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A global pandemic of Corona Virus Disease 2019 (COVID-19) caused by severe acute respiratory syndrome CoV-2 (SARS-CoV-2) is ongoing spread. It remains unclear whether the convalescing patients have a risk of reinfection. Rhesus macaques were rechallenged with SARS-CoV-2 during an early recovery phase from initial infection characterized by weight loss, interstitial pneumonia and systemic viral dissemination mainly in respiratory and gastrointestinal tracts. The monkeys rechallenged with the identical SARS-CoV-2 strain have failed to produce detectable viral dissemination, clinical manifestations and histopathological changes. A notably enhanced neutralizing antibody response might contribute the protection of rhesus macaques from the reinfection by SARS-CoV-2. Our results indicated that primary SARS-CoV-2 infection protects from subsequent reinfection. One Sentence SummaryNeutralizing antibodies against SARS-CoV-2 might protect rhesus macaques which have undergone an initial infection from reinfection during early recovery days.
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The outbreak of Corona Virus Disease 2019 caused by the severe acute respiratory syndrome coronavirus (SARS-CoV-2) is highly transmitted. The potential extra-respiratory transmission routes remain uncertain. Five rhesus macaques were inoculated with 1x106 TCID50 of SARS-CoV-2 via conjunctival (CJ), intratracheal (IT), and intragastric (IG) routes, respectively. Remarkably, the CJ inoculated-macaques developed mild interstitial pneumonia and viral load was detectable in the conjunctival swabs at 1 days post-inoculation (dpi). Only via IT inoculation, viral load was detected in the anal swab at 1-7 dpi and macaque showed weight loss. However, viral load was undetectable after IG inoculation. Comparatively, viral load was higher in the nasolacrimal system but lesions of lung were relatively mild and local via CJ inoculation compared with that via IT inoculation, demonstrating distinct characteristics of virus dispersion. Both the two routes affected the alimentary tract. Therefore the clinicians need to protect eye while working with patients.
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Objective To investigate the structural and functional changes of immune system in aging Sprague-Dawley rats. Methods Sixty SPF 4-6-week old SD rats(male:female=1:1)were used in this study. Ten of them were randomly taken and euthanized every 6 months. The dynamic changes of T cell proliferation,expression of cytokines,serum levels of SOD and MDA and histopathology were examined. Results Obvious histological changes of thymus and spleen were observed in the aging rats. Compared with the young SD rats,in the aging rats,the lymphocyte transformation ability was decreased(P<0.05,P<0.01),number of splenic cells was declined(P<0.05,P<0.01),NK(P<0.05,P<0.01)and T cell subset was reduced(P<0.05,P<0.01),and the production of IL-2 was decreased as well(P<0.05, P<0.01). The serum level of SOD in old rats was lower,MDA was increased,with significant differences(P<0.05,P<0.01). The immunohistochemical staining showed that more extensive staining was found in the nuclei of thymocytes from the aging rats,while the 8-OHdG formation in thymic tissues was mostly located in the thymic medulla. Conclusions Aging process is accompanied by immune impairment,oxidative stress can also impair the immune response in aging rats. Our findings indicate that structural and functional alterations of immune system in aging rats may be closely related with ox-idative damages.
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Objective To evaluate the efficacy of Ganoderma lucidum preparation on the behaviors,biochemistry,and autoimmunity parameters of mouse models of APP/PS-1 double transgenic Alzheimer's disease(AD).Methods A total of 44 4-month-old APP/PS-1 double transgenic AD mice were randomly divided into AD model group,Aricept group,Ganoderma lucidum middle-dose(LZ-M)group,and Ganoderma lucidum high-dose(LZ-H)group,with 11 mice in each group.In addition,10 4-month-old C57BL/6 mice were used as the control group.Water maze test was conducted to observe the behavior changes,and the protein expressions in brain tissues were detected by Western blot analysis.The autoimmune indicators were detected by indirect immunofluorescence method.Results In the navigation experiment,the time of finding the platform was gradually shortened since the 2day in the control,LZ-H,and LZ-M groups,and the time of searching the platform in the AD model group gradually increased.On the 5day,the time of finding platform was significantly shorter in control group (t=5.607,P=0.000) and LZ-H group(t=2.750,P=0.010)than AD model group.In the space exploration experiment,the number of crossing the target platform(t=2.452,P=0.025)and the residence time in the target quadrant(t=2.530,P=0.020)in AD model group mice was significantly smaller/shorter than those in control group;in addition,the number of crossing the target platform in the AD model group was significantly smaller than that in LZ-H group(t=2.317,P=0.030)and LZ-M group(t=2.443,P=0.030),while the residence time in target quadrant decreased significantly(t=2.770,P=0.020)compared with LZ-H group;the number of crossing through the target platform quadrant(t=2.493,P=0.022)and residence time in the target quadrant(t=2.683,P=0.015)in LZ-H group were significantly higher than in Aricept group.Western blot analysis showed that the expression of ApoA1 in the brain tissues of mice in LZ-H and LZ-M groups were significantly higher than those in AD model group(P<0.01,P<0.05);Aβ-40 expression in LZ-H group was significantly lower than that in AD model group(P<0.05);the expressions of Syt1,ApoE,and ABCA1 in brain tissues of mice in LZ-H group were significantly higher than those in model group(P<0.01,P<0.05).The plasma IgG level in Aricept group(t=30.945,P=0.000),LZ-M group(t=25.639,P=0.000)and LZ-H group(t=4.689,P=0.001)were significantly higher than that in the control group.Conclusion Ganoderma lucidum preparation can improve behavior disorders of AD model mice,promote the expressions of ApoA1,ApoE and Syt1,inhibit the expression of Aβ-40 protein,and improve the autoimmune function.
