Kesterite Cu_(2)ZnSn(S,Se)_(4)(CZTSSe)solar cells suffer from severe carrier recombination,limiting the photovoltaic performance.Unfavorable energy band alignment at the p-n junction and defective front interface are ...Kesterite Cu_(2)ZnSn(S,Se)_(4)(CZTSSe)solar cells suffer from severe carrier recombination,limiting the photovoltaic performance.Unfavorable energy band alignment at the p-n junction and defective front interface are two main causes.Herein,oxygen incorporation in CZTSSe via absorber air-annealing was developed as a strategy to optimize its surface photoelectric property and reduce the defects.With optimized oxygen incorporation conditions,the carrier separation and collection behavior at the front interface of the device is improved.In particular,it is found that oxygen incorporated absorber exhibits increased band bending,larger depletion region width,and suppressed absorber defects.These indicate the dynamic factors for carrier separation become stronger.Meanwhile,the increased potential difference between grain boundaries and intra grains combined with the decreased concentration of interface deep level defect in the absorber provide a better path for carrier transport.As a consequence,the champion efficiency of CZTSSe solar cells has been improved from 9.74%to 12.04%with significantly improved open-circuit voltage after optimized air-annealing condition.This work provides a new insight for interface engineering to improve the photoelectric conversion efficiency of CZTSSe devices.展开更多
Sb_(2)Se_(3) with unique one-dimensional(1D) crystal structure exhibits exceptional deformation tolerance,demonstrating great application potential in flexible devices.However,the power conversion efficiency(PCE) of f...Sb_(2)Se_(3) with unique one-dimensional(1D) crystal structure exhibits exceptional deformation tolerance,demonstrating great application potential in flexible devices.However,the power conversion efficiency(PCE) of flexible Sb_(2)Se_(3) photovoltaic devices is temporarily limited by the complicated intrinsic defects and the undesirable contact interfaces.Herein,a high-quality Sb_(2)Se_(3) absorber layer with large crystal grains and benign [hkl] growth orientation can be first prepared on a Mo foil substrate.Then NaF intermediate layer is introduced between Mo and Sb_(2)Se_(3),which can further optimize the growth of Sb_(2)Se_(3)thin film.Moreover,positive Na ion diffusion enables it to dramatically lower barrier height at the back contact interface and passivate harmful defects at both bulk and heterojunction.As a result,the champion substrate structured Mo-foil/Mo/NaF/Sb_(2)Se_(3)/CdS/ITO/Ag flexible thin-film solar cell delivers an obviously higher efficiency of 8.03% and a record open-circuit voltage(V_(OC)) of 0.492 V.This flexible Sb_(2)Se_(3) device also exhibits excellent stability and flexibility to stand large bending radius and multiple bending times,as well as superior weak light photo-response with derived efficiency of 12.60%.This work presents an effective strategy to enhance the flexible Sb_(2)Se_(3) device performance and expand its potential photovoltaic applications.展开更多
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 i...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.展开更多
Thichosanthin(Tk), a polypeptide with 249 amino acid residues isolated and purified from a Chinese medicinal herb, showed the capability of inducing abortion and was able to inhibit tumor growth and HIV replication. O...Thichosanthin(Tk), a polypeptide with 249 amino acid residues isolated and purified from a Chinese medicinal herb, showed the capability of inducing abortion and was able to inhibit tumor growth and HIV replication. Owing to sequence homology of the peptide with a ribosomeinactivating protein, the downward activity of Tk was suggested to be related to its cytotoxic property. We report here, however, that Tk could exert potent inhibitory effects on human lymphoproliferative responses in vitro to allogeneic, mitogenic and soluble antigens with 50% inhibition doses ranged between 0.05 and 0.5 μg/ml. The lowresponsiveness caused by Tk was not due to toxic cytolysis. Rather, evidences suggested that, in the dose range adopted, the Tk-induced inhibition was attributable, at least in part, to immune suppression, in view of (1) Tk was more effective in the early stage of alloreactivity; (2)Suppression also occurred if responder cells were pulsetreated with Tk rather than cocultured; (3) Irradiated Tk-pulsed cells were capable of inducing suppression in a Tk-free culture; (4) Suppression could also be transferred by the supernatants of Tk-pulsed cultured cells; (5) Tkinduced immune suppression was diminished by depletion of CD8+ cells from the culture, and, finally; (6) Adding CD8+ cells back to the culture could restore the suppres Trichosanthin-induced humall immune suppression sion. Thus the possibility that Tk might function as a down-regulator by immunological mechanisms in human immune responses is discussed.展开更多
T cell immunoglobulin and mucin domain 3 (Tim-3) is well known to negatively regulate T cells responses, but its role in burn-induced T cells immune suppression remains unclear. In the present study, in order to ide...T cell immunoglobulin and mucin domain 3 (Tim-3) is well known to negatively regulate T cells responses, but its role in burn-induced T cells immune suppression remains unclear. In the present study, in order to identify the relationship between Tim-3 expression and post-burn T cells immune suppression, C57BL/6 mice were subjected to burn injury or sham injury, and the liver and spleen were harvested at the day 1 after operation. The expression level of Tim-3 on hepatic or splenic T cells and the functional properties of Tim-3+ T cells were evaluated. It was found burn injury induced dramatically elevated Tim-3 expression on both hepatic and splenic CD4+ and CD8+ T cells in contrast with the post-burn depletion of T cells. Furthermore, Tim-3 expression was correlated with the suppressive phenotype of T cells following burn injury, including increased expression of anti-inflammatory cytokine IL-10, decreased expression of pro-inflammatory cytokines IFN-γ and TNF-α, reduced T cell proliferation and elevated co-expression of Tim-3 and PD-1. Moreover, Tim-3+ T cells subsets were more prone to spontaneous apoptosis than Tim-3- T cells subsets. Our findings reinforce the idea that the up-regulated expression of Tim-3 on T cells after burn injury plays an important role in the development and maintenance of burn-induced T cell immune suppression.展开更多
AIM: To investigated the interaction between toll-like receptor 4 (TLR4)-activated hepatoma cells and macrophages in the induction of tumor-immune suppression mediated by CD4+CD25high family of transcription factor P3...AIM: To investigated the interaction between toll-like receptor 4 (TLR4)-activated hepatoma cells and macrophages in the induction of tumor-immune suppression mediated by CD4+CD25high family of transcription factor P3 (FOXP3) regulatory T cells (Tregs). METHODS: The proportion of FOXP3+ Tregs was identified in peripheral blood and tumor tissues of 60 hepatocellular carcinoma (HCC) patients. TLR4 expression was examined in tumor tissues and cell lines. The correlation was examined between FOXP3+ Tregs in peripheral blood and TLR4 expression of HCC tissues. Following activation of TLR4 in H22 murine hepatoma cells pre-incubated with lipopolysaccharide (LPS) and co-cultured with macrophage cell line RAW246.7, the synthesis of cytokines tumor necrosis factor-α, CCL22, and interleukin (IL)-10 by the two cell lines was detected and analyzed. RESULTS: FOXP3+ Tregs were enriched in tumor sites, and circulating FOXP3+ Tregs were increased in HCC patients in correlation with multiple tumor foci and up-regulated TLR4 expression in HCC tissues. Semi-quantitative analysis indicated that TLR4 was over-expressed in HCC compared with the matched normal tissues. Cell cultivation experiments indicated that the mRNAs of IL-10 and CCL22 were significantly up-regulated in the RAW246.7 cell line when co-cultured with LPS preincubated H22 cells. CONCLUSION: In hepatoma cell lines, TLR4 may indirectly facilitate the recruitment of Tregs to the tumor site and promote intrahepatic metastasis through its interaction with macrophages.展开更多
