ABSTRACT
Loop-mediated isothermal amplification (LAMP) is a rapid and sensitive nucleic acid testing method for pathogen detection, yet the absence of a straightforward readout strategy remains challenging. We've successfully designed polyethyleneimine-stabilized gold nanoclusters (PEI-AuNCs) as a cationic AuNCs indicator tailored for distinguishing LAMP results, enabling direct visual inspection under UV light. Positive LAMP reactions with PEI-AuNCs, in combination with magnesium pyrophosphate crystals, yield red-fluorescent bulk precipitates visible to the naked eye. To address contamination concerns, we introduced a one-pot reaction by incorporating AuNCs into the lid recess. This one-pot LAMP assay demonstrates exceptional detection capability, identifying Salmonella enterica at concentrations as low as 101 CFU/mL within approximately 50 min, excluding nucleic acid extraction. The platform's versatility, achieved through customizable primers, positions it as a promising molecular diagnostic tool for rapid and visual pathogen detection across scientific disciplines.
ABSTRACT
Melatonin appears to be a promising supplement for obesity treatment. The antiobesity effects of melatonin on obese rodents are influenced by various factors, including the species, sex, the dosage of melatonin, treatment duration, administration via, daily treatment time, and initial body weight (IBW). Therefore, we conducted a meta-analysis and machine learning study to evaluate the antiobesity effect of melatonin on obese mice or rats from 31 publications. The results showed that melatonin significantly reduced body weight, serum glucose (GLU), triglycerides (TGs), low-density lipoprotein (LDL), and cholesterol (TC) levels in obese mice or rats but increased high-density lipoprotein (HDL) levels. Melatonin showed a slight positive effect on clock-related genes, although the number of studies was limited. Meta-regression analysis and machine learning indicated that the dosage of melatonin was the primary factor influencing body weight, with higher melatonin dosages leading to a stronger weight reduction effect. Together, male obese C57BL/6 mice and Sprague-Dawley rats with an IBW of 100-200 g showed better body weight reduction when supplemented with a dose of 10-30 mg/kg melatonin administered at night via injection for 5-8 weeks.
Subject(s)
Melatonin , Mice , Rats , Male , Animals , Melatonin/pharmacology , Melatonin/therapeutic use , Rodentia , Mice, Obese , Rats, Sprague-Dawley , Mice, Inbred C57BL , Obesity/drug therapy , Body Weight , Triglycerides , Weight Loss , Machine LearningABSTRACT
A multimodal analytical strategy utilizing different modalities to cross-validate each other, can effectively minimize false positives or negatives and ensure the accuracy of detection results. Herein, we establish a colorimetric, photothermal, and fluorescent triple modal CRISPR/Cas12a detection platform (CPF-CRISPR). An MNPs-ssDNA-HRP signal probe is designed to act as a substrate to trigger three signal outputs. In the presence of the DNA target, MNPs-ssDNA-HRP is cleaved by the activated CRISPR/Cas12a, resulting in the release of HRP and generating short DNA strands with 3-terminal hydroxyl on magnetic beads. The released HRP subsequently catalyzed TMB-H2O2 reaction and oxidized TMB is used for colorimetric and photothermal signal detection. Under the catalysis of terminal deoxynucleotidyl transferase (TdT), the remaining short DNA strands are used as primers to form poly-T and function as scaffolds to form copper nanoclusters for fluorescent signal output. To verify the practical application of CPF-CRISPR, we employed MRSA as a model. The results demonstrate the platform's high accuracy and sensitivity, with a limit of detection of 101 CFU/mL when combined with recombinase polymerase amplification. Therefore, by harnessing the programmability of CRISPR/Cas12a, the biosensor has the potential to detect various drug-resistant bacteria, demonstrating significant practical applicability.
