Statins and risk of venous thromboembolic diseases: A two-sample mendelian randomization study.

BACKGROUND AND AIMS: In observational studies, statins have been suggested to have protective effects on venous thromboembolism (VTE), including deep vein thrombosis (DVT) and pulmonary embolism (PE). To this aim, we performed a two-sample mendelian randomization (MR) analysis to determine whether these associations were causal. METHODS AND RESULTS: Data on the single nucleotide polymorphisms (SNPs) related to statin medication were obtained from the FinnGen study, and data for VTE, PE and DVT of lower extremities (LEDVT) were from the UK Biobank study, respectively. Inverse variance weighted (IVW) method was used as the principal analysis of MR, and sensitivity analysis was performed to detect horizontal pleiotropy and heterogeneity. MR estimates showed an inverse causal association between statin medication and the risk of VTE (odds ratio [OR]: 0.999, 95% CI: 0.998-1.000, P = 0.004), PE (OR: 0.999, 95% CI: 0.999-1.000, P = 0.011) and LEDVT (OR: 0.999, 95% CI: 0.999-1.000, P = 0.008). CONCLUSION: Our findings provide direct evidence that statins might decrease the risk of VTE, PE and LEDVT in agreement with observational studies. The specific mechanism of statin therapy for venous thromboembolism needs to be further studied.

Association between weight change and breast cancer prognosis.

PURPOSE: Results of the associations between weight change after breast cancer diagnosis and prognosis were inconsistent. The modification effects of menopausal status and endocrine therapy on the associations remain poorly understood. METHODS: A total of 2016 breast cancer patients were recruited between October 2008 and January 2018 and followed up until December 31, 2019 in Guangzhou. Multivariate Cox models were used to estimate the hazard ratios (HRs) and 95% confidence intervals (95% CIs) for progression-free survival (PFS) in association with weight change after diagnosis. RESULTS: Weight loss at 2 years (HR = 1.34, 95% CI 0.87-2.06) or more than 2 years (HR = 1.95, 95% CI 1.22-3.10) after diagnosis increased risk of breast cancer progression. The adverse effect of weight loss was significantly more pronounced in post-menopausal than pre-menopausal women, particularly for weight loss at 2 years after diagnosis, with the HRs and 95% CIs of 2.41 (1.25-4.63) and 0.90 (0.49-1.64), respectively. Weight gain tended to reduce the risk of disease progression among patients with endocrine therapy but not for those with non-endocrine therapy; the significant interaction between weight gain at 2 years after diagnosis and endocrine therapy was observed (Pinteraction = 0.042). CONCLUSION: Our finding suggested that weight loss was detrimental to breast cancer prognosis, particularly for post-menopausal women, while weight gain may be a potential beneficial indicator for the patients with endocrine therapy but not for those with non-endocrine therapy.

[Expression and significance of toll-like receptors 7 and 8 in brain and lung tissues of death cases caused by EV71 infection].

OBJECTIVE: To study the significance of toll-like receptors (TLR) -7 and -8 in the pathogenesis of infection caused by Enterovirus type 71 (EV71) through measuring the expression of TLR7 and TLR8 in brain and lung tissues from the death cases caused by EV71 infection. METHODS: Nine children who died of EV71 infection (EV71 group) were selected as study subjects, and 7 children who died of accidents or non-infectious diseases were used as the control group. Brain and lung tissues from the death cases in both groups at autopsy were collected, and immunohistochemistry was applied to detect the expression of TLR7 and TLR8 in lung and brain tissues in both groups. Integrated optical density (IOD) was applied for semi-quantitative analysis of the expression of TLR7 and TLR8. RESULTS: Immunohistochemical results showed that the expression of TLR7 and TLR8 in lung and brain tissues was strongly positive in the EV71 group, and the IOD values in the EV71 group were also significantly higher than those in the control group (P<0.05). There was no significant difference in the expression of TLR7 and TLR8 between lung and brain tissues in the EV71 group (P>0.05). CONCLUSIONS: TLR7 and TLR8 are highly expressed in lung and brain tissues from the patients who die of severe EV71 infection, suggesting that TLR7 and TLR8 may be involved in the pathogenesis of brain and lung damages caused by severe EV71 infection.

