Dear editors,Neurodegenerative diseases are now associated with the global obesity and diabetes epidemic in the developing and developed world.Neurodegenerative diseases are a heterogeneous group of disorders with com...Dear editors,Neurodegenerative diseases are now associated with the global obesity and diabetes epidemic in the developing and developed world.Neurodegenerative diseases are a heterogeneous group of disorders with complex factors such as neurohumoral,endocrine and environmental factors involved in induction of these neurodegenerative diseases.The future of science and medicine in neurodegenerative diseases is now dependent on nutritional genomics with insulin resistance a major factor in the induction of neurodegenerative diseases.Nutritional genomics now involves the anti-aging gene Sirtuin 1(Sirt 1)that is important to the prevention of insulin resistance with its critical involvement in the immune system(Martins,2018a,b).Sirt 1 inactivation leads to toxic immune reactions connected to the acceleration of neuron death in various communities.Appetite control with relevance to immunometabolism has become of critical importance to the treatment of neurodegeneration(Figure 1).Nutritional diets activate the heat shock gene Sirt 1 to prevent the increase in heat shock proteins connected to autoimmune disease,mitophagy(Martins,2018a,b)and irreversible programmed cell death in global populations(Figure 1).展开更多
The interplay between DNA replication stress and immune microenvironment alterations is known to play a crucial role in colorectal tumorigenesis,but a comprehensive understanding of their association with and relevant...The interplay between DNA replication stress and immune microenvironment alterations is known to play a crucial role in colorectal tumorigenesis,but a comprehensive understanding of their association with and relevant biomarkers involved in colorectal tumorigenesis is lacking.To address this gap,we conducted a study aiming to investigate this association and identify relevant biomarkers.We analyzed transcriptomic and proteomic profiles of 904 colorectal tumor tissues and 342 normal tissues to examine pathway enrichment,biological activity,and the immune microenvironment.Additionally,we evaluated genetic effects of single variants and genes on colorectal cancer susceptibility using data from genome-wide association studies(GWASs)involving both East Asian(7062 cases and 195745 controls)and European(24476 cases and 23073 controls)populations.We employed mediation analysis to infer the causal pathway,and applied multiplex immunofluorescence to visualize colocalized biomarkers in colorectal tumors and immune cells.Our findings revealed that both DNA replication activity and the flap structure-specific endonuclease 1(FEN1)gene were significantly enriched in colorectal tumor tissues,compared with normal tissues.Moreover,a genetic variant rs4246215 G>T in FEN1 was associated with a decreased risk of colorectal cancer(odds ratio=0.94,95%confidence interval:0.90–0.97,P_(meta)=4.70×10^(-9)).Importantly,we identified basophils and eosinophils that both exhibited a significantly decreased infiltration in colorectal tumors,and were regulated by rs4246215 through causal pathways involving both FEN1 and DNA replication.In conclusion,this trans-omics incorporating GWAS data provides insights into a plausible pathway connecting DNA replication and immunity,expanding biological knowledge of colorectal tumorigenesis and therapeutic targets.展开更多
The Miller Fisher variant is an uncommon but well known syndrome being described as a triad of areflexia, ataxia and complex ophthalmoplegia. It is characterized by antibodies against myelin that affects peripheral ne...The Miller Fisher variant is an uncommon but well known syndrome being described as a triad of areflexia, ataxia and complex ophthalmoplegia. It is characterized by antibodies against myelin that affects peripheral nerves, extraocular muscles and Schwann cells. Anti-ganglioside antibodies have been recognized in disease pathogenesis and decreasing antibody production is the mainstay of treatment. The course is usually benign with improvement after immunomodulation. This case report describes the approach to a patient suspected of having a demyelinating disorder. It delineates the subsets of immune mediated neuropathies in evaluating the diagnosis and emphasizes the need for early therapeutic intervention in achieving a good clinical outcome.展开更多
