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This study mainly introduced the research on Chinese medicine toxicology funded by the National Natural Science Foundation of China(NSFC) in 2012-2021 and analyzed the research content. Furthermore, key research topics and characteristic research projects were discussed, such as the toxicity mechanism, relationship between toxicity and efficacy, toxicity-alleviating mechanisms, and new technology and methods. The review suggested that researchers should gain an in-depth understanding of the "toxicity" of Chinese me-dicine, turned to characteristic research topics, and build a toxicological research paradigm suited to the characteristics of Chinese medicine in project application.
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China , Foundations , Medicine, Chinese Traditional , Natural Science DisciplinesABSTRACT
The solubility of nebivolol hydrochloride was determined in acidic aqueous media in the absence and presence of different concentration of NaCl, NaBr, or NaI at 37 ℃ in order to facilitate proper selection of dissolution media that have adequate discriminating power for enhancing the likelihood of a generic drug product to successfully pass in-vivo bioequivalence test. In the range of pH 5.0 to pH 1.0, the solubility of nebivolol hydrochloride decreased with the decrease in the pH of aqueous solution, and the solubility of nebivolol hydrochloride further decreased with the increase in the concentration of added sodium chloride. The solubility decrease of a few weakly basic drug molecules in acidic media and in higher concentration of added chloride was published previously by other researchers, and the observed decrease in the solubility in the presence of higher chloride concentration was interpreted in terms of common-ion effect. However, the results in this paper showed that the solubility of nebivolol hydrochloride also decreased when sodium chloride was replaced with sodium bromide or iodide. The approach described in this paper (i.e. substituting sodium chloride with sodium bromide or iodide) provides an effective method to verify whether common-ion effect is the true (or at least the sole) driving force behind the observed decrease in the solubility of nebivolol hydrochloride in the presence of sodium chloride. The solubility decrease reported in this paper can be interpreted in terms of salting-out effect of sodium chloride, bromide, and iodide. For hydrochloride salt of a weakly basic drug molecule like nebivolol hydrochloride, its solubility in an acidic dissolution medium can be purposely decreased to the lower end of sink condition by adding sodium chloride to make the resulting medium more discriminating. As shown in this paper, a medium at pH 1.2 with added sodium chloride is discriminating and this medium is shown to be bio-relevant to the in-vivo data collected under fasting condition (in-vivo study protocol was approved by Institutional Review Board).
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Objective: To explore the effect and mechanism of Wuzi Yanzong Fang (WZ) on proliferation of spermatogonial stem cells in aging rats by regulating miR-let-7-Imp axis.Method: A total of 40 18-month-old male SD rats were randomly divided into aging model group, and low, middle and high-dose WZ groups, with 10 rats in each group. Ten 2-month old rats were used as young control group. Low, middle and high-dose WZ groups were given by gastric WZ 0.4, 0.8, 1.6 g·kg-1 respectively. Young control group and aging model group were given normal saline for 4 months, which was suspended for 2 days every week. Rats were put to death after the final treatment with WZ, and then the testes were quickly removed from rats. The relative mRNA expression levels of miR-let-7 and Imp were detected by Real-time fluorescence quantitative polymerase chain reaction (Real-time PCR). The expressions and localization of p-JAK2/JAK2, phosphate(p)-signal transduction and transcriptional activators3 (STAT3)/STAT3 signaling pathway proteins were detected by Western blot and immunofluorescence. The numbers of spermatogonial stem cells and the expression levels of proliferating cell nuclear antigen (PCNA) were detected by immunofluorescence. The testicular tissue morphology was observed using htoxylin eosin (HE) staining.Result: Compared with young control group, the expression levels of miR-let-7 mRNA were significantly increased, while the expression levels of Imp mRNA were decreased in the aging model group(PPPPPPPConclusion: WZ effectively promote the proliferation of spermatogonial stem cells by regulating miR-let-7-imp axis in testis.
