Triacanthine enhances the sensitivity of colorectal cancer cells to 5-fluorouracil by regulating RRM2.

BACKGROUND: According to the literatures, triacanthine is isolated from the leaves of Gleditsia triacanthos L. and acts as an anti-hypertensive agent, also cardiotonic, antispasmodic and a respiratory analeptic. The 5-fluorouracil (5-FU) is widely used to treat the patients of colorectal cancer (CRC), but the resistance to 5-FU treatment restricts the therapeutic efficacy of CRC patients. PURPOSE: This study aims to explore a novel therapeutics regimen overcoming CRC resistance to 5-FU. METHODS: The cell proliferation of CRC cells was determined by SRB and colony formation assay. Transwell and wound-healing assay were applied to explore the potential metastatic abilities of CRC cells. qRT-PCR and Western blot were performed to evaluate the level of indicated mRNAs and proteins respectively. Xenograft assay was used to explore the anti-CRC effect of triacanthine. RESULTS: Triacanthine statistically restrained CRC proliferation both in vitro and in vivo. Triacanthine induced cell cycle G1/G0 phase arrest in CRC cells. Meanwhile, triacanthine also inhibited the migrative and invasive abilities of CRC cells. A Venn diagram was generated showing that O-6-Methylguanine-DNA Methyltransferase (MGMT) might be a molecular target of triacanthine in treating CRC. Furthermore, triacanthine plus 5-FU significantly suppressed the cell proliferation of CRC cells compared with single agent treatment alone, and highly synergistic anti-cancer effects were scored when 5-FU was combined with triacanthine in CRC cells. In addition, triacanthine sensitized the anti-cancer activity of 5-FU via regulating Ribonucleotide Reductase Regulatory Subunit M2 (RRM2). MGMT or RRM2 might be novel biomarkers for evaluating the therapeutical efficiency of 5-FU in CRC patients. CONCLUSION: We firstly demonstrated triacanthine suppressed cell proliferation and metastasis abilities and found the novel molecular targets of triacanthine in CRC cells. This is the first study to evaluate the anti-cancer efficiency of triacanthine plus 5-FU. Our study has revealed triacanthine as a pertinent sensitizer to 5-FU, and provided novel strategies for predicting outcomes and reversing resistance of 5-FU therapy.

Recent Advances in Folates and Autoantibodies against Folate Receptors in Early Pregnancy and Miscarriage.

Though firstly identified in cerebral folate deficiency, autoantibodies against folate receptors (FRAbs) have been implicated in pregnancy complications such as miscarriage; however, the underlying mechanism needs to be further elaborated. FRAbs can be produced via sensitization mediated by folate-binding protein as well as gene mutation, aberrant modulation, or degradation of folate receptors (FRs). FRAbs may interfere with folate internalization and metabolism through blocking or binding with FRs. Interestingly, different types of FRs are expressed on trophoblast cells, decidual epithelium or stroma, and macrophages at the maternal-fetal interface, implying FRAbs may be involved in the critical events necessary for a successful pregnancy. Thus, we propose that FRAbs may disturb pregnancy establishment and maintenance by modulating trophoblastic biofunctions, placental development, decidualization, and decidua homeostasis as well as the functions of FOLR2+ macrophages. In light of these findings, FRAbs may be a critical factor in pathological pregnancy, and deserve careful consideration in therapies involving folic acid supplementation for pregnancy complications.

TNF-α promotes CXCL-1/8 production in keratinocytes by downregulating galectin-3 through NF-κB and hsa-miR-27a-3p pathway to contribute psoriasis development.

