Chemical Constituents from the Fruits of Amomum kravanh and Their Role in Activating Alcohol Dehydrogenase.

Alcoholism is a worldwide health problem, and diseases caused by alcoholism are killing people every year. Amomum kravanh is a traditional Chinese medicine used to relieve hangovers. However, whether its bioactive components improve alcohol metabolism is not clear. In this study, ten new (amomumols A-J, 1-10) and thirty-five known (11-45) compounds were isolated from the fruits of Amomum kravanh by an activity-guided separation. Ten novel compounds were identified as four sesquiterpenoids (1-4), three monoterpene derivatives (5-7), two neolignans (8, 9), and a novel norsesquiterpenoid (10) with a new C14 nor-bisabolane skeleton. Their structures were determined by the comprehensive analysis of high-resolution electrospray ionization mass spectrometry (HRESIMS), nuclear magnetic resonance (NMR), and electronic circular dichroism (ECD) calculation. The effects of all isolated compounds on the activity of alcohol dehydrogenase were evaluated in vitro, and it was found that eight compounds (11, 12, 15, 18, 26, and 36-38) exhibited significant activation effects on the alcohol dehydrogenase at 50 µM.

Identification of key pharmacological components and targets for Aidi injection in the treatment of pancreatic cancer by UPLC-MS, network pharmacology, and in vivo experiments.

BACKGROUND: Pancreatic cancer is one of the most lethal cancers worldwide. Aidi injection (ADI) is a representative antitumor medication based on Chinese herbal injection, but its antitumor mechanisms are still poorly understood. MATERIALS AND METHODS: In this work, the subcutaneous xenograft model of human pancreatic cancer cell line Panc-1 was established in nude mice to investigate the anticancer effect of ADI in vivo. We then determined the components of ADI using ultra-performance liquid chromatography-tandem mass spectrometry (UPLC-MS) and explored the possible molecular mechanisms against pancreatic cancer using network pharmacology. RESULTS: In vivo experiments, the volume, weight, and degree of histological abnormalities of implanted tumors were significantly lower in the medium and high concentration ADI injection groups than in the control group. Network pharmacology analysis identified four active components of ADI and seven key targets, TNF, VEGFA, HSP90AA1, MAPK14, CASP3, P53 and JUN. Molecular docking also revealed high affinity between the active components and the target proteins, including Astragaloside IV to P53 and VEGFA, Ginsenoside Rb1 to CASP3 and Formononetin to JUN. CONCLUSION: ADI could reduce the growth rate of tumor tissue and alleviate the structural abnormalities in tumor tissue. ADI is predicted to act on VEGFA, P53, CASP3, and JUN in ADI-mediated treatment of pancreatic cancer.

Lipid extract from blue mussel (Mytilus edulis) improves glycemic traits in Chinese type 2 diabetic mellitus patients: a double-blind randomized controlled trial.

BACKGROUND: Studies have shown that blue mussel lipid extract (BMLE) has strong anti-inflammatory activity in both rheumatoid arthritis patients and animal arthritis models. Chronic inflammation was closely related to type 2 diabetes mellitus (T2DM). Though the beneficial effects cannot be completely attributed to n-3 polyunsaturated fatty acids, the aim of this study was to investigate whether BMLE can improve glycemic traits of T2DM patients. METHOD: In a double-blind randomized controlled trial, 133 Chinese T2DM participants were randomized to either fish oil (FO, n = 44), BMLE (n = 44), or corn oil (CO, n = 45) groups for 60 days. The participants were asked to take the corresponding oil capsules (two capsules per day, 0.8 g per capsule), which provided 1.6 g day-1 of FO (29.9% eicosapentaenoic acid + 20.4% docosahexaenoic acid), BMLE (20.7% eicosapentaenoic acid + 26.7% docosahexaenoic acid), or CO (53.5% linoleic acid). RESULTS: The fasting serum concentration of insulin (P = 0.005) and the homeostasis model of insulin resistance (P = 0.026) were significantly decreased in the BMLE group, whereas no significant change was found in the FO or CO groups. There was no significant difference between groups on serum glycosylated hemoglobin. Tumor necrosis factor-α was significantly decreased in the BMLE group (P = 0.003), but not in the FO or CO groups. A significant decrease of interleukin-1ß was observed in the BMLE and CO groups (P = 0.004 and P = 0.011 respectively), but not in the FO group. The total cholesterol was significantly decreased in the BMLE and CO groups (P < 0.001 and P < 0.001 respectively), but not in the FO group. Triacylglycerol was significantly decreased in the BMLE group (P = 0.007), but not in the FO or CO groups. High-density lipoprotein cholesterol was significantly lower in the BMLE and CO groups than in the FO group (P = 0.003). CONCLUSION: Blue mussel lipid supplements improved glycemic traits, inflammatory cytokines, and lipids profile in Chinese T2DM patients (Chinese Clinical Trial Registration number: ChiCTR1900025617). © 2022 Society of Chemical Industry.

