The m6A modification mediated-lncRNA POU6F2-AS1 reprograms fatty acid metabolism and facilitates the growth of colorectal cancer via upregulation of FASN.

BACKGROUND: Long noncoding RNAs (lncRNAs) have emerged as key players in tumorigenesis and tumour progression. However, the biological functions and potential mechanisms of lncRNAs in colorectal cancer (CRC) are unclear. METHODS: The novel lncRNA POU6F2-AS1 was identified through bioinformatics analysis, and its expression in CRC patients was verified via qRT-PCR and FISH. In vitro and in vivo experiments, such as BODIPY staining, Oil Red O staining, triglyceride (TAG) assays, and liquid chromatography mass spectrometry (LC-MS) were subsequently performed with CRC specimens and cells to determine the clinical significance, and functional roles of POU6F2-AS1. Biotinylated RNA pull-down, RIP, Me-RIP, ChIP, and patient-derived organoid (PDO) culture assays were performed to confirm the underlying mechanism of POU6F2-AS1. RESULTS: The lncRNA POU6F2-AS1 is markedly upregulated in CRC and associated with adverse clinicopathological features and poor overall survival in CRC patients. Functionally, POU6F2-AS1 promotes the growth and lipogenesis of CRC cells both in vitro and in vivo. Mechanistically, METTL3-induced m6A modification is involved in the upregulation of POU6F2-AS1. Furthermore, upregulated POU6F2-AS1 could tether YBX1 to the FASN promoter to induce transcriptional activation, thus facilitating the growth and lipogenesis of CRC cells. CONCLUSIONS: Our data revealed that the upregulation of POU6F2-AS1 plays a critical role in CRC fatty acid metabolism and might provide a novel promising biomarker and therapeutic target for CRC.

Nonverbal cues to deception: insights from a mock crime scenario in a Chinese sample.

Nonverbal behaviors could play a crucial role in detecting deception, yet existing studies on deception cues have largely centered on Western populations, predominantly university students, thus neglecting the influence of cultural and sample diversity. To address this gap, our study explored deception cues within an Asian cultural setting, utilizing a mock crime paradigm. Our sample comprised Chinese participants, including both men and women with various socioeconomic status (SES) backgrounds. Our findings revealed that compared to truth tellers, liars exhibited heightened emotions and an increased cognitive load. Furthermore, liars showed a higher frequency of self-adaptors and a longer duration of gaze aversion. Our findings contribute to a more profound understanding of deception cues within Asian culture and have implications for practical fields such as criminal interrogation.

Immunogenicity, safety and immune persistence of the sequential booster with the recombinant protein-based COVID-19 vaccine (CHO cell) in healthy people aged 18-84 years / 中华预防医学杂志

Objective: To evaluate the immunogenicity, safety, and immune persistence of the sequential booster with the recombinant protein-based COVID-19 vaccine (CHO cell) in healthy people aged 18-84 years. Methods: An open-label, multi-center trial was conducted in October 2021. The eligible healthy individuals, aged 18-84 years who had completed primary immunization with the inactivated COVID-19 vaccine 3 to 9 months before, were recruited from Shangyu district of Shaoxing and Kaihua county of Quzhou, Zhejiang province. All participants were divided into three groups based on the differences in prime-boost intervals: Group A (3-4 months), Group B (5-6 months) and Group C (7-9 months), with 320 persons per group. All participants received the recombinant COVID-19 vaccine (CHO cell). Blood samples were collected before the vaccination and after receiving the booster at 14 days, 30 days, and 180 days for analysis of GMTs, antibody positivity rates, and seroconversion rates. All adverse events were collected within one month and serious adverse events were collected within six months. The incidences of adverse reactions were analyzed after the booster. Results: The age of 960 participants was (52.3±11.5) years old, and 47.4% were males (455). The GMTs of Groups B and C were 65.26 (54.51-78.12) and 60.97 (50.61-73.45) at 14 days after the booster, both higher than Group A's 44.79 (36.94-54.30) (P value<0.05). The GMTs of Groups B and C were 23.95 (20.18-28.42) and 27.98 (23.45-33.39) at 30 days after the booster, both higher than Group A's 15.71 (13.24-18.63) (P value <0.05). At 14 days after the booster, the antibody positivity rates in Groups A, B, and C were 91.69% (276/301), 94.38% (302/320), and 93.95% (295/314), respectively. The seroconversion rates in the three groups were 90.37% (272/301), 93.75% (300/320), and 93.31% (293/314), respectively. There was no significant difference among these rates in the three groups (all P values >0.05). At 30 days after the booster, antibody positivity rates in Groups A, B, and C were 79.60% (238/299), 87.74% (279/318), and 90.48% (285/315), respectively. The seroconversion rates in the three groups were 76.92% (230/299), 85.85% (273/318), and 88.25% (278/315), respectively. There was a significant difference among these rates in the three groups (all P values <0.001). During the sequential booster immunization, the incidence of adverse events in 960 participants was 15.31% (147/960), with rates of about 14.38% (46/320), 17.50% (56/320), and 14.06% (45/320) in Groups A, B, and C, respectively. The incidence of adverse reactions was 8.02% (77/960), with rates of about 7.50% (24/320), 6.88% (22/320), and 9.69% (31/320) in Groups A, B, and C, respectively. No serious adverse events related to the booster were reported. Conclusion: Healthy individuals aged 18-84 years, who had completed primary immunization with the inactivated COVID-19 vaccine 3 to 9 months before, have good immunogenicity and safety profiles following the sequential booster with the recombinant COVID-19 vaccine (CHO cell).