Subject(s)
Biosensing Techniques , CRISPR-Cas Systems , Colorimetry , Hydrogen Peroxide , Bacteria/genetics , Coloring Agents , DNA, Single-StrandedABSTRACT
Controlling and mitigating infectious diseases caused by multiple pathogens or pathogens with several subtypes require multiplex nucleic acid detection platforms that can detect several target genes rapidly, specifically, sensitively, and simultaneously. Here, we develop a detection platform, termed Multiplex Assay of RPA and Collateral Effect of Cas12a-based System (MARPLES), based on multiplex nucleic acid amplification and Cas12a ssDNase activation to diagnose these diseases and identify their pathogens. We use the clinical specimens of hand, foot, and mouth disease (HFMD) and influenza A to evaluate the feasibility of MARPLES in diagnosing the disease and identifying the pathogen, respectively, and find that MARPLES can accurately diagnose the HFMD associated with enterovirus 71, coxsackievirus A16 (CVA16), CVA6, or CVA10 and identify the exact types of H1N1 and H3N2 in an hour, showing high sensitivity and specificity and 100% predictive agreement with qRT-PCR. Collectively, our findings demonstrate that MARPLES is a promising multiplex nucleic acid detection platform for disease diagnosis and pathogen identification.
Subject(s)
Hand, Foot and Mouth Disease , Influenza A Virus, H1N1 Subtype , Nucleic Acids , Humans , CRISPR-Cas Systems , Recombinases , Influenza A Virus, H3N2 Subtype , Sensitivity and Specificity , Nucleotidyltransferases , Multiplex Polymerase Chain ReactionABSTRACT
Objective: To examine the application effect of precision nursing strategies based on multidisciplinary collaboration model in older patients undergoing thoracoscopic surgery for lung cancer. Methods: A total of 100 patients who were admitted to our hospital for thoracoscopic surgery for lung cancer between July 2022 and March 2023 were prospectively enrolled for the study. They were assigned, with a random number table, to two groups, a control group receiving routine nursing care and an experimental group receiving nursing care based on multidisciplinary collaborative precision nursing strategies. Their lung function, anxiety and depression scores, and quality of life were assessed at three points of time, including upon admission, one week after surgery, and one month after surgery, and comparison was made between the two groups. Results: There were significant differences in forced expiratory volume in one second (FEV1) at the three time points ( F=156.787, P<0.001) and the ratio of FEV1 to forced vital capacity (FVC) (FEV1/FVC%) at the three time points ( F=25.587, P<0.001) between two groups. There were significant difference between the findings for FEV1, FEV1/FVC%, FVC, and maximum voluntary ventilation (MVV) indexes at 1 week and those at 1 month after surgery in the experimental group ( P<0.05). After the surgery, the pulmonary function of the experimental group was better than that of the control group. The anxiety and depression scores of the experimental group were lower than those of the control group, with the difference being statistically significant ( P<0.05), which suggested that the experimental group showed improvement in anxiety and depression in comparison with the control group. Regarding the quality of life, there were significant differences between the two groups in the scores for the functional dimension ( F=109.798, P<0.001), the symptom dimension ( F=106.936, P<0.001), other items ( F=78.798, P<0.001), and overall health dimensions ( F=174.307, P<0.001). At 1 week and 1 month after surgery, the experimental group had higher scores for the functional dimension and lower scores for the symptom dimension than the control group did, with the differences being statistically significant ( P<0.05). The overall health status of the experimental group was better than that of the control group. Conclusion: Precision nursing strategies based on multidisciplinary collaboration model can effectively help improve the lung function, the mood, and the quality of life of patients in the short term, showing considerable promise for wide clinical application.
Subject(s)
Lung Neoplasms , Quality of Life , Humans , Aged , Lung Neoplasms/surgery , Lung/surgery , Forced Expiratory Volume , ThoracoscopyABSTRACT
Accurate, rapid, and sensitive pathogenic detections play an important role in food safety. Herein, we developed a novel CRISPR/Cas12a mediated strand displacement/hybridization chain reaction (CSDHCR) nucleic acid assay for foodborne pathogenic colorimetric detection. A biotinylated DNA toehold is coupled on avidin magnetic beads and acts as an initiator strand to trigger the SDHCR. The SDHCR amplification allowed the formation of long hemin/G-quadruplex-based DNAzyme products to catalyze the TMB-H2O2 reaction. In the presence of the DNA targets, the trans-cleavage activity of CRISPR/Cas12a was activated to cleave the initiator DNA, resulting in the failure of SDHCR and no color change. Under optimal conditions, the CSDHCR has a satisfactory linear detection of DNA targets with a regression equation Y = 0.0531*X - 0.0091 (R2 = 0.9903) in the range of 10 fM to 1 nM, and the limit of detection was determined as 4.54 fM. In addition, Vibrio vulnificus, one foodborne pathogen, was used to verify the practical application of the method, and it showed satisfactory specificity and sensitivity with a limit of detection at 1.0 × 100 CFU/mL coupling with recombinase polymerase amplification. Our proposed CSDHCR biosensor could be a promising alternative method for ultrasensitive and visual detection of nucleic acids and the practical application of foodborne pathogens.
