1.Research progress on effect of ambient particulate matters on Alzheimer's disease and potential mechanisms
Lu YU ; Chihang ZHANG ; Jianshu GUO ; Dongxia FAN ; Jinzhuo ZHAO
Journal of Environmental and Occupational Medicine 2025;42(6):748-755
With the accelerating aging of world population, the prevalence and disease burden of dementia such as Alzheimer's disease is increasing annually. As one of the major risk factors for dementia, air pollution is still an urgent global concern. Studies on the association between ambient particulate matter (PM), one of the major air pollutants, and dementia, such as Alzheimer's disease, are gaining attention. This paper reviewed the current evidence of relevant epidemiological and toxicological studies to illustrate the possible mechanisms underlying the effects of PM exposure on Alzheimer's disease through inflammatory responses, oxidative stress, endocrine disruption, excitatory neurotoxicity, glial cell activation, and intestinal flora disruption, which may provide clues for mitigating the health risks of air pollution and preventing Alzheimer's disease.
2.Allergens can induce up-regulation of TLR7 expression in blood neutrophils of patients with airway allergic diseases
Jianshu WANG ; Junling WANG ; Huiyun ZHANG ; Shaoheng HE
Chinese Journal of Immunology 2024;40(9):1919-1924
Objective:To detect the expression of Toll-like receptor 7(TLR7)in blood neutrophils of patients with allergic rhi-nitis(AR),allergic asthma(AA)and allergic rhinitis combined with allergic asthma(ARA)before and after allergen challenge.Methods:A total of 44 AR,36 AA,19 ARA patients and 19 healthy control(HC)were recruited,the extracts of Artemisia siever-siana wild allergen(ASWE),house dust mite allergen(HDME)and Platanus pollen allergen(PPAE)were used to challenge periph-eral blood of HC as well as the patients,the expression of TLR7 in neutrophils was detected by flow cytometry.Results:In a resting state,compared with HC,upregulated expression of TLR7 in neutrophils in patients with airway allergy:the percentage of TLR7+neu-trophils in AR,AA,ARA patients increased 6 times,3.18 times and 6.15 times,respectively,and the mean fluorescence intensity(MFI)of TLR7 expression in neutrophil in ARA was enhanced by 24%.The results of allergen challenge tests showed that the expres-sion of neutrophils TLR7 did not change in HC subjects after the allergen challenge,whereas the expression of TLR7 in neutrophils of patients with airway allergy was upregulated after the allergens challenge.After HDME and PPAE challenge,the percentage of TLR7+neutrophils in peripheral of AR patients increased by 8.40%and 33.03%,respectively,and the MFI of TLR7 enhanced by 29.62%and 35.72%,respectively.After ASWE and PPAE challenge.The percentage of TLR7+neutrophils in peripheral of AA pa-tients increased by 59.18%and 1.06 times,respectively,and the MFI of TLR7 enhanced by 68.93%and 47.33%,respectively.How-ever,after HDME stimulation only enhanced the MFI of neutrophil TLR7 in AA patients by 66.14%;after HDME challenge,the per-centage of TLR7 and MFI in peripheral blood neutrophils of patients with ARA increased by 21.05%and 35.61%,respectively,while after PPAE challenge,the percentage of TLR7+cells in patients with ARA increased by 20.07%.Conclusion:The expression of TLR7 in blood neutrophils is increased in patients with allergic airway diseases after allergen stimulation,suggesting that allergens may be involved in the occurrence and development of allergic airway diseases by inducing TLR7 expression changes in neutrophils.
