Células madre en odontología: nuevas perspectivas / Stem cells in dentistry: new perspectives

En el campo de la odontología, prevalecen actualmente alternativas terapéuticas con una filosofía conservadora. Sin embargo, con el advenimiento de los tratamientos con células madre (CM), se amplían las posibilidades terapéuticas, que buscan la combinación y el equilibrio entre la intervención tradicional y las posibilidades de reposición de estructuras anatómicas dañadas, a través de la regeneración de tejidos utilizando células madre o sus derivados (AU)

In the dentistry field, therapeutic alternatives with a conservative philosophy currently prevail. However, with the advent of stem cell (SC) treatments, therapeutic possibilities are expanding, seeking a combination and balance between traditional intervention and the pos- sibility of replacing damaged anatomical structures through tissue regeneration, using stem cells or their derivatives (AU)

A 3D hydrogel loaded with exosomes derived from bone marrow stem cells promotes cartilage repair in rats by modulating immunological microenvironment / 南方医科大学学报

OBJECTIVE@#To assess the efficacy of GelMA hydrogel loaded with bone marrow stem cell-derived exosomes for repairing injured rat knee articular cartilage.@*METHODS@#The supernatant of cultured bone marrow stem cells was subjected to ultracentrifugation separate and extract the exosomes, which were characterized by transmission electron microscopy, particle size analysis and Western blotting of the surface markers. The changes in rheology and electron microscopic features of GelMA hydrogel were examined after loading the exosomes. We assessed exosome release from the hydrogel was detected by BCA protein detection method, and labeled the exosomes with PKH26 red fluorescent dye to observe their phagocytosis by RAW264.7 cells. The effects of the exosomes alone, unloaded hydrogel, and exosome-loaded hydrogel on the polarization of RAW264.7 cells were detected by q-PCR and immunofluorescence assay. We further tested the effect of the exosome-loaded hydrogel on cartilage repair in a Transwell co-culture cell model of RAW264.7 cells and chondrocytes in a rat model of knee cartilage injury using q-PCR and immunofluorescence assay and HE and Masson staining.@*RESULTS@#GelMA hydrogel loaded with exosomes significantly promoted M2-type polarization of RAW264.7 cells (P < 0.05). In the Transwell co-culture model, the exosome-loaded GelMA hydrogel significantly promoted the repair of injured chondrocytes by regulating RAW264.7 cell transformation from M1 to M2 (P < 0.05). HE and Masson staining showed that the exosome-loaded hydrogel obviously promoted cartilage repair in the rat models damage.@*CONCLUSION@#GelMA hydrogel loaded with bone marrow stem cell-derived exosomes can significantly promote the repair of cartilage damage in rats by improving the immune microenvironment.

Ameliorative Effect of Gramine on 2，4-Dinitrochlorobenzene-Induced Atopic Dermatitis in Mice / 中国实验方剂学杂志