Subject(s)
Colorimetry , DNA, Catalytic , Colorimetry/methods , Hydrogen Peroxide , CRISPR-Cas Systems , DNA , DNA, Catalytic/geneticsABSTRACT
The development of multifunctional nanomaterials with bacterial imaging and killing activities is of great importance for the rapid diagnosis and timely treatment of bacterial infections. Herein, peptide-functionalized gold nanoclusters (CWR11-AuNCs) with high-intensity red fluorescence were successfully synthesized via a one-step method using CWR11 as a template and by optimizing the ratio of CWR11 to HAuCl4, reaction time, pH, and temperature. The CWR11-AuNCs bound to bacteria and exhibited selective fluorescence microscopy imaging properties, which is expected to provide a feasible method for locating and imaging bacteria in complex in vivo environments. In addition, CWR11-AuNCs not only retained the antibacterial and bactericidal activities of CWR11 but also exhibited certain inhibitory or killing effects on gram-negative and gram-positive bacteria and biofilms. The MICs of CWR11-AuNCs against Escherichia coli and Staphylococcus aureus were 178 and 89 µg/ml, respectively. Surprisingly, cell viability in the CWR11-AuNC-treated group was greater than that in the CWR11-treated group, and the low cytotoxicity exhibited by the CWR11-AuNCs make them more promising for clinical applications.
ABSTRACT
As an alternative to natural enzymes, artificial enzymes based on nanomaterials have attracted a lot of attention owing to their outstanding catalytic activity and high stability as well as low cost. Cu-MOF loaded with platinum nanoparticles (labeled Cu-MOF@Pt) was prepared by simple one-step wrapping method using platinum nanoparticles, copper nitrate trihydrate and 1,3,5-tricarboxybenzene. It was confirmed that Cu-MOF@Pt exhibits peroxidase-like activity, which can quickly catalyze the oxidation of 3,3',5,5'-tetramethylbenzidine (TMB) and produce blue oxidized TMB (oxTMB) in the presence of hydrogen peroxide (H2O2). Additionally, steady-state kinetics showed that Cu-MOF@Pt exhibits stronger appetency to TMB and H2O2 compared with horseradish peroxidase. Thanks to the peroxidase-like activity of Cu-MOF@Pt, a highly selective colorimetric method for glucose detection has been successfully established, the linear range is 2-15 mM (R2 =0.9999) and the Limit of Detection (LOD) is 0.42 mM, with a detection range that meets clinical needs. Moreover, its good intra- and inter-assay precision and excellent stability make the results of glucose detection very reproducible. The detection performance of 90.09% was still maintained at 4 â for 2 months. In conclusion, a new nanocomposite was successfully prepared and its selective detection ability for glucose was proved, which established a good basis for the clinical development of new enzymes for biosensors.
Subject(s)
Metal Nanoparticles , Nanocomposites , Colorimetry/methods , Glucose , Hydrogen Peroxide , Peroxidase , Peroxidases , PlatinumABSTRACT
Objective: To explore the factors influencing the degree of disability in patients with multiple sclerosis (MS), and to provide evidence for its early diagnosis, prognostic evaluation and clinical intervention. Methods: This retrospective observational study included 72 patients with relapsing-remitting multiple sclerosis (RRMS) at the First Hospital of Shanxi Medical University. All patients completed craniocerebral and spinal cord MRI (with or without Gd enhancement) and were evaluated for Expanded Disability Status Score (EDSS) scores before receiving treatment. Results: Among 72 patients with RRMS, 45 (62.5%) had an EDSS score ≤3; A total of 27 patients (37.5%) had an EDSS score >3 points. Univariate analysis showed that age, annual recurrence rate (ARR), drug use, albumin (ALB), triglycerides (TG), and total number of lesions in groups with EDSS score ≤3 were significantly different from those with an EDSS score > 3 points (P < 0.05). Multivariate logistic regression analysis showed that ALB, total number of lesions, and drug use were independent influencing factors of the degree of disability in patients with MS, and the difference was statistically significant (P < 0.05). An ROC curve was constructed using ALB and the total number of lesions. The AUC of ALB was 0.681, P < 0.05, and the best cut-off value was 44.2 g/L. Its sensitivity to predict the degree of disability in patients with multiple sclerosis was 85.2%, while its specificity was 51.1%. The AUC of the total number of lesions was 0.665 (P < 0.05) and the best cut-off value was 5.5. Its sensitivity to predict the degree of disability in patients with multiple sclerosis was 70.4%, while its specificity was 64.4%. The AUC of the combined ALB, total number of lesions, and drug use was 0.795 (P < 0.05), sensitivity was 77.8, and specificity was 73.3%. The optimal diagnostic cut-off value of the regression equation for the EDSS score of patients with multiple sclerosis was 0.420. Conclusion: Serum ALB, total number of lesions, and drug use in patients with multiple sclerosis were independent factors influencing the degree of disability. These findings provide clinical evidence for the prognostic evaluation and early intervention of patients with multiple sclerosis.