Effects of Infection-Induced Fever and the Interaction with IL6 rs1800796 Polymorphism on the Prognosis of Breast Cancer.

BACKGROUND: Previous studies have found that acute febrile infection may decrease the risk of breast cancer. Meanwhile, it is well known that interleukin-6 (IL6) played dual roles in the tumor microenvironment. Fever may stimulate IL6 production, and IL6 rs1800796 also influences the expression of IL6. However, the impact of fever and its interaction with IL6 rs1800796 on breast cancer survival remains to be explored. METHODS: This was a prospective cohort study of 4,223 breast cancer patients. Exposures were pre-/postdiagnostic infection-induced fever and rs1800796 polymorphism. The endpoints were overall survival (OS) and progression-free survival (PFS). Adjusted hazard ratios were obtained using multivariate Cox proportional hazards regression models. RESULTS: Compared with women without prediagnostic fever, the adjusted hazard ratio (HR) of progression for those with prediagnostic fever was 0.81 (95% CI, 0.66-0.99), particularly for the CC genotype of IL6 rs1800796 (HR, 0.53; 95% CI, 0.36-0.79). OS was also better (HR, 0.59; 95% CI, 0.36-0.99) among women with the CC genotype exposed to prediagnostic fever, accompanied by a significant interaction (P = 0.021). Postdiagnostic fever conferred better PFS for breast cancer (HR, 0.72; 95% CI, 0.52-1.00). Irrespective of the genotype of IL6, lymph node-positive women with postdiagnostic fever (HR, 0.57; 95% CI, 0.37-0.89) had a lower risk of progression than lymph node-negative women (HR, 1.12; 95% CI, 0.70-1.79). CONCLUSIONS: Infection-induced fever was beneficial to breast cancer survival, particularly for women who were the CC genotype of IL6 rs1800796 or node positive. IMPACT: This study provides new insight into the roles of infection-induced fever as a potential prognostic marker and therapy regimen for breast cancer.

[Downregulation of cell-surface-expressed nucleolin inhibits the growth of hepatocellular carcinoma cells in vitro].

OBJECTIVE: To detect the cell-surface-expressed nucleolin and investigate its tumor suppressing effect on the growth of hepatocellular carcinoma cells. METHODS: To detect cell-surface-expressed nucleolin in the hepatocellular carcinoma cells by immunofluorescence and flow cytometry. To down-regulate the nucleolin expression level in hepatocellular carcinoma cells by RNA interference. The tumor-suppressing effect of cell-surface nucleolin on hepatocellular carcinoma cells was assessed by MTT and transwell chamber assays. RESULTS: Nucleolin was expressed in the nuclei, cytoplasm and on the cell surface of hepatocellular carcinoma cells. ShRNA markedly decreased the nucleolin expression level in the cytoplasm and on the cell surface (P < 0.01), but the nuclear nucleolin remained unchanged. After downregulation of cell-surface nucleolin, MTT assays showed that the cell growth rate of hepatocellular carcinoma cells in the shRNA interference group was significantly inhibited as compared with that in the control group (P < 0.01). The transwell chamber assay showed that the mean transmembrane cell number in the shRNA interference group was significantly lower than that in the control group. CONCLUSION: The results of this study show that downregulation of cell-surface nucleolin expression inhibits the growth of hepatocellular carcinoma cells in vitro.

[Suboccipital transtentorial approach to pineal region meningiomas by 3D-CTA assistance: surgical considerations].

