Specific immunoglobulin (IgY) from egg yolk against Aeromonas hydrophila was produced by immunization of White Leghorn hens with formalin-killed whole cells of A. hydrophila. ELISA test using A. hydrophila as the coat...Specific immunoglobulin (IgY) from egg yolk against Aeromonas hydrophila was produced by immunization of White Leghorn hens with formalin-killed whole cells of A. hydrophila. ELISA test using A. hydrophila as the coating antigen revealed that the specific antibody titer started to increase in the egg yolk at the 13th day post-immunization (P/N=2.18), reached the peak at the 56th day (P/N=13.82), and remained at high level until day 133 (P/N=7.03). The antibody was purified by saturated ammonium sulphate with a recovery rate of 63.5%. The specific IgY inhibited the growth of A. hydrophila at a concentration of 1.0 mg/ml during the 18 h incubation. Pre-treatment of polyploid gibel carps Carassius auratus Gibelio with specific IgY had a protection rate of 60% (6/10) against challenge with A. hydrophila, while none of the fishes in the control groups receiving sterile phosphate buffered saline (PBS) or non-specific IgY survived the challenge. Treatment of fishes with the specific IgY 4 h after the challenge also had lower mortality (70%, 7/10), a 30% reduction against the control PBS or non-specific IgY groups (10/10). These results indicate that specific IgY antibodies could be obtained easily from hens immunized with an inactivated A. hydrophila and could provide a novel alternative approach to control of diseases in fishes caused by this organism.展开更多
Shortage of appropriate donor grafts is the foremost current problem in organ transplantation. As a logical consequence, waiting times have extended and pretransplant mortality rates were significantly increasing. The...Shortage of appropriate donor grafts is the foremost current problem in organ transplantation. As a logical consequence, waiting times have extended and pretransplant mortality rates were significantly increasing. The implementation of a priority-based liver allocation system using the model of end-stage liverdisease(MELD) score helped to reduce waiting list mortality in liver transplantation(LT). However, due to an escalating organ scarcity, pre-LT MELD scores have significantly increased and liver recipients became more complex in recent years. This has finally led to posttransplant decreasing survival rates, attributed mainly to elevated rates of infectious and immunologic complications. To meet this challenging development, an increasing number of extended criteria donor grafts are currently accepted, which may, however, aggravate the patients' infectious and immunologic risk profiles. The administration of intravenous immunoglobulins(IVIg) is an established treatment in patients with immune deficiencies and other antibody-mediated diseases. In addition, IVIg was shown to be useful in treatment of several disorders caused by deterioration of the cellular immune system. It proved to be effective in preventing hyperacute rejection in highly sensitized kidney and heart transplants. In the liver transplant setting, the administration of specific Ig against hepatitis B virus is current standard in post-LT antiviral prophylaxis. The mechanisms of action of IVIg are complex and not fully understood. However, there is increasing experimental and clinical evidence that IVIg has an immuno-balancing impact by a combination of immuno-supporting and immuno-suppressive properties. It may be suggested that, especially in the context of a worsening organ shortage with all resulting clinical implications, liver transplant patients should benefit from immuno-regulatory capabilities of IVIg. In this review, perspectives of immune modulation by IVIg and impact on outcome in liver transplant patients are described.展开更多
Prevention of mother-to-child transmission(PMTCT)of HIV with highly active antiretroviral therapy(HARRT)allows the HIV^+pregnant mothers to have vaginal delivery and breastfeed.Here we investigated the maternal plasma...Prevention of mother-to-child transmission(PMTCT)of HIV with highly active antiretroviral therapy(HARRT)allows the HIV^+pregnant mothers to have vaginal delivery and breastfeed.Here we investigated the maternal plasma immunoglobulin,cytokine secretion and the outcome of the exposed infants among the HIV^+HAART treated pregnan women in Nigeria.In this study,different plasma immunoglobulins and cytokines were measured in the HIV^+HAART treated pregnant mothers.Pooled culture supernatants of B and T lymphocytes showed lower levels of IFN-γ,IL-10 and IL-4.There were lower IFN-γand IL-10 secretions at 1st trimester;however,IL-10 continued to be lower throughout 2nd and 3rd trimesters.TNF-αsecretion significantly decreased as pregnancy progressed to term.There were high plasma IgG and low IgM in the HIV^+HAART treated pregnant women.Plasma IgG was high during 1st and 3rd trimesters.After one year of follow up,all the exposed children were seronegative for HIV-1 and HIV-2.Vaginal delivery and breastfeeding among HIV^+HAART treated mothers have shown to be safe.The use of HAART by the infected mothers and the use of septrin and niverapin by the exposed infants prevented mother to-child transmission of HIV.展开更多
Muscular dystrophies are myopathies and tend to progressive, with ongoing degeneration and regeneration of muscle fibers. Spinal muscular atrophy (SMA), amyotrophic lateral sclerosis (ALS) and polio myelitis are essen...Muscular dystrophies are myopathies and tend to progressive, with ongoing degeneration and regeneration of muscle fibers. Spinal muscular atrophy (SMA), amyotrophic lateral sclerosis (ALS) and polio myelitis are essentially diseases of the anterior horn cells of the spine. It has been reported in literature that humoral immunity is manifested by the antibodies production. These are special chemical substances that react against foreign body. Antibodies are serum proteins, which are immunoglobulins and possess antibody activity and are classified according to antigens and stimulate their production such as IgA, JgG, IgM, IgD and IgE. All the immunological parameters such as of C3, C4, IgG, IgM and IgA, which are measured in Duchenne muscular dystrophy go down in comparison to healthy subjects. Complement C3 and Complement C4 go down about 44.3% and 78.57% respectively from the normal values. The serum IgG, IgM and IgA levels were also go down about 65%, 84% and 99.56% respectively in comparison to healthy subjects. A trend between all the immunoglobulins has been set up and it is rAG.M > rMA.G. > rGM.A, while we have a trend in DMD cases is rMA.G. > rAG.M > rGM.A We are in a position to say that our data have a relevance of high authenticity and reliability to accept that there is a deficit in immunity in DMD cases. The deficit in immunity may be a cause to damage muscle for abnormal functioning.展开更多
Background: Major Depressive Disorder (MDD) is a mental disorder characterized by a pervasive and persistent low mood which is accompanied by low self-esteem and loss of interest or pleasure in day to day activities t...Background: Major Depressive Disorder (MDD) is a mental disorder characterized by a pervasive and persistent low mood which is accompanied by low self-esteem and loss of interest or pleasure in day to day activities that adversely affects a person’s family, work, and personal life. There is no sufficient laboratory test for the diagnosis of MDD and it is expected that this investigation may be helpful for better diagnosis and management of MDD. We aimed to measure serum immunoglobulin levels in MDD patients and control subjects to meet the above demand. Methods: For this purpose, we recruited 88 MDD patients from the department of psychiatry, Bangabandhu Sheikh Mujib Medical University, Dhaka and 89 healthy volunteers from Dhaka city matched with age, sex and socioeconomic status to the patient group. Turbidimetry method was applied to measure serum levels of immunoglobulin A, G, and M where immunoglobulin kit was utilized. Results: The current study revealed that mean serum concentrations of immunoglobulin A, G, and M in patients were found to be 209.07 ± 104.93, 791.50 ± 235.67 and 107.92 ± 47.53 mg/dL while those were 195.34 ± 92.16, 763.81 ± 175.89 and 99.17 ± 48.78 mg/dL in control subjects, respectively. Conclusion: Our result indicates that serum concentrations of immunoglobulin A, G and M were not significant between the groups and further studies are required to establish these findings.展开更多
