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ObjectiveTo explore the scientific connotation of fried charcoal survivability of Lonicerae Japonicae Flos（LJF） by analyzing the correlation between the color change and the intrinsic components during the processing of LJF Carbonisata（LJFC）， and taking pH， charcoal adsorption and microscopic characteristics as indexes. MethodLJFC samples with different degrees of processing were prepared according to the stir-frying time of 0.0， 1.5， 3.0， 4.5， 6.0， 7.5， 9.0， 10.5 min（numbered S1-S8）， and the contents of gallic acid， chlorogenic acid， cryptochlorogenic acid， rutin， luteoloside， isochlorogenic acid A and isochlorogenic acid C were determined by high performance liquid chromatography（HPLC）， and the L*（brightness）， a*（red-greenness） and b*（yellow-blueness） of LJFC samples with different degrees of processing were determined by spectrophotometer， and the correlation analysis and principal component analysis（PCA） between the contents of seven representative components and the color of the samples were carried out by SPSS 26. 0 and SIMCA-P 14.1. Then pH， adsorption force and characteristic structure of different samples of LJFC were detected and the processing pattern of LJFC was analyzed. ResultThe results of quantitative analysis revealed that the contents of luteoloside， rutin， chlorogenic acid and isochlorogenic acid A gradually decreased， and the contents of cryptochlorogenic acid， isochlorogenic acid C and gallic acid firstly increased and then decreased. The L* and b* of the sample powders decreased， and a* showed a trend of increasing and then decreasing. The L* and b* were positively correlated with the contents of chlorogenic acid， rutin， luteoloside， isochlorogenic acid A， b* was positively correlated with the content of gallic acid， and a* was positively correlated with the contents of cryptochlorogenic acid and isochlorogenic acid C. PCA revealed that samples could be clearly divided into 3 groups， S1-S2 as one group， S3-S5 as one group， and S6-S8 as one group， with S3 having the highest score. The results of regression analysis showed that only isochlorogenic acid C could be used to predict the contents of components by colorimetric values combined with regression equations. Physicochemical analysis showed that pH of LJFC increased with the increase of degree of charcoal stir-frying， while adsorption force showed a tendency of increasing and then decreasing， with the highest adsorption force in the S5 sample， and the non-glandular hairs， calcium oxalate clusters and pollen grains had a varying degree of decreasing with the deepening of processing degree， and the microstructures of S6-S8 samples were obviously charred with pollen grains almost invisible. ConclusionThe changes in chemical composition and color characteristics of LJFC during the processing have certain correlations， combined with the changes in physicochemical properties， S5 sample is found to be the optimal processed products， which can provide a reference for the processing standardization and quality evaluation of LJFC， and enrich the scientific connotation of fried charcoal survivability of LJF.
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OBJECTIVE@#To compare the therapeutic effect between Fanzhen Jieci (warming acupuncture plus fast needling) combined with conventional acupuncture and simple conventional acupuncture on discogenic sciatica.@*METHODS@#A total of 76 patients with discogenic sciatica were randomized into a Fanzhen Jieci group and a conventional acupuncture group, 38 cases in each one. Conventional acupuncture was applied at Shenshu (BL 23), Dachangshu (BL 25), L1-L5 Jiaji (EX-B 2) and Huantiao (GB 30) on the affected side, etc. in the conventional acupuncture group. On the basis of the treatment in the conventional acupuncture group, Fanzhen Jieci was applied at L1-L5 Jiaji (EX-B 2) and Huantiao (GB 30) on the affected side in the Fanzhen Jieci group, i.e. warming acupuncture was applied at L1-L5 Jiaji (EX-B 2), and fast needling was applied at Huantiao (GB 30) on the affected side for a depth of 40-60 mm, so as to introduce a sensation of electric shock transmitting to lower limb, and then the needle was immediately withdrawn. The treatment was given once every other day, 3 times a week for 3 weeks in both groups. The visual analogue scale (VAS) score of leg and low back pain, the Oswestry disability index (ODI) score and the 36-item short form health survey (SF-36) score before and after treatment were compared between the two groups.@*RESULTS@#Compared before treatment, the VAS scores of leg and low back pain and the ODI scores after treatment were decreased in both groups (P<0.001), the changes of the VAS scores of leg and low back pain in the Fanzhen Jieci group were larger than those in the conventional acupuncture group (P<0.05). After treatment, except for the role emotional and health transition scores, the various scores of SF-36 were increased compared before treatment in the Fanzhen Jieci group (P<0.01); except for the role physical, role emotional and health transition scores, the various scores of SF-36 were increased compared before treatment in the conventional acupuncture group (P<0.01). After treatment, the physical functioning, role physical, bodily pain, mental health and general health scores of SF-36 in the Fanzhen Jieci group were higher than those in the conventional acupuncture group (P<0.05).@*CONCLUSION@#Fanzhen Jieci combined with conventional acupuncture can effectively relieve the pain and improve the mental state in patients with discogenic sciatica, its therapeutic effect is superior to simple conventional acupuncture.