ObjectiveTo explore the pharmacodynamic effect of gramine on 2，4-dinitrochlorobenzene （DNCB）-induced atopic dermatitis （AD） in mice and its potential mechanism. MethodThe mice were divided into the normal control group， model group， dexamethasone （0.05 g·kg-1） group， and high- and low-dose （0.12，0.06 g·kg-1） gramine groups. Mice in all groups except for the normal control group were stimulated with DNCB， followed by medication 13 d later. The changes in skin lesions were then observed， and the skin thickness， moisture content， and transepidermal water loss （TWEL） in each group were measured. The pathological changes in skin lesions were observed by hematoxylin-eosin （HE） staining， and the effects of drugs on CD4+/CD8+T-cell ratio in the spleen were detected by flow cytometry. The levels of immunoglobulin E （IgE）， interleukin （IL）-4， and IL-6 in serum were detected by enzyme-linked immunosorbent assay （ELISA）， and the changes in serum alanine aminotransferase （ALT）， aspartate aminotransferase （AST）， blood urea nitrogen （BUN）， and creatinine （CRE） by microplate method. The mRNA expression levels of inflammatory cytokines γ-interferon（IFN-γ）， IL-13， IL-17， IL-1β， IL-6， and tumor necrosis factor-α （TNF-α） in skin lesions were assayed by real-time polymerase chain reaction （Real-time PCR）， and the protein expression levels of nuclear transcription factor -κB (NF-κB) and NF-κB inhibitory protein α (IκBα) in skin lesions by Western blot. ResultCompared with the normal control group， the model group showed skin edema， erythema， scab， scratch， and lymphocyte and neutrophil infiltration， decreased skin moisture content， as well as increased skin thickness， TWEL （P<0.01）， spleen index， CD4+/CD8+ T-cell ratio in the spleen （P<0.05）， mRNA expression of IFN-γ， IL-13， IL-17， IL-1β， IL-6， and TNF-α in the skin lesions （P<0.05）， serum contents of IgE， IL-4， and IL-6 （P<0.05）， and protein expression of IκBα and NF-κB in skin lesions （P<0.05）. Compared with the model group， dexamethasone and gramine at different doses alleviated skin erythema， scale， scab， and inflammatory cell infiltration， elevated skin moisture content， inhibited skin thickening and TWEL， and decreased spleen index， CD4+/CD8+T-cell ratio in the spleen， mRNA expression of inflammatory factors in the skin lesions， serum contents of IgE and inflammatory factors， and protein expression of IκBα and NF-κB in skin lesions， especially in the dexamethasone group and the high- dose gramine group（P<0.05，P<0.01）. ConclusionGramine can inhibit the expression of related inflammatory factors and regulate the immune function of AD mice via the IκBα/NF-κB pathway， enabling it become a potential drug for treating AD.

Research Status of Tumor-associated Fibroblasts Regulating Immune Cells / 中国肺癌杂志

Cancer-associated fibroblasts (CAFs) and tumor-infiltrating immune cells are the most essential components of the tumor microenvironment (TME). They communicate with each other in tumor microenvironment and play a critical role in tumorigenesis and development. CAFs are very heterogeneous and different subtypes of CAFs display different functions. At the same time, it can contribute to the regulation of the function of tumor-infiltrating immune cells and eventually result in the carcinogenesis, tumor progression, invasion, metastasis and other biological behaviors of tumors by producting various growth factors and cytokines etc. Based on the current research results at home and abroad, this paper reviews the recent research progress on the regulation of CAFs on infiltrating immune cells in tumor microenvironment.
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New paradigms of immune regulation in glaucoma during the whole clinical process / 中华实验眼科杂志

Glaucoma is an irreversible blinding eye disease caused by the structural and functional damage of optic nerve induced by pathological increase of intraocular pressure (IOP), characterized by multiple causes and strong heterogeneity.The control of IOP to reduce the risk of optic damage has been the main therapeutic strategy of glaucoma for many years.However, in clinical experience, some patients show progress of optic nerve damage despite the effectively controlled IOP, the mechanism of non-IOP-dependent secondary damage is still an urgent problem to be solved and a research hotspot in the pathogenesis of glaucoma.With the continuous innovation of molecular biological technology, breakthroughs have been made in the field of basic research.Partial visual recovery can be boosted by alleviating local immune and inflammatory responses.Due to a lack of symbolic clinical application results, it has become an immediate priority to attach importance to the combination of basic clinical research and facilitate the transformation of results.Starting from the theory of glaucoma-immune inflammation, understanding the importance of the immune homeostasis of eyes, paying close attention to the linkage of eyes and brain in physiopathological process and the progression of diseases in the whole visual pathway, and fully understanding and effectively making good use of the opportunities and implications brought by new techniques will have significant effect in formulating clinical diagnosis and treatment plans.

Advances of mechanism of mesenchymal stem cells in animal experiments with bronchial asthma / 中华实用儿科临床杂志

Bronchial asthma is a common chronic airway inflammatory disease in children characterized by hyper-responsiveness, airway inflammation, and airway remodeling caused by immune responses.Currently, some limitations of glucocorticoid and allergen-specific immunotherapy restrict their application to asthma treatment.Based on the results of many animal experiments, mesenchymal stem cells (MSCs) are validated to reduce airway inflammation, improve airway hyper-responsiveness, and reverse airway remodeling through immunomodulation.Therefore, it has great application prospects as an effective therapeutic strategy for children with asthma.To explore the value of MSCs in the treatment of asthma, its underlying mechanisms are reviewed in the present study.

