Effects of Rosa roxburghii&edible fungus fermentation broth on immune response and gut microbiota in immunosuppressed mice

With the rise of probiotics fermentation in food industry,fermented foods have attracted worldwide attention.In this study,protective effects of Rosa roxburghii&edible fungus fermentation broth(REFB)on immune function and gut health in Cyclophosphamide induced immunosuppressed mice were investigated.Results showed that REFB could improve the immune organ index,and promote the proliferation and differentiation of splenic T lymphocytes.In addition,it attenuated intestinal mucosal damage and improved intestinal cellular immunity.REFB administration also up-regulated the expression of IL-4,INF-γ,TNF-α,T-bet and GATA-3 mRNA in small intestine.Furthermore,administration of REFB modulated gut microbiota composition and increased the relative abundance of beneficial genus,such as Bacteroides.It also increased the production of fecal short-chain fatty acids.These indicate that REFB has the potential to improve immunity,alleviate intestinal injury and regulate gut microbiota in immunosuppressed mice.

EFFECTS OF REINFORCED DECOCTION OF ANGELICAE SINENSIS FOR ENRICHING BLOOD ON THE IMMUNITY OF IMMUNOSUPPRESSED MICE

Objective To investigate the effect of reinforced Decoction of Angelicae Sinensis for enriching blood (RDAEB) on the immunity of immunosuppressed mice induced by cyclophosphamide (Cy). Methods Mice were given RDAEB through stomach perfusion for 10 d (50 mg/d). Then, RBC-C3bR rate,RBC-IC rate (as the index- es of erythrocyte immunity)and E-rosette forming rate,acidic a-naphthyl acetate esterase positive rate, lymphocyte transformation rate (as the indexes of cellular immunity) of mice were tested. Results RBC-C3Br rate, RBC-IC rat- e,E-rosette forming rate, acidic α-naphthyl acetate esterase positive rate and lymphocyte transformation rate in the Cy-RDAEB group were markedly higher than those in the Cy group (P<0.0l),and returned to the levels of normal group. Conclusion RDAEB is effective in recovering and enhancing cellular and erythrocyte immunity of immuno- suppressed mice.

Entecavir as treatment for reactivation of hepatitis B in immunosuppressed patients

AIM: To study the efficacy and safety of entecavir (ETV) as first-line therapy for hepatitis B virus (HBV) reactivation due to immunosuppression. METHODS: Four patients that were treated with different immunosuppressive regimens for hematological malignancies, who presented with HBV reactivation were treated with ETV. Clinical outcome, biochemical and virological factors, including quantitative hepatitis B surface antigen (HBsAg) were studied. RESULTS: In all patients, ETV induced suppression of HBV, and rapid clinical improvement without side effects. In one patient with an alanine aminotransferase (ALT) flare, tenofovir was added after 3 mo of treatment. Until death from disease progression at 6 mo after treatment initiation, this patient did not clear HBV infection. Retrospectively, it is highly probable that thepatient had been non-adherent. In the other three patients, the virological responses were associated with an expeditious decrease in quantitative HBsAg titers with negativity after 2 mo, and all three had HBsAg seroconversion. In one patient, HBV DNA reached a plateau after 3 mo, before becoming undetectable after 1 year, despite early ALT normalization and undetectable quantitative HBsAg. CONCLUSION: ETV seems to be effective and safe treatment for HBV reactivation. Monitoring of quantitative HBsAg might be an additional useful tool to monitor treatment response.

Management of hepatitis B reactivation in immunosuppressed patients: An update on current recommendations

The proportion of hepatitis B virus(HBV) previously exposed patients who receive immunosuppressive treatment is usually very small. However, if these individuals are exposed to potent immunosuppressive compounds, the risk of HBV reactivation(HBVr) increases with the presence of hepatitis B surface antigen(HBsAg) in the serum. Chronic HBsAg carriers have a higher risk than those who have a total IgG anticore as the only marker of resolved/occult HBV disease. The loss of immune control in these patients may results in the reactivation of HBV replication within hepatocytes. Upon reconstitution of the immune system, infected hepatocytes are once again targeted and damaged by immune surveillance in an effort to clear the virus. There are different virological scenarios, and a wide spectrum of associated drugs with specific and stratified risk for the development of HBVr. Some of this agents can trigger a severe degree of hepatocellular damage, including hepatitis, acute liver failure, and even death despite employment of effective antiviral therapies. Currently, HBVr incidence seems to be increasing around the world; a fact mainly related to the incessant appearance of more powerful immunosuppressive drugs launched to the market. Moreover, there is no consensus on the length of prophylactic treatment before the patients are treated with immunosuppressive therapy, and for how long this therapy should be extended once treatment is completed. Therefore, this review article will focus on when to treat, when to monitor, what patients should receive HBV therapy, and what drugs should be selected for each scenario. Lastly, we will update the definition, risk factors, screening, and treatment recommendations based on both current and different HBV management guidelines.

