Oncogenic functions of the EMT-related transcription factor ZEB1 in breast cancer.

Zinc finger E-box binding homeobox 1 (ZEB1, also termed TCF8 and δEF1) is a crucial member of the zinc finger-homeodomain transcription factor family, originally identified as a binding protein of the lens-specific δ1-crystalline enhancer and is a pivotal transcription factor in the epithelial-mesenchymal transition (EMT) process. ZEB1 also plays a vital role in embryonic development and cancer progression, including breast cancer progression. Increasing evidence suggests that ZEB1 stimulates tumor cells with mesenchymal traits and promotes multidrug resistance, proliferation, and metastasis, indicating the importance of ZEB1-induced EMT in cancer development. ZEB1 expression is regulated by multiple signaling pathways and components, including TGF-ß, ß-catenin, miRNA and other factors. Here, we summarize the recent discoveries of the functions and mechanisms of ZEB1 to understand the role of ZEB1 in EMT regulation in breast cancer.

Contributions of fat mass and fat distribution to hip bone strength in healthy postmenopausal Chinese women.

The fat and bone connection is complicated, and the effect of adipose tissue on hip bone strength remains unclear. The aim of this study was to clarify the relative contribution of body fat accumulation and fat distribution to the determination of proximal femur strength in healthy postmenopausal Chinese women. This cross-sectional study enrolled 528 healthy postmenopausal women without medication history or known diseases. Total lean mass (LM), appendicular LM (ALM), percentage of lean mass (PLM), total fat mass (FM), appendicular FM (AFM), percentage of body fat (PBF), android and gynoid fat amount, android-to-gynoid fat ratio (AOI), bone mineral density (BMD), and proximal femur geometry were measured by dual energy X-ray absorptiometry. Hip structure analysis was used to compute some variables as geometric strength-related parameters by analyzing the images of the hip generated from DXA scans. Correlation analyses among anthropometrics, variables of body composition and bone mass, and geometric indices of hip bone strength were performed with stepwise linear regression analyses as well as Pearson's correlation analysis. In univariate analysis, there were significantly inverse correlations between age, years since menopause (YSM), hip BMD, and hip geometric parameters. Bone data were positively related to height, body weight, LM, ALM, FM, AFM, and PBF but negatively related to AOI and amount of android fat (all P < 0.05). AFM and AOI were significantly related to most anthropometric parameters. AFM was positively associated with height, body weight, and BMI. AFM was negatively associated with age and YSM. AOI was negatively associated with height, body weight, and BMI. AOI positively associated with age and YSM. LM, ALM, and FM had a positive relationship with anthropometric parameters (P < 0.05 for all). PLM had a negative relationship with those parameters. The correlation between LM, ALM, FM, PLM, ALM, age, and YSM was not significant. In multivariate linear regression analysis, the hip bone strength was observed to have a consistent and unchanged positive association with AFM and a negative association with AOI, whereas its association with other variables of body composition was not significant after adjusting for age, years since menopause, height, body weight, and BMI. AFM may be a positively protective effect for hip bone strength while AOI, rather than android fat, shows a strong negative association with hip bone strength after making an adjustment for confounders (age, YSM, height, body weight, and BMI) in healthy postmenopausal Chinese women. Rational weight control and AOI reduction during menopause may have vital clinical significance in decreasing postmenopausal osteoporosis.

Prediction of hip osteoporotic fractures from composite indices of femoral neck strength.

OBJECTIVE: To clarify whether composite hip strength indices improve predictive ability for hip osteoporotic fractures independent of conventional bone mineral density (BMD). SUBJECTS AND METHODS: Three hundred and eighty-two health controls and 43 women with hip fractures (aged 28.2-87.7 years, mean age 59.5 ± 9.2 years) were measured by dual energy X-ray absorptiometry for femoral neck bone mineral density (FN_BMD) and proximal femur geometry parameters of hip, and composite hip strength indices (Compression strength index, Bending strength index, and Impact strength index). The association between the studied parameters and the fractures was modelled using multiple logistic regression, including age, height, weight, and menopausal status. Fracture-predicted probability was calculated for each predictor tested. ROC curve areas (AUCs) were calculated for the fracture status, having the calculated fracture-predicted probability as a test variable. AUCs were compared by the Hanley-McNeil test. RESULTS: Women with hip fractures had lower FN_BMD, composite hip strength indices, and longer hip axis length than controls, and no significant difference in femoral neck width. Logistic regression showed composite hip strength indices could predict hip fractures risk. To the same extent as FN BMD, Compression Strength Index (CSI) best predicted the risk for each fracture (AUC = 0.787 ± 0.028). When CSI was added to FN_BMD, there was a small but not statistically significant increase in AUC to 0.796 ± 0.027 (P = 0.9018). CONCLUSION: Composite indices of femoral neck strength may be valuable in the assessment of the biomechanics of bone fragility; however, they do not appear to add diagnostic value to the simple measurement of BMD.