OBJECTIVE: To evaluate the three-dimensional CT angiography (3D-CTA) assisted suboccipital transtentorial approach (Poppen's approach) in the treatment of pineal region meningioma. METHODS: During the period of January 2005 to January 2010, 8 patients with pineal region meningioma were successfully treated using Poppen's approach through cerebral falx and tentorium. There were three male patients and five female patients were aged at a range of 41 - 64 years, average age was (54 ± 10) years. According to the Karnofsky performance scale (KPS), 5 patients' KPS scores were more than or equal to 80 and 3 were less than 80. MRI was used for the diagnosis of meningioma. 3D-CTA was applied to detect meningioma staining and blood supply. For preoperative concurrent hydrocephalus, follow-up observations were given. If hydrocephalus didn't get better or even became worse, ventriculoperitoneal shunt should be considered. RESULTS: All the surgery were successfully performed, and venous complexes (VC) were well protected according to the CTA images. Out of the eight cases whose meningiomas were removed, one patient had got postoperative intracranial infection and recovered after given antibiotics. All patients were followed up for a period of 6 - 24 months. Preoperative concurrent hydrocephalus in 7 patients were improved. However, there was an aggravation of the hydrocephalus in one patient who was treated with ventriculoperitoneal shunt. The MRIs which were performed at the end of follow-up period, showed no recurrence of meningiomas, and preoperative symptoms were improved to varying degrees, 7 patients' KPS scores were more than or equal to 80 and 1 was less than 80. A χ(2) test was used to analyze and to make comparisons between preoperative and postoperative KPS. The significance was indicated (χ(2) = 1.33, P < 0.05). CONCLUSIONS: For meningiomas in the pineal region, 3D-CTA is of great clinical value to distinguish the anatomic relationship among the meningioma, blood supply and VC. This case study has strongly supported using Poppen's approach assisted by 3D-CTA to proceed with the operation.

PHLDA3 inhibition attenuates endoplasmic reticulum stress-induced apoptosis in myocardial hypoxia/reoxygenation injury by activating the PI3K/AKT signaling pathway.

Endoplasmic reticulum stress (ERS)-induced apoptosis serves a crucial role in the pathogenesis of myocardial ischemia/reperfusion injury (MIRI). Previous studies have confirmed that pleckstrin homology-like domain family A member 3 (PHLDA3) is an important mediator in ERS-associated apoptosis. The aim of the current study focused on whether PHLDA3 served protective effects on hypoxia/reoxygenation (H/R)-injured cardiomyocytes by inhibiting ERS-induced apoptosis. Furthermore, the molecular mechanisms associated with the PI3K/AKT signaling pathway were investigated. Primary neonatal rat cardiomyocytes were isolated and randomized into four groups: i) Control + adenovirus encoding scrambled short hairpin RNA (AdshRNA); ii) control + adenoviral vectors encoding PHLDA3 shRNA (AdshPHLDA3); iii) H/R+ AdshRNA and iv) H/R+AdshPHLDA3. AdshPHLDA3 was used to knock down PHLDA3. An H/R injury model was constructed by treatment with hypoxia for 4 h followed by reoxygenation for 6 h. A PI3K/AKT inhibitor, LY294002, was supplemented in mechanistic studies. Cell viability and LDH/CK releases were detected to evaluate myocardial damage. Flow cytometry assays were used to assess apoptotic response. Western blotting assays were used to detect protein expression. The results demonstrated that H/R induced myocardial damage and increased PHLDA3 expression. ERS-induced apoptosis was significantly increased following H/R injury, as indicated by increased apoptotic rates and ERS-associated protein expression, including those of CHOP, 78 kDa glucose-regulated protein and caspase-12. However, PHLDA3 inhibition following AdshPHLDA3 transfection reversed cell damage and ERS-associated apoptosis on H/R injury. Studies for molecular mechanisms concluded that the apoptosis-inhibition effects and cardioprotective roles of PHLDA3 inhibition were induced partly by the activation of the PI3K/AKT pathway, which was verified by LY294002 treatment. In conclusion, in the process of H/R injury, PHLDA3 inhibition reduced ERS-induced apoptosis and H/R injury by activating the PI3K/AKT pathway. PHLDA3 may be a therapeutic target for the treatment of MIRI.

Coexistent vestibular schwannoma and meningioma in a patient without neurofibromatosis: A case report and review of literature.

BACKGROUND: The simultaneous occurrence of schwannoma and meningioma in the absence of neurofibromatosis (NF) or a previous history of irradiation is exceedingly rare, as only 10 intracranial cases have been reported to date. Herein, we report a case of a coexistent cavernous sinus meningioma and ipsilateral vestibular schwannoma (VS) in a female patient without NF or a history of exposure to irradiation. CASE SUMMARY: A 63-year-old woman presented with progressive left-side hearing loss and tinnitus over the previous year. In the past 6 mo, she developed facial numbness and intermittent headaches. Magnetic resonance imaging showed two lesions that were located on the left side of the cerebellopontine angle and parasellar region. Both lesions were totally resected via the left retrosigmoid approach. Histopathological examination revealed a VS and a meningioma. The patient did not have a family history or clinical or radiological signs of NF. CONCLUSION: The coincident occurrence of VS and meningioma within close vicinity is very rare, and the pathogenesis is unclear. A careful whole-body examination needs to be conducted to exclude NF. Surgical treatment with the goal of total tumor resection is the best therapy. Additional studies are needed for a better understanding of the mechanisms that lead to the development of tumor growth in multiple locations.