Background: Breast cancer remains intractable and the leading cause of cancer related death among women. The appearance of breast tumour and its progression poses great clinical unpredictability before and after diagn...Background: Breast cancer remains intractable and the leading cause of cancer related death among women. The appearance of breast tumour and its progression poses great clinical unpredictability before and after diagnosis, therapy and appearance of recurrent secondary deposits. Various immunological changes occur during breast tumourigenesis, and can be of value in the surveillance of the diseases. In our environment, there is scanty information on the value of these immunological factors especially immunoglobulins in screening and surveillance of breast cancer—hence the need for this study. Methodology: A total of 59 females (mean age = 48.7 ± 8.7 yrs) with clinically and pathologically confirmed breast cancer were prospectively recruited alongside with 20 patients with benign breast tumour representing patients’ control group and 20 apparently healthy age and sex-matched control subjects (mean age = 47.5 ± 13.4 yrs). Breast cancer patients were further grouped into early stage breast cancer (N = 25) and advanced stage breast cancer (N = 34). Patients were subjected to standard treatment modalities and pre- and post-treatment samples collected at intervals. Samples were assayed for IgG & IgM by immunoenzymatic methods and IgA by immunoturbidimetric method. Questionnaires and measurements were used to obtain necessary demographic and anthropologic information from the subjects. Results: Results showed that in all stages of breast cancer and treatment groups, the mean serum IgG, IgM and IgA levels respectively were not significantly raised (P > 0.05) when compared. Results also showed that majority (59%) of the patients presented at advanced stage of the disease. Low level of education and low income were among the prevailing risk factors. Majority (63%) of the cases had body mass index suggesting obesity (>30 kg/m2). Conclusion: Results suggest that serum immunoglobulin (IgG, IgM and IgA) levels are of limited value in surveillance of breast cancer in our environment. Based on our findings, it could also be concluded that low levels of education and low income are among the risk factors. Advocacy and evidence based policies aimed at prevention and early detection of the disease should be prioritized.展开更多
Our findings show that the value of IgG in serum of Alzheimer’s Disease patients is (17.2059 ± 2.6317) g/l and in controls i.e. (17.6720 ± 3.1457) g/l. Values of IgM in AD patients go down up to 62.5% in co...Our findings show that the value of IgG in serum of Alzheimer’s Disease patients is (17.2059 ± 2.6317) g/l and in controls i.e. (17.6720 ± 3.1457) g/l. Values of IgM in AD patients go down up to 62.5% in comparison to healthy subjects. A sudden change was observed in the levels of IgA of AD patients. It has been put on the value 137.9% high in comparison to healthy subjects. The levels of complement C3 have also value of lower side and go down up to 52.66% in AD patients. The value of levels of complement C4 shows no deflection from the control values. On the basis of regression and multiple correlation analysis, we found that the partial correlation coefficients rGA.M, which has value 0.44815 in AD patients and 0.45555 in controls, do not show any resemblance. The multiple partial correlation rAM.G has value 0.3082 in AD patients and 0.3912 in controls slightly better correlated in comparison to healthy controls. Multiple RA.MG has strongly correlation in comparison to controls. RM.AG is also strongly correlated. Regression coefficients and regression equations are basic foundations of correlation measurements and show a specific character of variation. A relation between all the three multiple correlations has been established in the present work and it is given by the following relation RA.MG > RM.AG > RG.AM.展开更多
This experiment was conducted to investigate the effects of dietary ratios of n-6：n-3 polyunsaturated fatty acids （PUFA） on the performance of lactating sows and their piglets. Thirty pregnant Landrace sows were as...This experiment was conducted to investigate the effects of dietary ratios of n-6：n-3 polyunsaturated fatty acids （PUFA） on the performance of lactating sows and their piglets. Thirty pregnant Landrace sows were assigned to one of three treatments from d 108 of gestation until weaning （26-29 d） and were fed diets containing different ratios of n-6：n-3 PUFA including 3：1,9：1 and 13：1. The effects on sow and litter production traits were examined together with an assessment of sow body condition. No differences were detected among the treatments for the daily feed intake of sows or changes in sow weight and back-fat levels during lactation （P 〉 0.05）. Litter size at d 14 and d 21 were tended to increase in 3：1 treatment compared with 9：1 and 13：1 treatments （P 〈 0.10）. Litter weight gain （1.77 kg/d） from d 0 to d 14 was tended to increase in 9：1 groups compared with the other two treatments （P 〈 0.10）. A significant difference was observed for the content of a -linolenic acid, total n-3 PUFA, and the ratio of n-6：n-3 PUFA in the colostrum, milk, and piglets plasma （P 〈 0.01）. The effects of different ratios of n-6：n-3 PUFA in sow diets on colostrum, milk and piglet plasma immunoglobulin concentrations are studied. No difference was observed among treatments in the concentrations of IgM, and IgA in colostrum （P 〉 0.05）. A great significant difference for IgG concentration was observed among 3 group in colostrum. A great significant difference for IgA, and IgM （P〈 0.01） concentrations in piglet plasma at d14 and a significant difference for IgG（P 〈 0.05） was observed at d14. Furthermore, at d 21 of lactation, piglet plasma IgG and IgA concentration were greater in 3：1 compared with 13：1 group （P 〈 0.01）. In summary, the current study demonstrated that altering the ratio of n-6：n-3 PUFA in lactating sow diet had an effect on the immune component including immunoglobulin and cytokines, and it tended to increase the litter average daily gain and improve the immune status of piglets when dietary ratio of n-6：n-3 PUFA was 9：1.展开更多
The importance of immunoglobulin Y(IgY) as a specific antibody equivalent to mammalian immunoglobulin G(IgG) is well recognized. However, production of highly purified IgY is still difficult due to the lack of specifi...The importance of immunoglobulin Y(IgY) as a specific antibody equivalent to mammalian immunoglobulin G(IgG) is well recognized. However, production of highly purified IgY is still difficult due to the lack of specific purification methods. In this study, adsorption behaviors of Ig Y on four mixed-mode resins with functional ligands of 4-mercatoethyl-pyridine(MEP), 2-mercapto-1-methyli-midazole(MMI), 5-aminobenzi-midazole(ABI) and tryptophan-5-aminobenzi-midazole(W-ABI) were evaluated. The results showed that high adsorption ratio were found at p H 6.0–7.0 with little adsorption under acidic conditions. The resin with ABI ligand was then used to separate IgY from immunized chicken serum. An efficient process with Ig Y purity of 95% and recovery of 90% was developed after optimization of loading and elution p H and injection volume. The biological activity of the purified Ig Y was fully maintained. These results indicated that mixed-mode chromatography with specially-designed ligands has great potential for the separation of Ig Y from crude feedstock.展开更多
This experiment was conducted to investigate the effects of different ratios of n-6 ∶ n-3 polyunsaturated fatty acids （PUFA） in sow diets on the performance of lactating sows and their piglets at low digestible ene...This experiment was conducted to investigate the effects of different ratios of n-6 ∶ n-3 polyunsaturated fatty acids （PUFA） in sow diets on the performance of lactating sows and their piglets at low digestible energy intakes. Twenty-one pregnant Landrace sows were assigned to one of three diets from day 108 of gestation until weaning （26 to 29 d） ,containing n-6∶n-3 PUFA ratios of 3 ∶1,8 ∶1 and 11 ∶1. The effects on sow and litter production traits and on sow body condition were examined. There were no differences among treatments in daily feed intakes or in changes in sow weight and back-fat levels during lactation. Litter size,litter weight at birth and weaning and litter average daily weight gain were also unaffected by treatment. As expected, large differences were observed in n-6 and n-3 fatty acids in the colostrum and plasma of sows and piglets （P 〈 0. 01） . The ratio of n6 ∶ n-3 PUFA the diet was positively correlated with those in colostrum,sow plasma and piglet plasma （R 2= 0. 55,0. 80 and 0. 80,respectively） . Sow plasma insulin and IGF-I levels at weaning were unaffected by the treatments. Plasma leptin （P 〈 0. 05） concentrations were increased in sows fed the diet with a n-6∶n-3 ratio of 8 ∶ 1. Immunoglobulin concentrations in colostrum were not altered by dietary treatment. Plasma IgG concentrations at d 14 were highest in piglets from sows fed the 8 ∶ 1 ratio of n-6∶n-3. Furthermore,this group had the highest IgA concentrations at day 21 of lactation compared with the other two groups （P 〈 0. 05） . In summary,our study demonstrated that at low digestible energy levels,altering the ratio of n-6 ∶ n-3 PUFA in the diets for lactating sows affected immune components and the fatty acid composition of lactating sows and their piglets. Further studies are needed to examine whether higher levels of fat supplementation than those used in the present study （1. 5%） can successfully enhance performance.展开更多
