Loss-of-function mutations of microRNA-142-3p promote ASH1L expression to induce immune evasion and hepatocellular carcinoma progression

BACKGROUND Hepatocellular carcinoma(HCC)has been a pervasive malignancy throughout the world with elevated mortality.Efficient therapeutic targets are beneficial to treat and predict the disease.Currently,the exact molecular mechanisms leading to the progression of HCC are still unclear.Research has shown that the microRNA-142-3p level decreases in HCC,whereas bioinformatics analysis of the cancer genome atlas database shows the ASH1L expression increased among liver tumor tissues.In this paper,we will explore the effects and mechanisms of microRNA-142-3p and ASH1L affect the prognosis of HCC patients and HCC cell bioactivity,and the association between them.AIM To investigate the effects and mechanisms of microRNA-142-3p and ASH1L on the HCC cell bioactivity and prognosis of HCC patients.METHODS In this study,we grouped HCC patients according to their immunohistochemistry results of ASH1L with pathological tissues,and retrospectively analyzed the prognosis of HCC patients.Furthermore,explored the roles and mechanisms of microRNA-142-3p and ASH1L by cellular and animal experiments,which involved the following experimental methods:Immunohistochemical staining,western blot,quantitative real-time-polymerase chain reaction,flow cytometric analysis,tumor xenografts in nude mice,etc.The statistical methods involved in this study contained t-test,one-way analysis of variance,theχ^(2)test,the Kaplan-Meier approach and the log-rank test.RESULTS In this study,we found that HCC patients with high expression of ASH1L possess a more recurrence rate as well as a decreased overall survival rate.ASH1L promotes the tumorigenicity of HCC and microRNA-142-3p exhibits reduced expression in HCC tissues and interacts with ASH1L through targeting the ASH1L 3′untranslated region.Furthermore,microRNA-142-3p promotes apoptosis and inhibits proliferation,invasion,and migration of HCC cell lines in vitro via ASH1L.For the exploration mechanism,we found ASH1L may promote an immunosuppressive microenvironment in HCC and ASH1L affects the expression of the cell junction protein zonula occludens-1,which is potentially relevant to the immune system.CONCLUSION Loss function of microRNA-142-3p induces cancer progression and immune evasion through upregulation of ASH1L in HCC.Both microRNA-142-3p and ASH1L can feature as new biomarker for HCC in the future.

Meningeal lymphatic vessel crosstalk with central nervous system immune cells in aging and neurodegenerative diseases

Meningeal lymphatic vessels form a relationship between the nervous system and periphery, which is relevant in both health and disease. Meningeal lymphatic vessels not only play a key role in the drainage of brain metabolites but also contribute to antigen delivery and immune cell activation. The advent of novel genomic technologies has enabled rapid progress in the characterization of myeloid and lymphoid cells and their interactions with meningeal lymphatic vessels within the central nervous system. In this review, we provide an overview of the multifaceted roles of meningeal lymphatic vessels within the context of the central nervous system immune network, highlighting recent discoveries on the immunological niche provided by meningeal lymphatic vessels. Furthermore, we delve into the mechanisms of crosstalk between meningeal lymphatic vessels and immune cells in the central nervous system under both homeostatic conditions and neurodegenerative diseases, discussing how these interactions shape the pathological outcomes. Regulation of meningeal lymphatic vessel function and structure can influence lymphatic drainage, cerebrospinal fluid-borne immune modulators, and immune cell populations in aging and neurodegenerative disorders, thereby playing a key role in shaping meningeal and brain parenchyma immunity.

T cell interactions with microglia in immune-inflammatory processes of ischemic stroke

