1.Protective effect of vitamin D3 on alcohol⁃induced liver inj ury in mice
Huihui Wang ; Xiaoyu Wang ; Weiyi Gong ; Wenxiu Cheng ; Jingxin Gao ; Chunqiu Hu
Acta Universitatis Medicinalis Anhui 2023;58(5):707-710,717
Objective:
To investigate the protective effect of vitamin D3 on alcoholic liver injury in mice.
Methods:
Forty mice were randomly divided into 4 groups : normal Control (Control) group , vitamin D3 (VitD3 ) group , alcohol model (EtOH) group and alcohol + vitamin D3 (EtOH + VitD3 ) group. The mice were fed with the DeCarlialcohol liquid diet to establish alcoholic liver injury model. Serum levels of alanine aminotransferase (ALT) , aspartate aminotransferase (AST) and liver index were detected. HE staining was used to observe the pathological changes of liver. The relative expression levels of tumor necrosis factor α (TNF⁃α ) , transforming growth factor β (TGF⁃β) , interleukin⁃6 (IL⁃6) and interleukin⁃1β (IL⁃1β) mRNA were detected by quantitative real⁃time PCR (qRT⁃PCR) . The expressions of nuclear factor⁃kappa B (NF⁃κB) p65 and NF⁃κB p50 in liver were detected by Western blot.
Results:
The serum ALT , AST vitality , liver index and hepatic TNF⁃α , TGF⁃ β , IL⁃6 and IL⁃1β mRNA in
EtOH group were significantly higher than those in Control group. EtOH group disorganized hepatocyte and hepatic lobules boundary was not clear, and the hepatocytes showed apparent inflammatory cells infiltration of liver cells and fat cavitation. NF⁃κB p65 and NF⁃κB p50 protein expression increased significantly. Compared with EtOH group ,the serum ALT , AST vitality , liver index and hepatic TNF⁃α , TGF⁃ β , IL⁃6 and IL⁃1β mRNA in EtOH + VitD3 group decreased significantly. The pathological staining results showed that inflammatory cells infiltration and decrease in the number of fat vacuoles , and the liver cells returned to normal liver cell structure. At the same time the NF⁃κB p65 and NF⁃κB p50 protein expression level decreased significantly.
Conclusion
Vitamin D3 has a certain protective effect on alcohol⁃induced liver injury in mice , and its main mechanisms are related to the inhibition of NF⁃κB pathway and the reduction of inflammatory response.
2.Intravenous route to choroidal neovascularization by macrophage-disguised nanocarriers for mTOR modulation.
Weiyi XIA ; Chao LI ; Qinjun CHEN ; Jiancheng HUANG ; Zhenhao ZHAO ; Peixin LIU ; Kai XU ; Lei LI ; Fangyuan HU ; Shujie ZHANG ; Tao SUN ; Chen JIANG ; Chen ZHAO
Acta Pharmaceutica Sinica B 2022;12(5):2506-2521
Retinal pigment epithelial (RPE) is primarily impaired in age-related macular degeneration (AMD), leading to progressive loss of photoreceptors and sometimes choroidal neovascularization (CNV). mTOR has been proposed as a promising therapeutic target, while the usage of its specific inhibitor, rapamycin, was greatly limited. To mediate the mTOR pathway in the retina by a noninvasive approach, we developed novel biomimetic nanocomplexes where rapamycin-loaded nanoparticles were coated with cell membrane derived from macrophages (termed as MRaNPs). Taking advantage of the macrophage-inherited property, intravenous injection of MRaNPs exhibited significantly enhanced accumulation in the CNV lesions, thereby increasing the local concentration of rapamycin. Consequently, MRaNPs effectively downregulated the mTOR pathway and attenuate angiogenesis in the eye. Particularly, MRaNPs also efficiently activated autophagy in the RPE, which was acknowledged to rescue RPE in response to deleterious stimuli. Overall, we design and prepare macrophage-disguised rapamycin nanocarriers and demonstrate the therapeutic advantages of employing biomimetic cell membrane materials for treatment of AMD.
