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Hippophae rhamnoides is a traditional Chinese medicine with homology of medicine and food， which has the effects of relieving cough and resolving phlegm， strengthening the stomach and digestion， and promoting blood circulation and resolving blood stasis. H. rhamnoides contains not only flavonoids， phenols， proteins， vitamins， and amino acids but also abundant polysaccharides. In order to explore the functional value and current research status of H. rhamnoides polysaccharides， this study systematically summarized the extraction process， structural characteristics， pharmacological effects， and mechanism of action of H. rhamnoides polysaccharides by reviewing Chinese and foreign literature. The results showed that H. rhamnoides polysaccharides have anti-tumor， hypoglycemic， antioxidant， immune regulation， anti-inflammatory， and anti-hyperlipidemia functions and could improve intestinal microbiota. There were various extraction processes for polysaccharides， including hot water extraction， microwave extraction， ultrasonic extraction， enzymatic extraction， flash extraction， ultrasonic-microwave synergistic extraction， emerald hot water extraction， enzymatic-ultrasonic synergistic extraction， etc. Based on comprehensive analysis， hot water extraction is suitable for industrial development and application. However， multiple homogeneous polysaccharides have been isolated and purified from H. rhamnoides polysaccharides， but their efficacy， structure， and structure-activity relationship still need to be further explored and studied. This study can provide a reference for the research and development of H. rhamnoides polysaccharides.
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Outer membrane vesicle (OMV), originating from the outermost membrane of cells, is the extracellular vesicles released by gram-negative bacteria, containing bacterial outer membrane components such as phospholipids, lipopolysaccharide (LPS), outer membrane protein, and bacterial-specific antigens. OMV plays an important role in bacterial physiology and pathogenesis, involving in biofilm formation, horizontal gene transfer, stress and inflammatory responses, and delivery of toxins and other biomolecules. It also plays a vital role in immune regulation and the establishment and maintenance of balanced intestinal microflora. This article provides an overview of the roles of OMV in bacterial infections and immune regulation and the potential application value of OMV in tumor-targeted therapy and new vaccine preparation in the hope to provide new ideas for the prevention and treatment of bacterial infections.
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Objective:To investigate the role of miR-145 in inflammatory response and immune regulation after traumatic brain injury(TBI).Methods:Male C57BL/6 mice were randomly divided into sham operation group(Sham),model group(TBI),TBI+NC agomir group and TBI+miR-145 agomir group.Modified Nerve Injury Severity Score(mNSS)was used to evaluate neurological function after trauma.MWM test was used toevaluates neurocognitive function of mice after TBI.Flow cytometry was used to detect the number of Tregs in tbrain tissue of each group of mice.ELISA was used to detect expressions of inflammatory cytokines in hippocampus of each group of mice.Immunohistochemistry was used to detect expression of activated microglia/macrophage Iba-1 in hippocampus of each group of mice.RT-qPCR was used to detect expressions of M1/M2 microglia/macrophage marker genes iNOS,CD11b,CD206 and Arg1.TUNEL staining and neuronal nuclear immunity double staining with fluorescent label(NeuN)were used to detect neuronal apoptosis.Results:Compared with Sham group,expression of miR-145 in hippocampus of mice in TBI group was significantly decreased,the neurological damage was increased,and percentage of Tregs in CD4+T cell population in brain tissue was decreased.Expression levels of IL-1β,IL-6,TNF-α,IL-4,IL-10 and TGF-β in hippocampus were significantly increased,the number of activated microglia/macrophage IBA-1 was increased,expression levels of iNOS CD11b,CD206 and Arg1 were significantly increased,and the neuronal apoptosis was increased.Notch1,p21 and Hes1 mRNA and protein levels were significantly increased(all P<0.05).Compared with TBI+NC agomir group,expression of miR-145 in hippocampus of mice in TBI+miR-145 agomir group was significantly increased,and neurological damage was reduced.Percentage of Tregs in CD4+T cell population in brain tissue was significantly increased,expressions of pro-inflammatory cytokines IL-1β,IL-6,and TNF-α were decreased,while anti-inflammatory cytokines IL-4,IL-10 and TGF-β were significantly increased in hippocampus.The number of activated microglia/macrophage IBA-1 was significantly decreased,expression levels of iNOS and CD11b were decreased,while expression levels of CD206 and Arg1 were significantly increased.mRNA and protein levels of Notch1,p21 and Hes1 were significantly reduced(all P<0.05).Conclusion:Overexpression of miR-145 promotes M2 polarization of microglia to regulate post-traumatic neuroinflammatory response and improve behavioral dysfunction by increasing Treg level,which may be mediated by Notch signaling pathway.
