ABSTRACT
Background: As a prodromal stage of dementia, significant emphasis has been placed on the identification of modifiable risks of mild cognitive impairment (MCI). Research has indicated a correlation between exposure to air pollution and cognitive function in older adults. However, few studies have examined such an association among the MCI population inChina. Objective: We aimed to explore the association between air pollution exposure and MCI risk from the Hubei Memory and Aging Cohort Study. Methods: We measured four pollutants from 2015 to 2018, 3 years before the cognitive assessment of the participants. Logistic regression models were employed to calculate odds ratios (ORs) to assess the relationship between air pollutants and MCI risk. Results: Among 4,205 older participants, the adjusted ORs of MCI risk for the highest quartile of PM2.5, PM10, O3, and SO2 were 1.90 (1.39, 2.62), 1.77 (1.28, 2.47), 0.56 (0.42, 0.75), and 1.18 (0.87, 1.61) respectively, compared with the lowest quartile. Stratified analyses indicated that such associations were found in both males and females, but were more significant in older participants. Conclusions: Our findings are consistent with the growing evidence suggesting that air pollution increases the risk of mild cognitive decline, which has considerable guiding significance for early intervention of dementia in the older population. Further studies in other populations and broader geographical areas are warranted to validate these findings.
Subject(s)
Air Pollutants , Air Pollution , Cognitive Dysfunction , Dementia , Male , Female , Humans , Aged , Cohort Studies , Case-Control Studies , Environmental Exposure/adverse effects , Environmental Exposure/analysis , Air Pollution/adverse effects , Air Pollution/analysis , Air Pollutants/adverse effects , Air Pollutants/analysis , Cognitive Dysfunction/epidemiology , China/epidemiology , Particulate Matter/adverse effects , Particulate Matter/analysisABSTRACT
BACKGROUND: Glioma is the most frequent, highly aggressive primary intracranial malignant tumor. Circular RNA (circRNA) circ_0037655 has been reported to be a vital regulator in glioma. The different functional mechanism behind circ_0037655 was investigated in the current study. METHODS: The expression of circ_0037655, microRNA-1229-3p (miR-1229-3p) and integrin beta-8 (ITGB8) was detected via the quantitative reverse transcription-polymerase chain reaction (qRT-PCR). Cellular research was performed via colony formation assay for cell proliferation, flow cytometry for cell cycle and cell apoptosis, scratch assay for cell migration, as well as transwell assay for cell migration and invasion. Western blot was used for detection of ITGB8 protein and epithelial-mesenchymal transition (EMT) process. Dual-luciferase reporter assay was implemented for the binding analysis of potential targets. In vivo assay was administered via xenograft in mice. RESULTS: Upregulation of circ_0037655 was affirmed in glioma samples and cells. Tumor formation and metastasis of glioma were inhibited after circ_0037655 was downregulated. miR-1229-3p acted as a target of circ_0037655, and its upregulation was responsible for the function of si-circ_0037655 in glioma cells. miR-1229-3p functioned as a tumor inhibitor in glioma progression by targeting ITGB8. circ_0037655 modulated the ITGB8 expression by targeting miR-1229-3p. In vivo knockdown of circ_0037655 also suppressed glioma tumorigenesis by acting on the miR-1229-3p/ITGB8 axis. CONCLUSION: This study showed that downregulation of the expression of circ_0037655 could inhibit glioma progression by acting on the miR-1229-3p/ITGB8 axis. The specific circ_0037655/miR-1229-3p/ITGB8 axis was disclosed in glioma research.
ABSTRACT
Psoralea corylifolia (P corylifolia) has been popularly applied in traditional Chinese medicine decoction for treating osteoporosis and promoting fracture healing since centuries ago. However, the bioactive natural components remain unknown. In this study, applying comprehensive two-dimensional cell membrane chromatographic/C18 column/time-of-flight mass spectrometry (2D CMC/C18 column/TOFMS) system, neobavaisoflavone (NBIF), for the first time, was identified for the bioaffinity with RAW 264.7 cells membranes from the extracts of P corylifolia. Here, we revealed that NBIF inhibited RANKL-mediated osteoclastogenesis in bone marrow monocytes (BMMCs) and RAW264.7 cells dose dependently at the early stage. Moreover, NBIF inhibited osteoclasts function demonstrated by actin ring formation assay and pit-formation assay. With regard to the underlying molecular mechanism, co-immunoprecipitation showed that both the interactions of RANK with TRAF6 and with c-Src were disrupted. In addition, NBIF inhibited the phosphorylation of P50, P65, IκB in NF-κB pathway, ERK, JNK, P38 in MAPKs pathway, AKT in Akt pathway, accompanied with a blockade of calcium oscillation and inactivation of nuclear translocation of nuclear factor of activated T cells cytoplasmic 1 (NFATc1). In vivo, NBIF inhibited osteoclastogenesis, promoted osteogenesis and ameliorated bone loss in ovariectomized mice. In summary, P corylifolia-derived NBIF inhibited RANKL-mediated osteoclastogenesis by suppressing the recruitment of TRAF6 and c-Src to RANK, inactivating NF-κB, MAPKs, and Akt signalling pathways and inhibiting calcium oscillation and NFATc1 translocation. NBIF might serve as a promising candidate for the treatment of osteoclast-associated osteopenic diseases.