3.Molecular mechanism of adipose tissue inflammation induced by acute exposure to cooking oil fumes
Ge WANG ; Biao WU ; Jianshu GUO ; Dongxia FAN ; Lu YU ; Chihang ZHANG ; Lan MI ; Lina WANG ; Jinzhuo ZHAO
Journal of Environmental and Occupational Medicine 2024;41(4):349-355
Background Cooking oil fumes are closely related to immune response, and adipose tissue also plays an important role in immune regulation. At present, the biological effect and mechanism of inflammation of adipose tissue induced by oil fume exposure are not clear yet. Objective To investigate the inflammatory effect of different exposure duration of cooking fumes on adipose tissue in mice and explore the role of Nod-like receptor pyrin domain 3 (NLRP3)/cysteinyl aspartate specific proteinase 1 (Caspase 1)/interleukin (IL)-1β signaling pathway. Methods Forty 8-week-old female C57BL/6J mice were randomly divided into 3-day control group (CON3 group), 7-day control group (CON7 group), 3-day oil fume exposure group (COF3 group), and 7-day oil fume exposure group (COF7 group), with 10 mice in each group. The mice were exposed to oil fumes in a cooking oil fume formation and exposure equipment (COFFEE) for 20 min, followed by a 10-min pause, 1 h a day for consecutive 3 d or 7 d. General condition of mice was observed and body weight was measured every day. After exposure, blood was sampled from the eyeball. Serum levels of IL-6, IL-27, and IL-1β were detected by enzyme-linked immunosorbent assay (ELISA). The adipose tissue of mice was collected and observed after hematoxylin-eosin (HE) staining. The percentages of CD4+ and CD8+T cells in adipose tissue were detected by flow cytometry. Real-time quantitative PCR (RT-qPCR) was used to detect the expression levels of nuclear factor-κB (NF-κB), NLRP3, Caspase 1, and IL-1β in adipose tissue. Western blot was used to detect the expression levels of NLRP3, Caspase 1, and IL-1β in adipose. Results Compared with the corresponding control group, serum IL-6, IL-27, and IL-1β contents in the COF3 group and the COF7 group were significantly increased (P<0.05) except IL-6 in the COF3 group, and the levels in the COF7 group were significantly higher than those in the COF3 group (P<0.05). Vacuolar lipid droplets in adipocytes decreased, cytoplasm shrank, and inflammatory cells infiltrated in the COF7 group after HE staining. The flow cytometry results showed that the proportions of CD4+ and CD8+T cells in adipocytes of the COF3 group and the COF7 group were increased compared to the corresponding control group, with a significant increase in the COF7 group (P<0.05), and the CD4+/CD8+T ratio also significantly increased progressively in the two groups (P<0.05). The results of RT-qPCR showed that compared with the corresponding control group, the mRNA expression levels of NF-κB, NLRP3, Caspase 1, and IL-1β in adipose tissue of mice in the COF3 group and the COF7 group were significantly increased (P<0.05, P<0.01). The mRNA expression levels of mice in each exposure group gradually increased over time. The Western blot results showed that compared with the corresponding control group, the protein expressions of NLRP3 and Caspase 1 in the COF3 group were significantly increased (P<0.01), and the expression of IL-1β protein also increased but without statistical significance. The protein expressions of NLRP3, Caspase 1, and IL-1β in the COF7 group were significantly higher than those in the CON7 group (P<0.05, P<0.01). Conclusion Acute exposure to cooking oil fumes can induce significant inflammatory response in adipose tissue, and the effect gradually increases with the extension of exposure time. The mechanism of action may be related to the activation of NLRP3 inflammasome signaling pathway.
4.Effects of PM2.5 and heat/cold exposure on AKT/GLUT4 pathway in mouse skeletal muscle and white adipose tissue
Biao WU ; Dongxia FAN ; Jia ZHANG ; Jianshu GUO ; Ge WANG ; Lu YU ; Chihang ZHANG ; Jinzhuo ZHAO
Journal of Environmental and Occupational Medicine 2024;41(4):356-361