Crithidia deanei infection in normal and dexamethasone–immunosuppressed Balb/c mice

Monoxenous trypanossomatids protozoa are not believed to cause in vivo infection in verte- brate hosts throughout their life cycle. However, there are reports mentioning some cases of HIV- positive patients who have presented opportunistic infections caused by these protozoa. Recently, we have demonstrated the in vitro infection of mouse dermal fibroblasts by these protozoa. The aim of the present work is to investigate the possibility of Crithidia deanei, a endosymbiont-bearing monoxenous trypanossomatid, infect BALB/c mice under or not Dexamethasone treatment. To attend it, distinct gro- ups of adult BALB/c mice were immunosuppressed with 50 mg/kg of Dexamethasone. This immunosuppressor was administered 24 hours before infection and daily, for 15 days after C. deanei inoculation. Control groups: C. deanei–inoculated animals but non-immuno- suppressed and non-inoculated animals but immunosuppressed were also used. Light Microscopy analysis revealed an infection process characterized by the presence of the trypanossomatid inside dermal cells in the groups studied. The experimental inoculation resulted in a non-lethal infection characterized by the presence of the trypanossomatid inside dermal cells in the normal BALB/c mice, but notably, in the C. deanei–inoculated immunosuppressed group. These preliminary results lead to the following conclusions: 1) C. deanei is able to infect normal BALB/c mice;2) the immunosupressed mice seemed to be more susceptible to the C. deanei infection compared to the control group. Besides C. deanei in dexamethasone-immunosuppressed mice provides a useful model for studies of monoxenous trypanosomatids ‘in vivo’ infection, resembling that one presumably occurring in imunodeficient individuals with AIDS.

Abdominal Sonographic Findings in Severely Immunosuppressed Human Immunodeficiency Virus-Infected Patients Treated for Tuberculosis

Objective: We describe the abdominal sonographic findings among patients with HIV-tuberculosis (TB) co-infection with advanced immune suppression before initiation of ART and relate these findings to the patients’ abdominal symptoms and CD4 T-cell count. Methods: Consecutive HIV-TB co-infected patients, qualifying for ART, were prospectively enrolled in a cohort study at the Mulago National Tuberculosis and Leprosy Programme clinic in Kampala, Uganda. An abdominal ultrasound was performed at enrolment. Results: A total of 209 HIV-TB co-infected patients (76% with pulmonary, 19% with extrapulmonary TB and 5% with extrapulmonary and pulmonary TB) underwent an abdominal ultrasound scan. Only 49 patients (23.4%) had a normal abdominal ultrasound. The following sonographic abnormalities were found: multiple lymphadenopathy (38%), splenomegaly (18%), renal abnormalities (14%), gastro-intestinal tract abnormalities (thickened bowel loops, appendicitis) (13%), splenic abscesses (13%) and ascites (6%). The commonest groups of enlarged lymph nodes were in the porta-hepatis (19%) and peripancreatic (17%) area and 80% of the enlarged lymph nodes were hypoechoic. Conclusion: Most patients with advanced immune suppression and HIV-TB co-infection have sonographic evidence of generalized TB with abdominal involvement, therefore Ultrasound may assist in the early diagnosis of disseminated TB.