A study was conducted to determine if Se source fed during gestation and lactation affects passive transfer of immunoglobulins. Sixty days prior to breeding （d -60）, gilts were randomly assigned to one of three trea...A study was conducted to determine if Se source fed during gestation and lactation affects passive transfer of immunoglobulins. Sixty days prior to breeding （d -60）, gilts were randomly assigned to one of three treatments prior to breeding and throughout gestation： control （Control, no supplemental Se; n = 8）, inorganic Se （Inorganic Se, 0.3 ppm; n = 4） and organic Se （Organic Se, 0.3 ppm; n = 4）. Blood was collected on d -60, 57 and 113 of gestation and on d 21 of lactation and milk was collected at d 0, 1, 7, 14, and 21 of lactation. Blood was collected from piglets at d 0, 1, 7, 14, and 21 of age. Gilts fed organic Se had greater （P 〈 0.05） circulating concentrations of Se than Inorganic and Control gilts. Regardless of treatment, circulating concentrations of Se were greatest （P 〈 0.05） at d -60 compared to all other days. Serum concentrations of IgG were greatest （P 〈 0.05） in gilts at d 57 of gestation compared to d 113. Serum concentrations of IgA were greatest （P 〈 0.05） on d 113 of gestation and d 21 of lactation compared to d -60 and 57. Serum concentrations of IgM were greater （P 〈 0.05） at d 57 compared to d -60. Inorganic gilts had greater （P 〈 0.05） colostral and milk concentrations of IgG and IgM than Organic or Control gilts. Circulating concentrations of Se in piglets were greatest （P 〈 0.05） at d 14 and 21 of age compared to all other days. Piglets from gilts supplemented with organic Se had greater （P 〈 0.05） circulating concentrations of Se on d 1 versus piglets from gilts supplemented with no additional Se. The immunoglobulin concentrations of IgG, IgA, and IgM were lowest （P 〈 0.05） on d 0 and then different sources of Se did not affect the immunoglobulin ncreased when compared to d 1. The addition of concentrations in the gilt or piglet.展开更多
Therapeutic immunoglobulins are used in the treatment of immunodeficiencies as well as several autoimmune and inflammatory diseases. These intravenous immunoglobulins (IVIg) represent the healthy human IgG repertoire,...Therapeutic immunoglobulins are used in the treatment of immunodeficiencies as well as several autoimmune and inflammatory diseases. These intravenous immunoglobulins (IVIg) represent the healthy human IgG repertoire, which can be reactive for both self and non-self antigens. A better characterization of IVIg’s repertoire is an important aspect to enable its effective utilization as an immunomodulatory treatment. In this study we have investigated the reactivity of IgG1, IgG2, IgG3 and IgG4 present in IVIg for a small selection of antigens, including actin, DNA, ferritin and thyroglobulin. We observed that two commercial preparations of therapeutic immunoglobulins contain very high reactivity for thyroglobulin, which was predominantly detected by IgG4. Since IgG4 antibodies can have immunomodulatory properties, these result suggest that these anti-thyroglobulin may have a role in the IVIg treatment of autoimmune disease characterized by high avidity for anti-thyroglobulin antibodies such as Hashimoto’s disease.展开更多
Objective: To study the serum tumor markers, immunoglobulin, TNF-α and hs-CRP in breast cancer in different pathological stages of the concentration, and to analyze the clinical significance of early diagnosis of bre...Objective: To study the serum tumor markers, immunoglobulin, TNF-α and hs-CRP in breast cancer in different pathological stages of the concentration, and to analyze the clinical significance of early diagnosis of breast cancer. Methods: A total of 130 patients with breast cancer were divided into stage I, II, III and IV according to clinical pathology. In addition, 40 patients with benign breast disease and 35 healthy subjects were selected as benign breast disease group and control group. Serum tumor markers, immunoglobulins, TNF-αand hs-CRP concentrations were measured and compared of all subjects. Results: There were no significant difference in serum tumor markers, immunoglobulin and inflammatory factors between the control group and the benign breast cancer group. The level of serum tumor markers in breast cancer group was significantly higher than that in control group and benign breast cancer group. The levels of serum CA125, CA153 and CEA were gradually increased with the severity enhancing from stage I and IV of breast cancer, and he difference was statistically significant. The level of serum immunoglobulin in breast cancer group was significantly higher than that in control group and benign breast cancer group. The levels of serum IgG and IgM increased gradually severity enhancing from stage I and IV of breast cancer, and the difference was statistically significant. The level of serum TNF-α and hs-CRP in serum of breast cancer group was significantly higher than that of control group and benign breast cancer group. The serum levels of TNF-α and hs-CRP increased gradually with severity enhancing from stage I and IV of breast cancer, and the difference was statistically significant. Conclusion: The level of serum tumor markers in breast cancer patients is increasing. Humoral and inflammatory responses are activated to varying degrees and increase with the aggregation of disease. They may involve regulating the occurrence and metastasis of breast cancer and regulating the pathophysiological function of patients. Which may be a certain clinical significance for the early diagnosis of breast cancer and disease progression.展开更多
Objectives:The goal of this study was to develop novel compositions of edible protein coatings based on immunoglobulin(Ig)fraction from bovine milk.Protein coatings can be used to protect foods against microbial,chemi...Objectives:The goal of this study was to develop novel compositions of edible protein coatings based on immunoglobulin(Ig)fraction from bovine milk.Protein coatings can be used to protect foods against microbial,chemical,and physical damage.We developed novel compositions of edible protein coatings based on immunoglobulin(Ig)fraction from bovine milk.A lot of Ig could be obtained from under-utilized side streams of dairy industry.To the best of our knowledge,such use of the Ig fraction has not been published earlier.Materials and Methods:Bovine colostral Ig’s were incorporated in edible films based on various milk proteins and investigated the characteristics of the films including solubility of Ig’s and nisin and on technological properties of films.Ig’s specific to cariogenic bacteria Streptococcus mutans and Streptococcus sobrinus were produced to colostrums by hyperimmunizing cows before parturition.Results:The milk Ig rich fraction suited well as a component of milk protein films.The Ig’s dissolved from the films very rapidly.Nisin,commoly used for food protection,was used as a model of antimicrobial peptide.Nisin was released biologically active from bothβ-lactoglobulin(β-lg)andβ-lg/Ig films.Nisin exerted its bactericidal effect at clearly lower concentrations in theβ-lg/Ig films when compared withβ-lg film.Nisin also retained its activity better in film containing Ig-enriched whey.Incorporating Ig-enriched whey into films enhanced adhesion and tensile strength of the films.The Ig-enriched whey also affected strongly on the appearance of films based on commercial whey protein concentrate in a dose-dependent way by making the films more smooth,transparent,and clear which are all favoured properties in most food and pharmaceutical applications.Conclusions:Biologically active Ig’s can be successfully incorporated in and released from milk protein based edible films.The content of Igs in films affected considerably technological properties of these films.Composition of other proteins in films had effect on preservability and release of Igs.展开更多