Subject(s)
Genes, src/drug effects , Isoflavones/pharmacology , Osteogenesis/drug effects , RANK Ligand/metabolism , Signal Transduction/drug effects , TNF Receptor-Associated Factor 6/metabolism , Animals , Bone Marrow/drug effects , Bone Marrow/metabolism , Bone Resorption/drug therapy , Bone Resorption/metabolism , Cell Line , Female , Male , Mice , Mice, Inbred C57BL , Mitogen-Activated Protein Kinases/metabolism , Monocytes/drug effects , Monocytes/metabolism , NF-kappa B/metabolism , Osteoclasts/drug effects , Osteoclasts/metabolism , Proto-Oncogene Proteins c-akt/metabolism , RAW 264.7 CellsABSTRACT
BACKGROUND: Radiation therapy is the primary method of treatment for glioblastoma (GBM). Therefore, the suppression of radioresistance in GBM cells is of enormous significance. Ribophorin II (RPN2), a protein component of an N-oligosaccharyl transferase complex, has been associated with chemotherapy drug resistance in multiple cancers, including GBM. However, it remains unclear whether this also plays a role in radiation therapy resistance in GBM. METHODS: We conducted a bioinformatic analysis of RPN2 expression using the UCSC Cancer Genomics Browser and GEPIA database and performed an immunohistochemical assessment of RPN2 expression in biopsy specimens from 34 GBM patients who had received radiation-based therapy. We also studied the expression and function of RPN2 in radiation-resistant GBM cells. RESULTS: We found that RPN2 expression was upregulated in GBM tumors and correlated with poor survival. The expression of RPN2 was also higher in GBM patients with tumor recurrence, who were classified to be resistant to radiation therapy. In the radiation-resistant GBM cells, the expression of RPN2 was also higher than in the parental cells. Depletion of RPN2 in resistant cells can sensitize these cells to radiation-induced apoptosis, and overexpression of RPN2 had the reverse effect. Myeloid cell leukemia 1 (MCL1) was found to be the downstream target of RPN2, and contributed to radiation resistance in GBM cells. Furthermore, STAT3 was found to be the regulator of MCL1, which can be activated by RPN2 dysregulation. CONCLUSION: Our study has revealed a novel function of RPN2 in radiation-resistant GBM, and has shown that MCL1 depletion or suppression could be a promising method of therapy to overcome the resistance promoted by RPN2 dysregulation.
Subject(s)
Gene Expression Regulation, Neoplastic , Glioma/genetics , Glioma/metabolism , Hexosyltransferases/genetics , Proteasome Endopeptidase Complex/genetics , Radiation Tolerance/genetics , STAT3 Transcription Factor/metabolism , Signal Transduction , Cell Line, Tumor , Glioma/pathology , Glioma/radiotherapy , Hexosyltransferases/metabolism , Humans , Immunohistochemistry , Models, Biological , Myeloid Cell Leukemia Sequence 1 Protein/genetics , Myeloid Cell Leukemia Sequence 1 Protein/metabolism , Proteasome Endopeptidase Complex/metabolismABSTRACT
Myostatin is a crucial cytokine that is widely present in skeletal muscle and that negatively regulates the growth and development of muscle cells. Recent research has shown that myostatin might play an essential role in bone metabolism. In RAW264.7 cells and bone marrow monocytes (BMMCs), myostatin activates the expression of the II type receptor ActR II B. Here, we report that myostatin significantly promoted RANKL/M-CSF-induced osteoclastogenesis and activated NF-κB and MAPK pathways in vitro via the Ccdc50 gene. Overexpression of myostatin promoted osteoclastogenesis and osteoclastogenesis-related markers including c-Src, MMP9, CTR, CK, and NFATc1. Specifically, myostatin increased the phosphorylation of Smad2, which led to the activation of NF-κB and MAPK pathways to activate osteoclastogenesis. Ccdc50 was identified as a gene whose expression was highly decreased in osteoclastogenesis upon myostatin treatment, and it could inhibit the function of myostatin in osteoclastogenesis by blocking NF-κB and MAPKs pathways. Our study indicates that myostatin is a promising candidate target for inhibiting RANKL-mediated osteoclastogenesis and might participate in therapy for osteoporosis, and that the Ccdc50 gene plays a significant role in the regulatory process.