OBJECTIVE: Treatment with TNF-α inhibitors improve psoriasis with minimize/minor neutrophils infiltration and CXCL-1/8 expression in psoriatic lesions. However, the fine mechanism of TNF-α initiating psoriatic inflammation by tuning keratinocytes is unclear. Our previous research identified the deficiency of intracellular galectin-3 was sufficient to promote psoriasis inflammation characterized by neutrophil accumulation. This study aims to investigate whether TNF-α participated in psoriasis development through dysregulating galectin-3 expression. METHODS: mRNA levels were assessed through quantitative real-time PCR. Flow cytometry was used to detect cell cycle/apoptosis. Western blot was used to evaluate the activation of the NF-κB signaling pathway. HE staining and immunochemistry were used to detect epidermal thickness and MPO expression, respectively. Specific small interfering RNA (siRNA) was used to knock down hsa-miR-27a-3p while plasmids transfection was used to overexpress galectin-3. Further, the multiMiR R package was utilized to predict microRNA-target interaction. RESULTS AND DISCUSSION: We found that TNF-α stimulation altered cell proliferation and differentiation and promoted the production of psoriasis-related inflammatory mediators along with the inhibition of galectin-3 expression in keratinocytes. Supplement of galectin-3 could counteract the rise of CXCL-1/8 but not the other phenotypes of keratinocytes induced by TNF-α. Mechanistically, inhibition of the NF-κB signaling pathway could counteract the decrease of galectin-3 and the increase of hsa-miR-27a-3p expression whereas silence of hsa-miR-27a-3p could counteract the decrease of galectin-3 expression induced by TNF-α treatment in keratinocytes. Intradermal injection of murine anti-CXCL-2 antibody greatly alleviated imiquimod-induced psoriasis-like dermatitis. CONCLUSION: TNF-α initiates psoriatic inflammation by increasing CXCL-1/8 in keratinocytes mediated by the axis of NF-κB-hsa-miR-27a-3p-galectin-3 pathway.

[Effect of Shugan Tiaoshen acupuncture combined with western medication on depression-insomnia comorbidity due to COVID-19 quarantine: a multi-central randomized controlled trial].

OBJECTIVE: To observe the effect of Shugan Tiaoshen acupuncture (acupuncture for soothing the liver and regulating the mentality) combined with western medication on depression and sleep quality in the patients with depression-insomnia comorbidity due to COVID-19 quarantine, and investigate the potential mechanism from the perspective of cortical excitability. METHODS: Sixty patients with depression-insomnia comorbidity due to COVID-19 quarantine were randomly divided into an acupuncture group and a sham-acupuncture group, 30 cases in each one. The patients of both groups were treated with oral administration of sertraline hydrochloride tablets. In the acupuncture group, Shugan Tiaoshen acupuncture was supplemented. Body acupuncture was applied to Yintang (GV 24+), Baihui (GV 20), Hegu (LI 4), Zhaohai (KI 6), Qihai (CV 6), etc. The intradermal needling was used at Xin (CO15), Gan (CO12) and Shen (CO10). In the sham-acupuncture group, the sham-acupuncture was given at the same points as the acupuncture group. The compensatory treatment was provided at the end of follow-up for the patients in the sham-acupuncture group. In both groups, the treatment was given once every two days, 3 times a week, for consecutive 8 weeks. The self-rating depression scale (SDS) and insomnia severity index (ISI) scores were compared between the two groups before and after treatment and 1 month after the end of treatment (follow-up) separately. The cortical excitability indexes (resting motor threshold [rMT], motor evoked potential amplitude [MEP-A], cortical resting period [CSP]) and the level of serum 5-hydroxytryptamine (5-HT) were measured before and after treatment in the two groups. RESULTS: After treatment and in follow-up, SDS and ISI scores were decreased in both groups compared with those before treatment (P<0.05), and the scores in the acupuncture group were lower than those in the sham-acupuncture group (P<0.05), and the decrease range in the acupuncture group after treatment was larger than that in the sham-acupuncture group (P<0.05). After treatment, rMT was reduced (P<0.05), while MEP-A and CSP were increased (P<0.05) in the acupuncture group compared with that before treatment. The levels of serum 5-HT in both groups were increased compared with those before treatment (P<0.05). The rMT in the acupuncture group was lower than that in the sham-acupuncture group, while MEP-A and CSP, as well as the level of serum 5-HT were higher in the acupuncture group in comparison with the sham-acupuncture group (P<0.05). CONCLUSION: Shugan Tiaoshen acupuncture combined with western medication can relieve depression and improve sleep quality in the patients with depression-insomnia comorbidity due to COVID-19 quarantine, which is probably related to rectifying the imbalanced excitatory and inhibitory neuronal functions.