The temporal characterization of marrow lipids and adipocytes in a rabbit model of glucocorticoid-induced osteoporosis.

OBJECTIVE: To characterize the temporal changes in marrow lipids content and adipocytes in the development of glucocorticoid-induced osteoporosis (GIOP) in rabbits using MR spectroscopy. SUBJECTS AND METHODS: Twenty 20-week-old female rabbits were randomized to a control group and a GIOP group equally. Marrow lipids fraction and bone mineral density at the left proximal femur and L3-L4 vertebrae were measured by MR spectroscopy and dual-energy X-ray absorptiometry at week 0, 4, 8, and 12. Marrow adipocytes were quantitatively evaluated by histopathology. RESULTS: Marrow adiposity in the GIOP group showed a significant increase over time, with a variation of marrow lipids fraction (+35.9 %) at week 4 from baseline and it was maintained until week 12 (+75.2 %, p < 0.001 for all). The GIOP group demonstrated continuous deterioration of bone with significant difference between the two groups at week 8, followed by increased marrow fat with significant difference at week 4 (p < 0.05 for all). In comparison with the controls, marrow adipocyte density in the GIOP group increased by 57.1 % at week 8 and 35.4 % at week 12, respectively. A reduction (-13.3 %) in adipocyte mean diameter at week 8 (but an increase (+22.7 %) at week 12) were observed in the GIOP group compared with the control group (p < 0.05 for all). There was significant difference between two periods (p = 0.023) in adipocyte mean diameter in the GIOP group. The percentage area of marrow adipocytes in the GIOP group was 62.8 ± 8.7 % at week 8 and 79.2 ± 7.7 % at week 12, both of which were significantly higher than those of the controls (p < 0.05 for all). CONCLUSIONS: Marrow adipogenesis is synchronized with bone loss in the development of GIOP, which was characterized by a significant increase in the number of small-sized marrow adipocytes in the relatively early stage and concomitant volume increase later on. MR spectroscopy appears to be the most powerful tool for detecting the sequential changes in marrow lipid content.

MR spectroscopy and micro-CT in evaluation of osteoporosis model in rabbits: comparison with histopathology.

PURPOSE: To explore the evidence of regular alteration of bone quality in osteoporosis dynamically examined by MRS and micro-CT, comparing with histopathology. METHODS: Forty rabbits were allocated into two groups. Group A were used as sham. Group B underwent bilateral ovariectomy (OVX) combined with daily intramuscular methylprednisolone, underwent MR spectroscopy, micro-CT, and histopathology of L5 at 2, 4, 8, and 10 weeks after operation. RESULTS: Fat fraction as shown by MRS in Group B was significantly increased over the time course of osteoporosis development with significant difference between two groups at 4, 8, and 10 weeks after OVX. Continuous deterioration of cancellous bone architecture in Group B, was first detected at week 4. FF value in group B correlated with micro-CT parameters. Marrow fat as measured by MR and CT was positively correlated with both the mean density and diameter of adipocytes (both of which increased over time). CONCLUSIONS: Marrow adipogenesis occurs in synchrony with deterioration of trabecular microarchitecture.MRS may be valuable to assess the pathophysiological changes of bone marrow in osteoporosis in early stage. KEY POINTS: MRS revealed gradually increasing bone marrow fat in rabbits rendered osteoporotic. Marrow adipogenesis occurs in synchrony with deterioration of trabecular microarchitecture. Pathology revealed an early increase in number of marrow adipocytes in osteoporosis. MRS may help assess early pathophysiological bone marrow changes in osteoporosis.