Background It is unclear if there is any combined effect of air pollutants and non-optimal temperature on metabolic syndrome, or any molecular mechanisms of related signaling pathways in the process, which requires urgent systematic research. Objective To observe the effects of combined exposure to PM2.5 and non-optimal temperature on metabolic damage at gene and protein levels in mice, and elucidate the role of related signaling pathway in crucial organs. Methods A total of 60 six-week-old male C57BL/6J mice were randomly divided into six groups: a normal temperature-filter air group (TN-FA), a normal temperature-concentrated PM2.5 group (TN-PM), a heat-filter air group (TH-FA), a heat-concentrated PM2.5 group (TH-PM), a cold-filter air group (TC-FA), and a cold-concentrated PM2.5 group (TC-PM). The Shanghai Meteorological and Environmental Animal Exposure System (Shanghai-METAS) was used to provide combined exposure settings of air types [concentrated PM2.5 and filter air (FA)] and temperatures [normal (22°C), cold (4°C), and heat (30°C)] for 4 weeks. Skeletal muscle and white adipose tissue (WAT) of the mice were sampled at the end of exposure, and transcriptomics and Western blot (WB) assay were adopted to observe selected gene and protein expression levels in the samples respectively. Results The transcriptomics results indicated that the PM2.5 exposure enhanced the number of differentially expressed genes. Specifically, 4820 genes were differentially expressed in the TN-PM mice compared to the TN-FA mice at normal temperature, and 1143 genes were differentially expressed in the Tc-PM mice compared to the Tc-FA mice in the cold environment. The phosphatidylinositol 3-kinase/protein kinase B (PI3K/AKT) signaling pathway and the endoplasmic reticulum protein processing pathway were identified as the most significant pathways in metabolic injury resulting from combined exposure to PM2.5 and non-optimal temperature exposure. The WB results showed that exposure to PM2.5 in the normal temperature and the cold environments led to a significant increase in the expression of p-AKT in WAT (P<0.01, P<0.05) and a significant decrease in the expression of GLUT4 (P<0.05, P<0.01). In skeletal muscle, exposure to PM2.5 led to a significant decrease in GLUT4 (P<0.05) in all environments, with a consistent trend of change as observed in WAT. Conclusion Cold/heat exposure might promote PM2.5-induced metabolic disorder through suppression of the AKT/GLUT4 pathway, aggravating metabolic damage.
5.Research progress in oral frailty and cognitive function impairment in elderly people
Wei JIANG ; Jianshu ZHANG ; Qing MA ; Xia LI
Chongqing Medicine 2024;53(20):3168-3172
Oral frailty and cognitive impairment are the common geriatric syndromes.There may be similar correlation mechanism between them,which are related with polypharmacy,malnutrition,inflammato-ry responses and psychosocial factors.The occurrence of oral frailty could potentially increase the risk of cog-nitive impairments,in which tooth loss,reduced chewing function,swallowing difficulties,low tongue pres-sure,and diminished oral motor function are closely correlated with cognitive impairments.Understanding the correlation between the two is conducive to prevent and interfere the healthy status in elderly people,thus in-crease their quality of life and health level.
6.A preparation strategy for protein-oriented immobilized silica magnetic beads with Spy chemistry for ligand fishing
Yi YU ; Hu JIANMING ; Ding SHENWEI ; Mei JIANFENG ; Wang XUDONG ; Zhang YANLU ; Chen JIANSHU ; Ying GUOQING
Journal of Pharmaceutical Analysis 2022;12(3):415-423
Due to the complexity of bioactive ingredients in biological samples,the screening of target proteins is a complex process.Herein,a feasible strategy for directing protein immobilization on silica magnetic beads for ligand fishing based on SpyTag/SpyCatcher(ST/SC)-mediated anchoring is presented.Carboxyl functional groups on the surface of silica-coated magnetic beads(SMBs)were coupled with SC using the 1-ethyl-3-(3-dimethylaminopropyl)carbodiimide hydrochloride/N-hydroxysulfosuccinimide method,named SC-SMBs.The green fluorescent protein(GFP),as the capturing protein model,was ST-labeled and anchored at a specific orientation onto the surface of SC-SMBs directly from relevant cell lysates via ST/SC self-ligation.The characteristics of the SC-SMBs were studied via electron microscopy,energy dispersive spectroscopy,and Fourier transform infrared spectroscopy.The spontaneity and site-specificity of this unique reaction were confirmed via electrophoresis and fluorescence analyses.Although the alkaline stability of ST-GFP-ligated SC-SMBs was not ideal,the formed isopeptide bond was unbreakable under acidic conditions(0.05 M glycine-HCl buffer,pH 1-6)for 2 h,under 20%ethanol solution within 7 days,and at most temperatures.We,therefore,present a simple and universal strategy for the preparation of diverse protein-functionalized SMBs for ligand fishing,prompting its usage on drug screening and target finding.