Component identification and analysis in vivo of Sanhan Huashi formula / 中国中药杂志

Sanhan Huashi formula(SHF) is the intermediate of a newly approved traditional Chinese medicine(TCM) Sanhan Huashi Granules for the treatment of COVID-19 infection. The chemical composition of SHF is complex since it contains 20 single herbal medicines. In this study, UHPLC-Orbitrap Exploris 240 was used to identify the chemical components in SHF and in rat plasma, lung and feces after oral administration of SHF, and heat map was plotted for characterizing the distribution of the chemical components. Chromatographic separation was conducted on a Waters ACQUITY UPLC BEH C_(18)(2.1 mm×100 mm, 1.7 μm) using 0.1% formic acid(A)-acetonitrile(B) as mobile phases in a gradient elution. Electrospray ionization(ESI) source was used to acquire data in positive and negative mode. By reference to quasi-molecular ions and MS/MS fragment ions and in combination with MS spectra of reference substances and compound information in literature reports, 80 components were identified in SHF, including 14 flavonoids, 13 coumarins, 5 lignans, 12 amino-compounds, 6 terpenes and 30 other compounds; 40 chemical components were identified in rat plasma, 27 in lung and 56 in feces. Component identification and characterization of SHF in vitro and in vivo lay foundations for disclosure of its pharmacodynamic substances and elucidation of the scientific connotation.

Effect of Shugan Tiaoshen acupuncture combined with western medication on depression-insomnia comorbidity due to COVID-19 quarantine: a multi-central randomized controlled trial / 中国针灸

OBJECTIVE@#To observe the effect of Shugan Tiaoshen acupuncture (acupuncture for soothing the liver and regulating the mentality) combined with western medication on depression and sleep quality in the patients with depression-insomnia comorbidity due to COVID-19 quarantine, and investigate the potential mechanism from the perspective of cortical excitability.@*METHODS@#Sixty patients with depression-insomnia comorbidity due to COVID-19 quarantine were randomly divided into an acupuncture group and a sham-acupuncture group, 30 cases in each one. The patients of both groups were treated with oral administration of sertraline hydrochloride tablets. In the acupuncture group, Shugan Tiaoshen acupuncture was supplemented. Body acupuncture was applied to Yintang (GV 24+), Baihui (GV 20), Hegu (LI 4), Zhaohai (KI 6), Qihai (CV 6), etc. The intradermal needling was used at Xin (CO15), Gan (CO12) and Shen (CO10). In the sham-acupuncture group, the sham-acupuncture was given at the same points as the acupuncture group. The compensatory treatment was provided at the end of follow-up for the patients in the sham-acupuncture group. In both groups, the treatment was given once every two days, 3 times a week, for consecutive 8 weeks. The self-rating depression scale (SDS) and insomnia severity index (ISI) scores were compared between the two groups before and after treatment and 1 month after the end of treatment (follow-up) separately. The cortical excitability indexes (resting motor threshold [rMT], motor evoked potential amplitude [MEP-A], cortical resting period [CSP]) and the level of serum 5-hydroxytryptamine (5-HT) were measured before and after treatment in the two groups.@*RESULTS@#After treatment and in follow-up, SDS and ISI scores were decreased in both groups compared with those before treatment (P<0.05), and the scores in the acupuncture group were lower than those in the sham-acupuncture group (P<0.05), and the decrease range in the acupuncture group after treatment was larger than that in the sham-acupuncture group (P<0.05). After treatment, rMT was reduced (P<0.05), while MEP-A and CSP were increased (P<0.05) in the acupuncture group compared with that before treatment. The levels of serum 5-HT in both groups were increased compared with those before treatment (P<0.05). The rMT in the acupuncture group was lower than that in the sham-acupuncture group, while MEP-A and CSP, as well as the level of serum 5-HT were higher in the acupuncture group in comparison with the sham-acupuncture group (P<0.05).@*CONCLUSION@#Shugan Tiaoshen acupuncture combined with western medication can relieve depression and improve sleep quality in the patients with depression-insomnia comorbidity due to COVID-19 quarantine, which is probably related to rectifying the imbalanced excitatory and inhibitory neuronal functions.

Contribution to the knowledge of the genus Agalope Walker from mainland China, with descriptions of four new species (Lepidoptera, Zygaenidae, Chalcosiinae).