Effects of Total Flavonoids of Epimedium on Bone Marrow Adipose Tissue in Ovariectomized Rats.

Bone marrow adipose tissue has brown fat characteristics. Several studies have demonstrated that total flavonoids of Epimedium (TFE) could prevent bone loss and reduce the white adiposity in bone marrow induced by ovariectomy (OVX) in rats. However, the effects of TFE on marrow brown fat in OVX rats remain unclear. In this word, we addressed this question expected to provide a new target for preventing and treating osteoporosis. Thirty-six 3-month-old female Sprague-Dawley rats were equally divided into Sham controls, OVX controls, and OVX treated with TFE. Chemical shift coding magnetic resonance was performed to detect marrow fat fraction at the left femur at baseline, 6 and 12 weeks post-OVX. Bone mineral density at the lumbar spine and femur was measured by dual-energy x-ray absorptiometry. Serum bone biomarkers by ELISA, trabecular bone microarchitecture at the proximal tibia by micro-CT, quantitative parameters of marrow adipocyte by hematoxylin, and eosin staining were evaluated. The marrow adipocyte gene and protein expressions profile were determined by real-time quantitative PCR and immunostaining in whole tibiae. We found that TFE treatment could decrease bone turnover rate and improved bone mineral density and trabecular microarchitecture in OVX rats. OVX resulted in marrow adipogenesis as evidenced by increased marrow fat fraction, larger marrow adipocyte size, increased adipocyte number and percentage of adipocyte area, marrow white adipocyte gene, and protein expression, including PPARγ2 and FABP4. These pathological changes induced by estrogen deficiency were restored by TFE treatment. TFE also increased brown adipocyte expressions of the transcription factor Ucp1 and Prdm16 in whole tibiae. There was no detectible protein expression of brown adipocyte markers in the proximal tibia. Taken together, TFE regulation of bone marrow adiposity in OVX rats is mediated, at least in part, via maintaining the reciprocity of white and brown adipose tissue.

Impact of Acupuncture on Sleep and Comorbid Symptoms for Chronic Insomnia: A Randomized Clinical Trial.

STUDY OBJECTIVES: To evaluate the efficacy and safety of acupuncture at HT 7 (Shenmen) and KI 7 (Fuliu) on sleep and comorbid symptoms for chronic insomnia. METHODS AND DESIGN: A randomized, single-blind, parallel and sham-controlled trial consisted of an acupuncture group (n = 41) and a sham acupuncture group (n = 41). Setting: a tertiary hospital of integrated Chinese and Western medicine. Participants: 82 subjects with chronic insomnia based on the International Classification of Sleep Disorders, Third Edition (ICSD-3). Interventions: a 10-session acupuncture treatment at bilateral HT 7 and KI 7 or sham acupoints with shallow needling was performed over 3 weeks. Measurements: the Pittsburgh sleep quality index (PSQI) and insomnia severity index (ISI) were evaluated at baseline, posttreatment, and at two follow-ups as the primary outcome measures. Polysomnography (PSG) on two consecutive nights, the Beck anxiety inventory (BAI), the Beck depression inventory (BDI) fatigue severity scale (FSS) and the Epworth sleepiness scale (ESS) were evaluated at baseline and posttreatment as the secondary outcome measures. RESULTS: After the treatments, PSQI scores decreased by 5.04 in the acupuncture group and 2.92 in the sham acupuncture group. ISI scores decreased by 7.65 in the acupuncture group and 5.05 in the sham acupuncture group. The between-group differences in the primary outcome measures posttreatment were statistically significant. However, no differences were found between the two groups during the two follow-ups. Regarding the PSG data, there were significantly lower levels of sleep onset latency (SOL), a lower percentage of sleep stage N1 and a higher percentage of sleep stage N3 in the acupuncture group than in the sham acupuncture group. After treatment, there were lower levels of comorbid symptoms (BAI, BDI, FSS and ESS) in both groups. However, no significant differences were observed between the groups. CONCLUSION: Acupuncture at HT 7 and KI 7 is an effective and safe nonpharmacologic intervention option for chronic insomnia. CLINICAL TRIAL REGISTRATION: The study was registered at the Chinese Clinical Trial Registry, registration ID: ChiCTR1900023787, China.

Rapid remission of refractory synovitis, acne, pustulosis, hyperostosis, and osteitis syndrome in response to the Janus kinase inhibitor tofacitinib: A case report.

