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As a malleable and novel tool for antigen recognition and modulation, nanobodies have the advantages of small size, easiness of expression, screening and modification, as well as high affinity and stability. Nanobodies are capable of recognizing more cryptic antigenic epitopes that are difficult to be recognized by traditional antibodies, making them increasingly used in the diagnosis and treatment of various diseases and assays. Nanobodies are also playing an irreplaceable role in the basic research. This review summarized the recent development of nanobodies and their derivatives in the detection of small molecules, pathogenic microorganisms and diagnosis of diseases, as well as in the fields of targeted therapies, cellular and molecular imaging. Broad prospects of nanobodies in the field of protein conformation studies were also reviewed.
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Single-Domain AntibodiesABSTRACT
Objectives@#The aim of this study was to characterize the benefits of converting Electronic Medical Records (EMRs) to a common data model (CDM) and to assess the potential of CDM-converted data to rapidly generate insights for benefit-risk assessments in post-market regulatory evaluation and decisions. @*Methods@#EMRs from January 2013 to December 2016 were mapped onto the Observational Medical Outcomes Partnership-CDM (OMOP-CDM) schema. Vocabulary mappings were applied to convert source data values into OMOP-CDM-endorsed terminologies. Existing analytic codes used in a prior OMOP-CDM drug utilization study were modified to conduct an illustrative analysis of oral anticoagulants used for atrial fibrillation in Singapore and South Korea, resembling a typical benefit-risk assessment. A novel visualization is proposed to represent the comparative effectiveness, safety and utilization of the drugs. @*Results@#Over 90% of records were mapped onto the OMOP-CDM. The CDM data structures and analytic code templates simplified the querying of data for the analysis. In total, 2,419 patients from Singapore and South Korea fulfilled the study criteria, the majority of whom were warfarin users. After 3 months of follow-up, differences in cumulative incidence of bleeding and thromboembolic events were observable via the proposed visualization, surfacing insights as to the agent of preference in a given clinical setting, which may meaningfully inform regulatory decision-making. @*Conclusions@#While the structure of the OMOP-CDM and its accessory tools facilitate real-world data analysis, extending them to fulfil regulatory analytic purposes in the post-market setting, such as benefit-risk assessments, may require layering on additional analytic tools and visualization techniques.
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The rostral ventrolateral medulla (RVLM) is a key region in cardiovascular regulation. It has been demonstrated that cholinergic synaptic transmission in the RVLM is enhanced in hypertensive rats. Angiotensin-converting enzyme 2 (ACE2) in the brain plays beneficial roles in cardiovascular function in hypertension. The purpose of this study was to determine the effect of ACE2 overexpression in the RVLM on cholinergic synaptic transmission in spontaneously hypertensive rats (SHRs). Four weeks after injecting lentiviral particles containing enhanced green fluorescent protein and ACE2 bilaterally into the RVLM, the blood pressure and heart rate were notably decreased. ACE2 overexpression significantly reduced the concentration of acetylcholine in microdialysis fluid from the RVLM and blunted the decrease in blood pressure evoked by bilateral injection of atropine into the RVLM in SHRs. In conclusion, we suggest that ACE2 overexpression in the RVLM attenuates the enhanced cholinergic synaptic transmission in SHRs.
Subject(s)
Animals , Male , Rats , Acetylcholine , Metabolism , Blood Pressure , Physiology , Cardiovascular System , Metabolism , Cholinergic Neurons , Metabolism , Hypertension , Metabolism , Peptidyl-Dipeptidase A , Metabolism , Rats, Inbred SHR , MetabolismABSTRACT
Objective: To investigate the effect of capsaicin on the migration and invasion of human breast cancer MCF-7 cells and the underlying molecular mechanism. Method: Three capsaicin intervention groups of different concentrations (25, 50, 75 μmol·L-1) and a blank group were set up. After MCF-7 cells were treated with different concentrations of capsaicin (25, 50, 75 μmol·L-1) for 24 h, the cell migration and invasion abilities were assessed by Transwell migration and invasion assay, respectively. Meanwhile, the mRNA level of silent information regulator 2 homolog 1 (SIRT1) and DNA polymerase δ catalytic subunit p125 encoding gene POLD1 (POLD1) were detected by Real-time polymerase chain reaction (Real-time PCR). The protein levels of SIRT1 and DNA polymerase δ catalytic subunit p125 (p125) were detected by Western blot. Result: Compared with the blank group, the number of transmembrane cells was significantly reduced, and the mobility was significantly decreased (P-1) in MCF-7 cells for 24 h. Capsaicin (25, 50, 75 μmol·L-1) significantly down-regulated the mRNA and protein expressions of SIRT1 (P-1) in MCF-7 cells for 24 h. Furthermore, capsaicin (25, 50, 75 μmol·L-1) also significantly down-regulated the mRNA expression of POLD1 and the protein expression of p125 (P-1) in MCF-7 cells for 24 h. Conclusion: Capsaicin remarkably inhibits the cell migration and invasion of breast cancer MCF-7 cells, and the possible mechanism may be related to the down-regulation of SIRT1 and POLD1 mRNA expression levels and SIRT1 and p125 protein expression levels.