3.Relationship between TP53 gene mutation and overall survival time of myelodysplastic syndromes: a Meta-analysis
Yan SUN ; Haiyan XIAO ; Mingjing WANG ; Yumeng LI ; Teng FAN ; Xueying WANG ; Weiyi LIU ; Xiaomei HU
Journal of Leukemia & Lymphoma 2020;29(6):361-365
Objective:To investigate the relationship between TP53 gene mutation and overall survival (OS) time of myelodysplastic syndrome (MDS).Methods:Databases, including PubMed, Cochrane Library and Embase were searched for relevant studies published up to 20 October, 2019. The corresponding hazard ratio ( HR) and their 95% confidence interval ( CI) for OS from multivariate Cox proportional hazard models were extracted. The combined HR with their 95% CI was calculated by using fixed or random effect models. Meta-analysis was performed by using Revman 5.3 software. Results:A total of 1 033 patients from 6 studies were enrolled. Meta-analysis results showed that OS time in TP53 gene mutation group was shorter than that in wild type group for patients with MDS ( HR = 2.16, 95% CI 1.52-3.07, P < 0.01). The prognostic risk for post-transplantation patients with MDS ( HR = 2.69, 95% CI 1.63-4.43, P < 0.01) was lower compared with that for patients treated by azacitidine( HR = 2.89, 95% CI 1.37-6.08, P = 0.005). Conclusion:TP53 gene mutation is a risk factor affecting OS of MDS patients.
4. Comparison of clinical effects of Qinghuang powder, low-intensity chemotherapy and alternated treatment on elderly patients with acute myeloid leukemia progressed from myelodysplastic syndromes
Zhuo CHEN ; Teng FAN ; Haiyan XIAO ; Richeng QUAN ; Weiyi LIU ; Xudong TANG ; Yan LYU ; Chi LIU ; Liu LI ; Xiaomei HU
Journal of Leukemia & Lymphoma 2019;28(9):523-526
Objective:
To investigate the clinical effects of Qinghuang powder, low-intensity chemotherapy and Qinghuang powder alternated with low-intensity chemotherapy in the treatment of elderly acute myeloid leukemia patients progressed from myelodysplastic syndromes (MDS-AML).
Methods:
A total of 32 elderly patients with MDS-AML treated in Xiyuan Hospital, China Academy of Chinese Medical Sciences from January 2014 to December 2017 were retrospectively analyzed. Of them, 12 patients received Qinghuang powder (Qinghuang powder group), 6 patients received Qinghuang powder alternated with low-intensity chemotherapy (alternating group), and 14 patients received low-intensity chemotherapy (low-intensity chemotherapy group), based on the real world of patient's voluntary choice of treatment. The efficacy and adverse reactions in the 3 groups were observed.
Results:
The overall response number of Qinghuang powder, alternating, and low-intensity chemotherapy groups were 2, 2 and 4 cases, respectively, there was no significant difference among the 3 groups (
5. Gene mutations of patients with myelodysplastic syndromes
Weiyi LIU ; Richeng QUAN ; Pan ZHAO ; Hongmei ZHAO ; Haiyan XIAO ; Chi LIU ; Qianze ZHU ; Hongzhi WANG ; Liu LI ; Yan LYU ; Yonggang XU ; Jiayue QIN ; Rou MA ; Xiaomei HU
Journal of Leukemia & Lymphoma 2018;27(8):449-452
Objective:
To analyze the gene mutations in the patients with myelodysplastic syndromes (MDS).
Methods:
Forty-seven patients with MDS newly diagnosed in Xiyuan Hospital, China Academy of Chinese Medical Sciences from January 2016 to July 2017 were enrolled. NGS 127-gene panel was used to detect the gene mutations, and the relationship between the gene mutations and the clinicopathological features was also analyzed.