Mechanism of adrenocorticotropic hormone in the treatment of nephrotic syndrome / 中华实用儿科临床杂志

In recent years, it has been demonstrated in some studies that adrenocorticotropic hormone (ACTH) is effective in the treatment of certain steroid-resistant nephrotic syndrome, including membranous nephropathy, focal segmental glomerular sclerosis, minimal change nephropathy and so forth.ACTH can effectively relieve proteinuria and protect renal function, suggesting that there may be other mechanisms in addition to the adrenocorticotropic effect.This article mainly introduces the biological characteristics of ACTH, in combination with the clinical and basic studies on the treatment of nephrotic syndrome by ACTH, and clarifies several possible mechanisms, in an attempt to provide basis for clinical application.

Influência da Delfinidina como potencial modulador da capacidade imunorregulatória das Células-Tronco Mesenquimais / Influence of Delphinidin as a potential modulator of the immunoregulatory capacity of Mesenchymal Stem Cells

As Células-Tronco Mesenquimais (CTMs), são células multipotentes, presentes em diversos tecidos, sendo bastante estudada devido sua capacidade imunorregulatória por meio da liberação de fatores solúveis. Fatores estes que atuam sobre as funções de células do sistema imunitário. Simultaneamente, estudos indicam que os compostos flavonoides, em destaque a Delfinidina, presente em alguns frutos e flores, possuem atuação anti-inflamatória e inibitória sobre células do sistema imunitário. Todavia, são escassos os estudos em relação entre a capacidade imunorregulatória da CTM e a influência da Delfinidina, sendo este o objetivo deste estudo. Inicialmente, a Delfinidina 3-O-ß-D-glicosídeo foi escolhido, devido a sua maior estabilidade e a dose de 50 µM foi selecionada após análise por citometria de fluxo que mostrou aumento da fase proliferativa do ciclo celular. Posteriormente ao realizar análise da produção de fatores solúveis pelas CTM, os resultados mostraram aumento da produção de IL-10, TGF-ß e Oxido nítrico pelas CTM tratadas com Delfinidina. Bem como, diminuição da expressão de p-NF-κB/NF-κB pelas CTMs tratadas com Delfinidina, quando avaliadas por Wersten Blot. Adicionalmente, para analisar a Delfinidina sobre os efeitos imunorregulatórios da CTM sob macrófagos (RAW 264.7), célula esta, importante no sistema imune inato. Foram realizadas culturas condicionadas, com posterior análise da produção de fatores solúveis, os resultados mostraram aumento da produção de IL-10, e diminuição da produção de TNF-α, IL-1α e IL-12 pelos macrófagos, nas culturas condicionadas. Assim como, diminuição da expressão do fator p-NF-κB/NF-κB pelos macrófagos nas culturas condicionadas, quando avaliadas por Wersten Blot. Ademais, ao analisar a atividade metabólica dos macrófagos por ensaio de MTT, os resultados mostraram que as culturas condicionadas e a Delfinidina per si foi capaz de diminuir a atividade metabólica, sem alterar os efeitos anti-inflamatórios sobre a célula. Em síntese, a Delfinidina mostrou acentuar a atuação imunorregulatória da CTM sobre a linhagem macrofágica, célula esta, de grande importância para o sistema imune inato

