BACKGROUND/OBJECTIVES: The objectives of this study were to investigate the effects of lycopene on the migration, adhesion, tube formation capacity, and p38 mitogen-activated protein kinase (p38 MAPK) activity of endothelial progenitor cells (EPCs) cultivated with high glucose (HG) and as well as explore the mechanism behind the protective effects of lycopene on peripheral blood EPCs. MATERIALS/METHODS: Mononuclear cells were isolated from human peripheral blood by Ficoll density gradient centrifugation. EPCs were identified after induction of cellular differentiation. Third generation EPCs were incubated with HG (33 mmol/L) or 10, 30, and 50 microg/mL of lycopene plus HG. MTT assay and flow cytometry were performed to assess proliferation and apoptosis of EPCs. EPC migration was assessed by MTT assay with a modified boyden chamber. Adhesion assay was performed by replating EPCs on fibronectin-coated dishes, after which adherent cells were counted. In vitro vasculogenesis activity was assayed by Madrigal network formation assay. Western blotting was performed to analyze protein expression of both phosphorylated and non-phosphorylated p38 MAPK. RESULTS: The proliferation, migration, adhesion, and in vitro vasculogenesis capacity of EPCs treated with 10, 30, and 50 microg/mL of lycopene plus HG were all significantly higher comapred to the HG group (P < 0.05). Rates of apoptosis were also significantly lower than that of the HG group. Moreover, lycopene blocked phosphorylation of p38 MAPK in EPCs (P < 0.05). To confirm the causal relationship between MAPK inhibition and the protective effects of lycopene against HG-induced cellular injury, we treated cells with SB203580, a phosphorylation inhibitor. The inhibitor significantly inhibited HG-induced EPC injury. CONCLUSIONS: Lycopene promotes proliferation, migration, adhesion, and in vitro vasculogenesis capacity as well as reduces apoptosis of EPCs. Further, the underlying molecular mechanism of the protective effects of lycopene against HG-induced EPC injury may involve the p38 MAPK signal transduction pathway. Specifically, lycopene was shown to inhibit HG-induced EPC injury by inhibiting p38 MAPKs.
Apoptosis ; Blotting, Western ; Centrifugation, Density Gradient ; Ficoll ; Flow Cytometry ; Glucose* ; Humans ; p38 Mitogen-Activated Protein Kinases ; Phosphorylation ; Protein Kinases ; Signal Transduction ; Stem Cells*

BACKGROUND/OBJECTIVES: The objectives of this study were to investigate the effects of lycopene on the migration, adhesion, tube formation capacity, and p38 mitogen-activated protein kinase (p38 MAPK) activity of endothelial progenitor cells (EPCs) cultivated with high glucose (HG) and as well as explore the mechanism behind the protective effects of lycopene on peripheral blood EPCs. MATERIALS/METHODS: Mononuclear cells were isolated from human peripheral blood by Ficoll density gradient centrifugation. EPCs were identified after induction of cellular differentiation. Third generation EPCs were incubated with HG (33 mmol/L) or 10, 30, and 50 microg/mL of lycopene plus HG. MTT assay and flow cytometry were performed to assess proliferation and apoptosis of EPCs. EPC migration was assessed by MTT assay with a modified boyden chamber. Adhesion assay was performed by replating EPCs on fibronectin-coated dishes, after which adherent cells were counted. In vitro vasculogenesis activity was assayed by Madrigal network formation assay. Western blotting was performed to analyze protein expression of both phosphorylated and non-phosphorylated p38 MAPK. RESULTS: The proliferation, migration, adhesion, and in vitro vasculogenesis capacity of EPCs treated with 10, 30, and 50 microg/mL of lycopene plus HG were all significantly higher comapred to the HG group (P < 0.05). Rates of apoptosis were also significantly lower than that of the HG group. Moreover, lycopene blocked phosphorylation of p38 MAPK in EPCs (P < 0.05). To confirm the causal relationship between MAPK inhibition and the protective effects of lycopene against HG-induced cellular injury, we treated cells with SB203580, a phosphorylation inhibitor. The inhibitor significantly inhibited HG-induced EPC injury. CONCLUSIONS: Lycopene promotes proliferation, migration, adhesion, and in vitro vasculogenesis capacity as well as reduces apoptosis of EPCs. Further, the underlying molecular mechanism of the protective effects of lycopene against HG-induced EPC injury may involve the p38 MAPK signal transduction pathway. Specifically, lycopene was shown to inhibit HG-induced EPC injury by inhibiting p38 MAPKs.
Apoptosis ; Blotting, Western ; Centrifugation, Density Gradient ; Ficoll ; Flow Cytometry ; Glucose* ; Humans ; p38 Mitogen-Activated Protein Kinases ; Phosphorylation ; Protein Kinases ; Signal Transduction ; Stem Cells*

