In this study, we designed and synthesized 12 novel aloperine derivatives with different core structures. Among them, compound 3 with a ten-membered ring core was obtained through a special ring expansion reaction after γ-H Huffman elimination of quaternary ammonium salt, and the structure was verified by X-single crystal diffraction. Furthermore, their antiviral activity against human β-coronavirus HCoV-OC43 was evaluated by CCK-8 assay. Quaternary ammonium salt 2a and 3 had a good inhibitory effect against HCoV-OC43, and 2a had the highest anti-HCoV-OC43 activity with an EC₅₀ values of 3.77 μmol·L^-1 and a SI value of over 53.1. Schrӧdinger molecular docking results showed that both 2a and 3 might display their anti-HCoV-OC43 activity by directly acting on host TMPRSS2 and SR-B1. The results expanded the structural types of endocyclic aloperine and the function against coronavirus, and provided useful scientific data for the development of pharmaceutical applications of these compounds.

Objective To investigate the impact of one versus two distal locking bolts on the mechanical properties of tibial interlocking intramedullary nails. Methods Twenty 9-mm titanium alloy locking nails were divided into two equal groups in which the nails were fixed with only one and two distal locking bolts, respectively. Each group was further divided into two sub-groups for compression and torsion tests separately using a universal material-testing machine. Results In the compression tests, the average maximum strength of double bolts was greater than that of the single bolt (P＜0.05), but the number of the bolts did not significantly affect the results of the torsion tests in terms of the either the maximum torsion moment or angle (P＞0.05). Conclusion One distal bolt is sufficient for fixing stable fractures and double bolts are recommended for management of serious fractures. The model we used is convenient and economic for examining the biomechanics of the tibial nails, especially for comparative purposes.

Objective To investigate the implication of morphological changes of the proximal femur in femoral prosthesis selection in total hip replacement for treatment of ankylosing spondylitis (AS). Methods Twenty-four patients (36 hips)admitted for cementless total hip replacement (THR) because of AS were enrolled in this study along with the control group of 30 patients (45 hips) without AS. Measurement of the Singh index, canal flare index, morphological index of the cortex,cortical index and stem-canal fit was performed in the two groups on the basis of roentgenograms. Results The AS patients had more serious osteoporosis in their proximal femur. There were significant differences between the two groups in Singh index, canal flare index, morphological index of the cortex and stem-canal fit (P＜0.05), but not in the cortical index (P＞0.05).The AS patients were found to have severe osteoporosis in the upper femur and massive spongy bone loss, so that the morphology of the canal was almost orthostatic in the upper femur because of the thinned femoral cortex. Conclusion Cemented prosthesis is recommended for AS patients with severe osteoporosis, who should be treated with revised THR to ensure good fit of the prosthesis to the canal. Cementless prosthesis, however, can still achieve good therapeutic effect in AS patients without significant morphologic changes in the proximal femurs. Computer-aided design and manufacture of individualized prosthesis better suits the AS patients than the currently available prosthesis.

Objective To investigate the impact of one versus two distal locking bolts on the mechanical properties of tibial interlocking intramedullary nails. Methods Twenty 9-mm titanium alloy locking nails were divided into two equal groups in which the nails were fixed with only one and two distal locking bolts, respectively. Each group was further divided into two sub-groups for compression and torsion tests separately using a universal material-testing machine. Results In the compression tests, the average maximum strength of double bolts was greater than that of the single bolt (P＜0.05), but the number of the bolts did not significantly affect the results of the torsion tests in terms of the either the maximum torsion moment or angle (P＞0.05). Conclusion One distal bolt is sufficient for fixing stable fractures and double bolts are recommended for management of serious fractures. The model we used is convenient and economic for examining the biomechanics of the tibial nails, especially for comparative purposes.