[Methodology of Differentiation of Bone Marrow Cells into Megakaryocytes in Vitro].

OBJECTIVE: To explore the method for inducing the differentiation of bone marrow cells into megakaryocytes in vitro so as to use for evaluating the activity of traditional Chinese medicines. METHODS: The bone marrow cells were separated from femurs and tibias of mice. The experiments were divided into 4 groups: control (no adding cytokines), TPO (adding 50 ng/ml TPO), TPO+SCF (50 ng/ml+50 ng/ml) and TPO+SCF+IL-6+IL-9 (50 ng/ml+50 ng/ml+20 ng/ml+20 ng/ml). The bone marrow cells in 4 groups were cultured in vitro for 6 d. Then the cell growth status was observed by the inverted microscopy, and the cell count was detected by using the automatic cell counter. The ratio and absolute count of megakaryocytes were detected by flow cytometry. RESULTS: Compared with control, three induction methods could stimulate the differentiation of bone marrow cells into megakaryocytes in vitro. TPO could slightly enhance the differentiation of bone marrow cells into megakaryocytes. Both the combination of TPO and SCF, and the combination of TPO, SCF, IL-6 and IL-9 could intensively stimulate proliferation of bone morrow cells and promote the differentiation of bone marrow cells into megakaryocytes. The addition of IL-6 and IL-9 could decrease the proliferation of non-megakaryocytes, but promote the differentiation of bone marrow cells into megakaryocytes. CONCLUSION: The optimized differentiation of bone marrow cells into megakaryocytes has been completed by co-induction regimen of TPO, SCF, IL-6 and IL-9, which can be used to screen and evaluate traditional Chinese medicines promoting formation of platelets.

Can Medicinal Plants and Bioactive Compounds Combat Lipid Peroxidation Product 4-HNE-Induced Deleterious Effects?

The toxic reactive aldehyde 4-hydroxynonenal (4-HNE) belongs to the advanced lipid peroxidation end products. Accumulation of 4-HNE and formation of 4-HNE adducts induced by redox imbalance participate in several cytotoxic processes, which contribute to the pathogenesis and progression of oxidative stress-related human disorders. Medicinal plants and bioactive natural compounds are suggested to be attractive sources of potential agents to mitigate oxidative stress, but little is known about the therapeutic potentials especially on combating 4-HNE-induced deleterious effects. Of note, some investigations clarify the attenuation of medicinal plants and bioactive compounds on 4-HNE-induced disturbances, but strong evidence is needed that these plants and compounds serve as potent agents in the prevention and treatment of disorders driven by 4-HNE. Therefore, this review highlights the pharmacological basis of these medicinal plants and bioactive compounds to combat 4-HNE-induced deleterious effects in oxidative stress-related disorders, such as neurotoxicity and neurological disorder, eye damage, cardiovascular injury, liver injury, and energy metabolism disorder. In addition, this review briefly discusses with special attention to the strategies for developing potential therapies by future applications of these medicinal plants and bioactive compounds, which will help biological and pharmacological scientists to explore the new vistas of medicinal plants in combating 4-HNE-induced deleterious effects.

Neurosurgical brain tumor detection based on intraoperative optical intrinsic signal imaging technique: A case report of glioblastoma.

The delineation of brain tumor margins has been a challenging objective in neurosurgery for decades. Despite the development of various preoperative imaging techniques, the current methodology is still insufficient for clinical practice. We present an intraoperative optical intrinsic signal imaging system for brain tumor surgery and establish a data processing procedure model to localize tumors. From the experimental result of a glioblastoma patient, we observe a relative small oscillation of ΔHbD in tumor region and speculate that vessels in tumor region have poor ability to provide oxygen. We applied the same data processing procedure on the second time data and proclaimed a successful surgery. Figure: Merged ΔHbD image captured prior and posterior to tumor removal.