Immunogenicity, safety and immune persistence of the sequential booster with the recombinant protein-based COVID-19 vaccine (CHO cell) in healthy people aged 18-84 years / 中华预防医学杂志

Objective: To evaluate the immunogenicity, safety, and immune persistence of the sequential booster with the recombinant protein-based COVID-19 vaccine (CHO cell) in healthy people aged 18-84 years. Methods: An open-label, multi-center trial was conducted in October 2021. The eligible healthy individuals, aged 18-84 years who had completed primary immunization with the inactivated COVID-19 vaccine 3 to 9 months before, were recruited from Shangyu district of Shaoxing and Kaihua county of Quzhou, Zhejiang province. All participants were divided into three groups based on the differences in prime-boost intervals: Group A (3-4 months), Group B (5-6 months) and Group C (7-9 months), with 320 persons per group. All participants received the recombinant COVID-19 vaccine (CHO cell). Blood samples were collected before the vaccination and after receiving the booster at 14 days, 30 days, and 180 days for analysis of GMTs, antibody positivity rates, and seroconversion rates. All adverse events were collected within one month and serious adverse events were collected within six months. The incidences of adverse reactions were analyzed after the booster. Results: The age of 960 participants was (52.3±11.5) years old, and 47.4% were males (455). The GMTs of Groups B and C were 65.26 (54.51-78.12) and 60.97 (50.61-73.45) at 14 days after the booster, both higher than Group A's 44.79 (36.94-54.30) (P value<0.05). The GMTs of Groups B and C were 23.95 (20.18-28.42) and 27.98 (23.45-33.39) at 30 days after the booster, both higher than Group A's 15.71 (13.24-18.63) (P value <0.05). At 14 days after the booster, the antibody positivity rates in Groups A, B, and C were 91.69% (276/301), 94.38% (302/320), and 93.95% (295/314), respectively. The seroconversion rates in the three groups were 90.37% (272/301), 93.75% (300/320), and 93.31% (293/314), respectively. There was no significant difference among these rates in the three groups (all P values >0.05). At 30 days after the booster, antibody positivity rates in Groups A, B, and C were 79.60% (238/299), 87.74% (279/318), and 90.48% (285/315), respectively. The seroconversion rates in the three groups were 76.92% (230/299), 85.85% (273/318), and 88.25% (278/315), respectively. There was a significant difference among these rates in the three groups (all P values <0.001). During the sequential booster immunization, the incidence of adverse events in 960 participants was 15.31% (147/960), with rates of about 14.38% (46/320), 17.50% (56/320), and 14.06% (45/320) in Groups A, B, and C, respectively. The incidence of adverse reactions was 8.02% (77/960), with rates of about 7.50% (24/320), 6.88% (22/320), and 9.69% (31/320) in Groups A, B, and C, respectively. No serious adverse events related to the booster were reported. Conclusion: Healthy individuals aged 18-84 years, who had completed primary immunization with the inactivated COVID-19 vaccine 3 to 9 months before, have good immunogenicity and safety profiles following the sequential booster with the recombinant COVID-19 vaccine (CHO cell).