Compound fufangteng mixture affects the expression of CD69 on CD11b^(+) monocytes in immunosuppressed mice

Objective:To investigate the effects of Compound Fufangteng Mixture(CFM)on the expression levels of CD11b^(+)monocytes surface activation molecules CD2,CD69 and depleted molecules PD-1 and CD95 in spleen and peripheral blood of immunosuppressed mice.Methods:30 healthy SPF Balb/c male mice were randomly divided into Control,immunosuppressive model group(CTX group),high,medium and low dose intervention group(CTX+CFM-H group,CTX+CFM-M group,CTX+CFM-L group),Astragalus particles(AP)intervention group(CTX+AP group).The mice in each intervention group were injected intraperitoneally with cyclophosphamide(CTX)70 mg/kg for 3 consecutive days,and then administered for 10 d according to the group regimen,and the materials were taken 24 h after the last dose.Flow cytometry detected the expression of CD11b^(+)monocytes surface activation molecules(CD2,CD69)and depleting molecules(PD-1,CD95)in mouse peripheral blood.Results:Compared with the control group,the expression levels of CD11b^(+)and CD69+in the spleen of CTX+CFM-H,CTX+CFM-M and CTX+CFM-L groups showed an improvement trend,and decreased with the dose gradient of CFM.Conclusion:CFM could regulate the immune function of splenic CD11b+ CD69 cells in immunosuppressed mice.

Operative management of acute diverticulitis in immunosuppressed compared to immunocompetent patients: A systematic review

AIM: To determine short and long-term outcomes following operative management of acute diverticulitis in immunosuppressed(IMS) compared to immunocompetent(IMC) patients.METHODS: PRISMA guidelines were followed in conducting this systematic review. We searched Pub Med(1946 to present), OVID MEDLINE(R) In-Process and Other Non-Indexed Citations, OVID MEDLINE(R) Daily and OVID MEDLINE(R)(1946 to present), EMBASE on OVID platform(1947 to present), CINAHL on EBSCO platform(1981 to present), and Cochrane Library using a systematic search strategy. There were no restrictions on publication date and language. We systematically reviewed all published cohort comparative studies, casecontrol studies, and randomized controlled trials that reported outcomes on operative management of acute episode of colonic diverticulitis in IMS in comparison to IMC patients. RESULTS: Seven hundred and fifty-five thousand five hundred and eighty-three patients were included in this systematic review; of which 1478 were IMS and 754105 were IMC patients. Of the nine studies included there was one prospective cohort, seven retrospective cohorts, one retrospective case-control study, and no randomized controlled trials. With the exception of solid organ transplant patients, IMS patients appeared to be older than IMC when they presented with an acuteepisode of diverticulitis. IMS patients presented with more severe acute diverticulitis and more insidious onset of symptoms than IMC patients. In the emergency setting, peritonitis was the main indication for operative intervention in both IMS and IMC patients. IMS patients were more likely to undergo Hartmann's procedure and less likely to undergo reconstructive procedures compared to IMC patients. Furthermore, IMS patients had higher morbidity and mortality rates in the emergency setting compared to IMC patients. In the elective settings, it appeared that reconstruction with primary anastomosis with or without a diverting loop stoma is the procedure of choice in the IMS patients and carried minimal morbidity and mortality equivalent to IMC patients. CONCLUSION: Emergency operations for diverticulitis in IMS compared to IMC patients have higher morbidity and mortality, whereas, in the elective setting both groups have comparable outcomes.

Deep Morphea in an Immunosuppressed Patient With Anti-U1RNP Myositis:A Case Report

Introduction:Morphea is an inflammatory skin disease characterized by skin thickening due to increased collagen deposition in the dermis or subcutaneous tissues.Anti-U1RNP myositis is a newly described entity characterized by myositis,arthritis,interstitial lung disease,and Raynaud phenomenon.We present a case of a unique combination of deep morphea in a patient with anti-U1RNP myositis.Case presentation:A 64-year-old male with 5-year history of proximal muscle weakness,polyarthritis,Raynaud phenomenon,and dyspnea on multiple immunosuppressives presented with localized infiltrated,tight,and hyperpigmented plaques over the posterior thighs and mid-to-lower back developing over the last 2 years and limiting his movement.Autoimmune workup revealed a positive ANA,anti-U1RNP antibody,anti-Jo1 antibody,and anti-Ro52 antibody.Further workup showed restrictive lung disease,kidney disease,and arthritis.Patient was diagnosed with anti-U1RNP myositis.Skin biopsy of the back lesion showed deep morphea.Discussion:Association of deep morphea with anti-U1RNP myositis is not described prior in the literature.Treatment of morphea is challenging since the patient is already on immunosuppressive medications.The patient failed methotrexate prior and is currently on Mycophenolate mofetil and Deflazacort which are reported as potential treatment for morphea.Therefore,physical therapy plus topical Tacrolimus were suggested as an initial measure to preserve the range of motion of his posterior thighs and back.This is a case of progressive deep morphea developing in a patient with a unique autoimmune profile on immunosuppressive drugs.Conclusion:Anti-U1RNP myositis is a challenging diagnosis and should be always thought of in patients with positive anti-U1RNP,myositis,interstitial lung disease,arthritis,kidney disease,and Raynaud phenomenon.Moreover,deep morphea treatment in immunosuppressed patients is challenging and different measures should be considered.