Imaging Gliomas with Nanoparticle-Labeled Stem Cells.

OBJECTIVE:: Gliomas are the most common neoplasm of the central nervous system (CNS); however, traditional imaging techniques do not show the boundaries of tumors well. Some researchers have found a new therapeutic mode to combine nanoparticles, which are nanosized particles with various properties for specific therapeutic purposes, and stem cells for tracing gliomas. This review provides an introduction of the basic understanding and clinical applications of the combination of stem cells and nanoparticles as a contrast agent for glioma imaging. DATA SOURCES: Studies published in English up to and including 2017 were extracted from the PubMed database with the selected key words of "stem cell," "glioma," "nanoparticles," "MRI," "nuclear imaging," and "Fluorescence imaging." STUDY SELECTION:: The selection of studies focused on both preclinical studies and basic studies of tracking glioma with nanoparticle-labeled stem cells. RESULTS:: Studies have demonstrated successful labeling of stem cells with multiple types of nanoparticles. These labeled stem cells efficiently migrated to gliomas of varies models and produced signals sensitively captured by different imaging modalities. CONCLUSION: The use of nanoparticle-labeled stem cells is a promising imaging platform for the tracking and treatment of gliomas.

Iron-gold alloy nanoparticles serve as a cornerstone in hyperthermia-mediated controlled drug release for cancer therapy.

INTRODUCTION: The efficacy of a chemotherapy drug in cancer therapy is highly determined by the ability to control the rate and extent of its release in vivo. However, the lack of techniques to accurately control drug release drastically limits the potency of a chemotherapy drug. MATERIALS AND METHODS: Here, we present a novel strategy to precisely monitor drug release under magnetic stimulation. Methotrexate (MTX), an anticancer drug, was covalently functionalized onto iron-gold alloy magnetic nanoparticles (Fe-Au alloy nanoparticles or NFAs) through 2-aminoethanethiol grafting and the ability of this drug-nanoparticle conjugate (NFA-MTX) in limiting HepG2 (liver carcinoma) cell growth was studied. Well-dispersed NFAs were prepared through pyrolysis. RESULTS AND DISCUSSION: Transmission electron microscopy revealed the average nanoparticle size to be 7.22±2.6 nm, while X-ray diffraction showed distinct 2θ peaks for iron and gold, confirming the presence of iron and gold nanoparticles. Inductively coupled plasma mass spectrometry revealed that the amount of NFA-MTX conjugate ingested by HepG2 cancer cells was 1.5 times higher than that ingested by L929 fibroblasts, thereby proving a higher selective ingestion by cancer cells compared to normal cells. Fourier-transform infrared spectroscopy revealed the breakage of Au-S bonds by the heat generated under magnetic field stimulation to release MTX from the NFA-MTX conjugate, triggering a 95% decrease in cellular viability at 100 µg/mL. CONCLUSION: The ability of NFA-MTX to dissociate under the influence of an applied magnetic field provides a new strategy to induce cancer cell death via hyperthermia. Applications in drug delivery, drug development, and cancer research are expected.

Schidandrin B kills tumor cells by initiating apoptosis in glioma SHG-44 cells.

OBJECTIVE: To observe the proliferation inhibition, cell cycle, and apoptosis of human glioma cell line SHG-44 treated with different concentration of Schidandrin B and explore the effect of Schidandrin B on glioma SHG-44 cells. METHODS: Glioma SHG-44 cells were treated with Schidandrin B (0, 50, 100 or 200 µg/mL) for 24, 48, 72 and 96 h, and cells were treated with vehicle as control. Viability of cells were detected by 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide (MTT) analysis; cell cycle was examined with flow cytometry assay; apoptosis was detected with annexin V assay. Bax and caspase-3 proteins expression were checked by Western blot. RESULTS: MTT analysis showed that viability of glioma SHG-44 cells significantly decreased after exposure to Schidandrin B for the indicated time. Flow cytometry revealed that the number of cells in the sub G1 phase was increased, however, the number of cells in G0/G1, S and G2/M phases were decreased after treatment with 50, 100 or 200 µg/mL Schidandrin B, compared with the respective control group. Annexin V analysis confirmed that apoptosis rates of the control group, 50, 100, and 200 µg/mL Schidandrin B group were 1.76%±0.47%, 13.98%±5.05%, 19.64%±5.53% and 63.28%±6.88% respectively, apoptotic rate increased significantly with dose-dependent manner, and apoptosis of cells were observed under the inverted microscope after 100 µg/mL Schidandrin B treatment. Bax and caspase-3 protein were highly expressed in Schidandrin B group compared with the control group. CONCLUSION: The apoptosis could be induced by different concentration of Schidandrin B on glioma SHG-44 cells, and the mechanism may be directly excited by Schidandrin B in glioma SHG-44 cells through activating mitochondrial pathway.

