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1.
Nutrients ; 15(9)2023 Apr 29.
Article in English | MEDLINE | ID: mdl-37432305

ABSTRACT

Gut microbiota and its metabolites are related to the female reproductive system. Animal experiments have demonstrated the relationship between gut microbiota-derived short chain fatty acids (SCFAs) and embryo quality. However, few studies have linked SCFAs to clinical pregnancy outcomes in humans. This retrospective cross-sectional study recruited 147 patients undergoing in vitro fertilization or intracytoplasmic sperm injection and embryo transfer (IVF/ICSI-ET) (70 with no pregnancies and 77 with clinical pregnancies). The association between SCFAs levels and clinical pregnancy outcomes was evaluated using univariate and multivariate logistic regression analyses. The association between SCFAs and metabolic parameters was analyzed using a linear regression model. Receiver operating characteristic (ROC) curve analysis was used for assessing the efficiency of SCFAs to evaluate the clinical pregnancy outcomes. Fecal propionate levels were significantly higher in the no pregnancy group than in the clinical pregnancy group (p < 0.01). Fecal acetate and butyrate levels were not significantly different between females with and without clinical pregnancies (p > 0.05). There were positive relationships between fecal propionate levels and fasting serum insulin (FSI) (r = 0.245, p = 0.003), Homeostatic Model Assessment for Insulin Resistance (HOMA-IR) (r = 0.276, p = 0.001), and triglycerides (TG) (r = 0.254, p = 0.002). Multivariate analyses determined that fecal propionate (OR, 1.103; 95% CI, 1.045-1.164; p < 0.001) was an independent risk factor for no pregnancies. The area under the ROC curve (AUC) of fecal propionate was 0.702 (p < 0.001), with a sensitivity of 57.1% and a specificity of 79.2%. High fecal propionate concentration has a negative association on clinical pregnancy outcomes and is positively correlated with FSI, TG, and HOMA-IR.


Subject(s)
Gastrointestinal Microbiome , Insulin Resistance , Male , Animals , Pregnancy , Humans , Female , Pregnancy Outcome , Retrospective Studies , Sperm Injections, Intracytoplasmic , Propionates , Cross-Sectional Studies , Semen , Fatty Acids, Volatile , Fertilization in Vitro
2.
Front Bioeng Biotechnol ; 11: 1104015, 2023.
Article in English | MEDLINE | ID: mdl-36845190

ABSTRACT

Objective: The purpose of this study was to analyze the feasibility of repairing a ruptured intervertebral disc using a patch secured to the inner surface of the annulus fibrosus (AF). Different material properties and geometries for the patch were evaluated. Methods: Using finite element analysis, this study created a large box-shaped rupture in the posterior-lateral region of the AF and then repaired it with a circular and square inner patch. The elastic modulus of the patches ranged from 1 to 50 MPa to determine the effect on the nucleus pulposus (NP) pressure, vertical displacement, disc bulge, AF stress, segmental range of motion (ROM), patch stress, and suture stress. The results were compared against the intact spine to determine the most suitable shape and properties for the repair patch. Results: The intervertebral height and ROM of the repaired lumbar spine was similar to the intact spine and was independent of the patch material properties and geometry. The patches with a modulus of 2-3 MPa resulted in an NP pressure and AF stresses closest to the healthy disc, and produced minimal contact pressure on the cleft surfaces and minimal stress on the suture and patch of all models. Circular patches caused lower NP pressure, AF stress and patch stress than the square patch, but also caused greater stress on the suture. Conclusion: A circular patch with an elastic modulus of 2-3 MPa secured to the inner region of the ruptured annulus fibrosus was able to immediately close the rupture and maintain an NP pressure and AF stress similar to the intact intervertebral disc. This patch had the lowest risk of complications and produced the greatest restorative effect of all patches simulated in this study.

3.
J Clin Med ; 12(3)2023 Jan 26.
Article in English | MEDLINE | ID: mdl-36769605

ABSTRACT

This study aimed to assess the effects of GH adjuvant therapy on the cumulative live birth rate in patients with poor embryo quality and to determine the characteristics of patients who are more responsive to GH. A retrospective cohort study was carried out in patients who have suffered from previous IVF failure due to poor embryonic development and underwent IVF with or without a 6-week pretreatment with GH in the subsequent cycle from January 2018 to December 2020. Clinical parameters including the cumulative live birth rate between the (-) GH and (+) GH groups were compared. Multivariate analysis was performed to ascertain associations between clinical parameters and cumulative live birth rate. Upon analysis of the clinical data from 236 IVF cycles, 84 patients received GH and 152 did not receive GH. In frozen embryo transfer cycles, compared with the (-) GH group, the implantation rate and live birth rate were significantly higher in the (+) GH group (p < 0.05). After adjusting for possible confounding factors, GH improved cumulative live birth per oocyte retrieval cycle by 1.96 folds (p = 0.032). Furthermore, when patients were subdivided based on age and BMI, a significant increase in the cumulative live birth rate was found in the (+) GH group of patients between 35 and 42 years old and BMI ≥ 24 kg/m2, respectively (p < 0.05). GH may increase the live birth rate in women who experienced IVF failure because of poor embryonic development, particularly in obese patients and women with advanced age.

