1.Research and Application of Nanozymes in Disease Treatment
Hang LIU ; Yi-Xuan LI ; Zi-Tong QIN ; Jia-Wen ZHAO ; Yue-Jie ZHOU ; Xiao-Fei LIU
Progress in Biochemistry and Biophysics 2024;51(3):575-589
Nanozyme is novel nanoparticle with enzyme-like activity, which can be classified into peroxidase-like nanozyme, catalase-like nanozyme, superoxide dismutase-like nanozyme, oxidase-like nanozyme and hydrolase-like nanozyme according to the type of reaction they catalyze. Since researchers first discovered Fe3O4 nanoparticles with peroxidase-like activity in 2007, a variety of nanoparticles have been successively found to have catalytic activity and applied in bioassays, inflammation control, antioxidant damage and tumor therapy, playing a key role in disease diagnosis and treatment. We summarize the use of nanozymes with different classes of enzymatic activity in the diagnosis and treatment of diseases and describe the main factors influencing nanozyme activity. A Mn-based peroxidase-like nanozyme that induces the reduction of glutathione in tumors to produce glutathione disulfide and Mn2+, which induces the production of reative oxygen species (ROS) in tumor cells by breaking down H2O2 in physiological media through Fenton-like action, thereby inhibiting tumor cell growth. To address the limitation of tumor tissue hypoxia during photodynamic tumor therapy, the effect of photodynamic therapy is significantly enhanced by using hydrogen peroxide nanozymes to catalyze the production of oxygen from H2O2. In pathological states, where excess superoxide radicals are produced in the body, superoxide dismutase-like nanozymes are able to selectively regulate intracellular ROS levels, thereby protecting normal cells and slowing down the degradation of cellular function. Based on this principle, an engineered nanosponge has been designed to rapidly scavenge free radicals and deliver oxygen in time to save nerve cells before thrombolysis. Starvation therapy, in which glucose oxidase catalyzes the hydrolysis of glucose to gluconic acid and hydrogen peroxide in cancer cells with the involvement of oxygen, attenuates glycolysis and the production of intermediate metabolites such as nucleotides, lipids and amino acids, was used to synthesize an oxidase-like nanozyme that achieved effective inhibition of tumor growth. Furthermore, by fine-tuning the Lewis acidity of the metal cluster to improve the intrinsic activity of the hydrolase nanozyme and providing a shortened ligand length to increase the density of its active site, a hydrolase-like nanozyme was successfully synthesized that is capable of cleaving phosphate bonds, amide bonds, glycosidic bonds and even biofilms with high efficiency in hydrolyzing the substrate. All these effects depend on the size, morphology, composition, surface modification and environmental media of the nanozyme, which are important aspects to consider in order to improve the catalytic efficiency of the nanozyme and have important implications for the development of nanozyme. Although some progress has been made in the research of nanozymes in disease treatment and diagnosis, there are still some problems, for example, the catalytic rate of nanozymes is still difficult to reach the level of natural enzymes in vivo, and the toxic effects of some heavy metal nanozymes material itself. Therefore, the construction of nanozyme systems with multiple functions, good biocompatibility and high targeting efficiency, and their large-scale application in diagnosis and treatment is still an urgent problem to be solved. (1) To improve the selectivity and specificity of nanozymes. By using antibody coupling, the nanoparticles are able to specifically bind to antigens that are overexpressed in certain cancer cells. It also significantly improves cellular internalization through antigen-mediated endocytosis and enhances the enrichment of nanozymes in target tissues, thereby improving targeting during tumor therapy. Some exogenous stimuli such as laser and ultrasound are used as triggers to control the activation of nanozymes and achieve specific activation of nanozyme. (2) To explore more practical and safer nanozymes and their catalytic mechanisms: biocompatible, clinically proven material molecules can be used for the synthesis of nanoparticles. (3) To solve the problem of its standardization and promote the large-scale clinical application of nanozymes in biomonitoring. Thus, it can go out of the laboratory and face the market to serve human health in more fields, which is one of the future trends of nanozyme development.