Subject(s)
Humans , Acupuncture Points , Acupuncture Therapy , Low Back Pain/therapy , Sciatica/therapy , Treatment OutcomeABSTRACT
TANK-binding kinase 1 (TBK1), a core kinase of antiviral pathways, activates the production of interferons (IFNs). It has been reported that deacetylation activates TBK1; however, the precise mechanism still remains to be uncovered. We show here that during the early stage of viral infection, the acetylation of TBK1 was increased, and the acetylation of TBK1 at Lys241 enhanced the recruitment of IRF3 to TBK1. HDAC3 directly deacetylated TBK1 at Lys241 and Lys692, which resulted in the activation of TBK1. Deacetylation at Lys241 and Lys692 was critical for the kinase activity and dimerization of TBK1 respectively. Using knockout cell lines and transgenic mice, we confirmed that a HDAC3 null mutant exhibited enhanced susceptibility to viral challenge via impaired production of type I IFNs. Furthermore, activated TBK1 phosphorylated HDAC3, which promoted the deacetylation activity of HDAC3 and formed a feedback loop. In this study, we illustrated the roles the acetylated and deacetylated forms of TBK1 play in antiviral innate responses and clarified the post-translational modulations involved in the interaction between TBK1 and HDAC3.
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BACKGROUND@#Innovative coronavirus disease 2019 (COVID-19) vaccines, with elevated global manufacturing capacity, enhanced safety and efficacy, simplified dosing regimens, and distribution that is less cold chain-dependent, are still global imperatives for tackling the ongoing pandemic. A previous phase I trial indicated that the recombinant COVID-19 vaccine (V-01), which contains a fusion protein (IFN-PADRE-RBD-Fc dimer) as its antigen, is safe and well tolerated, capable of inducing rapid and robust immune responses, and warranted further testing in additional clinical trials. Herein, we aimed to assess the immunogenicity and safety of V-01, providing rationales of appropriate dose regimen for further efficacy study.@*METHODS@#A randomized, double-blind, placebo-controlled phase II clinical trial was initiated at the Gaozhou Municipal Centre for Disease Control and Prevention (Guangdong, China) in March 2021. Both younger (n = 440; 18-59 years of age) and older (n = 440; ≥60 years of age) adult participants in this trial were sequentially recruited into two distinct groups: two-dose regimen group in which participants were randomized either to follow a 10 or 25 μg of V-01 or placebo given intramuscularly 21 days apart (allocation ratio, 3:3:1, n = 120, 120, 40 for each regimen, respectively), or one-dose regimen groups in which participants were randomized either to receive a single injection of 50 μg of V-01 or placebo (allocation ratio, 3:1, n = 120, 40, respectively). The primary immunogenicity endpoints were the geometric mean titers of neutralizing antibodies against live severe acute respiratory syndrome coronavirus 2, and specific binding antibodies to the receptor binding domain (RBD). The primary safety endpoint evaluation was the frequencies and percentages of overall adverse events (AEs) within 30 days after full immunization.@*RESULTS@#V-01 provoked substantial immune responses in the two-dose group, achieving encouragingly high titers of neutralizing antibody and anti-RBD immunoglobulin, which peaked at day 35 (161.9 [95% confidence interval [CI]: 133.3-196.7] and 149.3 [95%CI: 123.9-179.9] in 10 and 25 μg V-01 group of younger adults, respectively; 111.6 [95%CI: 89.6-139.1] and 111.1 [95%CI: 89.2-138.4] in 10 and 25 μg V-01 group of older adults, respectively), and remained high at day 49 after a day-21 second dose; these levels significantly exceed those in convalescent serum from symptomatic COVID-19 patients (53.6, 95%CI: 31.3-91.7). Our preliminary data show that V-01 is safe and well tolerated, with reactogenicity predominantly being absent or mild in severity and only one vaccine-related grade 3 or worse AE being observed within 30 days. The older adult participants demonstrated a more favorable safety profile compared with those in the younger adult group: with AEs percentages of 19.2%, 25.8%, 17.5% in older adults vs. 34.2%, 23.3%, 26.7% in younger adults at the 10, 25 μg V-01 two-dose group, and 50 μg V-01 one-dose group, respectively.