Labeling of graphene oxide with [131I]AgI and its stability analysis.

To explore the new iodine labeling method of nanomaterials, graphene oxide (GO) was labeled by 131I with AgI nanoparticles. As a control, GO was also labeled by 131I with chloramine-T method. The stability of the two 131I labeling materials, viz. [131I]AgI-GO and [131I]I-GO was evaluated. The results show that [131I]AgI-GO is very stable in inorganic environment such as PBS and saline. However, it is not stable enough in serum. The instability of [131I]AgI-GO in serum can be attributed to the higher affinity of Ag to S of thiol group in cysteine than iodine ions and much more chance of interaction between thiol group and [131I]AgI nanoparticles on two-dimensional GO than in three-dimensional nanomaterials.

Targeting SMYD2 inhibits angiogenesis and increases the efficiency of apatinib by suppressing EGFL7 in colorectal cancer.

Angiogenesis is an essential factor affecting the occurrence and development of solid tumors. SET And MYND Domain Containing 2 (SMYD2) serves as an oncogene in various cancers. However, whether SMYD2 is involved in tumor angiogenesis remains unclear. Here, we report that SMYD2 expression is associated with microvessel density in colorectal cancer (CRC) tissues. SMYD2 promotes CRC angiogenesis in vitro and in vivo. Mechanistically, SMYD2 physically interacts with HNRNPK and mediates lysine monomethylation at K422 of HNRNPK, which substantially increases RNA binding activity. HNRNPK acts by binding and stabilizing EGFL7 mRNA. As an angiogenic stimulant, EGFL7 enhances CRC angiogenesis. H3K4me3 maintained by PHF8 mediates the abnormal overexpression of SMYD2 in CRC. Moreover, targeting SMYD2 blocks CRC angiogenesis in tumor xenografts. Treatment with BAY-598, a functional inhibitor of SMYD2, can also synergize with apatinib in patient-derived xenografts. Overall, our findings reveal a new regulatory axis of CRC angiogenesis and provide a potential strategy for antiangiogenic therapy.

Study on the mechanism of heterogeneous nuclear ribonucleoprotein L promoting the proliferation of hepatocellular carcinoma cells / 中华肝胆外科杂志

Objective:To investigate the effect of HNRNPL protein on the proliferative ability of primary hepatocellular carcinoma cells and its potential mechanism.Methods:Online public database and real-time quantitative PCR were used to analyze the difference of HNRNPL expression between cancer and adjacent tissues. The effects of HNRNPL on HCC cell MHCC97H and HepG2 proliferation and MAPK pathway were investigated by Western blot, cell counting assay, colony formation assay and nude mouse transplantation tumor experiments.Results:The level of HNRNPL mRNA was validated to be higher in HCC tissue (2.76±0.37) than in normal tissue (1.00±0.14) with statistical difference ( t=3.93, P=0.002). Colony formation assay showed that the colony numbers of two MHCC97H knockdown groups (33.3±7.7) and (43.3±2.2) were lower than their control group (84.3±6.2), and two HepG2 knockdown groups (59.0±15.5) and (41.7±4.8) were lower than their control group (200.3±6.2) with statistical difference (both P<0.01). HNRNPL knockdown decreased the proliferation ability and activation level of MAPK pathway in HCC cells. Overexpression of oncogene c-RAF partially alleviated the anti-proliferation effect of HNRNPL knockdown and rescued the tumorigenic capacity. Conclusion:HNRNPL can promote hepatocellular carcinoma cell proliferation by activating MAPK signaling pathway.

Preparation of Rubus parvifolius L.dispersible tablets and determination of its dissolution rate / 中国药师

Objective To optimize the preparation process of Rubus parvifolius L.dispersible tablets and determine its dissolution.Methods On the basis of single factor test,the formulation process of dispersible tablets was optimized by central composite design-response surface method with microcrystalline cellulose(MCC),polyvinyl polypyrrolidone(PVPP)and low substituted hydroxypropyl cellulose(L-HPC)as the influencing factors and disintegration time as the evaluation index.The total saponins of Rubus parvifolius L.was used as an indicator to determine the dissolution rate with reference to the method of Chinese Pharmacopoeia.Results The optimal prescription was 36.9％total saponin extract powder,42％MCC,13％PVPP,8％L-HPC and 0.1％microsilica gel,which showed a high correlation coefficient of the model.The disintegration time of the prepared dispersive tablets was less than 3 min,and the cumulative dissolution rate reached more than 88％at 50 min.Conclusion The optimized process is stable and reliable,and can be used for the preparation of Rubus parvifolius L.dispersible tablets.