BACKGROUND Anti-glomerular basement membrane(GBM)disease is a rare rapidly progressive glomerulonephritis,frequently associated with alveolar hemorrhage in the lungs and involving the kidney by crescentic glomerulonep...BACKGROUND Anti-glomerular basement membrane(GBM)disease is a rare rapidly progressive glomerulonephritis,frequently associated with alveolar hemorrhage in the lungs and involving the kidney by crescentic glomerulonephritis.It has been described in association with other glomerulonephritides[such as anti-neutrophilic antibody(ANCA)-glomerulonephritis,membranous nephropathy,and immunoglobulin(Ig)A nephropathy].CASE SUMMARY Herein we present an unusual case of concurrent anti-GBM disease,ANCAassociated crescentic glomerulonephritis and diffuse proliferative immune complex mediated glomerulonephritis with predominant staining for IgA and C3 by immunofluorescence.The patient is a 46-year-old Caucasian male who presented to the emergency department with acute onset of flank pain and was found to have high serum creatinine levels of 15 mg/dL,proteinuria,and hematuria.He rapidly deteriorated and became anuric.He was found to have high anti-GBM antibodies titers(151 units)and high anti-neutrophil cytoplasmic-ANCA.Despite prompt and early treatment,the patient’s condition worsened,and he succumbed to his illness.CONCLUSION Our case emphasizes the importance of a renal biopsy in anti-GBM disease,even in the presence of positive serum anti-GBM antibodies,to identify other potential causes of rapidly progressive glomerulonephritis.The challenge in treating such cases lies in the different therapy modalities.展开更多
Regulator of G-protein Signaling 10 （Rgsl0） plays an important function in osteoclast differentiation. However, the role of Rgsl0 in immune cells and inflammatory responses, which activate osteoclasts in inflam- mat...Regulator of G-protein Signaling 10 （Rgsl0） plays an important function in osteoclast differentiation. However, the role of Rgsl0 in immune cells and inflammatory responses, which activate osteoclasts in inflam- matory lesions, such as bacteria-induced periodontal disease lesions, remains largely unknown. In this study, we used an adeno-associated virus （AAV-） mediated RNAi （AAV-shRNA-Rgs10） knockdown approach to study Rgsl0＇s function in immune cells and osteoclasts in bacteria-induced inflammatory lesions in a mouse model of periodontal disease. We found that AAV-shRNA-Rgs10 mediated Rgs10 knockdown impaired osteoclastogenesis and osteoclast-mediated bone resorption, in vitro and in vivo. Interestingly, local injection of AAV-shRNA-Rgs10 into the periodontal tissues in the bacteria-induced inflammatory lesion greatly decreased the number of dendritic cells, T-cells and osteoclasts, and protected the periodontal tissues from local inflammatory damage and bone destruction. Importantly, AAV-mediated Rgs10 knockdown also reduced local expression of osteoclast markers and pro-inflammatory cytokines. Our results demonstrate that AAV- shRNA-Rgs10 knockdown in periodontal disease tissues can prevent bone resorption and inflammation simultaneously. Our data indicate that Rgsl0 may regulate dendritic cell proliferation and maturation, as well as the subsequent stimulation of T-cell proliferation and maturation, and osteoclast differentiation and acti- vation. Our study suggests that AAV-shRNA-Rgs10 can be useful as a therapeutic treatment of periodontal disease.展开更多
Objective:To study the effects of smilax bockii warb polysaccharide on inflammatory mediators, apoptosis and immune cell function in rats with chronic pelvic inflammatory disease.Methods:Female SD rats were chosen as ...Objective:To study the effects of smilax bockii warb polysaccharide on inflammatory mediators, apoptosis and immune cell function in rats with chronic pelvic inflammatory disease.Methods:Female SD rats were chosen as experimental animals and divided into control group, pelvic inflammation group and smilax bockii warb group, pelvic inflammation group and smilax bockii warb group were made into pelvic inflammation models, and smilax bockii warb group were given intragastric administration of smilax bockii warb. The contents of inflammatory mediators and the expression of apoptosis genes in uterine muscle as well as the contents of immune cells in peripheral blood were determined 21 d after molding and intervention.Results:TLR4, NF-κB, TNF-α, ICAM-1 and IL-8 