Morusin inhibits breast cancer-induced osteolysis by decreasing phosphatidylinositol 3-kinase (PI3K)-mTOR signalling.

Bone metastases caused by breast cancer pose a major challenge to the successful treatment of breast cancer patients. Many researchers have suggested that herbal medicines are extremely effective at preventing and treating cancer-associated osteolysis. Previous studies have revealed that Morusin (MOR) is cytotoxic to many cancer cells ex vivo. Nevertheless, how MOR contributes to osteolysis induced by breast cancer is still unknown, and the potential mechanism of action against osteolysis is worthy of further study. The protective effect and molecular mechanism of MOR in inhibiting breast cancer cell-induced osteolysis were verified by experiments and network pharmacology. Cell function was assessed by cell proliferation, osteoclast (OC) formation, bone resorption, and phalloidin staining. Tumour growth was examined by micro-CT scanning in vivo. To identify potential MOR treatments, the active ingredient-target pathway of breast cancer was screened using network pharmacology and molecular docking approaches. This study is the first to report that MOR can prevent osteolysis induced by breast cancer cells. Specifically, our results revealed that MOR inhibits RANKL-induced osteoclastogenesis and restrains the proliferation, invasion and migration of MDA-MB-231 breast cells through restraining the PI3K/AKT/MTOR signalling pathway. Notably, MOR prevented bone loss caused by breast cancer cell-induced osteolysis in vivo, indicating that MOR inhibited the development of OCs and the resorption of bone, which are essential for cancer cell-associated bone distraction. This study showed that MOR treatment inhibited osteolysis induced by breast cancer in vivo. MOR inhibited OC differentiation and bone resorption ex vivo and in vivo and might be a potential drug candidate for treating breast cancer-induced osteolysis.

The application of demographic characteristics of Ectropis grisescens (Lepidoptera: Geometridae) in pest risk assessment of IPM.

Ectropis grisescens Warren is one of the most important pests of tea plants. In this study, data on the development, survival, and fecundity of E. grisescens were collected at 15, 22, and 32 °C and analyzed by using the age-stage, two-sex life table. At 15 °C, the duration of the preadult period of E. grisescens was significantly prolonged (81.06 days), with high mortality (69.0%), and the proportion of emerged female adults was extremely low (7.0%). At 32 °C, the preadult period was significantly shortened (29.12 days), with high preadult mortality (74.0%), and a low proportion of emerged female adults (15.0%). At 22 °C, with low preadult mortality (24.0%), and a high proportion of emerged female adults (26.0%). The overall effects of the shorter preadult duration, higher preadult survival rate, higher proportion of emerged female adults, higher fecundity (F = 350.88 eggs/♀), and higher net reproductive rate (R0 = 91.23 offspring/individual) at 22 °C resulted in the highest values of the intrinsic rate of increase (r = 0.1054 days-1) and finite rate of increase (λ = 1.1112 days-1). Computer simulation showed that E. grisescens populations can increase much faster at 22 °C than at 15 and 32 °C. The weighted population size and cumulative weighted insect-days provided the dynamics necessary for estimating the damage potential of E. grisescens in devising economical pest management programs. Our results demonstrate that populations of E. grisescens were able to develop at a broad range of temperatures and adapt to the high temperatures. These finding can be utilized to improve the management of E. grisescens.

In-situ growth of nitrogen-doped carbonized polymer dots on black phosphorus for electrochemical DNA biosensor of Escherichia coli O157: H7.

Sensitive and accurate detection technology for pathogenic bacteria is of great social and economic significance in foodborne disease and food safety. In this paper, a novel portable electrochemical DNA biosensor for the detection of specific DNA sequence of Escherichia coli (E. coli) O157: H7 was constructed. To enhance the performance of the electrochemical sensor, a functionalized nitrogen-doped carbonized polymer dots in-situ grown on few-layer black phosphorus (N-CPDs@FLBP) was synthesized and used as the modifier on the surface of screen-printed electrode. Combining gold nanoparticles as immobilization matrix and methylene blue as electrochemical indicator, the analytical performance of this electrochemical DNA biosensor was evaluated using standard complementary ssDNA sequence in the linear concentration range from 1.0 × 10-19 to 1.0 × 10-6 mol/L with a low detection limit as 3.33 × 10-20 mol/L (3 σ). Furthermore, the portable electrochemical DNA biosensor was proposed based on polymerase chain reaction amplification for the detection of the E. coli O157: H7 genomic DNA from chicken meat, which verified the feasibility for practical samples detection. The research has great theoretical and practical significance for the development of electrochemical biosensor of pathogenic bacteria.

Tongue squamous cell carcinoma resists hyperthermia treatment by promoting Id-1 expression mediated EMT.

