ABSTRACT
Hallux valgus is a common foot deformity disease caused by various extrinsic and intrinsic factors, and systemic conditions, but the etiopathogenesis and pathogenesis of this deformity are still unknown. Hallux valgus affects 10-20% of Chinese adults. Although considered highly heritable, the candidate gene is unclear. We conducted the first candidate gene study of hallux valgus to identify the biological mechanism. Between June 2015 and July 2018, the records and radiographs of 80 patients diagnosed with hallux valgus and 80 controls who were treated were analyzed. In order to compare the differences in severity associated with this deformity, the charts of 80 patients were divided into 3 groups from the angle of hallux valgus. Clinical and basic studies were also statistically compared by PCR and data analysis. Patients and controls had significant differences in age and gender, however, there were no significant differences in age and gender among the light, moderate and severe groups. Post-operative groups resulted in significant improvements in all of the measured radiographic parameters compared with pre-operative groups. BsmI seemed to show a specific variation, and may serve as a useful bio-marker for the disease (OR = 5.88, 95% CI 1.54-22.35, P <0.001). In this paper, the article which proved the VDR polymorphisms (BsmI) playing an important role in hallux valgus were studied to understand and manage the hallux valgus more scientifically.
Subject(s)
Hallux Valgus , Receptors, Calcitriol/genetics , Asian People , Hallux Valgus/diagnostic imaging , Hallux Valgus/genetics , Humans , Polymorphism, Genetic , RadiographyABSTRACT
BACKGROUND: Angiogenesis is a critical biological process essential for solid cancer growth and metastasis. It has been shown that microRNAs (miRNAs) play a vital role in a variety of biological processes in cancers. However, whether miR-130b is involved in prostate cancer angiogenesis remains ill-defined. METHODS: We performed the miRNA microarray to analyze miRNA expression in human prostate cancer specimens. In vitro gain-of-function assays and loss-of-function assays were conducted to explore the potential functions of miR-130b in human prostate cancer cells. Correlation analysis and dual-luciferase reporter assay were performed to validate whether tumor necrosis factor-α (TNF-α) was a direct target of miR-130b. The Matrigel plug and tumor vascular imaging assays were performed to confirm the anti-angiogenic activity of miR-130b in nude mice. RESULTS: We found that miR-130b was one of the miRNAs being most significantly downregulated. Subsequently, we found that miR-130b expression was markedly downregulated in human prostate cancer cell lines. Down-regulation of miR-130b in prostate cancer cells significantly promoted the proliferation, invasion and tubule formation of human umbilical vein endothelial cells (HUVECs), while ectopic expression of miR-130b blocked prostate cancer angiogenesis in vitro and in vivo. Mechanistic analyses indicated that tumor necrosis factor-α (TNF-α) was regulated by miR-130b directly. MiR-130b attenuated nuclear factor-κB (NF-κB) signaling and its downstream gene vascular endothelial growth factor-A (VEGFA) by directly inhibiting TNF-α expression. Additionally, subsequent investigations identified that the ectopic level of VEGFA markedly abrogated the anti-angiogenic effect induced by miR-130b. Interestingly, VEGFA could in turn decrease the expression of miR-130b, thus forming a negative feedback loop that drives the angiogenesis of prostate cancer. CONCLUSION: These findings show that miR-130b/TNF-α/NF-κB/VEGFA feedback loop is significantly correlated with angiogenesis in prostate cancer and miR-130b could be regarded as potential therapeutic target for prostate cancer anti-angiogenesis treatment.
Subject(s)
Gene Expression Regulation, Neoplastic , MicroRNAs/genetics , NF-kappa B/metabolism , Neovascularization, Pathologic/pathology , Prostatic Neoplasms/blood supply , Tumor Necrosis Factor-alpha/metabolism , Vascular Endothelial Growth Factor A/metabolism , Animals , Apoptosis , Biomarkers, Tumor/genetics , Biomarkers, Tumor/metabolism , Cell Proliferation , Humans , Male , Mice , Mice, Inbred BALB C , Mice, Nude , NF-kappa B/genetics , Neovascularization, Pathologic/metabolism , Prognosis , Prostatic Neoplasms/genetics , Prostatic Neoplasms/metabolism , Prostatic Neoplasms/pathology , Signal Transduction , Survival Rate , Tumor Cells, Cultured , Tumor Necrosis Factor-alpha/genetics , Vascular Endothelial Growth Factor A/genetics , Xenograft Model Antitumor AssaysABSTRACT
OBJECTIVE: To determine the nucleotide sequence of cloned CD1 fragments from Leishmania mexicana and find ORFs predicted to have protein coding function. METHODS: CD1 element was separated by CHEF and recovered by agarase, and the digested CD1 fragments were cloned into pZero vector. Nucleotide sequences were determined by the dideoxy chain termination method with the automatic sequencing system ALF using the M13 universal primers. Sequences were analyzed using GCG-PCGENE computer programs. RESULTS: The sequence with 4,385 nucleotides was determined and two ORFs were considered to have protein coding function (encoding nucleotide-binding protein). CONCLUSION: Genes encoding nucleotide-binding protein were identified from the amplified CD1 element of Leishmania mexicana.
