Intracellular overexpression of cytoglobin (Cygb) has been shown to reduce extracellular matrix deposition and promote liver fibrosis recovery, but its mechanism is not yet clear. This study constructed and expressed a fusion protein (TAT-Cygb) of cell penetrating peptide TAT and Cygb, to investigate the effect of fusion protein TAT-Cygb on regulating hepatic stellate cells (HSCs) ferroptosis. Cultured human hepatic stellate cells line (LX2) were treated with TAT-Cygb and erastin in vitro, respectively. The effects of ferroptosis phenotype in LX2 cells induced by TAT-Cygb, including cell viability, cell morphology, iron ion (Fe²⁺) content, lipid peroxidation product levels, and antioxidant system indicators, were investigated using trypan blue staining, transmission electron microscopy, Prussian blue staining, and reagent kits detection. After co-treatment with TAT-Cygb and ferrostain-1, the levels of Fe²⁺, reactive oxygen species (ROS), malondialdehyde (MDA), 4-hydroxynonenal (4-HNE), nicotinamide adenine dinucleotide phosphate (NADPH) and glutathione (GSH) were measured by reagent kits. The protein expression levels of alpha smooth actin (α-SMA), collagen I and fibronectin were detected by Western blot, and the protein expression level of epidermal growth factor receptor (EGFR) and desmin relevant to fibrosis were observed by immunofluorescence. The results showed that TAT-Cygb could significantly reduce the viability of LX2 cells and trigger events relevant to ferroptosis, including promoting intracellular Fe²⁺ accumulation, and inducing mitochondrial morphological changes, and intensifying lipid peroxidation products accumulation, and decreasing the level of antioxidant indexes, which played a similar role as erastin; Fer-1 significantly weakened the increase in Fe²⁺, ROS, MDA, 4-HNE levels induced by TAT-Cygb, as well as the decrease in NADPH and GSH levels, while also weakening the TAT-Cygb-induced over-expression levels of α-SMA, collagen I and fibronectin, and TAT-Cygb-induced under-expression levels of EGFR and desmin. This cellular level study indicated that TAT-Cygb can induce ferroptosis of activated HSCs. This study revealed the potential mechanism of TAT-Cygb anti-liver fibrosis, and provided the experimental basis for further research on the molecular mechanism of TAT-Cygb realizing biological function by regulating the ferroptosis pathway.

In the past few decades,supercritical fluid chromatography(SFC)as a supplement to liquid chromatography(LC)separation technology has attracted people's interest,especially in the combination of SFC and mass spectrometry(MS),which has shown important application prospects in metabolomics,lipidomics,and other fields.Compared to the interface of LC-MS,the interface of SFC-MS presents some unique challenges that require special solutions to be designed.This article categorizes and summarizes the existing interfaces used for SFC-MS,focuses on the impact of different interface designs on detection performance,provides the applicable characteristics of different types of interfaces,and finally briefly introduces the application progress of SFC-MS in different fields.

Background: and Purpose The relationships among interleukin (IL)-10 levels, anxiety, and cognitive status after stroke remain controversial. We aimed to determine the associations of serum IL-10 levels with poststroke anxiety (PSA) and poststroke cognitive impairment (PSCI). Methods: We recruited 350 patients with stroke, of whom only 151 completed a 1-month follow-up assessment. The Mini Mental State Examination (MMSE) and Hamilton Anxiety Scale (HAMA) were used to assess the cognitive status and anxiety, respectively. Serum IL-10 levels were measured within 24 hours of admission. Results: IL-10 levels were significantly lower in the PSA group than in the non-PSA group, and they were negatively associated with HAMA scores (r=-0.371, p<0.001). After adjusting for all potential confounders, IL-10 levels remained an independent predictor of PSA (odds ratio=0.471, 95% confidence interval=0.237–0.936, p=0.032). IL-10 levels were strongly correlated with behavior during interviews, psychic anxiety, and somatic anxiety. Patients without PSCI had higher IL-10 levels were higher in non-PSCI patients than in PSCI patients, and they were positively associated with MMSE scores in the bivariate correlation analysis (r=0.169, p=0.038), and also with memory capacity, naming ability, and copying capacity.However, IL-10 did not predict PSCI in the univariable or multivariable logistic regression. Conclusions Low IL-10 levels were associated with increased risks of PSA and PSCI at a 1-month follow-up after stroke. Serum IL-10 levels may therefore be helpful in predicting PSA.