New information of the genus Agalope Walker, 1854 from mainland China is presented. Three new species of the Agalope pica species-group are described: A. haoi S.-Y. Huang sp. n. from Weixi County, Yunnan, A. chayuensis S.-Y. Huang Pan sp. n. from Chayu County, Southeastern Xizang and A. owadai S.-Y. Huang sp. n. from Bomi and Jiali Counties, Southeastern and Eastern Xizang. The little-known Agalope aurelia Oberthr, 1923 and A. lucia Oberthr, 1923 were rediscovered, with the male of the latter reported for the first time. Based on the newly discovered male, Agalope lucia is found to be a close relative of A. dejeani, hence it is excluded from the A. pica species-group and transferred to the A. bieti species-group. A new species of the Agalope hyalina species-group is also described: A. jianqingi S.-Y. Huang sp. n. from Pianma, Western Yunnan. Adults and genitalia of the aforementioned and related taxa are illustrated. An updated checklist of the genus is also provided.

Evaluation of the potential of ultrasound-mediated drug delivery for the treatment of ovarian cancer through preclinical studies.

Ovarian cancer (OC) has the greatest mortality rate among gynecological cancers, with a five-year survival rate of <50%. Contemporary adjuvant chemotherapy mostly fails in the case of OCs that are refractory, metastatic, recurrent, and drug-resistant. Emerging ultrasound (US)-mediated technologies show remarkable promise in overcoming these challenges. Absorption of US waves by the tissue results in the generation of heat due to its thermal effect causing increased diffusion of drugs from the carriers and triggering sonoporation by increasing the permeability of the cancer cells. Certain frequencies of US waves could also produce a cavitation effect on drug-filled microbubbles (MBs, phospholipid bilayers) thereby generating shear force and acoustic streaming that could assist drug release from the MBs, and promote the permeability of the cell membrane. A new class of nanoparticles that carry therapeutic agents and are guided by US contrast agents for precision delivery to the site of the ovarian tumor has been developed. Phase-shifting of nanoparticles by US sonication has also been engineered to enhance the drug delivery to the ovarian tumor site. These technologies have been used for targeting the ovarian cancer stem cells and protein moieties that are particularly elevated in OCs including luteinizing hormone-releasing hormone, folic acid receptor, and vascular endothelial growth factor. When compared to healthy ovarian tissue, the homeostatic parameters at the tissue microenvironment including pH, oxygen levels, and glucose metabolism differ significantly in ovarian tumors. US-based technologies have been developed to take advantage of these tumor-specific alterations for precision drug delivery. Preclinical efficacy of US-based targeting of currently used clinical chemotherapies presented in this review has the potential for rapid human translation, especially for formulations that use all substances that are deemed to be generally safe by the U.S. Food and Drug Administration.

Role of gut microbiota-derived branched-chain amino acids in the pathogenesis of Parkinson's disease: An animal study.

Neuroinflammation caused by the disorder of gut microbiota and its metabolites is associated with the pathogenesis of Parkinson's disease (PD). Thus, it is necessary to identify certain molecules derived from gut microbiota to verify whether they could become intervention targets for the treatment of PD. The branched-chain amino acids (BCAAs), as a common dietary supplement, could modulate brain function. Herein, we investigated the longitudinal shifts of microbial community in mice treated with rotenone for 0, 3 and 4 weeks by 16S rRNA gene sequencing to identify the microbial markers at different PD stages. Serum BCAAs were determined by gas chromatography-mass spectrometry. Then, rotenone-induced mice were given a high BCAA diet to evaluate the motor and non-motor functions, dopaminergic neuron loss, and inflammation levels. Using a PD mouse model, we discovered that during PD progression, the alterations of gut microbiota compositions led to the peripheral decrease of BCAAs. Based on the serum lipopolysaccharide binding protein concentrations and the levels of pro-inflammatory factors (including tumor necrosis factor-α, interleukin [IL]-1ß, and IL-6) in the colon and substantia nigra, we found that the high BCAA diet could attenuate the inflammatory levels in PD mice, and reverse motor and non-motor dysfunctions and dopaminergic neuron impairment. Together, our results emphasize the dynamic changes of gut microbiota and BCAA metabolism and propose a novel strategy for PD therapy: a high BCAA diet intervention could improve PD progression by regulating the levels of inflammation.

[CO2 laser moxibustion for endometriosis related pelvic pain of cold coagulation and blood stasis: a randomized controlled trial].

