BACKGROUND Grasping the underlying mechanisms of Alzheimer's disease(AD)is still a work in progress,and existing diagnostic techniques encounter various obstacles.Therefore,the discovery of dependable biomarkers i...BACKGROUND Grasping the underlying mechanisms of Alzheimer's disease(AD)is still a work in progress,and existing diagnostic techniques encounter various obstacles.Therefore,the discovery of dependable biomarkers is essential for early detection,tracking the disease's advancement,and steering treatment strategies.AIM To explore the diagnostic potential of serum CXCL12,sCD22,Lp-PLA2,and their ratios in AD,aiming to enhance early detection and inform targeted treatment strategies.METHODS The study was conducted in Dongying people's Hospital from January 2021 to December 2022.Participants included 60 AD patients(AD group)and 60 healthy people(control group).Using a prospective case-control design,the levels of CXCL12,sCD22 and Lp-PLA2 and their ratios were detected by enzyme-linked immunosorbent assay kit in the diagnosis of AD.The differences between the two groups were analyzed by statistical methods,and the corresponding ratio was constructed to improve the specificity and sensitivity of diagnosis.RESULTS Serum CXCL12 levels were higher in the AD group(47.2±8.5 ng/mL)than the control group(32.8±5.7 ng/mL,P<0.001),while sCD22 levels were lower(14.3±2.1 ng/mL vs 18.9±3.4 ng/mL,P<0.01).Lp-PLA2 levels were also higher in the AD group(112.5±20.6 ng/mL vs 89.7±15.2 ng/mL,P<0.05).Significant differences were noted in CXCL12/sCD22(3.3 vs 1.7,P<0.001)and Lp-PLA-2/sCD22 ratios(8.0 vs 5.2,P<0.05)between the groups.Receiver operating characteristic analysis confirmed high sensitivity and specificity of these markers and their ratios in distinguishing AD,with area under the curves ranging from CONCLUSION Serum CXCL12 and Lp-PLA2 levels were significantly increased,while sCD22 were significantly decreased,as well as increases in the ratios of CXCL12/sCD22 and Lp-PLA2/sCD22,are closely related to the onset of AD.These biomarkers and their ratios can be used as potential diagnostic indicators for AD,providing an important clinical reference for early intervention and treatment.展开更多
Both hepatitis B virus X protein(HBx)and microRNA-221(miR-221)have been implicated in the development of hepatitis B virus(HBV)-related hepatocellular carcinoma(HCC).The present study demonstrates that HBx promotes HC...Both hepatitis B virus X protein(HBx)and microRNA-221(miR-221)have been implicated in the development of hepatitis B virus(HBV)-related hepatocellular carcinoma(HCC).The present study demonstrates that HBx promotes HCC cell proliferation via the C-X-C motif chemokine ligand 12-C-X-C chemokine receptor type 4(CXCL12-CXCR4)axis.We predict that HBx/miR-221-mediated CXCL12/CXCR4 signaling induces NKT cells to promote HBV-related HCC.Methods:After miR-221 mimic,miR-221 mimic negative control,miR-221 inhibitor,miR-221 inhibitor negative control were transfected into cells,the expression of CXCL12 and miR-221 was detected by qPCR and western blot.Then we constructed a stable HBV-HCC cell line.HBV-HCC cells were injected into the nude mice,thus a HBV-HCC mouse model was constructed.Q-PCR and western blot were used to detect the expression of HBx,miR-221,CXCL12 and CXCR4 in tumor tissues.The expression of CXCL12 was detected by immunohistochemistry,and the expression of CXCR4,CD3 and CD56 was detected by immunofluorescence.The levels of CXCL12,IL-2 and TNF-αin serum of mice were detected by ELISA.Sixty-one patients with HBV-related HCC,61 patients with HBV-related cirrhosis,61 patients with chronic hepatitis B(CHB)and 30 healthy people were enrolled.CXCL12,cytokine levels,and clinicopathological parameters were tested.Results:Hepatitis B virus X protein upregulates the expression of miR-221 and CXCL12 in lentivirus(LV5)-HBx-transfected HepG2 cells.HBx protein promotes HepG2 cell proliferation in vitro.HBx protein promoted tumor growth via the miR-221/CXCL12/CXCR4 pathway in a mouse tumor model.HBx protein upregulated natural killer T cell expression via the CXCR4/CXCL12 pathway to promote tumor growth.The data demonstrated a positive correlation between CXCL12 concentration with Cre levels and Child-Pugh scores.CXCL12 had an inferior diagnostic efficiency compared to IL-2 and IL-6 for HBV-related HCC.Conclusions:We present evidence that HBx/miR-221-mediated CXCL12/CXCR4 signaling induces NKT cells to promote HBV-related HCC.展开更多