Plasma Homocysteine Levels Predict the Risk of Acute Cerebral Infarction in Patients with Carotid Artery Lesions.

This study examined the association between elevated plasma homocysteine (Hcy) levels and the risk of acute cerebral infarction in patients with carotid artery lesions. A total of 78 patients were divided into two groups, the high Hcy group (n = 38; Hcy levels >15 umol/L) and the low Hcy group (n = 40; Hcy levels ≤15 umol/L). High-resolution B-mode ultrasounds were performed to assess intima media thickness (IMT), infarcts, plaques, and stenosis in the extracranial carotid artery of these patients. All patients underwent 3 T MR scanners to evaluate cerebral artery stenosis in the intracranial cerebral artery. The plasma Hcy levels did not show any statistically significant differences when comparisons were based on gender, age, blood pressure, diabetes, hyperlipidemia, and systolic and diastolic pressures. Importantly, the incidence of carotid plaque and severe stenosis of intracranial and extracranial artery were significantly higher in the high Hcy group compared to the low Hcy group. Pearson's test indicated that plasma Hcy levels positively correlated with IMT, total number of plaques and unstable plaques. Overall, the elevated plasma Hcy levels correlated with increased frequency of carotid plaque formation, extra- and intracranial arterial stenosis, and the degree of stenosis. In conclusion, we find a significant correlation between elevated plasma Hcy levels and the increased incidence of acute cerebral infarction in patients with carotid artery lesions.

Elevated IL-6 and TNF-α Levels in Cerebrospinal Fluid of Subarachnoid Hemorrhage Patients.

The present study investigated the correlation between interleukin-6 (IL-6) and tumor necrosis factor alpha (TNF-α) levels in cerebrospinal fluid (CSF) and subarachnoid hemorrhage (SAH) progression. A meta-analysis was further conducted from pooled data to analyze the clinical value of IL-6 and TNF-α in SAH diagnosis. In our case-control study, a total of 57 SAH patients were assigned to two groups, CVS group (n = 27) and non-CVS group (n = 30), based on the presence of cerebral vasospasm (CVS). In addition, 65 healthy subjects were enrolled as controls. IL-6 and TNF-α levels in CSF were measured in all the study subjects by enzyme-linked immunosorbent assay (ELISA). For meta-analysis, an exhaustive literature search was conducted to identify relevant published articles and strict inclusion and exclusion criteria were applied to select studies for the present meta-analysis. Data extracted from these studies was analyzed using STATA 12.0 software. IL-6 and TNF-α levels in CSF of SAH patients were markedly higher than those of healthy controls (all P < 0.001). Further, CVS patients showed elevated IL-6 and TNF-α levels in CSF compared to non-CVS patients (all P < 0.001). The increase in IL-6 and TNF-α levels in CSF correlated with the increasing disease severity, based on Hunt-Hess grade, in SAH patients (all P < 0.05). Our meta-analysis also confirmed that IL-6 and TNF-α CSF levels were markedly higher in SAH patients compared to healthy controls (all P < 0.001). Ethnicity-stratified analysis showed that both IL-6 and TNF-α CSF levels were elevated in Asian SAH patients, compared to their healthy counterparts (all P < 0.05). The TNF-α CSF levels were significantly higher in Caucasian SAH patients (P < 0.001), but the IL-6 CSF levels showed no such differences compared to the healthy controls (P = 0.219). Subgroup analysis based on the presence of CVS showed that both IL-6 and TNF-α CSF levels were markedly higher in CVS patients than those in non-CVS patients (all P < 0.05). Our results provide strong evidence that IL-6 and TNF-α CSF levels are elevated in SAH patients and may participate in SAH development. Thus, these two cytokines could be important biomarkers for early diagnosis and disease monitoring in SAH patients.