OBJECTIVE: To observe the clinical therapeutic effect of CO2 laser moxibustion on endometriosis related pelvic pain of cold coagulation and blood stasis. METHODS: A total of 76 patients with endometriosis related pelvic pain of cold coagulation and blood stasis were randomized into a laser moxibustion group and a sham laser moxibustion group, 38 cases in each group. In the laser moxibustion group, moxibustion was applied at bilateral Zigong (EX-CA 1) using CO2 laser moxibustion instrument. In the sham laser moxibustion group, the manipulation of moxibustion was same as the laser moxibustion group, without laser output. The treatment was given once every other day, 30 min each time, 3 times a week for 4 weeks in both groups. Before and after treatment and follow-up of 3 months after treatment, the scores of Gracely box scale (GBS) and visual analogue scale (VAS) were observed, the usage of non-steroidal anti-inflammatory drug for the duration of the treatment and the average days of taking drugs were recorded in both groups. RESULTS: Compared before treatment, the GBS and VAS scores were decreased after treatment and during follow-up in the laser moxibustion group (P<0.05), while those in the sham moxibustion group had no significant differences (P>0.05). Compared with the sham moxibustion group, the GBS and VAS scores were decreased after treatment and during follow-up (P<0.05), the cases and average days of taking drugs were less in the laser moxibustion group (P<0.05). CONCLUSION: CO2 laser moxibustion can improve the pain symptom in patients with endometriosis related pelvic pain of cold coagulation and blood stasis, and reduce the use of analgesic drugs.

CO2 laser moxibustion for endometriosis related pelvic pain of cold coagulation and blood stasis: a randomized controlled trial / 中国针灸

OBJECTIVE@#To observe the clinical therapeutic effect of CO2 laser moxibustion on endometriosis related pelvic pain of cold coagulation and blood stasis.@*METHODS@#A total of 76 patients with endometriosis related pelvic pain of cold coagulation and blood stasis were randomized into a laser moxibustion group and a sham laser moxibustion group, 38 cases in each group. In the laser moxibustion group, moxibustion was applied at bilateral Zigong (EX-CA 1) using CO2 laser moxibustion instrument. In the sham laser moxibustion group, the manipulation of moxibustion was same as the laser moxibustion group, without laser output. The treatment was given once every other day, 30 min each time, 3 times a week for 4 weeks in both groups. Before and after treatment and follow-up of 3 months after treatment, the scores of Gracely box scale (GBS) and visual analogue scale (VAS) were observed, the usage of non-steroidal anti-inflammatory drug for the duration of the treatment and the average days of taking drugs were recorded in both groups.@*RESULTS@#Compared before treatment, the GBS and VAS scores were decreased after treatment and during follow-up in the laser moxibustion group (P<0.05), while those in the sham moxibustion group had no significant differences (P>0.05). Compared with the sham moxibustion group, the GBS and VAS scores were decreased after treatment and during follow-up (P<0.05), the cases and average days of taking drugs were less in the laser moxibustion group (P<0.05).@*CONCLUSION@#CO2 laser moxibustion can improve the pain symptom in patients with endometriosis related pelvic pain of cold coagulation and blood stasis, and reduce the use of analgesic drugs.

Reporting quality of systematic reviews with moxibustion.