levels as well as Fas, TNFR-1, GRP78, CHOP and Caspase-3 mRNA expression in uterine muscle tissue and CD3+CD8+T cell in peripheral blood of pelvic inflammation group were higher than those of control group whereas peripheral blood CD3+CD4+T cell, red blood cell C3b receptor rosette rate and erythrocyte immune complex rosette were lower than those of control group;TLR4, NF-κB, TNF-α, ICAM-1 and IL-8 levels as well as Fas, TNFR-1, GRP78, CHOP and Caspase-3 mRNA expression in uterine muscle tissue as well as CD3+CD8+T cell in peripheral blood of smilax bockii warb group were lower than those of pelvic inflammation group whereas peripheral blood CD3+CD4+T cell, red blood cell C3b receptor rosette rate and erythrocyte immune complex rosette were higher than those of pelvic inflammation group. Conclusion:Smilax bockii warb polysaccharide for chronic pelvic inflammatory disease intervention can inhibit the inflammatory mediator secretion, apoptosis and regulate the immune cell function.展开更多
Acute morphine administration is known to alter the course of herpes simplex virus infection. In this study, the effect of acute morphine administration on the reactivation of latent herpes was investigated in a mouse...Acute morphine administration is known to alter the course of herpes simplex virus infection. In this study, the effect of acute morphine administration on the reactivation of latent herpes was investigated in a mouse model. Because of the important role of cytolytic T lymphocyte （CTL） activity in the inhibition of herpes simplex virus type 1 （HSV-1） reactivation, the effect of acute morphine administration on CTL responses was also evaluated. Furthermore, lymphocyte proliferation and IFN-γ production were evaluated for their roles in the induction of the CTL response. The findings showed that acute morphine administration significantly reduced CTL responses, lymphocyte proliferation, and IFN-γ production. Furthermore, acute morphine administration has been shown to reactivate latent HSV-γ. Previous studies have shown that cellular immune responses have important roles in the inhibition of HSV reactivation. These findings suggest that suppression of a portion of the cellular immune response after acute morphine administration may constitute one part of the mechanism that induces HSV reactivation.展开更多
BACKGROUND According to the theory of traditional Chinese medicine(TCM),the spleen and stomach are the basis of acquired nature and the source of qi and blood biochemistry.After surgery and chemotherapy,patients with ...BACKGROUND According to the theory of traditional Chinese medicine(TCM),the spleen and stomach are the basis of acquired nature and the source of qi and blood biochemistry.After surgery and chemotherapy,patients with colorectal cancer often develop spleen and stomach qi deficiency syndrome,leading to decreased immune function.Buzhong Yiqi decoction,a classic TCM prescription,has the effect of tonifying middle-jiao and invigorating qi,boosting Yang,and suppressing immune-related inflammation.Moreover,it is widely used in the treatment of spleen and stomach qi deficiency syndrome.AIM To investigate the effect of Buzhong Yiqi decoction on spleen and stomach qi deficiency in patients with colorectal cancer.METHODS One hundred patients with colorectal cancer who underwent preoperative chemotherapy and laparoscopy at The First TCM Hospital of Changde from January 2022 to October 2023 were retrospectively analyzed.The patients were divided equally into control and observation groups.Both groups underwent conventional rehabilitation surgery,and the observation group was supplemented with Buzhong Yiqi decoction.SPSS 26.0 was used for statistical analyses.Theχ2 test was used for univariate analysis;independent sample t-tests were used in all cases.RESULTS No significant differences were observed preoperatively in the general characteristics of the two groups.Fourteen days post-surgery,the abdominal distension,emaciation,loose stool,loss of appetite,and vomiting scores were significantly lower in the observation group than in the control group(P<0.05).Immune function and interleukin(IL)-10 levels in the observation group were significantly higher than those of the control group,whereas IL-6,tumor necrosis factor-α,and C-reactive protein levels,tumor biological indexes,and adverse reactions in the observation group were significantly lower than those of the control group(P<0.05).One month after surgery,the patients’quality of life in the observation group was significantly higher than that of the patients in the control group(P<0.05).CONCLUSION Buzhong Yiqi decoction can regulate inflammatory responses and metabolic processes by enhancing immune function,thereby promoting overall immune nutrition and restoring the body’s balance.展开更多
