Objective To review the regulation of liver regeneration factors. Methods The literatures about liver regeneration related regulators in recent years were reviewed. Results With further advancement of researches on regulators of liver regeneration in recent years, there were more therapies for treatment of liver-related diseases. Regulators play important roles in the process of liver regeneration, as one of which, cell growth factor plays an essential role in liver cell proliferation, such as the proper expression of TNF-α and IL-6 promoting liver cell proliferation, HGF, TGF-α, EGF, ALR, FS, and others motivating liver cell proliferation, while TGF-β and IL-1 physically terminating liver cell proliferation. Conclusion By strengthening the studies on liver regeneration regulators, new methods may appear for treating liver-related diseases.
Objective To investigate the anti-rejection effect and the mechanism of triptolide （TPT） on islet allo- grafts in a murine model. Methods BALB/c mice were used as islet donor. C57BL/6 mice were rendered diabetic by streptozotocin （STZ） injection， and transplanted with islets under the left kidney capsule. The recipients were randomly （method of random digits table） divided into three groups （n=8）. The mice in the treatment groups were injected intrap-eritoneally with TPT at 50 μg/kg （low-dose TPT group， L-TPT group） or 100 μg/kg （high-dose TPT group， H-TPT group） daily in the first 5 days and then on alternate days until 14 days；while the mice in control group were given vehicles （1% tween 80）. Blood glucose after operation were monitored. The grafts were defined as rejection when two consecutive reading of blood glucose＞20 mmol/L. The left kidney of three recipients in each group were resected for pathological examination. The proportion of CD4＋CD25＋Foxp3＋ regulatory T cells in spleen tissues were tested by flow cytometry. Results The median survival time of islet allografts from the control group， L-TPT group， and H-TPT group were 12.6 days （9-16 days）， 21.4 days （14-27 days） ， and 27.6 days （19-34 days）， respectivly. The percentageof CD4＋CD25＋Foxp3＋regulatory T cells in spleen tissues of three groups were （5.2±0.6）%， （12.0±1.3）%， and（15.7±1.8）%， respectivly. Compared with control group， the median survival time of islet transplantation in mice exte-nded and the proportion of CD4＋CD25＋Foxp3＋ regulatory T cells in spleen tissues increased （P＜0.05）. Conclusions TPT could increase the percentage of CD4＋CD25＋Foxp3＋ regulatory T cells， reduce the rejection after islet transplanta-tion， and prolong the survival time of islet transplantation in mice. The immunosuppressive effect of TPT shows a dose-dependent.
Objective
To establish a method to isolate the CD4+CD25+ regulatory T cells (Tregs) and to identify the purity and function of these cells.
Methods
The peripheral blood (8 mL) were collected from the great saphenous vein of 10 rhesus monkeys (4 females and 6 males, aged 4-5 years, and weighing 5-8 kg). The mononuclear cells were isolated with density gradient centrifugation. CD4+ T cells were separated by the Magnetic cell sorting (MACS) negative selection and MACS positive selection. The cell yield rate, the cell viability, and the cell purity were compared between MACS negative selection and MACS positive selection. In CD4+ MACS negative selection, the anti-biotin MicroBeads and biotin-antibody cocktai in CD4+CD25+ Tregs isolation kit non-human primate were used, and in MACS positive selection, the anti-APC MicroBeads in CD4+CD25+ Tregs isolation kit non-human primate and CD4-APC were used. The CD4+ T cells separated by positive selection were selected to obtain CD4+CD25 Tregs with CD25 MicroBeads. The purity, activity, the FoxP3 level, and the suppressive function to concanavalin A (ConA) activated autologous CD4+CD24- effective T cells (Teffs) of CD4+CD25+ Tregs were detected by flow cytometry.
Results
After CD4+ T cells were separated by MACS negative selection and MACS positive selection, the cell viabilities were all up to 95%, showing no significant difference (P gt; 0.05). The cell yield rate and purity of CD4+ T cells by positive selection were significantly higher than those of CD4+ T cells by negative selection (P lt; 0.05). CD4+CD25+ Tregs can be successfully isolated by MACS double positive selection. The classifying purity was 76.2% ± 8.6%; the cell activity was 93.3% ± 4.7%; and the level of FoxP3 was 74.2% ± 6.9%. The CD4+CD25+ Tregs had suppressive effect on ConA activated autologous CD4+CD25- Teffs.
Conclusion
MACS double positive selection can be used to isolate high-purity CD4+CD25+ Tregs from the peripheral blood of rhesus monkeys and the process does not influence the activity of CD4+CD25+ Tregs.
In recent years, real-world evidence data (RWD) and real-world evidence (RWE) have gained substantial attentions from healthcare practitioners and health authorities worldwide. In particular, the needs from regulatory bodies have promoted the production and use of real-world evidence. In the context of drug and device evaluation and regulation decisions, the pattern for using real world evidence may differ. This article aimed to discuss the potential uses of RWE for pre-approval clinical evaluation, post-approval monitoring and evaluation, and associated regulatory decisions, which may ultimately improve the production and use of RWE for regulatory decisions.
