1.Fetal STR typing and paternity identification of early pregnancy aborted tissue based on next-generation sequencing technology
Jin ZHANG ; Kaihui LIU ; Jinping HAO ; Xueying YANG ; Xingkun ZHANG ; Wei PENG ; Xiaoyu XU ; Shan GAO ; Jingjing CHANG ; Bo LEI ; Mengnan ZHANG ; Qiujuan WANG ; Ying ZHANG
Chinese Journal of Forensic Medicine 2024;39(5):539-545
Fetal STR typing of aborted tissue has long been a major problem in forensic DNA.Especially for the first trimester abortion tissue,it is difficult to isolate the embryonic components by histomorphological means,resulting in the inability to accurately obtain the STR typing of the fetus.The mixed STR typing results of mother and fetus can provide a key basis for the identification of suspects in cases of rape-induced pregnancy.In this study,next generation sequencing was used to successfully detect mixed STR typing of mother and suspected fetus or single STR typing of suspected fetus in 4 rape-induced early pregnancy abortion tissues.Combined with Y-STR and flank sequence information,it provides a more comprehensive and reliable genetic basis for the identification of suspects.
2.The potential targets and mechanisms of modified Baihe dihuang decoction applied in post-stroke depression
Sixing HUANG ; Shuyi WU ; Ping ZHANG ; Jinping LUO ; Min WANG ; Yanlei GUO ; Hao LI ; Li ZHANG ; Zhe QIANG
China Pharmacy 2023;34(20):2483-2489
OBJECTIVE To explore the potential targets and mechanisms of the modified Baihe dihuang decoction (MBD/ BDD) applied in post-stroke depression (PSD). METHODS Network pharmacology was used to mine the potential targets and key pathways of MBD/BDD in the treatment of PSD. PSD model rats were induced by focal cerebral ischemia surgery combined with chronic unforeseen mild stress, and then were randomly divided into PSD model group, MBD/BDD group (12.6 g/kg, by raw drug), and fluoxetine hydrochloride (FLX) group (positive control, 2.3 mg/kg); a blank control group was also set up, with 8 rats in each group. Each administration group was given a corresponding medication solution by gavage once a day for 21 consecutive days. The intervention effect of MBD/BDD on depression-like symptoms in model rats was evaluated by open field and forced swimming tests. The brain tissues of rats in each group were dissected and total RNA was extracted for transcriptome sequencing and bioinformatics analysis. The mRNA and protein expressions of genes with significant changes and common neurotrophic factors were verified based on the above results. RESULTS A total of 131 MBD/BDD antidepressant-related target genes were obtained (such as IL1B and AKT1, etc.), which were closely related to neural active ligand-receptor interactions and cyclic adenosine monophosphate signaling pathway. MBD/BDD could significantly prolong or increase the total time spent and distance traveled in the central grid of qiangzhe@cqtcm.edu.cn PSD model rats, and significantly shorten the cumulative immobility time (P<0.05). After treatment with MBD/BDD, the number of genes that changed in rat brain tissue was much higher than that in the FLX group, and there were significant differences in gene profiles among the PSD model group, MBD/BDD group, and FLX group. There were 1 351 differentially expressed genes (DEGs) between the MBD/BDD group and the PSD model group, of which 178 were significantly down-regulated and 1 173 were significantly up-regulated (P<0.05). Above 1 351 DEGs were involved in neuronal differentiation, chemical synaptic transmission regulation. They were significantly enriched in axonal guidance, cholinergic synapses and neuroactive ligand-receptor interactions. The top 30 genes in terms of up-regulation in the brain tissue of rats of MBD/BDD group were all associated with neuronal proliferation, development, differentiation, and migration. After MBD/BDD intervention, the expressions of Fezf2, Arx, Ostn, Nrgn genes, brain-derived neurotrophic factor and tyrosine kinase receptor B protein in brain tissue of rats were significantly increased (P<0.05). CONCLUSIONS The anti-PSD effect of MBD/BDD may be related to the up-regulation of the expression of genes related to neuronal proliferation, development, differentiation and migration, as well as the promotion of neural structural and functional repair.
