[Identification and functional characterization of candidate genes involved in biosynthesis of ginsenoside Rg_1].

Panax ginseng is a perennial herb with the main active compounds of ginsenosides. Among the reported ginsenosides, ginsenoside Rg_1 not only has a wide range of medicinal functions and abundant content but also is one of the major ginsenoside for the quality evaluation of this herb in the Chinese Pharmacopoeia. The main biosynthesis pathway of ginsenoside Rg_1 in P. ginseng has been clarified, which lays a foundation for the comprehensive and in-depth analysis of the biosynthesis and regulatory mechanism of ginseno-side Rg_1. However, the biosynthesis of ginsenoside Rg_1 is associated with other complex processes involving a variety of regulatory genes and catalyzing enzyme genes, which remain to be studied comprehensively. With the transcriptome data of 344 root samples from 4-year-old P. ginseng plants and their corresponding ginsenoside Rg_1 content obtained in the previous study, this study screened out 217 differentially expressed genes(DEGs) with Rg_1 content changes by DEseq2 analysis in R language. Furthermore, the weighted gene co-expression network analysis(WGCNA) revealed 40 hub genes among the DEGs.Pearsoncorrelation analysis was further perforned to yield 20 candidate genes significantly correlated with ginsenoside Rg_1 content, and these genes were annotated to multiple metabolic processes including primary metabolism and secondary metabolism. Finally, the treatment of P. ginseng adventitious roots with methyl jasmonate indicated that 16 of these genes promoted the biosynthesis of ginsenoside Rg_1 in response to methyl jasmonate induction. Finally, one of the 16 genes was randomly selected to verify the function of the gene by genetic transformation and qRT-PCR and to confirm the rationality of the methodology of this study. The above results lay a foundation for studying the mechanism for regulation on the synthesis of ginsenoside Rg_1 and provide genetic resources for the industrial production of ginsenoside Rg_1.

Bibenzyl-Phenylpropane Hybrids with Immunosuppressive Activities from Dendrobium Nobile Lindl.

Fifteen bibenyls and four fluorenones, including five new bibenzyl-phenylpropane hybrids, were isolated from the aerial part of Dendrobium nobile Lindl. Their structures were determined by spectroscopic methods. Bioassay on the LPS-induced proliferations of mouse splenic B lymphocytes, and Con A-induced T lymphocytes showed that compounds 1, 2, and 14 showed excellent immunosuppressive activities with IC50 values of 1.23, 1.01, and 3.87 µM, respectively, while compounds 3-4, 7, 10, 13, and 15 exhibited moderate immunosuppressive activities with IC50 values ranging from 6.89 to 14.2 µM.

Immunosuppressive diarylpropane dimer and spirocyclic-monomers from Horsfieldia kingii.

Horsfiequinone G (1), a dimeric diarylpropane featuring an unprecedentedly oxo-6/7/6 fused ring system, a new flavane, horsfielenide F (2), three naturally occurring spirocyclic monomers containing all-carbon quaternary centers, horspirotone A (3), horspirotone B (4), and methyl spirobroussonin B (5), along with horsfiequinone A (6) were isolated from Horsfieldia kingii. Their structures and absolute configurations were determined by the inspection of extensive spectroscopic data and electronic circular dichroism (ECD) calculations. Biological evaluations of these isolates revealed that compounds 1 - 3 and 5 - 6 exhibited specifically immunosuppressive activities against Con A-induced T lymphocytes with IC50 values ranging from 2.07 to 12.34 µM (selectivity indices = 2.3-25.2). Compound 1 also suppressed the secretion of inflammatory factors like IL-1ß and IL-6 in RAW264.7 cells which could present a new class of nonsteroidal anti-inflammatory agent. Finally, the primary structure-activity relationship (SAR) was also discussed.

Chemical Synthesis Enables the Configurational Determination of Myristriol, a Highly Oxygenated Phenylpropanoid from Myristica fragrans Houtt.

A new phenylpropanoid, myristriol (1), along with 11 known ones were isolated from the seed kernel of Myristica fragrans Houtt. Their chemical structures were clearly elucidated by extensive spectroscopic analysis. In which, the relative configuration of 1 was finally determined as erythro-1 by comparison the NMR data of two synthetic erythro- and threo-diastereoisomers with that of natural 1.

The effects of bariatric surgery on cognition in patients with obesity: a systematic review and meta-analysis.