文摘BACKGROUND Grasping the underlying mechanisms of Alzheimer's disease(AD)is still a work in progress,and existing diagnostic techniques encounter various obstacles.Therefore,the discovery of dependable biomarkers is essential for early detection,tracking the disease's advancement,and steering treatment strategies.AIM To explore the diagnostic potential of serum CXCL12,sCD22,Lp-PLA2,and their ratios in AD,aiming to enhance early detection and inform targeted treatment strategies.METHODS The study was conducted in Dongying people's Hospital from January 2021 to December 2022.Participants included 60 AD patients(AD group)and 60 healthy people(control group).Using a prospective case-control design,the levels of CXCL12,sCD22 and Lp-PLA2 and their ratios were detected by enzyme-linked immunosorbent assay kit in the diagnosis of AD.The differences between the two groups were analyzed by statistical methods,and the corresponding ratio was constructed to improve the specificity and sensitivity of diagnosis.RESULTS Serum CXCL12 levels were higher in the AD group(47.2±8.5 ng/mL)than the control group(32.8±5.7 ng/mL,P<0.001),while sCD22 levels were lower(14.3±2.1 ng/mL vs 18.9±3.4 ng/mL,P<0.01).Lp-PLA2 levels were also higher in the AD group(112.5±20.6 ng/mL vs 89.7±15.2 ng/mL,P<0.05).Significant differences were noted in CXCL12/sCD22(3.3 vs 1.7,P<0.001)and Lp-PLA-2/sCD22 ratios(8.0 vs 5.2,P<0.05)between the groups.Receiver operating characteristic analysis confirmed high sensitivity and specificity of these markers and their ratios in distinguishing AD,with area under the curves ranging from CONCLUSION Serum CXCL12 and Lp-PLA2 levels were significantly increased,while sCD22 were significantly decreased,as well as increases in the ratios of CXCL12/sCD22 and Lp-PLA2/sCD22,are closely related to the onset of AD.These biomarkers and their ratios can be used as potential diagnostic indicators for AD,providing an important clinical reference for early intervention and treatment.
基金supported by the National Natural Science Foundation of Chongqing,China(No.cstc2019jcyj-msxm0314 of Yishu Tang)the National Key R&D Program of China(No.2017YFC0909902 of Yun Xia)the Natural Science Foundation of China(No.81501818 of Yishu Tang)。
文摘Both hepatitis B virus X protein(HBx)and microRNA-221(miR-221)have been implicated in the development of hepatitis B virus(HBV)-related hepatocellular carcinoma(HCC).The present study demonstrates that HBx promotes HCC cell proliferation via the C-X-C motif chemokine ligand 12-C-X-C chemokine receptor type 4(CXCL12-CXCR4)axis.We predict that HBx/miR-221-mediated CXCL12/CXCR4 signaling induces NKT cells to promote HBV-related HCC.Methods:After miR-221 mimic,miR-221 mimic negative control,miR-221 inhibitor,miR-221 inhibitor negative control were transfected into cells,the expression of CXCL12 and miR-221 was detected by qPCR and western blot.Then we constructed a stable HBV-HCC cell line.HBV-HCC cells were injected into the nude mice,thus a HBV-HCC mouse model was constructed.Q-PCR and western blot were used to detect the expression of HBx,miR-221,CXCL12 and CXCR4 in tumor tissues.The expression of CXCL12 was detected by immunohistochemistry,and the expression of CXCR4,CD3 and CD56 was detected by immunofluorescence.The levels of CXCL12,IL-2 and TNF-αin serum of mice were detected by ELISA.Sixty-one patients with HBV-related HCC,61 patients with HBV-related cirrhosis,61 patients with chronic hepatitis B(CHB)and 30 healthy people were enrolled.CXCL12,cytokine levels,and clinicopathological parameters were tested.Results:Hepatitis B virus X protein upregulates the expression of miR-221 and CXCL12 in lentivirus(LV5)-HBx-transfected HepG2 cells.HBx protein promotes HepG2 cell proliferation in vitro.HBx protein promoted tumor growth via the miR-221/CXCL12/CXCR4 pathway in a mouse tumor model.HBx protein upregulated natural killer T cell expression via the CXCR4/CXCL12 pathway to promote tumor growth.The data demonstrated a positive correlation between CXCL12 concentration with Cre levels and Child-Pugh scores.CXCL12 had an inferior diagnostic efficiency compared to IL-2 and IL-6 for HBV-related HCC.Conclusions:We present evidence that HBx/miR-221-mediated CXCL12/CXCR4 signaling induces NKT cells to promote HBV-related HCC.