Research progress on the correlation between genetic factors and sudden cardiac death in the elderly / 中华老年医学杂志

Sudden cardiac death(SCD)in the elderly is defined as a sudden accidental death in patients over 65 years of age within one hour of symptom onset or within 24 hours with no symptoms, possibly due to arrhythmia or abrupt hemodynamic changes.It is characterized by rapid onset, rapid progression, and high mortality.Sudden cardiac death in the elderly is the most serious clinical syndrome in elderly patients with heart disease.It accounts for more than 80% of all sudden death cases and is the cause of sudden death in the vast majority of elderly patients.Clinical methods for the detection of sudden cardiac death include mostly screening through family and personal history, physical examination, electrocardiogram analysis and echocardiography, but their drawbacks include lack specificity, low detection rates and relatively limited scenarios for their use.Genetic susceptibility is also responsible for sudden cardiac death.Genetic factors play an important role in the occurrence and development of sudden cardiac death.This review summarized the correlation between sudden death and genetic factors underlying different cardiovascular diseases, including the role of genetic polymorphisms in the occurrence of sudden cardiac death in older adults.

Factors Influencing and Adverse Reactions of Voriconazole Clearance in Patients with Hematological Diseases / 中国实验血液学杂志

OBJECTIVE@#To monitor the changes of voriconazole minimum concentration(Cmin) in patients with hematological diseases, and evaluate the factors influencing and adverse reactions of voriconazole clearance in patients with hematological diseases, so as to provide a theoretical basis for reasonable clinical use of voriconazole.@*METHODS@#136 patients with hematological diseases who used voriconazole in Wuhan NO.1 Hospital from May 2018 to December 2019 were selected. The correlation between C-reactive protein, albumin, creatinine and voriconazole Cmin were analyzed, and the changes of voriconazole Cmin after glucocorticoid treatment was also detected. In addition, stratified analysis was used to explore the adverse events of voriconazole.@*RESULTS@#Among 136 patients, 77 were male (56.62%) and 59 were female (43.38%). There were positive correlations between voriconazole Cmin and C-reactive protein and creatinine levels (r=0.277, r=0.208), while voriconazole Cmin was negatively correlated with albumin level (r=-2.673). Voriconazole Cmin in patients treated with glucocorticoid was decreased significantly (P<0.05). In addition, sratified analysis of voriconazole Cmin showed that compared with voriconazole Cmin 1.0-5.0 mg/L group, the incidence of adverse reactions of visual impairment in voriconazole Cmin> 5.0 mg/L group was increased (χ2=4.318, P=0.038).@*CONCLUSION@#The levels of C-reactive protein, albumin and creatinine are closely related to the voriconazole Cmin, which indicate that inflammation and hyponutrition may prevent the clearance of voriconazole in patients with hematological diseases. It is necessary to monitor the voriconazole Cmin of patients with hematological diseases, and adjust the dosage in time to reduce adverse reactions.

N7-methylguanosine-related lncRNAs: Distinction between hot and cold tumors and construction of predictive models in colon adenocarcinoma.

Colon adenocarcinoma (COAD) is a prevalent malignant tumor that severely threatens human health across the globe. Immunotherapy is an essential need for patients with COAD. N7-methylguanosine (m7G) has been associated with human diseases, and non-coding RNAs (lncRNAs) regulate various tumor-related biological processes. Nonetheless, the m7G-related lncRNAs involved in COAD regulation are limited. This study aims to construct the clustering features and prognostic model of m7G-related lncRNAs in COAD. First, The Cancer Genome Atlas (TCGA) database was used to identify m7G-related differentially expressed lncRNAs (DELs), based on which COAD cases could be classified into two subtypes. Subsequently, univariate Cox analysis was used to identify 9 prognostic m7G-related lncRNAs. Further, Five candidates were screened by LASSO-Cox regression to develop new models. The patients were divided into high-risk and low-risk groups based on the median risk score. Consequently, the Kaplan-Meier survival curve demonstrated a statistically significant overall survival (OS) between the high- and low-risk groups (P<0.001). Multivariate Cox regression analysis revealed that risk score is an independent prognostic factor in COAD patients (P<0.001). This confirms the clinical applicability of the model. Additionally, we performed Gene Set Enrichment Analysis (GSEA), which uncovered the biological and functional differences between risk subgroups, i.e., enrichment of immune-related diseases in the high-risk group and enrichment of metabolic-related pathways in the low-risk group. In a drug sensitivity analysis, high-risk group were more sensitive to some chemotherapeutics and targeted drugs than low-risk group. Eventually, the stability of the model was confirmed by qRT-PCR. Our study unraveled the features of different immune states of COAD and established a prognostic model, including five m7G-related lncRNAs for COAD patients. These results will bolster clinical treatment and survival prediction of COAD.