Subject(s)
DNA, Circular/genetics , GTP-Binding Proteins/genetics , Leishmania mexicana/genetics , Open Reading Frames , Amino Acid Sequence , Animals , Base Sequence , Cloning, Molecular , DNA, Circular/chemistry , Molecular Sequence DataABSTRACT
Two novel biosensors for urea based on immobilized corynebacterium glutamicum 617 and corynebacterium glutamicum ATCC13032 in calcium alginate gel coupled with an ammonia gas-sensing electrode, were designed and constructed. Calibration plots of measured potential difference (mV) vs. log of urea concentration were linear in the range of 5.6 x 10(-5)-1.4 x 10(-2) and 5.6 x 10(-5)-1.1 x 10(-2) mol l(-1), with slopes of 59.2 and 61.3 mV per decade respectively, in pH 8.0, 0.1 mol l(-1) phosphate buffer solution at 30 degrees C. The relationship between the initial response velocity and the substrate concentration was also discussed. The results indicate that the kinetic response process of the reaction catalyzed by bacteria is similar to that by isolated enzyme. Using an Eadie-Hofstee plot, the apparent Michaelis constant K(m) and the maximum initial response velocity V(m) for urease in the immobilized bacterial membrane were determined. The two urea biosensors were successfully applied for the actual measurement of urea in urine and were relatively stable for 20 and 40 days respectively.
ABSTRACT
The interaction of promastigotes of Leishmania with mouse peritoneal macrophage in vitro was studied by scanning electron microscopy. The results showed that when promastigotes had been incubated with 1/1,000 McAb for 1 h, morphological changes could be seen in most promastigotes, some promastigotes were lysed and some promastigotes although adhered to the macrophage, but no penetration could be seen. When 1/1,000 McAb had been inactivated at 56 degrees C for 1 h and then incubated with promastigotes, scanning electron microscopic examination showed the promastigotes closely adhered to the surface of macrophage with their anterior end "buried" within macrophage. The results of the present study suggested that the mechanism of promastigote-macrophage adhesion was ligand-receptor binding interaction (Figs. 1-11).
Subject(s)
Leishmania/pathogenicity , Macrophages, Peritoneal/parasitology , Animals , Antibodies, Monoclonal/pharmacology , Cell Adhesion , Leishmania/ultrastructure , Mice , Mice, Inbred BALB CABSTRACT
Monoclonal antibodies L12F7 against the target antigen of L. donovani promastigotes were used for the detection of circulating antigen (CAg) from sera of visceral leishmaniasis patients. The results showed that of 118 serum samples from visceral leishmaniasis tested, 105 were positive (88.9%). 55 normal serum samples were negative. No cross reaction with sera from patients with vivax malaria, schistosomiasis, leprosy and brucellosis, was found. The authors suggested that this assay may be used as a sensitive and new serodiagnostic test for detecting existing infection of visceral leishmaniasis for epidemiological survey and for assessment of cure after effective treatment.
Subject(s)
Antibodies, Monoclonal/immunology , Antigens, Protozoan/blood , Leishmania donovani/immunology , Leishmaniasis, Visceral/immunology , Animals , HumansABSTRACT
It has been reported by the authors that monoclonal antibody L12G9 produced from target antigens of L. donovani promastigotes, was very useful for detecting promastigotes from artificially infected sandflies. In the present study, detection of promastigotes from artificially infected sandflies by McAb showed that the positive rate correlated with the infection duration of sandflies. 4 days after feeding on infected Chinese hamsters, the sandflies were lightly infected with L. donovani promastigotes with a positive rate of 15.9%, but 10 days later, the sandflies were heavily infected, the positive rate being 100%. Observation has been made on the relationship between the number of promastigotes and mouse blood dilution. The results showed that satisfactory results could be obtained by using monoclonal antibodies in the detection of L. donovani, the number of promastigotes should be over 1 x 10(7)/ml, and the blood meals in sandflies completely digested. If very few promastigotes were present in naturally infected sandflies before identification by monoclonal antibody, the parasites must be grown in NNN medium. Positive result could then be obtained.