4.
Nutrients ; 14(19)2022 Sep 23.
Article in English | MEDLINE | ID: mdl-36235607

ABSTRACT

Trimethylamine-N-oxide (TMAO), an important gut microbiota (GM)-derived metabolite, has been shown to be abnormally increased in osteoporosis. However, the role and underlying mechanism of TMAO in regulating bone loss during osteoporosis have not been fully investigated. In the current study, we found that 100-400 µM TMAO dose-dependently enhanced TRAP-positive osteoclasts, F-actin ring formation, and resorption area on bovine bone slices and up-regulated osteoclast-related gene expression (Calcr, Traf6, Dcstamp, Acp5, C-Fos, and NFATc1). Western blotting validated that TMAO not only activated NF-κB signaling pathway but also stimulated c-Fos and NFATc1 protein expression in a dose-dependent manner. Furthermore, BAY 11-7082, an NF-κB inhibitor, pretreatment markedly suppressed TRAP-positive osteoclast formation and osteoclast-related genes under TMAO treatment. BAY 11-7082 also inhibited p-p65/p65, c-Fos, and NFATc1 protein expression promoted by TMAO. Moreover, TMAO significantly increased ROS production, which was inhibited by N-acetylcysteine (NAC), an ROS antagonist. In addition, we proved that NAC pretreatment could inhibit TMAO-promoted NF-κB activation. NAC also suppressed TRAP-positive osteoclast formation, osteoclast-related gene expression, and protein expression of c-Fos and NFATc1 under TMAO treatment. In vivo studies showed significantly decreased bone mass and increased TRAP-positive osteoclasts in TMAO-treated C57BL/6 mice. Moreover, western-blotting and immunohistochemical staining showed that TMAO administration markedly stimulated NF-κB p65 expression. Additionally, TMAO administration significantly promoted the gene and protein expression of C-Fos and NFATc1. In conclusion, TMAO could promote osteoclast differentiation and induce bone loss in mice by activating the ROS-dependent NF-κB signaling pathway.


Subject(s)
Bone Resorption , Osteoporosis , Acetylcysteine/metabolism , Actins/metabolism , Animals , Bone Resorption/metabolism , Cattle , Cell Differentiation , Methylamines , Mice , Mice, Inbred C57BL , NF-kappa B/metabolism , NFATC Transcription Factors/genetics , NFATC Transcription Factors/metabolism , Nitriles , Osteoclasts/metabolism , Osteogenesis , Osteoporosis/metabolism , Oxides/metabolism , Proto-Oncogene Proteins c-fos/genetics , Proto-Oncogene Proteins c-fos/metabolism , RANK Ligand/metabolism , Reactive Oxygen Species/metabolism , Signal Transduction , Sulfones , TNF Receptor-Associated Factor 6/metabolism
5.
Front Genet ; 13: 955643, 2022.
Article in English | MEDLINE | ID: mdl-35957679

ABSTRACT

Objective: The objective of the study was to investigate the effectiveness of applying the individualized guide plate which is based on digital image processing and 3D printing technology to percutaneous needle biopsy of periacetabular tumor. Methods: From July 2017 to August 2019, 11 patients (5 males and 6 females, aged 13-70 years, mean 42.3 years) with acetabular tumors diagnosed by needle biopsy in our hospital were enrolled in this retrospective study. Preoperative CT and MRI enhancement examination were performed routinely, and the DICOM data were collected and imported into Medraw Print software. According to the specific anatomical morphology of acetabula, this study adopted the reverse calculation and direct design to print the individualized puncture guide plate using 3D printing technology. The puncture point and sampling approaches were determined by the guide plate morphology and the "double guide-hole and slideable groove" design. First, we evaluated the fitness of the 3D guide plate to the local anatomical structure, its assisted-puncture accuracy was estimated by imaging examinations, and postoperative complications were recorded. The accuracy of the needle biopsy pathological result was estimated with reference to that of the tumor resection. Results: Our results showed that the 3D printing individualized guide plate matched the patients' pelvic skin well, the puncture approach was consistent with the preoperative design, and no significant anatomical injuries including vascular and neural complications occurred after surgery. Nine patients' (90%) biopsy results were consistent with their postoperative pathological results, and one patient gave up the tumor resection. Conclusion: Based on digital image processing and 3D printing technology, the individualized guide plate can be used to guide the needle biopsy of acetabular tumors which makes the operation simpler and more precise.