Objective: To describe the epidemiological distribution characteristics of peripheral blood mosaic chromosomal alteration (mCA) in community adults aged 30-79 years in 10 regions of China. Methods: A total of 100 297 participants with complete baseline information (demographic characteristics, lifestyle, physical examination, etc.) and genotyping data of blood-derived DNA in ten regions of the China Kadoorie Biobank study were included. The mCAs were detected with the Mosaic Chromosomal Alterations pipeline, and logistic regression models were used to compare the differences in the detection rate of mCAs in different regions and populations. Results: A total of 5 810 mCA carriers were detected, with the detection rate of 5.8%. The standardized detection rate was 5.1%. The baseline detection rate of mCA increased with age, which were 3.4%, 5.0%, and 9.4% in those aged 30-, 51-, and >60 years, respectively (trend test P<0.001). A more significant proportion of mCAs were found in men (8.0%) than women (4.0%), as well as in urban areas (6.4%) than in rural areas (5.3%), the difference was significant (P<0.001). After adjusting for age and gender, the detection rate of mCA was higher in current smokers or people quitting smoking due to illness and people with low physical activity level, and the mCA detection rate was lower in obesy people (5.3%) than that in people with normal body weight (5.9%) (P=0.006). Conclusions: The detection rate of mCAs varied with region and population in community adults aged 30-79 years in 10 regions of China. The study results might contribute to the molecular identification of aging populations and guide precision prevention of age-related diseases such as cancers.
Adult ; Female ; Humans ; Male ; Middle Aged ; China/epidemiology* ; Life Style ; Risk Factors ; Smoking/epidemiology* ; Aged

Aim To observe the effect of betulinic acid (BA) on the migration and invasion of human gastric cancer MKN-45 cells induced by transforming growth factor-pi (TGF-β1), and to explore the effect of BA on epithelial-mesenchymal transition (EMT) and the potential mechanism. Methods The MKN-45 cells were cultivated in vitro, and the effects of different concentrations of BA on the proliferation of MKN-45 cells at 24, 48 and 72 h were detected using CCK-8 method. The effects of BA (5, 10, 20 jjunol • L) and TGF-01 inhibitor LY2109761 (10 ^mol • L"

[Abstract] Objective To study whether the regulation of mammalian target of rapamycin complex 2(mTORC2) / Akt signaling pathway has a protective effect on SH-SY5Y cell line damaged by 6-hydroxydopamine (6-OHDA), and to clarify its molecular mechanism. Methods SH-SY5Y cells treated with retinoic acid (RA) were given 6-OHDA, mTORC2 signaling pathway inhibitor PP242 and agonist A-443654 respectively. The changes of cell number in each group were investigated by immunofluorescent staining; The total protein was extracted and the expression level and interaction of key proteins in mTORC2 signaling pathway were determined by Western blotting and co-immunoprecipitation (CoIP); The apoptosis rate of cells in each group was detected by flow cytometry. At the same time, the co-culture Parkinson’ s disease (PD) model was made using SH-SY5Y cell line and Bv-2 cell line; MTT colorimetric method was used to detect the cell viability of each group; ELISA was used to detect the content of tumor necrosis factor-α (TNF-α) and interleukin-1β (IL-1β) in cell culture supernatant. Results The number of tyrosine hydroxylase(TH) / proliferating cell nuclear antigen (PCNA) / hochest-, TH / 5-bronmo-2’ -deoxyuridine(BrdU) -labeled positive cells in 6-OHDA-lesioned PD cell model group was significantly lower than that in the normal group; The apoptosis rate was higher; The expression of Rictor, p-Akt and regulated in DNA damage and development 1(REDD1) was increased; There was an interaction between Rictor and p-Akt or REDD1; The cell viability was significantly reduced in the co-culture model; the content of TNF-α and IL-β increased in the cell culture supernatant. With further up-regulation of the abovementioned protein expressions, the cell survival, apoptosis and pro-inflammatory cytokine levels in A-443654 group were significantly ameliorated, while PP242 group showed the opposite changes. Conclusion A-443654 activates mTORC2 signaling pathway by p-Akt, which increases the expression of Rictor and REDD1 protein. These changes contribute to the amelioration in cell survival rate, apoptosis rate, and the proliferation and differentiation and decreasion of apoptosis rate of SH-SY5Y cells. These result improved 6-OHDA-induced cell damage and inhibited the release of pro-inflammatory cytokines.