2.Blueberry, blackberry, and blackcurrant differentially affect plasma lipids and pro-inflammatory markers in diet-induced obesity mice.
Bohkyung KIM ; Sang Gil LEE ; Young Ki PARK ; Chai Siah KU ; Tho X PHAM ; Casey J WEGNER ; Yue YANG ; Sung I KOO ; Ock K CHUN ; Ji Young LEE
Nutrition Research and Practice 2016;10(5):494-500
BACKGROUND/OBJECTIVES: Evidence indicates that berry anthocyanins are anti-atherogenic, antioxidant, and anti-inflammatory. However, berries differ vastly in their anthocyanin composition and thus potentially in their biological and metabolic effects. The present study compared hypolipidemic, antioxidant, and anti-inflammatory properties of blueberry (BB), blackberry (BK), and blackcurrant (BC) in a diet-induced obesity (DIO) mouse model. MATERIALS/METHODS: Male C57BL/6J mice were fed a high fat (HF; 35% fat, w/w) control diet or a HF diet supplemented with freeze-dried 5% BB, 6.3% BK or 5.7% BC for 12 weeks (10 mice/group) to achieve the same total anthocyanin content in each diet. Plasma lipids, antioxidant status and pro-inflammatory cytokines were measured. The expression of genes involved in antioxidant defense, inflammation, and lipid metabolism was determined in the liver, epididymal adipose tissue, proximal intestine, and skeletal muscle. Histological analysis was performed to identify crown-like structure (CLS) in epididymal fat pads to determine macrophage infiltration. RESULTS: No differences were noted between the control and any berry-fed groups in plasma levels of liver enzymes, insulin, glucose, ferric reducing antioxidant power, superoxide dismutase, and tumor necrosis factor α. However, BK significantly lowered plasma triglyceride compared with the HF control and other berries, whereas BC significantly reduced F4/80 mRNA and the number of CLS in the epididymal fat pad, indicative of less macrophage infiltration. CONCLUSIONS: The present study provides evidence that BB, BK and BC with varying anthocyanin composition differentially affect plasma lipids and adipose macrophage infiltration in DIO mice, but with no differences in their antioxidant capacity and anti-inflammatory potential.
Adipose Tissue
;
Animals
;
Anthocyanins
;
Blueberry Plant*
;
Cytokines
;
Diet
;
Fruit
;
Glucose
;
Humans
;
Inflammation
;
Insulin
;
Intestines
;
Lipid Metabolism
;
Liver
;
Macrophages
;
Male
;
Mice*
;
Muscle, Skeletal
;
Obesity*
;
Plasma*
;
RNA, Messenger
;
Rubus*
;
Superoxide Dismutase
;
Triglycerides
;
Tumor Necrosis Factor-alpha
3.Complications of upper gastrointestinal foreign body in children and related risk factors.
Yue-Sheng WANG ; Jing ZHANG ; Xiao-Qin LI ; Zhi-Dan YU ; Fang ZHOU
Chinese Journal of Contemporary Pediatrics 2020;22(7):774-779
OBJECTIVE:
To study the complications of upper gastrointestinal foreign body in children and related risk factors.
METHODS:
Clinical data were collected from 772 children with upper gastrointestinal foreign bodies who were treated at the outpatient service or were hospitalized from January 2014 to December 2018. A multivariate logistic regression analysis was used to investigate the risk factors for the development of complications in children with upper gastrointestinal foreign bodies.
RESILTS:
The upper gastrointestinal foreign bodies were taken out by electronic endoscopy for the 772 children. There were 414 boys and 358 girls, with a median age of 2.8 years. Children under 3 years old accounted for 59.5%. The foreign bodies were mainly observed in the esophagus (57.5%) and the stomach (28.9%), with a retention time of ≤24 hours in 465 children (60.2%) and >24 hours in 307 children (39.8%). The types of upper gastrointestinal foreign bodies mainly included round metal foreign bodies (37.2%), long foreign bodies (24.7%), sharp foreign bodies (16.2%), batteries (14.4%), corrosive substances (4.8%), and magnets (2.7%). As for the severity of complications, 47.7% (368 children) had mild complications, 12.7% (98 children) had serious complications, and 39.6% (306 children) had no complications. The logistic regression analysis showed that an age of <3 years, underlying diseases, location of foreign body, type of foreign body, and a retention time of >24 hours were risk factors for the development of complications in these children (OR=2.141, 7.373, 6.658, 8.892, and 6.376 respectively, P<0.05).