6.
Nutrients ; 14(15)2022 Aug 04.
Article in English | MEDLINE | ID: mdl-35956371

ABSTRACT

Infertility is defined as failure to achieve pregnancy within 12 months of unprotected intercourse in women. Trace elements, a kind of micronutrient that is very important to female reproductive function, are affected by intestinal absorption, which is regulated by gut microbiota. Enterotype is the classification of an intestinal microbiome based on its characteristics. Whether or not Prevotella-enterotype and Bacteroides-enterotype are associated with blood trace elements among infertile women remains unclear. The study aimed to explore the relationship between five main whole blood trace elements and these two enterotypes in women with infertility. This retrospective cross-sectional study recruited 651 Chinese women. Whole blood copper, zinc, calcium, magnesium, and iron levels were measured. Quantitative real-time PCR was performed on all fecal samples. Patients were categorized according to whole blood trace elements (low levels group, <5th percentile; normal levels group, 5th‒95th percentile; high levels group, >95th percentile). There were no significant differences in trace elements between the two enterotypes within the control population, while in infertile participants, copper (P = 0.033), zinc (P < 0.001), magnesium (P < 0.001), and iron (P < 0.001) in Prevotella-enterotype was significantly lower than in Bacteroides-enterotype. The Chi-square test showed that only the iron group had a significant difference in the two enterotypes (P = 0.001). Among infertile patients, Prevotella-enterotype (Log(P/B) > −0.27) predicted the low levels of whole blood iron in the obesity population (AUC = 0.894; P = 0.042). For the high levels of iron, Bacteroides-enterotype (Log(P/B) <−2.76) had a predictive power in the lean/normal group (AUC = 0.648; P = 0.041) and Log(P/B) <−3.99 in the overweight group (AUC = 0.863; P = 0.013). We can infer that these two enterotypes may have an effect on the iron metabolism in patients with infertility, highlighting the importance of further research into the interaction between enterotypes and trace elements in reproductive function.


Subject(s)
Gastrointestinal Microbiome , Infertility, Female , Trace Elements , Bacteroides , Copper , Cross-Sectional Studies , Female , Humans , Iron , Magnesium , Prevotella , Retrospective Studies , Zinc
7.
Genes (Basel) ; 13(4)2022 03 29.
Article in English | MEDLINE | ID: mdl-35456425

ABSTRACT

Senile osteoporosis is defined as an age-related bone metabolic disorder, which is characterized by bone loss and decreased bone fragility. Gut microbiota (GM) could regulate the bone metabolic process and be closely related to senile osteoporosis. Several genus-level GM were found to increase in osteoporotic animals and patients. However, to reveal the pathogenic bacteria in senile osteoporosis, further studies are still needed to investigate the complete characteristics of bacteria species. In the present study, the rats were equally divided into two groups: the control group (Con, 6-month-old) and the osteoporosis group (OP, 22-month-old). Fecal samples were freshly collected to conduct the shallow shotgun sequencing. Then, we compared the species numbers, microbial diversity, GM composition at genus and species-level, and functional metabolic pathways in the two groups. The results showed that the species number was lower in the OP group (1272) than in the control group (1413), and 1002 GM species were shared between the two groups. The OP group had the decreased α diversity compared with the control group. As for ß diversity, The PCA revealed that samples in the two groups had distinguishable ecological distance in each coordinate. At the species level, Bacteroide coprocola (B. coprocola), Acinetobacter baumannii (A. baumannii), Parabacteroides distasonis (P. distasonis), and Prevotella copri (P. copri) were higher in the OP group, while Corynebacterium stationis (C. stationis), Akkermansia muciniphila (A. muciniphila), and Alistipes indistinctus (A. indistinctus) were decreased. Moreover, functional metabolic analysis revealed that metabolic pathways of fatty acid biosynthesis, valine/isoleucine biosynthesis, GABA biosynthesis, and ubiquinone biosynthesis were enriched in the senile osteoporotic rats. In conclusion, GM at the species level in senile osteoporotic rats was significantly altered in structure, composition, and function. The altered GM structure, increased GM species such as P. copri, and decreased GM species such as A. muciniphila might be linked with the development of senile osteoporosis.


Subject(s)
Gastrointestinal Microbiome , Osteoporosis , Animals , Feces/microbiology , Gastrointestinal Microbiome/genetics , Humans , Osteoporosis/genetics , Prevotella , Rats
8.
Gene ; 817: 146205, 2022 Apr 05.
Article in English | MEDLINE | ID: mdl-35063575

ABSTRACT

Gut microbiota was verified to regulate bone metabolism and was closely associated with osteoporosis. Using 16S rRNA sequencing, gut microbiota at genus level such as Helicobacter, Bacteroides, and Prevotella were found to increase in the osteoporotic animals and people. However, the changes of species-level gut microbiota and related functional alterations were still unknown. Female SD rats were divided into the ovariectomized (OVX) group and the control group, and the fecal samples were collected at 4, 8, and 12 weeks to analyze the information of gut microbiota. Using Shallow shotgun sequencing, we compared the species-level gut microbiota structure, composition, and functional pathways of the OVX group with the control group. Alpha diversity of the OVX rats were significantly decreased than those in the control group. Beta diversity showed that samples in the two groups could be distinguished in each coordinate at different time points. Furthermore, the relative abundance of gut microbiota at species-level and differential analysis found that bacteria species such as Helicobacter rodentium, Lachnospiraceae bacterium 10 1, and Lachnospiraceae bacterium A4 were markedly increased in the OVX rats. Furthermore, differential analysis of KEGG functional pathway revealed that lysine metabolism was enriched in the OVX group.In conclusion, gut microbiota were significantly altered in structure and composition estrogen-deficiency osteoporotic rats at the species level. Functional metabolism of gut microbiota was also changed in osteoporotic group. These changes in gut microbiota at the species level might be closely associated with osteoporosis caused by estrogen deficiency.