The vast majority of high-performance perovskite solar cells(PSCs) are based on a formamidinium lead iodide(FAPbI_(3))-dominant composition. Nevertheless, the FA-based perovskite films suffer from undesirable phase tr...The vast majority of high-performance perovskite solar cells(PSCs) are based on a formamidinium lead iodide(FAPbI_(3))-dominant composition. Nevertheless, the FA-based perovskite films suffer from undesirable phase transition and defects-induced non-ideal interfacial recombination, which significantly induces energy loss and hinders the improvement of device performance. Herein, we employed 4-fluorophenylmethylammonium iodide(F-PMAI) to modulate surface structure and energy level alignment of the FA-based perovskite films. The superior optoelectronic films were obtained with reduced trap density, pure α-phase FAPbI_(3) and favorable energy band bending. The lifetime of photogenerated charge carriers increased from 489.3 ns to 1010.6 ns, and a more “p-type” perovskite film was obtained by the post-treatment with F-PMAI. Following this strategy, we demonstrated an improved power conversion efficiency of 22.59% for the FA-based PSCs with an open-circuit voltage loss of 399 m V.展开更多
Physiotherapeutic effects of infrared lasers have been proved in clinic.These infrared-based regulations of the bioelectrical activities can roughly be classied into enhancement and suppression of action potential(AP)...Physiotherapeutic effects of infrared lasers have been proved in clinic.These infrared-based regulations of the bioelectrical activities can roughly be classied into enhancement and suppression of action potential(AP),which are described by sodium(Na)and potassium(K)transmembrane current equations,named as Hodgkin and Huxley(HH)-model.The enhancement effect is able to evoke or strengthen the AP when infrared light is applied.Its corresponding mechanism is commonly ascribed to the changes of the cell membrane capacitance,which is transiently increased in response to the infrared radiation.The distinctive feature of the suppression effect is to inhibit or reduce the AP by the designed protocols of infrared radiation.However,its mechanism presents more complexity than that in enhancement cases.HH-model describes how the Na current determines the initial phase of AP.So,the enhancement and suppression of AP can be also ascribed to the regulations of the corresponding Na currents.Here,a continuous infrared light at the wavelength of 980 nm(CIS-980)was employed to stimulate a freshly isolated hippocampal neuron in vitro and a suppression effect on the Na currents of the neuron cell was observed.Both Na and K currents,which are named as whole cell currents,were simultaneously recorded with the cell membrane capacitance current by using a patch clamp combined with infrared irradiation.The results demonstrated that the CIS-980 was able to reversibly increase the capacitance currents,completely suppressed Na currents,but little changed K currents,which forms the steady outward whole cell currents and plays a major role on the AP repolarization.A conrmation experiment was designed and carried out by synchronizing tens of milliseconds of infrared stimulation on the same kinds of hippocampal neuron cells.After the blocked K channel,a reduction of Na current amplitude was still recorded.This proved that infrared suppression of Na current was irrelevant to K channel.A membrane capacitance mediation process was preliminarily proposed to explain the Na channel suppression process.展开更多
Chimeric antigen receptors(CARs)are a breakthrough in genetic engineering that have revolutio nized the field of adoptive cellular therapy(ACT).Cells expressing these receptors are rerouted to a predefined target by t...Chimeric antigen receptors(CARs)are a breakthrough in genetic engineering that have revolutio nized the field of adoptive cellular therapy(ACT).Cells expressing these receptors are rerouted to a predefined target by the inclusion of an antigen-specific binding region within the synthetic CAR construct.The advantage of cells with programmed specificity has been demonstrated clinically in the field of oncology,and it is clear that such cells have greater accuracy,potency,and reduced off-target therapeutic effects compared with their unmodified counterparts.In contrast to conventional T cells(Tconvs),regulatory T cells(Tregs)play a major role in suppressing immune activation and regulating the host immune response.CAR expression within Tregs has been proposed as a therapy for autoimmune and inflammatory diseases,graft-versus-host disease(GVHD),and organ transplant rejectio n.In the latter,they hold immense potential as mediators of immune tolerance for recipients of allotransplants.However,current research into CAR-Treg engineering is extremely limited,and there is uncertainty regarding optimal design for therapeutic use.This review examines the rationale behind the development of CAR-Tregs,their significance for human transplantation,potential designs,safety considerations,and comparisons of CAR-Tregs in transplantation models to date.展开更多
Objective:To investigate the effects of astragalus polysaccharides(APS)on bone marrow suppression and hematopoietic stem cells during chemotherapy in elderly patients with lung cancer.Methods:120 elderly patients with...Objective:To investigate the effects of astragalus polysaccharides(APS)on bone marrow suppression and hematopoietic stem cells during chemotherapy in elderly patients with lung cancer.Methods:120 elderly patients with lung cancer treated in the first hospital of Xingtai city from January 2019 to early December 2019 were divided into the treatment group and the control group by the random number table method,all of whom received pemetrexed+carboplatin chemotherapy,and the treatment group was treated with APS at the same time.The efficacy was evaluated after 2 cycles of chemotherapy,bone marrow suppression was observed,and levels of TCM symptoms score,peripheral blood T lymphocyte subgroup index,L-selectin(CD62L)and macrophage differentiation antigen-1(Mac-1)were measured before and after 2 cycles of chemotherapy.Results:The response rate(RR)was 56.67%in the treatment group and 45.00%in the control group,with no statistically significant difference(P>0.05);The disease control rate(DCR)in the treatment group was 81.67%,which was significantly higher than 65.00%in the control group(P<0.05);The reduction degree of leukopenia in the treatment group was significantly lower than that in the control group(P<0.05);The treatment group had a platelet reduction of grade 1+2 at a rate of 40.00%,and hemoglobin reduction of grade 1+2 at a rate of 28.33%,which were significantly lower than the control group at 65.00%and 58.33%(P<0.05);Compared with those before chemotherapy,the total score of TCM symptoms,serum CD62L and Mac-1 levels in the two groups all decreased significantly after chemotherapy,and they were significantly lower in the treatment group than in the control group(P<0.05);After chemotherapy,CD3+,CD4+and CD4+/CD8+in the treatment group increased significantly and they were all higher in the treatment group than in the control group,while CD8+decreased significantly and was lower in the treatment group than in the control group(P<0.05).There was no statistically significant difference in T lymphocyte subsets before and after chemotherapy in the control group(P>0.05).Conclusion:Astragalus polysaccharide can improve the chemotherapy effect and improve the bone marrow suppression in elderly patients with lung cancer,which may be related to its obvious enhancement of immune function and decrease of CD62L and Mac-1 levels.展开更多