ABSTRACT
The aim of the present study was to investigate the outcomes of surgical treatment of calcaneal fractures of Sanders type II and III using a minimally invasive technique and a locking plate. We reviewed 33 feet in 33 consecutive patients with Sanders type II and III calcaneal fractures who had undergone a minimally invasive technique using percutaneous reduction and locking plates. All operations were performed by the same surgeons. The postoperative evaluation included radiographs, determination of restoration of Böhler's angle and Gissane's angle, and administration of the American Orthopaedic Foot and Ankle Society ankle-hind foot scale, Maryland Foot Score, and visual analog scale of pain. The mean visual analog scale score was 1.6 ± 1.4 when radiographic fracture healing was observed. The median functional score of the 33 patients (33 feet) reached 82 (interquartile range 80 to 99) at the last follow-up evaluation according to the American Orthopaedic Foot and Ankle Society ankle-hind foot scale and 89 (interquartile range 80 to 99) according to Maryland Foot Score. All cases achieved restoration of a normal Böhler's angle and Gissane's angle. Postoperative superficial infections occurred in 2 patients, subtalar arthritis developed in 2, and no soft tissue necrosis was observed. For Sanders type II and III fractures of the calcaneus bone, treatment with a minimally invasive technique combining percutaneous reduction and locking plate fixation provided satisfactory clinical results, with a lower incidence of complications. However, longer term studies with a larger sample size and more randomized controlled trials are required to define the superiority of our minimally invasive technique compared with conventional surgical treatment of calcaneal fractures.
Subject(s)
Calcaneus/surgery , Foot Injuries/surgery , Fracture Fixation, Internal/methods , Intra-Articular Fractures/surgery , Adult , Bone Plates , Calcaneus/diagnostic imaging , Calcaneus/injuries , Female , Foot Injuries/diagnostic imaging , Fracture Fixation, Internal/instrumentation , Humans , Intra-Articular Fractures/diagnostic imaging , Male , Middle Aged , Minimally Invasive Surgical Procedures , Prospective Studies , Radiography , Treatment Outcome , Young AdultABSTRACT
The biological roles of stem cell marker LGR5, the receptor for the Wnt-agonistic R-spondins, for nervous system are poorly known. Bioinformatics analysis in normal human brain tissues revealed that LGR5 is closely related with neuron development and functions. Interestingly, LGR5 and its ligands R-spondins (RSPO2 and RSPO3) are specifically highly expressed in projection motor neurons in the spinal cord, brain stem and cerebral. Inhibition of Notch activity in neural stem cells (NSCs) increased the percentage of neuronal cells and promoted LGR5 expression, while activation of Notch signal decreased neuronal cells and inhibited the LGR5 expression. Furthermore, knockdown of LGR5 inhibited the expression of neuronal markers MAP2, NeuN, GAP43, SYP and CHRM3, and also reduced the expression of genes that program the identity of motor neurons, including Isl1, Lhx3, PHOX2A, TBX20 and NEUROG2. Our data demonstrated that LGR5 is highly expressed in motor neurons in nervous system and is involved in their development by regulating transcription factors that program motor neuron identity.
Subject(s)
Neural Stem Cells/physiology , Receptors, G-Protein-Coupled/metabolism , Brain/cytology , Brain/physiology , Cell Differentiation , Cells, Cultured , Humans , Motor Neurons/cytology , Motor Neurons/physiology , Neural Stem Cells/cytology , Spinal Cord/cytology , Spinal Cord/physiologyABSTRACT
OBJECTIVE: To compare the clinical effects between closed reduction and internal fixation (CRIF) and total hip arthroplasty (THA) for displaced femoral neck fracture. METHODS: In this prospective randomized study, 285 patients aged above 65 years with hip fractures (Garden III or IV) were included from January 2001 to December 2005. The cases were randomly allocated to either the CRIF group or THA group. Patients with pathological fractures (bone tumors or metabolic bone disease), preoperative avascular necrosis of the femoral head, osteoarthritis, rheumatoid arthritis, hemiplegia, long-term bed rest and complications affecting hip functions were excluded. RESULTS: During the 5-year follow-up, CRIF group had significantly higher rates of complication in hip joint, general complication and reoperation than THA group (38.3% vs. 12.7%, P<0.01; 45.3% vs. 21.7%, P<0.01; 33.6% vs. 10.2%, P<0.05 respectively). There was no difference in mortality between the two groups. Postoperative function of the hip joint in THA group recovered favorably with higher Harris scores. CONCLUSION: For displaced fractures of the femoral neck in elderly patients, THA can achieve a lower rate of complication and reoperation, as well as better postoperative recovery of hip joint function compared with CRIF.
