Aim To explore the signaling pathway of matrine derivative ZS10 in inhibiting proliferation and inducing apoptosis of BEL-7402 cells. Methods ZS10 was synthesized by organic synthesis. The inhibitory effect of ZS10 on the proliferation of BEL-7402 cells was analyzed by MTT method at the time of 24 h, 48 h and 72 h, respectively, and IC50 was calculated. DAPI staining was used to observe the state of BEL-7402 cells. Clone formation method was used to observe the colony formation of BEL-7402 cells, flow cytometry was used to observe the cell cycle arrest and apoptosis of BEL7402 cells, and Western blot was used to detect the expression level of PI3K/AKT pathway and related proteins. Results MTT results showed that the IC50 was(6.62±1.11)μmol·L-1; DAPI staining showed that the cell state changed significantly with the increase of drug concentration, and the results of colony formation showed that ZS10 significantly inhibited the colony formation of BEL-7402 cells. The results of flow cytometry showed that ZS10 induced S phase arrest and cycle apoptosis of BEL-7402 cells. Western blot showed that ZS10 at the concentration of 08 μ mol·L-1 could regulate the PI3K/AKT pathway and its related proteins in a dose-dependent manner. Compared with the control group, the expression of PI3K, AKT, P-AKT and anti-apoptotic protein Bcl-2 significantly decreased, the expression of pro-apoptotic protein Bax significantly increased, the expression of Cyclin D1 and CDK2 significantly decreased, and the expression of EGFR and N-cadherin, Vimentin significantly decreased in the treatment group. The expression of E-cadherin increased. Conclusions Matrine derivative ZS10 can inhibit the growth and proliferation of hepatocellular carcinoma cell line BEL-7402.

Objective: To observe the platinum drugs resistance effect of N-acetyltransferase 10 (NAT10) overexpression in breast cancer cell line and elucidate the underlining mechanisms. Methods: The experiment was divided into wild-type (MCF-7 wild-type cells without any treatment) group, NAT10 overexpression group (H-NAT10 plasmid transfected into MCF-7 cells) and NAT10 knockdown group (SH-NAT10 plasmid transfected into MCF-7 cells). The invasion was detected by Transwell array, the interaction between NAT10 and PARP1 was detected by co-immunoprecipitation. The impact of NAT10 overexpression or knockdown on the acetylation level of PARP1 and its half-life was also determined. Immunostaining and IP array were used to detect the recruitment of DNA damage repair protein by acetylated PARP1. Flow cytometry was used to detect the cell apoptosis. Results: Transwell invasion assay showed that the number of cell invasion was 483.00±46.90 in the NAT10 overexpression group, 469.00±40.50 in the NAT10 knockdown group, and 445.00±35.50 in the MCF-7 wild-type cells, and the differences were not statistically significant (P>0.05). In the presence of 10 μmol/L oxaliplatin, the number of cell invasion was 502.00±45.60 in the NAT10 overexpression group and 105.00±20.50 in the NAT10 knockdown group, both statistically significant (P<0.05) compared with 219.00±31.50 in wild-type cells. In the presence of 10 μmol/L oxaliplatin, NAT10 overexpression enhanced the binding of PARP1 to NAT10 compared with wild-type cells, whereas the use of the NAT10 inhibitor Remodelin inhibited the mutual binding of the two. Overexpression of NAT10 induced PARP1 acetylation followed by increased PARP1 binding to XRCC1, and knockdown of NAT10 expression reduced PARP1 binding to XRCC1. Overexpression of NAT10 enhanced PARP1 binding to LIG3, while knockdown of NAT10 expression decreased PARP1 binding to LIG3. In 10 μmol/L oxaliplatin-treated cells, the γH2AX expression level was 0.38±0.02 in NAT10 overexpressing cells and 1.36±0.15 in NAT10 knockdown cells, both statistically significant (P<0.05) compared with 1.00±0.00 in wild-type cells. In 10 μmol/L oxaliplatin treated cells, the apoptosis rate was (6.54±0.68)% in the NAT10 overexpression group and (12.98±2.54)% in the NAT10 knockdown group, both of which were statistically significant (P<0.05) compared with (9.67±0.37)% in wild-type cells. Conclusion: NAT10 overexpression enhances the binding of NAT10 to PARP1 and promotes the acetylation of PARP1, which in turn prolongs the half-life of PARP1, thus enhancing PARP1 recruitment of DNA damage repair related proteins to the damage sites, promoting DNA damage repair and ultimately the survival of breast cancer cells.
Breast Neoplasms/enzymology* ; Cell Line, Tumor ; Drug Resistance, Neoplasm ; Female ; Humans ; MCF-7 Cells ; N-Terminal Acetyltransferases/metabolism* ; Organoplatinum Compounds/pharmacology* ; Oxaliplatin/pharmacology* ; X-ray Repair Cross Complementing Protein 1

