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.

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.

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.

Unraveling the Effect of Stacking Configurations on Charge Transfer in WS_(2) and Organic Semiconductor Heterojunctions

Photoinduced interfacial charge transfer plays a critical role in energy conversion involving van der Waals(vdW)heterostructures constructed of inorganic nanostructures and organic materials.However,the effect of molecular stacking configurations on charge transfer dynamics is less understood.In this study,we demonstrated the tunability of interfacial charge separation in a type-Ⅱ heterojunction between monolayer(ML)WS_(2) and an organic semiconducting molecule[2-(3″′,4′-dimethyl-[2,2′:5′,2′:5″,2″′-quaterthiophen]-5-yl)ethan-1-ammonium halide(4Tm)]by rational design of relative stacking configurations.The assembly between ML-WS_(2) and the 4Tm molecule forms a face-to-face stacking when 4Tm molecules are in a selfaggregation state.In contrast,a face-to-edge stacking is observed when 4Tm molecule is incorporated into a 2D organic-inorganic hybrid perovskite lattice.The face-to-face stacking was proved to be more favorable for hole transfer from WS_(2) to 4Tm and led to interlayer excitons(IEs)emission.Transient absorption measurements show that the hole transfer occurs on a time scale of 150 fs.On the other hand,the face-to-edge stacking resulted in much slower hole transfer without formation of IEs.This inefficient hole transfer occurs on a similar time scale as A exciton recombination in WS_(2),leading to the formation of negative trions.These investigations offer important fundamental insights into the charge transfer processes at organic−inorganic interfaces.

Glucose and MMP-9 dual-responsive hydrogel with temperature sensitive self-adaptive shape and controlled drug release accelerates diabetic wound healing

Chronic diabetic wounds are an important healthcare challenge. High concentration glucose, high level of matrix metalloproteinase-9 (MMP-9), and long-term inflammation constitute the special wound environment of diabetic wounds. Tissue necrosis aggravates the formation of irregular wounds. All the above factors hinder the healing of chronic diabetic wounds. To solve these issues, a glucose and MMP-9 dual-response temperature-sensitive shape self-adaptive hydrogel (CBP/GMs@Cel&INS) was designed and constructed with polyvinyl alcohol (PVA) and chitosan grafted with phenylboric acid (CS-BA) by encapsulating insulin (INS) and gelatin microspheres con-taining celecoxib (GMs@Cel). Temperature-sensitive self-adaptive CBP/GMs@Cel&INS provides a new way to balance the fluid-like mobility (self-adapt to deep wounds quickly, approximately 37 ◦C) and solid-like elasticity (protect wounds against external forces, approximately 25 ◦C) of self-adaptive hydrogels, while simultaneously releasing insulin and celecoxib on-demand in the environment of high-level glucose and MMP-9. Moreover, CBP/ GMs@Cel&INS exhibits remodeling and self-healing properties, enhanced adhesion strength (39.65 ± 6.58 kPa), down-regulates MMP-9, and promotes cell proliferation, migration, and glucose consumption. In diabetic full-thickness skin defect models, CBP/GMs@Cel&INS significantly alleviates inflammation and regulates the local high-level glucose and MMP-9 in the wounds, and promotes wound healing effectively through the synergistic effect of temperature-sensitive shape-adaptive character and the dual-responsive system.

Construction of multifunctional hydrogel based on the tannic acid-metal coating decorated MoS2 dual nanozyme for bacteria-infected wound healing

Bacterial infection,tissue hypoxia and inflammatory response can hinder the infected wound repair process.To mitigate the above issues,tannic acid-chelated Fe-decorated molybdenum disulfide nanosheets(MoS2@TA/Fe NSs)with dual enzyme activities were developed and anchored to a multifunctional hydrogel.The hydrogel exhibited excellent antibacterial ability owing to the combined effects of photothermal therapy(PTT),glutathione(GSH)loss,and the peroxidase(POD)-like activity(catalyse H2O_(2)into⋅OH under acid condition)of MoS2@TA/Fe NSs.Benefitting from the catalase(CAT)-like activity,the hydrogel could decompose H2O_(2)into O_(2)at neutral pH to relieve hypoxia and supply adequate O_(2).POD-like activity was mainly attributed to MoS2 NSs,while CAT-like activity was primarily due to TA/Fe complex.Moreover,MoS2@TA/Fe NSs endowed the hydrogel with outstanding anti-oxidant ability to scavenge redundant reactive oxygen species(ROS)and reactive nitrogen species(RNS)under neutral environment to maintain the balance of antioxidant systems and prevent inflammation.In addition,the hydrogel could inhibit the release of inflammatory factors for the anti-inflammatory property of TA.TA retained partial phenolic hydroxyl groups,which cross-linked the nanosheets to the network structure of the hydrogel and promoted the adhesion of hydrogels.Due to the dynamic boron ester bonds between polyvinyl alcohol(PVA),dextran(Dex),MoS2@TA/Fe,and borax,the hydrogel demonstrated fast self-healing and rapid shape adaptability.This shape-adaptable adhesive hydrogel could fill the whole wound and closely contact the wound,ensuring that it achieved its functions with maximum efficiency.The MoS2@TA/Fe nanozyme-anchored multifunctional hydrogel showed high potential for bacteria-infected wound healing.