Subject(s)
Arthroplasty, Replacement, Hip/methods , Femoral Neck Fractures/surgery , Fracture Fixation, Internal/methods , Aged , Aged, 80 and over , Female , Femoral Neck Fractures/physiopathology , Humans , Male , Postoperative Complications/epidemiology , Prospective Studies , Treatment Failure , WalkingABSTRACT
The development of a bioactive nanocomposite for bone replacement has gained much interest in the field of bone grafting. In this study, a nano fluorapatite (n-FA)-poly(butylene succinate) (PBS) bioactive composite was fabricated using a co-solution method. The results showed that the n-FA-PBS composite had improved hydrophilicity, compressive strength and an elastic modulus, which were obviously higher than those of PBS alone. In addition, the n-FA-PBS composite could inhibit bacterial attachment, with the number of viable bacteria on the composite obviously lower than on pure PBS, indicating good antibacterial ability. Moreover, the attachment and proliferation of human mesenchymal stem cells (hMSCs) on the n-FA-PBS composite was significantly higher than on PBS, and the alkaline phosphatase (ALP) activity of hMSCs on the composite was expressed at significantly higher levels compared to PBS. Furthermore, the hMSCs showed intimate contact with the composite surface and the cells spread and grew significantly better on the composite compared to PBS. Therefore, incorporation of n-FA into PBS is a good way to prepare an inorganic-organic bioactive composite of a nano ceramic and a polymer, which supports cell attachment, proliferation and differentiation. The implantation of the n-FA-PBS composite into the femoral bone of rabbits confirmed that the new bone tissue could form on the composite surfaces, and the composite combined directly with the natural bone tissue without fibrous capsule tissue, showing good osteoconductivity. In short, the n-FA-PBS bioactive composite has good biocompatibility and bioactivity, and has potential application in bone regeneration.
ABSTRACT
OBJECTIVE: To compare the effectiveness between minimally invasive cannulated screw and open reduction and plate fixation in treatment of humeral greater tuberosity fracture by a prospective case-control study. METHODS: Between January 2008 and January 2011, 49 cases of humeral greater tuberosity fractures were treated with minimally invasive cannulated screw in 25 cases (trial group), and with open reduction and plate fixation in 24 cases (control group). There was no significant difference in gender, age, injury cause, disease duration, fracture displacement, injury side, and complications between 2 groups (P > 0.05). The length of incision, operation time, intraoperative blood loss, and hospitalization days were recorded. According to Neer grading system, the effectiveness was evaluated; fracture healing was observed by X-ray films. RESULTS: The trial group had smaller incision, shorter operation time, less blood loss, and shorter hospitalization days than the control group, showing significant differences (P < 0.01). Superficial infection occurred in 2 cases of the control group, and were cured after symptomatic treatment; primary healing of incision was obtained in the others of 2 groups. All patients were followed up 1-4 years (mean, 2.3 years). The fracture healing time was (7.0 + 2.3) weeks in the trial group, and was (7.8 +/- 2.1) weeks in the control group, showing no significant difference (t=1.24, P=0.22). No heterotopic ossification or loosening and breakage of internal fixation occurred during follow-up. The shoulder function Neer score of the trial group (86.3 +/- 2.8) was significantly higher than that of the control group (80.1 +/- 2.1) (t=6.37, P=0.00). The results were excellent in 14 cases, good in 8 cases, fair in 2 cases, and poor in 1 case with an excellent and good rate of 88.0% in the trial group; the results were excellent in 12 cases, good in 7 cases, fair in 2 cases, and poor in 3 cases with an excellent and good rate of 79.2% in the control group; and difference had no statistical significance (Z=0.83, P=0.41). CONCLUSION: Compared with open reduction and plate fixation, minimally invasive cannulated screw for greater tuberosity fracture has the advantages of simple operation, less trauma, less intraoperative blood loss, and good shoulder function recovery.