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Corneal transplantation is an effective treatment for corneal blindness, and it is the only hope for patients with corneal blindness. Cornea has no blood vessels and no lymphatic vessels, which is called immune privilege organ, so the success rate of corneal transplantation is significantly higher than that of other organ transplantation, but the rejection reaction after corneal transplantation is still the main reason for the failure of corneal transplantation. The directional movement of immune cells to lymphoid tissue and inflammatory sites is the mainly immune response after organ transplantation. And the regulatory T cells(Treg)play a key role in immune regulation, which can induce immune tolerance by regulating and inhibiting the activation of effector T cells and reduce the rejection reaction after corneal transplantation. In addition, this review also discussed the effectiveness of applying cordyceps sinensis extract FTY720 to enhance the function of Treg. Based on this, we briefly reviewed the sources, mechanism of action and treatment of Treg after corneal transplantation, so as to provide some reference for the subsequent clinical application transformation and basic research.
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@#Lactoferrin(LF),as a kind of iron-bound natural transferrin with wide functions,has become a research hotspot at home and abroad in recent years. Studies have shown that LF has a wide range of treatment,prevention and biological activity. This paper reviewed the clinical effects of LF in immune regulation,anti-tumor,regulation of obesity mechanism,antibacterial,anti-Alzheimer disease(AD)and bone regeneration mechanism in recent years,in order to provide a direction for the follow-up clinical application and research of LF.
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Background & objectives: Oral squamous cell carcinoma (OSCC) is widely prevalent in the Indian subcontinent mainly due to habit-associated aetiologies. Immune regulation and angiogenesis are the part of tumourigenesis that play a crucial role in metastasis and survival. However, the concurrent expression of vascular endothelial growth factor (VEGF) and CD3 (immune regulator receptor on T-lymphocyte) in the same OSCC tissue samples has not been reported in the Indian population. The present study evaluated the expression of CD3+ T-cells and VEGF in OSCC tissue samples and studied the clinicopathological correlation and survival analysis in an Indian population. Methods: This was a retrospective study conducted on 30 formalin-fixed and paraffin embedded sections which were histologically diagnosed as OSCC cases comprising of 15 metastatic OSCC and 15 non- metastatic OSCC with available clinical data and survival status. Results: Reduced expression of CD3+ T-cells and increased VEGF expression were observed in metastatic OSCC samples. The correlation of expression of CD3+ T-cells and VEGF with clinicopathological parameters showed a significant association between these markers with age, nodal status, site of the lesion and survival. Interpretation & conclusions: Reduced expression of CD3+ T-cells in OSCC was found to be associated with a significantly poor survival. VEGF was found to be over expressed in metastatic OSCC as compared to that in non-metastatic OSCC. The study findings suggest that the evaluation of CD3 and VEGF in incisional OSCC biopsies can be considered for predicting the survival outcome and metastasis
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Chronic graft-versus-host disease (cGVHD) is the main complication after allogeneic hematopoietic stem cell transplantation, which is also the major cause of non-relapse -related death. Due to its complex pathophysiological process, the response rate of conventional glucocorticoids combined with immunosuppressants is less than 50%. Second-line therapy should be given for patients with glucocorticoid-resistant cGVHD. Nevertheless, no consensus has been reached on current second-line therapy and the therapeutic effect is relatively poor. Mesenchymal stem cell (MSC) is one of the most common adult stem cells. Due to multi-dimensional and multi-target immune regulating function, MSC has been widely applied in the prevention and treatment of cGVHD. In addition, accumulated studies have confirmed the safety and efficacy of MSC in the treatment of cGVHD, which is expected to become a novel strategy for the prevention and management of cGVHD. In this article, research progress, mechanism and existing problems of prevention and treatment of cGVHD by MSC were reviewed, aiming to provide novel ideas for optimizing therapeutic regimens of MSC and enhancing the prevention and treatment effect of cGVHD in subsequent research.