The primary mechanism of secondary injury after cerebral ischemia may be the brain inflammation that emerges after an ischemic stroke,which promotes neuronal death and inhibits nerve tissue regeneration.As the first immune cells to be activated after an ischemic stroke,microglia play an important immunomodulatory role in the progression of the condition.After an ischemic stroke,peripheral blood immune cells(mainly T cells)are recruited to the central nervous system by chemokines secreted by immune cells in the brain,where they interact with central nervous system cells(mainly microglia)to trigger a secondary neuroimmune response.This review summarizes the interactions between T cells and microglia in the immune-inflammatory processes of ischemic stroke.We found that,during ischemic stroke,T cells and microglia demonstrate a more pronounced synergistic effect.Th1,Th17,and M1 microglia can co-secrete proinflammatory factors,such as interferon-γ,tumor necrosis factor-α,and interleukin-1β,to promote neuroinflammation and exacerbate brain injury.Th2,Treg,and M2 microglia jointly secrete anti-inflammatory factors,such as interleukin-4,interleukin-10,and transforming growth factor-β,to inhibit the progression of neuroinflammation,as well as growth factors such as brain-derived neurotrophic factor to promote nerve regeneration and repair brain injury.Immune interactions between microglia and T cells influence the direction of the subsequent neuroinflammation,which in turn determines the prognosis of ischemic stroke patients.Clinical trials have been conducted on the ways to modulate the interactions between T cells and microglia toward anti-inflammatory communication using the immunosuppressant fingolimod or overdosing with Treg cells to promote neural tissue repair and reduce the damage caused by ischemic stroke.However,such studies have been relatively infrequent,and clinical experience is still insufficient.In summary,in ischemic stroke,T cell subsets and activated microglia act synergistically to regulate inflammatory progression,mainly by secreting inflammatory factors.In the future,a key research direction for ischemic stroke treatment could be rooted in the enhancement of anti-inflammatory factor secretion by promoting the generation of Th2 and Treg cells,along with the activation of M2-type microglia.These approaches may alleviate neuroinflammation and facilitate the repair of neural tissues.

Correlation between gut microbiota and tumor immune microenvironment:A bibliometric and visualized study

BACKGROUND In recent years,numerous reports have been published regarding the relationship between the gut microbiota and the tumor immune microenvironment(TIME).However,to date,no systematic study has been conducted on the relationship between gut microbiota and the TIME using bibliometric methods.AIM To describe the current global research status on the correlation between gut microbiota and the TIME,and to identify the most influential countries,research institutions,researchers,and research hotspots related to this topic.METHODS We searched for all literature related to gut microbiota and TIME published from January 1,2014,to May 28,2024,in the Web of Science Core Collection database.We then conducted a bibliometric analysis and created visual maps of the published literature on countries,institutions,authors,keywords,references,etc.,using CiteSpace(6.2R6),VOSviewer(1.6.20),and bibliometrics(based on R 4.3.2).RESULTS In total,491 documents were included,with a rapid increase in the number of publications starting in 2019.The country with the highest number of publications was China,followed by the United States.Germany has the highest number of citations in literature.From a centrality perspective,the United States has the highest influence in this field.The institutions with the highest number of publications were Shanghai Jiao Tong University and Zhejiang University.However,the institution with the most citations was the United States National Cancer Institute.Among authors,Professor Giorgio Trinchieri from the National Institutes of Health has the most local impact in this field.The most cited author was Fan XZ.The results of journal publications showed that the top three journals with the highest number of published papers were Frontiers in Immunology,Cancers,and Frontiers in Oncology.The three most frequently used keywords were gut microbiota,tumor microenvironment,and immunotherapy.CONCLUSION This study systematically elaborates on the research progress related to gut microbiota and TIME over the past decade.Research results indicate that the number of publications has rapidly increased since 2019,with research hotspots including“gut microbiota”,“tumor microenvironment”and“immunotherapy”.Exploring the effects of specific gut microbiota or derived metabolites on the behavior of immune cells in the TIME,regulating the secretion of immune molecules,and influencing immunotherapy are research hotspots and future research directions.

Efficacy and safety of Tripterygium wilfordii glycosides tablets combined with Western medicine for patients with rheumatic immune diseases