The present study investigated the effect of active components of Descurainia sophia on allergic asthma and explored the underlying mechanism. SD male rats were randomly divided into a normal group(NC), a model group(M), a D. sophia decoction group(DS), a D. sophia fatty oil group(FO), a D. sophia flavonoid glycoside group(FG), a D. sophia oligosaccharide group(Oli), and a positive drug dexamethasone group(Y). The allergic asthma model was induced in rats by intraperitoneal injection of ovalbumin(OVA) and aluminum hydroxide gel adjuvant(sensitization) and atomization of OVA solution(excitation). After modeling, asthma-related indicators, tracheal phenol red excretion, inflammatory cell levels in the peripheral blood, lung permeability index(LPI), and oxygenation index(OI) of rats were detected. The pathological changes of lung tissues were observed by HE staining. Enzyme-linked immunosorbent assay(ELISA) was used to detect the content of inflammatory factors immunoglobulin E(IgE), interleukin-4(IL-4), and interferon-γ(IFN-γ) in the bronchoalveolar lavage fluid(BALF) and the content of endothelin-1(ET-1) and angiotensin-converting enzyme(ACE) in lung tissue homogenate. The serum content of nitric oxide(NO) was detected by colorimetry. Western blot was employed to determine the protein expression of Toll-like receptor 4(TLR4), nuclear factor κB-p65(NF-κB-p65), phosphorylated NF-κB-p65(p-NF-κB-p65), myosin light chain kinase(MLCK), vascular endothelial cadherin(VE cadherin), connexin 43, and claudin 5, and the mechanism of active components of D. sophia on allergic asthma was explored. As revealed by the results, the M group showed extensive infiltration of inflammatory cells around the bronchus of the lung tissues of the allergic asthma rats, thickened bronchial wall, severely deformed alveolar structure, increased number of wheezes, the content of IgE, IL-4, ET-1, and ACE, inflammatory cells, and LPI, and reduced latency of asthma, tracheal phenol red excretion, IFN-γ, NO content, and OI. After the intervention of the active components of D. sophia, the DS, FO, FG, Oli, and Y groups showed improved asthma-related indicators, tracheal phenol red excretion, and lung tissue lesions in allergic asthma rats, and the effects in the FO and Oli groups were superior. The content of inflammatory factors in BALF was recovered in the DS, FO, and Y groups and the FG and Oli groups. The number of inflammatory cells in rats was reduced in the DS and FO groups, and the FG, Oli, and Y groups to varying degrees, and the effect in the FO group was superior. DS, FO, Oli, and Y reduced ET-1, ACE, and LPI and increased NO and OI. FG recovered NO, ET-1, ACE, LPI, and OI to improve lung epithelial damage and permeability. Further investigation of inflammation-related TLR4/NF-κB pathways, MLCK, and related skeleton protein levels showed that TLR4, NF-κB-p65, p-NF-κB-p65, and MLCK levels were increased, and VE cadherin, connexin 43, and claudin 5 were reduced in the M group. DS, FO, FG, Oli, and Y could reduce the protein expression related to the TLR4 pathway to varying degrees, and regulate the protein expression of MLCK, VE cadherin, connexin 43, and claudin 5. It is inferred that the active components of D. sophia improve lung permeability in rats with allergic asthma presumedly by regulating the TLR4/NF-κB signaling pathway to improve airway inflammation, mediating MLCK and connexin, and regulating epithelial damage.
Animals ; Asthma/drug therapy* ; Bronchoalveolar Lavage Fluid ; Inflammation/metabolism* ; Lung ; Male ; Permeability ; Rats

Fabrication of conventional complete dentures involves a complex restoration method, requiring significant time and typically involving primary impressions, definitive impressions, jaw relation records, clinic try-in, and complete denture placement, which has been used for nearly a century without change. A novel digital system named Functionally Suitable Denture (FSD) was researched and developed so as to reduce clinical steps, operation difficulties and errors of complete denture restoration. It pioneered a unique diagnostic complete denture aided by computer aided design (CAD) & 3D printing, by which, the functional impression, jaw relation, and try-in (3 steps) were simplified to 1 step, thus the number of visits to the dentist was reduced by 2 times. Moreover, for the first time, it put forward a CAD software of template matching based on the expert design, which was an efficient and intelligent design scheme, and the excellent denture experts' experience and skills could be inherited and iterated. The system included the 3D scanner with appropriate accuracy and high efficiency, the CAD software, the special 3D printer and process software, and the innovative clinical operation process. The Patent Cooperation Treaty (PCT) patent international search report showed that all the 15 claims of the technology were of novelty, creativity and industrial utility. All the digital products were independently developed and made by Peking University School and Hospital of Stomatology, China. The design and manufacture process of denture prosthesis was fast, simple and accurate. At the same time, personalized functional and aesthetic matching of the patients after wearing prosthesis was realized. It effectively solved the global problems of "slow, difficult and inaccurate" of the traditional manual technology of complete denture, and brought good news to edentulous patients. Compared with the traditional complete denture treatment, FSD system has a wide range of applications for different types of edentulous patients, including those with severe resorption of the alveolar ridge or a high occlusal force. Furthermore, the low-cost of 3D printers, compared with expensive milling machines, may make the approach more accessible. This review describes that our research is related to the development of the FSD system, including multi-source data acquisition technology, three generations of complete denture design software, 3D printing systems of individual tray and complete denture pattern, the clinical and laboratory operation process of the FSD system.
China ; Computer-Aided Design ; Creativity ; Denture, Complete ; Humans ; Mouth, Edentulous