Results:
Thirty-one (66.0 %) cases had gene mutations in 47 patients with MDS, and 23 gene mutations were detected with clinical significances. There were 7 mutant genes with a mutation frequency over 5 % in the population, including U2AF1 (23.4 %), SF3B1 (12.8 %), ASXL1 (10.6 %), TET2 (8.5 %), BCOR (8.5 %), TP53 (8.5 %) and DNMT3A (6.4 %) in turn. Among 31 patients with gene mutations, 16 (51.6 %) patients had ≥ 2 synergistic mutations, and 12 cases had synergistic mutations in different genetic functional groups, which was higher than that in same genetic functional groups (4 cases). There was a tendency of coexistence in IDH2-KRAS, IDH2-SRSF2, IDH2-STAG2, KRAS-SRSF2, KRAS-STAG2, RUNX1-PHF6, EZH2-ASXL1, EZH2-ZRSR2, and NPM1-NRAS (all
6.Mechanism of JinShuiBao capsule in ameliorating rat pneumoconiosis model
Wei LIU ; Shufan JIANG ; Lei TU ; Weiyi HU ; Tao WANG ; Jing. WANG
Journal of China Pharmaceutical University 2018;49(4):476-482
To investigate the mechanism of JinShuiBao capsule on improving respiratory function and lung tissue pathology in rat pneumoconiosis model. Chronic pneumoconiosis rat model was established by tracheal injection of quartz dust. JinShuiBao was administrated orally by 600 and 300 mg/kg, once daily for 6 months. At the 1st, 3rd and 6th month of administration, 6 rats in each group were taken for hemorheology, vascular endothelial function, immunoinflammatory cytokines and oxidative stress. The results showed that high dose of JinShuiBao had a significant improvement on the plasma viscosity at each time point(P< 0. 05)during the 6-month trial, and partially improved the whole blood viscosity. Both dose of JinShuiBao capsule significantly decreased the levels of serum inflammatory cytokines such as TGF-β, TNF-α and IL-6(P< 0. 05, P< 0. 01), and high dose group could significantly decrease the level of CD4+/CD8+(P< 0. 01). The high dosage of JinShuiBao could obviously reduce the level of serum MDA and increase the activity of SOD(P< 0. 05), and obviously reduced the number of leukocytes in the bronchoalveolar lavage fluid of model rats. In the high-dose group, the levels of ET, NO and PC in bronchoalveolar lavage fluid were significantly improved in all the experimental periods(P< 0. 05, P< 0. 01), while the low-dose group also had a statistically significant improvement at 3 month later. These results suggested that the improvement of JinShuiBao capsule on pneumoconiosis rats involved various mechanism, including blood viscosity, systemic and pulmonary inflammatory response, vascular endothelial injury, and oxidative stress in the whole body and lung fibrosis.
7.Comparison of survival in elderly patients with acute myeloid leukemia treated with oral arsenic-containing Qinghuang Powder and low intensive chemotherapy
Yan LYU ; Weiyi LIU ; Richeng QUAN ; Haiyan XIAO ; Xudong TANG ; Chi LIU ; Liu LI ; Hongzhi WANG ; Yonggang XU ; Xiaoqing GUO ; Teng FAN ; Xiaomei HU
Journal of Leukemia & Lymphoma 2018;27(7):396-399
Objective To investigate the survival of oral arsenic-containing Qinghuang Powder (QHP) and low intensive chemotherapy (LIC) in the treatment of elderly patients with acute myeloid leukemia (AML).Methods Forty-two AML patients older than 60 years in Xiyuan Hospital from January 2015 to December 2017 were retrospectively analyzed.Of them,20 cases were treated with QHP (QHP group),22 cases were treated with LIC (LIC group).The survivals of the two groups were compared.Results There was no significant difference of median survival time (13 months vs.13.5 months,x2 =0.096,P =0.757),1-year survival rates (59.1% vs.70.0 %,x2 =0.543,P =0.461),2-year survival rates (13.6 % vs.15.0 %,x2 =0.016,P > 0.05),and 3-year survival rates (4.6 % vs.5.0 %,x2 =0.005,P > 0.05) between LIC and QHP groups.There was no significant difference of median survival time in age ≥75 year (12 months vs.12.5 months,x2 =1.317,P =0.251),performance status scores > 2 (12 months vs.12 months,x2 =0.834,P =0.361),hematopoietic stem cell transplantation with combined disease index > 2 (12 months vs.13 months,x2 =1.726,P =0.189),secondary AML (10 months vs.14 months,x2 =1.552,P =0.213),and poor cytogenetics (12 months vs.8 months,x2 =0.479,P =0.489) between LIC and QHP group.Conclusion The survival of elderly AML patients is considerable in patients treated with oral QHP and LIC,which suggests that oral QHP may be an equivalent alternative treatment since elderly AML (especially more than 75 years) patients refused to LIC therapy.