Mesenchymal Stem Cells (MSCs) are multipotent cells present in various tissues, being widely studied due to their immunoregulatory capacity through the release of soluble factors. These factors act on the functions of cells of the immune system. Simultaneously, studies indicate that flavonoid compounds, especially Delphinidin, present in some fruits and flowers, have anti inflammatory and inhibitory effects on immune system cells. However, there are few studies on the relationship between the immunoregulatory capacity of MSC and the influence of Delphinidin, which is the objective of this study. Initially, Delphinidin 3-O-ß-D-glycoside was chosen due to its greater stability and the 50 µM dose was selected after analysis by flow cytometry which showed an increase in the proliferative phase of the cell cycle. Subsequently, when analyzing the production of soluble factors by MSCs, the results showed an increase in the production of IL-10, TGF-ß and nitric oxide by MSCs treated with Delphinidin. As well as decreased expression of p-NF-κB/NF-κB by MSCs treated with Delphinidin, when evaluated by Wersten Blot. Additionally, to analyze Delphinidin on the immunoregulatory effects of MSC on macrophages (RAW 264.7), this cell is important in the innate immune system. Conditioned cultures were performed, with subsequent analysis of the production of soluble factors, the results showed an increase in the production of IL-10, and a decrease in the production of TNF-α, IL-1α and IL-12 by macrophages, in the conditioned cultures. As well as decreased expression of p-NF-κB/NF-κB factor by macrophages in conditioned cultures, when evaluated by Wersten Blot. Furthermore, when analyzing the metabolic activity of macrophages by MTT assay, the results showed that conditioned cultures and Delphinidin itself was able to decrease the metabolic activity, without altering the anti-inflammatory effects on the cell. In summary, Delphinidin has shown to enhance the immunoregulatory action of MSC on the macrophage lineage, a cell that is of great importance for the innate immune system

Research of immunoregulation effects of regulatory T cells in dry eye disease / 中华实验眼科杂志

Dry eye disease is a multifactorial disease affecting the ocular surface, lacrimal glands and meibomian glands.Its incidence is gradually increasing and tends to occur in the younger.Its main features are ocular surface inflammation caused by tear film instability and high osmotic pressure of tears.Moreover, there is a vicious circle between inflammation and ocular surface damage.Immune-related inflammatory responses play a key role in this process.Regulatory T cell (Treg) is a subset of T cells with immunoregulatory functions, which are closely related to the occurrence and development of dry eye, and can inhibit the inflammation of dry eyes by acting on antigen-presenting cells and T helper cell (Th)1/Th17.Recent studies have shown that Treg in dry eye is abnormal in number or function and closely related to the risk factors of dry eye such as age and gender.In addition, by increasing the number of Tregs and promoting their differentiation to alleviate inflammatory response can provide new treatment strategies in dry eye.The correlation between Treg and dry eye and its related research in the pathogenesis and treatment of dry eye were reviewed in this article.

Clinical characteristics of inflammatory bowel disease complicating neuroendocrine neoplasms / 中华消化内镜杂志

A case of inflammatory bowel disease (IBD) complicating neuroendocrine neoplasms (NENs) was reported and 69 cases in references were reviewed to analyze the clinical features of IBD complicating NENs and to explore the connection between IBD and NENs. Thirty-two cases of Crohn disease (CD) and 37 cases of ulcerative colitis (UC) were included in the study. The occurrence rate showed no significant difference between males and females ( P=0.151). NENs mostly occurred after the diagnosis of IBD. The median interval duration of NENs after CD was 4.5 years, which was significantly shorter than that of UC (17 years, P=0.002). Thirty-three cases discovered NENs occasionally with no special indications. Among those symptomatic patients, 11 of them suffered from intestinal obstruction. The location of NENs was similar to IBD, that was, ileum and appendix in CD (27 cases) while colon and rectal in UC (31 cases, P<0.001). Neuroendocrine tumors were more common in CD (26 cases) while neuroendocrine carcinomas were more common in UC (22 cases, P<0.001). There is possibility that IBD complicate with NENs with no specific clinical features. The etiology of this phenomenon is still not clear, which needs further exploration.

Research progress of new vaccine adjuvants / 生物工程学报

In recent years, the development of new vaccines such as nucleic acid vaccines, genetically engineered vaccines, and synthetic peptide vaccines has achieved rapid development. However, compared with traditional inactivated or live vaccines, these vaccines often have problems such as poor immunogenicity. Therefore, an adjuvant is needed to enhance its effect, and adjuvants have proven to be a key component in vaccines. There are many types of adjuvants, while currently no unified standard for the classification. At present, the most commonly used adjuvants are Aluminum adjuvant and Freund's adjuvant, but new generation vaccines will probably need new generation adjuvants. Thus, this review aims to showcase the current status of immune adjuvants, with the focus on immunomodulatory molecular adjuvant, antigen delivery adjuvant and compound adjuvant. This review provides new insights for the development of novel vaccine adjuvants.