CD46 is not only identified as a complement regulatory protein which protects host cells from complement attack,but also a new co-stimulatory molecule for human T cells.CD3/CD46 co-stimulation can induce a T-regulator...CD46 is not only identified as a complement regulatory protein which protects host cells from complement attack,but also a new co-stimulatory molecule for human T cells.CD3/CD46 co-stimulation can induce a T-regulatory 1 cell(Tr1)-specific cytokine phenotype in human CD4+ T cells.However,the role of CD46 as a co-stimulatory molecule in the modulation of the acquired immunity,such as transplant immunology,remains unclear.In this study,CD4+ T cells were isolated from human CD46-transgenic C57BL/6 mice by magnetic-activated cell sorting,and further induced by anti-CD3,anti-CD28 and anti-CD46 antibodies respectively,and anti-CD3/anti-CD28 antibodies,anti-CD3/anti-CD46 antibodies,or the monoclonal antibody panel against CD3/CD28/CD46.The levels of interleukin-2(IL-2),γ-interferon(γ-IFN),interleukin-10(IL-10) and transforming growth factor-β(TGF-β) were detected in the supernatants of different groups.Suppression of allogeneic T cell proliferation were assessed by using mixed lymphocyte reaction(MLR) assay,in which monoclonal antibodies against CD46 were added to the culture.The results showed that CD3/CD28,CD3/CD46 and CD3/CD28/CD46 co-stimulation could significantly induce stronger proliferation of T cells than CD3 stimulation(P<0.05),and CD3/CD28/CD46 co-stimulation significantly increased the proliferation of T cells when compared with CD3/CD28 or CD3/CD46 co-stimulation(P<0.05 for each).IL-2 and γ-IFN levels were much higher in CD3/CD28 co-stimulation group than in CD3,CD28,CD46 and CD3/CD46 groups(P<0.05 for each).IL-10 and TGF-β levels were dramatically increased in CD3/CD46 co-stimulation group as compared with those in the CD3,CD28,CD46 and CD3/CD28 groups(P<0.05 for each).CD3/CD46 co-stimulation significantly inhibited the T cell proliferation and allogenic immune responses through the secretion of IL-10 and TGF-β in MLR(P<0.05).These results suggested that CD3/CD46 can induce Tr1 cells to modulate allogenic immune responses,and it may become a novel target for the development of new therapeutic approach for T-cell-mediated diseases.CD46 plays an important role in regulating the T cell-mediated immune responses by bridging innate and acquired immunity.展开更多
Objective To construct and screen the suppression subtractive hybridization (SSH) library of human renal cell carcinoma (RCC). Methods Poly A+ RNA was isolated from RCC lines 786-O(tester) and renal cell(RC) lines HK-...Objective To construct and screen the suppression subtractive hybridization (SSH) library of human renal cell carcinoma (RCC). Methods Poly A+ RNA was isolated from RCC lines 786-O(tester) and renal cell(RC) lines HK-2 ( driver), respectiely. SSH procedure was performed according to the protocol of the PCR-Select cDNA Subtraction Kit ( Clontech), and PCR products were cloned into pT-Adv vector and transformed E. coli TOP10F’. All positive clones picked out were digested and some of which were sequenced. Results The SSH library contained 362 clones with SSH cDNA fragments distributed mainly from 0.3 to 0.9 kb. Among 50 clones sequenced randomly,2 represented unknown genes and the other 48 derived from 36 known genes. Conclusion The quality of the SSH library of human RCC is reliable and is construction is the basis for further screening differentially expressed genes of RCC. 6 refs,4 figs, 1 tab.展开更多
Objective This study aimed to investigate the changes of follicular helper T(TFH)and follicular regulatory T(TFR)cell subpopulations in patients with non-small cell lung cancer(NSCLC)and their significance.Methods Per...Objective This study aimed to investigate the changes of follicular helper T(TFH)and follicular regulatory T(TFR)cell subpopulations in patients with non-small cell lung cancer(NSCLC)and their significance.Methods Peripheral blood was collected from 58 NSCLC patients at different stages and 38 healthy controls.Flow cytometry was used to detect TFH cell subpopulation based on programmed death 1(PD-1)and inducible co-stimulator(ICOS),and TFR cell subpopulation based on cluster determinant 45RA(CD45RA)and forkhead box protein P3(FoxP3).The levels of interleukin-10(IL-10),interleukin-17a(IL-17a),interleukin-21(IL-21),and transforming growth factor-β(TGF-β)in the plasma were measured,and changes in circulating B cell subsets and plasma IgG levels were also analyzed.The correlation between serum cytokeratin fragment antigen 21-1(CYFRA 21-1)levels and TFH,TFR,or B cell subpopulations was further explored.Results The TFR/TFH ratio increased significantly in NSCLC patients.The CD45RA^(+)FoxP3^(int) TFR subsets were increased,with their proportions increasing in stages Ⅱ to Ⅲ and decreasing in stage IV.PD-1^(+)ICOS+TFH cells showed a downward trend with increasing stages.Plasma IL-21 and TGF-β concentrations were increased in NSCLC patients compared with healthy controls.Plasmablasts,plasma IgG levels,and CD45RA^(+)FoxP3^(int) TFR cells showed similar trends.TFH numbers and plasmablasts were positively correlated with CYFRA 21-1 in stages Ⅰ-Ⅲ and negatively correlated with CYFRA 21-1 in stage IV.Conclusion Circulating TFH and TFR cell subpopulations and plasmablasts dynamically change in different stages of NSCLC,which is associated with serum CYFRA 21-1 levels and reflects disease progression.展开更多
Background:Atherosclerosis forms the pathological basis for the development of cardiovascular disease.Since pathological processes initially develop without clinically relevant symptoms,the identification of early mar...Background:Atherosclerosis forms the pathological basis for the development of cardiovascular disease.Since pathological processes initially develop without clinically relevant symptoms,the identification of early markers in the subclinical stage plays an important role for initiating early interventions.There is evidence that regulatory T cells(Tregs)are involved in the development of atherosclerosis.Therefore,the present study aimed to identify and investigate associations with Tregs and their subsets in a cohort of healthy elderly individuals with and without subclinical atherosclerotic plaques(SAP).In addition,various lifestyle and risk factors,such as cardiorespiratory fitness,were investigated as associated signatures.Methods:A cross-sectional study was performed in 79 participants(male:n=50;age=63.6±3.7 years;body mass index=24.9±3.1 kg/m2;mean±SD)who had no previous diagnosis of chronic disease and were not taking medication.Ultrasound of the carotids to identify SAP,cardiovascular function measurement for vascular assessment and a cardiorespiratory fitness test to determine peak oxygen uptake were performed.Additionally,tests were conducted to assess blood lipids and determine glucose levels.Immunophenotyping of Tregs and their subtypes(resting(rTregs)and effector/memory(mTregs))was performed by 8-chanel flow cytometry.Participants were categorized according to atherosclerotic plaque status.Linear and logistic regression models were used to analyze associations between parameters.Results:SAP was detected in a total of 29 participants.The participants with plaque were older(64.8±3.6 years vs.62.9±3.5 years)and had higher peripheral systolic blood pressure(133.8±14.7 mmHg vs.125.8±10.9 mmHg).The participants with SAP were characterized by a lower percentage of rTregs(28.8%±10.7%vs.34.6%±10.7%)and a higher percentage of mTregs(40.3%±14.7%vs.30.0%±11.9%).Multiple logistic regression identified age(odds ratio(OR)=1.20(95%confidence interval(95%CI):1.011.42))and mTregs(OR=1.05(95%CI:1.021.10))as independent risk factors for SAP.Stepwise linear regression could reveal an association of peak oxygen uptake(β=0.441),low-density lipoprotein(LDL)(β=0.096),and SAP(β=6.733)with mTregs and LDL(β=0.104)with rTregs.Conclusion:While at an early stage of SAP,the total proportion of Tregs gives no indication of vascular changes,this is indicated by a shift in the Treg subgroups.Factors such as serum LDL or cardiopulmonary fitness may be associated with this shift and may also be additional diagnostic indicators.This could be used to initiate lifestyle-based preventive measures at an early stage,which may have a protective effect against disease progression.展开更多
Hepatitis B virus(HBV) infection is one the leading risk factors for chronic hepatitis, liver fibrosis, cirrhosis and hepatocellular cancer(HCC), which are a major global health problem. A large number of clinical stu...Hepatitis B virus(HBV) infection is one the leading risk factors for chronic hepatitis, liver fibrosis, cirrhosis and hepatocellular cancer(HCC), which are a major global health problem. A large number of clinical studies have shown that chronic HBV persistent infection causes the dysfunction of innate and adaptive immune response involving monocytes/macrophages, dendritic cells, natural killer(NK) cells, T cells. Among these immune cells, cell subsets with suppressive features have been recognized such as myeloid derived suppressive cells(MDSC),NK-reg, T-reg, which represent a critical regulatory system during liver fibrogenesis or tumourigenesis. However, the mechanisms that link HBVinduced immune dysfunction and HBV-related liver diseases are not understood.In this review we summarize the recent studies on innate and adaptive immune cell dysfunction in chronic HBV infection, liver fibrosis, cirrhosis, and HCC, and further discuss the potential mechanism of HBV-induced immunosuppressive cascade in HBV infection and consequences. It is hoped that this article will help ongoing research about the pathogenesis of HBV-related hepatic fibrosis and HBV-related HCC.展开更多