基金supported by grants from Edith Cowan Universitythe McCusker Alzheimer’s Research Foundationthe National Health and Medical Research Council
文摘Dear editors,Neurodegenerative diseases are now associated with the global obesity and diabetes epidemic in the developing and developed world.Neurodegenerative diseases are a heterogeneous group of disorders with complex factors such as neurohumoral,endocrine and environmental factors involved in induction of these neurodegenerative diseases.The future of science and medicine in neurodegenerative diseases is now dependent on nutritional genomics with insulin resistance a major factor in the induction of neurodegenerative diseases.Nutritional genomics now involves the anti-aging gene Sirtuin 1(Sirt 1)that is important to the prevention of insulin resistance with its critical involvement in the immune system(Martins,2018a,b).Sirt 1 inactivation leads to toxic immune reactions connected to the acceleration of neuron death in various communities.Appetite control with relevance to immunometabolism has become of critical importance to the treatment of neurodegeneration(Figure 1).Nutritional diets activate the heat shock gene Sirt 1 to prevent the increase in heat shock proteins connected to autoimmune disease,mitophagy(Martins,2018a,b)and irreversible programmed cell death in global populations(Figure 1).
基金supported by the National Natural Science Foundation of China(Grant No.82173601)Yili&Jiangsu Joint Institute of Health(Grant No.yl2021ms02).
文摘The interplay between DNA replication stress and immune microenvironment alterations is known to play a crucial role in colorectal tumorigenesis,but a comprehensive understanding of their association with and relevant biomarkers involved in colorectal tumorigenesis is lacking.To address this gap,we conducted a study aiming to investigate this association and identify relevant biomarkers.We analyzed transcriptomic and proteomic profiles of 904 colorectal tumor tissues and 342 normal tissues to examine pathway enrichment,biological activity,and the immune microenvironment.Additionally,we evaluated genetic effects of single variants and genes on colorectal cancer susceptibility using data from genome-wide association studies(GWASs)involving both East Asian(7062 cases and 195745 controls)and European(24476 cases and 23073 controls)populations.We employed mediation analysis to infer the causal pathway,and applied multiplex immunofluorescence to visualize colocalized biomarkers in colorectal tumors and immune cells.Our findings revealed that both DNA replication activity and the flap structure-specific endonuclease 1(FEN1)gene were significantly enriched in colorectal tumor tissues,compared with normal tissues.Moreover,a genetic variant rs4246215 G>T in FEN1 was associated with a decreased risk of colorectal cancer(odds ratio=0.94,95%confidence interval:0.90–0.97,P_(meta)=4.70×10^(-9)).Importantly,we identified basophils and eosinophils that both exhibited a significantly decreased infiltration in colorectal tumors,and were regulated by rs4246215 through causal pathways involving both FEN1 and DNA replication.In conclusion,this trans-omics incorporating GWAS data provides insights into a plausible pathway connecting DNA replication and immunity,expanding biological knowledge of colorectal tumorigenesis and therapeutic targets.
文摘The Miller Fisher variant is an uncommon but well known syndrome being described as a triad of areflexia, ataxia and complex ophthalmoplegia. It is characterized by antibodies against myelin that affects peripheral nerves, extraocular muscles and Schwann cells. Anti-ganglioside antibodies have been recognized in disease pathogenesis and decreasing antibody production is the mainstay of treatment. The course is usually benign with improvement after immunomodulation. This case report describes the approach to a patient suspected of having a demyelinating disorder. It delineates the subsets of immune mediated neuropathies in evaluating the diagnosis and emphasizes the need for early therapeutic intervention in achieving a good clinical outcome.