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Objective To observe the effects of 630 nm red light and 460 nm blue light emitting diode irradiation on the healing of skin wounds in Japanese big-ear white rabbits. Methods The skin wound model was established with 8 Japanese big-ear white rabbits. Three parts of vulnus in each rabbit were used:two parts of vulnus were irradiated vertically by red and blue LED light,respectively(15 min/time),and the distance between lights and wounds was 15 cm;the 3part of the wound was used as a control. On the 21day of the wounds exposure to light,the number of healing wounds and the percentage of healing area were recorded and the treatment effect of these two light sources was compared. HE staining was used to analyze the newborn tissue structure. Masson staining was used to observe the proliferation of skin collagen fibers. Immuohistochemical staining was used to analyze fibroblast growth factor(FGF),epidermal growth factor(EGF),endothelial growth factor(CD31),proliferating cell nuclear antigen(Ki-67),and inflammatory cytokines(CD68)infiltration in the skin. Results The healing rate in the red light,blue light,and control groups was 50.0%(4/8),25.0%(2/8),and 12.5%(1/8),respectively. Since the 12day after modeling,the healing area percentage in the red light group was significantly higher than those in the blue light and control groups(P<0.05,P<0.01). On the 21day after modeling,the skin thickness of the red light group was(2.95±0.34)mm,which was significantly higher than that in control group [(2.52±0.42)mm;F=3.182,P=0.016)]. The average optical density of collagen fibers was 0.15±0.03 in red light group,which was significantly higher than that of the blue light group(0.09±0.01;F=7.316,P=0.012)and control(0.07±0.01;F=7.316,P=0.003). The results of immunohistochemistry showed the expression levels of EGF,FGF,CD31 antigen,and Ki-67 in the red light group were significantly higher than those in the blue light and control groups,whereas the CD68 expression was significantly lower(P<0.05 or P<0.01). Conclusion LED red light irradiation can promote the healing of skin wounds in Japanese big-ear white rabbits,which may be achieved by the effect of red light irradiation in stimulating the proliferation of skin epidermal cells,vascular endothelial cells,and fiberous tissue.
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Objective To investigate the effect of cyaniding?3?glucoside (Cy3G) on glucose and lipid metabolism in the APPswe/PS1ΔE9 mouse model of Alzheimer’s disease (AD). Methods Seven?month?old APPswe/PS1ΔE9(PAP) mice were randomly divided into model group (PAP), Cy3G treatment group (PAPCy, 5 mg/kg/d) and negative?control group (nPAP). In addition, age?matched and normal wild?type of C57BL/6J mice were selected and divided into vehicle group (WT), Cy3G intervention group (WTCy, 5 mg/kg/d). Each group containing 12 mice, with equal number of male and female mice. After 8?week Cy3G supplementation, microPET/CT was used to measure cerebral glucose metabolism rate of mice in each group. Biochemical methods were used to detect the liver / kidney function as well as indicators associated with lipid metabolism. After weighting brain tissue, the brain coefficient was tested and pathological examination was used to observe tissues changes. Transmission electron microscope was used to observe neuropathological amyloid plaques deposition. Western?blot was used to determine protein levels of AKT and JNK. Results Compared with the WT group, PAP mice had low levels of 18 F?FDG uptake rates, especially in the regions of the frontal lobe and hippocampus accompanied by the decreased brain coefficient and amyloid plaques deposition in hippocampus. And levels of aspartate transaminase ( AST) and lactic dehydrogenase ( LDH) were also increased in PAP mice, but lipid metabolism index was relatively normal. In addition, the expression of JNK was decreased and AKT was increased in mice of PAP. However, in the PAPCy group, 18 F?FDG uptake rates were obviously increased in the regions of the frontal lobe and hippocampus compared with those in the PAP mice. And the reduction of brain atrophy and amyloid plaques deposition, normal lipid metabolism and no obvious liver/kidney toxicity were also observed. Cy3G also could reverse the changes of JNK and AKT protein. Conclusions Cy3G can improve glucose metabolism disorders instead of lipid metabolism, inhibit the senile plaques deposition in hippocampus and regulate insulin resistance and inflammatory reaction associated with JNK/AKT pathway. Thus, Cy3G has a good safety profile and may be used as an ideal alternative to traditional disease?modifying treatments against AD.