Gene-diet interaction in response to defatted flaxseed flour supplementation on obesity-related traits in Chinese overweight and obese adults: A randomized controlled trial.

Effects of dietary fiber on obesity-related traits in previous studies were inconsistent. The aim of the present study was to explore whether variants in genes related to satiety and appetite can modulate the effect of dietary fiber on obesity-related traits. Fifty-one overweight or obese adults were randomly allocated to two groups to consume control biscuits (n = 24) or biscuits containing defatted flaxseed flour (n = 27) at breakfast for 8 wk. Four single-nucleotide polymorphisms related to satiety and appetite were genotyped: rs11076023 on the FTO gene, rs16147 on the NPY gene, rs155971 on the PCSK1 gene, and rs6265 on the BDNF gene. A linear regression model was used to evaluate the gene-diet interaction between obesity-related traits. Compared with control biscuits, defatted flaxseed-flour biscuits significantly reduced body weight (P = 0.001) and body mass index (BMI) (P = 0.001) in A-allele carriers (AA + AT) of rs11076023 on the FTO gene but not in non-carriers (TT) (P for the interaction = 0.005 and 0.006) and decreased fasting serum glucose in participants with CC genotype (P = 0.019) but had less effect in T-allele carriers (TT + TC) (P = 0.021) of rs16147 on the NPY gene (P for the interaction = 0.002). Compared with the control biscuits, defatted flaxseed flour significantly reduced body weight (P < 0.001) in T-allele carriers (TT + TC) of rs155971 on the PCSK1 gene but not in non-carriers (CC) (P for the interaction = 0.041) and reduced body weight (P = 0.001) and BMI (P < 0.001) in A-allele carriers (AA + AG) of rs6265 on the BDNF gene but not non-carriers (GG) (P for the interaction = 0.017 and 0.018). Variants of genes related to satiety and appetite could modulate the effect of defatted flaxseed flour on obesity-related traits.

RNA binding protein IGF2BP1 meditates oxidative stress-induced granulosa cell dysfunction by regulating MDM2 mRNA stability in an m6A-dependent manner.

Both genetic and microenvironmental detrimental factors are involved in ovarian dysfunction, leading to the increasing rate of involuntary childlessness in recent years. Oxidative stress (OS), which is characterized by the imbalance of redox system with redundant reactive oxygen species (ROS) overwhelming the antioxidant defense, is regarded as one of the culprits of ovarian dysfunction. OS causes damage to various types of ovarian cells including granulosa cells (GCs), jeopardizing the ovarian microenvironment, disturbing follicular development and participating in various female reproductive disorders. However, the specific molecular pathological mechanisms underlying this process have not been fully elucidated. In this study, we found that 3-nitropropionic acid (3-NP) treatment led to significant IGF2BP1 downregulation via, at least partially, inducing ROS overproduction. IGF2BP1 regulates GCs viability, proliferation, cell cycle and cellular senescence by enhancing MDM2 mRNA stability in an m6A-dependant manner. IGF2BP1 overexpression partially rescued 3-NP induced GCs damages, while ectopically expressed MDM2 alleviated both 3-NP or IGF2BP1-knockdown induced GCs dysfunction. These results reveal an epigenetic molecular mechanism underlying OS-related GCs disorders, which may help to establish a novel potential clinical marker for predicting the GCs status as well as the follicular developmental potential.