3.Tetrahydroxy stilbene glycoside ameliorates neuroin-flammation for Alzheimer's disease via cGAS-STING
Jinping HAO ; Boya LI ; Cengceng ZHENG ; Beibei MIAO ; Li ZHANG ; Yali LI ; Lin LI ; Xingjie LI ; Dan GAO ; Lan ZHANG
Chinese Journal of Pharmacology and Toxicology 2023;37(7):515-515
OBJECTIVE Alzheimer's disease(AD)is the most common neurodegenerative disease worldwide.Neuroinflammation is a potential target for the patients with AD.It is attributed to activated microglia and the release of various inflammatory mediators from infec-tion,ischemia and toxin accumulation.Accumulating evi-dence has indicated that the cGAS-STING pathway driven neuroinflammation in neurological disease.TSG is a main natural active ingredient that derived from polyg-onum multiflorum.Previous research from our group found that TSG has beneficial effects of anti-aging,anti-inflammatory action and improving memory function in APP/PS1 transgenic AD mice.Here,we investigated the effects of TSG on cognitive impairment and neuroinflam-mation in APP/PS1-AD mice and explore the underly-ing mechanism by which TSG ameliorates memory func-tion in the cGAS-STING-mediated inflammatory response.METHODS The Morris water mace test and the novel object recognition test were performed to test the effects of TSG on spatial learning and cognitive and memory abil-ity in APP/PS1 double transgenic AD mice model.In addi-tion,real-time quantitative PCR,Western blotting,ELISA analysis,and flow cytometry to examine gene and pro-tein expression of cGAS-STING related pro-inflammatory cytokines and chemokines.Statistical analyses were ana-lyzed using the SPSS 25.0 package by analysis of vari-ance(ANOVA).Neuman-Keuls or Tukey's multiple-com-parisons test were conducted as ANOVA justified post hoc comparisons between group means.RESULTS We demonstrated that AD transgenic mice exhibited cognitive deficits accompanied by the elevated serum and brain inflammation.The expressions of serum inflammatory cytokines and the activation of microglia in cerebral cor-tex and hippocampus were suppressed after TSG treat-ment,which was probably attributable to the decrease of cyclic GMP-AMP synthase(cGAS)and stimulator of interferon genes(STING)triggered immune response.Additionally,the data showed that TSG treatment reduced the expression level of inflammatory cytokines(IL-1β,TNF-α,IFN-β,IFN-α)in microglial cells BV2 primed with LPS and IFN-γ.CONCLUSION TSG implicated the health benefits in preventing cognitive disorders by inhib-iting neuroinflammation via cGAS-STING signalling path-way in AD.
4.Icariin ameliorates behavioral deficits and neuropa-thology in a mouse model of multiple sclerosis
Dan GAO ; Cengceng ZHENG ; Jinping HAO ; Cuicui YANY ; Chaoying HU
Chinese Journal of Pharmacology and Toxicology 2023;37(7):515-516
Multiple sclerosis(MS)is a systemic inflammatory illness of the central nervous system that involves demyelinating lesions in the myelin-rich white matter and pathology in the grey matter.Despite signifi-cant advancements in drug research for MS,the dis-ease's complex pathophysiology makes it difficult to treat the progressive forms of the disease.In this study,we identified a natural flavonoid compound icariin(ICA)as a potent effective agent for MS in ameliorating the deterioration of symptoms including the neurological defi-cit score and the body weight in a murine experimental autoimmune encephalomyelitis(EAE)model.These improvements were associated with decreased demyelin-ation in the corpus callosum and neuron loss in the hippo-campus and cortex confirmed by immunohistochemistry analysis.Meanwhile,it was observed that the activation of microglia in cerebral cortex and hippocampus were inhibited followed by the neuroinflammatory cytokines downregulation such as IL-1β,IL-6 and TNF-α after ICA treatment,which was probably attributable to the sup-pression of microglial NLRP3 inflammasome activation.Additionally,molecular docking also revealed the binding force of ICA to NLRP3 inflammasome protein complexes in vitro.Taken together,our findings have demonstrated that ICA,as pleiotropic agent,prevents EAE-induced MS by improving demyelination and neuron loss,which inter-feres with the neuroinflammation via microglial NLRP3 inflammasome activation.