Objective:To assess the effectiveness of intravenous immunoglobulin(IVIg)therapy in patients diagnosed with Crimean-Congo hemorrhagic fever(CCHF)disease.Methods:A single-center retrospective cohort study was conducted...Objective:To assess the effectiveness of intravenous immunoglobulin(IVIg)therapy in patients diagnosed with Crimean-Congo hemorrhagic fever(CCHF)disease.Methods:A single-center retrospective cohort study was conducted on hospitalized patients with confirmed severe CCHF at a tertiary care hospital in Turkey between 2010 and 2022.Cases were categorized into two groups based on whether they received IVIg therapy,with the treatment plan determined by the primary healthcare provider.The clinical,epidemiological,and laboratory parameters of these patients were evaluated.Demographic,laboratory findings,platelet counts on the day of IVIg indication and the third day,bleeding status during follow-up beyond 24 hours after IVIg administration,and prognosis recorded in patient information forms were retrieved.Results:72 patients were included in the analysis,with IVIg administered to 42 cases(58.3%)and not given to 30 cases(41.7%).Among the patients,37(51.4%)were female.Fever(65.3%)was the most common clinical presentation.The overall mortality rate was 19.4%,and IVIg administration did not significantly impact overall survival outcomes(P=0.48).On Day 3 following IVIg administration or indication,the platelet count was higher in the IVIg-treated group compared to the non-treated group(P=0.02).Furthermore,during follow-up beyond 24 hours after IVIg administration,bleeding was observed in 19.0%of the IVIg-treated group,compared to 46.6% in the non-treated group(P=0.01).Conclusions:This study underscores the potential advantages of IVIg therapy in managing severe CCHF.Although IVIg administration did not significantly affect overall survival,it was associated with earlier improvement in platelet counts and a notable reduction in bleeding complications.These findings indicate that IVIg may serve as an adjunctive treatment in CCHF,particularly for addressing hemorrhagic manifestations.展开更多
The peripheral immune system has emerged as a regulator of neurodegenerative diseases such as Alzheimer’s disease.Microglia are resident immune cells in the brain that may orchestrate communication between the centra...The peripheral immune system has emerged as a regulator of neurodegenerative diseases such as Alzheimer’s disease.Microglia are resident immune cells in the brain that may orchestrate communication between the central nervous system and peripheral immune system,though the mechanisms are unclear.Here,we found that gamma-type immunoglobulin,a product originating from peripheral blood B cells,localized in the brain parenchyma of multiple mouse models with amyloid pathology,and was enriched on microglia but not on other brain cell types.Further experiments showed that gamma-type immunoglobulin bound to microglial cell membranes and led to diverse transcriptomic changes,including upregulation of pathways related to phagocytosis and immunity.Functional assays demonstrated that gamma-type immunoglobulin enhanced microglial phagocytic capacity for amyloid-beta fibrils via its Fc fragment,but not Fab fragment,fragment.Our data indicate that microglia,when exposed to gamma-type immunoglobulin,exhibit an enhanced capacity for clearing amyloid-beta fibrils,potentially via the gamma-type immunoglobulin Fc fragment signaling pathway.This suggests that parenchymal gamma-type immunoglobulin should be further investigated to determine whether it may play a beneficial role against Alzheimer’s disease by enhancing microglial function.展开更多
Neuromyelitis optica spectrum disorder-related optic neuritis involves various cellular responses to inflammation and degeneration.In most patients,the primary mechanism underlying neuromyelitis optica spectrum disord...Neuromyelitis optica spectrum disorder-related optic neuritis involves various cellular responses to inflammation and degeneration.In most patients,the primary mechanism underlying neuromyelitis optica spectrum disorder-related optic neuritis is the interaction of aquaporin-4 antibodies with the aquaporin-4 protein present on astrocytes within posterior optic nerve.This binding subsequently initiates a cascade of events leading to secondary demyelination of the optic nerve,ultimately culminating in optic nerve degeneration.Earlier studies on this disorder primarily used systemic-induced animal models,which often require prior activation of a systemic immune response.This can result in primary demyelination of the optic nerve,complicating the interpretation of experimental results.Such methodologies hinder the ability to isolate immune responses triggered by specific antibodies.Additionally,the lack of a detailed profile of disease progression over time limits our capacity to identify potential intervention windows.Therefore,constructing a targeted optic neuritis animal model induced by specific antibodies and elucidate the disease progression arecrucial for exploring the mechanisms underlying neuromyelitis optica spectrum disorder-related optic neuritis.In this study,specific antibodies against aquaporin-4 were precisely injected into the retrobulbar optic nerve of mice to induce a targeted inflammatory response in the posterior optic nerve,resulting in a more representative mouse model of neuromyelitis optica spectrum disorder-related optic neuritis than current models.The progression of the disease was then dynamically observed from both histological and functional perspectives over the course of 1 month following the induction of inflammation.By the first week,astrocytes were damaged,as evidenced by the loss of aquaporin-4 and glial fibrillary acidic protein,the activation of microglia,and the upregulation of microglia-related cytokines,including tumor necrosis factor,interleukin-6,interleukin-1β,C-X-C motif ligand 10,and brain-derived neurotrophic factor.Starting from the second week,there were signs of optic nerve demyelination and significant damage to axonal fibers and retinal ganglion cell bodies.Visual-evoked potentials and dark adaptation threshold responses in electroretinogram both indicated dysfunction in the visual pathway and retina,while optical coherence tomography revealed thinning of the retinal nerve fiber layer in live mice.In summary,in this study we conducted a dynamic exploration of the occurrence and progression of neuromyelitis optica spectrum disorder-related optic neuritis triggered by specific antibodies.Our results show pathological changes at various stages and correlate histological and molecular alterations with in vivo structural and functional deterioration.The findings from this study lay an important foundation for further research on neuromyelitis optica spectrum disorder-related optic neuritis.展开更多
Background:Humanized mouse models are essential for studying the human immune response and antibody development.However,conventional models show limited B cell maturation and antigen-specific humoral responses.To over...Background:Humanized mouse models are essential for studying the human immune response and antibody development.However,conventional models show limited B cell maturation and antigen-specific humoral responses.To overcome these limitations,we used the NOG-EXL mice expressing human interleukin 3(IL-3)and granulocyte-macrophage colony-stimulating factor(GM-CSF)to enhance myeloid and B-cell lineage differentiation.Methods:Human CD34^(+)hematopoietic stem cells(HSC)were transplanted into NOG-EXL mice to produce humanized immune systems.After immune cell reconstitution was confirmed across 12 weeks,the mice were immunized twice with inactivated severe fever with thrombocytopenia syndrome virus(SFTSV)antigens.Peripheral blood mononuclear cells and splenocytes were analyzed using multicolor flow cytometry to assess human immune cell subsets.Antigen-specific immunoglobulin G(IgG)production was quantified using enzyme-linked immunosorbent assay(ELISA),and virus-specific B cells were isolated using antigen-labeled recombinant protein probes.Results:Twelve weeks after transplantation of HSCs into NOG-EXL mice,they exhibited robust engraftment of human leukocytes,including T,B,and dendritic cells,compared to NOG mice.Unlike NOG mice,humanized NOG-EXL mice exhibited an increase in human IgG levels,indicating the production of human antibody responses to antigens.Humanized NOG-EXL mice were immunized twice every 2 weeks with inactivated SFTSV,and antigen-specific human antibodies against the virus were detected in the mouse sera by ELISA.Sera from SFTSV-immunized humanized mice demonstrated neutralizing activity against SFTSV,confirming the induction of functional virus-specific neutralizing antibodies.Antigen-binding IgG-positive human B cells were isolated from mouse splenocytes using recombinant protein probes.Conclusion:This model provides a valuable platform for evaluating humoral immunity and isolating B cells using high-affinity human monoclonal antibodies without genetic engineering.展开更多