Fructus ligustri lucidi suppresses inflammation and restores the microbiome profile in murine colitis models.

BACKGROUND: Ulcerative colitis (UC) is pathologically characterized by an inappropriate immune response to the gut commensal microbes accompanied by persistent epithelial barrier dysfunction, and its progression increases the susceptibility to colitis-associated cancer (CAC), as well as other complications. Fructus ligustri lucidi (FLL) has a long historical application in traditional Chinese medicine due to its various pharmacological effects, including antioxidation and anti-inflammation. The present study aimed to explore the molecular and cellular mechanisms of FLL in treating colitis. METHODS: A high-performance liquid chromatography (HPLC) combined with ultraviolet (UV) was performed to validate the quality of FLL; Network pharmacology analysis and weighted gene co-expression network analysis (WGCNA) based on The Cancer Genome Atlas (TCGA) database predicted the therapeutic value of FLL against UC and CAC; 2% dextran sodium sulfate (DSS) was administered to mice to establish murine models of experimental colitis, and FLL was given for the next 14 days at different concentrations; 16S rRNA sequencing and untargeted metabolomics were performed on fecal samples to delineate the alteration in microbiome profile; Western blotting, flow cytometry, and immunocytochemistry experiments were conducted to confirm the predicted cellular mechanisms. RESULTS: Network pharmacology analysis and WGCNA predicted that the targets of the FLL were associated with the progression of UC and the survival of patients with colorectal cancer by regulating tumor necrosis factor (TNF) and IL-17 signaling pathways, immune cell functions, responses to bacterial and reactive oxygen species (ROS), and cell proliferation. In vivo experiments corroborated that the high dose of FLL significantly attenuated the progression of experimental colitis by reversing the weight loss and bloody stool, reconstructing the integrity of colorectal epithelium, and suppressing the concentration of pro-inflammatory cytokines. Moreover, FLL treatment reduced the transition of macrophages (Mφs) to the proinflammatory phenotype and promoted Mφs-regulated wound healing, and suppressed the production of ROS in intestinal organoids (IOs) and crypts. 16S rRNA and untargeted metabolomics showed that the administration of FLL inhibited DSS-caused colonization of the potentially pathogenic gut microorganisms and reversed DSS-influenced metabolic profile. CONCLUSION: FLL is a potent anti-colitis drug by suppressing inflammation and rescuing dysbiosis.

Synergistic Effects of Folic Acid and n-3 Polyunsaturated Fatty Acid in Preventing Neural Tube Defects in Diabetic Mice.

The present study aimed to investigate whether a combination of folic acid (FA) and n-3 polyunsaturated fatty acids (PUFA) has a better preventive effect on maternal diabetes-induced neural tube defects (NTD) than FA alone. The experiment included five groups of pregnant mice: healthy control (HC), diabetes mellitus control (DMC), diabetes + n-3 PUFA (DMn-3), diabetes + FA (DMFA), and diabetes + FA + n-3 PUFA (DMFA + n-3). The incidence of NTD in DMFA + n-3 (1.04%) was significantly lower than that in DMFA (8.57%) and DMn-3 (7.82%). The incidence of NTD in DMFA and DMn-3 was significantly lower than that in DMC (19.41%). DMFA + n-3 had a lower apoptosis of neuroepithelial cells, a lower expression of P53 and Bax, and a higher expression of Pax3 and Bcl-2, compared with DMFA and DMn-3. Combination of FA and n-3 PUFA attenuated diabetes-induced hypermethylation of Pax3, overexpression and overactivity of Dnmt3b, abnormal expression of genes involved in one-carbon metabolism and elevation of homocysteine, and these improving effects were better than FA or n-3 PUFA alone. In conclusion, the combination of FA and n-3 PUFA has a synergistic effect on preventing maternal diabetes-induced NTD.

Bruceine A protects against diabetic kidney disease via inhibiting galectin-1.