BACKGROUND Rheumatic immune diseases are a group of chronic inflammatory diseases charac-terized by joint and systemic multi-organ involvement,including rheumatoid arthritis,systemic lupus erythematosus,and Sjogren’s syndrome,among others.The pathogenesis of these diseases is related to the abnormal activation and regulatory imbalance of the immune system.The prevalence and morbidity of rheumatic immune diseases are high,imposing a significant burden on patients'quality of life and socio-economic costs.Currently,the treatment of rheumatic immune diseases mainly relies on Western medicine,such as non-steroidal anti-inflammatory drugs,glucocorticoids,disease-modifying antirheumatic drugs,and biologics.However,the therapeutic effects of Western medicine are not ideal,some patients poorly respond or are resistant to Western medicine,and long-term use often causes various adverse reactions.AIM To systematically evaluate the efficacy and safety of Tripterygium wilfordii gly-cosides tablets combined with Western medicine in the treatment of patients with rheumatic immune diseases.METHODS This study conducted a meta-analysis to systematically evaluate the efficacy and safety of Tripterygium wilfordii glycosides tablets combined with Western medicine for patients with rheumatic immune diseases.Chinese and English databases were searched for randomized controlled trials(RCTs)on the treatment of rheumatic immune diseases with Tripterygium wilfordii glycosides tablets combined with Western medicine.The quality of the included studies was assessed using the Cochrane risk of bias assessment tool.Meta-analysis was performed using RevMan 5.4 software.RESULTS The meta-analysis included 11 RCTs involving 1026 patients with rheumatic immune diseases.The combined treatment significantly reduced the risk of disease recurrence(relative risk=1.07,95%confidence interval:1.01-1.15,P<0.05)and showed no significant heterogeneity(I2=0%,P=0.53),indicating that Tripterygium wilfordii glycosides tablets combined with Western medicine is an effective method to reduce the possibility of postoperative recurrence in patients with rheumatic immune diseases.However,due to the limited number and quality of the studies included,these results should be interpreted with caution.CONCLUSION Tripterygium wilfordii glycosides tablets combined with Western medicine is an effective and safe treatment option for patients with rheumatic immune diseases and can be considered a clinical choice.However,more high-quality research is needed to validate this conclusion and provide more solid evidence for clinical practice.

Effect of Astragalus polysaccharides on Erythrocyte Immune Adherence of Chickens Inoculated with Infectious Bursal Disease Virus

Two hundred and forty specific pathogen free leghorn chickens were randomly divided into four groups and reared in isolated pens. The tested chickens were negative to infectious bursal disease virus （IBDV） at 25 d old. Group 1 was treated with saline, whereas Groups 2, 3, and 4 were inoculated with 0.3 mL IBDV suspension intranasally the next day. Groups 3 and 4 were also administered with Astragalus polysaccharides （APS） intramuscularly twice daily at 5 or 10 mg kg-1 BW, respectively, until 31 d old. The erythrocyte-C3b receptor rosette rate （E-C3bRR） and the erythrocyte-C3b immune complex rosette rate （E-ICRR） were measured at 25, 29, 32, 35, and 38 d old. The results showed that IBDV significantly reduced E-C3bRR and E-ICRR when compared with the control group （P 〈 0.05）, while simultaneous administration of APS with 1BDV maintained E-C3bRR at similar levels to the control group （P 〉 0.05） and increased E-ICRR when compared with the control group and the group non-treated with APS （P 〈 0.05）. APS treatment reduced the morbidity and mortality of chickens inoculated with IBDV （P 〈 0.05）. The results suggest that APS may enhance the immune adherence of chickens erythrocytes by affecting the activity and/or the number of complement receptors on the erythrocyte membrane. These findings can be beneficial in providing an understanding of the basic mechanisms required for the rational application of APS in modern medicine.

Effect of different anesthesia methods on erythrocyte immune function in mice

Objective:To explore effect of different anesthesia methods and different anesthetics on erythrocyte immune function in mice.Methods:The mice were anesthetized by isoflurane and ether inhalation,and also under intraperitoneal anesthesia with sodium pentobarbital and chloral hydrate,Blood was collected from the ventro-cardinal vein.Automatic blood cell analyzer was used for routine blood examination,and the canthine oxidase method was used to measure the superoxide dismutase(SOD)activity.Lipid peroxidation product malondialdehyde(MDA)was measured with TBA,and glutathione peroxidase(GSH-Px)was measured with DTNB,and then the effect of different anesthesia methods and different anesthetics on erythrocyte immune function in mice was observed.Result:Hct level of chloral hydrate intraperitoneal injection group was significantly higher than the other three groups(P<0.05).And the MDA levels in the pentobarbital sodium group were significantly higher than the other three groups(P<0.05).SOD and GSH-Px of the chloral hydrate and sodium pentobarbital intraperitoneal injection group were significantly lower than the other two groups;RBC-C 3bRR and RBC-ICR of the chloral hydrate and sodium pentobarbital intraperitoneal injection group were significantly lower than the other two groups.Conclusions:Different drugs can induce changes in immune function of mice at different levels.Isoflurane and ether have less damage to animal body,while chloral hydrate and sodium pentobarbital intraperitoneal injection have a certain inhibitory effect on the animal body respiratory system and can cause greater damage to the body.Therefore,the reasonable selection and control of anesthetics are very important in order to avoid the experimental errors caused by anesthesia.