@*CONCLUSIONS@#The vaccine candidate V-01 appears to be safe and immunogenic. The preliminary findings support the advancement of the two-dose, 10 μg V-01 regimen to a phase III trial for a large-scale population-based evaluation of safety and efficacy.@*TRIAL REGISTRATION@#http://www.chictr.org.cn/index.aspx (No. ChiCTR2100045107, http://www.chictr.org.cn/showproj.aspx?proj=124702).
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Aged , Humans , Antibodies, Viral , COVID-19/therapy , COVID-19 Vaccines , Double-Blind Method , Immunization, Passive , Recombinant Fusion Proteins , SARS-CoV-2ABSTRACT
Objective:To investigate the effects of Shanxian granule on proliferation of Lewis lung cancer cells and anti-tumor immunity and immune microenvironment of Lewis lung cancer-bearing mice in order to explore the molecular mechanism of anti-tumor of Shanxian Granule and improve the anti-tumor immunity of the body, and provide further theoretical basis for its clinical application. Methods:Lewis lung cancer cells was transplanted to axillary skin to establish mouse tumor model. The mice divided into blank group,model group,chemotherapy group and Shanxian granule group. The tumor tissue of Lewis lung cancer tumor bearing mice was weighed and the tumor inhibition rate was calculated. Immunohistochemical method was used to detect the expression of CD and CD8 in spleen tissue. The effect of lymphocytes on the proliferation of Lewis lung cancer cells was detected by CCK-8 method. The level of IFN-γ,TNF-βand IL-10 in peripheral blood were detected by ELISA. Results:①The tumor inhibition rate of Lewis lung cancer was 45. 99% in Shanxian Granule group,which was significantly higher than that of chemotherapy group (P<0. 05).②The lymphocytes of mouse can inhibit the proliferation of Lewis lung cancer cells and have a positive correlation with lymphocyte concentration and duration of action. Moreover,CD4+ T cells,CD4+/CD8+ratio and lymphocyte inhibition rate of Lewis lung cancer cells in model group and chem-otherapy group were significantly lower than those in blank group (P<0. 05). Shanxian granule group was significantly higher than the model group and chemotherapy group ( P<0. 05 ) . However, there was no significant difference between Shanxian granule group and blank group(P>0. 05).③The levels of IFN-γand TNF-βin peripheral blood of model group and chemotherapy group were significantly lower than those in blank group,while IL-10 was significantly higher than that in blank group (P<0. 05). The levels of IFN-γand TNF-βin peripheral blood of mice in Shanxian granule group were significantly higher than those in model group and chemotherapy group, while IL-10 was significantly lower than that in model group and chemotherapy group (P<0. 05). There was no significant difference in IFN-γ,TNF-β and IL-10 in peripheral blood of mice between Shanxian granule group and blank group. Conclusion:Shanxian granule can significantly inhibit the growth of tumor tissue of Lewis lung cancer tumor bearing mice,increase the spleen index of mice,enhance the activity of T lymphocytes,upregulate IFN-γ and TNF-β in peripheral blood and decrease IL-I. These suggested that the anti-tumor effect of Shanxian granule may be achieved by regulating the content of CD4+ T lymphocyte,the ration of CD4+/CD8+ and Th1/Th2 ratio,in order to restore the immune steady function of tumor patients,improve the immune system and enhance the immune surveillance function.