Bruceine A is a natural quassinoid compound extracted from the fruit of the Traditional Chinese Medicine Brucea javanica (L.) Merr. that has various types of various biological activities. However, whether the compound has a protective effect on diabetic kidney disease remains unknown. Galectin-1 is actively involved in a variety of chronic inflammation-relevant human diseases including diabetic kidney disease. Here, we identified Bruceine A as a kidney protective molecule against a model of diabetic kidney disease in db/db mice with potent anti-inflammatory activity both in vitro and in vivo. Mechanistically, by selectively binding to the conserved carbohydrate-recognition domain of galectin-1 and disrupting the interaction between galectin-1 and the receptor for activated protein C kinase 1, Bruceine A was found to inhibit galectin-1-mediated inflammatory signal transduction under high glucose stress in rat mesangial HBZY-1 cells. Thus, our findings reveal Bruceine A as an unidentified galectin-1 inhibitor affording significant protection against diabetic kidney disease and may provide novel pharmacological therapeutics for the disease.

Baicalin suppresses the progression of Type 2 diabetes-induced liver tumor through regulating METTL3/m6A/HKDC1 axis and downstream p-JAK2/STAT1/clevaged Capase3 pathway.

BACKGROUND: Epidemiological and clinical evidence suggests that diabetes increases the risk of liver cancer. Although the co-occurrence of type 2 diabetes (T2D) and liver cancer is becoming more frequent, the underlying mechanisms remain unclear. Even though baicalin, extensively used in traditional Chinese medicine (TCM), can control T2D and inhibit liver cancer separately, minimal research is available regarding its possible effect on T2D-induced liver cancer. Thus, in the present study, we aimed to investigate the role of baicalin in T2D-induced hepatocellular cancer, and for the first time, we particularly emphasized the regulation of baicalin in genes RNA m6A in hepatocellular cancer. METHODS: Here, we constructed a cell culture model under a high concentration of glucose and a T2D-induced liver tumor model to evaluate the in vitro and in vivo role of baicalin in T2D-induced liver cancer progression. After confirming the suppressive effect of baicalin and the HKDC1 antibody on T2D-induced liver tumors, the epigenetic alterations (DNA 5mC and RNA m6A) of the baicalin-regulated HKDC1 gene were detected using MS and q-PCR. Next, the METTL3 gene-regulated m6A (2854 site) was investigated using SELECT PCR. Finally, the impact of the other three baicalin analogs (baicalein, wogonoside, and wogonin) on tumor inhibition was tested in vivo while verifying the related RNA m6A mechanism. RESULTS: The results showed that baicalin and the HKDC1 antibody suppressed T2D-induced liver tumor progression in vitro and in vivo. Furthermore, baicalin significantly inhibited the epigenetic modification (DNA 5mC and RNA m6A) of HKDC1 in HepG2 tumors, mainly targeting the RNA m6A site (2854). The m6A-related gene, METTL3, regulated the RNA m6A site (2854) of HKDC1, which was also restricted by baicalin. Moreover, the study verified that baicalin regulated the METTL3/HKDC1/JAK2/STAT1/caspase-3 pathway in liver cancer cells when exposed to a high glucose concentration. In addition, the three baicalin analogs were proven to regulate the m6A (2854 site) of HKDC1 and suppress T2D-induced liver tumors. CONCLUSIONS: The findings of this study revealed that baicalin suppressed T2D-induced liver tumor progression by regulating the METTL3/m6A/HKDC1 axis, which might support its potential application for preventing and treating T2D-induced liver cancer.

Acupuncture combined with Chinese herbal medicine on non-alcoholic fatty liver disease: A protocol for systematic review and meta-analysis.