CONCLUSIONS
An understanding of the above high-risk factors for the complications of upper gastrointestinal foreign bodies is helpful to choose appropriate intervention methods and thus reduce the incidence of serious complications.
Child, Preschool
;
Endoscopy, Gastrointestinal
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Esophagus
;
Female
;
Foreign Bodies
;
Humans
;
Male
;
Retrospective Studies
;
Risk Factors
;
Upper Gastrointestinal Tract
4.Risk factors for delayed bleeding after intestinal polypectomy in children.
Yue-Sheng WANG ; Jing ZHANG ; Fu-Min XUE ; Jing YU ; Xiao-Qin LI
Chinese Journal of Contemporary Pediatrics 2024;26(1):48-53
OBJECTIVES:
To investigate the clinical characteristics and risk factors of delayed bleeding after intestinal polypectomy in children, and to provide a theoretical basis for clinical surgical intervention of intestinal polyps.
METHODS:
A retrospective analysis was conducted on the clinical data of 2 456 children with intestinal polyps who underwent endoscopic high-frequency electrocoagulation loop resection in the Endoscopy Center of Children's Hospital Affiliated to Zhengzhou University from January 2014 to December 2021. According to the presence or absence of delayed bleeding after surgery, they were divided into bleeding group with 79 children and non-bleeding group with 2 377 children. A multivariate logistic regression analysis was used to investigate the risk factors for delayed bleeding. The receiver operating characteristic (ROC) curve was used to investigate the value of various indicators in predicting delayed bleeding.
RESULTS:
Of all 2 456 children, 79 (3.22%) experienced delayed bleeding, among whom 5 children with severe delayed bleeding underwent emergency colonoscopy for hemostasis and 74 received conservative treatment, and successful hemostasis was achieved for all children. There were significant differences between the bleeding and non-bleeding groups in age, body mass index, constipation rate, location of lesion, time of endoscopic procedure, resection method (P<0.05). Children with a diameter of polyps of 6-10 mm and >20 mm were more likely to develop delayed bleeding after resection (P<0.05). The multivariate logistic regression analysis showed that endoscopic operation time, polyp diameter, and resection method were significantly associated with delayed bleeding (P<0.05). The ROC curve analysis showed that the endoscopic operation time, polyp diameter, and resection method had a good value in predicting delayed bleeding after intestinal polypectomy, with an area under the ROC curve of 0.706, 0.688, and 0.627, respectively.
CONCLUSIONS
Endoscopic high-frequency electrocoagulation loop resection has a lower incidence of delayed bleeding in children with intestinal polyps, and the endoscopic operation time, polyp diameter, and resection method are closely associated with the occurrence of postoperative delayed bleeding.
Child
;
Humans
;
Retrospective Studies
;
Intestines
;
Hemorrhage
;
Intestinal Polyps/surgery*
;
Risk Factors
5.Activity of curcumin against human cytomegalovirus infection in vitro.
Xiang DING ; Jirong YUE ; Birong DONG ; Leng SEAN X
Journal of Biomedical Engineering 2022;39(6):1158-1164
This study aimed to investigate the effect of curcumin (Cur) against human cytomegalovirus (HCMV) in vitro. Human embryonic lung fibroblasts were cultured in vitro. The tetrazolium salt (MTS) method was used to detect the effects of Cur on cell viability. The cells were divided into control group, HCMV group, HCMV + (PFA) group and HCMV + Cur group in this study. The cytopathic effect (CPE) of each group was observed by plaque test, then the copy number of HCMV DNA in each group was detected by quantitative polymerase chain reaction (qPCR), and the expression of HCMV proteins in different sequence was detected by Western blot. The results showed that when the concentration of Cur was not higher than 15 μmol/L, there was no significant change in cell growth and viability in the Cur group compared with the control group (P>0.05). After the cells were infected by HCMV for 5 d, the cells began to show CPE, and the number of plaques increased with time. Pretreatment with Cur significantly reduced CPE in a dose-dependent manner. After the cells were infected by HCMV, the DNA copy number and protein expression gradually increased in a time-dependent manner. Pretreatment with Cur significantly inhibited HCMV DNA copies and downregulate HCMV protein expression levels in a concentration-dependent manner, and the difference was statistically significant (P<0.05). In conclusion, Cur may exert anti-HCMV activity by inhibiting the replication of HCMV DNA and down-regulating the expression levels of different sequence proteins of HCMV. This study provides a new experimental basis for the development of anti-HCMV infectious drugs.