Mesenchymal stem cells (MSCs), derived from adult tissues, are multipotent progenitor cells, which hold great promise for regenerative medicine. Recent studies have shown that MSCs are immunosuppressive in vivo and ...Mesenchymal stem cells (MSCs), derived from adult tissues, are multipotent progenitor cells, which hold great promise for regenerative medicine. Recent studies have shown that MSCs are immunosuppressive in vivo and in vitro in both animals and humans. However, the mechanisms that govern these immune modulatory functions of MSCs remain largely elusive. Some studies with bulk populations of MSCs indicated that soluble factors such as PGE2 and TGFβ are important, while others support a role for cell-cell contact. In this study, we intended to clarify these issues by examining immunosuppressive effects of cloned MSCs. We derived MSC clones from mouse bone marrow and showed that the majority of these clones were able to differentiate into adipocytes and osteoblast-like cells. Importantly, cells from these clones exhibited strong inhibitory effects on TCR activation-induced T cell proliferation in vitro, and injection of a small number of these cells promoted the survival of allogeneic skin grafts in mice. Conditioned medium from MSC cultures showed some inhibitory effect on anti-CD3 induced lymphocyte proliferation independent of PGE2 and TGFβ. In comparison, direct co-culture of MSCs with stimulated lymphocytes resulted in much stronger immunosuppressive effect. Interestingly, the suppression was bi-directional, as MSC proliferation was also reduced in the presence of lymphocytes. Taking together, our findings with cloned MSCs demonstrate that these cells exert their immunosuppressive effects through both soluble factor(s) and cell-cell contact, and that lymphocytes and MSCs are mutually inhibitory on their respective proliferation.展开更多
BACKGROUND: Recent studies show that mesenchymal stem cells (MSCs) have immunomodulatory properties. They suppress the immune response to alloantigen and modify the proliferation of T cells. CD4(+)CD25(+) regulatory T...BACKGROUND: Recent studies show that mesenchymal stem cells (MSCs) have immunomodulatory properties. They suppress the immune response to alloantigen and modify the proliferation of T cells. CD4(+)CD25(+) regulatory T cells have strong immunomodulatory potential. However, little is known about the effects of rat MSCs (rMSCs) on the development of regulatory T cells. METHODS: MSCs were obtained from bone marrow of male Sprague-Dawley rats, and co-cultured with CD3(+) T cells from allogeneic spleen cells. The proportion of CD4(+)CD25(+) regulatory T cells was analyzed by flow cytometry. To further confirm the immunosuppressive activity of rMSCs, we used MTT assay and flow cytometry of CD3(+) T cells to investigate the proliferative responses of CD3(+) T cells to mitogenic stimuli. Enzyme-linked immunosorbent assay was performed to detect alterations of the cytokines TNF-alpha, TGF-beta and IL-10. RESULTS: The proliferation of CD3(+) T cells decreased when co-cultured with rMSCs, and the degree of inhibition was concentration-dependent. The percentage of CD4(+)CD25(+) regulatory T cells increased when CD3(+) T cells were co-cultured with different concentrations of rMSCs. The levels of pro-inflammatory cytokine (TNF-alpha) decreased while anti-inflammatory JGF-beta, IL-10) cytokines increased in mixed lymphocyte reaction. CONCLUSIONS: rMSCs inhibit allogeneic T cell proliferation in mixed cell cultures. This immunosuppressive effect seems to be mediated by inducing the generation of CD4(+)CD25(+) regulatory T cells and soluble factors.展开更多
Milk fat globule membrane(MFGM),which contains abundant glycoproteins and phospholipids,exerts beneficial effects on intestinal health and immunomodulation.The aim of this study was to evaluate the protective effects ...Milk fat globule membrane(MFGM),which contains abundant glycoproteins and phospholipids,exerts beneficial effects on intestinal health and immunomodulation.The aim of this study was to evaluate the protective effects and possible underlying mechanisms of MFGM on cow’s milk allergy(CMA)in aβ-lactoglobulin(BLG)-induced allergic mice model.MFGM was supplemented to allergic mice induced by BLG at a dose of 400 mg/kg body weight.Results demonstrated that MFGM alleviated food allergy symptoms,decreased serum levels of lipopolysaccharide,pro-inflammatory cytokines,immunoglobulin(Ig)E,Ig G1,and Th2 cytokines including interleukin(IL)-4,while increased serum levels of Th1 cytokines including interferon-γand regulatory T cells(Tregs)cytokines including IL-10 and transforming growth factor-β.MFGM modulated gut microbiota and enhanced intestinal barrier of BLG-allergic mice,as evidenced by decreased relative abundance of Desulfobacterota,Rikenellaceae,Lachnospiraceae,and Desulfovibrionaceae,while increased relative abundance of Bacteroidetes,Lactobacillaceae and Muribaculaceae,and enhanced expressions of tight junction proteins including Occludin,Claudin-1 and zonula occludens-1.Furthermore,MFGM increased fecal short-chain fatty acids(SCFAs)levels,which elevated G protein-coupled receptor(GPR)43 and GPR109A expressions.The increased expressions of GPR43 and GPR109A induced CD103+dendritic cells accumulation and promoted Tregs differentiation in mesenteric lymph node to a certain extent.In summary,MFGM alleviated CMA in a BLG-induced allergic mice model through enhancing intestinal barrier and promoting Tregs differentiation,which may be correlated with SCFAs-mediated activation of GPRs.These findings suggest that MFGM may be useful as a promising functional ingredient against CMA.展开更多
AIM: To develop a practical method for isolation, purification and culture of hepatic Kupffer cells (KCs) and to observe their suppressive effects on the proliferation of alloreactive T cells.METHODS: Perfusion in...AIM: To develop a practical method for isolation, purification and culture of hepatic Kupffer cells (KCs) and to observe their suppressive effects on the proliferation of alloreactive T cells.METHODS: Perfusion in situ in vivo combined with density gradient centdfugation was applied in isolation, purification and culture of hepatic KC. The suppression by KCs on the T cell proliferation in mixed lymphocyte reaction (MLR) was observed.RESULTS:(1.1± 0.2) ×10^7 KCs per liver, (93.5% ±1.8%) viable cells, over 90% purity and positive for FD-2. After the first 24 h in culture, a great number of KCs which exhibited typical characteristics were observed. Using 3H-TdR incorporation assay, non-irradiated KCs significantly suppressed allo-MLR. The KCs recovered from accepted liver allografts in groups D and F were more effective in suppressing allo-MLR.CONCLUSION: A standardized procedure for isolation of highly purified rat KCs is proposed and KCs have suppressive effects on the proliferation of alloreactive T cells, especially those derived from accepted liver allografts.展开更多
基金supported by the National Natural Science Foundation of China(62074052,61974173,52072327)the Joint Talent Cultivation Funds of NSFC-HN(U1904192)the Science and Technology Innovation Talents in Universities of Henan Province(21HASTIT023)。
文摘Kesterite Cu_(2)ZnSn(S,Se)_(4)(CZTSSe)solar cells suffer from severe carrier recombination,limiting the photovoltaic performance.Unfavorable energy band alignment at the p-n junction and defective front interface are two main causes.Herein,oxygen incorporation in CZTSSe via absorber air-annealing was developed as a strategy to optimize its surface photoelectric property and reduce the defects.With optimized oxygen incorporation conditions,the carrier separation and collection behavior at the front interface of the device is improved.In particular,it is found that oxygen incorporated absorber exhibits increased band bending,larger depletion region width,and suppressed absorber defects.These indicate the dynamic factors for carrier separation become stronger.Meanwhile,the increased potential difference between grain boundaries and intra grains combined with the decreased concentration of interface deep level defect in the absorber provide a better path for carrier transport.As a consequence,the champion efficiency of CZTSSe solar cells has been improved from 9.74%to 12.04%with significantly improved open-circuit voltage after optimized air-annealing condition.This work provides a new insight for interface engineering to improve the photoelectric conversion efficiency of CZTSSe devices.