8.Methods and progress of biological omics technology in regenerative medicine
Xiaohang WU ; Jinna LIN ; Yixin HU ; Weiyi LAI ; Haotian LIN
International Journal of Biomedical Engineering 2018;41(4):314-318
Transplantations for repairing tissue and organ defects caused by disease and injury require a large number of donor tissues and organs.Therefore,people are increasingly hoping to restore or rebuild normal physical functions by establishing the body's own regenerative capacity.For this reason,regenerative medicine is rapidly emerging and becoming a research hotspot.The regeneration of tissues and organs is a complex process involving multiple layers of structures and requiring multiple factors to interact.Compared with traditional biomolecular technologies,biological omics based on biomolecular groups has obvious advantages in regenerative medicine researches and has became an important tool correlational researches.In this paper,the methods and progress of biomedical techniques for regenerative medicine researches in recent years were summarized,and the advantages of biological omics technology in regenerative medicine were analyzed and prospected.
9.Screening of different metabolites in serum of children with Kaschin-Beck disease by the metabonomics technique
Weiyi WANG ; Jian HU ; Lihua WANG
Chinese Journal of Endemiology 2018;37(3):177-180
Objective To search the different metabolites related with Kaschin-Beck disease (KBD) in serum of children with KBD. Methods Among the children aged 7 - 15 years old in the KBD areas in Qinghai Province,by the X ray and clinical examination,56 KBD patients(case group) and 51 non-KBD children (internal control group)were selected.Meantime,in non-KBD areas where the economic level and living habits was similar to that of the KBD areas, 50 healthy children were selected as external control group. Children's fasting blood samples were collected, and the metabolic profile in serum was determined by ultra performance liquid chromatography coupled with quadrupole-time of flight mass spectrometry (UPLC/QTOF-MS) technique. Combined with multivariate statistical analysis, database searching was applied to explore and search the different endogenic metabolites associated with KBD, to find biologically targeted makers. Results There were 1 384 serum metabolites with significant differences in case group, internal control group and external control group, 670 serum metabolites with significant differences in case group and external control group, including 25 KBD related endogenous differential metabolites. Among them, the relative contents of kynurenic acid and arachidonic acid in case group were higher than that of external control group, and the relative contents of N-α-acetylarginine, 6-hydroxymelatonin and sphinganine in case group were lower than that of external control group (P < 0.05). Conclusions The serum metabolic profile of children in KBD areas and children in non-KBD areas is significantly different. N-α-acetylarginine, kynurenic acid, 6-hydroxymelatonin, sphinganine and arachidonic acid are more closely related with KBD,and they can be considered as a clue in screening KBD biomarkers.
10.Screening of different metabolites in urine of children with Kaschin-Beck disease by the metabonomics technique
Jian HU ; Weiyi WANG ; Shiyu LIU ; Lihua WANG
Chinese Journal of Endemiology 2018;37(4):296-300
Objective To search the different metabolites related with Kaschin-Beck disease (KBD) in urine of children with KBD by metabolomics technique,in order to provide clues in researching KBD biomarkers.Methods Among the children aged 7-15 years old in the KBD areas in Qinghai Province,the urine samples of 56 KBD children (case group),51 health children from the same area as the control group (internal control group) and 50 health children from non diseased areas (external control group) were examined by quadrupole-time of flight mass spectrometry (UPLC/QTOF-MS).Partial least squares discriminate analysis (PLS-DA) and multivariate statistical analysis were applied to explore and search the different endogenic metabolites associated with KBD.Results A obvious separation among three groups was observed,and the difference was significant among case group and internal,external control groups (P < 0.05).Twenty-two different endogenic metabolites associated with KBD were found,compared with the external control group,21 metabolites were increased in the case group(P < 0.05).Among them,14 kinds of metabolites (L-Cystine,isobutyryl carnitine,butyryl-L-carnitine,aspartyl-Asparagine,asparaginylAspartate and ubiquinone Q2,etc.) showed significant differences between the case group and internal control group (P < 0.05).There were 4 kinds of metabolites showing significant differences between the two control groups(P < 0.05).Condusion The metabolic profile in the urine of KBD children and healthy children is obviously different and the metabolites of L-Cystine,isobutyryl carnitine,butyryl-L-carnitine,aspartyl-Asparagine,asparaginyl-Aspartate and ubiquinone Q2 are more closely related with KBD,which can be considered as the clues in screening KBD biomarkers.


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