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Objective:To investigate the effects of Shanxian granule on proliferation of Lewis lung cancer cells and anti-tumor immunity and immune microenvironment of Lewis lung cancer-bearing mice in order to explore the molecular mechanism of anti-tumor of Shanxian Granule and improve the anti-tumor immunity of the body, and provide further theoretical basis for its clinical application. Methods:Lewis lung cancer cells was transplanted to axillary skin to establish mouse tumor model. The mice divided into blank group,model group,chemotherapy group and Shanxian granule group. The tumor tissue of Lewis lung cancer tumor bearing mice was weighed and the tumor inhibition rate was calculated. Immunohistochemical method was used to detect the expression of CD and CD8 in spleen tissue. The effect of lymphocytes on the proliferation of Lewis lung cancer cells was detected by CCK-8 method. The level of IFN-γ,TNF-βand IL-10 in peripheral blood were detected by ELISA. Results:①The tumor inhibition rate of Lewis lung cancer was 45. 99% in Shanxian Granule group,which was significantly higher than that of chemotherapy group (P<0. 05).②The lymphocytes of mouse can inhibit the proliferation of Lewis lung cancer cells and have a positive correlation with lymphocyte concentration and duration of action. Moreover,CD4+ T cells,CD4+/CD8+ratio and lymphocyte inhibition rate of Lewis lung cancer cells in model group and chem-otherapy group were significantly lower than those in blank group (P<0. 05). Shanxian granule group was significantly higher than the model group and chemotherapy group ( P<0. 05 ) . However, there was no significant difference between Shanxian granule group and blank group(P>0. 05).③The levels of IFN-γand TNF-βin peripheral blood of model group and chemotherapy group were significantly lower than those in blank group,while IL-10 was significantly higher than that in blank group (P<0. 05). The levels of IFN-γand TNF-βin peripheral blood of mice in Shanxian granule group were significantly higher than those in model group and chemotherapy group, while IL-10 was significantly lower than that in model group and chemotherapy group (P<0. 05). There was no significant difference in IFN-γ,TNF-β and IL-10 in peripheral blood of mice between Shanxian granule group and blank group. Conclusion:Shanxian granule can significantly inhibit the growth of tumor tissue of Lewis lung cancer tumor bearing mice,increase the spleen index of mice,enhance the activity of T lymphocytes,upregulate IFN-γ and TNF-β in peripheral blood and decrease IL-I. These suggested that the anti-tumor effect of Shanxian granule may be achieved by regulating the content of CD4+ T lymphocyte,the ration of CD4+/CD8+ and Th1/Th2 ratio,in order to restore the immune steady function of tumor patients,improve the immune system and enhance the immune surveillance function.