基金supported by the National Natural Science Foundation of China(Grant Nos.62104156,62074102)the Guangdong Basic and Applied Basic Research Foundation(Grant Nos.2023A1515011256,2022A1515010979)China+1 种基金Science and Technology plan project of Shenzhen(Grant Nos.20220808165025003,20200812000347001)Chinasupported by the open foundation of Guangxi Key Laboratory of Processing for Non-ferrous Metals and Featured Materials,State Key Laboratory of Featured Metal Materials and Life-cycle Safety for Composite Structures,Guangxi University(Grant No.2022GXYSOF13)。
文摘Sb_(2)Se_(3) with unique one-dimensional(1D) crystal structure exhibits exceptional deformation tolerance,demonstrating great application potential in flexible devices.However,the power conversion efficiency(PCE) of flexible Sb_(2)Se_(3) photovoltaic devices is temporarily limited by the complicated intrinsic defects and the undesirable contact interfaces.Herein,a high-quality Sb_(2)Se_(3) absorber layer with large crystal grains and benign [hkl] growth orientation can be first prepared on a Mo foil substrate.Then NaF intermediate layer is introduced between Mo and Sb_(2)Se_(3),which can further optimize the growth of Sb_(2)Se_(3)thin film.Moreover,positive Na ion diffusion enables it to dramatically lower barrier height at the back contact interface and passivate harmful defects at both bulk and heterojunction.As a result,the champion substrate structured Mo-foil/Mo/NaF/Sb_(2)Se_(3)/CdS/ITO/Ag flexible thin-film solar cell delivers an obviously higher efficiency of 8.03% and a record open-circuit voltage(V_(OC)) of 0.492 V.This flexible Sb_(2)Se_(3) device also exhibits excellent stability and flexibility to stand large bending radius and multiple bending times,as well as superior weak light photo-response with derived efficiency of 12.60%.This work presents an effective strategy to enhance the flexible Sb_(2)Se_(3) device performance and expand its potential photovoltaic applications.
基金supported by the National Natural Science Foundation of China,Nos.82104560(to CL),U21A20400(to QW)the Natural Science Foundation of Beijing,No.7232279(to XW)the Project of Beijing University of Chinese Medicine,No.2022-JYB-JBZR-004(to XW)。
文摘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.
文摘Thichosanthin(Tk), a polypeptide with 249 amino acid residues isolated and purified from a Chinese medicinal herb, showed the capability of inducing abortion and was able to inhibit tumor growth and HIV replication. Owing to sequence homology of the peptide with a ribosomeinactivating protein, the downward activity of Tk was suggested to be related to its cytotoxic property. We report here, however, that Tk could exert potent inhibitory effects on human lymphoproliferative responses in vitro to allogeneic, mitogenic and soluble antigens with 50% inhibition doses ranged between 0.05 and 0.5 μg/ml. The lowresponsiveness caused by Tk was not due to toxic cytolysis. Rather, evidences suggested that, in the dose range adopted, the Tk-induced inhibition was attributable, at least in part, to immune suppression, in view of (1) Tk was more effective in the early stage of alloreactivity; (2)Suppression also occurred if responder cells were pulsetreated with Tk rather than cocultured; (3) Irradiated Tk-pulsed cells were capable of inducing suppression in a Tk-free culture; (4) Suppression could also be transferred by the supernatants of Tk-pulsed cultured cells; (5) Tkinduced immune suppression was diminished by depletion of CD8+ cells from the culture, and, finally; (6) Adding CD8+ cells back to the culture could restore the suppres Trichosanthin-induced humall immune suppression sion. Thus the possibility that Tk might function as a down-regulator by immunological mechanisms in human immune responses is discussed.
基金supported by grants from National Natural Science Foundation of China (No. 30700799, 81172803)Doctoral Fund of Ministry of Education of China (No. 20070487119)Natural Science Foundation of Hubei Province (No. 2007AD A201)
文摘T cell immunoglobulin and mucin domain 3 (Tim-3) is well known to negatively regulate T cells responses, but its role in burn-induced T cells immune suppression remains unclear. In the present study, in order to identify the relationship between Tim-3 expression and post-burn T cells immune suppression, C57BL/6 mice were subjected to burn injury or sham injury, and the liver and spleen were harvested at the day 1 after operation. The expression level of Tim-3 on hepatic or splenic T cells and the functional properties of Tim-3+ T cells were evaluated. It was found burn injury induced dramatically elevated Tim-3 expression on both hepatic and splenic CD4+ and CD8+ T cells in contrast with the post-burn depletion of T cells. Furthermore, Tim-3 expression was correlated with the suppressive phenotype of T cells following burn injury, including increased expression of anti-inflammatory cytokine IL-10, decreased expression of pro-inflammatory cytokines IFN-γ and TNF-α, reduced T cell proliferation and elevated co-expression of Tim-3 and PD-1. Moreover, Tim-3+ T cells subsets were more prone to spontaneous apoptosis than Tim-3- T cells subsets. Our findings reinforce the idea that the up-regulated expression of Tim-3 on T cells after burn injury plays an important role in the development and maintenance of burn-induced T cell immune suppression.
文摘AIM: To investigated the interaction between toll-like receptor 4 (TLR4)-activated hepatoma cells and macrophages in the induction of tumor-immune suppression mediated by CD4+CD25high family of transcription factor P3 (FOXP3) regulatory T cells (Tregs). METHODS: The proportion of FOXP3+ Tregs was identified in peripheral blood and tumor tissues of 60 hepatocellular carcinoma (HCC) patients. TLR4 expression was examined in tumor tissues and cell lines. The correlation was examined between FOXP3+ Tregs in peripheral blood and TLR4 expression of HCC tissues. Following activation of TLR4 in H22 murine hepatoma cells pre-incubated with lipopolysaccharide (LPS) and co-cultured with macrophage cell line RAW246.7, the synthesis of cytokines tumor necrosis factor-α, CCL22, and interleukin (IL)-10 by the two cell lines was detected and analyzed. RESULTS: FOXP3+ Tregs were enriched in tumor sites, and circulating FOXP3+ Tregs were increased in HCC patients in correlation with multiple tumor foci and up-regulated TLR4 expression in HCC tissues. Semi-quantitative analysis indicated that TLR4 was over-expressed in HCC compared with the matched normal tissues. Cell cultivation experiments indicated that the mRNAs of IL-10 and CCL22 were significantly up-regulated in the RAW246.7 cell line when co-cultured with LPS preincubated H22 cells. CONCLUSION: In hepatoma cell lines, TLR4 may indirectly facilitate the recruitment of Tregs to the tumor site and promote intrahepatic metastasis through its interaction with macrophages.