Subject(s)
Gastrointestinal Microbiome , Osteoporosis, Postmenopausal/microbiology , Animals , Biodiversity , Disease Models, Animal , Female , Humans , Ovariectomy , Rats , Rats, Sprague-Dawley , Sequence Analysis, DNA
9.
Calcif Tissue Int ; 110(2): 225-235, 2022 02.
Article in English | MEDLINE | ID: mdl-34480200

ABSTRACT

Gut microbiota (GM) dysbiosis is closely related to several metabolic diseases such as hypertension, obesity, and Alzheimer's disease. However, little is known about the causal relationship between GM dysbiosis and osteoporosis. In our work, 32 3-month-old female SD rats were randomly divided into two groups: the fecal microbiota transplantation (FMT) group and the control group. The supernatant of feces from senile osteoporotic rats was transplanted to the FMT group and the same amount of sterile saline was given to the control rats. After 12 and 24 weeks, all rats were sacrificed, and the serum, bone, fecal feces, and intestine tissue were collected for the subsequent analysis. The osteocalcin (OC), CTX, and P1NP of the FMT group increased significantly at 12 and 24 weeks compared with the control group (P < 0.05). Furthermore, the BV, BV/TV, Tb.N, and Tb.Th decreased significantly in the FMT group (P < 0.05). The alpha diversity (ACE, Chao) of the FMT group was higher than the control at 24 weeks (P < 0.05). The beta diversity was close between the FMT rats and the donor rats. In addition, GM from donor rats changed the GM composition and function of the FMT rats, which was similar to that of the donor rats at 24 weeks. The impaired intestinal structure and the decreased expression of occludin, claudin, and ZO-1 were found in FMT rats. In conclusion, GM dysbiosis by transferring the feces from senile osteoporotic rats to young rats could induce osteoporosis. The changed GM and the impaired intestinal barrier contributed to the pathogenesis of osteoporosis.


Subject(s)
Gastrointestinal Microbiome , Osteoporosis , Animals , Dysbiosis , Fecal Microbiota Transplantation , Female , Rats , Rats, Sprague-Dawley
10.
PeerJ ; 9: e12293, 2021.
Article in English | MEDLINE | ID: mdl-34721980

ABSTRACT

BACKGROUND: Gut microbiota (GM) dysbiosis is closely related to bone loss and the occurrence of osteoporosis in animals and human. However, little is known about the effect and the mechanisms of fecal microbiota transplantation (FMT) on bone in the treatment of senile osteoporosis. METHODS: Aged female rats were randomly divided into the FMT group and the control group. 3-month-old female rats were used as fecal donors. The rats were sacrificed at 12 and 24 weeks following transplantation and the serum, intestine, bone, and feces were collected for subsequent analyses. RESULTS: The bone turnover markers of osteocalcin, procollagen type 1 N-terminal propeptide (P1NP), and carboxy-terminal peptide (CTX) decreased significantly at 12 and 24 weeks following FMT (P < 0.05). At 12 weeks following transplantation, histomorphometric parameters including the bone volume (BV), trabecular bone volume fraction (BV/TV), trabecular number (Tb.N), and trabecular thickness (Tb.Th) of the FMT group were comparable to the control group. However, at 24 weeks following transplantation, these parameters of the FMT group were significantly higher than those of the control group (P < 0.05). Besides, the GM aggregated at 12 and 24 weeks following FMT, and the ecological distance was close between the rats in the FMT group and the donor rats. Alpha diversity, shown by the Shannon index and Simpson index, and the Firmicutes/Bacteroidetes ratio decreased significantly after FMT at 24 weeks. Furthermore, FMT restored the GM composition in aged rats at the phylum and family level, and the intestinal microbiota of the aged rats was similar to that of the donor rats. Correlation network analysis indirectly suggested the causality of FMT on alleviating osteoporosis. FMT improved the intestinal structure and up-regulated the expression of tight junction proteins of occludin, claudin, and ZO-1, which might be associated with the protective effects of FMT on bone. CONCLUSIONS: GM transplanted from young rats alleviated bone loss in aged rats with senile osteoporosis by improving gut microbiome composition and intestinal barrier function. These data might provide a scientific basis for future clinical treatment of osteoporosis through FMT.