Effect of lead exposure on the immune function of lymphocytes and erythrocytes in preschool children

Objective: To investigate the influence of lead exposure on the immune function of lymphocytes and erythrocytes in preschool children. Materials and methods: A group of 217 children three to six years of age from a rural area were given a thorough physical examination and the concentration of lead in blood samples taken from each subject was determined. The indices of lymphocyte immunity (CD^+3CD^+4, CD^+3CD^+8, CD^+4CD^+8, CDˉ3CD^+19) and erythrocyte immunity (RBC-C3b, RBC-IC, RFER, RFIR, CD35 and its average fluorescence intensity) of 40 children with blood lead levels above 0.483 μmol/L were measured and compared with a control group. Results: The blood lead levels of the 217 children ranged from 0.11 μmol/L to 2.11 μmol/L. The CD^+3CD^+4and CD^+4CD^+8 cells were lower (P＜0.01) and the CD^+3CD^+8 cells were higher in the lead-poisoned subjects than those in the control group (P＜0.05). CD^+3 and CDˉ3CD^+19 did not show significant differences. Although the RBC-C3b rosette forming rate was lower and the RBC-IC rosette forming rate was higher in the lead-poisoned group, this difference could not be shown to be statistically significant (P＞0.05). RFIR was found to be lower in the lead-poisoned group (P＜0.01). Compared with the control group, the positive rate of CD35 was not found to be significantly different in a group of 25 lead-poisoned children (P＞0.05), while the average fluorescence intensity was lower in the lead-poisoned group (P＜0.05). Conclusion: Lead exposure can result in impaired immune function oft lymphocytes and erythrocytes in preschool children.

Effects of Dangguibuxue Decoction on Immune Organs and Erythrocyte Immune in Broilers

[ Objective] To study the effects of Dangguibuxue decoction on immune organ and erythrocyte immune in broilers. [ Method] One hun- dred 1 -day-old healthy Sanhuang chickens were randomly divided into five groups, 20 in each group. They were immunized with Newcastle disease vaccine via intranasal inoculation at 7 days old. The chickens in group I, II and III drank water added the Danggguibuxue decoction at proportion of 2%, 5% and 10% （ V/V）, respectively. The chickens in the group IV drank water added Astragalus polysaccharide at proportion of 2% （V/V）. And those in the group V drank water without addition of any drug. Blood was collected via jugular vein at 14, 21 and 28 days old, respectively, and then they were dissected. The immune organ indexes, erythrocyte C3b receptor rosette rate （E-C3b RR） and erythrocyte immune complex rosette rate （E-ICRR） were measured. [ Result] The Dangguibuxue decoction had no significant effect on thymus index but significantly increased spleen index and bursa of Fabricius index. The best peripheral and humoral immunity was observed in the broilers drinking water added the Dangguibuxue decoction at proportion of 10% （ V/ V）, and its immune enhancement was better than that of Astragalus polysaccharide added at proportion of 2% （V/V）. [ Coaclusion] Dangguibuxue decoction can promote maturation of immune organs and enhance erythrocyte immune functions; thus, it can be used as immunolootentiator.

STUDY ON THE IMMUNE FUNCTION OF ERYTHROCYTE IN PATIENT WITH NIDDM

The author measured the immune function of erythrocyte in 50 cases of noninsulin dependent diabetes mellitus(NIDDM),and researched the effect of erythrocyte immune adherence adjustmeat factor on the immune function of erythrocyte. The results showed that in patients with NIDDM,erythrocyte C3b receptor rosette forming rate(ECRRFR)was much higher(P<0.01),erythrocyte immune adherence exciting factor(EIAEF)was much lower than that of normal controlgroup(P<0.01);erythrocyte immune complexes rosette forming rate(EICRFR)was much lower,and erythrocyte immune adherence inhibiting factor(EIAIF)was much nigher than that of normalPersons(P<0.01).The study also showed that a significant positive correlation was found betweenthe activation of erythrocyte C3b receptor and EIAEF,and a significant negative correlation wasfound between the activation of erythrocyte C3b receptor and EIAIF.

