OBJECTIVES: To investigate the effect of curcumin on lipid metabolism in non-small cell lung cancer (NSCLC) and its molecular mechanism. METHODS: The inhibitory effect of curcumin (0-70 μmol/L) on proliferation of A549 and H1299 cells was assessed using MTT assay, and 20 and 40 μmol/L curcumin was used in the subsequent experiments. The effect of curcumin on lipid metabolism was evaluated using cellular uptake assay, wound healing assay, triglyceride (TG)/free fatty acid (NEFA) measurements, and Oil Red O staining. Western blotting was performed to detect the expressions of PGC-1α, PPAR-α, and HIF-1α in curcumin-treated cells. Network pharmacology was used to predict the metabolic pathways, and the results were validated by Western blotting. In a nude mouse model bearing A549 cell xenograft, the effects of curcumin (20 mg/kg) on tumor growth and lipid metabolism were assessed by measuring tumor weight and observing the changes in intracellular lipid droplets. RESULTS: Curcumin concentration-dependently inhibited the proliferation of A549 and H1299 cells and significantly reduced TG and NEFA levels and intracellular lipid droplets. Western blotting revealed that curcumin significantly upregulated PGC-1α and PPAR‑α expressions in the cells. KEGG pathway enrichment analysis predicted significant involvement of the HIF-1 signaling pathway in curcumin-treated NSCLC, suggesting a potential interaction between HIF-1α and PPAR‑α. Western blotting confirmed that curcumin downregulated the expression of HIF-1α. In the tumor-bearing mice, curcumin treatment caused significant reduction of the tumor weight and the number of lipid droplets in the tumor cells. CONCLUSIONS Curcumin inhibits NSCLC cell proliferation and lipid metabolism by downregulating the HIF-1α pathway.
Curcumin/pharmacology* ; Humans ; Hypoxia-Inducible Factor 1, alpha Subunit/metabolism* ; Animals ; Lipid Metabolism/drug effects* ; Carcinoma, Non-Small-Cell Lung/pathology* ; Lung Neoplasms/pathology* ; Mice, Nude ; Down-Regulation ; Mice ; Cell Proliferation/drug effects* ; Cell Line, Tumor ; Peroxisome Proliferator-Activated Receptor Gamma Coactivator 1-alpha ; PPAR alpha/metabolism* ; Signal Transduction/drug effects* ; A549 Cells

In this study, high-throughput promoter screening was employed to optimize the heterologous expression of Mesorhizobium loti carbonic anhydrase (MlCA) in order to reduce the costs associated with carbon capture and storage (CCS). To simplify the complexity of traditional vectors, a fusion protein expression system was constructed using superfolder green fluorescent protein (sfGFP) and MlCA. The synthetic promoter library in Escherichia coli was utilized for efficient one-step screening. Based on fluorescence intensity on agar plates, a total of 143 monoclonal colonies were identified, forming a library with varying expression levels. The top four recombinants with the highest fluorescence intensity were selected, among which MlCA driven by the promoter 342042/+ exhibited the highest enzymatic activity, with a specific activity of the 34.6 Wilbur-Anderson units (WAU)/mg. Optimization experiments revealed that MlCA exhibited the best performance when cultured for 4 days under pH 7.0 and 40 ℃ conditions. The Michaelis constant (K_m·hdy) and maximum reaction rate (V_max·hdy) for CO₂ hydration were determined to be 62.46 mmol/L and 0.164 mmol/(s·L), respectively. For esterase hydrolysis, MlCA showed the K_m and V_max of 639.8 mmol/L and 0.035 mmol/(s·L), respectively. MlCA accelerated the CO₂ hydration process, promoting CO₂ mineralized into CaCO₃ within 9 min at low pH and room temperature conditions. Scanning electron microscopy (SEM) and X-ray diffraction (XRD) analyses confirmed that the precipitated product was calcite. This study provides a low-cost and environmentally friendly alternative for future CCS applications.
Carbonic Anhydrases/biosynthesis* ; Promoter Regions, Genetic/genetics* ; Escherichia coli/metabolism* ; Carbon Sequestration ; Carbon Dioxide/metabolism* ; Green Fluorescent Proteins/metabolism*

Objective To analyze the relationship between serum hyaluronic acid levels and Child classification of liver function in Steatosis patients. Methods A total of 110 Steatosis patients admitted to Shaanxi People's Hospital from January 2017 to September 2018 were selected There were 23 cases in Child a group, 52 cases in Child B group and 35 cases in Child C Group. Sex, age, body mass index (BMI) and serum hyaluronic acid (ha) were compared among the three groups. Results There were no significant differences in sex, age and BMI among Child A, Child B and Child C groups (P>0.05) . The level of serum hyaluronic acid in Child class C (91.39±24.67) was significantly higher than that in Child class B (38.26.9.36) and Child class A (29.55±6.97)（P<0.05）. There was no significant difference in serum hyaluronic acid levels between Child B (38.26.9.36) and Child A (29.55 ± 6.97) groups (P > 0.05). Conclusion Serum hyaluronic acid levels are high in Steatosis patients with poor liver function.