11.
Biomaterials ; 268: 120537, 2021 01.
Article in English | MEDLINE | ID: mdl-33260096

ABSTRACT

Hypoxia has been firmly correlated to the drug resistance of solid tumors. Alleviation of hypoxia by tumor reoxygenation is expected to sensitize the chemotherapy toward solid tumors. Alternatively, ferroptosis provides a therapeutic strategy to overcome apoptotic resistance and multidrug resistance of solid tumors, collaboratively strengthening the chemotherapy toward hypoxic tumors. Herein, an ultrasound (US)-activatable nanomedicine was developed for overcoming hypoxia-induced resistance to chemotherapy and efficiently inhibiting tumor growth by inducing sensitized apoptosis and collaborative ferroptosis of tumor cells. This nanomedicine was constructed by integrating ferrate and doxorubicin into biocompatible hollow mesoporous silica nanoplatforms, followed by assembling a solid-liquid phase-change material of n-heneicosane. The US-induced mild hyperthermia initiates the phase change of n-heneicosane, enabling US-activated co-release of ferrate and doxorubicin. Results reveal that the released ferrate effectively reacts with water as well as the over-expressed hydrogen peroxide and glutathione in tumor cells, achieving tumor-microenvironment-independent reoxygenation and glutathione-depletion in tumors. The reoxygenation down-regulates expressions of hypoxia-inducible factor 1α and multidrug resistance gene/transporter P-glycoprotein in tumor cells, sensitizing the apoptosis-based doxorubicin chemotherapy. More importantly, exogenous iron metabolism from the nanomedicine initiates intracellular Fenton reactions, leading to reactive oxygen species overproduction and iron-dependent ferroptotic death of tumor cells. Furthermore, the glutathione-depletion inactivates the glutathione peroxidase 4 (GPX4, a critical regulatory target in ferroptosis), inhibiting the reduction of lipid peroxides and reinforcing the ferroptotic cell death. The sensitized chemotherapy together with the iron-dependent ferroptosis of tumor cells play a synergistic role in boosting the growth suppression of hypoxic osteosarcoma in vivo. Additionally, the nanomedicine acts as a nanoprobe for in vivo photoacoustic imaging and glutathione tracking, showing great potential as theranostic agents for hypoxic solid tumors treatment.


Subject(s)
Ferroptosis , Apoptosis , Cell Line, Tumor , Humans , Hypoxia , Nanomedicine
12.
Aging (Albany NY) ; 12(11): 10736-10753, 2020 06 02.
Article in English | MEDLINE | ID: mdl-32484785

ABSTRACT

As a critical factor involved in the maintenance of physiological homeostasis, the gut microbiota (GM) reportedly plays a key role in bone development. To date, the association between the GM and steroid deficiency-induced osteoporosis remains poorly understood. Forty female Sprague Dawley rats were divided into an ovariectomy (OVX) or control group. We performed 16S rRNA and metagenome sequencing, to compare diversity, taxonomic differences, and functional genes. The GM composition did not change in the control group and the number of operational taxonomic units increased significantly following ovariectomy. Alpha diversity, determined by ACE estimator, CHAO estimator, the Shannon index, and the Simpson index showed an increasing trend after ovariectomy. Samples in the OVX group were well clustered both pre- and post-ovariectomy, as demonstrated by principal coordinate 1 (PC1) and PC2. Functional genes of GM, including those involved in synthesis and metabolism of carbohydrates and nucleotides, microbial structure, and heme, as well as hemin uptake and utilization, increased at the early stage of osteoporosis. We observed that Ruminococcus flavefaciens exhibited the greatest variation in abundance among the GM and this was also associated with osteoclastic indicators and the estrobolome. Specific changes in fecal microbiota are associated with the pathogenesis of steroid deficiency-induced osteoporosis.


Subject(s)
Bone Development/physiology , Bone and Bones/metabolism , Gastrointestinal Microbiome/physiology , Osteoporosis, Postmenopausal/metabolism , Animals , Biomechanical Phenomena , Disease Models, Animal , Feces/microbiology , Female , Humans , Ovariectomy , RNA, Ribosomal, 16S/analysis , Rats , Rats, Sprague-Dawley , Ruminococcus/isolation & purification
13.
Aging (Albany NY) ; 12(11): 10795-10808, 2020 06 02.
Article in English | MEDLINE | ID: mdl-32487781

ABSTRACT

Recently, more interest has been paid to the association between bone mass and gut microecological dysbiosis. The results of clinical studies comparing gut microbiota (GM) in osteoporosis patients have been inconsistent due to different inclusion and exclusion criteria. To date, the association between the GM and senile osteoporosis remains poorly understood. Here, we utilized an aged rat model (22 months old) of senile osteoporosis to study the association of the composition and function of the GM with osteoporosis by 16S rRNA and metagenomic sequencing. The results showed that there was a significant reduction in alpha diversity and the F/B (Firmicutes/Bacteroidetes) ratio in aged rats. At the genus level, the enrichment of Helicobacter was potentially related to osteoporosis as a risk factor. Metagenomics results based on two databases indicated that shifts in the GM contribute to senile osteoporosis through metabolic pathways and subsequent immune disorders. In conclusion, our study reveals the association of gut microbiota composition and function with senile osteoporosis in an aged rat model in a brand new way, and variations in the GM might contribute to senile osteoporosis through metabolic pathways.


Subject(s)
Gastrointestinal Microbiome , Gastrointestinal Tract/microbiology , Osteoporosis/microbiology , Animals , Bone Density , Female , Metabolic Networks and Pathways , Metagenomics , RNA, Ribosomal, 16S/genetics , Rats , Rats, Sprague-Dawley
14.
Calcif Tissue Int ; 107(1): 60-71, 2020 07.
Article in English | MEDLINE | ID: mdl-32274533

