Efficacy and Safety of Jiawei Suanzaoren Decoction Combined with Lorazepam for Chronic Insomnia: A Parallel-Group Randomized Controlled Trial.

BACKGROUND: Chronic insomnia is a major public health problem, but there are limited effective therapies. Jiawei Suanzaoren Decoction (JW-SZRD) has been used as an alternative option for treating insomnia. This study aimed to investigate the long-term efficacy and safety of JW-SZRD in combination with lorazepam for chronic insomnia. METHODS: A total of 207 participants were analyzed in this study. The treatment group (TG) received JW-SZRD and lorazepam orally, and the control group (CG) received lorazepam alone. The Insomnia Severity Index (ISI), the Self-Rating Depression Scale (SDS), the Self-Rating Anxiety Scale (SAS), and the Somatic Self-rating Scale (SSS) were evaluated at baseline, weeks 4, 8, and 12. The MOS 36-item Short Form Health Survey (SF-36) was assessed at baseline and week 12. Adverse effects (AEs) were evaluated by the Treatment Emergent Symptom Scale (TESS). RESULTS: Both TG and CG showed obvious improvements in the sleep onset latency (SOL) (P=0.001 and 0.005) and total sleep time (TST) (P=0.001 and 0.005) and total sleep time (TST) (P=0.001 and 0.005) and total sleep time (TST) (P=0.001 and 0.005) and total sleep time (TST) (P=0.001 and 0.005) and total sleep time (TST) (P=0.001 and 0.005) and total sleep time (TST) (d = 1.28). The ISI reduction rate in TG was higher than that in CG at weeks 4, 8, and 12 (P=0.001 and 0.005) and total sleep time (TST) (P=0.001 and 0.005) and total sleep time (TST) (P=0.001 and 0.005) and total sleep time (TST) (P=0.001 and 0.005) and total sleep time (TST) (P=0.001 and 0.005) and total sleep time (TST) (P=0.001 and 0.005) and total sleep time (TST) (. CONCLUSION: The combination of JW-SZRD with lorazepam can significantly improve sleep quality with fewer AEs. It is an effective treatment and superior to lorazepam alone for chronic insomnia.

[Protective effect of Wuzi Yanzong recipe on testicular germ cell apoptosis in natural ageing rats through endoplasmic reticulum stress].

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-eif2α, 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-eif2α, 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.

[Protective effect of Wuzi Yanzong recipe on testicular DNA oxidative damage in natural ageing rats].

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.

Omega-3 polyunsaturated fatty acids and reduction of depressive symptoms in older adults: A systematic review and meta-analysis.

OBJECTIVE: The aim of this study is to systematically review the efficacy of omega-3 polyunsaturated fatty acid (n-3 PUFA) supplements in reducing depressive symptoms among older adults aged 60 and above. METHODS: Relevant electronic databases were searched from their inception to June 4, 2018, including Medline, Embase, Web of Science, Cochrane Library, PsycINFO, Global Health, CINAHL, ClinicalTrials.gov and Chinese Biomedical Medicine Database. Two reviewers independently screened for eligible studies, extracted data, and assessed risk of bias of the included studies. The effect size data were analyzed using robust variance estimation in meta-regression. RESULTS: Nine studies were included. The overall treatment effects of n-3 PUFA supplements in reducing depressive symptoms for older adults was not statistically significant (d = -0.202, 95% CI = -0.463, 0.060). Meta-regression found interventions with dosage of n-3 PUFA greater than 1.5 g/d had an average effect size of -0.428, with a 95% confidence interval of [-0.822, -0.035], which is statistically significant. Meta-regression did not find significant moderating effects of comorbidity, baseline depression, intervention duration, and EPA-DHA ratio, potentially due to limited statistical power. LIMITATIONS: The current review only included 9 studies based on literature search in major English and Chinese databases, which provided limited statistical power for moderator analysis and the results are suggestive only. CONCLUSIONS: The meta-analysis of 9 RCTs found mixed findings of the efficacy of n-3 PUFA in the treatment of depressive symptoms among older adults aged 60 and above. More high-quality, large-scale RCTs are needed to confirm the current conclusions.

Protective effect of Wuzi Yanzong recipe on testicular germ cell apoptosis in natural ageing rats through endoplasmic reticulum stress / 中国中药杂志

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.

Cantharidin and norcantharidin inhibit the ability of MCF-7 cells to adhere to platelets via protein kinase C pathway-dependent downregulation of α2 integrin.

Cancer metastasis is a highly coordinated and dynamic multistep process in which cancer cells interact with a variety of host cells. Morphological studies have documented the association of circulating tumor cells with host platelets, where a surface coating of platelets protects tumor cells from mechanical trauma and the immune system. Cantharidin is an active constituent of mylabris, a traditional Chinese medicine. Cantharidin and norcantharidin are potent protein phosphatase 2A (PP2A) inhibitors that exhibit in vitro and in vivo antitumor activity against several types of cancer, including breast cancer. We investigated whether cantharidin and norcantharidin could repress the ability of MCF-7 breast cancer cells to adhere to platelets. Using MTT, clone formation, apoptosis, adhesion and wound-healing assays, we found that cantharidin and norcantharidin induced apoptosis and repressed MCF-7 cell growth, adhesion and migration. Moreover, we developed a flow cytometry-based analysis of tumor cell adhesion to platelets. We proved that cantharidin and norcantharidin repressed MCF-7 cell adhesion to platelets through downregulation of α2 integrin, an adhesion molecule present on the surface of cancer cells. The repression of α2 integrin expression was found to be executed through the protein kinase C pathway, the activation of which could have been due to PP2A inhibition.

Synergistic effects of biotic and abiotic elicitors on the production of tanshinones in Salvia miltiorrhiza hairy root culture / 中国中药杂志

<p><b>OBJECTIVE</b>To investigate the synergistic effects of a biotic elicitor yeast extract and different abiotic elicitors (Ag+, Co2+ and alpha-amino isobutyric acid) on the production of tanshinones in Salvia miltiorrhiza hairy root.</p><p><b>METHOD</b>Different elicitors and their combinations were added to S. miltiorrhiza hairy root culture and the contents of three major tanshinones (crypotanshinone, tanshinone I and tanshinone II A) were analyzed by HPLC.</p><p><b>RESULT</b>The combinations of yeast extract with different abiotic elicitors had notable synergistic effects on the tanshinone I and tanshinone II A production but not on crypotanshinone. The combination of yeast extract and Ag+ (300 micromol x L(-1)) yielded the highest tanshinone I content, which was nearly 14-fold of the control, and the synergistic elicitation coefficient was 3.0. The combination of yeast extract and Co2+ (100 micromol L(-1)) led to the highest tanshinone IIA content, which was about 14.5-fold of the control, and the synergistic elicitation coefficient was 2.1. Only yeast extract combined with alpha-amino isobutyric acid (200 micromol x L(-1)) increased the crypotanshinone content more effectively than single elicitors. The highest crypotanshinone content was 1.28 mg x g(-1), about 30-fold of the control with a synergistic elicitation coefficient of 1.3.</p><p><b>CONCLUSION</b>The elicitation by the combination of a biotic elicitor and an abiotic elicitor can generate a synergistic effect, which is more effective than single elicitors to promote secondary metabolite production in plant tissue cultures.</p>