OBJECTIVETo investigate the expression characteristics of the gene of coiled-coil domain-containing protein 70 (Ccdc70) in the mouse testis and its potential role in spermatogenesis.

METHODSUsing expression profile microarray, we screened the mouse testis-specific gene Ccdc70, studied its expression characteristics in the mouse testis by RT-PCR, real-time PCR, Western blot and immunohistochemistry, followed by bioinformatic analysis of the Ccdc70 protein.

RESULTSThe Ccdc70 gene was expressed highly in the testis but lowly in the epididymis of the mice. The Ccdc70 protein was expressed mainly in the spermatocytes and round spermatids of the testis and in the epithelial cells of the epididymis. Bioinformatic analysis showed a structural domain in the Ccdc70 protein, which was highly conserved in mammalian evolution.

CONCLUSIONThe Ccdc70 gene is highly expressed in the mouse testis and mainly in the spermatocytes, round spermatids, and epididymal epithelial cells, which indicates that it is involved in the regulation of spermatogenesis and epididymal sperm maturation.

Animals ; Computational Biology ; Gene Expression Regulation, Developmental ; Male ; Mice ; Proteins ; genetics ; Spermatogenesis ; genetics ; Testis ; metabolism

OBJECTIVETo study the effect of lycopene on red blood cell and the level of blood lipid.

METHODSAccording to the level of serum total cholesterol and weight, forty-eight adult male SD rats were divided randomly into six groups: normal control (group A), fed by normal feed; hyperlipidemia group (group B): fed by high fat diet; positive control group (group C): fed by high fat diet plus 10 mg * kg(-1) * d(-1) fluvastatin sodium; lycopene groups: fed by high fat diet plus 11 (group D), 22 (group E), 44 mg * kg(-1) * d(-1) (group F) lycopene through gavage, respectively. For all six groups, the level of serum total cholesterol (TC) and total triglyceride (TG) were measured at the end of 0, 1, 3 weeks of the study by taking samples from tail vein. At the end of the experiment, RBC and HGB were measured.

RESULTSAfter the rats were fed with high-fat feed for a week, models of hyperlipidemia rats were established. At the end of 3 weeks, TC of group A, B, C, D, E and F were (1.31 +/- 0.05), (19.40 +/- 0.54), (4.66 +/- 0.07), (7.18 +/- 0.06), (5.30 +/- 0.28), (4.49 +/- 0.23) mmol/L (F = 4395.72, P = 0.00), respectively;and TG were (0.42 +/- 0.01), (2.29 +/- 0.42), (0.69 +/- 0.03), (1.10 +/- 0.05), (0.63 +/- 0.02), (0.62 +/- 0.04) mmol/L (F = 127.26, P = 0.00), respectively; HGB were (143.13 +/- 6.33), (112.63 +/- 2.56), (124.75 +/- 3.62), (124.63 +/- 7.78), (132.38 +/- 6.41), (142.13 +/- 5.54) g/L (F = 34.14, P = 0.00), respectively; RBC were (6.75 +/- 0.60) x 10(12)/L, (5.08 +/- 0.75) x 10(12)/L, (7.14 +/- 0.82) x 10(12)/L, (5.94 +/- 1.09) x 10(12)/L, (6.18 +/- 0.36) x 10(12)/L and (7.31 +/- 0.58) x 10(12)/L (F = 10.35, P = 0.00), respectively.

CONCLUSIONLycopene have some protective effects on red blood cells of the hyperlipidemic rats by regulating the blood lipid and antioxidant.

Animals ; Carotenoids ; pharmacology ; Cholesterol ; blood ; Cholesterol, LDL ; blood ; Erythrocytes ; drug effects ; Hypercholesterolemia ; blood ; Lipids ; blood ; Male ; Rats ; Rats, Sprague-Dawley ; Triglycerides ; blood

OBJECTIVETo analyze the clinical and laboratory features of chronic lymphocytic leukemia (CLL).