Objective To explore the effect of activation of mammalian target of rapmycin complex 2(mTORC2)/Akt signaling pathway on dopaminergic neurons and behavior in 6-hydroxydopamine (6-OHDA) model mice and its possible mechanism. Methods Selecting 36 mice which The Nestin-CreERTM and ROSA26-LacZ reporter genes were detected at the same time in 3-month-old male C57BL/6J mice weighing 20-25 g divideng them into 4 gruops, NS+ corn oil group, 6-OHDA+corn oil group, 6-OHDA+PP242 group and 6-OHDA+A-443654 group, and 6-OHDA was injected into the right striatum of the brain to replicate the Parkinson’s disease (PD) model of mice, and then daily intraperitoneal injection of mTORC2/Akt signaling pathway agonist A-443654 or inhibitor PP242. Serum interleukin-1β (IL-1β) and tumor necrosis factor-α(TNF-α)levels were measured by enzyme-linked immunosorbent assay. Immunohistochemistry and immunofluorescence staining were performed to investigate the change of microglia, dopaminergic neurons as well as neural progenitor cells (NPCs). Western blotting was used to detect the expression of related protein of mTORC2/Akt signaling pathway including rictor, p-Akt and regulated in development and DNA dgmage responses 1(REDD1) and the interaction between them were verified by immunoprecipitation. Finally, the behavioral performance of each group of mice was observed. Results With the activation of microglia and the increase of inflammatory factors in PD model mice, the number of dopaminergic neurons in the substantia nigra(SN) decreased significantly, and the motor function of the mice was impaired, but the number of NPCs increased significantly compared with the control mice, mTORC2/Akt signaling pathway related protein expression was also significantly up-regulated. A-443654 treatment further up-regulated the expression of these proteins, meanwhile the indicators mentioned above were ameliorated. However, the inhibitor PP242 treatment group showed completely opposite result with the agonist group. Conclusion A-443654 can promote the proliferation of NPCs and the number of new-born dopaminergic neurons by up-regulating related proteins of mTORC2/Akt signaling pathway, and reducing the activation of microglia and the level of inflammation factors, which ultimately lead to the amelioration of SN-striatal dopaminergic neurons and behavioral performance in PD model mice.

OBJECTIVE: To systematically review the therapeutic effect of acupuncture and moxibustion on postoperative gastrointestinal dysfunction (GID) of gastric cancer with meta-analysis. METHODS: The articles of randomized controlled trials (RCTs) of acupuncture and moxibustion treatment for postoperative GID of gastric cancer were retrieved from the following databases from the time of database establishment to December 31, 2020, including PubMed, EMbase, Cochrane Central Register of Controlled Trials (CENTRAL), China National Knowledge Infrastructure (CNKI), Wanfang database, VIP database and China Biomedical Literature Database (SinoMed). RevMan5.3 software was used for meta-analysis. Using Stata16.0 software, sensitivity analysis and publication bias test were performed. RESULTS: A total of 16 RCTs were included finally, including 1 360 patients, of which, there were 681 cases in the intervention group and 679 cases in the control group. Meta-analysis results showed that acupuncture and moxibustion shortened the time of first flatus (P<0.000 01, MD =-14.52, 95%CI = [-17.31, -11.74]), the time of first bowel sound (P<0.000 01, MD =-10.50, 95%CI =[-13.99, -7.01]) and the time of first defecation (P<0.000 1, MD =-13.79, 95%CI =[-20.09, -7.50]). Meanwhile, acupuncture and moxibustion shortened the time of the first food intake (P<0.000 1, MD =-3.23, 95%CI = [-3.45, -3.00]) and the hospital stay (P<0.000 01, MD =-1.94, 95%CI =[-2.20, -1.69]) after gastric cancer operation, and reduced the incidences of postoperative adverse reactions, i.e. nausea and vomiting (P =0.000 3, RR =0.43, 95%CI =[0.28, 0.68]) and abdominal distention (P =0.000 5, RR =0.41, 95%CI =[0.25, 0.68]). CONCLUSION Acupuncture and moxibustion can promote the recovery of postoperative gastrointestinal function in the patients with gastric cancer. But, for the comparison among different measures of acupuncture and moxibustion intervention, it needs more high-quality trials for a further verification.
Acupuncture Therapy/methods* ; Humans ; Moxibustion/methods* ; Nausea ; Stomach Neoplasms/surgery* ; Vomiting