Humans
;
Curcumin/therapeutic use*
;
Cytomegalovirus/genetics*
;
Cytomegalovirus Infections/drug therapy*
;
Plaque, Atherosclerotic
6.Efficacy of polyetheretherketone rod hybrid surgery in preventing proximal junctional failure after adult spinal deformity surgery.
Y ZHAO ; B Y XU ; L T QI ; L YUE ; R L ZHU ; Z R YU ; X D YI ; C D LI
Chinese Journal of Surgery 2023;61(8):656-665
Objective: To investigate the clinical outcome and preventive effect of polyetheretherketone(PEEK) rod hybrid surgery on proximal junction failure(PJF) after long-segment fusion of adult spinal deformity. Methods: A retrospective study was conducted to analyze patients with degenerative scoliosis/kyphosis who underwent long-segment decompression and fusion surgery at Department of Orthopedics, Peking University First Hospital from January 2017 to December 2021. A total of 75 patients were included in the study, including 14 males and 61 females, aged (67.2±6.8)years (range:55 to 84 years). According to the operation method chosen by the patients, the patients were divided into PEEK rod hybrid group (20 cases) and traditional titanium rod group (55 cases). The general information of the patients was collected, and the coronal and sagittal parameters of the spine were measured before operation, at 1 month after operation, and at the last follow-up. The clinical effect of surgery was judged by the visual analogue scale (VAS) and Oswestry disability index (ODI). Whether proximal junctional kyphosis (PJK) and PJF occurred during the follow-up and the time of occurrence were recorded. Comparisons between groups were performed using independent sample t test, Mann-Whitney U test, χ2 test and Fisher's exact probability method. The data before and after surgery in the same group were compared using the paired sample t test and the Wilcoxon test. Results: There were no significant differences in age, gender, body mass index, bone mineral density, distal instrumented vertebrae, surgical segments, osteotomy method, operation time, and intraoperative bleeding between the two groups (all P>0.05). The follow-up time of the PEEK rod group was shorter(M(IQR)16.5(4.8) vs. 25.0(12.0),Z=-4.230,P<0.01). There were no significant differences in coronal, sagittal parameters, VAS and ODI between the two groups before operation (all P>0.05). Postoperative coronal Cobb angle, pelvic incidence, pelvic tilt, sacral slope, lumbar lordosis, thoracic kyphosis, sagittal vertical axis (SVA), VAS and ODI were significantly improved in both groups(all P<0.05). At the last follow-up, the SVA of the PEEK rod hybrid group was(3.74±2.40)cm, which was significantly lower than that of the titanium rod group (6.28±4.06)cm (t'=-3.318, P=0.002). At the last follow-up, the ODI of the PEEK rod hybrid group was 30.7±6.1, significantly better than the titanium rod group 39.3±17.2(t=-3.203, P=0.046). PJK occurred in 2 patients (10.0%) in the PEEK rod hybrid group, and no PJF phenomenon was observed. In the titanium rod group, 18 patients (32.7%) developed PJK, and 11 patients (20.0%) developed PJF. There was a statistically significant difference in the incidence of PJF between the PEEK rod hybrid group and the titanium rod group (P=0.031). Conclusions: PEEK rod hybrid surgery can achieve good clinical results in the treatment of adult spinal deformities. Compared with traditional titanium rod surgery, it can significantly reduce the incidence of postoperative PJF and improve the clinical function of patients.