Somatic Alteration Characteristics of Early-Onset Gastric Cancer.

Gastric cancer is one of the most common and deadly cancer types worldwide, which brings millions of dollars of economic loss each year. Patients diagnosed with early-onset gastric cancer were reported to have a worse prognosis compared to other gastric cancer patients, while the mechanisms behind such phenomenon are unknown. To identify age-dependent somatic alternations in gastric cancer, next-generation sequencing targeting 425 genes was performed on 1688 gastric tumor tissues and corresponding plasma samples. In our study, the microsatellite instability (MSI) and chromosomal instability score (CIS) values increased along with the age of patients, which indicates that older patients display a less genomic stability pattern. The differences of somatic alternations between young and old groups were compared. Somatic mutations CDH1 and copy number gains of FGFR2 were identified to enrich in the younger gastric cancer patients, which may contribute to the worse prognosis of early-onset gastric cancer patients.

CD36: an emerging therapeutic target for cancer and its molecular mechanisms.

Tumor cells need to rewire their metabolic pathways to regulate the nutrient uptake and metabolism to sustain the energy production. Lipids are important components of energy sources for tumor metabolism. Tumor cells rely on various transporters to mediate the trafficking of lipids for oxidation or activate oncogenic signaling pathways. CD36, a membrane glycoprotein presenting on the surface of cells, binds fatty acids to facilitate their transport for lipid utilization. Upregulated CD36 expression has been observed in multiple cancer types including acute myeloid leukemia, breast cancer, colorectal cancer, gastric cancer, etc. Moreover, CD36 is correlated with poor clinical outcomes and adverse clinicopathological features in various cancer types. In vitro and vivo studies have confirmed that CD36 participates in the regulation of tumor growth, metastasis, drug resistance through diverse molecular mechanisms. Thus, we firstly discussed the role of CD36 in the regulation of metabolic phenotypes, especially in glucose and fatty acid metabolism. Furthermore, we specifically focused on the molecular mechanisms of CD36 in the occurrence and development of multiple tumor types. Collectively, we explored the connection between CD36 and tumors, providing new insights for developing potential therapeutic strategies and tumor stratification targeting CD36.

Study on factors associated with non-variceal upper gastrointestinal bleeding in hospitalized elderly patients / 中华老年医学杂志

Objective:To investigate factors related to non-variceal upper gastrointestinal bleeding(NVUGIB)in hospitalized elderly patients.Methods:A retrospective study was conducted to collect the medical records of 1 085 elderly patients at the Affiliated Hospital of Qingdao University from January 1, 2018 to January 1, 2019.According to whether NVUGIB occurred during hospitalization, they were divided into the bleeding group(173 cases)and the control group(912 cases). General information(age, sex, smoking and drinking), diseases, medications and laboratory test results for the two groups were compared and analyzed, and factors related to NVUGIB were analyzed via binary Logistic regression.Results:There were significant differences in age, smoking, drinking, peptic ulcer, tumor, coronary heart disease, atrial fibrillation, stroke, helicobacter pylori(HP)infection, acute respiratory failure, use of anti-coagulant, anti-platelet drugs, nonsteroidal anti-inflammatory drugs and glucocorticoids, leukocyte counts, hemoglobin, C-reactive protein, procalcitonin, prothrombin time and international normalized ratio(INR), D-dimer, triglycerides, albumin and glycosylated hemoglobin(all P<0.05). Multivariate Logistic regression analysis showed that history of tumor( OR=1.552, 95% CI: 1.028-2.344), peptic ulcer( OR=4.797, 95% CI: 2.263-10.165), HP infection( OR=7.199, 95% CI: 1.825-28.571), acute respiratory failure( OR=2.977, 95% CI: 1.314-6.757), use of anti-coagulant and anti-platelet drugs( OR=2.715, 95% CI: 1.769-4.167), prolonged INR( OR=21.314, 95% CI: 2.321-195.727), increased leukocyte count( OR=10.370, 95% CI: 6.521-16.493)and hypoproteinemia( OR=1.970, 95% CI: 1.304-2.976)were independent risk factors for NVUGIB in hospitalized elderly patients. Conclusions:For hospitalized elderly patients, attention should be paid to their history of tumor, peptic ulcer, HP infection, acute respiratory failure, prolonged INR, elevated leukocyte counts, hypoalbuminemia and the use of anti-coagulant and anti-platelet drugs.The occurrence of NVUGIB, early evaluation and intervention should be carefully monitored or carried out to reduce its incidence in hospitalized elderly patients.