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To study the protective effects of Wuzi Yanzong recipe on testis germ cell apoptosis in natural ageing rats through endoplasmic reticulum stress (ERS), 16-month-old male SPF grade SD rats were randomly divided into three groups: ageing model group, and low and high-dose Wuzi Yanzong recipe groups (WZ, 1 and 4 g·kg⁻¹), with 10 rats in each group. In addition, 2-month-old SD male rats were used as adult control group. The ageing model group and the adult control group were fed with normal diet for 4 months. WZ groups were given the medicated feed for 4 months. After fasting for 12 hours, the rats were put to death. Then, the testes were immediately collected. The change of testicular tissue morphology was observed by HE staining. The expression levels of ER stress-related proteins GRP78, p-PERK, p-eif2, ATF4, p-IRE1, XBP1, ATF6 and apoptosis-related proteins CHOP, caspase12 and p-JNK in testes were detected by Western blot. Compared with the ageing model group, Wuzi Yanzong recipe alleviated the morphological changes of testicular tissue. Western blot results showed that Wuzi Yanzong recipe significantly increased the expression levels of endoplasmic reticulum stress-related proteins GRP78, p-PERK, p-eif2, ATF4, p-IRE1, XBP1, ATF6 and significantly decreased the expression levels of endoplasmic reticulum-induced apoptosis-related proteins CHOP, caspase 12 and p-JNK. In conclusion, Wuzi Yanzong recipe can alleviate the ageing-related apoptosis of testicular germ cells in natural ageing rats by regulating endoplasmic reticulum stress.
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Animals , Male , Rats , Aging , Apoptosis , Drugs, Chinese Herbal , Pharmacology , Endoplasmic Reticulum Stress , Germ Cells , Rats, Sprague-Dawley , TestisABSTRACT
To study the protective effects of Wuzi Yanzong recipe on DNA oxidative damage of testis germ cells in natural ageing rats based on Nrf2/HO-1 signaling pathway and base excision repair (BER). In the study, 16-month-old SPF grade male SD rats were randomly divided into three groups, namely ageing model group, and low and high-dose Wuzi Yanzong recipe groups (WZ, 1, 4 g·kg⁻¹). In addition, 2-month-old SD rats were used as adult control group (10 rats in each group). The ageing model group and the adult control group were fed with normal diet for 4 months. WZ groups were given medicated feed for 4 months. After fasting for 12 hours, the rats were put to death. Then, the testes were immediately removed. The vitality of superoxide dismutase (SOD) and malondialdehyde (MDA) content in testis were detected by xanthine oxidase method and thiobarbituric acid (TBA) method. The levels of Nrf2 and 8-OHdG were detected by immunofluorescence. The protein expression levels of Nrf2, HO-1, NQO1, APE1, OGG1 and XRCC1 were detected by Western blot. Compared with the ageing model group, WZ significantly increased the SOD vitality and decreased MDA content of testis. In addition, immunofluorescence results showed that WZ significantly attenuated testicular DNA oxidative damage and improved antioxidant capacity. Such changes were accompanied by the down-regulation of DNA oxidative damage response protein 8-OHdG levels and the up-regulation of Nrf2 levels. Moreover, Western blot results showed that WZ significantly increased the protein expression levels of Nrf2, HO-1 and NQO1 of the testis germ cells, when compared with ageing model group. In parallel, the protein expression levels of APE1, OGG1 and XRCC1 were significantly decreased. In conclusion, WZ improves ageing-related DNA oxidative damage via Nrf2/HO-1 and BER pathways.
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To study the protective effect of Wuzi Yanzong recipe on testicular DNA damage and apoptosis in natural ageing rats, SPF grade 16-month-old SD male rats were randomly divided into three groups: ageing model group, low and high dose Wuzi Yanzong recipe groups (WZ, 1， 4 g·kg⁻¹). In addition, 2-month-old SD rats were used as adult control group (10 rats in each group). The ageing model group and the adult control group were fed with normal diet for 4 months. Wuzi Yanzong groups received medicated feed for 4 months. After fasting for 12 hours, the rats were sacrificed. Then testis tissues were taken and weighed to calculate the testis index. The change of testicular tissue morphology was observed by HE staining. Expression and localization of DNA damage-associated protein ATR were observed by immunofluorescence. The expressions of DNA damage-related proteins γ-H2AX, Chk1, p-p53 and apoptosis-related proteins Bcl-2 and Bax in testes were detected by Western blot. The apoptosis of testis tissue in rats was detected by using TUNEL. The results showed that as compared with the youth control group, the protein expression levels of γ-H2AX, Chk1, p-p53 and Bax were significantly increased while Bcl-2 protein expression level was significantly decreased intestis tissues of ageing model group. Wuzi Yanzong recipe significantly decreased protein expression levels of γ-H2AX, Chk1, p-p53 and Bax and increased Bcl-2 protein expression level as well as Bcl-2/Bax ratio. Immunofluorescence results showed that Wuzi Yanzong recipe could significantly decrease the ageing-induced ATR, increase in testis tissues. TUNEL results showed that Wuzi Yanzong recipe could significantly attenuate the germ cell apoptosis in testicular tissues. All the above results suggest that Wuzi Yanzong recipe could protect the germ cell in testicular tissues of natural ageing rates from DNA damage and apoptosis, and the mechanism may be associated with regulating p53 signaling pathway.