Effect of Selenium Poisoning on Immune Function and Oxygen Free Radicals in Erythrocyte of Pig

[ Objective] This study was to investigate the effect of selenium（Se） on immune function and oxygen free radicals in erythrocyte of pig. [ Method] Fifteen weanling Landrace piglets as experimental animals were divided into three groups, two testing groups and one control group. For each group, Se content in whole blood, immune function of erythrocytes, activity of whole blood glutathione peroxidase（GSH-Px）, activity of blood plasma superoxide dismutase（SOD）, and blood plasma malondialdehyde（MDA） content were determined. [ Result] Compared with the control group, Se content in whole blood and blood plasma MDA content increased remarkably, while whole blood GSH-Px activity and blood plasma SOD activity decreased; RBC-C1 RR assumed a rise-fall trend, and RBC-ICR showed no obvious change. [Condusion] Se poisoning can reduce the activity of antioxidant enzymes, disturb the balance of oxygen free radicals metabolism, thereby inducing erythrooyte immune function in piglets.

EFFECT OF SELENIUM ON IMMUNE FUNCTION OF ERYTHROCYTE IN KASHIN-BECK DISEASE

Objective To investigate the relationship between erythrocyte immune function and selenium (Se) level. Methods Forty-nine Kashin-Beck patients in endemic area aged 13-16 years were divided into two groups and were orally given either selenized yeast or sodium selenite to provide 200 μ g selenium per day for 12 weeks. Erythrocyte selenium level, glutathione peroxidase activity, the rosette formation rates of red blood cells complement receptor typeⅠ(CR1), the immune function of red blood cells, and circulating immune complexes(CIC) were determined. Results After supplementing with selenium for 12 weeks, erythrocyte selenium level, glutathione peroxidase activity, the rosette formation rates of red blood cells CR1 were significantly increased. But the difference in rosette formation rates of IC and CIC content was not significant between before and after Se supplementation. Conclusion The increase of the immune function of the erythrocyte by selenium-supplement may be one of the effective mechanisms for the prevention of Kashin-Beck disease.

Changes of microelement content and erythrocyte immune function in patients with cerebral infarction complicated by pneumonia and their relationship with infection indexes

Objective: To study the changes of microelement content and erythrocyte immune function in patients with cerebral infarction complicated by pneumonia and their relationship with infection indexes. Methods: Patients with cerebral infarction complicated by pneumonia who were treated in Huangshi Central Hospital between April 2014 and February 2017 were selected as the infection group of the research, and patients with cerebral infarction who were treated in Huangshi Central Hospital during the same period were selected as the control group of the research. Serum was collected to determine the contents of trace elements Zn, Fe, Cu, Se and Ca as well as infection index PCT, and peripheral blood was collected to determine the erythrocyte immune function indexes. Results: Serum PCT content of infection group was greatly higher than that of control group. Serum zinc and Fe contents as well as peripheral blood RBC-ICR, RBC-C3bR, FEER, CD58 and CD59 levels of infection group were greatly lower than those of control group, FEIR level in peripheral blood was obviously higher than that of control group, and Cu, Se and Ca contents were not greatly different from those of control group;serum zinc and Fe contents as well as peripheral blood RBC-ICR, RBC-C3bR, FEER, CD58 and CD59 levels of infection group of patients with high PCT content were remarkably lower than those of patients with low PCT content, FEIR level in peripheral blood was significantly higher than that of patients with low PCT content, and Cu, Se and Ca contents were not greatly different from those of patients with low PCT content. Conclusion:The deficiency of microelements Zn and Fe as well as the weakening of erythrocyte immune function is closely related to the degree of infection in the patients with cerebral infarction complicated by pneumonia.

Effect of continuous blood purification on inflammatory state, immune response and erythrocyte glycometabolism in patients with multiple injury and sepsis

Objective:To analysis the effect of continuous blood purification on inflammatory state, immune response and erythrocyte glycometabolism in patients with multiple injury and sepsis. Methods: A total of 78 patients with multiple injury and sepsis were randomly divided into observation group (n=39) and control group (n=39), control group received routine therapy, observation group received continuous blood purification treatment, and then the differences in inflammatory state, immune response, erythrocyte glycometabolism and other indexes were compared between the two groups after treatment.Results: Inflammatory factor hs-CRP, TNF-α, PCT, sTREM-1 and HBP content in serum of observation group after treatment were significantly lower than those of control group;Th1 cytokines IL-2 and IFN-γ content in serum were lower than those of control group while Th2 cytokines IL-4 and IL-10 content were higher than those of control group;PFK and EGSH content in erythrocyte solution were higher than those of control group while G-6PD, AR and ELPO content were lower than those of control group;fluorescence intensity of CD11a, CD54, CD106 and CD49d in peripheral blood were significantly lower than those of control group.Conclusions: Continuous blood purification can significantly reduce the systemic inflammatory response in patients with multiple injury and sepsis, and promote the immune function and erythrocyte metabolism to return to normal.