BACKGROUND: Synovitis, acne, pustulosis, hyperostosis, and osteitis (SAPHO) syndrome is a rare autoinflammatory disease for which clinical treatment has not been standardized. Janus kinase (JAK) inhibitors represent a novel therapeutic option for rheumatoid arthritis, psoriatic arthritis, and some other autoinflammatory diseases. However, the clinical utility of JAK inhibitors in treating SAPHO syndrome has not been thoroughly investigated. In this study, we describe a patient with SAPHO syndrome who failed to respond to conventional treatment but demonstrated a remarkable and rapid response to the JAK inhibitor tofacitinib. CASE SUMMARY: A 62-year-old female patient presented with swelling and pain at the sternoclavicular joints, back pain that limited her activities, arthralgia in the right knee, and cutaneous lesions. Her symptoms were unresponsive to nonsteroidal anti-inflammatory drugs, disease-modifying antirheumatic drugs, Tripterygium wilfordii hook f, and bisphosphonates. SAPHO syndrome was diagnosed in accordance with dermatological and osteoarticular manifestations and abnormal inflammatory factors. Multiple image studies have illustrated bone lesions and pathological fractures of vertebral bodies. Oral treatment with tofacitinib at 5 mg twice daily with methotrexate and bisphosphonates was initiated. The patient reported that her pain symptoms were relieved after 3 d and her cutaneous lesions were reduced after 4 wk of treatment. Vertebral lesions were improved after 6 mo on tofacitinib. No serious adverse effects were noted. CONCLUSION: JAK inhibitor therapy may be a promising strategy to treat SAPHO syndrome.

Analysis of the Differentially Expressed Genes Induced by Cisplatin Resistance in Oral Squamous Cell Carcinomas and Their Interaction.

BACKGROUND: Oral squamous cell carcinoma (OSCC) is a solid tumor, which originates from squamous epithelium, with about 400,000 new-cases/year worldwidely. Presently, chemoradiotherapy is the most important adjuvant treatment for OSCC, mostly in advanced tumors. However, clinical resistance to chemotherapy still leads to poor prognosis of OSCC patients. Via high-throughput analysis of gene expression database of OSCC, we investigated the molecular mechanisms underlying cisplatin resistance in OSCC, analyzing the differentially expressed genes (DEGs) and their regulatory relationship, to clarify the molecular basis of OSCC chemotherapy resistance and provide a theoretical foundation for the treatment of patients with OSCC and individualized therapeutic targets accurately. METHODS: Datasets related to "OSCC" and "cisplatin resistance" (GSE111585 and GSE115119) were downloaded from the GEO database and analyzed by GEO2R. Venn diagram was used to obtain drug-resistance-related DEGs. Functional enrichment analysis and Kyoto encyclopedia of genes and genomes (KEGG) pathway analysis were performed on DEGs using The Database for Annotation, Visualization and Integrated Discovery (DAVID) software. Protein-protein interaction (PPI) network was constructed by STRING (search tool for recurring instances of neighbouring genes) database. Potential target genes of miRNA were predicted via miRDB, and cBioportal was used to analyze the function and survival of the potential functional genes. RESULTS: Forty-eight upregulated DEGs and 49 downregulated DEGs were obtained from the datasets, with cutoff as p < 0.01 and |log FC| > 1. The DEGs in OSCC mainly enriched in cell proliferation regulation, and chemokine activity. In PPI network with hub score > 300, the hub genes were identified as NOTCH1, JUN, CTNNB1, CEBPA, and ETS1. Among miRNA-mRNA targeting regulatory network, hsa-mir-200c-3p, hsa-mir-200b-3p, hsa-mir-429, and hsa-mir-139-5p were found to simultaneously regulate multiple hub genes. Survival analysis showed that patients with high CTNNB1 or low CEBPA expression had poor outcome. CONCLUSIONS: In the OSCC cisplatin-resistant cell lines, NOTCH1, JUN, CTNNB1, CEBPA, and ETS1 were found as the hub genes involved in regulating the cisplatin resistance of OSCC. Members of the miR-200 family may reverse drug resistance of OSCC cells by regulating the hub genes, which can act as potential targets for the treatment of OSCC patients with cisplatin resistance.