Male
;
Female
;
Animals
;
Humans
;
Adult
;
Retrospective Studies
;
Titanium
;
Kyphosis/etiology*
;
Sacrum
;
Osteotomy/adverse effects*
;
Spinal Fusion/methods*
;
Lumbar Vertebrae
;
Treatment Outcome
;
Postoperative Complications/epidemiology*
7.The correlation between No. 6 and No. 14v lymph node metastasis and the value of dissecting these lymph nodes in radical gastrectomy.
Q C YANG ; H K ZHOU ; C YUE ; W D WANG ; R Q GAO ; Z C MO ; P P JI ; J P WEI ; X S YANG ; P F YU ; X H LI ; G JI
Chinese Journal of Gastrointestinal Surgery 2023;26(1):38-43
Radical gastrectomy with D2 lymphadenectomy has been widely performed as the standard surgery for patients with gastric cancer in major medical centers in China and abroad. However, the exact extent of lymph node dissection is still controversial. In the latest version of the Japanese Gastric Cancer Treatment Guidelines, No. 14v lymph nodes (along the root of the superior mesenteric vein) are again defined as loco-regional lymph nodes, and it is clarified that distal gastric cancer presenting with infra-pyloric regional lymph node (No.6) metastasis is recommended for D2+ superior mesenteric vein (No. 14v) lymph node dissection. To explore the relevance and clinical significance of No.6 and No.14v lymphadenectomy in radical gastric cancer surgery, a review of the national and international literature revealed that No.6 lymph node metastasis was associated with No.14v lymph node metastasis, that No.6 lymph node status was a valid predictor of No.14v lymph node negative status and false negative rate, and that for gastric cancer patients with No. 14v lymph node negative and No.6 lymph node positive, the dissection of No.14v lymph node may also have some significance. The addition of No. 14v lymph node dissection in radical gastrectomy is safe, but it is more important to distinguish the patients who can benefit from it. Professor Liang Han of Tianjin Medical University Cancer Hospital is currently leading a multicenter, large-sample, prospective clinical trial (NCT02272894) in China, which is expected to provide higher level evidence for the clinical significance of lymph node dissection in No.14v.
Humans
;
Stomach Neoplasms/pathology*
;
Lymphatic Metastasis/pathology*
;
Prospective Studies
;
Retrospective Studies
;
Lymph Nodes/pathology*
;
Lymph Node Excision
;
Gastrectomy
;
Multicenter Studies as Topic
8.Trichinella spiralis: RNAi-mediated silencing of serine protease results in reduction of intrusion, development and fecundity
Yang, D.Q. ; Zeng, J. ; Sun, X.Y. ; Yue, X. ; Hu, C.X. ; Jiang, P. ; Liu, R.D. ; Cui, J. ; Wang, Z.Q.
Tropical Biomedicine 2020;37(No.4):932-946
In previous studies, a Trichinella spiralis serine protease (TsSP) was identified in
excretion/secretion (ES) products from intestinal infective L1 larvae (IIL1) using
immunoproteomics. The complete cDNA sequence of TsSP gene was 1372 bp, which encoded
429 amino acids with 47.55 kDa. The TsSP was transcribed and expressed at all T. spiralis life
cycle phases, as well as mainly located at the cuticle and stichosome of the parasitic nematode.
Recombinant TsSP bind to intestinal epithelial cells (IEC) and promoted larva invasion, however,
its exact function in invasion, development and reproduction are still unknown. The aim of
this study was to confirm the biological function of TsSP during T. spiralis invasion and
growth using RNA interference (RNAi) technology. The results showed that on 1 day after
electroporation using 2.5 µM siRNA156, TsSP mRNA and protein expression of muscle larvae
(ML) was suppressed by 48.35 and 59.98%, respectively. Meanwhile, silencing of TsSP gene
by RNAi resulted in a 61.38% decrease of serine protease activity of ML ES proteins, and a
significant reduction of the in vitro and in vivo invasive capacity of IIL1 to intrude into the
IEC monolayer and intestinal mucosa. When mice were infected with siRNA 156-transfected
larvae, adult worm and muscle larva burdens were decreased by 58.85 and 60.48%,
respectively. Moreover, intestinal worm growth and female fecundity were evidently inhibited
after TsSP gene was knockdown, it was demonstrated that intestinal adults became smaller
and the in vitro newborn larval yield of females obviously declined compared with the
control siRNA group. The results indicated that knockdown of TsSP gene by RNAi significantly
reduced the TsSP expression and enzymatic activity, impaired larvae intrusion and growth,
and lowered the female reproductive capacity, further verified that TsSP might participate in
diverse processes of T. spiralis life cycle, it will be a new prospective candidate molecular
target of anti-Trichinella vaccines.