Given the growing importance of real-world data (RWD) in drug development, efficacy evaluation, and regulatory decision-making, establishing a scientific and systematic data quality regulatory framework has become a strategic priority for global pharmaceutical regulatory authorities. This paper analyzed the European Union's (EU's) advanced practices in RWD quality regulation, compared the RWD quality regulatory systems of China and the EU, and aimed to derive implications for enhancing China's own framework. The EU has made significant progress by promoting the interconnection, intercommunication, and efficient utilization of data resources, implementing a collaborative responsibility mechanism spanning the entire data lifecycle, developing a standardized, tool-based quality assessment system, and facilitating international cooperation and alignment of rules. While China has established an initial regulatory system for RWD quality, it still confronts challenges such as unclear mechanisms for data acquisition and utilization, underdeveloped operational standards, and unclear responsibility delineation. In contrast, by adapting relevant EU experience, China can refine its regulatory framework, establish mechanisms for the interconnection, intercommunication, and efficient utilization of RWD, develop more practical quality assessment toolkits, improve the lifecycle responsibility-sharing mechanism, and promote the alignment of RWD quality regulation with international standards. These enhancements will advance the standardization and refinement of RWD quality regulation in China, ultimately strengthening the scientific rigor and reliability of regulatory decisions.
Legionella, one of the causative pathogens of atypical pneumonia, firstly outbroked during the period of American Legion’s convention in 1976, Philadelphia. Legionella infection can accompany multisystem involvement. In addition to pulmonary lesions, it also accompanies extrapulmonary manifestations, including gastrointestinal symptoms (primarily diarrhea and hepatic dysfunction), neurological symptoms (primarily headache, disorientation and confusion of consciousness), urinary symptoms (primarily hematuria, proteinuria and acute kidney injury), rhabdomyolysis, as well as electrolyte disorder mainly characterized by hyponatremia and hypophosphatemia. This article reviews the extrapulmonary manifestations and its regulatory mechanism of Legionella infection.
Regulatory B cells (Bregs) are a subset of B cells with immunomodulatory effects. The study of Bregs began with a variety of animal models of immune diseases. Studies in patients with autoimmune diseases have further clarified that Bregs are a group of immune cells that secrete inhibitory cytokines such as interleukin-10. Abnormal functions and numbers of Bregs have been found in a variety of autoimmune diseases. The study of the negative immune regulatory network involving Bregs is expected to provide new therapeutic ideas for diseases such as immune diseases, cancer, infection and inflammation. Starting from the discovery and immune regulation mechanism of Bregs, this paper focuses on its regulatory mechanism and clinical research value in the occurrence and development of autoimmune diseases, tumors, infectious diseases and inflammation.
Objective To assess the effects of different immunosuppressive drugs on proliferation and function of regulatory T cells (Tregs). Methods We searched MEDLINE (1966 to November 2009), EMbase (from inception to September 2009), and The Cochrane Library (Issue 4, 2009) for clinical and basic research about the effects of various immunosuppressive drugs on Tregs. Data were extracted and methodological quality was assessed by two independent reviewers. Outcome measures for clinical research included blood Tregs levels, acute rejection episodes, and graft function. Outcome measures for basic research included percentage of Tregs proliferation, function, Tregs phenotype, and evidence for possible mechanisms. We analyzed data qualitatively. Results Forty-two studies, including 19 clinical trials and 23 basic studies, were included. The immunosuppressive drugs studied were calcineurin inhibitors (CNIs), Rapa, anti-metabolism drugs, IL-2 receptor-blocking antibodies, T-cell depleting antibodies, and co-stimulation blockade antibodies. Most of the studies were on Rapa and CNIs. Eight basic studies on Rapa and CNIs showed that Rapa could promote the proliferation and function of Tregs, while CNIs could not. Five clinical trials involving a total of 158 patients showed that patients taking Rapa had higher blood concentration of Tregs than those taking CNIs, but no differences were found in graft function (6-42-month follow-up). Conclusion There is substantial evidence that Rapa favors Tregs survival and function. However, the larger number of the blood Tregs in the patients treated with Rapa does not show any correlation with better graft function. Large-sample and high-quality clinical studies with longer follow-up are needed to thoroughly assess the efficacy of immunosuppressive drugs on Tregs and to reveal whether a relationship exists between Tregs and graft function.
Regulatory T cells (Treg) are critical for regulation of tolerance, control immune responses to self-antigens thereby preventing autoimmunity, and limiting responses to foreign antigens thereby minimizing T cell-mediated immunopathology. Recent data indicate that suppression of organ-specific autoimmunity is dependent on the antigen specificity of Treg. An emerging model of Treg action is that organ-specific Treg acquire suppressive activity through activation by dendritic cells expressing specific antigens. Thus, the efficacy of Treg-based therapy should be increased by using antigen-specific Treg rather than polyclonal Treg. It is necessary to identify relevant antigens and to expand antigen-specific Treg from polyclonal populations. Here, we discuss recent techniques for expansion of antigen-specific Treg, function and antigen specificity of Treg and the therapeutic potential of Treg in controlling autoimmune disease and inducing transplant tolerance.
Objective To investigate the efficacy of continuous blood purification ( CBP) in the treatment of severe sepsis, and explore the related immune regulatory mechanisms. Methods Forty-eight patients with severe sepsis were randomly divided into a control group ( n =23) and a CBP group ( n =25) .CD4 + CD25 + regulatory T cells ( Treg% ) in peripheral blood and APACHEⅡ score were measured dynamically before treatment and 12, 24, 36, 48, 60, 72 hours after treatment. Meanwhile the length of ICUstay, duration of mechanical ventilation, and 28 day mortality were determined. Results Compared with the control group, the length of ICU stay, ventilator time, incidence of multiple organ failure, and mortality decreased significantly in the CBP group ( P lt; 0. 05) . And CBP also decreased Treg% and APACHEⅡ score significantly. There was a positive correlation between Treg% and APACHEⅡ score ( r =0. 804, P lt;0. 01) .Conclusion Early CBP treatment can reduce Treg%, improve cellular immunity and improve the prognosis of sepsis.