The transcriptional STAT3 is a potential target, whereas transcriptional STAT5A/5B/6 are new biomarkers for prognosis in human breast carcinoma.

Signal Transducer and Activators of Transcription (STAT) is a set of transcription factors, involved in diverse cellular functions. Evidences from cell lines, mouse models and human tissues implicate these transcription factors in the oncogenesis of breast cancer. However, the diverse expression patterns and prognostic values of 7 STATs remain to be elucidated. In the current study, we mined the transcriptional and survival data of STATs in patients with breast carcinoma (BC) through ONCOMINE, bc-GenExMiner, Kaplan-Meier Plotter and cBioPortal. It was found that STAT1/2 were up-regulated, whereas STAT3/4/5A/5B were down-regulated in BC patients compared with the normal tissues. The expressions of STAT5A/5B/6 were correlated with decreased levels of histological differentiation. In survival analyses through the Kaplan-Meier plotter database, high transcription levels of STAT2/4/5A/5B/6 were associated with better relapse-free survival (RFS) in all BC patients. Conversely, high STAT3 predicted shorter RFS in BC patients, suggesting that STAT3 is potential targets for precision therapy to BC patients. These data also provided STAT5A/5B/6 as new biomarker for BC prognosis.

Mining distinct aldehyde dehydrogenase 1 (ALDH1) isoenzymes in gastric cancer.

Aldehyde dehydrogenase 1 (ALDH1) consists of a family of intracellular enzymes, highly expressed in stem cells populations of leukemia and some solid tumors. Up to now, 6 isoforms of ALDH1 have been reported. However, the expression patterns and the identity of ALDH1 isoenzymes contributing to ALDH1 activity, as well as the prognostic values of ALDH1 isoenzymes in cancers all remain to be elucidated. Here, we studied the expressions of ALDH1 transcripts in gastric cancer (GC) compared with the normal controls using the ONCOMINE database. Through the Kaplan-Meier plotter database, which contains updated gene expression data and survival information of 876 GC patients, we also investigated the prognostic values of ALDH1 isoenzymes in GC patients. It was found that when compared with normal tissues, ALDH1A1 mRNA expression was downregulated, whereas ALDH1A3 and ALDH1B1 were upregulated in GC patients. In survival analyses, high ALDH1A1 and ALDH1B1 expressions were associated with better overall survival (OS) in all GC patients. In addition, high transcription activity of ALDH1A1 predicted better OS in gastric intestinal type adenocarcinoma, but not in diffuse gastric adenocarcinoma. GC patients with high mRNA level of ALDH1B1 showed better OS in gastric intestinal type, and worse OS in diffuse type. Oppositely, high transcription activities of ALDH1A2, ALDH1A3 and ALDH1L1 predicted worsen overall survival in GC patients, suggesting that these isoenzymes might be responsible mainly for the ALDH1 activities in GC. These data provides ALDH1A2, ALDH1A3 and ALDH1L1 as excellent potential targets for individualized treatment of GC patients.

Panax notoginseng saponins mitigate ovariectomy-induced bone loss and inhibit marrow adiposity in rats.

OBJECTIVE: Previous data have suggested that Panax notoginseng saponins (PNS) can prevent estrogen deficiency-induced bone loss by dual action: stimulation of new bone formation and inhibition of bone resorption. Marrow adipogenesis has been identified as a negative indicator of skeletal strength and integrity. This study assessed the effects of early PNS supplementation on bone microarchitecture preservation and marrow fat content in an ovariectomized rat model. METHODS: Forty adult female Sprague-Dawley rats were randomly assigned to four equal groups for 12 weeks of treatment: (1) sham operation (SHAM) + vehicle; (2) ovariectomy (OVX) + vehicle; (3) OVX + 17ß-estradiol (25 µg/kg); (4) OVX + PNS (300 mg/kg/d, PO). Marrow fat content of the femur was determined, using fat/water magnetic resonance imaging (MRI), at baseline and 6 and 12 weeks after operation. At the end of the experiment, bone turnover, trabecular microarchitecture, and marrow adipocytes were assessed by serum biomarkers, micro-computed tomography (micro-CT), and histopathology, respectively. The effects of PNS on adipocytic differentiation were reflected by expression levels of the adipogenic genes PPARγ2 and C/EBPα, as determined by reverse transcription-polymerase chain reaction. RESULTS: Ovariectomized rats experienced remarkable increases in marrow fat content across time points, which were accompanied by elevated rate of bone turnover, global volumetric bone density, and trabecular microarchitecture deterioration. These OVX-induced pathological changes are reversible in that most of them could be mostly corrected upon 17ß-estradiol treatment. PNS treatment significantly reduced marrow adipogenesis (adipocyte density, -27.2%; size, -22.7%; adipocyte volume-to-tissue volume ratio, -53.3%; all P < 0.01) and adipocyte marker gene expression, and prevented bone mass loss and microarchitecture deterioration. Moreover, PNS enhanced osteoblast activity but suppressed osteoclast turnover, as evidenced by decreased levels of serum C-terminal telopeptides of type I collagen and elevated levels of alkaline phosphatase. CONCLUSIONS: PNS mitigates estrogen deficiency-induced deterioration of trabecular microarchitecture and suppresses marrow adipogenesis.