Research progress in immune regulation mechanism of Polygonati Rhizoma polysaccharide / 中国药理学与毒理学杂志

Polygonati Rhizoma is the dry rhizome of Liliaceae plants Polygonatum kingianum coil ethemsl, Polygona?tum sibiricum Redoute and Polygonatum cyrtonem Hua. It tastes sweet and has a flat nature. It belongs to the spleen, lung and kidney channels. Polygonati Rhizoma contains a variety of chemical components, including polysaccharides, alkaloids, steroidal saponins, lignans, phytosterols, and so on. Polygonati Rhizoma polysaccharide (PSP) is one of the main bioactive components of Polygonati Rhizoma. It is widely used. It has the effects of enhancing immunity, anti-inflammatory, anti-virus and regulating blood lipid. In recent years, the immunomodulatory function of PSP has been paid more and more attention by researchers. PSP can play an immunomodulatory role through a variety of mecha?nisms. (1) Effects of PSP on innate immunity. ① Macrophages have a strong ability to phagocytize and clear foreign bodies. When polysaccharides bind to macrophage specific membrane receptors, the immune response will be officially activated. RAW264.7 cells can be activated by PSP MR and TLR4 mediated signal pathway to improve the pinocytosis and phagocytosis of RAW264.7 cells. ② Natural killer cell (NK cell) is a very important immune cell in the body. It is a non-specific immune killer cell naturally existing in the body. It has the dual functions of immune regulation and cytotoxic?ity. It was found that the signal pathway mediated by PSP CR3 and TRL2 may play a major role in the stimulation of NK cells. (2) Effects of PSP on adaptive immune response. ① Lymphocytes can be divided into two forms: T cells and B cells due to different differentiation and maturation sites. T lymphocytes are the general name of thymus dependent lym?phocytes. B lymphocytes differentiate and mature from animal bone marrow cells and exert their humoral immune func?tion by secreting different antibodies. It was found that PSP could activate T/B lymphocytes and increase the ratio of CD4+/CD8+in lymph cells to promote the regulation of immune system.②Thymus and spleen index refers to the level of body immunity through the development of immune organs and the functional status of immune cells. The higher the index of thymus and spleen, the higher the immune activity. A large number of studies have found that PSP can improve immune activity by promoting the proliferation of spleen lymphocytes and regulating organ index, so as to increase the weight and index of thymus and spleen induced by CY. ③ Antibody is a glycoprotein secreted by B cells after antigen stimulation and a series of proliferation and differentiation into plasma cells. Antibody production level is one of the main indicators of nonspecific immune function. PSP can not only improve the serum antibody level of mice by regulating the phagocytosis of mouse macrophages and the level of serum hemolysin, but also enhance the concentration of IL-2 secreted by spleen lymphocytes in vitro to increase the level of antibody response, and then improve the humoral immune function of the body. (3) Effect of PSP on cytokines. ① A large number of experiments have proved that PSP has a significant effect on promoting the production of interleukin (IL). PSP can combine with specific receptors on the surface of immune cells to activate various intracellular signal transduction pathways, enhance the secretion of cytokines such as IL-2, IL-4, IL-6 and IL-10 by spleen lymphocytes in vitro, make them directly kill target cells and regulate the immune function of the body at the molecular level. ② Interferon (IFN) is a special protein or glycoprotein produced by human or animal cells in response to various stimuli. It plays an important role in anti-virus, immune regulation and cell proliferation control. It was found that PSP could increase IFN-γsecreted by T cells and NK cells, activate macrophages to regulate immune function. ③ Tumor necrosis factor (TNF) is mainly produced by activated macrophages, NK cells and activated T cells. It is a cytokine with important biological activity in antitumor immune response.④ Tumor necrosis factor (TNF) is mainly produced by activated macrophages, NK cells and activated T cells. It is a cytokine with important biological activity in antitumor immune response. PSP can promote the proliferation and phagocytic activity of macro?phage RAW264.7 to reduce its apoptosis rate. By increasing the secretion of TNF-α, PSP can promote the dissociation between NF-κВprotein and IκВp65 protein after phosphorylation, so as to start the expression and transcription of related immune genes. In conclusion, PSP can improve immunity and has a good application prospect in the development of immunomodulatory drugs.