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Objective To investigate the effects of panax notoginseng saponins (PNS) combined with total flavonoids from epimedium (TFE) on testicular dysfunction in natural aging rats; To discuss its mechanism of action. Methods Thirty 18-month old male SD rats were randomly divided into natural aging group, PNS combined with TFE low and high dose groups, with 10 rats in each group. Another 10 2-month old rats were set as young control group. PNS combined with TFE low and high dose groups were given gastric gavage of 10 mg/kg PNS combined with 10 mg/kg TFE, and 20 mg/kg PNS combined with 20 mg/kg TFE, respectively. Rats in young control group and natural aging group were given saline for 6 d each week, lasting for 4 months. Then, rats were sacrificed, and the testes were obtained to calculate the testicular weight and the testicular index. The testicular tissue morphology was observed by using HE staining. Testicular germ cell apoptosis was detected by using TUNEL method. The levels of Bcl-2, Bax and γ-H2 AX protein expression in testicular tissue were detected by Western blot. Results Compared with natural aging group, low and high dose of PNS combined with TFE significantly elevated the testicular weight and testicular index, improved the histological changes of testicular seminiferous tubule, significantly reduced number of apoptosis of spermatogenic cells in the testis, upregulated the expression of Bcl-2 protein in the testis, downregulated the expression of Bax and γ-H2 AX protein, and decreased the ratio of Bax/Bcl-2. Conclusion PNS combined with TFE can improve testicular dysfunction in natural aging rats by inhibiting apoptosis and DNA damage of germ cells.
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<p><b>OBJECTIVE</b>To investigate the protective effect of six Kaixin San formulas on simulated cells model of depression, Alzheimer's disease and Parkinson's disease.</p><p><b>METHOD</b>The in vitro simulated cells model of depression, Alzheimer's disease and Parkinson's disease was established by injuring SH-SY5Y cells with corticosterone (0.4 mmol x L(-1)) , injuring PC12 cells with neurotoxic amyloid peptide (Abeta25-35) (20 micromol x L(-1)) and injuring SH-SY5Y cells with 1-methyl-4-phenylpyridinium ion (MPP+) (250 micromol x L(-1)). The cell survival rate was assayed with MTT method and the degree of cell injury was detected with LDH.</p><p><b>RESULT</b>100, 500 mg x L(-1) Dingzhixiao Wan prepared as mentioned in Beiji Qianjin Yaofang could significantly increase the survival ratio of SH-SY5Y cells injured by corticosterone and reduce LDH concentration released. All of the Kaixin San formulas could significantly increase the survival ratio of PC12 cells injured by Abeta25-35 and reduce LDH concentration released. Particularly, Kaixin San (10, 100, 500 mg L(-1)) prepared as mentioned in Beiji Qianjin Yaofang shown the best effect. And 500 mg x L(-1) Fushen Wan prepared as mentioned in Gujin Luyan could significantly increase survival ratio of SH-SY5Y cell injured by MPP and reduce LDH concentration released.</p><p><b>CONCLUSION</b>Dingzhixiao Wan prepared as mentioned in Beiji Qianjin Yaofang could protect corticosterone-induced SH-SY5Ycells injury, showing a potential antidepressant effect. All of the six Kaixin San formulas could protect Abeta25-35-induced PC12 cells injury, but Kaixin San prepared as mentioned in Beiji Qianjin Yaofang shown the best potential effect for Alzheimer's disease. Fushen Wan prepared as mentioned in Gujin Luyan could protect MPP(+)-induced SH-SY5Y cells injury to some extent.</p>
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Animals , Humans , Rats , 1-Methyl-4-phenylpyridinium , Toxicity , Alzheimer Disease , Drug Therapy , Amyloid beta-Peptides , Toxicity , Cell Survival , Drugs, Chinese Herbal , Pharmacology , Neurons , Cell Biology , Neuroprotective Agents , Pharmacology , PC12 Cells , Parkinson Disease , Drug Therapy , Peptide Fragments , ToxicityABSTRACT
@#ObjectiveTo observe the retinal function and nerve fiber layer (RNFL) thickness after laser in situ keratomileusis (LASIK). MethodsLASIK was performed in 15 cases (30 eyes) with myopia after strict preoperative examination. All examinations such as vision, correction vision, diopter, intraocular pressure, corneal thickness, ocular axis, topography scan and fundus of eye examination were performed before and 1 day, 1 week, 1 month,3 months and 6 months after operation, as well as electroretinography (ERG), visual evoked potential (VEP), optical coherece tomography at same time. ResultsThere was not significant difference in the intraocular pressure, ERG and VEP 1 day after LASIK. The thickness of RNFL decreased 1 week after LASIK (P<0.05) and recovered 1～6 months later. ConclusionLASIK does not disturb the retinal function and RNFL thickness irreversiblely.