Pleurotus nebrodensis polysaccharide(PN-S) enhances the immunity of immunosuppressed mice

In the present study, the effects of Pleurotus nebrodensis polysaccharide(PN-S) on the immune functions of immunosuppressed mice were determined. The immunosuppressed mouse model was established by treating the mice with cyclophosphamide(40 mg/kg/2d, CY) through intraperitoneal injection. The results showed that PN-S administration significantly reversed the CY-induced weight loss, increased the thymic and splenic indices, and promoted proliferation of T lymphocyte, B lymphocyte, and macrophages. PN-S also enhanced the activity of natural killer cells and increased the immunoglobulin M(Ig M) and immunoglobulin G(Ig G) levels in the serum. In addition, PN-S treatment significantly increased the phagocytic activity of mouse peritoneal macrophages. PN-S also increased the levels of interleukin-6(IL-6), tumor necrosis factor-α(TNF-α), interferon-γ(INF-γ), and nitric oxide(NOS) in splenocytes. q RT-PCR results also indicated that PN-S increased the m RNA expression of IL-6, TNF-α, INF-γ, and nitric oxide synthase(i NOS) in the splenocytes. These results suggest that PN-S treatment enhances the immune function of immunosuppressed mice. This study may provide a basis for the application of this fungus in adjacent immunopotentiating therapy against cancer and in the treatment of chemotherapy-induced immunosuppression.

Bidirectional regulation of the brain-gut-microbiota axis following traumatic brain injury

Traumatic brain injury is a prevalent disorder of the central nervous system.In addition to primary brain parenchymal damage,the enduring biological consequences of traumatic brain injury pose long-term risks for patients with traumatic brain injury;however,the underlying pathogenesis remains unclear,and effective intervention methods are lacking.Intestinal dysfunction is a significant consequence of traumatic brain injury.Being the most densely innervated peripheral tissue in the body,the gut possesses multiple pathways for the establishment of a bidirectional“brain-gut axis”with the central nervous system.The gut harbors a vast microbial community,and alterations of the gut niche contribute to the progression of traumatic brain injury and its unfavorable prognosis through neuronal,hormonal,and immune pathways.A comprehensive understanding of microbiota-mediated peripheral neuroimmunomodulation mechanisms is needed to enhance treatment strategies for traumatic brain injury and its associated complications.We comprehensively reviewed alterations in the gut microecological environment following traumatic brain injury,with a specific focus on the complex biological processes of peripheral nerves,immunity,and microbes triggered by traumatic brain injury,encompassing autonomic dysfunction,neuroendocrine disturbances,peripheral immunosuppression,increased intestinal barrier permeability,compromised responses of sensory nerves to microorganisms,and potential effector nuclei in the central nervous system influenced by gut microbiota.Additionally,we reviewed the mechanisms underlying secondary biological injury and the dynamic pathological responses that occur following injury to enhance our current understanding of how peripheral pathways impact the outcome of patients with traumatic brain injury.This review aimed to propose a conceptual model for future risk assessment of central nervous system-related diseases while elucidating novel insights into the bidirectional effects of the“brain-gut-microbiota axis.”