BACKGROUND: Non-alcoholic fatty liver disease (NAFLD) is a global health burden. However, there are no approved drugs for NAFLD. A number of studies have shown that acupuncture combined with Chinese herbal medicine (CHM) can be beneficial for NAFLD. However, high-quality trials are still lacking. Therefore, we aimed to conduct a systematic review and meta-analysis to assess the effectiveness and safety of acupuncture combined with CHM for NAFLD. METHODS: Eight electronic databases including PubMed, the Cochrane Library, Web of Science, EMBASE, China National Knowledge Infrastructure, Chinese Scientific and Technical Journals Database, and Wan-fang Database from inception to November 2021 will be searched. We will also search for Clinical Trials Registry Platforms as a supplement. Randomized controlled trials on acupuncture combined with CHM for NAFLD will be included. Literature screening, data extraction, and risk of bias assessment were independently conducted by 2 reviewers. All differences between the 2 reviewers will be discussed and resolved by a third reviewer. Revman5.3 software will be used for meta-analysis. RESULT: This study aimed to evaluate the effectiveness and safety of acupuncture combined with CHM for NAFLD. CONCLUSION: The findings of this study will provide more evidence to determine whether acupuncture combined with CHM for NAFLD is an effective and safe intervention for NAFLD.

N-3 polyunsaturated fatty acids effectively protect against neural tube defects in diabetic mice induced by streptozotocin.

Folate cannot prevent all neural tube defects (NTD), indicating that other pathogeneses still exist except for the folate deficiency. Maternal diabetes mellitus during pregnancy can increase the risk of offspring NTD. Our previous study showed that polyunsaturated fatty acids (PUFA) were lower in the placenta of human NTD cases than in healthy controls, and the supplementation of fish oil (rich in long-chain (LC) n-3 PUFA, mainly C20:5n-3 and C22:6n-3) had a better prevention effect against sodium valproate induced NTD than corn oil (rich in C18:2n-6) and flaxseed oil (rich in C18:3n-3). The aim of the present study was to investigate whether PUFA could prevent diabetes-induced NTD in mice. Streptozotocin (STZ)-induced diabetic pregnant mice were fed with a normal diet (DMC), a diet containing a low dose of fish oil (DMLn-3), a diet containing a high dose of fish oil (DMHn-3) or a diet rich in corn oil (DMn-6). Healthy pregnant mice were fed with a normal diet (HC). Compared with the DMC group, the rate of NTD was significantly lower in the DMHn-3 group (4.44% vs. 12.50%), but not in the DMLn-3 (11.11%) or DMn-6 group (12.03%). The NTD rate in the DMHn-3 group was comparable with that in the HC group (1.33%) (p = 0.246), and lower than that in the DMn-6 group (p = 0.052). The NTD rate in DMLn-3 and DMn-6 groups was significantly higher than that in the HC group. No significant difference was observed in NTD rate between DMLn-3 and DMHn-3 groups, and between DMLn-3 and DMn-6 groups. Compared with the HC group, the DMC group had a significantly lower C22:6n-3 in both serum and embryos. Fish oil supplementation ameliorated neuroepithelial cell apoptosis, and the apoptotic rate was comparable between DMHn-3 and HC groups. Although the apoptotic rate was significantly lower in the DMn-6 group than the DMC group, it was still much higher than that in the HC group. The proteins P53 and Bax in embryos were higher, while the proteins Bcl-2 and Pax3 were lower in the DMC group than in the HC group. The disturbance of Pax3, P53 and Bax induced by diabetes was abolished in DMLn-3, DMHn-3 and DMn-6 groups. Importantly, Bcl-2 in embryos was restored to the normal level only in the DMHn-3 group but not in the DMLn-3 or DMn-6 group. In conclusion, LC n-3 PUFA enriched fish oil has a protective effect against NTD in diabetes induced by STZ through improving neuroepithelial cell apoptosis, and the mechanism may be by increasing the anti-apoptosis protein Bcl-2 independently of Pax3 and P53.

Selenium supplementation alleviates cadmium-induced damages in tall fescue through modulating antioxidant system, photosynthesis efficiency, and gene expression.