METHODSRetrospective investigation of 263 patients with CLL in our hospital between Feb. 2000 and Jan. 2007.

RESULTSThe median age was 60 years with male/female ratio of 2.17 : 1. Patients who were asymptomatic at diagnosis (35.4%) had low Rai grades. Fatigue and lymphadenopathy (54.8%) were the most common features at presentation. Infections, connective tissue diseases and secondary tumors frequently occurred in CLL. WBC counts were between (10 - 100) x 10(9)/L, with lymphocytes percentages more than 0.50 in 97.1% patients. Bone marrow was normal- to hyper-cellularity with lymphocytes percentages more than 0.300 in 99.4% patients. Diffuse infiltrations in bone marrow section were found in 72.2% patients. There were lower CD5 (85.1%) and higher CD25 (78.9%) positivities in the present series as compared with that in other reports. Hypogammaglobulinemia, especially hypo-IgM, usually occurred. Chromosome abnormality were rarely found by routine chromosome examination.

CONCLUSIONSThere were some clinical and laboratory characteristics different from that of abroad data. Further exploration of new markers is required for prognosis prediction and treatment choice.

Adult ; Aged ; Aged, 80 and over ; Female ; Humans ; Leukemia, Lymphocytic, Chronic, B-Cell ; genetics ; pathology ; Male ; Middle Aged ; Retrospective Studies

This study was aimed to investigate various factors influencing long-term survival in patients with acute promyelocytic leukemia. A single institutional retrospective study with long-term follow-up was performed to better define the prognostic factors and a rationale for the use of ATRA, chemotherapy, and As(2)O(3) in the treatment of newly diagnosed APL patients. Newly diagnosed patients with APL entering complete remission (CR) were followed up for 6 to 185 months (n = 170) from January 1990 to December 2004. Univariate and multivariate analysis of 8 potential factors influencing survival and prognosis were carried out with Log-Rank and Cox regression method, including sex, age, initial WBC count, the level of lactic hydrogenase (LDH), first induction regimen, time from induction therapy to CR, post-remission therapy, negative or positive rate of PML-RAR alpha and follow-up of reverse transcription-polymerase chain reaction (RT-PCR). The results showed that the estimated 5-year overall survival (OS) and relapse-free survival (RFS) were 80.9% +/- 4.0% and 71.0% +/- 4.0% respectively. The 23 patients relapsed at the median time of 15 months (6 - 70) after CR. Univariate analysis revealed that initial WBC count, first induction regimen, time from induction therapy to CR, type of post-remission therapy and persistent negative RT-PCR in remission were important prognostic factors for long-term survival. Multivariate study demonstrated that only type of post-remission therapy was associated with RFS and OS. It is concluded that the post-remission treatment combining ATRA, As(2)O(3) and chemotherapy would significantly improve the long-term survival of APL patients entering CR(1).
Adolescent ; Adult ; Aged ; Antineoplastic Combined Chemotherapy Protocols ; therapeutic use ; Arsenicals ; administration & dosage ; Child ; Female ; Follow-Up Studies ; Humans ; Leukemia, Promyelocytic, Acute ; drug therapy ; mortality ; Male ; Middle Aged ; Oncogene Proteins, Fusion ; metabolism ; Oxides ; administration & dosage ; Prognosis ; Proportional Hazards Models ; Remission Induction ; Retrospective Studies ; Survival Analysis ; Survival Rate ; Tretinoin ; administration & dosage

Objective To develop a shear force-induced intervertebral disc degeneration (IDD) in vivo animal model, and investigate the relationship between shear stress and IDD. Methods A total of 20 Japanese white rabbits were randomly divided into two groups. In loading group (n=10), shear force of 50 N was applied on the disc of L4/5 for 4 weeks by a custom-made external shear force loading device. In control group (n=10), the animals underwent a sham operation with the external loading device situated, but their discs remained unloaded. After 4 weeks, all the intervertebral discs of L4/5 were executed for the pathologic examination. Results The postoperative radiographic examination showed a perfect position of the loading device, and the operation process and implanted loading device had no effect on daily activities and diet of the experiment animals. The pathological examination showed an irregular arrangement of annulus fibrosus and a significant decrease of normal nucleus pulposus cells in loading group. Conclusions The new custom made device greatly reduced the wounds on animal vertebra and provided a reliable shear force. The development of in vivo animal model indicates that IDD can be induced by shear force, which is of significance to further study the relationship between loading and IDD.