5.The ATP/P2X7 axis⁃mediated K + efflux promotes NLRP3 inflammasome activation in NDV⁃infected ECA109 cells
Xu Cao ; Caixia Wu ; Jinping Lan ; Jing Wang ; Zhaoxia Jia ; Hao Liu ; Kaiyang Liu
Acta Universitatis Medicinalis Anhui 2023;58(1):42-47
Objective :
To explore whether the NLRP3 inflammasome is activated after Newcastle disease virus (NDV) exposure to esophageal cancer ECA109 cells , whether its activation is related to K + efflux , and the effect of ATP/P2X7 axis on the activation of NLRP3 inflammasome.
Methods:
The expression of NLRP3 and IL⁃1β was detected by Western blot; the content of IL⁃1β in the supernatant was detected by ELISA ; the formation of ASC spots was detected by fluorescence immunoassay; the change of intracellular K + concentration was detected by fluorescent probe technology; Interventions with ATPase , ATP and P2X7 receptor inhibitors were used to investigate their role in NLRP3 inflammasome activation.
Results:
Compared with the control group , the expression of NLRP3 , IL⁃1β and ASC protein in cells was up⁃regulated after NDV F3 infection ; the intracellular potassium concen tration decreased with the prolongation of infection time (P < 0. 05) . After the intervention of P2X7 receptor inhibitor, the efflux of intracellular K + was blocked. With the increase of inhibitor concentration , the efflux of K + was maximally inhibited at 10 μmol/L (P < 0. 05) . The results of ATPase and ATP intervention showed that ATPase inhibited K + efflux , while ATP promoted K + efflux. Western blot results showed that compared with the control group , P2X7 receptor was inhibited , and the expressions of NLRP3 and IL⁃1β were down⁃regulated ; after ATPase intervened cells , the expressions of NLRP3 and IL⁃1β decreased ; After ATP intervention in cells , the protein expressions of NLRP3 and IL⁃1β were up⁃regulated (P < 0. 05) .
Conclusion
NDV F3 infection of ECA109 cells can activate the NLRP3 inflammasome , the mechanism may be related to the ATP/P2X7 axis.
6.Central nervous system complications in patients with carotid artery stenosis undergoing off-pump coronary artery bypass grafting: A retrospective cohort study
Yalin LIU ; Hao DENG ; Sumin YANG ; Yuhui WU ; Hong ZHANG ; Jinping WANG
Chinese Journal of Clinical Thoracic and Cardiovascular Surgery 2022;29(06):736-741
Objective To analyze the effect of carotid artery stenosis degree and intervention for carotid artery stenosis on the incidence of central nervous system complications after off-pump coronary artery bypass grafting (OPCABG) and explore the influencing factors. Methods A total of 1 150 patients undergoing OPCABG in our hospital from June 2018 to June 2021 were selected and divided into two groups according to whether there were central nervous system complications, including a central nervous system complication group [n=61, 43 males and 18 females with a median age of 68.0 (63.0, 74.0) years] and a non-central nervous system complication group [n=1 089, 796 males and 293 females with a median age of 65.5 (59.0, 70.0) years]. The risk factors for central nervous system complications after OPCABG were analyzed. Results Univariate analysis showed that age, smoking, hyperlipidemia, preoperative left ventricular ejection fraction, intra-aortic ballon pump (IABP), postoperative arrhythmia, postoperative thoracotomy and blood transfusion volume were associated with central nervous system complications. The incidence of central nervous system complications in patients with severe carotid artery stenosis or occlusion (11.63%) was higher than that in the non-stenosis and mild stenosis patients (4.80%) and moderate stenosis patients (4.76%) with a statistical difference (P=0.038). The intervention for carotid artery stenosis before or during the operation did not reduce the incidence of central nervous system complications after the operation (42.11% vs. 2.99%, P<0.001). Age, postoperative arrhythmia, severe unilateral or bilateral carotid artery stenosis and occlusion were independent risk factors for postoperative central nervous system complications (P<0.05). Conclusion The age, smoking, hyperlipidemia, preoperative left ventricular ejection fraction, intraoperative use of IABP, postoperative arrhythmia, secondary thoracotomy after surgery, blood transfusion volume and OPCABG are associated with the incidence of postoperative central nervous system complications in patients. Age, postoperative arrhythmia, severe unilateral or bilateral carotid artery stenosis and occlusion are independent risk factors for postoperative central nervous system complications. In patients with severe carotid artery stenosis, preoperative treatment of the carotid artery will not reduce the incidence of central nervous system complications.