Selenium (Se) is beneficial for plant growth under different stressful conditions. In this study, we investigated the protective effects of Se supply from Cd-induced damages in tall fescue under Cd stress. Tall fescue seedlings (40 days old) were treated with Cd (30 mg/L, as CdSO4·8/3 H2O) and Se (0.1 mg/L, as Na2SeO3) individually and in combination using 1/2 Hoagland's solution system for 7 days. Various physiological parameters, photosynthetic behaviors, and gene expressions were measured. The results showed that Cd-stressed plants displayed obvious toxicity symptoms such as leaf yellowing, decreasing plant height, and root length. Cd stress significantly increased the malondialdehyde (MDA) content and electrolyte leakage (EL), and remarkably reduced the chlorophyll and soluble protein content, antioxidant enzyme activities, and photosynthetic efficiency. Cd stress significantly inhibited the expression of two photosynthesis-related genes (psbB and psbC), but not psbA. In addition, it significantly inhibited the expression of antioxidant system-related genes such as ChlCu/ZnSOD, CytCu/ZnSOD, GPX, and pAPX, but significantly increased the expression of GR. However, Se improved the overall physiological and photosynthetic behaviors of Cd-stressed plants. Se significantly enhanced the chlorophyll and soluble protein content and CAT and SOD activities, but decreased MDA contents, EL, and Cd content and translocation in tall fescue under Cd stress. Furthermore, under Cd stress, Se increased the expression of psbA, psbB psbC, ChlCu/ZnSOD, CytCu/ZnSOD, GPx, and PAPx. The result suggests that Se alleviated the deleterious effects of Cd and improved Cd resistance in tall fescue through upregulating the antioxidant system, photosynthesis activities, and gene expressions.

Porphyrin Production and Regulation in Cutaneous Propionibacteria.

Porphyrins are intermediate metabolites in the biosynthesis of vital molecules, including heme, cobalamin, and chlorophyll. Bacterial porphyrins are known to be proinflammatory, with high levels linked to inflammatory skin diseases. Propionibacterium species are dominant skin commensals and play essential roles in defending against pathogens and in triggering an inflammatory response. To better understand how the inflammatory potential of the skin microbiome may vary depending on its propionibacterial composition, we compared the production levels of porphyrins among Propionibacterium acnes, Propionibacterium granulosum, Propionibacterium avidum, and Propionibacterium humerusii strains. We found that porphyrin production varied among these species, with P. acnes type I strains producing significantly larger amounts of porphyrins than P. acnes type II and III strains and other Propionibacterium species. P. acnes strains that are highly associated with the common skin condition acne vulgaris responded to vitamin B12 supplementation with significantly higher porphyrin production. In contrast, vitamin B12 supplementation had no effect on the porphyrin production of health-associated P. acnes strains and other propionibacteria. We observed low-level porphyrin production in most Propionibacterium strains harboring the deoR repressor gene, with the exception of P. acnes strains belonging to type I clades IB-3 and IC. Our findings shed light on the proinflammatory potential of distinct phylogenetic lineages of P. acnes as well as other resident skin propionibacteria. We demonstrate that the overall species and strain composition is important in determining the metabolic output of the skin microbiome in health and disease.IMPORTANCE Porphyrins are a group of metabolites essential to the biosynthesis of heme, cobalamin, and chlorophyll in living organisms. Bacterial porphyrins can be proinflammatory, with high levels linked to human inflammatory diseases, including the common skin condition acne vulgaris. Propionibacteria are among the most abundant skin bacteria. Variations in propionibacteria composition on the skin may lead to different porphyrin levels and inflammatory potentials. This study characterized porphyrin production in all lineages of Propionibacterium acnes, the most dominant skin Propionibacterium, and other resident skin propionibacteria, including P. granulosum, P. avidum, and P. humerusii We revealed that P. acnes type I strains produced significantly more porphyrins than did type II and III strains and other Propionibacterium species. The findings from this study shed light on the proinflammatory potential of the skin microbiome and can be used to guide the development of effective acne treatments by modulating the skin microbiome and its metabolic activities.

Ouabain impairs cancer metabolism and activates AMPK-Src signaling pathway in human cancer cell lines.