ABSTRACT
Contamination with the fungus Alternaria spp. is often considered to have originated from laboratory sources, which occasionally causes infection in immunocompromised patients, termed as phaeohyphomycosis. Here, we have reported a case of cutaneous alternariosis caused by Alternaria alternata. This diagnosis was based on microscopic examination and mycological culturing of patient's vesicular lesions, with the use of 5 molecular markers (namely, ITS, ATPase, Actin, rpb2, and tef1) for strain identification. We noted that Alternaria infection caused an increase in the serum level of (1-3)-ß-D-glucan (BG) in the patients. To the best of our knowledge, no such finding has been reported in previously in the literature.
Subject(s)
Alternariosis , beta-Glucans , Alternaria , Alternariosis/diagnosis , Alternariosis/drug therapy , Antifungal Agents/therapeutic use , Humans , Immunocompromised HostABSTRACT
In the previous study, we screened a novel lncRNA-ITGB2-AS1, which was down-regulated by bone morphogenetic protein 9 (BMP9) in breast cancer cell. Studying ITGB2-AS1 will lay the foundation for the exploring mechanism of the BMP9 inhibitory effect on breast cancer. The expression analysis related to ITGB2-AS1 in clinical samples was conducted on online websites. The overexpression plasmid or siRNA fragment was transfected into breast cancer cells to alter its gene expression. The MTT assay and flow cytometry were used to measure cell viability and cell cycle. Additionally, cell migration and invasion were detected by wound healing and transwell assay. The results of biological function experiments showed that ITGB2-AS1 could promote the migration and invasion of breast cancer. Furthermore, ITGB2-AS1 increased the mRNA and protein expression of ITGB2. Consistent with ITGB2-AS1, ITGB2 exerted the promotion effect on the migration and invasion of breast cancer and activated integrin-related FAK signaling. The OL plasmid expressing the truncation of ITGB2-AS1, which was complementary to ITGB2, was essential for activation of FAK signaling. In conclusion, LncRNA ITGB2-AS1 could promote the migration and invasion of breast cancer cells by up-regulating ITGB2.
Subject(s)
Breast Neoplasms/genetics , Integrin beta3/genetics , Neoplasm Invasiveness/genetics , RNA, Long Noncoding/genetics , Breast Neoplasms/pathology , Cell Cycle/genetics , Cell Line, Tumor , Cell Movement/genetics , Cell Proliferation/drug effects , Epithelial-Mesenchymal Transition/genetics , Female , Gene Expression Regulation, Neoplastic , Humans , Neoplasm Invasiveness/pathology , RNA, Messenger/genetics , Transcriptional Activation/genetics , TransfectionABSTRACT
As the most common malignant tumor of the urinary system worldwide, the bladder tumor has a high mortality rate, which is mainly due to its onset of concealment. Therefore, research into novel diagnostic markers and treatment of bladder cancer is urgently needed. BMP9 (Bone morphogenetic protein 9) is a member of BMP, which belongs to the TGF-ß (transforming growth factor-ß) superfamily. It has been associated with multiple tumors. We found that BMP9 is highly expressed in bladder cancer cells and it could significantly promote the proliferation and migration of bladder cancer cells. In the study of the mechanism of this effect, we found that BMP9 can increase the expression of lncRNA UCA1 (Urothelial cancer associated 1) through phosphorylated AKT. The promoting effect of BMP9 on bladder cancer cells was rescued after interfering with UCA1 in BMP9 overexpressed bladder cancer cells both in vitro and in vivo. Our research confirms that BMP9 promotes the proliferation and migration of bladder cancer cells through up-regulated lncRNA UCA1. It also shows that BMP9 is a novel diagnostic marker and a potential therapeutic target in bladder cancer.