7.Discussion on the sharing mechanism of cerebration of constructing the sharing platform for respiratory disease biobank
Wenting LUO ; Pan CHEN ; Yongjie DING ; Zhiyuan ZHENG ; Bingrong ZHAO ; Chuangli HAO ; Dongbo TIAN ; Chunhua WEI ; Xueqin LI ; Qingyun LI ; Jinping ZHENG
Chinese Journal of Medical Science Research Management 2021;34(1):12-17
Objective:Standardized sample resources and high-quality clinical big data are important resources for medical research, only through resource sharing can maximize its utilization.Which can be utilized to the max only through resource sharing.Methods:This paper attempts to explore the sharing mechanism of the resource sharing platform and proposes some aspects such as the platform construction background, management regulations, legal ethical system, data sharing principles, benefit distribution, etc.This article attempts to explore the sharing mechanism based on the resource sharing platform of the respiratory disease biobank, proposes the contents that should be included in the sharing mode.Detailed information including the platform construction background, management procedures, legal and ethical system, data sharing principles and benefit distribution should take into consideration in the operating mechanism of the platform.Results:Establishing a resource sharing platform matches the development of clinical research in China.The tailored sharing model which is suitable for the field of respiratory diseases will also guide the rapid development of clinical research.Conclusions:The construction of a respiratory disease biobank sharing platform is conducive to promoting the opening and sharing of biological samples and information resources in the context of big data.
8. Comparison of changes in liver function in patients with different types of hepatic alveolar echinococcosis after radiofrequency ablation
Jide A ; Jinping CHAI ; Hao WANG ; Wei GAO ; Xiangqian WANG ; Qingshan TIAN ; Shunyun ZHAO
Chinese Journal of Hepatobiliary Surgery 2019;25(9):656-659
Objective:
To compare the changes in liver function in patients with different types of hepatic alveolar echinococcosis after radiofrequency ablation.
Methods:
The data of 32 patients with hepatic alveolar echinococcosis treated by radiofrequency ablation from December 2016 to December 2018 at the Qinghai Provincial People's Hospital were retrospectively analyzed. There were 12 males and 20 females. The patients were divided into the single lesion group (
9.Effects of baicalin on mitochondria apoptotic pathway of trophoblast cells in a preeclampsia rat model
Yonghong WANG ; Jiao SONG ; Jinping DONG ; Taotao YANG ; Min HAO
Chinese Journal of Perinatal Medicine 2016;19(12):933-939
Objective To explore the effects of baicalin in the treatment of a preeclampsia (PE) rat model by detecting the expression of X-linked inhibitor of apoptosis protein (XIAP) and cysteine containing aspartate-9 (Caspase-9) and observing the ultrastructure of mitochondria in trophoblast cells.Methods Forty-eight pregnant Wistar rats were randomly divided into two groups:12 in the control group and 36 in the PE model group.The PE model was established with subcutaneous injection of l-nitro arginine methyl ester with 100 mg/kg per day from the 13th day of pregnancy.Beginning from the 16th day of pregnancy,the PE rats were injected with different doses of baicalin till cesarean section,and divided into three groups:non-intervention PE model group treated with saline (NIP group),low-dose baicalin intervention group (IDB group) at 50 mg/kg per day,and high-dose baicalin intervention group (HDB group) at 100 mg/kg per day.The rat tail artery blood pressure and 24-h urine protein level were measured at pregnant day 10,16 and 20.The levels of XIAP and Caspase-9 in placenta were measured by immunohistochemistry.The ultrastructure of mitochondria of trophoblast cells of the rat placenta was observed under electron microscope.T test,F