Epithelial-mesenchymal transition (EMT) is a key initial step in the recurrence and metastasis of tongue squamous cell carcinoma (TSCC). Hyperthermia (HT) may reduce the rate of postoperative recurrence and distant metastasis by reversing the process of EMT of tumor cells, but the molecular mechanism is unclear. This study aims to investigate the role of inhibitor of differentiation/DNA binding-1 (Id-1) in HT mediated reversal of EMT of TSCC cells, and to provide a new approach for the treatment of TSCC using therapeutic gene targeting. After the combination of RNA interference with Id-1 and HT, the morphology of TSCC cells changed from spindle-like to pebble-like, and the arrangement of cells changed from loose and disorderly to compact and orderly. The silencing of Id-1 gene enhances the efficacy of HT by affecting the expression of EMT markers in TSCC cells. This study suggests that the Id-1 gene in TSCC cells can regulate transforming growth factor-beta 1, thereby affecting the expression of EMT markers, to achieve the effect of reducing HT.

[Role of ferroptosis in cerebellar injury of mice following lead exposure].

OBJECTIVE: To investigate the role of ferroptosis in cerebellar injury of mice following lead exposure. METHODS: A total of forty SPF C57 mice were randomly divided into control group, low-dose lead exposure group, middle-dose lead exposure group and high-dose lead exposure group, with 10 mice in each group. Mice in three lead exposure groups were given 0.25, 0.50, 1.00 g/L lead acetate through drinking water for twelve weeks respectively. Lead concentration was detected by inductively coupled plasma mass spectrometer. The motor function was detected by beam walking test and open field test. Pathological changes of cerebellum in mice were observed by H&E staining. Western blotting was used to detect the protein expression of transferrin receptor-1(TFR-1), ferroportin(FPN-1), solute carrier family 7 member 11(SLC7 A11), glutathione peroxidase 4(GPX4), NF-E2-related factor 2(Nrf2) and heme oxygenase-1(HO-1). RESULTS: The lead concentration in cerebellum of mice in low lead group, medium lead group and high lead group were(1.05±0.11), (1.21±0.10) and(1.48±0.1) µg/g, respectively, which were significantly higher than that in the control group. The time to traverse the beam in low lead group, medium lead group and high lead group was 1.34, 1.64 and 2.02 folds of that in control group, respectively. Open field test showed that the central residence time and standing times of mice in low lead group, medium lead group and high lead group were significantly lower than that in control. Purkinje cells in the cerebellum of mice exposed to different doses of lead showed irregular arrangement, small cell bodies and deep staining, especially in the high lead group. The relative levels of iron in low lead group, medium lead group and high lead group was 1.77, 2.29 and 3.77 folds of that in control group, respectively. The content of MDA in cerebellum of mice in three lead exposure groups increased significantly, while the GHS decreased significantly. Compared with the control group, the expression of TFR-1 protein increased significantly in the lead exposure group, while the expression of FPN-1 protein decreased significantly only in the medium lead group and high lead group, which was 60% and 50% of the control group. Compared with the control group, the expressions of oxidative stress regulatory proteins SLC7 A11 and GPX4 in medium lead group and high lead group decreased significantly. Lead exposure significantly decreased the expression of Nrf2 and HO-1 protein in cerebellum, especially in high lead group. CONCLUSION: In this experiment condition, lead may induce ferroptosis in cerebellum of mice, of which, Nrf2/HO-1 signaling pathway might be involved in, and then further result in motor dysfunction of mice.

Effectiveness and safety of 3 different traditional Chinese therapies for asthma in minors: A protocol for systematic review and network meta-analysis.

INTRODUCTION: Traditional Chinese medicine has been widely used in the treatment of asthma, but currently there has been no comprehensive evaluation on the efficacy and safety of different traditional Chinese medicine therapies, based on network meta-analysis (NMA). METHODS AND ANALYSIS: The retrieval strategy was strictly followed in the English databases PubMed, Embase, Cochrane Library, and Chinese databases: CNKI and Wanfang. The retrieval time was limited from the beginning of each database construction to September 12, 2020. Meanwhile, in order to prevent data missing, we compared the previous meta-analysis to determine the final inclusion results. The main indexes were Spirometry, the secondary indexes were Asthma Quality of Life Questionnaire and adverse events. Methodological quality of articles was assessed using the Cochrane Collaborative tool, and evidence quality was assessed using the Recommended Scoring, Development, and Evaluation tool. Completed The NMA using Stata statistical software (Version 14.0, Stata Corporation, College Station, TX). The Cochrane Collaboration's Tool was used to evaluate the methodological quality of articles, the Grading of Recommendations Assessment, Development, and Evaluation instrument was used to evaluate the quality of evidence. NMA was completed by using Stata Statistical Software (Version 14.0, Stata Corporation, College Station, TX). RESULTS: The study will rank 3 traditional Chinese medicine treatments for asthma. CONCLUSION: This study is the first time to use NMA to compare the efficacy and safety of traditional Chinese medicine for the treatment of asthma, which will provide ideas and methods for the clinical treatment for asthma. INPLASY REGISTRATION NUMBER: INPLASY202090052.