7.Application analysis of quantitative fecal immunochemical test in opportunistic screening of colorectal cancer
Daiyi ZHANG ; Yan XU ; Zhengyan WU ; Xiang ZHENG ; Jianshu YANG ; Jianhong PU ; Su YAN
Chinese Journal of Digestion 2022;42(10):701-707
Objective:To analyze and evaluate the application of quantitative fecal immunochemical test(FIT) in opportunistic screening of colorectal cancer in asymptomatic population undergoing health checkups.Methods:From January 1, 2018 to December 31, 2021, at the Health Management Center of the First Affiliated Hospital of Soochow University, 53 319 subjects who underwent routine health checkups and with quantitative FIT opportunistic screening for colorectal cancer were selected. Those with positive quantitative FIT results and received colonoscopy were enrolled in the FIT positive group, and those with negative quantitative FIT results and received colonoscopy were enrolled in the FIT negative group. The participation rate and positive rate of quantitative FIT were analyzed. The results of colonoscopy and pathological findings were taken as the gold standard, including normal, non-polyposis lesions, polyposis (hyperplastic and(or) inflammatory polyps, non-advanced adenoma, advanced adenoma), and colorectal cancer, the detection rates of various lesions of the FIT positive and negative groups, the quantitative FIT measurement value of subjects, and the sensitivity and negative predictive value of quantitative FIT for colorectal cancer and advanced adenoma were analyzed. The receiver operating characteristic curve (ROC) was drawn and the area under the curve (AUC) was calculated, the screening efficacy of quantitative FIT for colorectal cancer and advanced adenoma was evaluated. Chi-square test or Fisher exact probability method and Wilcoxon rank sum test were used for statistical analysis.Results:A total of 51 420 cases had completed quantitative FIT, and the total participation rate was 96.44% (51 420/53 319). Quantitative FIT was positive in 2 483 cases (4.83%). The participation rate of colonoscopy in FIT positive group was 26.22% (651/2 483), of which 540 cases were enrolled in FIT positive group. The colonoscopy participation rate of FIT negative group was 1.18% (576/48 937), of which 523 cases were enrolled in the FIT negative group. The detection rates of colorectal cancer and advanced adenoma in FIT positive group were both higher than those of the FIT negative group(3.9%, 21/540 vs. 0, 0/523; 16.1%, 87/540 vs. 3.3%, 17/523), and the differences were statistically significant(Fisher exact probability method and χ2=49.79; both P<0.001). Populations with quantitative FIT values from high to low were those with colorectal cancers, advanced adenomas, non-polyp lesions, non-advanced adenomas, normal, and hyperplastic and (or) inflammatory polyps (1 052.0 ng/mL(390.5 ng/mL, 3 058.0 ng/mL); 294.5 ng/mL (116.8 ng/mL, 951.8 ng/mL); 131.5 ng/mL (10.5 ng/mL, 327.3 ng/mL); 97.0 ng/mL (11.0 ng/mL, 238.0 ng/mL); 20.0 ng/mL (0.0 ng/mL, 175.3 ng/mL); 14.0 ng/mL (0.0 ng/mL, 171.0 ng/mL)), and the difference was statistically significant( H=120.53, P<0.001). The sensitivities(95% confidence interval (95% CI)) of quantitative FIT in colorectal cancer and advanced adenoma were 100.0%(80.8% to 100.0%) and 83.6%(74.8% to 89.9%), respectively. The negative predictive values (95% CI) were 100.0%(99.1% to 100.0%) and 96.7%(94.7% to 98.0%), respectively. The results of ROC analysis showed that the AUCs(95% CI) of quantitative FIT in colorectal cancer and advanced adenoma were 0.874(0.820 to 0.928) and 0.723(0.675 to 0.770), respectively. Conclusions:In this study, the participation rate of quantitative FIT is high. More patients with advanced adenomas and colorectal cancers are found in the high risk popolation with positive quantitative FIT. Quantitative FIT has a good sensitivity and a negative predictive value for colorectal cancer and advanced adenoma. Therefore, positive quantitative FIT-colonoscopies sequential screening should be advocated in population undergoing health checkups for colorectal cancer screening, and it may be applicable to large-scale population screening in China.
8.Application of coding navigation index and specialized placement scheme for surgical instruments
Jianshu CAI ; Zhou LI ; Luping LI ; Hai′ou QI ; Chao ZHANG ; Xiaoling HUANG
Chinese Journal of Hospital Administration 2021;37(10):860-863
As the operation volume in hospitals is increasing year by year, surgical instruments are widely used, which pose a great challenge to the daily management of surgical instruments. The authors investigated the existing problems which occurred in the management of surgical instruments, and came out with instruments coding navigation index and specialized placement scheme for the operating room as solutions. The specific measures included dividing sterile items into specialized categories, setting cabinets respectively for specialized and general subjects, building equipment coding and identification, establishing surgical instruments navigation index and carrying out training program, to serve as reference for efficient and fine management of surgical instruments.