Objective: To explore the association of spicy food consumption and risk of lip, oral cavity, and pharynx cancers (LOCPs) in Chinese adults. Methods: Based on the baseline survey and long-term follow-up of the China Kadoorie Biobank (CKB) study, Cox proportional hazard regression models were used to estimate hazard ratios (HR) and 95% confidence intervals (95%CI) for associations between spicy food consumption and LOCPs incidence. Results: Of the 510 145 participants included at baseline, 30.1% reported daily spicy food consumption. During a mean follow-up of 10.8 (2.0) years, we documented 767 LOCPs cases. Multivariate adjusted analyses showed that the risk of LOCPs incidence decreased with the frequency of spicy food intake (trend P=0.003), with HR of 0.69 (95%CI:0.54-0.88) for daily spicy food consumers, compared with never or occasional consumers. Participants who preferred moderate pungency degrees had the lowest risk of LOCPs, with a 33%[0.67(95%CI:0.52-0.87)] reduced risk compared to those who consumed spicy food less than once per week. The later the starting age, the lower the risk (trend P=0.004). Those who started eating spicy food after 18 years old had the lowest risk of LOCPs incidence, with adjusted HR (95%CI) of 0.70(0.54-0.92). Conclusions: Spicy food intake might be associated with a decreased risk of LOCPs incidence. Such association was independent of healthy lifestyles. Advocating moderate-pungency spicy food consumption and healthy lifestyles might help prevent LOCPs.
Adolescent ; Adult ; China/epidemiology* ; Humans ; Lip ; Pharyngeal Neoplasms/epidemiology* ; Prospective Studies ; Risk Factors ; Spices

Objective: To explore the correlation between sleep status and frailty in adults aged 30-79 years in China, and explore the potential effect modification of general and central obesity. Methods: Based on the baseline data of the China Kadoorie Biobank, we used multinomial logistic regression to analyze the correlation between long and short sleep duration, insomnia disorder, snoring, and unhealthy sleep score with risks of pre-frailty and frailty. Both overall and obesity-stratified analyses were performed. Result: Among the 512 724 participants, 2.3% had frailty and 40.1% had pre-frailty. There was a U-shaped relationship between sleep duration and frailty score. Short (OR=1.21, 95%CI: 1.19-1.23) or long sleep duration (OR=1.19, 95%CI: 1.17-1.21), insomnia disorder (OR=2.09, 95%CI: 2.02-2.17), and snoring (OR=1.61, 95%CI: 1.59-1.63) were all positively correlated with pre-frailty, and dose-response relationships were observed between unhealthy sleep score and pre-frailty (P for trend<0.001), with OR values of 1.46 (1.44-1.48), 1.97 (1.93-2.00) and 3.43 (3.21-3.67) respectively for those having unhealthy sleep score of 1 to 3. These sleep problems were also positively correlated with frailty. Compared with the overweight or obesity group, stronger relationships were observed between short sleep duration and frailty or pre-frailty and between insomnia disorder and pre-frailty, while the relationships between snoring and frailty and pre-frailty were weaker in the participants with normal weight (P for interaction <0.007 for all). We also observed similar effect modification by central obesity. Conclusion: Long or short sleep duration, insomnia disorder, snoring and higher unhealthy sleep scores were positively correlated with pre-frailty or frailty, general and central obesity status could modify the relationships.
Adult ; China/epidemiology* ; Frailty/epidemiology* ; Humans ; Obesity ; Obesity, Abdominal ; Sleep/physiology* ; Sleep Initiation and Maintenance Disorders/epidemiology* ; Sleep Wake Disorders ; Snoring/epidemiology*