ABSTRACT

Autophagy is an evolutionarily conserved dynamic process and present in variety of cells at basal levels to maintain homeostasis and to promote cell survival in response to stresses. The early bone loss with excessive glucocorticoids (GCs) was reported to be related with the extension of the life span of osteoclasts. However, the connection between GCs induced bone loss and osteoclast autophagy remains to be elucidated. Autophagy was detected in a Dexamethasone (Dex) induced osteoporotic mice model and primary osteoclast cultures by autophagosome detection kit, and autophagy-related proteins were assayed by Western blotting and Immunostaining. The bone morphology was examined by micro-CT and TRAP staining. The trabecular bone micro-architecture was deteriorated, and the osteoclast number and spread area were increased in the Dex-treated mice compared with the control group (P < 0.01). Meanwhile, autophagy in pre-osteoclasts was increased in mice under Dex administration evidenced by the increased number of autophagosome and up-regulation of autophagy-related protein levels. Further, the enhanced autophagy under Dex treatment was verified in primary cultured osteoclasts, as shown by the increased levels of Beclin 1 and LC3-II/LC3-I and the autophagy complex formation members including Atg1, Atg13, and Atg7. However, the expressions of PI3K, p-Akt and p-mTOR in primary cultured osteoclasts were inhibited under Dex induced autophagy. Using the selective PTEN inhibitor SF1670 to activate the PI3K/Akt/mTOR pathway reversed this osteoclast autophagy under Dex treatment. Our study suggests that osteoclast autophagy was enhanced in glucocorticoids induced bone loss, and the PI3K/Akt/mTOR signaling pathway mediated the increased autophagy in primary cultured osteoclasts under glucocorticoids treatment.


Subject(s)
Autophagy , Glucocorticoids/adverse effects , Osteoclasts/cytology , Signal Transduction , Animals , Cells, Cultured , Mice , Phosphatidylinositol 3-Kinases/metabolism , Proto-Oncogene Proteins c-akt/metabolism , TOR Serine-Threonine Kinases/metabolism
15.
Orthop Surg ; 8(1): 68-74, 2016 Feb.
Article in English | MEDLINE | ID: mdl-27028383

ABSTRACT

OBJECTIVE: To compare the biomechanical properties of a novel annular incision technique, an oblique incision made approximately 60° to the spinal column, with the traditional transverse and longitudinal annular slit incision in an ex vivo sheep lumbar spine model. METHODS: Sixteen sheep lumbar spines were used for the current ex vivo biomechanical comparative study. Functional spine unit (FSU) specimens composed of two vertebrae and one disc in the middle was cut from the whole lumbar spine. Annular slit incisions of 5 mm were made in different directions with a 15-blade knife at the intervertebral disc, following which partial discectomy was performed to produce the following groups: control with no incision, transverse slit, longitudinal slit and oblique slit groups. The specimens were then subjected to flexion-extension, lateral bending, axial rotation and compression tests. RESULTS: As expected, the control group showed the least range of motion (ROM) in the flexion-extension test. The oblique slit group showed a trend toward a smaller ROM than the transverse and longitudinal groups in 1, 2, 3 and 5 Nm flexion-extension tests; these differences were not statistically significant (P > 0.05). In addition, the transverse (5.80° ± 0.20°), longitudinal (5.77° ± 0.67°) and oblique (5.47° ± 0.43°) slit groups showed a significantly larger ROM than the control group (3.22° ± 0.28°) in 2 Nm lateral bending tests (P < 0.05). Compared with the transverse and longitudinal groups, the oblique group also showed a trend toward a smaller ROM in lateral bending tests (P > 0.05). Following increments in the axial torsion force, the ROM was greater in all four experimental groups than the ROM with 1 Nm axial torsion. Furthermore, a significantly smaller axial rotational ROM was found in the oblique than the transverse group for 1 and 5 Nm force (P < 0.05). With increase in the axial force to 5 Nm, the ROM in the oblique slit group (4.71° ± 0.52°) was significantly smaller than that in the transverse group (7.25° ± 0.46°, P < 0.05), but not significantly different from that of the longitudinal slit group (5.84° ± 0.23°, P > 0.05). Comparable ultimate loads to failure were found in the oblique, transverse and longitudinal groups; the highest ultimate load to failure being in the control group (P > 0.05). CONCLUSION: The novel oblique slit annular incision to the intervertebral disc showed a trend toward better biomechanical properties than the traditional transverse and longitudinal slit incisions.


Subject(s)
Diskectomy/methods , Intervertebral Disc/physiology , Intervertebral Disc/surgery , Lumbar Vertebrae/physiology , Lumbar Vertebrae/surgery , Animals , Biomechanical Phenomena , Random Allocation , Range of Motion, Articular , Sheep
16.
Clin Spine Surg ; 29(8): 352-7, 2016 10.
Article in English | MEDLINE | ID: mdl-25099974

