in herbal medicines, and then discusses its application prospects, in order to broaden applications of the affinity chromatography in drug screening.
Animals ; Chromatography, Affinity ; methods ; trends ; Drug Evaluation, Preclinical ; methods ; trends ; Drugs, Chinese Herbal ; chemistry ; isolation & purification ; pharmacology ; Humans ; Plants, Medicinal ; chemistry

Objective To screen and analyse the dominated related factors for medical discipline construction and development,and provide evidences for the reinforcement of discipline connotation construction.Methods The candidate medical disciplines of State Key Disciplines Evaluation of 2007 were served as study subjects.Disciplines from the results of State Key Discipline Evaluation were divided into "new discipline" group(n=51),"breeding discipline" group(n=33)and "failed discipline" group(n=81).The differences between results of State Key Discipline Evaluation and corresponding data of past years(2001 to 2006)in academic team,scientific research,graduate education and lab construction were analysed by nonparametric Kruskal-Wallis test.Results There were significant differences in academic leader,state key project,prize level,graduates quality and scientific research base among the results of State Key Discipline Evaluation(P≤0.05),and the dominated factors for the unsuccessful result were lack of high-level academic leader,state key discipline,prize,gruaduates and scientific research base.Conclusion The adoption of appropriate measures for the construction of academic team,the reinforcement of scientific research and the establishment of academic achievement evaluation may help to upgrade the academic level.

Objective To explore the effect of excessive fluoride on expression of mRNA and protein of Wnt3a and β-catenin in rats' osteoblasts and its correlation with pathogenic mechanism of fluorosis.Methods Thirty-six healthy SD rats,weighting 100-120 g and according to body mass,were randomly divided into three groups(twelve in each group).The rats of control were fed wich tap water(fluoride ＜ 1 mg/L) and the experimental rats were exposed to NaF(low-fluoride group:5 mg/L,high-fluoride group:50 mg/L) added to the drinking water to establish the chronic fluorosis model.After fed for eight morth,all rats were killed and metaphysic of femoral was collected.Rat dental fluorosis was observed and bone fluorine was detected by ashing-fluorin ion selective electrode method.The content of bone alkaline phosphatase (BALP) and tartrate-resistant acid phosphatase 5b(TRACP 5b) in rats' serum was detected by enzyme-linked immunosorbent assay (ELISA).The morphologic changes of the bone were observed by microscopy.The expression of mRNA and protein of Wnt3a and β-catenin in osteoblasts of rats was analyzed with gray scale by hybridization in situ and immunohistochemistry methods,respectively.Results Detection rate of dental fluorosis,fluoride contents of urine and bone were significantly increased [control group:0.0％,(1.26 + 0.17)mg/L,(305.58 ± 91.26)mg/kg; low-fluoride group:66.7％,(2.06 ± 0.64)mg/L,(632.33 ±123.21)mg/kg; high-fluoride group:91.7％,(7.69 ± 1.96)mg/L,(1088.75 ± 156.16) mg/kg] in the rats treated with fluoride,the difference between groups was statistically significant(χ2 =21.6; F =36.57,467.02; all P ＜0.05).The contents of BALP and TRACP-5b in rats' serum were significantly different between groups(F =89.57,7.68; all P ＜ 0.05).Compared with control group[(16.24 + 1.57)U/L],the contents of BALP in rats' serum of the low-fluoride and high-fluoride groups[(31.47 ± 5.30) and (54.61 ± 2.27)U/L] were increased gradually(all P ＜0.05).Compared with the low-fluoride group,the value in the high-fluoride group decreased significantly (P ＜ 0.05).The contents of TRACP-5b in rats' serum of low-fluoride group[(3.45 ± 1.85)U/L] were elevated significantly(all P ＜ 0.05) compared with the control group[(1.26 ± 0.23)U/L] and the high-fluoride group[(2.74 ± 1.85)U/L].The bone cortices were thickened and the bone trabecula was broadened,arranged closely together in chronic fluorosis rats with significant difference compared with the control group.In the low-fluoride and high-fluoride groups,the expression levels of Wnt3a and β-catenin mRNA (low-fluoride group:132.87 ± 5.72 and 132.57 ± 9.56; highfluoride group:135.60 ± 6.64 and 137.87 ± 9.16) were markedly elevated with significant difference,respectively (F =12.47,5.96; all P ＜ 0.05) compared with those in control groups(119.86 ± 5.04 and 120.58 ± 7.84) by hybridization in situ(P ＜ 0.05),but there was no statistical significance (P ＞ 0.05) of the level of Wnt3a and β-catenin mRNA between low-fluoride and high-fluoride groups.In the low-fluoride and high-fluoride groups,the protein expression of Wnt3a and β-catenin (low-fluoride group:137.50 ± 4.32 and 140.85 + 3.54; high-fluoride group:142.65 ± 11.84 and 152.52 ± 4.64) were markedly elevated with significant difference,respectively (F =10.07,53.82; all P ＜ 0.05) compared with those in control group (124.01 ± 2.63 and 126.75 ± 4.65) by immunohistochemistry(all P＜ 0.05),Wnt3a protein production in the low-fluoride group was increased without statistical significance compared with the high-fluoride group (P ＞ 0.05).But the protein production of β-catenin in the lowfluoride group was elevated with significant difference compared with the high-fluoride group(P ＜ 0.05).The mRNA and protein production of Wnt3a were positively correlated with the mRNA and protein production of β-catenin (r =0.731,0.658; all P ＜ 0.05).Conclusions Rat bone tissue lesions caused by excessive fluoride may be associated with an increased expression of Wnt3a and β-catenin mRNA and protein in osteoblasts.In chronic fluorosis,fluoride stimulates the overexpression of Wnt3a and β-catenin in the Wnt signal transduction pathway,enhances bone osteogenesis and causes skeletal fluorosis.

Animals ; Dose-Response Relationship, Drug ; Male ; Mice ; Mice, Inbred Strains ; Nickel ; toxicity ; Oxidative Stress ; physiology ; Testis ; drug effects ; metabolism