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@#To investigate the effects of Shengmai formula (SMF) on tissue damages, serum inflammatory factors and the proportion of innate immunocytes in peripheral blood, sepsis models using either intraperitoneal injection of 20 mg/kg lipopolysaccharide (LPS) or cecal ligation and puncture (CLP) were established.The role of gut microbiota in septic mice during SMF treatment was further investigated.LPS-induced sepsis model was carried out 4 days after daily gavage administration with 0.3 g/kg, 0.6 g/kg, 1.2 g/kg SMF or intraperitoneal injection with 0.6 g/kg SMF.Survival rates of septic mice were determined.Histological evaluations of liver, lung and kidney were analyzed by H&E staining. Serum IL-6, TNF-α, Alanine transaminase (ALT), Aspartate aminotransferase (AST), Blood urea nitrogen (BUN) and Creatinine (Cr) levels were determined.LPS and CLP-induced sepsis models were established, and the proportion of monocytes, macrophages and neutrophils in peripheral blood were analyzed by flow cytometry after gavage administration or intraperitoneal injection of SMF.The therapeutic effects of SMF after antibiotics treatment were further determined, and the therapeutic effects of fecal microbiota from SMF-treated mice were investigated.The results show that LPS-induced sepsis caused death of mice, damages in liver, lung and kidney with increased infiltration of leukocytes and elevated levels of serum IL-6, ALT, AST, BUN and Cr, which were all reversed by gavage administration of SMF.Gavage administration of SMF could significantly reduce the proportion of peripheral macrophages in LPS model and monocytes, macrophages, neutrophils in CLP model.Intraperitoneal injection of SMF showed no therapeutic benefits in septic mice.Depletion of gut microbiota using antibiotics cocktail reversed the therapeutic effects of SMF on sepsis, indicating the involvement of gut microbiota.Fecal microbiota from SMF-treated donors was transplanted into pseudo-sterile recipients, and we found FMT could significantly ameliorate sepsis of recipients.These results showed that gavage administration of SMF reduced serum inflammatory factors and alleviated tissue damages in septic mice by regulating gut microbiota. This study provides a theoretical basis for the treatment of clinical sepsis with SMF.
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Helminth infections may trigger host innate and adaptive immune responses. Group 2 innate lymphoid cells (ILC2) are an important factor involved in type 2 immune responses, and produce a large number of T helper 2 cell (Th2) cytokines following stimulation by interleukin (IL)-25, IL-33 and thymic stromal lymphopoietin (TSLP), which play a critical role in parasite clearance and tissue repair. Following helminth infections, autocrine factors, mast cells, enteric nervous system and Th2 cells have been recently found to be involved in regulation of ILC2. Unraveling the role of ILC2 in immune response against helminth infections is of great value for basic research and drug development. This review summarizes the research progress on ILC2 and its role in helminth infections.
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Bilirubin has good anti-inflammatory， antioxidant and immunomodulatory effects， but its poor water solubility and low bioavailability greatly limit its clinical application. Researchers have developed bilirubin into various nanoparticles， which effectively eliminate the limitation of low solubility of bilirubin with the advantage of dosage form， so that they can maximize its pharmacological activities such as anti-inflammatory， anti-oxidation and immune regulation. Bilirubin nanoparticles have great application potential in a variety of gastrointestinal diseases， liver and kidney diseases， skin diseases， autoimmune diseases， islet transplantation and targeted therapy of tumors （both as a direct anti-tumor drug and as a drug delivery system）. The study of bilirubin nanoparticles will promote the clinical application of bilirubin and the development of related new drugs.
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@#Periodontitis is a chronic infectious disease that occurs in periodontal support tissues. Plaque microorganisms are its initiating factor, while local inflammation and alveolar bone loss resulting from periodontitis are the most common causes of tooth loss. Interleukin-17 (IL-17), which plays an important role in the immune response to periodontitis, mostly originates from T helper cell 17 (Th17) and γδT cells. In periodontitis, the role of Th17 cells has been demonstrated broadly, but the role of γδT cells was not revealed until recent years. As a highly heterogeneous group of T lymphocytes, γδT cells are considered a link between innate immunity and adaptive immunity. Studies have found that γδT cells are mostly distributed in the oral epithelium near the biofilm, where they can interact with microorganisms to produce IL-17, recruit neutrophils, macrophages, etc., and participate in the host immune response to periodontitis. They also play a role in the association between periodontitis and relevant systemic diseases. In addition, γδT cells have been proven to produce tissue repair-related factors with a protective effect against periodontitis. The possible mechanism of γδT cells in periodontitis is discussed in this review.