Objective To investigate the effect of oxaliplatin on the activation of hepatic stellate cells(HSCs),as well as the association of oxaliplatin with microRNA-30a-5p and autophagy.Methods HSC-LX2 cells were cultured and divided into groups according to the following three protocols:control group,PDGF treatment group,oxaliplatin treatment group,oxaliplatin+PDGF treatment group;control group,microRNA-30a-5p transfection group,PDGF treatment group,microRNA-30a-5p transfection+PDGF treatment group;control group,3-MA group,microRNA-30a-5p inhibitor group,microRNA-30a-5p inhibitor+3-MA group.Western Blot was used to measure the expression of HSC activation-related proteins(Collagen-I and alpha-smooth muscle actin[α-SMA])and HSC autophagy-related proteins(Beclin-1,P62,and LC3B);LysoTracker staining and immunofluorescence assay were used to measure the expression of LC3B autophagosomes;RT-PCR was used to measure the expression level of microRNA-30a-5p;bioinformatics techniques were used to predict the potential targets of microRNA-30a-5p in HSCs.The independent-samples t test was used for comparison of normally distributed continuous data between two groups;a one-way analysis of variance was used for comparison between multiple groups,and the least significant difference t-test was used for further comparison between two groups.Results After the cells were treated with oxaliplatin,RT-PCR results showed that the oxaliplatin treatment group had a significantly higher expression level of microRNA-30a-5p than the control group(P＜0.01);Western Blot showed that the oxaliplatin treatment group had significant reductions in the expression levels of the HSC activation-related proteins α-SMA and Collagen-Ⅰ and the autophagy-related proteins Beclin 1 and LC3BⅡ/Ⅰ(all P＜0.001);immunofluorescence assay showed that the oxaliplatin treatment group had a significantly lower number of autophagosomes than the control group(P＜0.05).After HSC-LX2 cells were transfected with microRNA-30a-5p mimic,compared with the control group,the microRNA-30a-5p mimic group had significant reductions in the expression levels of the autophagy-related proteins Beclin 1 and LC3BⅡ/Ⅰ(P＜0.05)and the HSC activation-related protein Collagen-Ⅰ(P＜0.001);after HSC-LX2 cells were transfected with microRNA-30a-5p inhibitor,Western Blot showed that compared with the control group,the microRNA-30a-5p inhibitor group had significant increases in the expression levels of the HSC activation-related proteins Collagen-Ⅰ and α-SMA and the autophagy-related protein Beclin 1(t=2.41,2.32,and 4.57,all P＜0.05).Western Blot showed that compared with the control group,the microRNA-30a-5p inhibitor group had significant increases in the expression levels of the HSC autophagy-related protein Beclin 1 and the HSC activation-related protein α-SMA(both P＜0.05),and after the treatment with the autophagy inhibitor 3-MA,there were no significant differences in the expression of these proteins between the two groups(P＞0.05).The bioinformatics analysis using TargetScan,PicTar,and miRanda databases showed that the autophagy-related protein Beclin-1 might be a potential target of miRNA-30a-5p.Conclusion Oxaliplatin can inhibit the activation of HSCs by upregulating the expression of microRNA-30a-5p,which provides new ideas and a new target for the treatment of liver fibrosis.

Objectives:To analyze the status and temporal changes of disability-adjusted life year (DALY) for stomach and colorectal cancers among registered permanent residents in Changning District of Shanghai Municipality, and provide scientific basis for the prevention and treatment of stomach and colorectal cancers in this district.Methods:Using the cancer registration data of stomach and colorectal cancers from 2002 to 2019, we estimated the indices such as the DALYs, the DALY crude rates, the age-standardized DALY rates, etc. Then we used the Joinpoint regression model to calculate the average annual percent change (AAPC) and annual percent change (APC) to explore the temporal variations in different periods.Results:The DALYs of stomach and colorectal cancers in Changning District from 2002 to 2019 were 55 931 person years and 65 252 person years, respectively. The crude rates of DALY were 512.16/10 5 and 597.51/10 5, respectively. We observed a higher disease burden in men than in women, and the peak rate of DALY in stomach cancer was in the 75-79 years age group, while in colorectal cancer the rate was in the 85-years-or-older age group. Joinpoint regression analysis showed that from 2002 to 2019, the age-standardized DALY rate of stomach cancer showed a downward trend (AAPC=-3.86%, P＜0.05), while the trend of colorectal cancer was not statistically significant(AAPC=-0.08%, P＞0.05). However, the trends in the age-standardized DALY rates of colorectal cancer were different between males and females, with males showing an upward trend (AAPC=1.24%, P＜0.05) and females showing a downward trend (AAPC=-1.67%, P＜0.05). Conclusions:The DALY of stomach and colorectal cancers in Changning District of Shanghai showed a decreasing trend. Males and the middle-aged and elderly populations are still the key targets for disease prevention and control in this district.