基金funded by the National Natural Science Foundation of China(62004165)the China Postdoctoral Science Foundation(2020M670036)+2 种基金the Natural Science Foundation of Shaanxi Province,China(2020JQ195)the Joint Research Funds of Department of Science&Technology of Shaanxi Province and Northwestern Polytechnical University(2020GXLH-Z-007,2020GXLH-Z-025)the Fundamental Research Funds for the Central Universities。
文摘The vast majority of high-performance perovskite solar cells(PSCs) are based on a formamidinium lead iodide(FAPbI_(3))-dominant composition. Nevertheless, the FA-based perovskite films suffer from undesirable phase transition and defects-induced non-ideal interfacial recombination, which significantly induces energy loss and hinders the improvement of device performance. Herein, we employed 4-fluorophenylmethylammonium iodide(F-PMAI) to modulate surface structure and energy level alignment of the FA-based perovskite films. The superior optoelectronic films were obtained with reduced trap density, pure α-phase FAPbI_(3) and favorable energy band bending. The lifetime of photogenerated charge carriers increased from 489.3 ns to 1010.6 ns, and a more “p-type” perovskite film was obtained by the post-treatment with F-PMAI. Following this strategy, we demonstrated an improved power conversion efficiency of 22.59% for the FA-based PSCs with an open-circuit voltage loss of 399 m V.
基金This study was financially supported by the National Natural Science Foundation of China(No.31370835)National Science and Technology Major Special Project on new drug innovation(No.2012ZX09503-001-003)funding from the Dalian University of Technology for the corresponding author(No.DUT21YG121).
文摘Physiotherapeutic effects of infrared lasers have been proved in clinic.These infrared-based regulations of the bioelectrical activities can roughly be classied into enhancement and suppression of action potential(AP),which are described by sodium(Na)and potassium(K)transmembrane current equations,named as Hodgkin and Huxley(HH)-model.The enhancement effect is able to evoke or strengthen the AP when infrared light is applied.Its corresponding mechanism is commonly ascribed to the changes of the cell membrane capacitance,which is transiently increased in response to the infrared radiation.The distinctive feature of the suppression effect is to inhibit or reduce the AP by the designed protocols of infrared radiation.However,its mechanism presents more complexity than that in enhancement cases.HH-model describes how the Na current determines the initial phase of AP.So,the enhancement and suppression of AP can be also ascribed to the regulations of the corresponding Na currents.Here,a continuous infrared light at the wavelength of 980 nm(CIS-980)was employed to stimulate a freshly isolated hippocampal neuron in vitro and a suppression effect on the Na currents of the neuron cell was observed.Both Na and K currents,which are named as whole cell currents,were simultaneously recorded with the cell membrane capacitance current by using a patch clamp combined with infrared irradiation.The results demonstrated that the CIS-980 was able to reversibly increase the capacitance currents,completely suppressed Na currents,but little changed K currents,which forms the steady outward whole cell currents and plays a major role on the AP repolarization.A conrmation experiment was designed and carried out by synchronizing tens of milliseconds of infrared stimulation on the same kinds of hippocampal neuron cells.After the blocked K channel,a reduction of Na current amplitude was still recorded.This proved that infrared suppression of Na current was irrelevant to K channel.A membrane capacitance mediation process was preliminarily proposed to explain the Na channel suppression process.
基金supported by the European Union’s Horizon 2020 Research and Innovation Program(RESHAPE,825392)to Joanna Hester and Fadi Issasupported by the Restore Research Trust。
文摘Chimeric antigen receptors(CARs)are a breakthrough in genetic engineering that have revolutio nized the field of adoptive cellular therapy(ACT).Cells expressing these receptors are rerouted to a predefined target by the inclusion of an antigen-specific binding region within the synthetic CAR construct.The advantage of cells with programmed specificity has been demonstrated clinically in the field of oncology,and it is clear that such cells have greater accuracy,potency,and reduced off-target therapeutic effects compared with their unmodified counterparts.In contrast to conventional T cells(Tconvs),regulatory T cells(Tregs)play a major role in suppressing immune activation and regulating the host immune response.CAR expression within Tregs has been proposed as a therapy for autoimmune and inflammatory diseases,graft-versus-host disease(GVHD),and organ transplant rejectio n.In the latter,they hold immense potential as mediators of immune tolerance for recipients of allotransplants.However,current research into CAR-Treg engineering is extremely limited,and there is uncertainty regarding optimal design for therapeutic use.This review examines the rationale behind the development of CAR-Tregs,their significance for human transplantation,potential designs,safety considerations,and comparisons of CAR-Tregs in transplantation models to date.
基金Project Description of Xingtai Science and Technology Plan(No.2019ZC206)
文摘Objective:To investigate the effects of astragalus polysaccharides(APS)on bone marrow suppression and hematopoietic stem cells during chemotherapy in elderly patients with lung cancer.Methods:120 elderly patients with lung cancer treated in the first hospital of Xingtai city from January 2019 to early December 2019 were divided into the treatment group and the control group by the random number table method,all of whom received pemetrexed+carboplatin chemotherapy,and the treatment group was treated with APS at the same time.The efficacy was evaluated after 2 cycles of chemotherapy,bone marrow suppression was observed,and levels of TCM symptoms score,peripheral blood T lymphocyte subgroup index,L-selectin(CD62L)and macrophage differentiation antigen-1(Mac-1)were measured before and after 2 cycles of chemotherapy.Results:The response rate(RR)was 56.67%in the treatment group and 45.00%in the control group,with no statistically significant difference(P>0.05);The disease control rate(DCR)in the treatment group was 81.67%,which was significantly higher than 65.00%in the control group(P<0.05);The reduction degree of leukopenia in the treatment group was significantly lower than that in the control group(P<0.05);The treatment group had a platelet reduction of grade 1+2 at a rate of 40.00%,and hemoglobin reduction of grade 1+2 at a rate of 28.33%,which were significantly lower than the control group at 65.00%and 58.33%(P<0.05);Compared with those before chemotherapy,the total score of TCM symptoms,serum CD62L and Mac-1 levels in the two groups all decreased significantly after chemotherapy,and they were significantly lower in the treatment group than in the control group(P<0.05);After chemotherapy,CD3+,CD4+and CD4+/CD8+in the treatment group increased significantly and they were all higher in the treatment group than in the control group,while CD8+decreased significantly and was lower in the treatment group than in the control group(P<0.05).There was no statistically significant difference in T lymphocyte subsets before and after chemotherapy in the control group(P>0.05).Conclusion:Astragalus polysaccharide can improve the chemotherapy effect and improve the bone marrow suppression in elderly patients with lung cancer,which may be related to its obvious enhancement of immune function and decrease of CD62L and Mac-1 levels.