Subject(s)
Bone Screws , Fracture Fixation, Internal/methods , Fractures, Closed/surgery , Humeral Fractures/surgery , Minimally Invasive Surgical Procedures/methods , Adult , Aged , Bone Plates , Case-Control Studies , Female , Fracture Fixation, Internal/instrumentation , Fracture Healing , Fractures, Closed/complications , Humans , Humeral Fractures/complications , Internal Fixators , Male , Middle Aged , Prospective Studies , Range of Motion, Articular , Recovery of Function , Shoulder Dislocation/etiology , Shoulder Dislocation/surgery , Shoulder Joint/physiopathology , Shoulder Joint/surgery , Treatment Outcome , Young AdultABSTRACT
The biological functional roles of LGR5 (leucine-rich repeat containing G protein-coupled receptor 5, also known as GPR49), a novel potential marker for stem-like cells in glioblastoma (GSCs), is poorly acknowledged. Here, we demonstrated that LGR5 was detected in glioblastoma tissues and GSCs. Bioinformatics analysis revealed that LGR5 is closely related to neurogenesis and neuronal functions, and preferentially expressed in Proneural subtype of GBMs. Furthermore, LGR5 is regulated by Proneural factor OLIG2, which is important for both neurogenesis and GSC maintenance. Biological experiments in GSC cells validated the bioinformatics analysis results and revealed that LGR5 regulated the tumor sphere formation capacity, an important stem cell property for GSCs. Therefore, LGR5 expression may be functionally correlated with the neurogenic competence, and be regulated by OLIG2 in GSCs.
Subject(s)
Basic Helix-Loop-Helix Transcription Factors/metabolism , Glioma/metabolism , Glioma/pathology , Neoplastic Stem Cells/metabolism , Neoplastic Stem Cells/pathology , Nerve Tissue Proteins/metabolism , Receptors, G-Protein-Coupled/metabolism , Adolescent , Adult , Aged , Basic Helix-Loop-Helix Transcription Factors/genetics , Brain Neoplasms/genetics , Brain Neoplasms/pathology , Cell Differentiation/genetics , Computational Biology , Databases, Genetic , Female , Gene Expression Profiling , Gene Expression Regulation, Neoplastic , Gene Regulatory Networks/genetics , Glioblastoma/genetics , Glioblastoma/pathology , Glioma/genetics , Humans , Male , Middle Aged , Nerve Tissue Proteins/genetics , Neurons/pathology , Oligodendrocyte Transcription Factor 2 , Principal Component Analysis , Receptors, G-Protein-Coupled/genetics , Spheroids, Cellular/metabolism , Spheroids, Cellular/pathology , Tumor Cells, Cultured , Young AdultABSTRACT
BACKGROUND: A proportion of glioblastoma stemlike cells (GSCs) expressing endothelial cell marker CDH5 (vascular-endothelial-cadherin or CD144) can transdifferentiate into endothelial cells and form blood vessels. However, the implications of CDH5 expression in gliomas and how it is regulated in GSCs remain to be clarified. METHODS: The mRNA and protein levels of CDH5 were detected in glioma samples and cultured cell lines, and the prognostic value of the CDH5 expression level for GBM patients was evaluated. Bioinformatics analysis was performed to reveal the potential functional roles of CDH5 in glioblastoma multiforme. Gene knockdown induced by short hairpin RNA, chromatin immunoprecipitation analysis, and a vasculogenic tube formation assay were performed to investigate the relationships among hypoxia, CDH5 expression level, and angiogenesis. RESULTS: CDH5 was overexpressed in gliomas, correlated with tumor grades, and was an independent adverse prognostic predictor for glioblastoma multiforme patients. CDH5 was specifically activated in GSCs but not in non-GSCs or neural stem cells, and CDH5(+) cells could produce xenografts in immunocompromised mice. Bioinformatics analysis demonstrated that CDH5 might interact directly with hypoxia-inducible factor (HIF)2α. CDH5 expression was significantly upregulated in GSCs, but not in non-GSCs or normal neural stem cells, under a 1% O2 condition. Both HIF1α and HIF2α positively regulated CDH5 level in GSCs and could bind to the promoter of CDH5. Furthermore, CDH5 contributed to the vasculogenic mimicry of GSCs, especially under hypoxic conditions. CONCLUSIONS: The specific expression of CDH5 in GSCs may contribute to GSC-derived neovasculogenesis in glioblastoma multiforme, especially under hypoxic conditions, revealing novel tumorigenic mechanisms contributed by GSCs.