9.Prevalence of HIV infection and syphilis and related behaviors in clients in Ya'an of Sichuan province.
P L LI ; D M LI ; L GE ; X YUE ; L LIANG ; W GUO ; Y CUI
Chinese Journal of Epidemiology 2018;39(3):329-332
Objective: To understand the prevalence of HIV infection and syphilis in clients in Ya'an of Sichuan province. Methods: A survey was conducted in clients recruited through snowball method in Ya'an of Sichuan from April 2014 to December 2015. The information of the clients, including basic demography characteristics, AIDS knowledge awareness, high-risk behaviors and others, were collected through face-to-face interviews. Blood sample (5 ml) was taken from each client to test antibodies against HIV and syphilis. Statistical software SPSS 18.0 was used for data analysis. Results: Among the 708 clients, the constituent ratio of those aged ≥50 years was 51.27% (363/708), those in Han ethnic group was 99.72% (706/708), those with junior high school educational level or below was 90.11% (638/708), those who got married or cohabitated with others was 74.15% (525/708), and those who used condoms at each sex was 27.40% (194/708). Seven HIV positive cases were detected and 4 cases were aged ≥50 years. Seven syphilis cases were detected and all the cases were aged ≥50 year. No HIV-syphilis co-infection case was detected. The prevalence of HIV infection and syphilis were all 0.99% (95%CI: 0.30%-1.70%). Results from the multivariate logistic regression analysis showed that the clients who had their first commercial sex behavior at age <30 years (OR=6.61, 95%CI: 1.09-40.18) would have higher HIV positive rate. Conclusion: The rate of condom use was low in the clients in Ya'an and they didn't pay enough attention to their self-protection in sexual activities. Especially the clients aged ≥50 years were with low educational level and had high risk commercial sexual behaviors for HIV infection and syphilis. Close attention needs to be paid to them.
Aged
;
Coinfection/epidemiology*
;
Condoms/statistics & numerical data*
;
HIV Infections/ethnology*
;
Humans
;
Middle Aged
;
Prevalence
;
Risk Factors
;
Sex Work
;
Sexual Behavior/ethnology*
;
Surveys and Questionnaires
;
Syphilis/ethnology*
10.Reduced Firing of Nucleus Accumbens Parvalbumin Interneurons Impairs Risk Avoidance in DISC1 Transgenic Mice.
Xinyi ZHOU ; Bifeng WU ; Wenhao LIU ; Qian XIAO ; Wei HE ; Ying ZHOU ; Pengfei WEI ; Xu ZHANG ; Yue LIU ; Jie WANG ; Jufang HE ; Zhigang ZHANG ; Weidong LI ; Liping WANG ; Jie TU
Neuroscience Bulletin 2021;37(9):1325-1338
A strong animal survival instinct is to approach objects and situations that are of benefit and to avoid risk. In humans, a large proportion of mental disorders are accompanied by impairments in risk avoidance. One of the most important genes involved in mental disorders is disrupted-in-schizophrenia-1 (DISC1), and animal models in which this gene has some level of dysfunction show emotion-related impairments. However, it is not known whether DISC1 mouse models have an impairment in avoiding potential risks. In the present study, we used DISC1-N terminal truncation (DISC1-N
Animals
;
Interneurons/metabolism*
;
Mice
;
Mice, Transgenic
;
Nerve Tissue Proteins/metabolism*
;
Neurons/metabolism*
;
Nucleus Accumbens/metabolism*
;
Parvalbumins/metabolism*