Research progress on AMPK/mTOR signaling pathway involved in immunometabolic regulation in sepsis / 中国小儿急救医学

The occurrence, development and prognosis of sepsis are closely related to immune regulation.Immunometabolism has been the research hotspot of immune intervention in sepsis in recent years.AMP-activated protein kinase(AMPK)and mammalian target of rapamycin(mTOR)are star molecules involved in metabolic regulation.As an important way of immunometabolic regulation in sepsis, AMPK-mTOR is involved in the process of chemotaxis of neutrophils, the polarization of macrophages, the development and differentiation of natural killer cells and dendritic cells, and the development and functional regulation of T cells.This article reviewed the research progress of AMPK-mTOR signaling pathway on regulating metabolic reprogramming in immune cells, which contributes to immunoregulation in sepsis.

Research progress of natural polysaccharides and their nano-sized drug delivery systems in regulating tumor microenvironment / 药学学报

Natural polysaccharides with good biocompatibility and unique tumor immunomodulatory activity are becoming an important adjuvant anticancer therapy in clinic. In the field of pharmaceutics, natural polysaccharides can be used as not only bioactive components but also drug delivery carriers, as well as tumor-targeted ligands. Besides, various novel drug delivery systems based on natural polysaccharides exhibit unique advantages in regulating tumor immune microenvironment. In this review, we summarize the progress on natural polysaccharides in tumor microenvironment (TME) regulation and the designs of nano-sized drug delivery system, and point out challenges of polysaccharide-based drug delivery systems in the future application, and also give the potential solutions for these issues.

Research Progress in Pharmacology of Lianhua Qingwen Preparation / 中国实验方剂学杂志

Lianhua Qingwen preparation （LHQW） is a Chinese traditional patent medicine approved by China Food and Drug Administration （CFDA）， and divided into two dosage forms， namely capsules and granules. Based on TCM theory， its therapeutic functions are contagion-clearing， detoxification， antipyretic， and lung-ventilating regulation， with influenza as its indication. In this paper， its pharmacological activities were reviewed. LHQW had a significant anti-virus effect characterized by a broad-spectrum pattern. It was reported that it not only possessed definitely suppressive effect on a series of influenza viruses， respiratory syncytial virus， coxsackie， enterovirus， herpes simplex virus，but also displayed a significant inhibitory effect on both the new corona pneumonia virus （SARS-CoV-2） and SARS coronavirus （SARS-CoV）. Studies showed that LHQW has obvious anti-inflammatory effects on a variety of inflammation models. It can significantly increase the delayed hypersensitivity of immunocompromised mice （caused by hydrocortisone） against 2， 4-dinitrofluorobenzene， and improve their cellular immune function. It can improve the phagocytosis function of peritoneal macrophages， the serum hemolysin antibody level and the humoral immune function of mice with a low immune function， with a immunomodulatory effect. In addition， LHQW has therapeutic effects on the symptoms induced by respiratory tract infections， such as fever， cough and phlegm， so as to block the vicious circle of multiple pathological links of the disease， and bring the advantages of multi-target， multi-link and multi-approach overall treatment of TCM into play.