9.Two-in-one strategy: a remineralizing and anti-adhesive coating against demineralized enamel.
Ailin HOU ; Jun LUO ; Min ZHANG ; Jianshu LI ; Wenlin CHU ; Kunneng LIANG ; Jiaojiao YANG ; Jiyao LI
International Journal of Oral Science 2020;12(1):27-27
Tooth enamel is prone to be attacked by injurious factors, leading to a de/remineralization imbalance. To repair demineralized enamel and prevent pulp inflammation caused by biofilm accumulation, measures are needed to promote remineralization and inhibit bacterial adhesion on the tooth surface. An innovative material, poly (aspartic acid)-polyethylene glycol (PASP-PEG), was designed and synthesized to construct a mineralizing and anti-adhesive surface that could be applied to repair demineralized enamel. A cytotoxicity assay revealed the low cytotoxicity of synthesized PASP-PEG. Adsorption results demonstrated that PASP-PEG possesses a high binding affinity to the hydroxyapatite (HA)/tooth surface. In vitro experiments and scanning electron microscopy (SEM) demonstrated a strong capacity of PASP-PEG to induce in situ remineralization and direct the oriented growth of apatite nanocrystals. Energy dispersive X-ray spectroscopy (EDS), X-ray diffraction analysis (XRD) and Vickers hardness tests demonstrated that minerals induced by PASP-PEG were consistent with healthy enamel in Ca/P ratio, crystal form and surface micro-hardness. Contact angle tests and bacterial adhesion experiments demonstrated that PASP-PEG yielded a strong anti-adhesive effect. In summary, PASP-PEG could achieve dual effects for enamel repair and anti-adhesion of bacteria, thereby widening its application in enamel repair.
10.Stimulating effects of conjunctival sac implants after eye enucleation on orbital bone tissue in rabbits
Xiaoying LIU ; Zhulin HU ; Jianshu KANG ; Hong ZHANG
Chinese Journal of Experimental Ophthalmology 2018;36(10):761-766
Objective To investigate the stimulating effects of conjunctival sac implants following eye enucleation on orbital bone tissue in rabbits model.Methods Eighty 1-month-old New Zealand rabbits were randomly divided into normal control group,only eyeball enucleation group,2-week interval group and 4-week interval group.The right eyeballs were enucleated in the rabbits in the only eyeball enucleation group,2-week interval group and 4-week interval group,and conjunctival sac implants were placed intraoperatively.Then a larger implant was replaced in a 2-week interval or 4-week interval in different groups,respectively.Spiral CT scan was used to evaluate the orbital bone development with aging.The peripheral blood of 3 ml was collected in the rabbits for the detection of osteocalcin and alkaline phosphatase using osteocalcin test kit (N-MID Osteocalcin) and alkaline phosphatase assay kit (NPP substrate-AMP buffer method),respectively.The animals were sacrificed at 3 months after operation for the histopathological examination of orbital bone tissue.Results The operation was successful in all the rabbits and no infection occurred after operation.The variance of orbital bone CT value was obvious in all the rabbits.The intercalated osteocalcin concentration was (48.55 ± 7.99),(59.80 ± 2.96),(57.94 ± 5.20) and (55.96 ± 3.22) μg/L and the alkaline phosphatase concentration was (284.66± 132.69),(232.96±54.39),(232.40± 118.23),(284.20± 130.41) μg/L in the normal control group,only eyeball enucleation group,2-week interval group and 4-week interval group,respectively,showing insignificant differences among the four groups (F =2.710,0.281,both at P > 0.05).Similar pathological findings were in the 2-week interval group and 4-week interval group,such as no obvious orbital bone malformations,weak bone absorption and few bone osteoclasts under the optical microscope.Varying degrees of orbital deformities and bone tissue absorption were found in the only eyeball enucleation group.No orbital bone developing abnormality was seen in the normal control group and the left eyes in various groups under the optical microscope.Conclusions Compared with the only eyeball enucleated eyes,the orbital bone tissue has a well developed process in conjunctiva sac implant eyes following eyeball enucleation.Conjunctiva sac implant is an effective method to stimulate orbital growth and orbital volume increasing.

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