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Objective: To investigate the inhibitory effect of capsaicin on the growth of breast cancer MDA-MB-231 cells transplanted tumour in nude mice and its possible molecular mechanism. Method: Transplanted tumor model of breast cancer MDA-MB-231 cells in nude mice were established. Then the tumor-bearing mice were randomly divided into 4 groups:model group, and low, medium and high-dose capsaicin groups (5, 10, 20 mg·kg-1). Mice of low, medium and high-dose capsaicin groups (5, 10, 20 mg·kg-1) were intraperitoneally injected with the corresponding dose of capsaicin, and the model group was injected with the same volume of phosphate buffer saline (PBS), once every 3 days, for a total of 8 times in succession. Body weight of mice and transplantation tumor volume were measured before each injection of capsaicin. Mice of each group were put to death 24 h after the last administration, and then the tumor volume, mass and the tumor inhibitory rate were calculated. The protein expression levels of high mobility group box 1 (HMGB1) and Toll-like receptors 4(TLR4) were measured by immunohistochemistry and Western blot. Result: No significant difference was observed between each group in body weight. However, compared with the model group, capsaicin (5, 10, 20 mg·kg-1) remarkably inhibited the tumor volume and mass (PPP-1) also markedly inhibited the protein expression levels of HMGB1 and TLR4 (PConclusion: Capsaicin remarkably inhibits the growth of breast cancer MDA-MB-231 cells transplanted tumour in nude mice, and the possible mechanism may be related to the down-regulation of HMGB1 and TLR4 at the protein level.
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This work aimed to observe the effects of short hairpin RNA (shRNA)-silenced FBI-1 (factor that binds to the inducer of short transcripts of human immunodeficiency virus-1) on proliferation and apoptosis of triple-negative breast cancer cell line MDA-MB-231. qRT-PCR and Western blot analysis were applied to detect the mRNA and/or protein expression of FBI-1, Bcl-2, Bax, cleaved-Caspase 3 and Survivin. RNA interference method was used to silence FBI-1 expression in MDA-MB-231 cells. CCK-8 and colony formation assay were employed to detect the cell proliferation. Flow cytometry was employed for examining cell apoptosis. In vivo tumorigenicity of MDA-MB-231 cells was detected by tumor transplantation in nude mice. The results showed that the mRNA and protein expressions of FBI-1 were higher in MDA-MB-231 cells compared with those in normal human mammary epithelial cells MCF-10A. FBI-1 gene silencing inhibited proliferation and induced apoptosis of MDA-MB-231 cells in vitro, together with decreased Bcl-2 and Survivin protein expression, increased Bax protein expression and activated Caspase 3. Moreover, FBI-1 gene silencing inhibited the tumorigenesis of MDA-MB-231 cells in vivo. These results suggest that silencing of FBI-1 gene inhibits proliferation, induces apoptosis and suppresses the tumorigenesis of MDA-MB-231 cells.
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Objective:To investigate the effects of electroacupuncture (EA) at Neiguan (PC 6) and Baihui (GV 20) by observing the changes of CCAAT/enhancer-binding protein(C/EBP) homologous protein (CHOP) and caspase-12 gene expressions in rats after cerebral ischemia-reperfusion injury (IRI), and explore whether the apoptosis pathway of endoplasmic reticulum stress (ERS) is involved in the protective mechanisms of EA. Methods:Sixty rats were randomly assigned to five groups (12 in each group): a normal control group (group A), a sham-operation group (group B), an operation group (group C), an Edaravone group (group D) and an EA group (group E). The cerebral IRI rat model was induced by middle cerebral artery occlusion (MCAO) using intraluminal monofilament. 2,3,5-triphenyl tetrazolium chloride (TTC) staining was adopted in the measurement of cerebral infarction volume. Real-time polymerase chain reaction (RT-PCR) was used to determine the mRNA expressions of CHOP and caspase-12. Results: Compared with group A and group B, the volume of cerebral infarction and mRNA expressions of CHOP and caspase-12 in group C, group D and group E were increased, with statistical significances (P0.05). Conclusion:EA at Neiguan (PC 6) and Baihui (GV 20) can effectively suppress the volume of cerebral infarction. Furthermore, the underlying mechanism of EA at Neiguan (PC 6) and Baihui (GV 20) is possibly related to the down-regulation of CHOP and caspase-12 mRNA expressions, so as to decrease cell apoptosis.