Subject(s)
Cell Movement , Cell Proliferation , Gene Expression Regulation, Neoplastic , Growth Differentiation Factors/metabolism , RNA, Long Noncoding/genetics , Urinary Bladder Neoplasms/metabolism , Animals , Cell Line, Tumor , Growth Differentiation Factor 2 , Growth Differentiation Factors/genetics , Humans , Male , Mice , Mice, Nude , RNA, Long Noncoding/metabolism , Up-Regulation , Urinary Bladder Neoplasms/genetics , Urinary Bladder Neoplasms/pathologyABSTRACT
The inhibitor of ß-catenin and TCF (ICAT) blocks the binding of TCF to ß-catenin and has been demonstrated as a suppressor of the Wnt/ß-catenin signaling pathway. It has been reported to exert a different function around a wide variety of cancers. However, its function and underlying mechanisms in human cervical cancer remains unknown. In the present study, the expression of ICAT in 41 human cervical cancer tissues and 30 normal cervical tissues was evaluated by immunohistochemical analysis. ICAT was found highly expressed in cancer tissues. ICAT overexpression significantly promoted SiHa cell proliferation in vitro by causing G1 arrest, and enhanced cell migration and invasion whereas, ICAT knockdown induced opposite effects in Caski cells which have higher expression of ICAT. Downregulation or overexpression of ICAT resulted in an altered expression of the epithelial-mesenchymal transition (EMT). Furthermore, immunoprecipitation assays revealed that ICAT pormoted cervical cancer EMT by competing in E-cadhenin binding to ß-caterin. Overexpression of ICAT in SiHa cells promoted tumor growth and EMT was also demonstrated by the xenograft mouse experiment. These results demonstrate that ICAT contributed to the progression of cervical cancer and may play a role in the regulation of EMT by distrupting the E-cadherin/ß-catenin complex. It may be a novel potential therapeutic target for therapy in human cervical cancer.
Subject(s)
Cadherins/metabolism , Intracellular Signaling Peptides and Proteins/genetics , Intracellular Signaling Peptides and Proteins/metabolism , Uterine Cervical Neoplasms/pathology , beta Catenin/metabolism , Adaptor Proteins, Signal Transducing , Animals , Antigens, CD , Cell Line, Tumor , Cell Movement , Cell Proliferation , Epithelial-Mesenchymal Transition , Female , Gene Expression Regulation, Neoplastic , HeLa Cells , Humans , Mice , Neoplasm Metastasis , Neoplasm Transplantation , Up-Regulation , Uterine Cervical Neoplasms/genetics , Uterine Cervical Neoplasms/metabolismABSTRACT
Bone morphogenetic protein 9 (BMP9) possesses multiple functions, but its effects on breast cancer cells in adipose microenvironment are still unclear. This study aimed to investigate whether BMP9 is able to modulate the interaction between pre-adipocytes/adipocytes and breast cancer cells. An in vitro co-culture system was established by using pre-adipocytes/adipocytes and MDA-MB-231 breast cancer cells with BMP9 over-expression. The leptin expression and leptin-induced signaling pathway were evaluated in this co-culture system. MTT assay, EdU assay and flow cytometry were used to assess the proliferation of MDA-MB-231 cells. Wound-healing assay and Transwell migration assay were used to assess the migration of MDA-MB-231 cells. Immunofluorescence staining was used to detect the expression of leptin recepter (ObR) in MDA-MB-231 cells. The expression of key molecules in leptin signaling pathway in co-culture system were detected by Western blotting. MDA-MB-231 cells and pre-adipocytes/adipocytes were inoculated into nude mice, the tumor volume was measured, and the protein expression of key molecules in leptin signaling pathway was detected. Results showed BMP9 inhibited breast tumor growth in vitro and in vivo and reduced the migration of breast cancer cells in vitro. MDA-MB-231 cells with BMP9 over-expression decreased leptin expression in pre-adipocytes/adipocytes and had reduced phosphorylation of STAT3, ERK1/2 and AKT. Taken together, our study indicates that BMP9 can inhibit the growth and metastasis of breast cancer cells, which may be related to interaction between pre-adipocytes/adipocytes and MDA-MB-231 cells via leptin signaling pathway.