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Polysaccharides have significant immunomodulatory activity and have good development value in food and medicine fields. At present, there are many studies on the chemical structure and immune activity of polysaccharides, but the relationship between them of polysaccharides has not been fully explained, which limits the further development and utilization of polysaccharide resources. The immune activity of polysaccharides is closely related to their own structure. This paper systematically summarized the relationship between the relative molecular weight, monosaccharide composition, glycosidic bond types, chemical modification, and advanced conformation of polysaccharides and the immune regulation, aiming to provide references for the profound study of polysaccharide structure-activity relationship and utilization of polysaccharides.
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Monosaccharides/chemistry , Structure-Activity Relationship , Molecular Weight , Antioxidants/pharmacology , Polysaccharides/chemistryABSTRACT
Establish a production line with controllable process and high intelligence, contribute to improve the quality and production efficiency of aconite processed by microwave, and promote the transformation and application of aconite processed by microwave. According to the principle of aconite detoxification and the characteristics of industrial microwave equipment, an industrial production line of aconite processed by microwave was established with diester alkaloids and monoester alkaloids as indicators, and pilot production was carried out. At the same time, the content of active constituents and efficacy were compared with that of the main processed products, such as Shengfupian, Baifupian and Heishunpian. The results showed that the industrial production of aconite processed by microwave can be divided into two stages: "Liquid seal to detoxification - drying and puffing". The content of monoester alkaloids in 10 batches of aconite processed by microwave was 0.071%-0.166% and the content of diester alkaloids was 0.004%-0.016%, which met the relevant requirements of the Chinese Pharmacopoeia in 2020. Compared with Heishunpian and Baifupian, the retention rate of the effective components of aconite processed by microwave was higher. Pharmacological experiments showed that aconite processed by microwave not only retained the anti-inflammatory and analgesic activities of Heishunpian and Baifupian, but also significantly increased the levels of leukocytes and lymphocytes in mice with liver cancer chemotherapy, enhanced the CD4/CD8 ratio in spleen cells of mice (P < 0.05), thus regulating the body's immunity. However, this effect of Baifupian was weak, while Heishunpian and Shengfupian had no such effect. Through the above research, this study established microwave processing line with controllable process and high intelligence, as well produced the aconite processed by microwave with low toxicity and stable quality. It laid a foundation for the industrialized continuous production and clinical positioning of aconite by microwave processed, and provided scientific support for the development and application of microwave technology in the field of traditional Chinese medicine. All animal experiments in this study were reviewed and approved by the Experimental Animal Ethics Committee of Chengdu University of Traditional Chinese Medicine before being carried out (Approval No. 2020-28).
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Functional peptides refer to peptides that are beneficial to life activities or have special physiological activities, also known as bioactive peptides. Oyster is rich in protein and is a good material for developing bioactive peptides, which has great potential as a functional food and great application value in pharmaceutical and medical industry. With the development of modern biotechnology and medical technology, the method innovation of oyster peptide preparation，the absorptivity and biological activity of oyster peptide have been enhanced significantly, which lead to deep recognition of the biological function of oyster peptide and offer the boarder application prospect. The researches on the diversification activities of oyster peptides were summarized in this review, which provided clues and ideas for the development of the oyster peptide applications.