Outcomes for Hyperthermia Combined with Concurrent Radiochemotherapy for Patients with Cervical Cancer.

PURPOSE: To evaluate the effect of hyperthermia combined with concurrent radiochemotherapy (RCT) and treatment-related toxicity in patients with cervical cancer (CC) stage IB-IV. METHODS AND MATERIALS: This study was conducted between 2009 and 2013 in patients with International Federation of Gynecology and Obstetrics (FIGO) stage IB-IV CC. The patients were randomly assigned into 2 treatment groups: RCT and RCT plus hyperthermia (RCHT). Five-year survival, treatment-related toxicity, and other prognostic factors were evaluated. RESULTS: Three hundred seventy-three patients completed treatment and were analyzed by per-protocol (PP) analysis. The 5-year overall survival (OS) in the RCHT group (81.9%) was better than that in RCT group (72.3%), and the log-rank test showed a statistically significant difference between the 2 groups (P = .040). Univariate and multivariate Cox regression analysis for 5-year OS showed a statistically significant difference (P = .043, P = .045, respectively). The 5-year local relapse-free survival in RCHT (86.8%) was also better than that in RCT (82.7%), but the difference was not significant. Acute or late toxicity was not significantly different between the 2 groups. Advanced clinical stage (FIGO) and larger tumor size showed higher risk of death and a relatively poor prognosis in univariate and multivariate analysis. CONCLUSIONS: The study confirmed that hyperthermia combined with RCT yielded a better 5-year OS in CC. Acute and late toxicity was similar between the RCT and RCHT groups. Clinical stage (FIGO) and tumor size were independent prognostic factors in CC.

Research Progress on the Molecular Mechanisms of Toxicology of Ethanol-Aconitine Induced Arrhythmia / 法医学杂志

Aconitum is one of the most widely used Chinese herbal medicines, and aconitine is the major toxic component in it. Aconitine can induce a variety of arrhythmias, resulting in death. Acute ethanol consumption causes arrhythmia as well. Poisoning cases caused by aconitum medicinal liquor are frequently encountered in the practice of forensic medicine. The molecular mechanisms of myocardial toxicity of these two drugs have much in common, and both of them affect the sodium channel, calcium channel and potassium channel of myocardial cell membrane and so on. This paper analyzes and discusses the possible co-effects of ethanol-aconitine on cardiomyocyte channel proteins, by reviewing researches on the mechanism of cardiotoxicity of ethanol and aconitine in recent years, in order to provide ideas and references for the research on the molecular mechanism of arrhythmia caused by combined poisoning.

Synthesis, biological evaluation and molecular modeling of aloe-emodin derivatives as new acetylcholinesterase inhibitors.

A series of aloe-emodin derivatives were designed, synthesized and evaluated as acetylcholinesterase inhibitors. Most of the new prepared compounds showed remarkable acetylcholinesterase inhibitory activities. Among them, the compound 1-((4,5-dihydroxy-9,10-dioxo-9,10-dihydroanthracen-2-yl) methyl) pyridin-1-ium chloride (C3) which has a pyridinium substituent possessed the best inhibitory activity of acetylcholinesterase (IC(50)=0.09 µM). The docking study performed with AUTODOCK demonstrated that C3 could interact with the catalytic active site (CAS) and the peripheral anionic site (PAS) of acetylcholinesterase.

[Multi-central clinical evaluation of ginger-partitioned moxibustion for treatment of leukopenia induced by chemotherapy].

OBJECTIVE: To prove the therapeutic effect of ginger-partitioned moxibustion on leukopenia induced by chemotherapy and effect on life quality of the patient with tumor after chemotherapy. METHODS: Randomized, controlled, multi-central cooperative method was used and the patients confirmed to the enrolled criteria were divided in-to two groups. The test group were treated with ginger-partitioned moxibustion at Dazhui (GV 14), Geshu (BL 17), Pishu (BL 20), etc.; and the control group with oral administration of Chinese patent medicine. RESULTS: Out of the 221 cases confirmed to program analysis, 113 cases were in the test group and 108 cases in the control group. After 10 days, the cured rate and the effective rate were 84.1% and 66.4% in the test group and 35.2% and 33.3% in the control group, respectively, with very significant differences between the two groups (both P < 0.01); fifteen days later, the therapeutic effects in the two groups were maintained. The two methods could improve clinical symptoms, with the test group being better than the control group. Any adverse response was not found in the two groups, and the injuries of functions of the heart, lung and kidney induced by chemotherapy had some improvement. CONCLUSION: The therapeutic effect of ginger-partitioned moxibustion on luekopenia induced by chemotherapy is reliable and is better than oral administration of Chinese patent medicine, with a better duplication.