Subject(s)
Antigens, CD/metabolism , Brain Neoplasms/pathology , Cadherins/metabolism , Glioblastoma/pathology , Hypoxia , Neoplastic Stem Cells/pathology , Neovascularization, Pathologic/pathology , Neural Stem Cells/pathology , Adult , Animals , Antigens, CD/genetics , Apoptosis , Blotting, Western , Brain Neoplasms/metabolism , Brain Neoplasms/mortality , Cadherins/antagonists & inhibitors , Cadherins/genetics , Cell Proliferation , Cells, Cultured , Chromatin Immunoprecipitation , Endothelium, Vascular/cytology , Endothelium, Vascular/metabolism , Enzyme-Linked Immunosorbent Assay , Female , Flow Cytometry , Glioblastoma/metabolism , Glioblastoma/mortality , Humans , Hypoxia-Inducible Factor 1, alpha Subunit/genetics , Hypoxia-Inducible Factor 1, alpha Subunit/metabolism , Immunoenzyme Techniques , Male , Mice , Mice, Nude , Middle Aged , Neoplasm Grading , Neoplastic Stem Cells/metabolism , Neovascularization, Pathologic/metabolism , Neural Stem Cells/metabolism , RNA, Messenger/genetics , RNA, Small Interfering/genetics , Real-Time Polymerase Chain Reaction , Reverse Transcriptase Polymerase Chain ReactionABSTRACT
We report the synthesis of nanoapatite crystals via a hydrothermal reaction of hydroxyapatite precipitates. The impact of the reaction conditions on the properties of the crystals obtained were evaluated. The hydrothermal reaction that takes place markedly affected the crystallinity, morphology, and size of the nanoapatite crystals formed. High crystallinity and large crystal size were obtained at higher hydrothermal temperatures and longer hydrothermal reaction times. The nanoapatite crystals were needle-like when prepared under ambient pressure conditions and rod-like when prepared under increased pressure. The crystals prepared at ambient pressure had a larger aspect ratio compared with those prepared under increased pressure. The aging time of the initial hydroxyapatite precipitate significantly affected growth of the nanoapatite crystals. With other hydrothermal reaction conditions being equal, the fresh hydroxyapatite precipitate produced notably larger crystals than the aged hydroxyapatite precipitate. The influence of apatite morphology on osteoblast viability was studied by MTT assay. The results indicate that the rod-like apatite showed a better biological response than needle-like apatite in promoting cell growth. Transmission electron microscopy showed that large quantities of needle apatite entered into cells and damaged their morphology.
Subject(s)
Apatites/chemistry , Crystallization/methods , Nanoparticles/chemistry , Water/chemistry , Hot Temperature , Materials Testing , Molecular Conformation , Particle Size , Surface PropertiesABSTRACT
A bone-implanted porous scaffold of mesoporous bioglass/polyamide composite (m-BPC) was fabricated, and its biological properties were investigated. The results indicate that the m-BPC scaffold contained open and interconnected macropores ranging 400-500 µm, and exhibited a porosity of 76%. The attachment ratio of MG-63 cells on m-BPC was higher than polyamide scaffolds at 4 hours, and the cells with normal phenotype extended well when cultured with m-BPC and polyamide scaffolds. When the m-BPC scaffolds were implanted into bone defects of rabbit thighbone, histological evaluation confirmed that the m-BPC scaffolds exhibited excellent biocompatibility and osteoconductivity, and more effective osteogenesis than the polyamide scaffolds in vivo. The results indicate that the m-BPC scaffolds improved the efficiency of new bone regeneration and, thus, have clinical potential for bone repair.
Subject(s)
Bone Regeneration/drug effects , Bone Substitutes/chemistry , Glass/chemistry , Nylons/chemistry , Tissue Scaffolds/chemistry , Analysis of Variance , Animals , Bone Substitutes/pharmacology , Cell Adhesion/drug effects , Cell Line, Tumor , Femur/drug effects , Femur/pathology , Femur/physiology , Histocytochemistry , Humans , Materials Testing , Nylons/pharmacology , Porosity , RabbitsABSTRACT
BACKGROUND: The pituitary is a critical neuroendocrine gland that is comprised of five hormone-secreting cell types, which develops in tandem during the embryonic stage. Some essential genes have been identified in the early stage of adenohypophysial development, such as PITX1, FGF8, BMP4 and SF-1. However, it is likely that a large number of signaling molecules and transcription factors essential for determination and terminal differentiation of specific cell types remain unidentified. High-throughput methods such as microarray analysis may facilitate the measurement of gene transcriptional levels, while Expressed sequence tag (EST) sequencing, an efficient method for gene discovery and expression level analysis, may no-redundantly help to understand gene expression patterns during development. RESULTS: A total of 9,271 ESTs were generated from both fetal and adult pituitaries, and assigned into 961 gene/EST clusters in fetal and 2,747 in adult pituitary by homology analysis. The transcription maps derived from these data indicated that developmentally relevant genes, such as Sox4, ST13 and ZNF185, were dominant in the cDNA library of fetal pituitary, while hormones and hormone-associated genes, such as GH1, GH2, POMC, LHbeta, CHGA and CHGB, were dominant in adult pituitary. Furthermore, by using RT-PCR and in situ hybridization, Sox4 was found to be one of the main transcription factors expressed in fetal pituitary for the first time. It was expressed at least at E12.5, but decreased after E17.5. In addition, 40 novel ESTs were identified specifically in this tissue. CONCLUSION: The significant changes in gene expression in both tissues suggest a distinct and dynamic switch between embryonic and adult pituitaries. All these data along with Sox4 should be confirmed to further understand the community of multiple signaling pathways that act as a cooperative network that regulates maturation of the pituitary. It was also suggested that EST sequencing is an efficient means of gene discovery.