Objective : To investigate the clinical efficacy and degree of impact of placebo in the patients with primary insomnia. Methods ¡¤ Databases including PubMed, Cochrane, and Embase were searched. The Consolidated Standards of Reporting Trials (CONSORT) was used as a reference standard for enrollment and evaluation. The objective and subjective sleep assessment indicators were collected before and after pla-cebo treatment. Meta-analysis was performed using RevMan 5.3 and Comprehensive Meta-Analysis V2 softwares. Results ¡¤ A total of 17 arti-cles (18 studies) were included in the systematic review, and the total sample size was 1 980. These indicators were analyzed by age subgroups (adults and elderly adults). The objective indicators showed that the number of awaking was only statistically different in elderly adults group (P=0.043), while the latency period of sleep, wakefulness time after sleep onset and total sleep time were statistically different in both groups (P<0.05). The absolute value of total effect range was 0.153-0.414. Subjective indicators showed that the subjective total sleep time, subjective wakefulness time after sleep onset, and subjective number of awaking were statistically different in both groups (P<0.05), while subjective la-tency period of sleep was only statistically different in adults group (P=0.000). The absolute value of total effect range was 0.289-0.474. Con-clusion ¡¤ Placebo in the patients with primary insomnia can improve objective and subjective sleep assessment indicators, but the effect is small.

Objective:To investigate the clinical efficacy of Shashen Maidongtang plus total glucosides of paeony capsule on primary Sjogren's syndrome (pSS) based on the theory of fluid metabolism. Method:In this study, 84 patients of Qi-Yin deficiency type pSS admitted in Zhengzhou Chinese Medicine Hospital from January 2018 to January 2019 were divided into observation group (42 cases) and control group (42 cases) on the basis of random number table. The control group was orally given total glucosides of paeony capsule and iguratimod tablet, while the observation group was orally given Shashen Maidongtang combined with glucosides of paeony capsule. After 3 months of continuous treatment to all subjects, the clinical efficacy was evaluated, and side effects were recorded. Before and after the treatment, the saliva flow rate and basal tear secretion Schirmer I test (SIt) value were measured, European League Against Rheumatism Sjogren's syndrome patient reported index and Sjogren's syndrome disease activity index (ESSPRI and ESSDAI) were scored, the erythrocyte sedimentation rate (ESR) was determined by Westergren, and the levels of serum rheumatoid factor (RF) and immunoglobulin (Ig) G were tested by immunoturbidimetry and rate scattering turbidimetry, respectively. Result:The overall effective rate of the observation group was 90.48% (38/42), which was much higher than 69.05% (29/42) of the control group (χ²=5.974，P<0.05). After treatment, the saliva flow rates and SIt values of both groups got significantly increased compared with those before the treatment (P<0.05), but the saliva flow and SIt of the observation group were significantly better than those of the control group over the same period after treatment (P<0.05). After treatment, both groups had a great decrease in ESSPRI and ESSDAI scores compared with those before the treatment (P<0.05), and the above scores of the observation group were dramatically lower than those of the control group over the same period (P<0.05). After treatment, ESR, serum RF, and IgG levels of both groups were significantly lower than those before the treatment (P<0.05), and the observation group showed higher levels of ESR, serum RF and IgG than the control group over the same period after treatment (P<0.05). Side effects were few and mild in both groups. Conclusion:In treating patients of Qi-Yin deficiency type pSS, Shashen Maidongtang plus total glucosides of paeony capsule was proven to be effective generally. It could significantly inhibit excessive inflammation and hyperhumoral immunity in patients, and control their disease activity. This may be related to the effect of Shashen Maidong decoction and its decomposed recipes in correcting body fluid infusion and metabolic disorder in patients of Qi-Yin deficiency type pSS.