Objective To study the effect of high-dose methylprednisolone intravenous pulse therapy on immunoglobulins and CD series in patients with active moderate-to-severe Graves orbitopathy.Methods Twenty-seven patients with...Objective To study the effect of high-dose methylprednisolone intravenous pulse therapy on immunoglobulins and CD series in patients with active moderate-to-severe Graves orbitopathy.Methods Twenty-seven patients with active moderate-to-severe Graves orbitopathy were enrolled in this study.All the patients received iv methylprednisolone pulse therapy for 12 weeks according to the 2016 European Thyroid Association/European Group on Graves Orbitopathy(EUGOGO)Guidelines.展开更多
基金Project (No. 2004C26026) supported by the Science and Technology Department of Zhejiang Province, China
文摘Specific immunoglobulin (IgY) from egg yolk against Aeromonas hydrophila was produced by immunization of White Leghorn hens with formalin-killed whole cells of A. hydrophila. ELISA test using A. hydrophila as the coating antigen revealed that the specific antibody titer started to increase in the egg yolk at the 13th day post-immunization (P/N=2.18), reached the peak at the 56th day (P/N=13.82), and remained at high level until day 133 (P/N=7.03). The antibody was purified by saturated ammonium sulphate with a recovery rate of 63.5%. The specific IgY inhibited the growth of A. hydrophila at a concentration of 1.0 mg/ml during the 18 h incubation. Pre-treatment of polyploid gibel carps Carassius auratus Gibelio with specific IgY had a protection rate of 60% (6/10) against challenge with A. hydrophila, while none of the fishes in the control groups receiving sterile phosphate buffered saline (PBS) or non-specific IgY survived the challenge. Treatment of fishes with the specific IgY 4 h after the challenge also had lower mortality (70%, 7/10), a 30% reduction against the control PBS or non-specific IgY groups (10/10). These results indicate that specific IgY antibodies could be obtained easily from hens immunized with an inactivated A. hydrophila and could provide a novel alternative approach to control of diseases in fishes caused by this organism.
文摘Shortage of appropriate donor grafts is the foremost current problem in organ transplantation. As a logical consequence, waiting times have extended and pretransplant mortality rates were significantly increasing. The implementation of a priority-based liver allocation system using the model of end-stage liverdisease(MELD) score helped to reduce waiting list mortality in liver transplantation(LT). However, due to an escalating organ scarcity, pre-LT MELD scores have significantly increased and liver recipients became more complex in recent years. This has finally led to posttransplant decreasing survival rates, attributed mainly to elevated rates of infectious and immunologic complications. To meet this challenging development, an increasing number of extended criteria donor grafts are currently accepted, which may, however, aggravate the patients' infectious and immunologic risk profiles. The administration of intravenous immunoglobulins(IVIg) is an established treatment in patients with immune deficiencies and other antibody-mediated diseases. In addition, IVIg was shown to be useful in treatment of several disorders caused by deterioration of the cellular immune system. It proved to be effective in preventing hyperacute rejection in highly sensitized kidney and heart transplants. In the liver transplant setting, the administration of specific Ig against hepatitis B virus is current standard in post-LT antiviral prophylaxis. The mechanisms of action of IVIg are complex and not fully understood. However, there is increasing experimental and clinical evidence that IVIg has an immuno-balancing impact by a combination of immuno-supporting and immuno-suppressive properties. It may be suggested that, especially in the context of a worsening organ shortage with all resulting clinical implications, liver transplant patients should benefit from immuno-regulatory capabilities of IVIg. In this review, perspectives of immune modulation by IVIg and impact on outcome in liver transplant patients are described.
文摘Prevention of mother-to-child transmission(PMTCT)of HIV with highly active antiretroviral therapy(HARRT)allows the HIV^+pregnant mothers to have vaginal delivery and breastfeed.Here we investigated the maternal plasma immunoglobulin,cytokine secretion and the outcome of the exposed infants among the HIV^+HAART treated pregnan women in Nigeria.In this study,different plasma immunoglobulins and cytokines were measured in the HIV^+HAART treated pregnant mothers.Pooled culture supernatants of B and T lymphocytes showed lower levels of IFN-γ,IL-10 and IL-4.There were lower IFN-γand IL-10 secretions at 1st trimester;however,IL-10 continued to be lower throughout 2nd and 3rd trimesters.TNF-αsecretion significantly decreased as pregnancy progressed to term.There were high plasma IgG and low IgM in the HIV^+HAART treated pregnant women.Plasma IgG was high during 1st and 3rd trimesters.After one year of follow up,all the exposed children were seronegative for HIV-1 and HIV-2.Vaginal delivery and breastfeeding among HIV^+HAART treated mothers have shown to be safe.The use of HAART by the infected mothers and the use of septrin and niverapin by the exposed infants prevented mother to-child transmission of HIV.
文摘Muscular dystrophies are myopathies and tend to progressive, with ongoing degeneration and regeneration of muscle fibers. Spinal muscular atrophy (SMA), amyotrophic lateral sclerosis (ALS) and polio myelitis are essentially diseases of the anterior horn cells of the spine. It has been reported in literature that humoral immunity is manifested by the antibodies production. These are special chemical substances that react against foreign body. Antibodies are serum proteins, which are immunoglobulins and possess antibody activity and are classified according to antigens and stimulate their production such as IgA, JgG, IgM, IgD and IgE. All the immunological parameters such as of C3, C4, IgG, IgM and IgA, which are measured in Duchenne muscular dystrophy go down in comparison to healthy subjects. Complement C3 and Complement C4 go down about 44.3% and 78.57% respectively from the normal values. The serum IgG, IgM and IgA levels were also go down about 65%, 84% and 99.56% respectively in comparison to healthy subjects. A trend between all the immunoglobulins has been set up and it is rAG.M > rMA.G. > rGM.A, while we have a trend in DMD cases is rMA.G. > rAG.M > rGM.A We are in a position to say that our data have a relevance of high authenticity and reliability to accept that there is a deficit in immunity in DMD cases. The deficit in immunity may be a cause to damage muscle for abnormal functioning.
文摘Background: Major Depressive Disorder (MDD) is a mental disorder characterized by a pervasive and persistent low mood which is accompanied by low self-esteem and loss of interest or pleasure in day to day activities that adversely affects a person’s family, work, and personal life. There is no sufficient laboratory test for the diagnosis of MDD and it is expected that this investigation may be helpful for better diagnosis and management of MDD. We aimed to measure serum immunoglobulin levels in MDD patients and control subjects to meet the above demand. Methods: For this purpose, we recruited 88 MDD patients from the department of psychiatry, Bangabandhu Sheikh Mujib Medical University, Dhaka and 89 healthy volunteers from Dhaka city matched with age, sex and socioeconomic status to the patient group. Turbidimetry method was applied to measure serum levels of immunoglobulin A, G, and M where immunoglobulin kit was utilized. Results: The current study revealed that mean serum concentrations of immunoglobulin A, G, and M in patients were found to be 209.07 ± 104.93, 791.50 ± 235.67 and 107.92 ± 47.53 mg/dL while those were 195.34 ± 92.16, 763.81 ± 175.89 and 99.17 ± 48.78 mg/dL in control subjects, respectively. Conclusion: Our result indicates that serum concentrations of immunoglobulin A, G and M were not significant between the groups and further studies are required to establish these findings.