BACKGROUND: Moxibustion is one of the major interventions of Chinese medicine (CM). The systematic reviews (SRs) are essential references for evaluating the efficacy and safety of moxibustion interventions. This study aimed to assess the reporting quality of these SRs, particularly whether necessary information related to moxibustion was adequately reported. METHODS: Seven databases (including four English and three Chinese databases) were systematically searched for SRs of moxibustion that were published up to 31 December 2019. The primary analysis was to assess their reporting quality based on 27-item of the Preferred Reporting Items for SRs and Meta-Analyses (PRISMA) and 14-item of moxibustion-related information designed according to CM theory and the STandards for Reporting Interventions in Clinical Trials Of Moxibustion (STRICTOM). Descriptive statistics were also used to analyze their baseline characteristics. RESULTS: A total of 97 SRs of moxibustion were identified from 2011 to 2019. For 27-item of PRISMA, except item 5, 8, 16 and 23, the remaining 23 items had the reporting compliances higher than 55%, of which 2 items (item 20 and 26) were fully reporting (100%). However, for moxibustion-related information, 69.1% (67/97) SRs did not provide the specific type of moxibustion, 39.2% (38/97) lacked details regarding the materials, procedure and technique used for moxibustion, 67.0% (65/97) did not report the selection criteria of acupoints for moxibustion, 28.9% (28/97) did not provide the number or duration of treatment sessions, 69.1% (67/97) did not provide any information about safety evaluation, and 94.8% (92/97) SRs did not report the treatment environment. For 51 (55.4%) of 92 SRs that included meta-analysis, it was impossible to assess whether meta-analysis had been properly conducted due to inadequate reporting of moxibustion interventions. CONCLUSION: The reporting quality of SRs of moxibustion need further improvements in terms of adequate reporting of moxibustion interventions and of moxibustion-related rationales. Reporting guideline of "PRISMA extension for moxibustion interventions" should be developed thus to improve their quality.

PRISMA extension for moxibustion 2020: recommendations, explanation, and elaboration.

BACKGROUND: Moxibustion is a common intervention of Chinese medicine (CM). Systematic reviews (SRs) on moxibustion are increasing. Although the Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) statement provides guidelines for SRs, the quality of moxibustion-related SRs is still not satisfactory. In particular, descriptions of the interventions and the rationale for using moxibustion are insufficient. To address these inadequacies, the working group developed this PRISMA extension for reporting SRs of moxibustion (PRISMA-M 2020). METHODS: A group of CM clinical professionals, methodologists of SRs, reporting guideline developers, and journal editors developed this PRISMA-M 2020 through a comprehensive process that includes registration, literature review, consensus meetings, Delphi exercises for soliciting comments, and revision, resulting in this final draft. RESULTS: Seven of the 27 PRISMA checklist items, namely title (1), rationale (3), eligibility criteria (6), data item (11), additional analyses (16), study characteristics (18), and additional analysis (23), were extended, with specific reference to the application of moxibustion. Illustrative examples and explanations for each item are provided. CONCLUSION: The PRISMA-M 2020 will help improve the reporting quality of SRs with moxibustion. SYSTEMATIC REVIEW REGISTRATION: We have registered it on the EQUATOR (Enhancing the QUAlity and Transparency Of health Research) network, particularly under the item of PRISMA-TCM: http://www.equator-network.org/library/reporting-guidelines-under-development/reporting-guidelines-under-development-for-systematic-reviews/#65 .

Optimization of extraction of loquat flowers polyphenolics and its antioxidant and anti-polyphenol oxidase properties.

In this study, the conditions of extraction of loquat flowers polyphenolics were optimized through response surface methodology (RSM). Proper extraction conditions were: solid to liquid ratio 1 g per 50 mL and ethanol concentration 50% at 61°C for 9 min. Furthermore, the antioxidant and anti-polyphenol oxidase (PPO) activity of purified total polyphenolics (PTP) were investigated. PTP displayed strong antioxidant activity with IC50 values of 126.3 ± 8.9, 162.4 ± 6.3 and 94.97 mg ascorbic acid equivalent/g dry weight (mg AAE/d.w.) for ABTS, DPPH, and FRAP assays. In addition, PTP has a substantial inhibitory activity on PPO (IC50 = 115 ± 9.2 µg/mL). From the kinetics analysis, it was proved to be a reversible and mixed-type inhibitor of PPO with KI and KIS values of 76.77 µg/mL and 227.86 µg/mL, respectively. Further, the molecular mechanism underlying the inhibition of PPO by PTP was investigated by molecular docking techniques. The results showed that PTP units could form interaction with the catalytic pocket of PPO through the interaction with amino acid residues in the enzyme active center. The antioxidant activities of PTP together with its effect on PPO activity provide a strong starting point for their practical usage in the food industry.

Reporting quality of Cochrane systematic reviews with Chinese herbal medicines.