文摘BACKGROUND Anti-glomerular basement membrane(GBM)disease is a rare rapidly progressive glomerulonephritis,frequently associated with alveolar hemorrhage in the lungs and involving the kidney by crescentic glomerulonephritis.It has been described in association with other glomerulonephritides[such as anti-neutrophilic antibody(ANCA)-glomerulonephritis,membranous nephropathy,and immunoglobulin(Ig)A nephropathy].CASE SUMMARY Herein we present an unusual case of concurrent anti-GBM disease,ANCAassociated crescentic glomerulonephritis and diffuse proliferative immune complex mediated glomerulonephritis with predominant staining for IgA and C3 by immunofluorescence.The patient is a 46-year-old Caucasian male who presented to the emergency department with acute onset of flank pain and was found to have high serum creatinine levels of 15 mg/dL,proteinuria,and hematuria.He rapidly deteriorated and became anuric.He was found to have high anti-GBM antibodies titers(151 units)and high anti-neutrophil cytoplasmic-ANCA.Despite prompt and early treatment,the patient’s condition worsened,and he succumbed to his illness.CONCLUSION Our case emphasizes the importance of a renal biopsy in anti-GBM disease,even in the presence of positive serum anti-GBM antibodies,to identify other potential causes of rapidly progressive glomerulonephritis.The challenge in treating such cases lies in the different therapy modalities.
基金supported by NIH grants RC1DE-020533 (Y.P.L.) and AR-055307 (Y.P.L.)
文摘Regulator of G-protein Signaling 10 （Rgsl0） plays an important function in osteoclast differentiation. However, the role of Rgsl0 in immune cells and inflammatory responses, which activate osteoclasts in inflam- matory lesions, such as bacteria-induced periodontal disease lesions, remains largely unknown. In this study, we used an adeno-associated virus （AAV-） mediated RNAi （AAV-shRNA-Rgs10） knockdown approach to study Rgsl0＇s function in immune cells and osteoclasts in bacteria-induced inflammatory lesions in a mouse model of periodontal disease. We found that AAV-shRNA-Rgs10 mediated Rgs10 knockdown impaired osteoclastogenesis and osteoclast-mediated bone resorption, in vitro and in vivo. Interestingly, local injection of AAV-shRNA-Rgs10 into the periodontal tissues in the bacteria-induced inflammatory lesion greatly decreased the number of dendritic cells, T-cells and osteoclasts, and protected the periodontal tissues from local inflammatory damage and bone destruction. Importantly, AAV-mediated Rgs10 knockdown also reduced local expression of osteoclast markers and pro-inflammatory cytokines. Our results demonstrate that AAV- shRNA-Rgs10 knockdown in periodontal disease tissues can prevent bone resorption and inflammation simultaneously. Our data indicate that Rgsl0 may regulate dendritic cell proliferation and maturation, as well as the subsequent stimulation of T-cell proliferation and maturation, and osteoclast differentiation and acti- vation. Our study suggests that AAV-shRNA-Rgs10 can be useful as a therapeutic treatment of periodontal disease.