文摘Background: Breast cancer remains intractable and the leading cause of cancer related death among women. The appearance of breast tumour and its progression poses great clinical unpredictability before and after diagnosis, therapy and appearance of recurrent secondary deposits. Various immunological changes occur during breast tumourigenesis, and can be of value in the surveillance of the diseases. In our environment, there is scanty information on the value of these immunological factors especially immunoglobulins in screening and surveillance of breast cancer—hence the need for this study. Methodology: A total of 59 females (mean age = 48.7 ± 8.7 yrs) with clinically and pathologically confirmed breast cancer were prospectively recruited alongside with 20 patients with benign breast tumour representing patients’ control group and 20 apparently healthy age and sex-matched control subjects (mean age = 47.5 ± 13.4 yrs). Breast cancer patients were further grouped into early stage breast cancer (N = 25) and advanced stage breast cancer (N = 34). Patients were subjected to standard treatment modalities and pre- and post-treatment samples collected at intervals. Samples were assayed for IgG & IgM by immunoenzymatic methods and IgA by immunoturbidimetric method. Questionnaires and measurements were used to obtain necessary demographic and anthropologic information from the subjects. Results: Results showed that in all stages of breast cancer and treatment groups, the mean serum IgG, IgM and IgA levels respectively were not significantly raised (P > 0.05) when compared. Results also showed that majority (59%) of the patients presented at advanced stage of the disease. Low level of education and low income were among the prevailing risk factors. Majority (63%) of the cases had body mass index suggesting obesity (>30 kg/m2). Conclusion: Results suggest that serum immunoglobulin (IgG, IgM and IgA) levels are of limited value in surveillance of breast cancer in our environment. Based on our findings, it could also be concluded that low levels of education and low income are among the risk factors. Advocacy and evidence based policies aimed at prevention and early detection of the disease should be prioritized.
文摘Our findings show that the value of IgG in serum of Alzheimer’s Disease patients is (17.2059 ± 2.6317) g/l and in controls i.e. (17.6720 ± 3.1457) g/l. Values of IgM in AD patients go down up to 62.5% in comparison to healthy subjects. A sudden change was observed in the levels of IgA of AD patients. It has been put on the value 137.9% high in comparison to healthy subjects. The levels of complement C3 have also value of lower side and go down up to 52.66% in AD patients. The value of levels of complement C4 shows no deflection from the control values. On the basis of regression and multiple correlation analysis, we found that the partial correlation coefficients rGA.M, which has value 0.44815 in AD patients and 0.45555 in controls, do not show any resemblance. The multiple partial correlation rAM.G has value 0.3082 in AD patients and 0.3912 in controls slightly better correlated in comparison to healthy controls. Multiple RA.MG has strongly correlation in comparison to controls. RM.AG is also strongly correlated. Regression coefficients and regression equations are basic foundations of correlation measurements and show a specific character of variation. A relation between all the three multiple correlations has been established in the present work and it is given by the following relation RA.MG > RM.AG > RG.AM.
基金the State Key Laboratory of Animal Nutrition(2004DA125184-0810)of China
文摘This experiment was conducted to investigate the effects of dietary ratios of n-6：n-3 polyunsaturated fatty acids （PUFA） on the performance of lactating sows and their piglets. Thirty pregnant Landrace sows were assigned to one of three treatments from d 108 of gestation until weaning （26-29 d） and were fed diets containing different ratios of n-6：n-3 PUFA including 3：1,9：1 and 13：1. The effects on sow and litter production traits were examined together with an assessment of sow body condition. No differences were detected among the treatments for the daily feed intake of sows or changes in sow weight and back-fat levels during lactation （P 〉 0.05）. Litter size at d 14 and d 21 were tended to increase in 3：1 treatment compared with 9：1 and 13：1 treatments （P 〈 0.10）. Litter weight gain （1.77 kg/d） from d 0 to d 14 was tended to increase in 9：1 groups compared with the other two treatments （P 〈 0.10）. A significant difference was observed for the content of a -linolenic acid, total n-3 PUFA, and the ratio of n-6：n-3 PUFA in the colostrum, milk, and piglets plasma （P 〈 0.01）. The effects of different ratios of n-6：n-3 PUFA in sow diets on colostrum, milk and piglet plasma immunoglobulin concentrations are studied. No difference was observed among treatments in the concentrations of IgM, and IgA in colostrum （P 〉 0.05）. A great significant difference for IgG concentration was observed among 3 group in colostrum. A great significant difference for IgA, and IgM （P〈 0.01） concentrations in piglet plasma at d14 and a significant difference for IgG（P 〈 0.05） was observed at d14. Furthermore, at d 21 of lactation, piglet plasma IgG and IgA concentration were greater in 3：1 compared with 13：1 group （P 〈 0.01）. In summary, the current study demonstrated that altering the ratio of n-6：n-3 PUFA in lactating sow diet had an effect on the immune component including immunoglobulin and cytokines, and it tended to increase the litter average daily gain and improve the immune status of piglets when dietary ratio of n-6：n-3 PUFA was 9：1.
基金Supported by the National Natural Science Foundation of China(21776243,21476198)the International Science&Technology Cooperation Program of China(2015DFG42070)
文摘The importance of immunoglobulin Y(IgY) as a specific antibody equivalent to mammalian immunoglobulin G(IgG) is well recognized. However, production of highly purified IgY is still difficult due to the lack of specific purification methods. In this study, adsorption behaviors of Ig Y on four mixed-mode resins with functional ligands of 4-mercatoethyl-pyridine(MEP), 2-mercapto-1-methyli-midazole(MMI), 5-aminobenzi-midazole(ABI) and tryptophan-5-aminobenzi-midazole(W-ABI) were evaluated. The results showed that high adsorption ratio were found at p H 6.0–7.0 with little adsorption under acidic conditions. The resin with ABI ligand was then used to separate IgY from immunized chicken serum. An efficient process with Ig Y purity of 95% and recovery of 90% was developed after optimization of loading and elution p H and injection volume. The biological activity of the purified Ig Y was fully maintained. These results indicated that mixed-mode chromatography with specially-designed ligands has great potential for the separation of Ig Y from crude feedstock.
基金completed at the State Key Laboratory of Animal Nutrition (2004DA125184-0810) of China
文摘This experiment was conducted to investigate the effects of different ratios of n-6 ∶ n-3 polyunsaturated fatty acids （PUFA） in sow diets on the performance of lactating sows and their piglets at low digestible energy intakes. Twenty-one pregnant Landrace sows were assigned to one of three diets from day 108 of gestation until weaning （26 to 29 d） ,containing n-6∶n-3 PUFA ratios of 3 ∶1,8 ∶1 and 11 ∶1. The effects on sow and litter production traits and on sow body condition were examined. There were no differences among treatments in daily feed intakes or in changes in sow weight and back-fat levels during lactation. Litter size,litter weight at birth and weaning and litter average daily weight gain were also unaffected by treatment. As expected, large differences were observed in n-6 and n-3 fatty acids in the colostrum and plasma of sows and piglets （P 〈 0. 01） . The ratio of n6 ∶ n-3 PUFA the diet was positively correlated with those in colostrum,sow plasma and piglet plasma （R 2= 0. 55,0. 80 and 0. 80,respectively） . Sow plasma insulin and IGF-I levels at weaning were unaffected by the treatments. Plasma leptin （P 〈 0. 05） concentrations were increased in sows fed the diet with a n-6∶n-3 ratio of 8 ∶ 1. Immunoglobulin concentrations in colostrum were not altered by dietary treatment. Plasma IgG concentrations at d 14 were highest in piglets from sows fed the 8 ∶ 1 ratio of n-6∶n-3. Furthermore,this group had the highest IgA concentrations at day 21 of lactation compared with the other two groups （P 〈 0. 05） . In summary,our study demonstrated that at low digestible energy levels,altering the ratio of n-6 ∶ n-3 PUFA in the diets for lactating sows affected immune components and the fatty acid composition of lactating sows and their piglets. Further studies are needed to examine whether higher levels of fat supplementation than those used in the present study （1. 5%） can successfully enhance performance.