Prognostic impact of hypernatremia for septic shock patients in the intensive care unit

BACKGROUND Hypernatremia represents a significant electrolyte imbalance associated with numerous adverse outcomes,particularly in cases of intensive care unit(ICU)-acquired hypernatremia(IAH).Nevertheless,its relevance in patients with septic shock remains uncertain.AIM To identify independent risk factors and their predictive efficacy for IAH to improve outcomes in patients with septic shock.METHODS In the present retrospective single-center study,a cohort of 157 septic shock patients with concurrent hypernatremia in the ICU at The First Affiliated Hospital of Soochow University,between August 1,2018,and May 31,2023,were analyzed.Patients were categorized based on the timing of hypernatremia occurrence into the IAH group(n=62),the non-IAH group(n=41),and the normonatremia group(n=54).RESULTS In the present study,there was a significant association between the high serum sodium concentrations,excessive persistent inflammation,immunosuppression and catabolism syndrome and chronic critical illness,while rapid recovery had an apparent association with normonatremia.Moreover,multivariable analyses revealed the following independent risk factors for IAH:Total urinary output over the preceding three days[odds ratio(OR)=1.09;95%CI:1.02–1.17;P=0.014],enteral nutrition(EN)sodium content of 500 mg(OR=2.93;95%CI:1.13–7.60;P=0.027),and EN sodium content of 670 mg(OR=6.19;95%CI:1.75–21.98;P=0.005)were positively correlated with the development of IAH.Notably,the area under the curve for total urinary output over the preceding three days was 0.800(95%CI:0.678–0.922,P=0.001).Furthermore,maximum serum sodium levels,the duration of hypernatremia,and varying sodium correction rates were significantly associated with 28-day in-hospital mortality in septic shock patients(P<0.05).CONCLUSION The present findings illustrate that elevated serum sodium level was significantly associated with a poor prognosis in septic shock patients in the ICU.It is highly recommended that hypernatremia be considered a potentially important prognostic indicator for the outcome of septic shock.

Immunomodulatory effects of egg white peptides on immunosuppressed mice and sequence identification of immunomodulatory peptides

In this study,egg white peptides(EWP)were prepared using preheat treatment combined with a bienzymatic hydrolysis.Results on peptide yield and molecular weight distribution showed that preheat treatment could obviously promote egg white hydrolysis.The yield of EWP obtained from neutral-alkaline protease treatment was 74.62%±0.23%and 92.69%of EWP was between 200 Da and 500 Da.Supplementation with 750 mg/kg/d EWP significantly alleviated the decrease of immune organ index in immunosuppressed male BLAB/c mice caused by cyclophosphamide.The pathological changes of spleen showed that EWP could also alleviate the damage of spleen tissue.The number of white blood cells in peripheral blood and the levels of serum cytokines(IL-6,IL-2 and TNF-α)in 750 mg/kg/d EWP group were significantly higher than the model group.The immunomodulatory effects of EWP might be related to the presence of abundant branched-chain amino acids,which were important components of immunomodulatory peptides.Eight possible immunomodulatory peptides were identified from EWP by High Performance Liquid Chromatography-Mass Spectrometry in combination with ProteinLynx Global SERVER and mass spectral database.Therefore,EWP may have potential as a natural immunomodulator for the prevention of immune damage caused by external influences.

Florfenicol can inhibit chick growth and lead to immunosuppression

Florfenicol(FLO)is a chemically synthesized broad-spectrum antimicrobial agent of amide alcohols for animals,which is one of the most widely used antimicrobials in livestock,poultry,and aquaculture.With the use of FLo,more and more attention has been paid to its hematopoietic toxicity,immunotoxicity,genotoxicity,and embryotoxicity.In this study,SPF chicks.at the age of 3 d began to drink water with the FLO at a dose of 100 mg L^(-1)for 6 consecutive days,and the growth performance of chicks was monitored,the effect of FLO on immune organs was detected by pathological examination and TdT-mediated dUTP nick-end labeling(TUNEL)apoptosis staining.In order to evaluate the level of organism immunity,the level of Newcastle disease virus antibody in serum was detected by hemagglutination inhibition test,the content of cytokines(IL-1,IL-2,IL-6,TNF-α,IFN-γ)in serum was detected by enzyme linked immunosorbent assay(ELISA),and the transcription of interferon-related genes(IRF-7,2′-5′OAS,Mx1)and cytokine genes(IL-6,TNF-α,IFN-γ)in immune organs were detected by real time fluorescence quantitative PCR.The results showed that the early application of FLO could inhibit the growth and development of chicks,and the body weight and immune organ index of the treatment group were lower than those of the control group.Histopathological examination showed that there was a decrease in the number of lymphocytes in the bursa of Fabricius in the treatment group in the early stage of drug withdrawal,and the results of TUNEL apoptosis staining in the bursa of Fabricius showed that obvious lymphocyte apoptosis occurred in the FLO treatment group.Compared with the control group,the transcription levels of interferon-related genes IRF-7,2′-5′OAS,and cytokine genes IL-6,TNF-αand IFN-γin FLO treatment group decreased to a certain extent,while the transcription level of Mx1 gene had no significant difference at all time points.The level of serum Newcastle disease virus(NDV)antibody and the contents of cytokines IL-1,IL-2 and IFN-γin the FLO treatment group were significantly lower than those in the control group in the early stage of drug withdrawal,but recovered gradually in the later stage.This study showed that FLO has a certain degree of effect on the immune function of chicks,and the results of the study laid the foundation for further research on the mechanism of FLO-induced immunotoxicity.