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Objective:To investigate the effect of berberine on immune regulation and phosphoinositide 3-kinase (PI3K)/protein kinase B (Akt) signal pathway in lung cancer rats.Methods:The lung cancer rat model was established by perfusing a carcinogenic lipiodol solution. The 36 male Wistar rats were randomly divided into the model group ( n = 12), the berberine group ( n = 12), and the normal group ( n = 12). The rats in the berberine group were ig berberine 15 mg/kg, once daily. The rats in the model group and the normal group were ig the same dose of normal saline, once daily. The intervention was conducted continuously for 16 weeks for each group. The spleen index and lung index, tumor inhibition rate, T lymphocyte subgroup level, PI3K, and Akt protein expression of rats in each group were compared. Results:The spleen index of the model group and berberine group was lower than that of the normal group, while the lung index was higher than that of the normal group (all P < 0.05). The spleen index of the berberine group was higher than that of the model group, while the lung index was lower than that of the model group (all P < 0.05). The tumor weight of the berberine group was lower than that of the model group ( P < 0.05). The tumor inhibition rate of the berberine group was 43.12%. The CD3 +, CD4 +, and CD4 +/CD8 + levels of the model group and berberine group were lower than those of the normal group, CD8 + level was higher than that of the normal group (all P < 0.05), and the CD3 +, CD4 + and CD4 +/CD8 + levels of the berberine group higher than those of the model group, while CD8 + level was opposite (all P < 0.05). The gray values of PI3K and Akt protein of the model group and berberine group were higher than those of the normal group (all P < 0.05), and this value of the berberine group was lower than that of the model group (all P < 0.05). Conclusions:Berberine can effectively inhibit tumor growth in lung cancer rats, promote spleen development and differentiation, regulate immune function, and downregulate the expression of PI3K/Akt signaling pathway.
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The study aimed to elucidate the modulatory role of MMP14 on mCD100 shedding and sCD100 production,and its subsequent effects on CD8+T cell dysfunction in lung cancer patients.Total of 56 non-small cell lung cancer(NSCLC)patients were from January 2020 to January 2023 and compared them with 88 healthy controls.Bronchoalveolar lavage fluid(BALF)was obtained from both tumor and non-tumor sites of the patient group.Peripheral blood mononuclear cells(PBMC)were isolated from both groups,and the expression of CD72 and mCD100 in PBMC were assessed via flow cytometry.CD8+T cells from tumor sites were stimulated with recombinant human MMP14 and CD100.Post-cultivation,supernatant levels of TNF-α and IFN-γ were determined by ELISA,while granulysin B and perforin levels were analyzed through an ELISPOT assay.The rate of target cell death was also observed.Data showed no significant difference in the proportion of CD3+mCD100+,CD3+CD72+ cells,and the average fluorescence intensity of CD72 in CD100 and CD3+ monocytes in CD3+CD8+T cells between the patient and control groups.However,as compared with non-tumor sites,these indexes of tumor sites were significantly elevated.Stimulation with CD100 led to increase in IFN-γ,TNF,perforin,and granulozyme B secretion levels in CD8+T cells.After MMP14 stimulation,the proportions of CD3+mCD10 0+ and target cell death,along with sCD100,TNF-α,IFN-γ,and granulozyme B levels in CD8+T cells from NSCLC tumor sites,were notably increased.Interestingly,the addition of anti-CD100 to MMP14-stimulated CD8+T cells resulted in a significant drop in the levels of sCD100,TNF-α,IL-1β,and granulozyme B,as well as in the proportion of target cell death.Taken together,in NSCLC patients,the inhibition of CD100 shedding in CD8+T cells at tumor sites and the blockade of sCD100 production result in impaired CD8+T cell killing function.MMP14 appears to enhance mCD100 shedding and sCD100 production,thereby potentially restoring the cytotoxic function of CD8+T cells against primary NSCLC cells.
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TAM(tumor-associated macrophage)is a kind of immune cell in tumor microenvironment,which mainly exists in tumor matrix to mediate inflammatory reaction.Generally,TAM can be stimulated by different cytokines to polarize into M1 macrophage or M2 macrophage with different phenotypes.In the early stage of tumor,M1 macrophages in TAM exhibit pro-inflammatory and anti-tumor activities,while as tumor progresses,TAMs tend to polarize into M2 macrophages to play anti-inflammatory and tumor-promoting roles.A large number of studies have shown that TAM is closely related to tumor growth,invasion,metastasis and poor prognosis.Therefore,targeting TAM has become the focus of anti-tumor immunotherapy.This paper has summarized the origin of TAM,and introduced the specific roles of TAM in promoting tumor proliferation,angiogenesis,migration and invasion and the formation of immunosuppressive environment.At the same time,the research progress of TAM-targeted anti-tumor immu-notherapy in recent years was discussed from 3 aspects:inhibiting monocyte recruitment,promoting TAM apoptosis and reshaping TAM phenotype.