Survival stratification for colorectal cancer via multi-omics integration using an autoencoder-based model.

Prognosis stratification in colorectal cancer helps to address cancer heterogeneity and contributes to the improvement of tailored treatments for colorectal cancer patients. In this study, an autoencoder-based model was implemented to predict the prognosis of colorectal cancer via the integration of multi-omics data. DNA methylation, RNA-seq, and miRNA-seq data from The Cancer Genome Atlas (TCGA) database were integrated as input for the autoencoder, and 175 transformed features were produced. The survival-related features were used to cluster the samples using k-means clustering. The autoencoder-based strategy was compared to the principal component analysis (PCA)-, t-distributed random neighbor embedded (t-SNE)-, non-negative matrix factorization (NMF)-, or individual Cox proportional hazards (Cox-PH)-based strategies. Using the 175 transformed features, tumor samples were clustered into two groups (G1 and G2) with significantly different survival rates. The autoencoder-based strategy performed better at identifying survival-related features than the other transformation strategies. Further, the two survival groups were robustly validated using "hold-out" validation and five validation cohorts. Gene expression profiles, miRNA profiles, DNA methylation, and signaling pathway profiles varied from the poor prognosis group (G2) to the good prognosis group (G1). miRNA-mRNA networks were constructed using six differentially expressed miRNAs (let-7c, mir-34c, mir-133b, let-7e, mir-144, and mir-106a) and 19 predicted target genes. The autoencoder-based computational framework could distinguish good prognosis samples from bad prognosis samples and facilitate a better understanding of the molecular biology of colorectal cancer.

Risk factors of senile degenerative valvular heart disease / 中华老年医学杂志

Objective:To explore the clinical characteristics and related risk factors of senile degenerative valvular heart disease(SDHVD), and to provide clinical basis for early prevention intervention of SDHVD.Methods:Clinical data of 1568 elderly patients ≥60 years old hospitalized in our hospital from January 2022 to June 2022 were collected to compare the clinical characteristics and analyze the risk factors of patients in the degenerative heart valve disease group and the non-degenerative heart valve disease group.Results:Age(per 10-year increase)( OR=2.107, 95% CI=1.518-2.924), blood calcium( OR=8.934, 95% CI=2.023-39.447), total cholesterol( OR=1.167, 95% CI=1.044-1.304), female( OR=2.098, 95% CI=1.305-3.374), and reduced mean platelet volume(MPV)( OR=0.818, 95% CI=0.682-0.981)were independent risk factors for the development of SDHVD( P<0.05).Post hoc two-by-two comparisons showed that different degrees of calcification were associated with age( P<0.05); apoA, UA, P, and FT3 were statistically significant in the no-calcification group compared with the control group( P<0.05); E/e′, PASP, and NT-ProBNP were statistically significant in the moderate calcification group compared with the control group( P<0.05); TC was statistically significant in the no-calcification and mild calcification groups compared with the control group There was statistical significance( P<0.05)compared with the control group. Conclusions:Age, blood calcium, total cholesterol, female, and reduced MPV are independent risk factors for SDHVD.