文摘A study was conducted to determine if Se source fed during gestation and lactation affects passive transfer of immunoglobulins. Sixty days prior to breeding （d -60）, gilts were randomly assigned to one of three treatments prior to breeding and throughout gestation： control （Control, no supplemental Se; n = 8）, inorganic Se （Inorganic Se, 0.3 ppm; n = 4） and organic Se （Organic Se, 0.3 ppm; n = 4）. Blood was collected on d -60, 57 and 113 of gestation and on d 21 of lactation and milk was collected at d 0, 1, 7, 14, and 21 of lactation. Blood was collected from piglets at d 0, 1, 7, 14, and 21 of age. Gilts fed organic Se had greater （P 〈 0.05） circulating concentrations of Se than Inorganic and Control gilts. Regardless of treatment, circulating concentrations of Se were greatest （P 〈 0.05） at d -60 compared to all other days. Serum concentrations of IgG were greatest （P 〈 0.05） in gilts at d 57 of gestation compared to d 113. Serum concentrations of IgA were greatest （P 〈 0.05） on d 113 of gestation and d 21 of lactation compared to d -60 and 57. Serum concentrations of IgM were greater （P 〈 0.05） at d 57 compared to d -60. Inorganic gilts had greater （P 〈 0.05） colostral and milk concentrations of IgG and IgM than Organic or Control gilts. Circulating concentrations of Se in piglets were greatest （P 〈 0.05） at d 14 and 21 of age compared to all other days. Piglets from gilts supplemented with organic Se had greater （P 〈 0.05） circulating concentrations of Se on d 1 versus piglets from gilts supplemented with no additional Se. The immunoglobulin concentrations of IgG, IgA, and IgM were lowest （P 〈 0.05） on d 0 and then different sources of Se did not affect the immunoglobulin ncreased when compared to d 1. The addition of concentrations in the gilt or piglet.
文摘Therapeutic immunoglobulins are used in the treatment of immunodeficiencies as well as several autoimmune and inflammatory diseases. These intravenous immunoglobulins (IVIg) represent the healthy human IgG repertoire, which can be reactive for both self and non-self antigens. A better characterization of IVIg’s repertoire is an important aspect to enable its effective utilization as an immunomodulatory treatment. In this study we have investigated the reactivity of IgG1, IgG2, IgG3 and IgG4 present in IVIg for a small selection of antigens, including actin, DNA, ferritin and thyroglobulin. We observed that two commercial preparations of therapeutic immunoglobulins contain very high reactivity for thyroglobulin, which was predominantly detected by IgG4. Since IgG4 antibodies can have immunomodulatory properties, these result suggest that these anti-thyroglobulin may have a role in the IVIg treatment of autoimmune disease characterized by high avidity for anti-thyroglobulin antibodies such as Hashimoto’s disease.
文摘Objective: To study the serum tumor markers, immunoglobulin, TNF-α and hs-CRP in breast cancer in different pathological stages of the concentration, and to analyze the clinical significance of early diagnosis of breast cancer. Methods: A total of 130 patients with breast cancer were divided into stage I, II, III and IV according to clinical pathology. In addition, 40 patients with benign breast disease and 35 healthy subjects were selected as benign breast disease group and control group. Serum tumor markers, immunoglobulins, TNF-αand hs-CRP concentrations were measured and compared of all subjects. Results: There were no significant difference in serum tumor markers, immunoglobulin and inflammatory factors between the control group and the benign breast cancer group. The level of serum tumor markers in breast cancer group was significantly higher than that in control group and benign breast cancer group. The levels of serum CA125, CA153 and CEA were gradually increased with the severity enhancing from stage I and IV of breast cancer, and he difference was statistically significant. The level of serum immunoglobulin in breast cancer group was significantly higher than that in control group and benign breast cancer group. The levels of serum IgG and IgM increased gradually severity enhancing from stage I and IV of breast cancer, and the difference was statistically significant. The level of serum TNF-α and hs-CRP in serum of breast cancer group was significantly higher than that of control group and benign breast cancer group. The serum levels of TNF-α and hs-CRP increased gradually with severity enhancing from stage I and IV of breast cancer, and the difference was statistically significant. Conclusion: The level of serum tumor markers in breast cancer patients is increasing. Humoral and inflammatory responses are activated to varying degrees and increase with the aggregation of disease. They may involve regulating the occurrence and metastasis of breast cancer and regulating the pathophysiological function of patients. Which may be a certain clinical significance for the early diagnosis of breast cancer and disease progression.
基金We also wish to thank the Finnish Funding Agency for Innovation(Tekes)and Ministry of Agriculture and Forestry for financial support.
文摘Objectives:The goal of this study was to develop novel compositions of edible protein coatings based on immunoglobulin(Ig)fraction from bovine milk.Protein coatings can be used to protect foods against microbial,chemical,and physical damage.We developed novel compositions of edible protein coatings based on immunoglobulin(Ig)fraction from bovine milk.A lot of Ig could be obtained from under-utilized side streams of dairy industry.To the best of our knowledge,such use of the Ig fraction has not been published earlier.Materials and Methods:Bovine colostral Ig’s were incorporated in edible films based on various milk proteins and investigated the characteristics of the films including solubility of Ig’s and nisin and on technological properties of films.Ig’s specific to cariogenic bacteria Streptococcus mutans and Streptococcus sobrinus were produced to colostrums by hyperimmunizing cows before parturition.Results:The milk Ig rich fraction suited well as a component of milk protein films.The Ig’s dissolved from the films very rapidly.Nisin,commoly used for food protection,was used as a model of antimicrobial peptide.Nisin was released biologically active from bothβ-lactoglobulin(β-lg)andβ-lg/Ig films.Nisin exerted its bactericidal effect at clearly lower concentrations in theβ-lg/Ig films when compared withβ-lg film.Nisin also retained its activity better in film containing Ig-enriched whey.Incorporating Ig-enriched whey into films enhanced adhesion and tensile strength of the films.The Ig-enriched whey also affected strongly on the appearance of films based on commercial whey protein concentrate in a dose-dependent way by making the films more smooth,transparent,and clear which are all favoured properties in most food and pharmaceutical applications.Conclusions:Biologically active Ig’s can be successfully incorporated in and released from milk protein based edible films.The content of Igs in films affected considerably technological properties of these films.Composition of other proteins in films had effect on preservability and release of Igs.
文摘Objective:To assess the effectiveness of intravenous immunoglobulin(IVIg)therapy in patients diagnosed with Crimean-Congo hemorrhagic fever(CCHF)disease.Methods:A single-center retrospective cohort study was conducted on hospitalized patients with confirmed severe CCHF at a tertiary care hospital in Turkey between 2010 and 2022.Cases were categorized into two groups based on whether they received IVIg therapy,with the treatment plan determined by the primary healthcare provider.The clinical,epidemiological,and laboratory parameters of these patients were evaluated.Demographic,laboratory findings,platelet counts on the day of IVIg indication and the third day,bleeding status during follow-up beyond 24 hours after IVIg administration,and prognosis recorded in patient information forms were retrieved.Results:72 patients were included in the analysis,with IVIg administered to 42 cases(58.3%)and not given to 30 cases(41.7%).Among the patients,37(51.4%)were female.Fever(65.3%)was the most common clinical presentation.The overall mortality rate was 19.4%,and IVIg administration did not significantly impact overall survival outcomes(P=0.48).On Day 3 following IVIg administration or indication,the platelet count was higher in the IVIg-treated group compared to the non-treated group(P=0.02).Furthermore,during follow-up beyond 24 hours after IVIg administration,bleeding was observed in 19.0%of the IVIg-treated group,compared to 46.6% in the non-treated group(P=0.01).Conclusions:This study underscores the potential advantages of IVIg therapy in managing severe CCHF.Although IVIg administration did not significantly affect overall survival,it was associated with earlier improvement in platelet counts and a notable reduction in bleeding complications.These findings indicate that IVIg may serve as an adjunctive treatment in CCHF,particularly for addressing hemorrhagic manifestations.