BACKGROUND: Chinese herbal medicines (CHMs) are the major interventions of traditional Chinese medicine (TCM), which are typically administered as either single herbs or formulas. The Cochrane systematic reviews (SRs) of CHMs are essential references for evaluating the efficacy and safety of CHMs interventions; they are expected to be accurate and reliable. This study aimed to assess the reporting quality of these SRs, particularly whether necessary information related to CHM was adequately reported. METHODS: The Cochrane Database was systematically searched for all SRs of CHM that were published up to 31 December 2017. The primary analysis was to assess their reporting quality based on 27-item of the Preferred Reporting Items for Systematic reviews and Meta-Analyses (PRISMA) and 9-item of CHM-related information designed according to TCM theory. Descriptive statistics were additionally used to analyze their baseline characteristics. RESULTS: A total of 109 Cochrane SRs of CHM were identified from 1999 to 2017. For 27-item of PRISMA, 26 had the reporting compliances higher than 50%, of which 11 were fully reporting (100%). However, for CHM-related information, 65 (59.6%) SRs did not report the specific name of the CHM in the title, 42 (38.5%) lacked TCM-related rationales in the introduction, 62 (56.9%) did not include CHM-related characteristics in the additional analyses, and 77 (70.6%) did not analyze CHM results in terms of TCM-related theories in the discussion. Of 97 SRs that included clinical trials, 38 (39.2%) did not provide the details of composition and dosage of CHMs, 85 (87.6%) did not report the CHM sources, 13 (13.4%) did not provide the dosage form, 95 (97.9%) lacked CHM quality control information, and 57 (58.8%) did not describe details of the controls. For 62 (72.9%) of 85 SRs that included meta-analysis, it was impossible to assess whether meta-analysis had been properly conducted due to inadequate reporting of CHM interventions. CONCLUSION: Although the Cochrane SRs of CHM showed reporting compliance with PRISMA checklist, their reporting quality needs improvement, especially about full reporting of CHM interventions and of TCM-related rationales. Reporting guideline of "PRISMA extension for CHM interventions" should be developed thus to improve their quality.

Consumption Patterns and Importance-Performance Analysis of Home Meal Replacements by Level of Taurine-Related Nutritional Knowledge in Korean Adults.

The purpose of this study was to investigate consumption patterns and perform Importance-Performance Analysis (IPA) of selective attributes of Home Meal Replacement (HMR) products according to taurine-related nutritional knowledge levels in Koreans aged 40-64 years as a basis for developing additional HMR products. The study included 793 adults (297 males and 496 females) who had experience in consuming HMR products and who lived in Seoul and its metropolitan areas, Korea. Data were collected using self-administered questionnaires. Statistical analysis was performed by using the SPSS 18.0 program. The subjects were classified into a high-level group (HG, 467 adults) and low-level group (LG, 326 adults) based on their taurine-related nutritional knowledge scores. Analysis of HMR consumption patterns showed that the frequency of HMR consumption in the HG was one to two times a month in 41.1% of the subjects and once every 3-4 months in 22.7% of the subjects, whereas, in the LG, it was one to two times a month in 39.3% of the subjects and four to six times a month in 24.5% of the subjects. With regarding to the reasons for purchasing HMR products, there was no significant difference between HG and LG (p = 0.089). The IPA analysis of HMR selective attributes included factor analysis of 14 selective attributes that were divided into three factors: 'convenience and taste', 'reliability and health', and 'brand and awareness'. The average importance scores of the first (p < 0.01), second (p < 0.001), and third (p < 0.01) factors in the HG were significantly higher than those in the LG. In addition, the average satisfaction with the first factor (p < 0.01) in the HG was significantly higher than that in the LG. Based on the IPA results, the selective attributes with low satisfaction and high importance were price, origin, food additives, and nutrient content in both the HG and LG. In the second IPA quadrant was safety, but only in the LG. Multiple regression analysis revealed that the importance of the reliability and health factor and the satisfaction with the convenience and taste factor were positively influenced by the subject's taurine-related nutritional knowledge score. These results suggest that reliability and safety of HMR products need to be improved to meet the expectations of Korean consumers aged 40 years and older with a high level of taurine-related nutritional knowledge. Therefore, there is a need to produce HMR products that use safe and reliable food ingredients.

Transcriptomic analysis of de novo folate biosynthetic genes in Lactobacillus plantarum strain 4_3 in fermented soybean.