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Intestinal flora plays an important role in maintaining the body's immune balance, digestion, and nutrient absorption. Thyroid function mainly includes the synthesis and secretion of thyroid hormones and the regulation of metabolic balance in the body. When the body’s thyroid hormone synthesis and secretion are too little or too much, it will lead to thyroid diseases. Studies have shown that intestinal flora may affect the occurrence and development of thyroid diseases by participating in thyroid metabolism, immune regulation, cross immunoreaction, and interaction with thyroid-related predisposing factors. Understanding the structural changes and functional mechanisms of intestinal flora during the occurrence and development of thyroid diseases can provide a new basis for the diagnosis and treatment of thyroid diseases and improvement of clinical prognosis.
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ObjectiveTo observe the effect of Qinggan Jianpi Huoxue prescription（QGJPHXP） on the polarization of M1/M2 macrophages in rats with hepatic fibrosis induced by carbon tetrachloride（CCl4）. MethodA rat hepatic fibrosis model was established by intraperitoneal injection of 40% CCl4-olive oil suspension twice a week at the dosage of 2.0 mL·kg-1 for 8 weeks. After the model was successfully established， these rats were randomly divided into the model group， QGJPHXP group（32.084 g·kg-1） and Biejiajian pills（BJJP） group（0.925 5 g·kg-1）， with 12 rats in each group. The blank group was injected intraperitoneally with the same amount of olive oil. The rats in the administration groups were given the corresponding solution according to the dose， and the blank and model groups were given the same dose of purified water， once a day. After 4 weeks of continuous administration， the liver tissues of rats were taken and stained with hematoxylin-eosin（HE） and Masson to observe the pathological changes. The serums were collected to detect the alanine aminotransferase（ALT） and aspartate aminotransferase（AST） levels. Interleukin（IL）-6， IL-12， IL-10， IL-1β， transforming growth factor-β1（TGF-β1） and tumor necrosis factor-α（TNF-α） levels in liver tissues were measured by enzyme-linked immunosorbent assay（ELISA）. The expression levels of CD86 and CD206 were detected by immunohistochemistry（IHC）. Western blot and real-time fluorescence quantitative polymerase chain reaction（Real-time PCR） were used to detect the protein and mRNA expression levels of inducible nitric oxide synthase（iNOS）， arginase-1（Arg-1）， phosphorylated p38 mitogen-activated protein kinase（p-p38 MAPK）， nuclear transcription factor-κB p65（NF-κB p65） in liver tissues of rats. ResultCompared with the blank group， the hepatic cell plate was irregularly arranged, and local inflammatory cell infiltration and fibrous hyperplasia were observed， while the serum levels of ALT and AST were significantly increased in the model group（P<0.01）， and IL-1β， IL-6， IL-12， TGF-β1， TNF-α， CD86， CD206， iNOS， p-p38 MAPK，p38 MAPK and NF-κB p65 levels in liver tissues were obviously increased（P<0.05， P<0.01）， while the levels of IL-10 and Arg-1 were obviously decreased（P<0.05， P<0.01）. Compared with the model group， QGJPHXP group reduced the degree of liver cell fibrosis，and serum levels of ALT and AST（P<0.01）， and IL-1β， IL-6， IL-12， TGF-β1， TNF-α， CD86， iNOS， p-p38 MAPK， p38 MAPK， and NF-κB p65 levels in liver tissues were obviously decreased（P<0.05， P<0.01）， the levels of IL-10， CD206 and Arg-1 were obviously increased in the QGJPHXP group（P<0.05， P<0.01）. ConclusionQGJPHXP has ability to inhibit the activation of pro-inflammatory M1 macrophages， induce the secretion of anti-inflammatory cytokines by M2 macrophages， reduce the release of pro-fibrogenic cytokines， and promote the macrophage polarization of M1 to M2 in liver for tissue repair， thereby serving as an anti-inflammatory and anti-hepatic fibrosis drug.
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Exosomes are vesicle-like bodies carrying proteins, RNA, lipids and other bioactive substances, which are secreted from intracellular to extracellular and act on target cells to play their biological functions. Colorectal cancer is one of the malig¬nant tumors with high morbidity and mortality. It has been found that immune cell-derived exosomes participate in the regulation of colorectal cancer growth, invasion, metastasis and other processes. It also plays an obvious role in tumor diagnosis,treat¬ment and post-treatment monitoring. In this review we summa¬rize the research progress of immune cell-derived exosomes in colorectal cancer.