In addition to the well-known cardiotonic effects, cardiac glycosides (CGs) produce potent anticancer effects with various molecular mechanisms. We previously show that ouabain induces autophagic cell death in human lung cancer cells by regulating AMPK-mediated mTOR and Src-mediated ERK1/2 signaling pathways. However, whether and how AMPK and Src signaling interacts in ouabain-treated cancer cells remains unclear. Given the pivotal role of AMPK in metabolism, whether ouabain affects cancer cell metabolism remains elusive. In this study we showed that treatment with ouabain (25 nM) caused simultaneous activation of AMPK and Src signaling pathways in human lung cancer A549 cells and human breast cancer MCF7 cells. Cotreatment with AMPK inhibitor compound C or siRNA greatly abrogates ouabain-induced Src activation, whereas cotreatment with Src inhibitor PP2 has little effect on ouabain-induced AMPK activity, suggesting that AMPK served as an upstream regulator of the Src signaling pathway. On the other hand, ouabain treatment greatly depletes ATP production in A549 and MCF7 cells, and supplement of ATP (100 µM) blocked ouabain-induced AMPK activation. We further demonstrated that ouabain greatly inhibited the mitochondrial oxidative phosphorylation (OXPHOS) in the cancer cells, and exerted differential metabolic effects on glycolysis depending on cancer cell type. Taken together, this study reveals that the altered cancer cell metabolism caused by ouabain may contribute to AMPK activation, as well as its cytotoxicity towards cancer cells.

Shi-Style Cervical Mobilizations Versus Massage for Cervical Vertigo: A Multicenter, Randomized, Controlled Clinical Trial.

Objectives: Large sample and high-quality evidence to evaluate the preliminary safety of the mobilizations and massage for cervical vertigo are not yet available. Thus, the present study aimed to investigate the comparative effectiveness and preliminary safety of Shi-style cervical mobilizations (SCM) compared with traditional massage (TM) in cervical vertigo patients. Design: A prospective, multicenter, open-label, randomized, controlled clinical trial with a 1:1 allocation ratio. Settings: Five academic medical centers. Subjects: A total of 360 adult patients with a diagnosis of cervical vertigo. Interventions: The patients were randomly allocated to either an SCM (n = 180) or TM (n = 180) group. The patients were treated during six sessions over 2 weeks. The primary outcome was the Dizziness Handicap Inventory (DHI) total scale score, and secondary outcomes included the DHI subscales, Chinese version of the Short-Form 36 Health Survey (CSF-36), and adverse events (AEs). Outcomes were assessed in the short term at 2 weeks, 1 month, and 3 months, and in the intermediate term at 6 months after randomization. Results: Significant changes were observed from the baseline in the DHI total scale and subscales at 2 weeks and 1, 3, and 6 months in both groups (all p < 0.05). However, the differences between the two groups were not significant (all p > 0.05). Furthermore, we noted significant changes from the baseline in SF-36 scores at 2 weeks in both groups (all p < 0.05), whereas CSF-36 scores were not significantly higher in the SCM group (all p > 0.05) compared with the TM group. No serious AEs were reported in either of the two groups. Conclusions: No differences in outcomes were detected between the SCM and TM groups in terms of treatment of cervicogenic dizziness. Efficacy trials are required to determine whether the improvement observed for each treatment was causally related to the interventions.

Transcriptome analysis reveals novel insights into the continuous cropping induced response in Codonopsis tangshen, a medicinal herb.

Codonopsis tangshen Oliv. (C. tangshen Oliv.), a famous medicinal herb in China, is seriously affected by continuous cropping (C-cro). The physiological and biochemical results indicated that C-cro significantly affected the malonaldehyde (MDA) and chlorophyll content, as well as activities of catalase (CAT) and superoxide dismutase (SOD) when compared with the non-continuous cropping (NC-cro) group. Transcriptome profiling found 762 differentially expressed genes, including 430 up-regulated and 332 down-regulated genes by C-cro. In addition, pathway enrichment analysis revealed that genes related to 'Tyrosine degradation I', 'Glycogen synthesis' and 'Phenylalanine and tyrosine catabolism' were up-regulated, and genes associated with 'Signal transduction', 'Immune system', etc. were down-regulated by C-cro. The expression of target genes was further validated by Q-PCR. In this study, we demonstrated the effects of C-cro on C. tangshen at the transcriptome level, and found possible C-cro responsive candidate genes. These findings could be further beneficial for improving the continuous cropping tolerance.