Icariin prevents ovariectomy-induced bone loss and lowers marrow adipogenesis.

OBJECTIVE: Icariin prevents bone loss by stimulating new bone formation and by inhibiting bone resorption. However, less is known about how icariin affects marrow adiposity. This lack of information is a vital problem, as the degree of marrow adipogenesis may be an alternative indicator of the severity of osteoporosis in relation to the degree of osteogenesis and osteoblastogenesis. To explore this question, we tested the effects of icariin on bone mineral density (BMD) and marrow fat content in a rat model of postmenopausal osteoporosis. METHODS: Thirty-six 3-month-old female Sprague-Dawley rats were randomly assigned to one of the following treatment groups: sham operation, ovariectomized controls, and ovariectomized rats treated orally with either 17ß-estradiol or icariin for 12 weeks. BMD and marrow fat fraction were dynamically measured on weeks 0, 6, and 12. After 12 weeks of treatment, serum 17ß-estradiol and bone biomarker levels were measured, and marrow adipocytes were quantitatively evaluated by histopathology. RESULTS: Ovariectomized controls experienced a marked increase in fat fraction over time, with increases of 40% between weeks 0 and 6 and 69.4% between weeks 6 and 12 (P < 0.001). Marrow adiposity in ovariectomized controls was dramatically higher than that in sham rats on week 6; however, a reduction in BMD was detected in ovariectomized rats on week 12 (P < 0.001). Ovariectomized rats had levels of serum alkaline phosphatase and serum C-terminal telopeptide of type I collagen that were 49.4% and 67.2% higher, respectively, than those of sham rats (P < 0.001). The density, size, and volume of marrow adipocytes in ovariectomized controls were 57.3%, 29.5%, and 163% higher, respectively, than those in sham rats. Early icariin treatment decreased bone biomarker levels, inhibited bone degeneration, and restored marrow fat infiltration and adipocyte parameters to the levels observed in sham rats. Overall, the osteoprotective effect of icariin was comparable with that of 17ß-estradiol; however, icariin did not produce uterine estrogenicity. CONCLUSIONS: Early icariin treatment restores marrow adiposity in the estrogen-deficient rat model.

Influence of early zoledronic acid administration on bone marrow fat in ovariectomized rats.

Although the primary target cell of bisphosphonates is the osteoclast, increasing attention is being given to other effector cells influenced by bisphosphonates, such as osteoblasts and marrow adipocytes. Early zoledronic acid (ZA) treatment to ovariectomized (OVX) rats has been found to fully preserve bone microarchitecture over time. However, little is known regarding the influence of ZA on marrow adipogenesis. The purpose of this study was to monitor the ability of early administration of ZA in restoring marrow adiposity in an estrogen-deficient rat model. Thirty female Sprague-Dawley rats were randomly divided into sham-operated (SHAM), OVX + vehicle, and OVX + ZA groups (n=10/group). Dual-energy x-ray absorptiometry and water/fat magnetic resonance imaging were performed at baseline, 6 weeks, and 12 weeks after treatment to assess bone mineral density and marrow fat fraction. Serum biochemical markers, bone remodeling, and marrow adipocyte parameters were analyzed using biochemistry, histomorphometry, and histopathology, respectively. The expression levels of osteoblast, adipocyte, and osteoclast-related genes in bone marrow were assessed using RT-PCR. The OVX rats showed marked bone loss, first detected at 12 weeks, but estrogen deficiency resulted in a remarked increase in marrow fat fraction, first detected at 6 weeks compared with the SHAM rats (all P < .001). Similarly, the OVX rats had a substantially larger percent adipocyte area (+163.0%), mean diameter (+29.5%), and higher density (+57.3%) relative to the SHAM rats. Bone histomorphometry, levels of osteoclast-related gene expression, and a serum resorption marker confirmed that ZA significantly suppressed bone resorption activities. Furthermore, ZA treatment returned adipocyte-related gene expression and marrow adipocyte parameters toward SHAM levels. These data suggest that a single dose of early ZA treatment acts to reverse marrow adipogenesis occurring during estrogen deficiency, which may contribute to its capacity to reduce bone loss.