Effect of Wasp Venom Extract on Collagen-induced Arthritis in Rats / 中国药学杂志

OBJECTIVE: The rat model of collagen-induced arthritis (CIA) was successfully established to investigate the therapeutic effect of wasp venom extract on rheumatoid arthritis (RA) rats. METHODS: The rats were randomly divided into normal group, model group, positive control group (bee venom lyophilized powder for injection, 1.25 mg•kg-1) and low, medium and high dose (0.125, 0.25, 0.5 mg•kg-1) of wasp venom extract groups, in addition the normal group, the other group rats were induced by chicken type Ⅱ collagen and complete Freund′s adjuvant which was multi-point injected into the left hindfoot of rats, once every 7 d for 14 d. After successful modeling, the rats were given corresponding dose of drugs continuous administration for 14 d. The diameter and perimeter of the ankle joint and AI score of the rats were measured before modeling, on the 14th day of modeling and on the 14th of administration, respectively; The changes of organ index and HE staining in ankle tissue were observed. The contents of inflammatory factor (IL-1β, IL-6, TNF-α, IL-8, PGE-2, COX-2) and rheumatoid factors (IgG, IgA, IgM) in serum of rats were detected by ELISA. The changes of T lymphocyte subsets in spleen tissue of rats were detected by flow cytometry. RESULTS: Compared with the model group, the extract of wasp venom had significant inhibitory effect on joint swelling (diameter and perimeter) of CIA rats (P<0.01), The joint index scores of CIA rats was decreased(P<0.01 or P<0.05). The organs index of rats restored to varying degrees (P<0.01 or P<0.05), to improved pathological structure of ankle joint, and decreased the expression of inflammatory and rheumatoid factors in serum of rats (P<0.01 or P<0.05), to regulate and improve the proportion of T lymphocyte subsets(P<0.01 or P<0.05). CONCLUSION: The extract of wasp venom has significant therapeutic effect on CIA rats, which is related to its regulation of inflammatory cytokine network and immunity.

Inhibition of CD96 enhances interferon-γ secretion by natural killer cells to alleviate lung injury in mice with pulmonary infection / 南方医科大学学报

OBJECTIVE@#To assess the effect of neutralizing CD96 on natural killer (NK) cell functions in mice with pulmonary infection and explore the possible mechanism.@*METHODS@#Male BALB/c mice were randomly divided into infection group (Cm group), anti-CD96 treatment group (anti-CD96 group) and control group (=5). In the former two groups, was inoculated intranasal administration to establish mouse models of pulmonary infection, and the mice in the control group received intranasal administration of the inhalation buffer. In anti-CD96 group, the mice were injected with anti-CD96 antibody intraperitoneally at the dose of 250 μg every 3 days after the infection; the mice in Cm group received intraperitoneal injections of saline. The body weight of the mice was recorded daily. The mice were sacrificed 5 days after infection, and CD96 expression was detected by quantitative real-time PCR and Western blotting. HE staining and pathological scores were used to evaluate pneumonia of the mice. The inclusion body forming units (IFUs) were detected in the lung tissue homogenates to assess lung tissue chlamydia load. Flow cytometry and ELISA were used to assess the capacity of the lung NK cells to produce interferon-γ (IFN-γ) and regulate macrophages and Th1 cells.@*RESULTS@# infection inhibited CD96 expression in NK cells of the mice. Compared with those in Cm group, the mice in antiCD96 mice showed significantly milder lung inflammation ( < 0.05) and reduced chlamydia load in the lung tissue ( < 0.05). Neutralizing CD96 with anti-CD96 significantly enhanced IFN-γ secretion by the NK cells ( < 0.05) and augmented the immunoregulatory effect of the NK cells shown by enhanced responses of the lung macrophages ( < 0.05) and Th1 cells ( < 0.05).@*CONCLUSIONS@#Inhibition of CD96 alleviates pneumonia in -infected mice possibly by enhancing IFN-γ secretion by NK cells and augmenting the immunoregulatory effect of the NK cells on innate and adaptive immunity.

Novel and potent inhibitors targeting DHODH are broad-spectrum antivirals against RNA viruses including newly-emerged coronavirus SARS-CoV-2

Emerging and re-emerging RNA viruses occasionally cause epidemics and pandemics worldwide, such as the on-going outbreak of the novel coronavirus SARS-CoV-2. Herein, we identified two potent inhibitors of human DHODH, S312 and S416, with favorable drug-likeness and pharmacokinetic profiles, which all showed broad-spectrum antiviral effects against various RNA viruses, including influenza A virus, Zika virus, Ebola virus, and particularly against SARS-CoV-2. Notably, S416 is reported to be the most potent inhibitor so far with an EC of 17 nmol/L and an SI value of 10,505.88 in infected cells. Our results are the first to validate that DHODH is an attractive host target through high antiviral efficacy in vivo and low virus replication in DHODH knock-out cells. This work demonstrates that both S312/S416 and old drugs (Leflunomide/Teriflunomide) with dual actions of antiviral and immuno-regulation may have clinical potentials to cure SARS-CoV-2 or other RNA viruses circulating worldwide, no matter such viruses are mutated or not.