Subject(s)
Adipocytes/metabolism , Breast Neoplasms/metabolism , Cell Communication , Growth Differentiation Factor 2/metabolism , 3T3-L1 Cells , Animals , Apoptosis , Breast Neoplasms/genetics , Breast Neoplasms/pathology , Cell Line, Tumor , Cell Movement , Cell Proliferation , Coculture Techniques , Disease Models, Animal , Female , Gene Expression , Growth Differentiation Factor 2/genetics , Heterografts , Humans , Leptin/metabolism , Mice , Neoplasm Metastasis , Signal TransductionABSTRACT
Objective To investigate the effect of overexpressed inhibitor of ß-catenin and T cell factor (ICAT) on the proliferation and migration of human cervical cancer Caski cells. Methods Caski cells were transfected with ICAT recombinant adenovirus (AdICAT). The levels of ICAT mRNA and protein were detected by quantitative real-time PCR (qRT-PCR) and Western blotting, respectively. Effect of ICAT overexpression on proliferation, cell cycle and migration in Caski cells was respectively evaluated by MTT assay, flow cytometry and TranswellTM migration assays. Results The expression of ICAT remarkably increased in Caski cells after AdICAT infection. Overexpression of ICAT promoted Caski cells' proliferation, arrested the cell cycle in the S phase and enhanced cell migration. Conclusion Overexpression of ICAT can promote the proliferation and migration of Caski cervical cancer cells.
Subject(s)
Cell Movement/physiology , Cell Proliferation/physiology , Intracellular Signaling Peptides and Proteins/metabolism , Uterine Cervical Neoplasms/metabolism , Adaptor Proteins, Signal Transducing , Blotting, Western , Cell Cycle/genetics , Cell Cycle/physiology , Cell Line, Tumor , Cell Movement/genetics , Cell Proliferation/genetics , Female , Flow Cytometry , Humans , Intracellular Signaling Peptides and Proteins/genetics , RNA, Messenger , Reverse Transcriptase Polymerase Chain Reaction , Uterine Cervical Neoplasms/pathology , beta Catenin/genetics , beta Catenin/metabolismABSTRACT
Bone marrow stroma plays a critical role in the bone metastasis of breast cancer. Bone marrow-derived mesenchymal stem cells (BMSC) are critical to facilitate cancer progression. Human bone morphogenetic protein 9 (BMP9) is the most potent osteogenic factor and one of bone-stored growth factors involved in both promotion and inhibition of different cancers. However, it is unclear whether BMP9 correlates with the bone metastasis of breast cancer. This study was to evaluate the role of BMP9 in the interaction between BMSC and breast cancer cells (BCC). To determine whether BMP9 is able to block the tumor promoting effect of BMSC, an in vitro model was developed using breast cancer MDA-MB-231 cells co-cultured with bone marrow-derived mesenchymal stem cells HS-5 with-BMP9 overexpression. The expressions of metastasis-related genes were detected to identify important factors mediating the role of BMP9 in breast cancer cells. Results showed BMP9 could inhibit invasion and promote apoptosis of MDA-MB-231 cells. The expressions of interleukin-6 (IL-6), matrix metalloproteinase-2 (MMP-2) and monocyte chemoattratctant protein-1 (MCP-1) decreased in the MDA-MB-231 cells of BMP9 over-expression group, and the expressions of epithelial-mesenchymal transition (EMT)-related molecules was also reduced. On the other hand, the expression of stromal cell derived factor-1 (SDF-1) decreased in HS-5 cells of BMP9 over-expression group. Taken together, BMP9 is able to inhibit the migration and promote the apoptosis of breast cancer by regulating the interaction between MDA-MB-231 cells and HS-5 cells in which SDF-1/CXCR4-PI3K pathway and EMT are involved.