Subject(s)
Expressed Sequence Tags , Gene Expression Regulation, Developmental , Pituitary Gland/growth & development , Adult , Animals , DNA, Complementary/metabolism , Fetus/metabolism , Gene Expression Profiling , Humans , Male , Mice , Mice, Inbred C57BL , Oligonucleotide Array Sequence Analysis , Pituitary Gland/metabolism , SOXC Transcription Factors/genetics , SOXC Transcription Factors/metabolismABSTRACT
Invasive pituitary adenomas (IPA) involving the skull base extend from the sella region, and invade surrounding structures. In the present study, we reviewed the therapeutic efficacy in a group of patients with IPA treated with endoscopic endonasal transsphenoidal surgery. Data from 78 IPA patients at our hospital were retrospectively reviewed. The diagnostic modalities, surgical techniques, and outcomes were reviewed. Diagnosis was confirmed by endocrinological profile and CT or MRI in all patients. Surgery was performed via an endoscopic endonasal transsphenoidal approach. Thirty-five patients (44.9%) had hormonally active tumors, and 43 (55.1%) had nonfunctioning tumors. Complete removal of the tumor was achieved in 62 patients (79.5%) and subtotal removal in 12 (15.4%); partial removal was achieved in the remaining four patients (5.1%) who had fibrous or dumbbell-shaped adenomas. The mean follow-up was 43.2 months in 65 patients and the clinical symptoms in all patients improved to varying degrees. In 52 patients, the tumors completely disappeared on follow-up imaging. Visual symptoms improved in 96.4% of the patients who had presented with visual impairment. These surgical results show that endoscopic endonasal transsphenoidal surgery for resection of IPA has advantages. We suggest that the endoscopic endonasal transsphenoidal surgery method is a safe, minimally invasive and efficient surgical technique for removal of IPA, providing good visualization of the operative field, generally complete tumor removal, short procedure duration, and minimal postoperative complications.
Subject(s)
Adenoma/surgery , Hypophysectomy/methods , Neuroendoscopy/methods , Pituitary Neoplasms/surgery , Sphenoid Bone/surgery , Adenoma/pathology , Adolescent , Adult , Aged , Female , Humans , Magnetic Resonance Imaging , Male , Middle Aged , Pituitary Neoplasms/pathology , Retrospective Studies , Treatment OutcomeABSTRACT
Hemorrhagic pituitary adenoma (HPA) is an acute clinical event in neurosurgery. Emergency surgical decompression is the most effective treatment. We retrospectively reviewed 65 cases collected from the Xijing Institute of Clinical Neuroscience from 1995 to 2005 with HPA. The majority of the patients (81.5%) experienced the acute symptoms of pituitary apoplexy including headache, ocular paresis, visual field deficits and hypopituitarism. On imaging features, 34 adenomas (52.3%) showed marked suprasellar extension, 17 (26.2%) showed moderate extension, and 6 (9.2%) had slight extension, another eight (12.3%) were intrasellar. All patients were treated promptly by emergency surgical decompression usually within 24h after the hospitalization. Twenty four patients operated on by the traditional transsphenoidal microsurgery; whereas 41 patients operated on by the endoscopic endonasal transsphenoidal surgery. Total removal of tumors was achieved in 59 cases (90.8%) and subtotal removal in 6 cases (9.2%). Postoperative radiotherapy, suppressive drug therapy and endocrine replacement therapy were required in seven patients with either remaining tumor or tumor recurrence. In a median follow-up period of 49 months for 54 cases, most patients' clinical symptoms had markedly improved. Visual acuity and visual fields improved in 88.4% and 92.7% of the patients who had preoperative visual symptoms, respectively. The majority of the HPA often occurred in patients with macroadenomas. With emergency surgical treatment, most patients with HPA could have quick improvement of symptoms, especially for altered consciousness and visual acuity or visual fields impairments.