Effect of low-intensity millimeter wave irradiation on the immune adhesion function of erythrocytes and lymphocytes in tumor patients

Objective To study the effects of low-intensity millimeter wave(MMW)irradiation on the immune adhesion f unction of ery-throcytes and lymphocytes in tumor patients.Methods MMW(36GHz,0.73-1.46mW/cm 2 )was used to irradiate the vein blood f rom tumor patients in irradiation group for 30minutes.Control group received fal se irradiation using the same method.Then test tumor RBC-C 3b receptor rosettes rate(RCR),tumor-RBC rosette rate(TRR)and tumor lmphocyte rosette rate(TLR).Result In irradiation group,the RBC-C 3b TRR and TLR were higher than control grou p’ s(P <0.01).Conclusion Low-intensity MMWirradiation can i mprove the immune adhesion function of erythrocytes and lymphocytes in tumor patients.

Immune checkpoint inhibitor-associated gastritis:Patterns and management

Immune checkpoint inhibitors(ICIs)are widely used due to their effectiveness in treating various tumors.Immune-related adverse events(irAEs)are defined as adverse effects resulting from ICI treatment.Gastrointestinal irAEs are a common type of irAEs characterized by intestinal side effects,such as diarrhea and colitis,which may lead to the cessation of ICIs.Although irAE gastritis is rarely reported,it may lead to serious complications such as gastrorrhagia.Furthermore,irAE gastritis is often difficult to identify early due to its diverse symptoms.Although steroid hormones and immunosuppressants are commonly used to reverse irAEs,the best regimen and dosage for irAE gastritis remains uncertain.In addition,the risk of recurrence of irAE gastritis after the reuse of ICIs should be considered.In this editorial,strategies such as early identification,pathological diagnosis,mana-gement interventions,and immunotherapy rechallenge are discussed to enable clinicians to better manage irAE gastritis and improve the prognosis of these patients.

Interplay between mesenchymal stromal cells and the immune system after transplantation: implications for advanced cell therapy in the retina

Advanced mesenchymal stromal cell-based therapies for neurodegenerative diseases are widely investigated in preclinical models.Mesenchymal stromal cells are well positioned as therapeutics because they address the underlying mechanisms of neurodegeneration,namely trophic factor deprivation and neuroinflammation.Most studies have focused on the beneficial effects of mesenchymal stromal cell transplantation on neuronal survival or functional improvement.However,little attention has been paid to the interaction between mesenchymal stromal cells and the host immune system due to the immunomodulatory properties of mesenchymal stromal cells and the long-held belief of the immunoprivileged status of the central nervous system.Here,we review the crosstalk between mesenchymal stromal cells and the immune system in general and in the context of the central nervous system,focusing on recent work in the retina and the importance of the type of transplantation.

Hepatocellular carcinoma immune microenvironment and check point inhibitors-current status

Hepatocellular carcinoma(HCC)is the most common primary tumor of the liver and has a high mortality rate.The Barcelona Clinic Liver Cancer staging system in addition to tumor staging also links the modality of treatment available to a particular stage.The recent description of the tumor microenvironment(TME)in HCC has provided a new concept of immunogenicity within the HCC.Virusrelated HCC has been shown to be more immunogenic with higher expression of cytotoxic T lymphocytes and decreased elements for immunosuppression such as regulatory T cells.This immunogenic milieu provides a better response to immunotherapy especially immune checkpoint inhibitors(ICIs).In addition,the recent data on combining locoregional therapies and other strategies may convert the less immunogenic state of the TME towards higher immunogenicity.Therefore,data are emerging on the use of combinations of locoregional therapy and ICIs in unresectable or advanced HCC and has shown better survival outcomes in this difficult population.

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.