AN EXPERIMENTAL TRIAL OF ARTEMETHER IN TREATMENT OF PNEUMOCYSTIS CARINII IN IMMUNOSUPPRESSED RATS

An immunosuppressed rat model was establisbed by injecting cortisone acetate 25 mg/rat twice a week for 4 weeks and 12.5mg/rat for another 2 weeks subcutaneously.A development of Pneumocystis carinii pneumonia(PCP) was found at the end of the 6th week in all rats.

Providing care for kidney transplant recipients:An overview for generalists

Kidney transplantation is the preferred treatment for patients with advanced chronic kidney disease and end-stage kidney disease,offering superior quality of life and survival compared to dialysis.This manuscript provides an updated overview of post-transplant care,highlighting recent advancements and current practices to assist generalists in managing these patients.It covers key areas such as immunosuppression strategies,drug interactions,and the management of transplant-specific acute kidney injury.The focus includes the use of sodium-glucose cotransporter-2 inhibitors and cell-free DNA monitoring for evaluating allograft health and immune-mediated injury.The manuscript reviews the fundamentals of immunosuppression,including both induction and maintenance therapies,and underscores the importance of monitoring kidney function,as well as addressing hypertension,diabetes,and infections.It also provides recommen-dations for vaccinations and cancer screening tailored to kidney transplant reci-pients and emphasizes lifestyle management strategies,such as exercise and so-dium intake,to reduce post-transplant complications.

Optimizing risk management for post-amputation wound complications in diabetic patients: Focus on glycemic and immunosuppressive control

This study highlights the importance of identifying and addressing risk factors associated with wound complications following transtibial amputation in diabetic patients.These amputations,often necessitated by severe diabetic foot ulcers,carry significant risks of postoperative complications such as infection and delayed wound healing.Elevated hemoglobin A1c levels,indicative of poor glycemic control,and a history of kidney transplantation,due to required immunosuppressive therapy,are key factors influencing these outcomes.This paper emphasizes the need for enhanced glycemic management and personalized postoperative care,particularly for immunocompromised individuals,to minimize complications and improve patient prognosis.Future research should focus on prospective studies to validate targeted interventions and optimize care strategies,ultimately aiming to reduce the healthcare burden associated with diabetic foot complications.

Colony-stimulating factor 3 and its receptor promote leukocyte immunoglobulin-like receptor B2 expression and ligands in gastric

