Ginsenoside Rk3 modulates gut microbiota and regulates immune response of group 3 innate lymphoid cells to against colorectal tumorigenesis

The gut microbiota plays a pivotal role in the immunomodulatory and protumorigenic microenvironment of colorectal cancer(CRC).However,the effect of ginsenoside Rk3(Rk3)on CRC and gut microbiota remains unclear.Therefore,the purpose of this study is to explore the potential effect of Rk3 on CRC from the perspective of gut microbiota and immune regulation.Our results reveal that treatment with Rk3 significantly suppresses the formation of colon tumors,repairs intestinal barrier damage,and regulates the gut microbiota imbalance caused by CRC,including enrichment of probiotics such as Akkermansia muciniphila and Barnesiella intestinihominis,and clearance of pathogenic Desulfovibrio.Subsequent metabolomics data demonstrate that Rk3 can modulate the metabolism of amino acids and bile acids,particularly by upregulating glutamine,which has the potential to regulate the immune response.Furthermore,we elucidate the regulatory effects of Rk3 on chemokines and inflammatory factors associated with group 3 innate lymphoid cells(ILC3s)and T helper 17(Th17)signaling pathways,which inhibits the hyperactivation of the Janus kinase-signal transducer and activator of transcription 3(JAK-STAT3)signaling pathway.These results indicate that Rk3 modulates gut microbiota,regulates ILC3s immune response,and inhibits the JAK-STAT3 signaling pathway to suppress the development of colon tumors.More importantly,the results of fecal microbiota transplantation suggest that the inhibitory effect of Rk3 on colon tumors and its regulation of ILC3 immune responses are mediated by the gut microbiota.In summary,these findings emphasize that Rk3 can be utilized as a regulator of the gut microbiota for the prevention and treatment of CRC.

From concept to reality-A review to the primary test stand and its preliminary application in high energy density physics

Pulsed power technology,whereas the electrical energy stored in a relative long period is released in much shorter timescale,is an efficient method to create high energy density physics(HEDP)conditions in laboratory.Around the beginning of this century,China Academy of Engineering Physics(CAEP)began to build some experimental facilities for HEDP investigations,among which the Primary Test Stand(PTS),a multi-module pulsed power facility with a nominal current of 10 MA and a current rising time~90 ns,is an important achievement on the roadmap of the electro-magnetically driven inertial confinement fusion(ICF)researches.PTS is the first pulsed power facility beyond 10 TW in China.Therefore,all the technologies have to be demonstrated,and all the engineering issues have to be overcome.In this article,the research outline,key technologies and the preliminary HEDP experiments are reviewed.Prospects on HEDP research on PTS and pulsed power development for the next step are also discussed.

High efficiency production of ginsenoside compound K by catalyzing ginsenoside Rb1 using snailase

The rare ginsenoside Compound K （C-K） is attracting more attention because of its good physiological activity and urgent need. There are many pathways to obtain ginsenoside C-K, including chemical and biological methods. Among these, the conversion of PPD-type ginsenosides by enzymatic hydrolysis is a trend due to its high efficiency and mild conditions. For effectively extracting from the other panaxadiol saponins, the conversion process for ginsenoside C-K was investigated using snailases in this study. The univariate experimental design and response surface methodology were used to determine the optimal hydrolysis conditions for the conversion of ginsenoside Rbl into ginsenoside C-K by snailases. The optimum conditions were as follows： pH 5,12, temperature 51 ℃, ratio of snailase/substrate 0.21, and reaction time 48 h. On the basis of these parameters, the addition of 1.0 mmol· L- 1 ferric ion was found to significantly improve the enzymolysis ofsnailases for the first time. With the above conditions, the maximum conversion rate reached 89.7%, suggesting that the process can obviously increase the yield of ginsenoside C-K. The bioassay tests indicated that the ginsenoside C-K showed anti-tumor activity in a series of tumor cell lines. Based on these results, we can conclude that the process of rare ginsenoside C- K production by enzymolysis with snailase is feasible, efficient, and suitable for the industrial production and application.

Ginsenoside Rk3 is a novel PI3K/AKT-targeting therapeutics agent that regulates autophagy and apoptosis in hepatocellular carcinoma

Hepatocellular carcinoma(HCC)is the third leading cause of cancer death worldwide.Ginsenoside Rk3,an important and rare saponin in heat-treated ginseng,is generated from Rg1 and has a smaller molecular weight.However,the anti-HCC efficacy and mechanisms of ginsenoside Rk3 have not yet been characterized.Here,we investigated the mechanism by which ginsenoside Rk3,a tetracyclic triterpenoid rare ginsenoside,inhibits the growth of HCC.We first explored the possible potential targets of Rk3 through network pharmacology.Both in vitro(HepG2 and HCC-LM3 cells)and in vivo(primary liver cancer mice and HCC-LM3 subcutaneous tumor-bearing mice)studies revealed that Rk3 significantly inhibits the proliferation of HCC.Meanwhile,Rk3 blocked the cell cycle in HCC at the G1 phase and induced autophagy and apoptosis in HCC.Further proteomics and siRNA experiments showed that Rk3 regulates the phosphatidylinositol 3-kinase(PI3K)/protein kinase B(AKT)pathway to inhibit HCC growth,which was validated by molecular docking and surface plasmon resonance.In conclusion,we report the discovery that ginsenoside Rk3 binds to PI3K/AKT and promotes autophagy and apoptosis in HCC.Our data strongly support the translation of ginsenoside Rk3 into novel PI3K/AKT-targeting therapeutics for HCC treatment with low toxic side effects.

First results from a 760-GW linear transformer driver module for Z-pinch research

In this paper,the results of tests on a 0.76-TW linear transformer driver(LTD)module for Z-pinch research are presented for the first time.Ten LTD cavities,each generating a 1-MA/90-kV pulse on a matched load,were connected in series with a magnetically insulated voltage adder to drive the e-beam diode.Three inner stalks with different radii were tested,and the results indicate that the output parameters of the ten cavities are sensitive to the cathode radii.As an intermediate step,a high-current pulse with 832 kV/912 kA/130 ns was obtained on the e-beam diode.To date,this is the maximum power generated directly by a fast LTD with mega-ampere current output.

Dietary phytochemicals: As a potential natural source for treatment of Alzheimer's Disease

Alzheimer's disease(AD)is a common neurodegenerative disease,which seriously impairs human health and life.At present,scientists have proposed more than a dozen hypotheses about the pathogenesis of AD,including the tau propagation hypothesis.However,the exact ultimate pathogenic factor of AD remains unknown.Based on the current hypotheses,some anti-AD drugs(e.g.,donepezil and Ketamine)have been developed and used in clinical treatment,which fall into two main categories,acetylcholinesterase inhibitors(AChEIs)and N-methyl-D-aspartate(NMDA)receptor antagonists,the former representative drug is donepezil,and the latter representative drug is memantine.Since these drugs have undesirable side effects,it is necessary to find safer alternatives for AD treatment.Interestingly,dietary phytochemicals have the advantages of wide source,safety,and high biological activity,which is the natural route for screening anti-AD drugs.In this study,several representatives’dietary phytochemicals with anti-AD effect,including resveratrol,lycopene,gallic acid,berberine,ginsenoside Rg1,pseudoginsenoside-F11,ginsenoside Rh2,artemisinin,and torularhodin were selected from the published data over the last 10 years and their potential molecular mechanisms and clinical applications reviewed in the treatment of AD.