Bisphenol A is a common environmental factor and endocrine disruptor that exerts a negative impact on male reproductive ability. By exploring bisphenol A-induced testicular cell death using the Institute of Cancer Research (ICR) mouse model, we found that a ferroptosis phenomenon may exist. Mice were divided into six groups and administered different doses of bisphenol A via intragastric gavage once daily for 45 consecutive days. Serum was then collected to determine the levels of superoxide dismutase and malondialdehyde. Epididymal sperm was also collected for semen analysis, and testicular tissue was collected for ferritin content determination, electron microscope observation of mitochondrial morphology, immunohistochemistry, real-time quantitative polymerase chain reaction, and western blot analysis. Exposure to bisphenol A was found to decrease sperm quality and cause oxidative damage, iron accumulation, and mitochondrial damage in the testes of mice. In addition, bisphenol A was confirmed to affect the expression of the ferroptosis-related genes, glutathione peroxidase 4 (GPX4), ferritin heavy chain 1 (FTH1), cyclooxygenase 2 (COX2), and acyl-CoA synthetase 4 (ACSL4) in mouse testicular tissues. Accordingly, we speculate that bisphenol A induces oxidative stress, which leads to the ferroptosis of testicular cells. Overall, the inhibition of ferroptosis may be a potential strategy to reduce male reproductive toxicity caused by bisphenol A.
Male ; Mice ; Animals ; Testis/metabolism* ; Ferroptosis ; Semen ; Oxidative Stress

Alzheimer's disease (AD), the most common type of dementia, is becoming a major challenge for global health and social care. However, the current understanding of AD pathogenesis is limited, and no early diagnosis and disease-modifying therapy are currently available. During the past year, significant progress has been made in clinical research on the diagnosis, prevention, and treatment of AD. In this review, we summarize the latest achievements, including diagnostic biomarkers, polygenic hazard score, amyloid and tau PET imaging, clinical trials targeting amyloid-beta (Aβ), tau, and neurotransmitters, early intervention, and primary prevention and systemic intervention approaches, and provide novel perspectives for further efforts to understand and cure the disease.
Alzheimer Disease ; diagnosis ; physiopathology ; therapy ; Animals ; Biomarkers ; blood ; Biomedical Research ; methods ; Disease Progression ; Humans ; Magnetic Resonance Imaging

Platelets are reprogrammed by cancer via a process called education, which favors cancer development. The transcriptional profile of tumor-educated platelets (TEPs) is skewed and therefore practicable for cancer detection. This intercontinental, hospital-based, diagnostic study included 761 treatment-naïve inpatients with histologically confirmed adnexal masses and 167 healthy controls from nine medical centers (China, n = 3; Netherlands, n = 5; Poland, n = 1) between September 2016 and May 2019. The main outcomes were the performance of TEPs and their combination with CA125 in two Chinese (VC1 and VC2) and the European (VC3) validation cohorts collectively and independently. Exploratory outcome was the value of TEPs in public pan-cancer platelet transcriptome datasets. The AUCs for TEPs in the combined validation cohort, VC1, VC2, and VC3 were 0.918 (95% CI 0.889-0.948), 0.923 (0.855-0.990), 0.918 (0.872-0.963), and 0.887 (0.813-0.960), respectively. Combination of TEPs and CA125 demonstrated an AUC of 0.922 (0.889-0.955) in the combined validation cohort; 0.955 (0.912-0.997) in VC1; 0.939 (0.901-0.977) in VC2; 0.917 (0.824-1.000) in VC3. For subgroup analysis, TEPs exhibited an AUC of 0.858, 0.859, and 0.920 to detect early-stage, borderline, non-epithelial diseases and 0.899 to discriminate ovarian cancer from endometriosis. TEPs had robustness, compatibility, and universality for preoperative diagnosis of ovarian cancer since it withstood validations in populations of different ethnicities, heterogeneous histological subtypes, and early-stage ovarian cancer. However, these observations warrant prospective validations in a larger population before clinical utilities.
Humans ; Female ; Blood Platelets/pathology* ; Biomarkers, Tumor/genetics* ; Ovarian Neoplasms/pathology* ; China