ABSTRACT

STUDY DESIGN: Retrospective cohort study. OBJECTIVE: To determine whether an association exists between high body mass index (BMI>25 kg/m) and surgical outcomes in revision adult scoliosis patients. SUMMARY OF BACKGROUND DATA: Obesity is thought to be associated with increased surgical complications and inferior clinical outcomes in adults. There are no studies analyzing the effect of obesity on surgical outcomes in revision patients for adult scoliosis. METHODS: Forty-five consecutive revision adult scoliosis patients (35 women and 10 men; mean age, 62.7±9.3 y) with a minimum follow-up of 2 years were included in this study. Patients were divided into 2 groups according to BMI: overweight (BMI≥25 kg/m, n=27) and nonoverweight (<25 kg/m, n=18). Radiographic measures, Oswestry Disability Index (ODI), Visual Analog Scale (VAS), as well as comorbidities and complications were reviewed and compared at preoperative and 2-year follow-up. RESULTS: No significant differences in surgical methods, complication rates, or radiographic measures were found between the 2 groups except for the greater preoperative and final follow-up thoracic kyphosis in the overweight group (P<0.05). A higher comorbidity rate of circulatory disorders (33.3% vs. 0%, P=0.018) and diabetes (25.9% vs. 0%, P=0.053) was observed in the overweight group, as well as a higher preoperative VAS score (7.1±1.7 vs. 5.2±2.9, P=0.031). At 2-year follow-up, VAS and ODI improvements for both groups showed significant and similar improvement from preoperative (P<0.01). CONCLUSIONS: Overweight revision adult scoliosis patients had higher thoracic kyphosis and more significant preoperative pain compared with normal-weight individuals. Overweight patients also had significantly higher rates of medical comorbidities. However, BMI did not affect the functional outcome of surgical correction or perioperative complication rates. Overweight patients benefited from surgery just as much as nonoverweight patients at 2-year follow-up.


Subject(s)
Body Mass Index , Pain/etiology , Reoperation/methods , Scoliosis/surgery , Spinal Fusion/adverse effects , Treatment Outcome , Aged , Cohort Studies , Female , Humans , Male , Middle Aged , Obesity/complications , Obesity/surgery , Postoperative Complications , Scoliosis/complications , Severity of Illness Index
17.
Exp Ther Med ; 9(5): 1967-1973, 2015 May.
Article in English | MEDLINE | ID: mdl-26136924

ABSTRACT

Large animal models of osteoporosis are essential for osteoporosis research. However, the time required to establish an accurate osteoporosis model is unknown. Therefore, the aim of the present study was to establish a large animal model of osteoporosis in goats. In total, 14 Chinese goats were divided into an ovariectomized (OVX, n=7) or sham-operated (SHAM, n=7) group. Vertebral bodies were used to measure the bone mineral density (BMD) prior to the ovariectomy and at 24 months after the ovariectomy. In addition, the BMD of the femoral neck, femoral diaphysis and tibial diaphysis were measured 24 months postoperatively. Bone samples from the vertebral body, femoral head and femoral neck were scanned by micro-computed tomography (CT) to visualize the trabecular and cortical microstructure. Furthermore, the vertebral body, femoral head, femoral neck and tibial diaphysis were analyzed for mechanical strength. The BMD of vertebral body of the OVX group decreased significantly (P<0.01) at 24 months after the ovariectomy when compared with the baseline measurements. Micro-CT scans of the vertebral body revealed that the bone volume fraction, trabecular number, trabecular thickness and the degree of anisotropy decreased by 37.1, 36.7, 10.5 and 16.5%, respectively (P<0.01) in the OVX group when compared with the SHAM group. Additionally, the specific bone surface and trabecular spacing significantly increased by 37.7 and 62%, respectively in the OVX group (P<0.001). Cortical bone porosity in the vertebral body and femoral neck was greater in the OVX group when compared with the SHAM group (P<0.05). In addition, mechanical testing revealed a statistically significant difference between the vertebral bodies of the OVX group and the SHAM group. In conclusion, the present study demonstrated that an ovariectomy was able to induce significant osteoporosis and deterioration of mechanical properties in the bones of goats.

18.
Int Orthop ; 39(6): 1129-36, 2015 Jun.
Article in English | MEDLINE | ID: mdl-25432324

ABSTRACT

PURPOSE: A variety of bone substitutes have been successfully used to fill PEEK cages in cervical interbody fusion in order to avoid the complications related to bone harvesting from the donor site. However, no controlled study has previously been conducted to compare the effectiveness of PEEK interbody cages containing calcium sulphate/ demineralized bone matrix (CS/DBM) with autogenous cancellous bone for the treatment of cervical spondylosis. The objective of this prospective, randomized clinical study was to evaluate the effectiveness of implanting PEEK cages containing CS/DBM for the treatment of cervical radiculopathy and/or myelopathy. METHODS: Sixty-eight patients with cervical radiculopathy and/or myelopathy were randomly assigned to receive one- or two-level discectomy and fusion with PEEK interbody cages containing CS/DBM or autogenous iliac cancellous bone (AIB). The patients were followed up for two years postoperatively. The radiological and clinical outcomes were assessed during a two-year follow-up. RESULTS: The mean blood loss was 75 ± 18.5 ml in the CS/DBM group and 100 ± 19.6 ml (P < 0.01) in the AIB group. The fusion rate was 94.3 % in the CS/DBM group and 100 % in the AIB group at 12-month follow-up. The fusion rate was 100 % at final follow-up in both groups. No significant difference (P > 0.05) was found regarding improvement of JOA score and segmental lordosis as well as neck and arm pain at all time intervals between the two groups. The total complication rate was significantly higher (P < 0.05) in the AIB group than in the CS/DBM group, but there was no significant difference between the two groups (P > 0.05) when comparing the complications in the neck. CONCLUSIONS: In conclusion, the PEEK interbody fusion cage containing CS/DBM or AIB following one- or two-level discectomy had a similar outcome for cervical spondylotic radiculopathy and/or myelopathy. The rate of fusion and the recovery rate of JOA score between the two groups were the same. The filling of CS/DBM in the PEEK cage instead of AIB has the advantage of less operative blood loss and fewer complications at the donor site.