Multi-central clinical evaluation of ginger-partitioned moxibustion for treatment of leukopenia induced by chemotherapy / 中国针灸

<p><b>OBJECTIVE</b>To prove the therapeutic effect of ginger-partitioned moxibustion on leukopenia induced by chemotherapy and effect on life quality of the patient with tumor after chemotherapy.</p><p><b>METHODS</b>Randomized, controlled, multi-central cooperative method was used and the patients confirmed to the enrolled criteria were divided in-to two groups. The test group were treated with ginger-partitioned moxibustion at Dazhui (GV 14), Geshu (BL 17), Pishu (BL 20), etc.; and the control group with oral administration of Chinese patent medicine.</p><p><b>RESULTS</b>Out of the 221 cases confirmed to program analysis, 113 cases were in the test group and 108 cases in the control group. After 10 days, the cured rate and the effective rate were 84.1% and 66.4% in the test group and 35.2% and 33.3% in the control group, respectively, with very significant differences between the two groups (both P < 0.01); fifteen days later, the therapeutic effects in the two groups were maintained. The two methods could improve clinical symptoms, with the test group being better than the control group. Any adverse response was not found in the two groups, and the injuries of functions of the heart, lung and kidney induced by chemotherapy had some improvement.</p><p><b>CONCLUSION</b>The therapeutic effect of ginger-partitioned moxibustion on luekopenia induced by chemotherapy is reliable and is better than oral administration of Chinese patent medicine, with a better duplication.</p>

[Preventive and treatment effect of composite Rhodiolae on acute lung injury in patients with severe pulmonary hypertension during extracorporeal circulation].

OBJECTIVE: To investigate the possibility of early prevention and treatment of acute lung injury by using composite Rhodiolae (CR) in patients with severe pulmonary hypertension during extracorporeal circulation. METHODS: Seventy-six patients with severe pulmonary hypertension screened out by color 2D-Doppler ultrasonography were randomly divided into the treated group (n = 40) and the control group (n = 36). The general treatment for the two groups, including preoperational preparation, operational procedure and conventional drug therapy, was the same. To the treated group, CR was administered 4 g every day (half the dose in children) at 7-10 day before and 5-7 day after the operation. The life signs, pulmonary ventilation parameters, arterial blood gas analysis were monitored and blood levels of TXB2, 6-keto-PGF1 alpha in both groups were determined in the fixed time points. RESULTS: The various parameters in the treated group were all better than those in the control group (P < 0.05 or P < 0.01), the occurrence rate of acute lung injury and its mortality in the treated group were 7.5% (3/40) and 0% (0/3) respectively, while in the control group were 19.4% (7/36) and 43% (3/7) respectively. CONCLUSION: CR has good preventive and treatment effect in treating complicated acute lung injury during extracorporeal circulation (cardiopulmonary bypass) in patients with pulmonary hypertension.

Preventive and treatment effect of composite Rhodiolae on acute lung injury in patients with severe pulmonary hypertension during extracorporeal circulation / 中国中西医结合杂志

<p><b>OBJECTIVE</b>To investigate the possibility of early prevention and treatment of acute lung injury by using composite Rhodiolae (CR) in patients with severe pulmonary hypertension during extracorporeal circulation.</p><p><b>METHODS</b>Seventy-six patients with severe pulmonary hypertension screened out by color 2D-Doppler ultrasonography were randomly divided into the treated group (n = 40) and the control group (n = 36). The general treatment for the two groups, including preoperational preparation, operational procedure and conventional drug therapy, was the same. To the treated group, CR was administered 4 g every day (half the dose in children) at 7-10 day before and 5-7 day after the operation. The life signs, pulmonary ventilation parameters, arterial blood gas analysis were monitored and blood levels of TXB2, 6-keto-PGF1 alpha in both groups were determined in the fixed time points.</p><p><b>RESULTS</b>The various parameters in the treated group were all better than those in the control group (P < 0.05 or P < 0.01), the occurrence rate of acute lung injury and its mortality in the treated group were 7.5% (3/40) and 0% (0/3) respectively, while in the control group were 19.4% (7/36) and 43% (3/7) respectively.</p><p><b>CONCLUSION</b>CR has good preventive and treatment effect in treating complicated acute lung injury during extracorporeal circulation (cardiopulmonary bypass) in patients with pulmonary hypertension.</p>