Objective To investigate the relationship of the proliferation and activation of immunocytes in gastric mucosa with the disease progression in HIV-infected individuals.Methods Thirty-six HIV-infected individuals,and 10 persons without HIV infection serving as control,were enrolled in present study,and biopsy of gastric mucosal tissues was performed by fiberoptic gastroscopy.Immunohistochemistry(SP) was used to detect the expressions of CD38 and Ki-67 in gastric mucosa.Masson stain was used to observe collagen deposition in gastric mucosa.Results Compared with the non-infected controls,the expression of CD38 remarkably increased in HIV-infected individuals(97.384±11.573 vs 86.215±12.396,P 0.05).In HIV-infected individuals,Ki-67 positive cells were mainly located in gastric foveola,lamina propria gland and stroma.As compared with the non-infected controls,Ki-67 positive immunocytes were remarkably decreased in stroma(20.933±2.719 vs 29.091±21.949,P 0.05).The Ki-67 positive cells were mostly lymphocytes in the lymphoid follicle of gastric mucosa in asymptomatic HIV carriers,while connective tissue cells such as fibroblasts were predominant in AIDS patients.There was more abundant collagen deposition in stroma and lymphatic follicles in AIDS patients than in asymptomatic HIV carriers.In AIDS patients,the follicle fibrous septum was found to be increased and widened in some region.Conclusion After HIV infection,the disequilibrium of activation and proliferation of immunocytes,as well as collagen deposition in mucosa,are probably the main pathogenetic factors of AIDS.
Although the political democratization in the Philippines has been under progress for more than 50 years,it has not reached its targets.There are many factors that lead to the setbacks of this democratization,one of which is the concept of the political culture and the outlook on value rooted in the civilians.The paper tries to analyze the factors affecting this democratization in the Philippines in the perspective of civil political culture.
To evaluate the interaction of intraocular pressure(IOP)–lowering medications with physiologic day and night changes in aqueous humor dynamics in participants with ocular hypertension.Thirty participants were enrolled in thisdouble-masked, randomized, crossover study. Each participant underwent aqueous humor dynamics measurements at baseline and at 2 weeks of dosing in random order with latanoprost in the evening and placebo in the morning, timolol maleate twice daily, and dorzolamide hydrochloride twice daily. Measurements included central corneal thickness by ultrasound pachymetry, anterior chamber depth by A-scan, seated and habitual IOP by pneumatonometry, blood pressure by sphygmomanometry,episcleral venous pressure by venomanometry,and aqueous flow by fluorophotometry. Outflow facility was assessed by fluorophotometry and by tonography. Uveoscleral outflow was mathematically calculated using the Goldmann equation.Latanoprost use significantly decreased IOP during the day and night. It increased daytime uveoscleral outflow by a mean (SD) of 0.90 (1.46) μL/min (P=.048), but a nighttime increase of 0.26 (1.10) μL/min (P=.47)did not reach statistical significance. Timolol use decreased IOP during the day by reducing aqueous flow by 25%. Dorzolamide use lowered IOP only at the noon measurement and reduced daytime aqueous flow by 16%. Neither dorzolamide nor timolol use added to the physiologic 47% reduction in nighttime aqueous flow.The daytime IOP-lowering effects of latanoprost are mediated by an increase in uveoscleral outflow,and those of timolol and dorzolamide are mediated by aqueous flow suppression. Nighttime physiologic changes in uveoscleral outflow limit the nighttime pharmacodynamic efficacy of latanoprost. Aqueous flow suppression with timolol and dorzolamide was ineffective in obtaining IOP lowering at night.
The purpose of the study was to determine whether hematopoietic stem cell (HSCs) mobilization can regulate early diabetic retinopathy in mice.Mice were divided into four groups: control group, normal mice HSC-mobilized group, diabetic mice control group and diabetic mice HSC-mobilized group. Murine stem cell growth factor (SCF) and recombined human granulocyte colony stimulating factor (rhG-csf) were administered to the mice with diabetes and without diabetes for continuous 5 days to induce autologous HSCs mobilization, and subcutaneous injection of physiological saline was used as control. The changes associated with autologous HSCs mobilization were characterized using flow cytometry, Immunohistochemistry and semiquantitative RT-PCR. Evans blue quantitative test was used to measure the breakdown level of blood-retina barrier.HSCs were marked by CD34-/low and Sca1+ in this study. The acceleration of endothelial cell regeneration was observed. A decrease of VEGF expression due to autologous stem cell mobilization was found. HSCs could increase the content of VEGFR-2 in mouse retina and significantly downregulated the expression of VEGF and ang-2 in diabetic mice.The experiment suggest that autologous HSCs mobilization can be approach of therapeutic vascular reconstruction and functional restoration of blood-retina barrier in mice.
Retinal neovascularization (NV) is a major cause of blindness. Recent research suggests that factors other than VEGF participate in this process. This study aimed to determine the role of ephrin-A4 in retinal NV.The expression and effect of ephrin-A4 was investigated in a mouse model of oxygen-induced retinopathy (OIR) and the RF/6A retina endothelial cell line. Ephrin-A4 expression and VEGF signaling pathway phosphorylation were determined by PCR, immunohistochemistry, and western blot analyses. ShRNA was used to silence ephrin-A4 in vitro and in vivo. Retinal flat mounts and tube formation assays were performed to evaluate ephrin-A4 function in the NV process in vivo and in vitro.Ephrin-A4 was overexpressed in the retina of OIR mice and in RF/6A and RPE cells after CoCl₂ stimulation. In vitro, Ephrin-A4/Fc treatment significantly increased the tube number of RF/6A cells on a membrane preparation and the phosphorylation levels of VEGR2, Akt1, and ERK1/2 in RF/6A cells. Moreover, ephrin-A4 knockout markedly suppressed pathologic neovascularization in vivo and inhibited the proliferation and tube formation capacity of RF/6A cells in vitro. Furthermore, in the absence of ephrin-A4, the phosphorylation of VEGFR2, Akt1, and ERK1/2 was defective under VEGF₁₆₅ stimulation, and the proangiogenic function of VEGF₁₆₅ was also compromised.This study suggests that ephrin-A4 plays an important role in retinal NV and is a potential target against retinal NV. The proangiogenic function of ephrin-A4 may be linked to its crucial role in the VEGF signaling pathway.