BACKGROUND Colony-stimulating factor 3(CSF3)and its receptor(CSF3R)are known to promote gastric cancer(GC)growth and metastasis.However,their effects on the immune microenvironment remain unclear.Our analysis indicated a potential link between CSF3R expression and the immunosuppressive receptor leukocyte immunoglobulin-like receptor B2(LILRB2)in GC.We hypothesized that CSF3/CSF3R may regulate LILRB2 and its ligands,angiopoietin-like protein 2(ANGPTL2)and human leukocyte antigen-G(HLA-G),contributing to immunosuppression.AIM To investigate the relationship between CSF3/CSF3R and LILRB2,as well as its ligands ANGPTL2 and HLA-G,in GC.METHODS Transcriptome sequencing data from The Cancer Genome Atlas were analyzed,stratifying patients by CSF3R expression.Differentially expressed genes and immune checkpoints were evaluated.Immunohistochemistry(IHC)was performed on GC tissues.Correlation analyses of CSF3R,LILRB2,ANGPTL2,and HLA-G were conducted using The Cancer Genome Atlas data and IHC results.GC cells were treated with CSF3,and expression levels of LILRB2,ANGPTL2,and HLA-G were measured by quantitative reverse transcriptase-polymerase chain reaction and western blotting.RESULTS Among 122 upregulated genes in high CSF3R expression groups,LILRB2 showed the most significant increase.IHC results indicated high expression of LILRB2(63.0%),ANGPTL2(56.5%),and HLA-G(73.9%)in GC tissues.Strong positive correlations existed between CSF3R and LILRB2,ANGPTL2,and HLA-G mRNA levels(P<0.001).IHC confirmed positive correlations between CSF3R and LILRB2(P<0.001),and HLA-G(P=0.010),but not ANGPTL2(P>0.05).CSF3 increased LILRB2,ANGPTL2,and HLA-G expression in GC cells.Heterogeneous nuclear ribonucleoprotein H1 modulation significantly altered their expression,impacting CSF3’s regulatory effects.CONCLUSION The CSF3/CSF3R pathway may contribute to immunosuppression in GC by upregulating LILRB2 and its ligands,with heterogeneous nuclear ribonucleoprotein H1 playing a regulatory role.

Impaired upregulation of keratinocyte growth factor in injured lungs induced by Pseudomonas aeruginosa in immunosuppressed rats

Background The number of immunosupressed patients has increased in the past decades. Among them Pseudomonas aeruginosa （P. aeruginosa） is one of the leading bacteria for pneumonia that are associated with poor prognosis. However, the pathogenesis of P. aeruginosa pneumonia in immunosupressed patients is not understood completely. Previous reports showed keratinocyte growth factor （KGF） is associated with lung injury in immunocompetent hosts. In this study, we investigated the different reactions of lung injury, lung pathology and KGF expressions in P aeruginosa pneumonia between immunosuppressed and immunocompetent rats. Methods Immunosuppression of male rats was induced by injecting immunosuppressive subcutaneously. Pneumonia was established by instilling P aeruginous tracheally. The immunocompetent rats were the control group. Survival rate, lung histopathology, pulmonary permeability and oedema, KGF mRNA and protein expressions in lungs of both groups were investigated. Results The survival rate of immunosuppressed group was lower than that of immunocompetent group （33.3% vs 83.3%）. After exposure to bacteria, pulmonary permeability and wet/dry ratio in immunosuppressed group were higher than those in immunocompetent group. Pulmonary congestion and haemorrhage were more intensive in immunosuppressed group compared to immunocompetent group. Apoptosis and necrosis were also observed in infected lungs of immunosuppressed rats. Although we detected KGF expressions in lungs of both groups after infection, the expressions of KGF protein and mRNA gene in immunosuppressed group were much lower than in immunocompetent group. Conclusions Compared with immunocompetent group, there was more intensive lung injury in immunosuppressed group. Severe lung injury may contribute to the poor prognosis of pneumonia. KGF expressions of pneumonia in immunosuppressed rats were less than those in immunocompetent ones.

Mechanisms of tumor immunosuppressive microenvironment formation in esophageal cancer

As a highly invasive malignancy,esophageal cancer(EC)is a global health issue,and was the eighth most prevalent cancer and the sixth leading cause of cancerrelated death worldwide in 2020.Due to its highly immunogenic nature,emerging immunotherapy approaches,such as immune checkpoint blockade,have demonstrated promising efficacy in treating EC;however,certain limitations and challenges still exist.In addition,tumors may exhibit primary or acquired resistance to immunotherapy in the tumor immune microenvironment(TIME);thus,understanding the TIME is urgent and crucial,especially given the importance of an immunosuppressive microenvironment in tumor progression.The aim of this review was to better elucidate the mechanisms of the suppressive TIME,including cell infiltration,immune cell subsets,cytokines and signaling pathways in the tumor microenvironment of EC patients,as well as the downregulated expression of major histocompatibility complex molecules in tumor cells,to obtain a better understanding of the differences in EC patient responses to immunotherapeutic strategies and accurately predict the efficacy of immunotherapies.Therefore,personalized treatments could be developed to maximize the advantages of immunotherapy.