Objective To investigate the implication of morphological changes of the proximal femur in femoral prosthesis selection in total hip replacement for treatment of ankylosing spondylitis (AS). Methods Twenty-four patients (36 hips)admitted for cementless total hip replacement (THR) because of AS were enrolled in this study along with the control group of 30 patients (45 hips) without AS. Measurement of the Singh index, canal flare index, morphological index of the cortex,cortical index and stem-canal fit was performed in the two groups on the basis of roentgenograms. Results The AS patients had more serious osteoporosis in their proximal femur. There were significant differences between the two groups in Singh index, canal flare index, morphological index of the cortex and stem-canal fit (P＜0.05), but not in the cortical index (P＞0.05).The AS patients were found to have severe osteoporosis in the upper femur and massive spongy bone loss, so that the morphology of the canal was almost orthostatic in the upper femur because of the thinned femoral cortex. Conclusion Cemented prosthesis is recommended for AS patients with severe osteoporosis, who should be treated with revised THR to ensure good fit of the prosthesis to the canal. Cementless prosthesis, however, can still achieve good therapeutic effect in AS patients without significant morphologic changes in the proximal femurs. Computer-aided design and manufacture of individualized prosthesis better suits the AS patients than the currently available prosthesis.

Pheochromocytoma is a tumor derived from chromaffin tissue in the adrenergic system with excessive secretion of catecholamine .Pheochromocytoma occurs at any age of patients ,commonly in 40-60 years,and the incidence is slightly higher in women than in men .In recent years , studies have shown that the mutations of von Hippel-Lindau gene ( VHL ) , rearranged during transfaction gene ( RET ) , neurofibromatosis type 1 gene ( NF-1 ) , succinate dehydrogenase gene ( SDH ) , transmembrane protein 127 gene ( TMEM127 ) , myelocytomatosis oncogene-associated factor X gene ( MAX ) are associated with pheochromocytoma .Immunohistochemical studies have revealed that a number of molecular markers ,such as telomerase,vascular endothelial growth factor , cyclooxygenase-2 , adrenomedullin , plasma chromaffin protein A,signal transducer and activator of transcription-3 are of velue in identification of tumor origin, its biological behaviors and differentiation of pheochromocytoma .This article reviews the newest research progresses in molecular biology of pheochromocytoma .

This study investigated the effect of advanced glycation end products (AGEs) on differentiation of naïve CD4(+) T cells and the role of the receptor of AGEs (RAGE) and peroxisome proliferator-activated receptors (PPARs) activity in the process in order to gain insight into the mechanism of immunological disorders in diabetes. AGEs were prepared by the reaction of bovine serum albumin (BSA) with glucose. Human naïve CD4(+) T cells, enriched from blood of healthy adult volunteers with negative selection assay, were cultured in vitro and treated with various agents including AGEs, BSA, high glucose, PGJ2 and PD68235 for indicated time. In short hairpin (sh) RNA knock-down experiment, naïve CD4(+) T cells were transduced with media containing shRNA-lentivirus generated from lentiviral packaging cell line, Lent-X(TM) 293 T cells. Surface and intracellular cytokine stainings were used for examination of CD4(+) T cell phenotypes, and real-time PCR and Western blotting for detection of transcription factor mRNA and protein expression, respectively. The suppressive function of regulatory T (Treg) cells was determined by a [(3)H]-thymidine incorporation assay. The results showed that AGEs induced higher pro-inflammatory Th1/Th17 cells differentiated from naïve CD4(+) T cells than the controls, whereas did not affect anti-inflammatory Treg cells. However, AGEs eliminated suppressive function of Treg cells. In addition, AGEs increased RAGE mRNA expression in naïve CD4(+) T cells, and RAGE knock-down by shRNA eliminated the effect of AGEs on the differentiation of CD4(+) T cells and the reduction of suppressive function of Treg cells. Furthermore, AGEs inhibited the mRNA expression of PPARγ, not PPARα PPARγ agonist, PGJ2, inhibited the effect of AGEs on naïve CD4(+) T cell differentiation and reversed the AGE-reduced suppressive function of Treg cells; on the other hand, PPARγ antagonist, PD68235, attenuated the blocking effect of RAGE shRNA on the role of AGEs. It was concluded that AGEs may promote CD4(+) T cells development toward pro-inflammatory state, which is associated with increased RAGE mRNA expression and reduced PPARγ activity.
Adult ; Animals ; Blotting, Western ; CD4-Positive T-Lymphocytes ; drug effects ; metabolism ; Cattle ; Cell Differentiation ; drug effects ; Cells, Cultured ; Glucose ; pharmacology ; Glycation End Products, Advanced ; pharmacology ; HEK293 Cells ; Humans ; Interferon-gamma ; metabolism ; Interleukin-17 ; metabolism ; PPAR gamma ; agonists ; genetics ; metabolism ; Prostaglandin D2 ; analogs & derivatives ; pharmacology ; RNA Interference ; Receptor for Advanced Glycation End Products ; Receptors, Immunologic ; genetics ; metabolism ; Reverse Transcriptase Polymerase Chain Reaction ; Serum Albumin, Bovine ; pharmacology ; T-Lymphocytes, Regulatory ; drug effects ; metabolism ; Th1 Cells ; drug effects ; metabolism ; Th17 Cells ; drug effects ; metabolism