ABSTRACT
OBJECTIVE: To investigate if a six-year intensive lifestyle intervention in people with pre-diabetes lead to reduction of cardiovascular events and cardiovascular disease (CVD) mortality in subsequent 23 years. METHODS: Five hundreds and nineteen subjects with normal glucose tolerance (NGT) and 577 subjects with impaired glucose tolerance (IGT) in Da Qing city were recruited in the study in 1986. The IGT subjects randomly assigned to either the no-intervention group or one of three lifestyle intervention groups (diet, exercise, or diet plus exercise) to receive a 6-year lifestyle intervention. In 2009, the participants were followed up to assess the primary outcomes of cardiovascular events and CVD mortality by a questionnaire and medical records. RESULTS: Subjects in IGT no-intervention group had the highest incidences of cardiovascular events (44.44%) and CVD mortality (20.00%), while those in NGT group had the lowest incidences of cardiovascular events (29.59%) and CVD mortality (7.52%) after 23-year follow-up. The incidences of cardiovascular events and CVD mortality in IGT intervention subjects were 37.84% and 12.53%, respectively. The multivariable analyses showed that, after controlling of age, gender, BMI smoking, blood pressure and cardiovascular event at baseline, the CVD mortality and incidence of cardiovascular events in IGT no-intervention group was 1.89 (HR = 1.89, 95%CI 1.11-3.22, P = 0.02) and 1.38 (HR = 1.38, 95%CI 1.01-1.90, P = 0.04) times of those in NGT group. However, the CVD mortality and incidence of cardiovascular events were not different in the IGT intervention group compared with those in the NGT group (HR = 1.39, 95%CI 0.89-2.18, P = 0.15 and HR = 1.25, 95%CI 0.98-1.59, P = 0.07, respectively). CONCLUSIONS: Subjects with IGT were at high risk for cardiovascular events and mortality. A six-year lifestyle intervention in this population can reduce both the incidence of cardiovascular event and CVD mortality.
Subject(s)
Blood Glucose/metabolism , Cardiovascular Diseases/mortality , Diabetes Complications/epidemiology , Diabetes Mellitus, Type 2/prevention & control , Glucose Intolerance/complications , Life Style , Blood Pressure/physiology , Cardiovascular Diseases/blood , Cardiovascular Diseases/prevention & control , Case-Control Studies , China/epidemiology , Diabetes Mellitus, Type 2/blood , Diabetes Mellitus, Type 2/epidemiology , Diabetes Mellitus, Type 2/mortality , Exercise , Female , Follow-Up Studies , Glucose Intolerance/epidemiology , Humans , IncidenceABSTRACT
PURPOSE: Breast cancer cells frequently metastasize to distant organs, including bone. Interactions between breast cancer cells and the bone microenvironment are known to enhance tumor growth and osteolytic damage. Here we investigated whether BMP9 (a secretary protein) may change the bone microenvironment and, by doing so, regulate the cross-talk between breast cancer cells and bone marrow-derived mesenchymal stem cells. METHODS: After establishing a co-culture system composed of MDA-MB-231 breast cancer cells and HS-5 bone marrow-derived mesenchymal stem cells, and exposure of this system to BMP9 conditioned media, we assessed putative changes in migration and invasion capacities of MDA-MB-231 cells and concomitant changes in osteogenic marker expression in HS-5 cells and metastases-related genes in MDA-MB-231 cells. RESULTS: We found that BMP9 can inhibit the migration and invasion of MDA-MB-231 cells, and promote osteogenesis and proliferation of HS-5 cells, in the co-culture system. We also found that the BMP9-induced inhibition of migration and invasion of MDA-MB-231 cells may be caused by a decreased RANK ligand (RANKL) secretion by HS-5 cells, leading to a block in the AKT signaling pathway. CONCLUSIONS: From our data we conclude that BMP9 inhibits the migration and invasion of breast cancer cells, and promotes the osteoblastic differentiation and proliferation of bone marrow-derived mesenchymal stem cells by regulating cross-talk between these two types of cells through the RANK/RANKL signaling axis.