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<p><b>OBJECTIVE</b>To investigate the relation between expression of angiogenesis-related factors, namely vascular endothelial growth factor (VEGF) and transforming growth factor-beta1 (TGFbeta(1)), and microvessel count (MVC) in invasive breast cancer and analyze its clinical implications.</p><p><b>METHODS</b>VEGF, TGFbeta (1) and CD34 expressions in 62 surgical specimens of invasive breast cancer and 12 normal breast specimens were examined by immunohistochemistry and HE staining. MVC was calculated according to the quantification of positive CD34 expression. Clinicopathological characteristics of the patients including age, tumor size, histological type and auxiliary lymph node metastasis were recorded and compared with the results of MVC VEGF and TGFbeta1 expression and detection.</p><p><b>RESULTS</b>MVC and of VEGF and expressions TGFbeta (1) in invasive breast cancer group (55.62-/+11.07, 51.61%, 56.45%, respectively) were greater than those in the normal control group (12.65-/+5.73, 16.67%, 16.67%, respectively, P<0.05). MVC and the positivity rates of VEGF and TGFbeta (1) expressions were 65.53-/+20.36, 68.75% and 78.13%, respectively, in invasive breast cancer patients with axillary lymph node metastasis, significantly higher than those without metastasis (P<0.05). MVC was correlated with VEGF and TGFbeta (1) expressions in that MVC was significantly higher in patients positive for VEGF and TGFbeta (1) (62.82-/+16.31 and 59.35-/+12.76) than in those negative for their expressions (51.16-/+12.53 and 50.80-/+15.62, P<0.05). Significant correlation was also found between VEGF and TGFbeta (1) expressions (P<0.05).</p><p><b>CONCLUSION</b>The interaction between VEGF and TGFbeta (1) mediates angiogenesis, and MVC and VEGF and TGFbeta (1) expressions are correlated to lymph node metastasis, which may provide reference for prognostic evaluation of invasive breast cancer.</p>
Subject(s)
Adult , Aged , Female , Humans , Middle Aged , Breast Neoplasms , Metabolism , Pathology , Carcinoma, Ductal, Breast , Metabolism , Pathology , Immunohistochemistry , Neoplasm Invasiveness , Neovascularization, Pathologic , Metabolism , Prognosis , Transforming Growth Factor beta , Vascular Endothelial Growth Factor AABSTRACT
Objective To investigate expression and significance of matrix metalloproteinase-2(MMP-2),MMP-9 and tissue inhibitor of metalloproteinase-1(TIMP-1) in rats with glomerular sclerosis made by doxorubicin.Methods Forty Wistar male rats(8-week-old) were randomly assigned into 2 groups:sham operated and model groups.Rats in model group were nephrectomized after anesthesia and injected with adriamycin(5 mg/kg) after 1 week.Rats in sham operated group was subjected to sham operation and injected with normal saline after 1 week through the tail vein.All rats were killed in the 12th week.Immuno-histochemistry was performed on renal tissue to detect Collagen Ⅳ(Col-Ⅳ),fibronectin(FN),MMP-2,-9 and TIMP-1.Results Immunohistochemistry staining indicated that expressions of MMP-2,-9 in model group decreased significantly compared to sham operated group(Pa
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Objective To study the expression of ?-smooth muscle actin(?-SMA)in glomerulosclerosis rats and its relationship with renal function.Methods Forty healthy Wistar rats were equally divided into 2 groups including sham operated group and model control group.Rats in model groups were uninephrectomized and injected with daunorubicin(5 mg/kg)after 1 week through the tail vein.Twenty-four hours of urinary protein excretion,serum creatinine(Scr),blood urea nitrogen(BUN)were measured at the 12th week.Renal pathology was evaluated.Immunohistochemistry(SupervisionTM)was performed on renal glomeruli tissue to detect the expression of ?-SMA.Reverse transcription polymerase chain reaction(RT-PCR)was used to examine the expression levels of ?-SMA mRNA in glomeruli.SPSS 13.0 software was used to analyze the two variables.Results In model control group,the urinary protein,Scr,BUN significantly increased(Pa
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Aim To investigate the effects of all-trans retinoic acid and benazepril on the expression of ?-smooth muscle actin in rats with glomerulosclerosis.Methods 80 Wistar male Rats were randomly assigned into the following groups: control group,model group,ATRA treatment group and benazepril treatment group,20 rats in each group.GS rats were uninephrectomized and injected with adriamycin(5mg?kg-1) after one week through the tail vein.All rats were sacrificed at the 12th week,GS was evaluated by glomerulosclerosis index(GSI) system.The expression of ?-SMA was assessed by reverse transcription-polymerase chain reaction(RT-PCR) and immunohistochemistry.Results Comparing with control group,the expression of ?-SMA mRNA and protein were decreased significantly in ATRA treatment group and benazepril treatment group(P0.05).Conclusions The postponed effects of ATRA and benazepril on GS were evident and equivalent.