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Objective To observe the influence of silymarin on expressions of transforming growth factor-?1(TGF-?1) and collagen type Ⅲ(Col Ⅲ) in rats with experimental tubulointerstitial fibrosis(TIF) induced by unilateral ureteral obstruction(UUO).Methods Se-venty-two Sprague-Dawley rats were randomly divided into 3 groups:sham operation group(n=24),model group(n=24) and silymarin treatment group(n=24).The rats in model group and treatment group were operated by ligation of left-ureter.The rats in sham opera-tion group operated by dissociating left-ureter were taken as controls.Rats in treatment group were fed with silymarin [30 mg/(kg?d)]24 h before operation,and rats in model group and sham operation group were treated by intragastric administration with the same volume nomal saline at the same time.Eight rats were killed at day 7,14,and 21,respectively.The score of TIF changes,histologically,was evaluated under light microscope.Expressions of TGF-?1 and Col Ⅲ in tubulointerstitial tissue in 3 groups were investigated by immunohistochemistry.Results 1.The TIF pathological index in treatment group was less than that in model group,but more than sham operation group at day 14 and 21(Pa
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The phytase gene phyA(m) from Aspergillus niger N25 was recombined into E. coli expression vector pET-30b(+). Recombined at expression vectors pET30b-FphyA(m) was served as a template to amplify phytase gene, and the PCR product named elongation mutation gene phyA(e) was expanded with a 13 amino acid sequence from pET-30b-FphyA(m) vector at C-terminal of phytase gene phyA(m). Furthermore, phyA(e) gene was recombined into expression vector pPIC9k and expressed in Pichia pastoris. The comparison experiment of mutant phytase PP-NP0 with wild-type phytase PP-NP(m)-8 showed that: the optimum temperature of PP-NPe was increased by 3 degrees C, and its thermostability was increased by 21% when it was exposed to 10 min at 75 degrees C. Its effective reaction pH range with catalysis efficiency above 70% was pH 4.6 - pH 6.6, and wider 0.4 pH value than that of wild-type phytase.
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6-Phytase , Genetics , Amino Acid Sequence , Aspergillus niger , Genetics , Enzyme Stability , Genetics , Escherichia coli , Genetics , Fungal Proteins , Genetics , Hot Temperature , Molecular Sequence Data , MutationABSTRACT
@#ObjectiveTo investigate the effect of filtering surgery on glaucoma.Methods50 glaucoma cases (60 eyes) were underwent trabeculectomy, including paracentesis in advance, suturing of sclera flap and conjunctiva flap, using mitomycin (MMC) and forming anterior chamber as soon as finished operation. All cases were followed up 1 year.ResultsPostoperative IOP was lower than 21 mmHg in 54 eyes, 6 eyes were <30 mmHg when treated with drugs. After operation, there were only 2 eyes had lower vision, the others had higher vision. Two eyes had conjunctiva filtering, two eyes had choroidal separation, but they recovered after non surgical therapy.ConclusionFiltering surgery can decrease common complications, increase vision of early stage, and make IOP recovered to normal.
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As a kind of additive in feed of monogastric animals, the application of natural phytase is limited due to its disadvantages. In this paper, the strategies of phytse reform was introduced. Furthermore, the research and progress on protein engineering of feed phytase was reviewed, including phytase over-expression, phytase thermostability, catalytic efficiency and optimum pH.