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Based on the review of literature, the evaluation method and application of medication and functional exercise compliance of patients with stroke were summarized, to provide reference for nursing staff about the effective evaluation of medication and exercise compliance of patients with stroke, as well as the early and accurate judgment of patient′s compliance, further taking nursing intervention measures, to provide a basis for improving the medication and functional exercise compliance of patients with stroke and their rehabilitation effect.
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Objective To analyze the perceived control of lung cancer patients undergoing chemotherapy and to explore its influencing factors. Methods A total of 185 patients with lung cancer were recruited and assessed by homemade general information questionnaire and the Cancer Experience and Efficacy Scale. Results The total score of cancer experience during chemotherapy in patients with lung cancer was (62.50±6.99) points. The total score of efficacy during chemotherapy in patients with lung cancer was (42.52±8.08) points. Single factor analysis showed the influencing factors of perceived control were personal income, sex, education, metastasis, surgical treatment and stage of disease. Conclusions The cancer-related experience and efficacy of patients with lung cancer is at middle level. Health-care worker should pay attention to the impact of lung cancer patients and take effective measures to mitigate the negative cancer-related experience, thereby improving the perceived control of the lung cancer patients.
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Microglia are resident macrophages of central nervous system (CNS), and thus act as the crucial stuff of immune response and play very important roles in the progress of various CNS diseases. There are two different polarization statuses of activated microglia, M1 and M2 phenotypes. M1 polarized microglia are important for eradicating bacterial and promoting inflammation, whereas M2 cells are characterized by anti-inflammation and tissue remodeling. Recently, more and more evidence indicated that different polarized microglia showed diverse microRNA (miRNA) expression profiles. MiRNAs regulate microglia polarization, and thus affect the progress of CNS diseases. Fully exploring the polarization status of microglia during CNS diseases and the role of miRNAs in microglia polarization will be very helpful for a deep understanding of the roles of microglia in immunopathologic mechanism of different CNS diseases and offer the theoretical foundation of searching more effective therapies for these disorders.
Subject(s)
Humans , Central Nervous System Diseases , Inflammation , Macrophages , Physiology , MicroRNAs , Physiology , Microglia , PhysiologyABSTRACT
Objective To determine the role of the nucleus tractus solitarii (NTS) superoxide in mediating the chronic heart failure (CHF)-induced reduction in baroreflex control of sympathetic activity. Methods CHF model was produced by coronary ligation in SD rats, and rats receiving sham operation (Sham) served as controls. Changes in renal sympathetic nerve activity (RSNA) and baroreflex sensitivity control of sympathetic activity were observed after microinjections of SOD mimic Tempol into the NTS in Shamand CHF rats. Results In anesthetized rats, the baseline level of sympathetic nerve activity was significantly higher in CHF group than in Sham group (P<0. 05), whereas the baroreflex sensitivity control of sympathetic activity was lower in CHF group than in Sham group. Bilateral microinjection of Tempol (10 nmol in 50 nL) into the NTS had no effect on baseline RSNA and baroreflex sensitivity in the Sham group. In contrast, injection of Tempol notably reduced the baseline RSNA and increased baroreflex sensitivity in CHF group. Conclusion Superoxide in the NTS contributes to sympathetic overactivity and baroreflex impairment in rats with CHF, suggesting that increased oxidative stress in the NTS is responsible for cardiovascular dysfunctions in CHF.
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<p><b>BACKGROUND</b>To study the correlativity between HBV-DNA and the markers of hepatitis B virus infection and different clinical types of hepatitis B.</p><p><b>METHODS</b>The fluorescence quantitation (FQ) of HBV-DNA of 105 patients with hepatitis B was performed by PCR, and the correlativity between the fluorescence quantitation of HBV-DNA and the markers of hepatitis B virus and different clinical types of hepatitis B was analyzed.</p><p><b>RESULTS</b>Ninety-seven percent of the patients were found HBsAg(+), HBeAg(+), HBcAb(+); 75% were HBsAg(+), HBeAb(+), HBcAb(+); 60% were HBsAg(+), HBcAb(+); 40% were HBsAg(+); in HBsAb(+), HBeAb(+), HBcAb(+) (or both HBsAb and HBcAb were positive) group the HBV DNA was undetectable. The analysis indicated that there was a significant difference among different groups (P less than 0.05).HBV-DNA was detected in 72.2% in acute hepatitis B group, in 75% of chronic hepatitis B group, and in 70% of cases of liver cirrhosis with hepatitis B group. The analysis indicated that there was no significant difference among the different clinical types of hepatitis (P greater than 0.05).</p><p><b>CONCLUSION</b>The levels of viral replication were not correlated with different clinical types of hepatitis B; the concentration of HBV-DNA in serum was related to hepatitis B antigen.</p>