test and LSD-t test were applied for statistical analysis.Results (1) On pregnant day 10,no significant differences were observed in rat tail artery systolic blood pressure,diastolic blood pressure and 24-h urine protein level between the control group and PE model group (all P>0.05).On pregnant day 16 and 20,the systolic blood pressure,diastolic blood pressure and 24-h urine protein level of NIP,IDB and HDB groups were significantly higher than those of control group [pregnant day 16:systolic blood pressure:(137.74±5.21),(136.15±4.86),(138.28±4.79) and (110.57±3.79) mmHg (1 mmHg=0.133 kPa),diastolic blood pressure:(89.58 ± 5.50),(88.45 ± 8.59),(89.42 ± 6.29) and (80.28 ± 7.36) mmHg,24-h urine protein:(7.78 ± 0.45),(7.53 ± 0.54),(7.86± 0.57) and (6.45 ± 0.56) mg;pregnant day 20:systolic blood pressure:(145.26 ± 4.67),(131.28 ± 4.34),(130.93 ± 5.33) and (110.40 ± 6.92) mmHg,diastolic blood pressure:(89.87±6.55),(85.34±7.33),(84.64±7.36) and (80.19±7.34) mmHg,24-h urine protein:(11.18±0.42),(9.65±0.54),(9.06±0.56) and (6.31 ±0.45) mg] (all P<0.01).On pregnant day 20,the systolic and diastolic blood pressure and 24-h urine protein level in IDB and HDB groups were significantly lower than in NIP group (all P<0.05),but showed no significant differences between IDB and HDB groups (allP>0.05).(2) Compared with NIP group,the expression of XIAP in control group,IDB and HDB groups were significantly increased(210.39±0.78,180.56±0.82,195.36±0.96 and 192.84± 1.06,all P<0.01).There was no significant difference in the expression of XIAP between IDB and HDB groups (P=0.66).The expression of Caspase-9 in control group,IDB and HDB groups were significantly decreased compared with NIP group (210.36±0.55,195.53±0.96,198.42± 1.01 and 185.25±0.64,all P<0.01).There was no significant difference in the expression of Caspase-9 between IDB and HDB groups (P=0.65).Ultrastructure of mitochondria in NIP group showed different degrees of damage,matrix swelling,and mitochondrial cristae bresk or disappearance.In IDB group,mitochondrial matrix swelling was not obvious,and mitochondrial cristae were visible.In HDB group,mitochondrial cristae were neat and clear.Conclusions Baicalin may play an important role in the treatment of preeclampsia by reversing the trophoblast apoptosis and improving the ultrastructure of mitochondria through its regulation of XIAP expression and downregulation of Caspase-9 expression.
10.Repurposing old drugs for a new life:metformin shows promising in cancer care
Jinping LI ; Zhifeng NING ; Fuxing LIU ; Hao ZHANG
Chinese Journal of Biochemical Pharmaceutics 2016;36(8):16-21
Development of small molecule drugs is important for targeted and personalized therapy for cancers.However,it is staggering to take new compounds from the research bench to clinical trial pipelines and eventually to the clinical practice,due to the time,effort and costs.Most drugs need five years of development after discovery in the laboratory before they are ready to be tested for efficacy and safety.Compared to development of new drugs from scratch, increasing research efforts have been made to turn existing drugs to new uses to treat cancers, which may bypass years of costly work.Metformin used in cancer care is a good example of giving old drugs a new life.The activity of metformin on anti-cancer has recently drawn significant attention.Epidemiological and experimental studies have shown that metformin can cut down the incidence of cancer in diabetic patients and reduce metabolism-related cancers.Meanwhile, recent study has found metformin can induce autophagy of esophageal cancer cells by inhibiting inflammatory signaling pathway.In recent years, increasing studies have shown that metformin plays a major role in suppressing cancers via multiple mechanisms.In this mini-review,we summarize the updates of the research on metformin in cancer prevention and treatment.


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