Pheochromocytoma is a tumor derived from chromaffin tissue in the adrenergic system with excessive secretion of catecholamine.Pheochromocytoma occurs at any age of patients,commonly in 40-60 years,and the incidence is slightly higher in women than in men.In recent years,studies have shown that the mutations of von Hippel-Lindau gene (VHL),rearranged during transfection gene (RET),neurofibromatosis type 1 gene (NF-1),succinate dehydrogenase gene (SDH),transmembrane protein 127 gene (TMEM127),myelocytomatosis oncogene-associated factor X gene (MAX) are associated with pheochromocytoma.Immunohistochemical studies have revealed that a number of molecular markers,such as telomerase,vascular endothelial growth factor,cyclooxygenase-2,adrenomedullin,plasma chromaffin protein A,signal transducer and activator of transcription-3 are of value in identification of tumor origin,its biological behaviors and differentiation of pheochromocytoma. This article reviews the newest research progresses in molecular biology of pheochromocytoma.
Adrenal Gland Neoplasms ; genetics ; Biomarkers, Tumor ; genetics ; Humans ; Mutation ; Pheochromocytoma ; genetics

BACKGROUNDInterleukin-13 (IL-13) has been implicated to be responsible for recruitment of inflammatory cells from the blood to the lung, regulation of matrix metalloproteinase and induction of mucin production and secretion in chronic obstructive pulmonary disease (COPD). We determined plasma IL-13 levels in patients with COPD and investigated its association with common polymorphisms of IL-13 gene in a case-control study.

METHODSWe genotyped 160 cases and 175 control subjects in a local hospital using Mass-Array(TM) Technology Platform then tested the association of four SNPs in IL-13 (rs1295685, rs1800925, rs1881457, rs20541) with COPD, and then determined plasma IL-13 levels in patients with COPD and controls.

RESULTSAssociation was found between IL-13 gene SNPs (rs20541 and rs1800925) and an increased risk of COPD. By linkage disequilibrium (LD) analysis, two blocks (rs1881457 and rs1800925; rs20541 and rs1295685) were found. The risk of COPD was found associated with the IL-13 gene polymorphism among southern Chinese Han population. Plasma IL-13 level was increased in COPD patients compared with controls.

CONCLUSIONSThe polymorphism of the IL-13 gene is associated with an increased risk of COPD in southern Chinese Han population. Plasma IL-13 levels were found elevated in patients with COPD.

Adult ; Aged ; Asian Continental Ancestry Group ; genetics ; Case-Control Studies ; Gene Frequency ; genetics ; Genetic Predisposition to Disease ; genetics ; Genotype ; Haplotypes ; genetics ; Humans ; Interleukin-13 ; genetics ; Linkage Disequilibrium ; genetics ; Male ; Middle Aged ; Polymorphism, Single Nucleotide ; genetics ; Pulmonary Disease, Chronic Obstructive ; genetics

Objective To express human vascular endothelial growth factor (hVEGF165) in E. coli JM109 in the form of fusion protein by genetic engineering and test the biological activity and immunological competence of the expressed protein.Methods hVEGF165 gene was subcloned by PCR and inserted into pQE30 plasmid. hVEGF165 fusion protein was expressed in E. coli JM109 and purified by Ni2+-NTA. The immunological competence of the expressed protein was tested by means of Western blotting and enzyme-linked immunosorbent assay (ELISA), and its biological activity was assayed by chicken chorioallantoic membrane (CAM) and Matrigel angiogenesis assay. Results The recombinant hVEGF165 fusion protein was successfully expressed in E. coli JM109 and its expression accounted for 30% of the total cellular protein. The purified protein presented a single band of 23 kD in SDS-PAGE. Western blotting, ELISA, CAM and matrigel angiogenesis assay showed excellent immunologic competence and biological activity of the recombinant protein. Conclusion Recombinant hVEGF165protein with excellent biological activity has been successfully expressed in E. coli JM109, which may facilitate future study in construction of prefabricated tissue-engineered bone graft.