Obesity impairs cognition. Bariatric surgery can result in substantial weight loss in patients with severe obesity; however, the impact of bariatric surgery on cognitive function remains controversial. To quantify the effect of bariatric surgery on cognition in patients with severe obesity, we performed a meta-analysis of 20 studies retrieved from PubMed, Cochrane, and Embase. Of these, 6 cohort studies found that Roux-en-Y gastric bypass leads to better performance for immediate verbal memory function (standardized mean difference [SMD] = .56; 95% confidence interval [CI]: .30-.82, P < .0001; I2 = 0%) and delayed memory function (SMD = .64; 95% CI: .38-.90, P < .00001; I2 = 0%) during in the short term. Similarly, positive impacts on immediate verbal memory function (SMD = .46; 95% CI: .09-.83, P < .00001) and delayed memory function (SMD = .84; 95% CI: .46-1.22, P < .0001) were identified during a long-term follow-up. The Roux-en-Y gastric bypass group showed no improvements in attention, cognitive speed, and executive function compared with the control obese group. In 14 longitudinal studies (12 single-arm pre-post comparison studies and 2 cohort studies whose control group had no follow-up cognitive data), patients performed better postoperatively than preoperatively in all cognitive domains during repeated assessments. The analysis for the 20 operative groups showed that individuals treated with bariatric surgery had higher scores after repeated assessment of most neuropsychological tests except for animal fluency and letter fluency than baseline scores. These findings suggest that patients with severe obesity may obtain immediate verbal and delayed memory function benefits from Roux-en-Y gastric bypass.

Effects of bleomycin on tooth eruption: a novel potential application.

There are many kinds of potentially undesirable teeth. At present, surgical extraction is the most efficient way to eliminate these teeth, but it's very complex and invasive. In this study, we investigated the effects of bleomycin (BLM) on dental follicle and tooth eruption as a potential conservative therapy for undesirable teeth. Our data showed that local injection of 0.2 U/kg BLM had no significant effects on tooth eruption compared to the control group in Wistar rats. With higher dose of BLM (0.5 or 2 U/kg), the eruption of treated teeth was interrupted and their root formation failed until 4 weeks postnatal without significant systemic toxicity. Additionally, those effects were not depending on the toxicity of overdose evidenced by TUNEL assay. In summary, injecting BLM into dental follicle at an early stage could interrupt tooth development and eruption, and may prevent the potentially clinical problems resulting from undesirable teeth instead of surgical removal.

The trimeric Hef-associated nuclease HAN is a 3'→5' exonuclease and is probably involved in DNA repair.

Nucleases play important roles in nucleic acid metabolism. Some archaea encode a conserved protein known as Hef-associated nuclease (HAN). In addition to its C-terminal DHH nuclease domain, HAN also has three N-terminal domains, including a DnaJ-Zinc-finger, ribosomal protein S1-like, and oligonucleotide/oligosaccharide-binding fold. To further understand HAN's function, we biochemically characterized the enzymatic properties of HAN from Pyrococcus furiosus (PfuHAN), solved the crystal structure of its DHH nuclease domain, and examined its role in DNA repair. Our results show that PfuHAN is a Mn2+-dependent 3'-exonuclease specific to ssDNA and ssRNA with no activity on blunt and 3'-recessive double-stranded DNA. Domain truncation confirmed that the intrinsic nuclease activity is dependent on the C-terminal DHH nuclease domain. The crystal structure of the DHH nuclease domain adopts a trimeric topology, with each subunit adopting a classical DHH phosphoesterase fold. Yeast two hybrid assay confirmed that the DHH domain interacts with the IDR peptide of Hef nuclease. Knockout of the han gene or its C-terminal DHH nuclease domain in Haloferax volcanii resulted in increased sensitivity to the DNA damage reagent MMS. Our results imply that HAN nuclease might be involved in repairing stalled replication forks in archaea.

Relationship of a low ankle-brachial index with all-cause mortality and cardiovascular mortality in Chinese patients with metabolic syndrome after a 6-year follow-up: a Chinese prospective cohort study.

OBJECTIVE: Peripheral arterial disease (PAD) is a common clinical manifestation of the systemic atherosclerotic process, and the ankle-brachial index (ABI) is an ideal tool to diagnose PAD. Currently, there have been few long-term follow-up studies focused on the associations of the ABI with all-cause mortality and cardiovascular disease (CVD) mortality in Chinese MetS patients. The aim of this study was to evaluate the usefulness of ABI to predict the prognosis of CVD in hospitalized Chinese patients with metabolic syndrome (MetS). METHODS: Participants from multi-center departments were followed up from November 2004 to January 2011. The study sample actually comprised 1,266 valid participants whose age was ≥35 years. Patients were separated into four groups, with an ABI ≤0.4, 0.41-0.7, 0.71-0.9 and 0.91-1.4. An ABI ≤0.9 was defined as PAD, and subjects with an ABI >1.4 were excluded because of the false negative rate. Factors related to all-cause and cardiovascular mortality were observed by Cox models and the log rank test. Potential confounding variables with values of p<0.10 were adjusted for the multivariate analysis. RESULTS: An abnormal ABI value was strongly, independently, and inversely correlated with the all-cause and cardiovascular mortality. After adjusting for age and other covariates, Cox models revealed that an abnormal ABI value was still correlated with the all-cause mortality (relative risk/RR/=1.82, 95% confidence interval/CI/=1.45-2.34 p<0.01), and CVD mortality (RR=1.88, 95% CI=1.51-2.90 p<0.01). CONCLUSION: An abnormal ABI value was not only a significant and independent risk factor for CVD, but also for the survival rate in Chinese MetS patients. Routine ABI evaluation could therefore be helpful for identifying high risk patients, especially MetS patients.