基金supported by the National Natural Science Foundation of China,Nos.82171082(to ZX),32000727(to TZ),32370731(to YZ)Guangdong Basic and Applied Basic Research Foundation,No.2024A151501069(to ZX)+1 种基金Shenzhen Science and Technology Program,Nos.JCYJ20210324101603009(to ZX),GJHZ20220913142807015(to TZ),JCYJ20220531100204010(to TZ),JCYJ20230807091308018(to YZ)Shenzhen Medical Research Funds,No.A2303068(to TZ).
文摘The peripheral immune system has emerged as a regulator of neurodegenerative diseases such as Alzheimer’s disease.Microglia are resident immune cells in the brain that may orchestrate communication between the central nervous system and peripheral immune system,though the mechanisms are unclear.Here,we found that gamma-type immunoglobulin,a product originating from peripheral blood B cells,localized in the brain parenchyma of multiple mouse models with amyloid pathology,and was enriched on microglia but not on other brain cell types.Further experiments showed that gamma-type immunoglobulin bound to microglial cell membranes and led to diverse transcriptomic changes,including upregulation of pathways related to phagocytosis and immunity.Functional assays demonstrated that gamma-type immunoglobulin enhanced microglial phagocytic capacity for amyloid-beta fibrils via its Fc fragment,but not Fab fragment,fragment.Our data indicate that microglia,when exposed to gamma-type immunoglobulin,exhibit an enhanced capacity for clearing amyloid-beta fibrils,potentially via the gamma-type immunoglobulin Fc fragment signaling pathway.This suggests that parenchymal gamma-type immunoglobulin should be further investigated to determine whether it may play a beneficial role against Alzheimer’s disease by enhancing microglial function.
基金The study was partially supported by the General Research Fund(GRF)from the Research Grants Council(RGC)of the Hong Kong Special Administrative Region,China,No.15103522(to ST)the Internal Research Grant from the Hong Kong Polytechnic University 2021-23,No.P0035512(to ST)and P0035375(to HHLC)+1 种基金the Innovation and Technology Commission of the Hong Kong Special Administrative Region(ITC InnoHK CEVR Project)The Hong Kong Polytechnics University Research Center for Sharp Vision,No.P0039595.
文摘Neuromyelitis optica spectrum disorder-related optic neuritis involves various cellular responses to inflammation and degeneration.In most patients,the primary mechanism underlying neuromyelitis optica spectrum disorder-related optic neuritis is the interaction of aquaporin-4 antibodies with the aquaporin-4 protein present on astrocytes within posterior optic nerve.This binding subsequently initiates a cascade of events leading to secondary demyelination of the optic nerve,ultimately culminating in optic nerve degeneration.Earlier studies on this disorder primarily used systemic-induced animal models,which often require prior activation of a systemic immune response.This can result in primary demyelination of the optic nerve,complicating the interpretation of experimental results.Such methodologies hinder the ability to isolate immune responses triggered by specific antibodies.Additionally,the lack of a detailed profile of disease progression over time limits our capacity to identify potential intervention windows.Therefore,constructing a targeted optic neuritis animal model induced by specific antibodies and elucidate the disease progression arecrucial for exploring the mechanisms underlying neuromyelitis optica spectrum disorder-related optic neuritis.In this study,specific antibodies against aquaporin-4 were precisely injected into the retrobulbar optic nerve of mice to induce a targeted inflammatory response in the posterior optic nerve,resulting in a more representative mouse model of neuromyelitis optica spectrum disorder-related optic neuritis than current models.The progression of the disease was then dynamically observed from both histological and functional perspectives over the course of 1 month following the induction of inflammation.By the first week,astrocytes were damaged,as evidenced by the loss of aquaporin-4 and glial fibrillary acidic protein,the activation of microglia,and the upregulation of microglia-related cytokines,including tumor necrosis factor,interleukin-6,interleukin-1β,C-X-C motif ligand 10,and brain-derived neurotrophic factor.Starting from the second week,there were signs of optic nerve demyelination and significant damage to axonal fibers and retinal ganglion cell bodies.Visual-evoked potentials and dark adaptation threshold responses in electroretinogram both indicated dysfunction in the visual pathway and retina,while optical coherence tomography revealed thinning of the retinal nerve fiber layer in live mice.In summary,in this study we conducted a dynamic exploration of the occurrence and progression of neuromyelitis optica spectrum disorder-related optic neuritis triggered by specific antibodies.Our results show pathological changes at various stages and correlate histological and molecular alterations with in vivo structural and functional deterioration.The findings from this study lay an important foundation for further research on neuromyelitis optica spectrum disorder-related optic neuritis.
基金The Korea Centers for Disease Control and Prevention,Grant/Award Number:2022-ER1701-00,2022-NI-041-02,2024-ER1702-00 and 2025-NI-014-00。
文摘Background:Humanized mouse models are essential for studying the human immune response and antibody development.However,conventional models show limited B cell maturation and antigen-specific humoral responses.To overcome these limitations,we used the NOG-EXL mice expressing human interleukin 3(IL-3)and granulocyte-macrophage colony-stimulating factor(GM-CSF)to enhance myeloid and B-cell lineage differentiation.Methods:Human CD34^(+)hematopoietic stem cells(HSC)were transplanted into NOG-EXL mice to produce humanized immune systems.After immune cell reconstitution was confirmed across 12 weeks,the mice were immunized twice with inactivated severe fever with thrombocytopenia syndrome virus(SFTSV)antigens.Peripheral blood mononuclear cells and splenocytes were analyzed using multicolor flow cytometry to assess human immune cell subsets.Antigen-specific immunoglobulin G(IgG)production was quantified using enzyme-linked immunosorbent assay(ELISA),and virus-specific B cells were isolated using antigen-labeled recombinant protein probes.Results:Twelve weeks after transplantation of HSCs into NOG-EXL mice,they exhibited robust engraftment of human leukocytes,including T,B,and dendritic cells,compared to NOG mice.Unlike NOG mice,humanized NOG-EXL mice exhibited an increase in human IgG levels,indicating the production of human antibody responses to antigens.Humanized NOG-EXL mice were immunized twice every 2 weeks with inactivated SFTSV,and antigen-specific human antibodies against the virus were detected in the mouse sera by ELISA.Sera from SFTSV-immunized humanized mice demonstrated neutralizing activity against SFTSV,confirming the induction of functional virus-specific neutralizing antibodies.Antigen-binding IgG-positive human B cells were isolated from mouse splenocytes using recombinant protein probes.Conclusion:This model provides a valuable platform for evaluating humoral immunity and isolating B cells using high-affinity human monoclonal antibodies without genetic engineering.
文摘Objective To study the effect of high-dose methylprednisolone intravenous pulse therapy on immunoglobulins and CD series in patients with active moderate-to-severe Graves orbitopathy.Methods Twenty-seven patients with active moderate-to-severe Graves orbitopathy were enrolled in this study.All the patients received iv methylprednisolone pulse therapy for 12 weeks according to the 2016 European Thyroid Association/European Group on Graves Orbitopathy(EUGOGO)Guidelines.