Subject(s)
Adenoma/therapy , Emergencies , Hemorrhage/surgery , Pituitary Neoplasms/therapy , Adenoma/complications , Adenoma/diagnosis , Adult , Aged , Female , Follow-Up Studies , Hemorrhage/diagnosis , Hemorrhage/etiology , Hormone Replacement Therapy , Humans , Male , Microsurgery , Middle Aged , Pituitary Neoplasms/complications , Pituitary Neoplasms/diagnosis , Postoperative Complications , Radiotherapy, Adjuvant , Retrospective Studies , Treatment Outcome , Vision Disorders/etiology , Vision Disorders/surgeryABSTRACT
OBJECTIVE: To assess the clinical curative effect of the endonasal transsphenoidal approach for removing pituitary adenoma (PA) under neuroendoscope-assisted. METHODS: There were 215 patients who had undergone neuroendoscopic transsphenoidal surgery. Each patient received CT or MRI examination which showed the size and surrounding structural of tumor. RESULTS: Among the 215 patients, 190 cases (88.4%) had total removal, 17 cases (7.9%) achieved subtotal removal and the remaining 8 cases (3.7%) with fibrous tumor was carried out partial removal. Two patients (0.9%) died after operation. Postoperative follow-up period was 1 to 10 months (the average was 3.5 months). In 182 patients, 150 cases (90.9%) got vision recovered rapidly compared with their preoperative symptoms, such as diminished acuities and visual field defects, and 15 cases (9.1%) had gotten improvements to some extend among 165 who diagnosed as pituitary macroadenoma (PMaA); There were 17 patients who diagnosed as microadenoma (PMiA) showed that the pituitary dyshormonism recovered gradually. CONCLUSIONS: The endonasal transsphenoidal surgery under the neuroendoscope-assisted appears to be a safe, effective and micro-invasive method for PA.
Subject(s)
Adenoma/surgery , Hypophysectomy/methods , Pituitary Neoplasms/surgery , Sphenoid Sinus/surgery , Adolescent , Adult , Aged , Female , Follow-Up Studies , Humans , Male , Middle Aged , Nasal Cavity/surgery , Neuroendoscopy , Retrospective Studies , Treatment OutcomeABSTRACT
Pituitary, a master gland of neuroendocrine system, secretes hormones that orchestrate many physiological processes, under the regulation of multiple signaling pathways. To investigate the genes involved in hormones expression of human pituitary, homemade cDNA microarray containing 14,800 human genes/ESTs were used to profile the gene expression in both fetal and adult pituitaries. Seven hundred and twelve known genes changed over 2-fold between the both tissues. Of which, 23 genes were changed with hormones expression in aging were confirmed by RT-PCR, not only the known regulators such as Pit1, GATA4, ESRRA, GABA-A, and EMK, but also LOC55884, DUSP3, PNN, and RCL, which had not been reported to be involved in the hormones expression. Correspondingly, the mRNAs of GH, PRL, POMC, TSH-beta, FSH-beta, and LH-beta, was increased as much as 6- to 20-fold in adult pituitary than those in fetal pituitary, by real-time quantitative RT-PCR assay. In addition, the mRNAs of signaling pathways, such as cAMP-PKA-CREB, PI3K-Akt, and PKA-ERK were further investigated. Of them, it was only cAMP-PKA-CREB pathway, but not PI3K-Akt and PKA-ERK have the same expressing pattern as hormones. It suggested that cDNA microarray is highly advantages to profile the differential expressed genes that were involved in hormones expression of human pituitary, but it might ignore some responding proteins regulated posttranscriptionally.
Subject(s)
Gene Expression Profiling , Gene Expression Regulation, Developmental/genetics , Oligonucleotide Array Sequence Analysis , Pituitary Gland/metabolism , Pituitary Hormones/genetics , Signal Transduction/genetics , Adult , Aged , Aging/genetics , Aging/physiology , Female , Fetus/metabolism , Humans , Male , Middle Aged , Pituitary Hormones/metabolism , RNA, Messenger/analysis , Signal Transduction/physiologyABSTRACT
A library of benzoindolizines (pyrrolo [1,5-a] quinolines 10 and pyrrolo [1,5-a] quinolines 9) has been synthesized using poly(ethylene glycol) (PEG) as soluble polymer support. The PEG-supported isoquinolinium salt 4 reacted, respectively, with active alkenes 11 using tetrakispyridinecobalt(II) dichromate (TPCD) as oxidant or alkynes 12 to give 10, of which yields were from moderate to high. By analogy, the reaction of PEG-supported quinolinium salt 3 with 12 was to produce 9. However, in the presence of TPCD the reaction of 3 with 11 afforded indolizines 8, which was discovered firstly.