基金supported by a grant from National Natural Sciences Foundation of China (No.30600573)
文摘CD46 is not only identified as a complement regulatory protein which protects host cells from complement attack,but also a new co-stimulatory molecule for human T cells.CD3/CD46 co-stimulation can induce a T-regulatory 1 cell(Tr1)-specific cytokine phenotype in human CD4+ T cells.However,the role of CD46 as a co-stimulatory molecule in the modulation of the acquired immunity,such as transplant immunology,remains unclear.In this study,CD4+ T cells were isolated from human CD46-transgenic C57BL/6 mice by magnetic-activated cell sorting,and further induced by anti-CD3,anti-CD28 and anti-CD46 antibodies respectively,and anti-CD3/anti-CD28 antibodies,anti-CD3/anti-CD46 antibodies,or the monoclonal antibody panel against CD3/CD28/CD46.The levels of interleukin-2(IL-2),γ-interferon(γ-IFN),interleukin-10(IL-10) and transforming growth factor-β(TGF-β) were detected in the supernatants of different groups.Suppression of allogeneic T cell proliferation were assessed by using mixed lymphocyte reaction(MLR) assay,in which monoclonal antibodies against CD46 were added to the culture.The results showed that CD3/CD28,CD3/CD46 and CD3/CD28/CD46 co-stimulation could significantly induce stronger proliferation of T cells than CD3 stimulation(P<0.05),and CD3/CD28/CD46 co-stimulation significantly increased the proliferation of T cells when compared with CD3/CD28 or CD3/CD46 co-stimulation(P<0.05 for each).IL-2 and γ-IFN levels were much higher in CD3/CD28 co-stimulation group than in CD3,CD28,CD46 and CD3/CD46 groups(P<0.05 for each).IL-10 and TGF-β levels were dramatically increased in CD3/CD46 co-stimulation group as compared with those in the CD3,CD28,CD46 and CD3/CD28 groups(P<0.05 for each).CD3/CD46 co-stimulation significantly inhibited the T cell proliferation and allogenic immune responses through the secretion of IL-10 and TGF-β in MLR(P<0.05).These results suggested that CD3/CD46 can induce Tr1 cells to modulate allogenic immune responses,and it may become a novel target for the development of new therapeutic approach for T-cell-mediated diseases.CD46 plays an important role in regulating the T cell-mediated immune responses by bridging innate and acquired immunity.
文摘Objective To construct and screen the suppression subtractive hybridization (SSH) library of human renal cell carcinoma (RCC). Methods Poly A+ RNA was isolated from RCC lines 786-O(tester) and renal cell(RC) lines HK-2 ( driver), respectiely. SSH procedure was performed according to the protocol of the PCR-Select cDNA Subtraction Kit ( Clontech), and PCR products were cloned into pT-Adv vector and transformed E. coli TOP10F’. All positive clones picked out were digested and some of which were sequenced. Results The SSH library contained 362 clones with SSH cDNA fragments distributed mainly from 0.3 to 0.9 kb. Among 50 clones sequenced randomly,2 represented unknown genes and the other 48 derived from 36 known genes. Conclusion The quality of the SSH library of human RCC is reliable and is construction is the basis for further screening differentially expressed genes of RCC. 6 refs,4 figs, 1 tab.
基金supported by grants from the National Natural Science Foundation of China(No.82271755,No.81871230)Peking University People's Hospital Scientific Research Development Funds(RZ 2022-06).
文摘Objective This study aimed to investigate the changes of follicular helper T(TFH)and follicular regulatory T(TFR)cell subpopulations in patients with non-small cell lung cancer(NSCLC)and their significance.Methods Peripheral blood was collected from 58 NSCLC patients at different stages and 38 healthy controls.Flow cytometry was used to detect TFH cell subpopulation based on programmed death 1(PD-1)and inducible co-stimulator(ICOS),and TFR cell subpopulation based on cluster determinant 45RA(CD45RA)and forkhead box protein P3(FoxP3).The levels of interleukin-10(IL-10),interleukin-17a(IL-17a),interleukin-21(IL-21),and transforming growth factor-β(TGF-β)in the plasma were measured,and changes in circulating B cell subsets and plasma IgG levels were also analyzed.The correlation between serum cytokeratin fragment antigen 21-1(CYFRA 21-1)levels and TFH,TFR,or B cell subpopulations was further explored.Results The TFR/TFH ratio increased significantly in NSCLC patients.The CD45RA^(+)FoxP3^(int) TFR subsets were increased,with their proportions increasing in stages Ⅱ to Ⅲ and decreasing in stage IV.PD-1^(+)ICOS+TFH cells showed a downward trend with increasing stages.Plasma IL-21 and TGF-β concentrations were increased in NSCLC patients compared with healthy controls.Plasmablasts,plasma IgG levels,and CD45RA^(+)FoxP3^(int) TFR cells showed similar trends.TFH numbers and plasmablasts were positively correlated with CYFRA 21-1 in stages Ⅰ-Ⅲ and negatively correlated with CYFRA 21-1 in stage IV.Conclusion Circulating TFH and TFR cell subpopulations and plasmablasts dynamically change in different stages of NSCLC,which is associated with serum CYFRA 21-1 levels and reflects disease progression.
基金funded by the Central Hessen Research Campus,Flexi Fund,Project No.20121_1_1.
文摘Background:Atherosclerosis forms the pathological basis for the development of cardiovascular disease.Since pathological processes initially develop without clinically relevant symptoms,the identification of early markers in the subclinical stage plays an important role for initiating early interventions.There is evidence that regulatory T cells(Tregs)are involved in the development of atherosclerosis.Therefore,the present study aimed to identify and investigate associations with Tregs and their subsets in a cohort of healthy elderly individuals with and without subclinical atherosclerotic plaques(SAP).In addition,various lifestyle and risk factors,such as cardiorespiratory fitness,were investigated as associated signatures.Methods:A cross-sectional study was performed in 79 participants(male:n=50;age=63.6±3.7 years;body mass index=24.9±3.1 kg/m2;mean±SD)who had no previous diagnosis of chronic disease and were not taking medication.Ultrasound of the carotids to identify SAP,cardiovascular function measurement for vascular assessment and a cardiorespiratory fitness test to determine peak oxygen uptake were performed.Additionally,tests were conducted to assess blood lipids and determine glucose levels.Immunophenotyping of Tregs and their subtypes(resting(rTregs)and effector/memory(mTregs))was performed by 8-chanel flow cytometry.Participants were categorized according to atherosclerotic plaque status.Linear and logistic regression models were used to analyze associations between parameters.Results:SAP was detected in a total of 29 participants.The participants with plaque were older(64.8±3.6 years vs.62.9±3.5 years)and had higher peripheral systolic blood pressure(133.8±14.7 mmHg vs.125.8±10.9 mmHg).The participants with SAP were characterized by a lower percentage of rTregs(28.8%±10.7%vs.34.6%±10.7%)and a higher percentage of mTregs(40.3%±14.7%vs.30.0%±11.9%).Multiple logistic regression identified age(odds ratio(OR)=1.20(95%confidence interval(95%CI):1.011.42))and mTregs(OR=1.05(95%CI:1.021.10))as independent risk factors for SAP.Stepwise linear regression could reveal an association of peak oxygen uptake(β=0.441),low-density lipoprotein(LDL)(β=0.096),and SAP(β=6.733)with mTregs and LDL(β=0.104)with rTregs.Conclusion:While at an early stage of SAP,the total proportion of Tregs gives no indication of vascular changes,this is indicated by a shift in the Treg subgroups.Factors such as serum LDL or cardiopulmonary fitness may be associated with this shift and may also be additional diagnostic indicators.This could be used to initiate lifestyle-based preventive measures at an early stage,which may have a protective effect against disease progression.