Subject(s)
Bone Substitutes/therapeutic use , Calcium Sulfate/therapeutic use , Cervical Vertebrae , Spinal Fusion , Spondylosis/surgery , Adult , Aged , Autografts , Bone Demineralization Technique , Cervical Vertebrae/surgery , Diskectomy , Female , Humans , Male , Middle Aged , Prospective Studies , Radiculopathy/surgery , Transplantation, Autologous , Treatment Outcome
19.
Spine (Phila Pa 1976) ; 39(24): 2049-55, 2014 Nov 15.
Article in English | MEDLINE | ID: mdl-25202938

ABSTRACT

STUDY DESIGN: Retrospective cohort analysis of prospectively collected data. OBJECTIVE: To determine whether an association exists between body mass and surgical outcomes in patients with degenerative scoliosis after long instrumented spinal arthrodesis (≥ 4 discs). SUMMARY OF BACKGROUND DATA: Obesity is thought to be associated with increased surgical complications and inferior clinical outcomes in adults. There are no studies analyzing the effect of obesity on surgical outcomes in patients with degenerative scoliosis after long instrumented spinal arthrodesis. METHODS: Eighty-four consecutive patients with degenerative scoliosis (69 females and 15 males; mean age, 68.6 ± 8.0 yr) with a minimum follow-up of 2 years were included in this study. Patients were divided into 3 groups according to body mass index (BMI): obese (BMI ≥ 30 kg/m², n = 19), overweight (BMI = 25-29.9 kg/m², n = 35), and normal weight (BMI < 25 kg/m², n = 30). Radiographical measures, Oswestry Disability Index, visual analogue scale score, as well as comorbidities and complications were reviewed and analyzed for all patients preoperatively and at 1- and 2-year follow-ups. RESULTS: Compared with the normal weight group, no significant differences in surgical methods, comorbidities, complication rates, curve correction, or radiographical measures were found in the obese and overweight groups, except for a greater preoperative lumbar lordosis in the overweight group (-40.3° ± 13.8° vs. -26.0° ± 18.9°, P < 0.05). At 2-year follow-up, Oswestry Disability Index and visual analogue scalescores improved significantly in all groups compared with preoperatively (P < 0.01). The changes of Oswestry Disability Index and visual analogue scalescores from preoperatively to final follow-up were similar in the 3 groups (P > 0.05). CONCLUSION: Obesity did not affect the amount of deformity correction and did not increase comorbidities and postoperative complication rates. Overweight patients had a greater lumbar lordosis before surgery than normal weight patients. Obese and overweight patients benefited from surgery just as much as normal weight patients at 2-year follow-up.


Subject(s)
Body Mass Index , Lumbar Vertebrae/surgery , Obesity/complications , Scoliosis/surgery , Spinal Fusion , Aged , Female , Follow-Up Studies , Humans , Ideal Body Weight , Lordosis/complications , Male , Middle Aged , Radiography , Retrospective Studies , Scoliosis/complications , Scoliosis/diagnostic imaging , Severity of Illness Index , Spinal Fusion/adverse effects , Treatment Outcome
20.
Spine (Phila Pa 1976) ; 39(10): 805-11, 2014 May 01.
Article in English | MEDLINE | ID: mdl-24583728

ABSTRACT

STUDY DESIGN: Retrospective cohort analysis of prospectively collected data. OBJECTIVE: To compare clinical outcomes and postoperative complications in patients with lumbar degenerative scoliosis who underwent primary (P) versus revision (R) surgery. SUMMARY OF BACKGROUND DATA: Revision surgery for spinal deformity is technically challenging and may be associated with greater risks of complications and inferior clinical outcomes. There is a paucity of data in the literature comparing primary versus revision surgery in patients with degenerative scoliosis with respect to their clinical outcomes and complications. METHODS: An analysis of 84 consecutive patients with degenerative scoliosis who underwent primary versus revision surgery between 2002 and 2010 with a minimum 2-year follow-up was performed. RESULTS: There were 53 patients in the primary group and 31 in the revision group. The average number of previously operated levels in the revision group was 3.5 ± 2.6. Mean age at surgery, sex, and body mass index were similar between the 2 groups, as well as comorbidities and postoperative complication rates (P > 0.05). Although a greater preoperative coronal imbalance was noticed in the revision group (P: 2.5 cm vs. R: 4.8 cm, P = 0.022), the final radiographical measures were comparable between the 2 groups. At 2-year follow-up, Oswestry Disability Index and visual analogue scale scores improved significantly in both groups compared with preoperatively (P < 0.001). The improvement in scores of Oswestry Disability Index and visual analogue scale preoperatively to final follow-up was similar between the 2 groups (P > 0.05). CONCLUSION: Revision patients achieved the same radiographical and clinical outcomes as primary patients. The complication rates were similar between primary and revision patients. Revision patients benefit from surgery just as much as primary patients at 2-year follow-up.


Subject(s)
Lumbar Vertebrae/surgery , Postoperative Complications/etiology , Scoliosis/surgery , Spinal Fusion/adverse effects , Aged , Female , Humans , Male , Middle Aged , Reoperation , Retrospective Studies , Spinal Fusion/methods , Treatment Outcome
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