Marrow adiposity recovery after early zoledronic acid treatment of glucocorticoid-induced bone loss in rabbits assessed by magnetic resonance spectroscopy.

BACKGROUND: Although there is an inverse relationship between bone mass and marrow adiposity, the reversal function of zoledronic acid (ZOL) on increased marrow fat has not been studied. The aim of our study is to use the 3T magnetic resonance spectroscopy (MRS) to characterize the dynamical change process of the marrow fat responding to early ZOL treatment in the rabbit model with glucocorticoid-induced bone loss. METHODS: Fifteen 20-week-old female New Zealand White rabbits were randomized to control group, methylprednisolone (MPS) group, and MPS+ZOL group equally. Bone mineral density (BMD) and marrow fat fraction (FF) at L3-L4 vertebrae and left proximal femur were measured by Dual-energy X-ray absorptiometry and MRS at week 0, 4, 8, and 12. The animals were euthanized at the end of our experiment and their left femurs were dissected out for the histopathological examination. RESULTS: The MPS group demonstrated a remarkable increase in FF but a reduction in BMD compared with the controls at week 4 and 8, respectively (P<0.05 for all). Early treatment of ZOL can inhibit bone degeneration, although the bone mass would not recover to its original level. FF in MPS group exhibited a dramatic increase over time, with an increased FF variation (+31.6%, P=0.009) at week 4 from baseline and it was maintained until week 12 (+75.2%, P<0.001). In MPS+ZOL group, the FF returned to baseline value after the ZOL treatment. Comparing with the controls, larger marrow adipocyte density, the mean of the adipocyte diameter, and the percentage area of the adipocyte were observed in the MPS group (P<0.05 for all), whereas there were no significant differences in quantitative parameters of marrow adipocytes between the ZOL-treated group and the normal rabbits. CONCLUSION: An increase of the marrow adiposity is synchronized with the deterioration of the MPS-induced bone mass. A single dose of early ZOL can reverse the marrow adiposity to its original level completely.

Characterizing venous vasculatures of hepatocellular carcinoma using a multi-breath-hold two-dimensional susceptibility weighted imaging.

The aim of our study is to characterize the venous vasculatures of hepatocellular carcinoma (HCC) using a multi-breath-hold two-dimensional (2D) susceptibility weighted imaging (SWI) in comparison with conventional Magnetic Resonance Imaging (MRI) sequences. Twenty-nine patients with pathologically confirmed HCC underwent MR examination at a 3.0 T scanner. The number of venous vascularity in or around the lesion was counted and the image quality was subjectively evaluated by two experienced radiologists independently based on four image sets: 1) SWI, 2) T1-weighted sequence, 3) T2-weighted sequence, and 4) T1-weighted dynamic contrast-enhanced (DCE) sequence. Of the 29 patients, a total of 33 liver lesions were detected by both SWI and conventional MR sequences. In the evaluation of the conspicuity of venous vascularity, a mean of 10.7 tumor venous vessels per mass was detected by the SWI and 3.9 tumor vasculatures were detected by T1-weighted DCE (P<0.0001), while none was detected by T1-, T2-weighted sequences. The Pearson correlation coefficients between the lesion sizes and the number of tumor vasculatures detected by T1-weighted DCE was 0.708 (P<0.001), and 0.883 by SWI (P<0.001). Our data suggest that SWI appears to be a more sensitive tool compared to T1-weighted DCE sequence to characterize venous vasculature in liver lesions.