文摘Objective:To study the effects of smilax bockii warb polysaccharide on inflammatory mediators, apoptosis and immune cell function in rats with chronic pelvic inflammatory disease.Methods:Female SD rats were chosen as experimental animals and divided into control group, pelvic inflammation group and smilax bockii warb group, pelvic inflammation group and smilax bockii warb group were made into pelvic inflammation models, and smilax bockii warb group were given intragastric administration of smilax bockii warb. The contents of inflammatory mediators and the expression of apoptosis genes in uterine muscle as well as the contents of immune cells in peripheral blood were determined 21 d after molding and intervention.Results:TLR4, NF-κB, TNF-α, ICAM-1 and IL-8 levels as well as Fas, TNFR-1, GRP78, CHOP and Caspase-3 mRNA expression in uterine muscle tissue and CD3+CD8+T cell in peripheral blood of pelvic inflammation group were higher than those of control group whereas peripheral blood CD3+CD4+T cell, red blood cell C3b receptor rosette rate and erythrocyte immune complex rosette were lower than those of control group;TLR4, NF-κB, TNF-α, ICAM-1 and IL-8 levels as well as Fas, TNFR-1, GRP78, CHOP and Caspase-3 mRNA expression in uterine muscle tissue as well as CD3+CD8+T cell in peripheral blood of smilax bockii warb group were lower than those of pelvic inflammation group whereas peripheral blood CD3+CD4+T cell, red blood cell C3b receptor rosette rate and erythrocyte immune complex rosette were higher than those of pelvic inflammation group. Conclusion:Smilax bockii warb polysaccharide for chronic pelvic inflammatory disease intervention can inhibit the inflammatory mediator secretion, apoptosis and regulate the immune cell function.
基金supported by the Neuroscience research center, Kerman University of Medical Sciences.
文摘Acute morphine administration is known to alter the course of herpes simplex virus infection. In this study, the effect of acute morphine administration on the reactivation of latent herpes was investigated in a mouse model. Because of the important role of cytolytic T lymphocyte （CTL） activity in the inhibition of herpes simplex virus type 1 （HSV-1） reactivation, the effect of acute morphine administration on CTL responses was also evaluated. Furthermore, lymphocyte proliferation and IFN-γ production were evaluated for their roles in the induction of the CTL response. The findings showed that acute morphine administration significantly reduced CTL responses, lymphocyte proliferation, and IFN-γ production. Furthermore, acute morphine administration has been shown to reactivate latent HSV-γ. Previous studies have shown that cellular immune responses have important roles in the inhibition of HSV reactivation. These findings suggest that suppression of a portion of the cellular immune response after acute morphine administration may constitute one part of the mechanism that induces HSV reactivation.
文摘BACKGROUND According to the theory of traditional Chinese medicine(TCM),the spleen and stomach are the basis of acquired nature and the source of qi and blood biochemistry.After surgery and chemotherapy,patients with colorectal cancer often develop spleen and stomach qi deficiency syndrome,leading to decreased immune function.Buzhong Yiqi decoction,a classic TCM prescription,has the effect of tonifying middle-jiao and invigorating qi,boosting Yang,and suppressing immune-related inflammation.Moreover,it is widely used in the treatment of spleen and stomach qi deficiency syndrome.AIM To investigate the effect of Buzhong Yiqi decoction on spleen and stomach qi deficiency in patients with colorectal cancer.METHODS One hundred patients with colorectal cancer who underwent preoperative chemotherapy and laparoscopy at The First TCM Hospital of Changde from January 2022 to October 2023 were retrospectively analyzed.The patients were divided equally into control and observation groups.Both groups underwent conventional rehabilitation surgery,and the observation group was supplemented with Buzhong Yiqi decoction.SPSS 26.0 was used for statistical analyses.Theχ2 test was used for univariate analysis;independent sample t-tests were used in all cases.RESULTS No significant differences were observed preoperatively in the general characteristics of the two groups.Fourteen days post-surgery,the abdominal distension,emaciation,loose stool,loss of appetite,and vomiting scores were significantly lower in the observation group than in the control group(P<0.05).Immune function and interleukin(IL)-10 levels in the observation group were significantly higher than those of the control group,whereas IL-6,tumor necrosis factor-α,and C-reactive protein levels,tumor biological indexes,and adverse reactions in the observation group were significantly lower than those of the control group(P<0.05).One month after surgery,the patients’quality of life in the observation group was significantly higher than that of the patients in the control group(P<0.05).CONCLUSION Buzhong Yiqi decoction can regulate inflammatory responses and metabolic processes by enhancing immune function,thereby promoting overall immune nutrition and restoring the body’s balance.