Objectives:To analyze the status and temporal changes of disability-adjusted life year (DALY) for stomach and colorectal cancers among registered permanent residents in Changning District of Shanghai Municipality, and provide scientific basis for the prevention and treatment of stomach and colorectal cancers in this district.Methods:Using the cancer registration data of stomach and colorectal cancers from 2002 to 2019, we estimated the indices such as the DALYs, the DALY crude rates, the age-standardized DALY rates, etc. Then we used the Joinpoint regression model to calculate the average annual percent change (AAPC) and annual percent change (APC) to explore the temporal variations in different periods.Results:The DALYs of stomach and colorectal cancers in Changning District from 2002 to 2019 were 55 931 person years and 65 252 person years, respectively. The crude rates of DALY were 512.16/10 5 and 597.51/10 5, respectively. We observed a higher disease burden in men than in women, and the peak rate of DALY in stomach cancer was in the 75-79 years age group, while in colorectal cancer the rate was in the 85-years-or-older age group. Joinpoint regression analysis showed that from 2002 to 2019, the age-standardized DALY rate of stomach cancer showed a downward trend (AAPC=-3.86%, P＜0.05), while the trend of colorectal cancer was not statistically significant(AAPC=-0.08%, P＞0.05). However, the trends in the age-standardized DALY rates of colorectal cancer were different between males and females, with males showing an upward trend (AAPC=1.24%, P＜0.05) and females showing a downward trend (AAPC=-1.67%, P＜0.05). Conclusions:The DALY of stomach and colorectal cancers in Changning District of Shanghai showed a decreasing trend. Males and the middle-aged and elderly populations are still the key targets for disease prevention and control in this district.

Objective To analyze the risk factors of intraoperative hypothermia in patients undergoing radical thyroidectomy under laparoscopy and to construct a nomogram prediction model. Methods A total of 336 patients who underwent laparoscopic radical thyroidectomy were selected as study subjects. According to intraoperative body temperature, they were divided into hypothermia group (195 cases) and normal temperature group (141 cases). The risk factors of intraoperative hypothermia in patients undergoing laparoscopic radical thyroidectomy were analyzed using the Logistic regression model. The nomogram prediction model was constructed using R software. The prediction performance of the nomogram prediction model was evaluated using the receiver operating characteristic (ROC) curve, calibration curve, and Hosmer-Lemeshow goodness-of-fit test. Results There were significant differences in age, intraoperative blood loss, amount of fluid infusion, and operation time between the two groups (P < 0.05). Multivariate Logistic regression analysis showed that age>60 years, intraoperative blood loss >60 mL, amount of fluid infusion>1 000 mL, and operation time>2.5 h were risk factors for intraoperative hypothermia in patients undergoing laparoscopic radical thyroidectomy (P < 0.05). A nomogram prediction model was constructed based on the four risk factors. The ROC curve showed that the area under the curve was 0.912 (95%CI, 0.884 to 0.941). The calibration curve and Hosmer-Lemeshow goodness-of-fit test showed that the slope of the calibration curve was close to 1 (χ²=9.140, P=0.243). Conclusion The nomogram prediction model based on age, intraoperative blood loss, amount of fluid infusion, and operation time has good predictive value for intraoperative hypothermia in patients undergoing laparoscopic radical thyroidectomy.