Novel and potent inhibitors targeting DHODH are broad-spectrum antivirals against RNA viruses including newly-emerged coronavirus SARS-CoV-2

Emerging and re-emerging RNA viruses occasionally cause epidemics and pandemics worldwide, such as the on-going outbreak of the novel coronavirus SARS-CoV-2. Herein, we identified two potent inhibitors of human DHODH, S312 and S416, with favorable drug-likeness and pharmacokinetic profiles, which all showed broad-spectrum antiviral effects against various RNA viruses, including influenza A virus, Zika virus, Ebola virus, and particularly against SARS-CoV-2. Notably, S416 is reported to be the most potent inhibitor so far with an EC of 17 nmol/L and an SI value of 10,505.88 in infected cells. Our results are the first to validate that DHODH is an attractive host target through high antiviral efficacy in vivo and low virus replication in DHODH knock-out cells. This work demonstrates that both S312/S416 and old drugs (Leflunomide/Teriflunomide) with dual actions of antiviral and immuno-regulation may have clinical potentials to cure SARS-CoV-2 or other RNA viruses circulating worldwide, no matter such viruses are mutated or not.

Immunoregulation of allograft rejection: A role played by human CD200+ sub-population from human placenta-derived mesenchymal stem cells / 中国组织工程研究

BACKGROUND: Immune rejection of skin allograft is a clinical problem to be solved. Our previous study has shown that human placenta-derived CD200+ mesenchymal stem cells may have a strong capability of immunoregulation. OBJECTIVE: To investigate the effects of human placenta-derived CD200+ mesenchymal stem cells on rejection of skin allograft. METHODS: Skin allograft models of c57/BL6 mice were established and divided into three groups as control group, human placenta-derived mesenchymal stem cells group (PMSCs group), and CD200+ mesenchymal stem cells group (CD200+-PMSCs group). PBS (control group), normal PMSCs and CD200+-PMSCs were injected into the mice through the tail vein, respectively. The necrotic time, survival time and situation of grafted skin were observed. The number of peripheral white blood cells was counted after 7 days of treatment. The expression levels of interleukin-10, interferon-γ and tumor necrosis factor-α were detected by Q-PCR and ELISA. RESULTS AND CONCLUSION: (1) Compared with the control group, in the PMSCs and CD200+-PMSCs groups, the condition of skin allograft was better, and the survival time was significantly prolonged (P < 0.001). The condition and survival time of skin allograft in the CD200+-PMSCs group were significantly superior to those in the PMSCs group (P < 0.01). (2) After 7 days of treatment, the number of peripheral white blood cells in the PMSCs and CD200+-PMSCs groups was significantly less than that in the control group (P < 0.01). (3) Compared with the control group, the mRNA expression level of interleukin-10 in the spleen was significantly increased in the CD200+-PMSCs group (P < 0.05), and the mRNA expression levels of interferon-γ and tumor necrosis factor-α in the spleen were significantly down-regulated in the PMSCs and CD200+-PMSCs groups (P < 0.05, P < 0.01). The mRNA expression levels of interferon-γ and tumor necrosis factor-α in the spleen in the CD200+-PMSCs group were significantly lower than those in the PMSCs group (P < 0.01, P < 0.05). (4) Compared with the control group, the expression level of interleukin-10 in the blood was significantly increased (P < 0.05, P < 0.001), and the expression levels of interferon-γ and tumor necrosis factor-α in the blood were significantly down-regulated in the CD200+-PMSCs and PMSCs groups (P < 0.05, P < 0.001; P < 0.01, P < 0.001). The expression levels of interferon-γ and tumor necrosis factor-α in the blood in the CD200+-PMSCs group were significantly lower than those in the PMSCs group (P < 0.05). These results indicate that human placenta-derived mesenchymal stem cells have immunosuppressive effect on the rejection of skin allograft, and CD200+ cells may have better immunoregulatory effects by regulating the expressions of interleukin-10, interferon-γ and tumor necrosis factor-α