Nanoparticles as a vaccine adjuvant of anti-idiotypic antibody against schistosomiasis.

BACKGROUND: The development of new adjuvants for human use has been the focus of attention. This study's aim is to explore the possibility of using nanoparticle Ca nanoparticles (CA) as a vaccine adjuvant of anti-idiotypic antibody NP30 against schistosomiasis and its protective mechanisms. METHODS: Nanoparticle CA-NP30 conjugate (CA-NP30) was fabricated. BALB/c mice were immunized actively with CA-NP30 to evaluate its effects of protective immunity on mice. The serum levels of specific IgG, IgG1 and IgG2a antibodies against NP30 and the concentrations of IFN-gamma and IL-4 in supernatant of splenocytes were determined via ELISA. RESULTS: Nanoparticle CA could enhance significantly the protective immunity of NP30 against infection of Schistosoma japonicum and the worm reduction rose from 36.0% (NP30 alone) to 52.6%. The serum levels of specific IgG, IgG1 and IgG2a antibodies against NP30 increased remarkably, as compared with those of the group immunized with NP30 alone. The concentration of IFN-gamma in supernatant of splenocyte was drastically elevated [the groups immunized with CA-NP30 and NP30 alone were (493.80 +/- 400.74) pg/ml and (39.03 +/- 39.58) pg/ml, respectively], but the concentration of IL-4 showed no significant difference from that of NP30 alone [(27.94 +/- 9.84) pg/ml vs (27.28 +/- 14.44) pg/ml]. CONCLUSIONS: Nanoparticle CA could act as a vaccine adjuvant of anti-idiotypic antibody NP30 against schistosomiasis. The mechanism could be that CA-NP30 enhances humoral and cellular immune responses in mice.

[Construction and expression of single chain Fv gene of anti-idiotypic monoclonal antibody NP30 of Schistosoma japonicum].

OBJECTIVE: To construct single chain Fv (scFv) gene of anti-idiotypic monoclonal antibody NP30 of Schistosoma japonicum. METHODS: The heavy and light chain variable region genes of anti-idiotypic monoclonal antibody NP30 of Schistosoma japonicum were inserted into two corresponding sites of expression vector pTHA90, and a scFv gene was constructed with a short peptide (Gly4Ser)3 linker gene. The recombinants were determined by digesting with XhoI/SpeI, XbaI/EcoRI and XhoI/EcoRI, and then were introduced into E. coli Top10. The antigen binding activity of expressed product was detected with ELISA. RESULTS: The recombinants were determined by digesting with endonucleases and expected bands were identified. The value of expressed scFv was 3 times higher than negative control by ELISA(OD492 = 1.06). CONCLUSION: The scFv gene of anti-idiotypic monoclonal antibody NP30 of Schistosoma japonicum was successfully cloned, and the expressed scFv fragment could interact specifically with antigen NP48.

Up-regulating of RASD1 and apoptosis of DU-145 human prostate cancer cells induced by formononetin in vitro.

Prostate cancer is one of the most prevalent malignant cancers in men. The isoflavone formononetin is a main active component of red clover plants. In the present study, we assessed the effect of formononetin on human prostate cancer DU-145 cells in vitro, and elucidated possible mechanisms. DU-145 cells were treated with different concentrations of formononetin and cell proliferation was assessed by MTT assay, cell apoptosis by Hoechst 33258 and flow cytometry, and protein levels of RASD1, Bcl-2 and Bax by Western blotting. The results showed that formononetin inhibited the proliferation of DU-145 cells in a dose-dependent manner. DU-145 cells treated with different concentrations of formononetin displayed obvious morphological changes of apoptosis under fluorescence microscopy. In addition, formononetin increased the proportion of early apoptotic DU-145 cells, down-regulated the protein levels of Bcl-2 and up-regulated those of RASD1 and Bax. The level of RASD1 reached its maximum at 48 h post-treatment, and rapidly decreased thereafter. Together, we present evidence that formononetin triggered cell apoptosis through the mitochondrial apoptotic pathway by up-regulating RASD1.