基金the National Natural Science Foundation of China,No.81373143 and No.81571535 to Tu ZKKey Projects of Basic Research and Applied Basic Research in Universities of Guangdong Province,No.2018KZDXM055 to Tu ZK
文摘Hepatitis B virus(HBV) infection is one the leading risk factors for chronic hepatitis, liver fibrosis, cirrhosis and hepatocellular cancer(HCC), which are a major global health problem. A large number of clinical studies have shown that chronic HBV persistent infection causes the dysfunction of innate and adaptive immune response involving monocytes/macrophages, dendritic cells, natural killer(NK) cells, T cells. Among these immune cells, cell subsets with suppressive features have been recognized such as myeloid derived suppressive cells(MDSC),NK-reg, T-reg, which represent a critical regulatory system during liver fibrogenesis or tumourigenesis. However, the mechanisms that link HBVinduced immune dysfunction and HBV-related liver diseases are not understood.In this review we summarize the recent studies on innate and adaptive immune cell dysfunction in chronic HBV infection, liver fibrosis, cirrhosis, and HCC, and further discuss the potential mechanism of HBV-induced immunosuppressive cascade in HBV infection and consequences. It is hoped that this article will help ongoing research about the pathogenesis of HBV-related hepatic fibrosis and HBV-related HCC.
文摘Mesenchymal stem cells (MSCs), derived from adult tissues, are multipotent progenitor cells, which hold great promise for regenerative medicine. Recent studies have shown that MSCs are immunosuppressive in vivo and in vitro in both animals and humans. However, the mechanisms that govern these immune modulatory functions of MSCs remain largely elusive. Some studies with bulk populations of MSCs indicated that soluble factors such as PGE2 and TGFβ are important, while others support a role for cell-cell contact. In this study, we intended to clarify these issues by examining immunosuppressive effects of cloned MSCs. We derived MSC clones from mouse bone marrow and showed that the majority of these clones were able to differentiate into adipocytes and osteoblast-like cells. Importantly, cells from these clones exhibited strong inhibitory effects on TCR activation-induced T cell proliferation in vitro, and injection of a small number of these cells promoted the survival of allogeneic skin grafts in mice. Conditioned medium from MSC cultures showed some inhibitory effect on anti-CD3 induced lymphocyte proliferation independent of PGE2 and TGFβ. In comparison, direct co-culture of MSCs with stimulated lymphocytes resulted in much stronger immunosuppressive effect. Interestingly, the suppression was bi-directional, as MSC proliferation was also reduced in the presence of lymphocytes. Taking together, our findings with cloned MSCs demonstrate that these cells exert their immunosuppressive effects through both soluble factor(s) and cell-cell contact, and that lymphocytes and MSCs are mutually inhibitory on their respective proliferation.
基金supported by grants from the National Natural Science Foundation of China(No.30571768)the Scientific Research Fund of Zhejiang Education Department(No.20061385)
文摘BACKGROUND: Recent studies show that mesenchymal stem cells (MSCs) have immunomodulatory properties. They suppress the immune response to alloantigen and modify the proliferation of T cells. CD4(+)CD25(+) regulatory T cells have strong immunomodulatory potential. However, little is known about the effects of rat MSCs (rMSCs) on the development of regulatory T cells. METHODS: MSCs were obtained from bone marrow of male Sprague-Dawley rats, and co-cultured with CD3(+) T cells from allogeneic spleen cells. The proportion of CD4(+)CD25(+) regulatory T cells was analyzed by flow cytometry. To further confirm the immunosuppressive activity of rMSCs, we used MTT assay and flow cytometry of CD3(+) T cells to investigate the proliferative responses of CD3(+) T cells to mitogenic stimuli. Enzyme-linked immunosorbent assay was performed to detect alterations of the cytokines TNF-alpha, TGF-beta and IL-10. RESULTS: The proliferation of CD3(+) T cells decreased when co-cultured with rMSCs, and the degree of inhibition was concentration-dependent. The percentage of CD4(+)CD25(+) regulatory T cells increased when CD3(+) T cells were co-cultured with different concentrations of rMSCs. The levels of pro-inflammatory cytokine (TNF-alpha) decreased while anti-inflammatory JGF-beta, IL-10) cytokines increased in mixed lymphocyte reaction. CONCLUSIONS: rMSCs inhibit allogeneic T cell proliferation in mixed cell cultures. This immunosuppressive effect seems to be mediated by inducing the generation of CD4(+)CD25(+) regulatory T cells and soluble factors.
基金supported by the National Key Research and Development Program of China(Grant No.2019YFC1605000)National Natural Science Foundation of China(Grant No.31871806)the Beijing Livestock Industry Innovation Team(BAIC05-2023)。
文摘Milk fat globule membrane(MFGM),which contains abundant glycoproteins and phospholipids,exerts beneficial effects on intestinal health and immunomodulation.The aim of this study was to evaluate the protective effects and possible underlying mechanisms of MFGM on cow’s milk allergy(CMA)in aβ-lactoglobulin(BLG)-induced allergic mice model.MFGM was supplemented to allergic mice induced by BLG at a dose of 400 mg/kg body weight.Results demonstrated that MFGM alleviated food allergy symptoms,decreased serum levels of lipopolysaccharide,pro-inflammatory cytokines,immunoglobulin(Ig)E,Ig G1,and Th2 cytokines including interleukin(IL)-4,while increased serum levels of Th1 cytokines including interferon-γand regulatory T cells(Tregs)cytokines including IL-10 and transforming growth factor-β.MFGM modulated gut microbiota and enhanced intestinal barrier of BLG-allergic mice,as evidenced by decreased relative abundance of Desulfobacterota,Rikenellaceae,Lachnospiraceae,and Desulfovibrionaceae,while increased relative abundance of Bacteroidetes,Lactobacillaceae and Muribaculaceae,and enhanced expressions of tight junction proteins including Occludin,Claudin-1 and zonula occludens-1.Furthermore,MFGM increased fecal short-chain fatty acids(SCFAs)levels,which elevated G protein-coupled receptor(GPR)43 and GPR109A expressions.The increased expressions of GPR43 and GPR109A induced CD103+dendritic cells accumulation and promoted Tregs differentiation in mesenteric lymph node to a certain extent.In summary,MFGM alleviated CMA in a BLG-induced allergic mice model through enhancing intestinal barrier and promoting Tregs differentiation,which may be correlated with SCFAs-mediated activation of GPRs.These findings suggest that MFGM may be useful as a promising functional ingredient against CMA.
文摘AIM: To develop a practical method for isolation, purification and culture of hepatic Kupffer cells (KCs) and to observe their suppressive effects on the proliferation of alloreactive T cells.METHODS: Perfusion in situ in vivo combined with density gradient centdfugation was applied in isolation, purification and culture of hepatic KC. The suppression by KCs on the T cell proliferation in mixed lymphocyte reaction (MLR) was observed.RESULTS:(1.1± 0.2) ×10^7 KCs per liver, (93.5% ±1.8%) viable cells, over 90% purity and positive for FD-2. After the first 24 h in culture, a great number of KCs which exhibited typical characteristics were observed. Using 3H-TdR incorporation assay, non-irradiated KCs significantly suppressed allo-MLR. The KCs recovered from accepted liver allografts in groups D and F were more effective in suppressing allo-MLR.CONCLUSION: A standardized procedure for isolation of highly purified rat KCs is proposed and KCs have suppressive effects on the proliferation of alloreactive T cells, especially those derived from accepted liver allografts.