Effect of hyperbaric oxygen therapy on myocardial fibrosis and expression of oxidative stress-related indicators in D-galactose-induced senescent model mice / 中华老年医学杂志

Objective:To investigate the protective effect of hyperbaric oxygen therapy(HBOT)on myocardial fibrosis and oxidative stress induced by D-galactose(D-gal)in senescent model mice and its possible mechanism.Methods:Three-month-old male Kunming mice(n=27)were randomized into control, D-gal, and D-gal + HBOT groups.The control group received subcutaneous sterilized saline(5 ml · kg -1· d -1)for 8 weeks; the remaining 2 groups received subcutaneous D-gal(200 mg · kg -1· d -1)for 8 weeks. The D-gal + HBOT group underwent HBOT intervention at week 7~8.At the end of the experiment, the histopathological changes were analyzed by hematoxylin-eosin(HE)staining, and the fibrosis changes were analyzed by Masson staining and Sirius red staining.Oxidative stress kit was used to detect catalase(CAT), total superoxide dismutase(T-SOD)activity and malon-di-aldehyde(MDA)content in serum of mice.Western blotting was used to detect the expression levels of the aging-related proteins p53 and p16 in mouse heart tissue, the heart-function-related proteins atrial natriuretic peptide(ANP)and brain natriuretic peptide(BNP), and the oxidative stress-related protein superoxide dismutase 1(SOD1), superoxide dismutase 2(SOD2)and catalase(CAT). Results:Cardiac morphologic staining indicated that as compared with the control group, mice of D-gal group exhibited features of senescence and the increased fibrosis area, and senescence and fibrosis were obviously improved after HBOT intervention as compared with the D-gal group.The findings of the oxidative stress kit measurement indicated that as compared with the control group, the D-gal group had markedly decreased activities of CAT and T-SOD, significantly increased MDA content in the serum.After HBOT treatment, as compared with d-gal group, serum CAT and T-SOD activities were increased, while MDA content was decreased( F=126.85, 32.89, 157.50, all P<0.05).Furthermore, as compared with the control group, the D-gal group had obviously increased contents of p53, p16, ANP and BNP, while the content of CAT, SOD1 and SOD2 were obviously decreased.After HBOT intervention, as compared with the D-gal group, the contents of p53, p16, ANP、BNP were reduced, while the content of CAT, SOD1 and SOD2 were increased( F=36.37, 14.81, 23.28, 58.41, 12.79, 80.08, 6.63, all P<0.05). Conclusions:HBOT intervention could protects against cardiac injury in aging mice, which may be related to attenuating myocardial fibrosis, inducing the expression of antioxidant enzymes, and reducing oxidative stress.

Quiescin Sulfhydryl Oxidase 2 Overexpression Predicts Poor Prognosis and Tumor Progression in Patients With Colorectal Cancer: A Study Based on Data Mining and Clinical Verification.

Background: As a member of the atypical thiol oxidase family, quiescin sulfhydryl oxidase 2 (QSOX2) has been reported to play an important role in several biological processes, but the expression and function of QSOX2 in colorectal cancer (CRC) remains elusive. Methods: The difference of QSOX2 expression, and its relationship with clinicopathological features and prognosis in CRC, was analyzed by bioinformatic analysis and validated by clinical CRC specimen cohort. The functional characterization of QSOX2 was detected via in vitro and vivo experiments in CRC cell lines, while the potential signaling pathways were predicted by Gene Set Enrichment Analysis (GSEA). Results: Our data based on bioinformatical analysis and clinical validation demonstrated that the expression of QSOX2 in CRC tissues was significantly upregulated. Additionally, the chi-square test, logistic regression analysis, and Fisher's exact test showed that QSOX2 overexpression was significantly correlated with advanced clinicopathological parameters, such as pathological stage and lymph node metastasis. The Kaplan-Meier curves and univariate Cox regression model showed that QSOX2 overexpression predicts poor overall survival (OS) and disease-free survival (DFS) in CRC patients. More importantly, multivariate Cox regression model showed that QSOX2 overexpression could serve as an independent factor for CRC patients. In vitro and vivo data showed that the proliferation and metastasis ability of CRC cells were suppressed on condition of QSOX2 inhibition. In addition, GSEA showed that the QSOX2 high expression phenotype has enriched multiple potential cancer-related signaling pathways. Conclusion: QSOX2 overexpression is strongly associated with malignant progression and poor oncological outcomes in CRC. QSOX2 might act as a novel biomarker for prognosis prediction and a new target for biotherapy in CRC.