Subject(s)
Breast Neoplasms/genetics , Cell Communication/genetics , Growth Differentiation Factors/genetics , Mesenchymal Stem Cells/metabolism , Animals , Blotting, Western , Breast Neoplasms/metabolism , Breast Neoplasms/pathology , Cell Communication/drug effects , Cell Line , Cell Line, Tumor , Cell Movement/drug effects , Cell Proliferation/drug effects , Cell Proliferation/genetics , Coculture Techniques , Culture Media, Conditioned/pharmacology , Female , Gene Expression Regulation, Neoplastic , Growth Differentiation Factor 2 , Growth Differentiation Factors/metabolism , HCT116 Cells , Humans , Immunohistochemistry , Mesenchymal Stem Cells/cytology , Mice, Nude , Osteogenesis/drug effects , Osteogenesis/genetics , Proto-Oncogene Proteins c-akt/metabolism , RANK Ligand/metabolism , Reverse Transcriptase Polymerase Chain Reaction , Signal Transduction/drug effects , Xenograft Model Antitumor Assays/methodsABSTRACT
Childhood adiposity is increasingly recognized as a significant predictor of cardiometabolic risks in later life. The aim of this study was to investigate factors associated with longitudinal changes in weight during childhood and the development of metabolic disease risk factors. Four hundred twenty-four children from DaQing city, China, were recruited at 5 y old and followed up for 5 y. Birth weight, television (TV) viewing time at 5 y old, blood pressure, anthropometric measurements, fasting plasma insulin (FI), and triglycerides (TG) levels were measured at 5 and 10 y old. Both birth weight and TV viewing time at 5 y old significantly correlated with percentage of ideal weight for height (WFH) at 5 y old (WFH5; p = 0.0032 and p = 0.01), but only TV time was significantly correlated with WFH at 10 y old (WFH10; p < 0.0001). Blood pressures, FI, homeostasis model assessment for insulin resistance (HOMA-IR), and TG at 10 y old were significantly greater in those children who had greater change in WFH from 5 to 10 y old (ΔWFH). We concluded that TV viewing time was the stronger determinant of later childhood adiposity. A greater ΔWFH was associated with increased cardiometabolic risk factors at 10 y old.
Subject(s)
Adiposity , Metabolic Syndrome/etiology , Metabolic Syndrome/physiopathology , Adult , Anthropometry , Blood Glucose/metabolism , Blood Pressure/physiology , Body Mass Index , Child , Child, Preschool , China , Cohort Studies , Female , Humans , Insulin/blood , Insulin Resistance/physiology , Longitudinal Studies , Male , Obesity/etiology , Risk Factors , TelevisionABSTRACT
BACKGROUND: Intensive lifestyle interventions can reduce the incidence of type 2 diabetes in people with impaired glucose tolerance, but how long these benefits extend beyond the period of active intervention, and whether such interventions reduce the risk of cardiovascular disease (CVD) and mortality, is unclear. We aimed to assess whether intensive lifestyle interventions have a long-term effect on the risk of diabetes, diabetes-related macrovascular and microvascular complications, and mortality. METHODS: In 1986, 577 adults with impaired glucose tolerance from 33 clinics in China were randomly assigned to either the control group or to one of three lifestyle intervention groups (diet, exercise, or diet plus exercise). Active intervention took place over 6 years until 1992. In 2006, study participants were followed-up to assess the long-term effect of the interventions. The primary outcomes were diabetes incidence, CVD incidence and mortality, and all-cause mortality. FINDINGS: Compared with control participants, those in the combined lifestyle intervention groups had a 51% lower incidence of diabetes (hazard rate ratio [HRR] 0.49; 95% CI 0.33-0.73) during the active intervention period and a 43% lower incidence (0.57; 0.41-0.81) over the 20 year period, controlled for age and clustering by clinic. The average annual incidence of diabetes was 7% for intervention participants versus 11% in control participants, with 20-year cumulative incidence of 80% in the intervention groups and 93% in the control group. Participants in the intervention group spent an average of 3.6 fewer years with diabetes than those in the control group. There was no significant difference between the intervention and control groups in the rate of first CVD events (HRR 0.98; 95% CI 0.71-1.37), CVD mortality (0.83; 0.48-1.40), and all-cause mortality (0.96; 0.65-1.41), but our study had limited statistical power to detect differences for these outcomes. INTERPRETATION: Group-based lifestyle interventions over 6 years can prevent or delay diabetes for up to 14 years after the active intervention. However, whether lifestyle intervention also leads to reduced CVD and mortality remains unclear.