OBJECTIVE: To explore the ovarian function and its influencing factors in women of childbearing age with systemic lupus erythematosus (SLE). METHODS: A total of 107 female patients diagnosed with SLE at Peking University People' s Hospital from January 2017 to May 2024, aged between 20 and 40 years, were included in the study. At the same time, 40 matched healthy women aged between 20 and 40 years were selected as controls. Serum levels of anti-Müllerian hormone (AMH) were measured using the chemiluminescence method in both the control group and the SLE patients. The general clinical characteristics and medication history (including hormones, immunosuppressants, and biological agents) of the SLE patients were obtained through case retrieval. Changes in serum AMH levels before and after treatment with biological agents in the SLE patients were analyzed. RESULTS: (1) The AMH levels in the SLE patients were significantly lower than those in the healthy control group [1.475 (0.344, 3.030) μg/L vs. 2.934 (1.893, 4.761) μg/L, P < 0.001]. (2) The level of AMH in the SLE patients with normal menstruation was significantly higher than that in the patients with irregular menstruation [1.931 (0.638, 3.414) μg/L vs. 0.335 (0.159, 1.527) μg/L, P=0.004]. No statistical differences were found in clinical characteristics and laboratory indicators between the groups with decreased AMH group and normal AMH group. (3) The multivariate logistic regression analysis revealed that age (OR=1.124, 95%CI: 1.033-1.224, P=0.007) and disease duration (OR=1.100, 95%CI: 1.017-1.190, P=0.018) were identified as significant risk factors for the decline in AMH levels. (4) After 6 months of treatment with telitacicept, the AMH level was significantly higher than that before treatment [2.050 (0.763, 4.259) μg/L vs. 1.988 (0.473, 2.822) μg/L, P=0.043]. There was no significant difference in AMH level between patients receiving rituximab treatment for 6 months [2.026 (0.376, 2.267) μg/L vs. 1.545 (0.503, 3.414) μg/L, P=0.127]. CONCLUSION Ovarian function is decreased in SLE patients of childbearing age, and age and disease duration are the risk factors. The utilization of biological agents demonstrates favorable safety profiles regarding ovarian function in childbearing-age patients with SLE.
Humans ; Female ; Lupus Erythematosus, Systemic/physiopathology* ; Anti-Mullerian Hormone/blood* ; Adult ; Ovary/physiopathology* ; Young Adult ; Case-Control Studies ; Menstruation Disturbances/etiology* ; Ovarian Reserve

The immune checkpoint blockade therapy has profoundly revolutionized the field of cancer immunotherapy. However, despite great promise for a variety of cancers, the efficacy of immune checkpoint inhibitors is still low in colorectal cancer (CRC). This is mainly due to the immunosuppressive feature of the tumor microenvironment (TME). Emerging evidence reveals that certain chemotherapeutic drugs induce immunogenic cell death (ICD), demonstrating great potential for remodeling the immunosuppressive TME. In this study, the potential of ginsenoside Rg3 (Rg3) as an ICD inducer against CRC cells was confirmed using in vitro and in vivo experimental approaches. The ICD efficacy of Rg3 could be significantly enhanced by quercetin (QTN) that elicited reactive oxygen species (ROS). To ameliorate in vivo delivery barriers associated with chemotherapeutic drugs, a folate (FA)-targeted polyethylene glycol (PEG)-modified amphiphilic cyclodextrin nanoparticle (NP) was developed for co-encapsulation of Rg3 and QTN. The resultant nanoformulation (CD-PEG-FA.Rg3.QTN) significantly prolonged blood circulation and enhanced tumor targeting in an orthotopic CRC mouse model, resulting in the conversion of immunosuppressive TME. Furthermore, the CD-PEG-FA.Rg3.QTN achieved significantly longer survival of animals in combination with Anti-PD-L1. The study provides a promising strategy for the treatment of CRC.

Bisecting N-acetylglucosamine(GlcNAc),a GlcNAc linked to the core β-mannose resi-due via a β1,4 linkage,is a special type of N-glycosylation that has been reported to be involved in various biological processes,such as cell adhesion and fetal development.This N-glycan structure is abundant in human trophoblasts,which is postulated to be resistant to natural killer cell-mediated cytotoxicity,enabling a mother to nourish a fetus without rejection.In this study,we hypothesized that the human amniotic membrane,which serves as the last barrier for the fetus,may also express bisected-type glycans.To test this hypothesis,glycomic analysis of the human amniotic membrane was performed,and bisected N-glycans were detected.Furthermore,our pro-teomic data,which have been previously employed to explore human missing proteins,were ana-lyzed and the presence of bisecting GlcNAc-modified peptides was confirmed.A total of 41 glycoproteins with 43 glycopeptides were found to possess a bisecting GlcNAc,and 25 of these gly-coproteins were reported to exhibit this type of modification for the first time.These results provide insights into the potential roles of bisecting GlcNAc modification in the human amniotic membrane,and can be beneficial to functional studies on glycoproteins with bisecting GlcNAc modifications and functional studies on immune suppression in human placenta.