Electroacupuncture for postoperative pain management after total knee arthroplasty: Protocol for a systematic review and meta-analysis.

BACKGROUND: Total knee arthroplasty (TKA) is one of the most common joint replacement surgeries in the United States. Postoperative pain is still a major complication after TKA. Electroacupuncture (EA) has been commonly used in clinical practice for pain after TKA, but its effects and safety remain uncertain. This protocol is described for a systematic review to investigate the beneficial effects and safety of EA for postoperative pain after TKA. METHODS: Randomized controlled trials (RCTs) related to EA treatment of pain after TKA will be collected from 3 databases of English literature, namely PubMed, Embase, and Cochrane Library, and 4 databases of Chinese literatures, namely CBM, CNKI, VIP and Wanfang database. The retrieved trials will be those published from the time when the respective databases were built to January 2018. The therapeutic effects according to the change from baseline in the amount of pain measured by the visual analogue scale (VAS) or numerical rating scale, will be accepted as the primary outcomes. We will use RevMan V.5.3 software as well to compute the data synthesis carefully when a meta-analysis is allowed. RESULTS: This systematic review and meta-analysis will provide a high-quality synthesis of current evidence of EA for pain after TKA. CONCLUSION: The conclusion of our systematic review will provide evidence to judge whether EA is an effective intervention for patient with postoperative pain after TKA. PROSPERO REGISTRATION NUMBER: PROSPERO CRD 42018082407.

Toxicology studies of furosine in vitro/in vivo and exploration of the related mechanism.

AIM: Furosine is one of the Maillard reaction products (MRPs) and is found in a variety of heat-processed food. Yet its toxicity is still unclear. The present study was designed to assess furosine toxicity in cell models and in CD-1 mice, respectively. METHODS: In vitro, the effects of furosine on the cell viability, cell cycle and apoptosis (Hek293, HepG2, SK-N-SH and Caco2) were detected and evaluated, sensitive cell lines and proper dosage of furosine for further animal experiment were determined, and the mechanisms of toxicity were explored. In vivo, the acute toxicity studieswere performed, organ index, hematology parameters, functions of liver/kidney and pathological changes were detected and the target organs were uncovered. RESULTS: Hek293 cells and HepG2 cells were themost sensitive to furosine with respect to cytotoxicity and apoptosis. Furosine inhibited mice weight gain, and affected the functions of liver and kidney. CONCLUSIONS: Furosine posed toxic effects on mice liver and kidney, suggested thatthey were the target organs for furosine toxicity. This study for the first time provides evidence that high dosages of furosine pose adverse biological effects on the health of animals through induction of cell apoptosis and activation of inflammatory necrosis response.

High-effective approach from amino acid esters to chiral amino alcohols over Cu/ZnO/Al2O3 catalyst and its catalytic reaction mechanism.

Developing the high-efficient and green synthetic method for chiral amino alcohols is an intriguing target. We have developed the Mg(2+)-doped Cu/ZnO/Al2O3 catalyst for hydrogenation of L-phenylalanine methyl ester to chiral L-phenylalaninol without racemization. The effect of different L-phenylalanine esters on this title reaction was studied, verifying that Cu/ZnO/Al2O3 is an excellent catalyst for the hydrogenation of amino acid esters to chiral amino alcohols. DFT calculation was used to study the adsorption of substrate on the catalyst, and showed that the substrate adsorbs on the surface active sites mainly by amino group (-NH2) absorbed on Al2O3, and carbonyl (C=O) and alkoxy (RO-) group oxygen absorbed on the boundary of Cu and Al2O3. This catalytic hydrogenation undergoes the formation of a hemiacetal intermediate and the cleavage of the C-O bond (rate-determining step) by reacting with dissociated H to obtain amino aldehyde and methanol ad-species. The former is further hydrogenated to amino alcohols, and the latter desorbs from the catalyst surface.