Background Inborn errors of metabolism (IEMs) are rare diseases caused by inherited defects in various biochemical pathways that strongly correlate with early neonatal mortality and stunting. Currently, no studies have reported on the incidence of IEMs of multi-ethnic groups in Huaihua, China. Methods A total of 206,977 neonates with self-reported ethnicity who underwent IEM screening at Huaihua from 2015 to 2021 were selected for observation. Among them, 69 suspected IEM-positive neonates were referred for urine gas chromatography-mass spectrometry analysis, biochemical detection, next-generation sequencing, and Sanger sequencing. Results Sixty-nine newborns were diagnosed with IEMs, with an overall incidence of 1:3,000. The two most common disorders were 2-methylbutyryl glycinuria (1:7,137) and phenylalanine hydroxylase deficiency (1:22,997). Moreover, the incidence of IEMs in the minority ethnic group (Miao, Dong, Tujia and Yao) (1:1,852) was markedly higher than in the Han ethnic group (1:4,741). Some ethnic features variants were identified; NM_001609.4:c.1165A>G in the ACADSB gene for Miao and Dong ethnic groups, NM_014251.2:c.852_855del in the SLC25A13 gene for Miao ethnic groups. Conclusion This study revealed the IEM incidence within the minority ethnic groups is markedly higher than among the Han nationality and the gene variant spectrum is dramatically different in Huaihua, China. Hence, It serves as a theoretical reference for the screening and diagnosing of neonatal IEMs of multi-ethnic groups in the Huaihua area, and across China.
Background: In western patients, the association of Fusobacterium nucleatum (F. nucleatum) with colorectal carcinoma (CRC) has been established, but the underlying mechanism remains unclear. There is no report about F. nucleatum infection status and its potential role in CRC patients in China. This study aimed to evaluate infection status and infection load of F. nucleatum and its correlation with clinicopathological features and prognosis of CRC patients in China.Methods: Fresh tumor and adjacent normal mucosa tissues were obtained at surgery from 152 CRC patients, and then DNA was assayed for infection of F. nucleatum by quantitative PCR. Then the association of infection with clinicopathological features and prognosis was evaluated. In addition, MMP9, MMP11, CD45RO and FOXP3 expression levels was assessed by immunohistochemistry to explore the potential role of F. nucleatum.Results: The infection rate of F. nucleatum in CRC tissues was significantly higher than that in adjacent normal tissues (77.6% vs. 57.2%, P<0.001), and median F. nucleatum copy number was also significantly higher in CRC tissues than in adjacent normal tissues (87 vs. 37, P<0.001). F. nucleatum infection of tumor tissues was related with poorer tumor differentiation (P<0.001), deeper tumor invasion (P<0.001), lymph node metastasis (P=0.01), distant metastasis (P=0.001) and advanced TNM stage (P=0.034). Specimens with higher infection load contained fewer CD45RO+ T lymphocytes and more FOXP3+ regulatory T lymphocytes than those with lower infection load. And high-copy group had a poorer postoperative survival than the low-copy group (P=0.027). In the subset of CRC patients with F. nucleatum infection, tumor stage and F. nucleatum infection were independent prognostic factors. Advanced tumor stage and high-load infection were correlated poorer prognosis (P=0.023 and 0.032, respectively).Conclusions: Infection rate and load of F. nucleatum are higher in carcinoma tissues than in adjacent normal tissues from CRC patients in Chian. F. nucleatum infection was correlated with tumor metastasis and overall postoperative survival of colorectal cancer patients, so it can help to improve prevention, diagnosis and treatment of CRC in China.
This study was conducted to determine whether paeoniflorin (PF) could prevent H₂O₂-induced oxidative stress in ARPE-19 cells and to elucidate the molecular pathways involved in this protection.Cultured ARPE-19 cells were subjected to oxidative stress with H₂O₂ in the presence and absence of PF. The preventive effective of PF on reactive oxygen species (ROS) production and retinal pigment epithelium (RPE) cell death induced by H₂O₂ was determined by 2',7'- dichlorodihydrofluorescein diacetate (H₂DCFDA) fluorescence and 3-(4, 5-dimethylthiazol-2-yl)-2, 5 diphenyl tetrazolium bromide (MTT) assay. The ability of PF to protect RPE cells against ROS-mediated apoptosis was assessed by caspase-3 activity and 4', 6-diamidino-2-phenylindole (DAPI) staining. Furthermore, the protective effect of PF via the mitogen-activated protein kinase (MAPK) pathway was determined by western blot analysis.PF protected ARPE-19 cells from H₂O₂-induced cell death with low toxicity. H₂O₂-induced oxidative stress increased ROS production and caspase-3 activity, which was significantly inhibited by PF in a dose-dependent manner. Pretreatment with PF attenuated H₂O₂-induced p38MAPK and extracellular signal regulated kinase (ERK) phosphorylation in human RPE cells, which contributed to cell viability in ARPE-19 cells.This is the first report to show that PF can protect ARPE-19 cells from the cellular apoptosis induced by oxidative stress. The results of this study open new avenues for the use of PF in treatment of ocular diseases, such as age-related macular degeneration (AMD), where oxidative stress plays a major role in disease pathogenesis.
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