Folate is an important intermediate in cellular metabolism. However, because of a lack of key enzymes in the folate biosynthetic pathway, humans require supplementation with dietary folate. Some Lactobacillus plantarum strains have the ability to produce folate. To gain a better understanding of the folate biosynthetic pathway in the L. plantarum strain 4_3, which generates high folate yields, L. plantarum strain 4_3 was grown in folic acid casei medium (FACM) and fermented soybean, after obtaining a draft genome sequence. The pH values and folate yields were monitored during culturing, as were the transcriptomic profiles of cultured bacteria. The folate content increased for 12 h and then decreased before increasing again. All the genes involved in the de novo biosynthesis of folate were detected in both the genomic and transcriptomic data. The upregulation of the para-aminobenzoate biosynthesis pathway could explain the folate production in fermented soybean. Soybeans are a good substrate for the production of functional foods because of their well-suited cultivation and nutritional quality. The results of this study provide a good explanation for the high folate production observed during the fermentation of soybeans.

YY1 directly suppresses MYCT1 leading to laryngeal tumorigenesis and progress.

YY1 is a key transcription factor and plays different roles in various cancers. However, role and mechanism of YY1 in laryngeal cancer are still unknown. YY1 and MYCT1 mRNA and protein levels were detected by Real-time RT-PCR and Western Blot methods, respectively. Binding of YY1 to MYCT1 promoter was predicted and confirmed by bioinformatics and chromatin immunoprecipitation assays, respectively. MYCT1 promoter activity was assessed by dual luciferase assay system. Laryngeal cancer cell proliferation, migration, and apoptosis were evaluated by cell viability, colony formation, cell scratch assay, transwell assay, and flow cytometry methods, respectively. YY1 and MYCT1 were upregulated and downregulated at transcriptional level in laryngeal cancer, respectively, which showed a negative correlation between YY1 and MYCT1 expression in laryngeal cancer. Significantly higher expression of YY1 and lower expression of MYCT1 were found in laryngeal cancer tissues of patients with lymphatic metastasis than those without metastasis.YY1 directly bound to MYCT1 promoter region and inhibited its promoter activity. YY1 silence had similar biological functions as MYCT1 overexpression in repressiveness of proliferation and migration, and promotion of apoptosis in laryngeal cancer cells. However, the effects of YY1 silence were recovered by MYCT1 knockdown. YY1 promotes proliferation and migration with suppression of apoptosis via directly inhibiting MYCT1 in laryngeal cancer cells, suggesting that YY1 is a useful target as a potential oncogene in laryngeal cancer development and progression.

Agglutinin isolated from Arisema heterophyllum Blume induces apoptosis and autophagy in A549 cells through inhibiting PI3K/Akt pathway and inducing ER stress / 中国天然药物

Arisaema heterophyllum Blume is one of the three medicinal plants known as traditional Chinese medicine Rhizoma Arisaematis (RA). RA has been popularly used to treat patients with convulsions, inflammation, and cancer for a long time. However, the underlying mechanisms for RA effects are still unclear. The present study was designed to determine the cytotoxicity of agglutinin isolated from Arisema heterophyllum Blume (AHA) and explore the possible mechanisms in human non-small-cell lung cancer A549 cells. AHA with purity up to 95% was isolated and purified from Arisaema heterophyllum Blume using hydrophobic interaction chromatography. AHA dose-dependently inhibited the proliferation of A549 cells and induced G phase cell cycle arrest. AHA induced apoptosis by up-regulating pro-apoptotic Bax, decreasing anti-apoptotic Bcl-2, and activating caspase-9 and caspase-3. In A549 cells treated with AHA, the PI3K/Akt pathway was inhibited. Furthermore, AHA induced increase in the levels of ER stress markers such as phosphorylated eukaryotic initiation factor 2α (p-eIF2α), C/EBP-homologous protein (CHOP), inositol-requiring enzyme 1α (IRE1α), and phosphorylated c-Jun NH-terminal kinase (p-JNK). AHA also induced autophagy in A549 cells. Staining of acidic vesicular organelles (AVOs) and increase in the levels of LC3II and ATG7 were observed in AHA-treated cells. These findings suggested that AHA might be one of the active components with anti-cancer effects in Arisaema heterophyllum Blume. In conclusion, cytotoxicity of AHA on cancer cells might be related to its effects on apoptosis and autophagy through inhibition of PI3K/Akt pathway and induction of ER stress.