Publications by authors named "Bailing Chen"

43 Publications

Comparison of Percutaneous Kyphoplasty and Pedicle Screw Fixation for Treatment of Thoracolumbar Severe Osteoporotic Vertebral Compression Fracture with Kyphosis.

World Neurosurg 2021 Aug 12;152:e589-e596. Epub 2021 Jun 12.

Department of Spine Surgery, The First Affiliated Hospital, Sun Yat-sen University, Guangzhou, People's Republic of China; Guangdong Provincial Key Laboratory of Orthopedics and Traumatology, The First Affiliated Hospital, Sun Yat-sen University, Guangzhou, People's Republic of China. Electronic address:

Background: Pedicle screw fixation (PSF) has been considered the preferred surgery for the treatment of severe osteoporotic vertebral compression fracture (sOVCF), and sOVCF was traditionally regarded as a relative contraindication to minimally invasive percutaneous kyphoplasty (PKP). Debate has continued regarding the selection of the best surgical method for sOVCF. In the present study, we compared the efficacy and safety between PKP and PSF.

Methods: PKP was performed in 376 patients in group 1 and PSF in 121 patients in group 2. The visual analog scale (VAS), Oswestry disability index (ODI), local kyphotic angle, fractured vertebral body height, and complications were evaluated.

Results: In the immediate postoperative analysis, the mean VAS score for group 1 was 2.4, significantly lower than the VAS score of 4.7 for group 2. The mean ODI score was 44.4% for group 1, lower than the ODI score of 57.1% for group 2. In addition, group 1 had had a significantly better ODI score at 1 year of follow-up. The local kyphotic angle and fractured vertebral body height had recovered better in group 2. In group 1, 113 patients had experienced cement leakage, and 29 patients had undergone PKP for adjacent new vertebral fractures. In group 2, 2 patients had developed wound infections, 4 had developed pneumonia, 2 had developed urinary tract infection, 3 had experienced asymptomatic screw loosening, and 7 had undergone PKP to treat new vertebral fractures and 1 had undergone removal of internal fixation because of back pain.

Conclusions: The results of the clinical and radiological evaluations showed that PKP is comparable to PSF for the treatment of sOVCF with kyphosis, with PKP having the advantages of minimal invasion, quick postoperative pain relief, and functional recovery.
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http://dx.doi.org/10.1016/j.wneu.2021.06.030DOI Listing
August 2021

High prevalence of osteoporosis in patients undergoing spine surgery in China.

BMC Geriatr 2021 06 13;21(1):361. Epub 2021 Jun 13.

Department of Spine Surgery, The First Affiliated Hospital of Sun Yat-sen University, Guangzhou, China.

Background: With the increase in life expectancy, a large number of patients with osteoporosis (OP) are undergoing spine surgery, which may adversely affect the surgical success rate. The prevalence of OP varies in different regions, and no data are available that represent the prevalence of OP among Chinese patients over 50 years of age who are undergoing spine surgery. It was the first multicenter study to assess OP in these patients. Aiming to obtain comprehensive data, this study combined bone mineral density (BMD) measurements and visual radiography assessment (VRA) to analyze the prevalence of OP in patients aged > 50 years who underwent spine surgery.

Methods: Data from 1,856 patients aged over 50 years undergoing spine surgery who resided in northern, central, and southern China were reviewed between 2018 and 2019. Based on the perioperative BMD and X-ray data, we calculated the prevalence of OP in this special population according to sex, age, and spine degenerative disease.

Results: A total of 1,245 patients (678 females and 567 males) were included in the study. The prevalence of OP diagnosed by BMD was 52.8 % in females and 18.7 % in males. When we combined with BMD and VRA, the prevalence of OP increased from 52.8 to 65.9 % in females and from 18.7 to 40.6 % in males. Although OP was more severe in females than in males, a significant difference in the rate of vertebral fracture (VF) was not observed between females and males with a normal BMD and osteopenia (females vs. males: aged 50-59 years, P = 0.977; 60-69 years, P = 0.302; >70 years, P = 0.172). Similarly, no significant difference in the vertebral fracture rate was observed within different age groups of patients with a normal BMD and osteopenia (females: P = 0.210; males, P = 0.895). The incidence of OP in patients with degenerative scoliosis was higher than that in the remaining patients (females: 63.6 % vs. 42.4 %, P = 0.018; males: 38.9 % vs. 13.8 %, P = 0.004).

Conclusions: A high prevalence of OP was identified in patients aged > 50 years undergoing spine surgery, especially in patients whose primary diagnosis was degenerative scoliosis. BMD and VRA evaluations should be included in the clinical routine for these patients prior to surgery.
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http://dx.doi.org/10.1186/s12877-021-02313-8DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8201731PMC
June 2021

Early surgery with antibiotic medication was effective and efficient in treating pyogenic spondylodiscitis.

BMC Musculoskelet Disord 2021 Mar 18;22(1):288. Epub 2021 Mar 18.

Department of Orthopedic Surgery, the First Affiliated Hospital, Sun Yat-sen University, Guangzhou, China.

Background: Pyogenic spondylodiscitis (PSD) is challenging to the orthopedist with regards to diagnosis and treatment. The present study was designed to assess and suggest the most indicative diagnostic method and evaluate the effect of surgery comprising of debridement, instrumentation and fusion in treating PSD.

Methods: Seventy-six patients with PSD who underwent surgical intervention were retrospectively enrolled. Their medical documents, corrections of spinal alignment and improvements in neurological function were assessed. Surgical approaches were compared in lumbar surgeries regarding the improvements in lordotic angle and neurological function.

Results: Elevated c-reactive protein (CRP) and erythrocyte sedimentation rate (ESR) were found in 77.6 and 71.1% patients respectively. Infectious lesions were found at lumbar (85.5%), cervical (10.5%) and thoracic (3.9%), ascertained with contrast-enhanced MRI. For lumbar patients, surgery was performed through the anterior (26.2%), posterior (49.2%) or combined approach (24.6%), and differences in improvement of lordosis and neurological function between each approach were insignificant. The pathogen was identified in 22.4% of the patients. Postoperative antibiotic therapy was managed against the result of susceptibility test, or empirically given to patients with negative cultures. All antibiotic therapy was initiated intravenously for 4-6 weeks and orally for 6 weeks.

Conclusion: Elevated CRP and/or ESR, with focal hyper-intensity on contrast-enhanced MRI are suggestive of possible PSD. Surgical intervention comprising of debridement, short-segment instrumentation and fusion that early applied to the PSD patients followed by postoperative antibiotic therapy have demonstrated preferable outcomes, but require further study.

The Translational Potential Of This Article: This article advocates early surgery to enable prompt diagnosis and treatment of PSD, and thus guarantee favorable outcomes for patients, as is shown in our study. In addition, different surgical approaches to the lesions were compared and discussed in this manuscript, but no differences in outcome between approaches were found. This suggests that thorough debridement should be prioritized over selection of surgical approach. In summary, this article has large translational potential to be applied clinically.
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http://dx.doi.org/10.1186/s12891-021-04155-2DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7977180PMC
March 2021

Effect of Teriparatide on pain relief, and quality of life in postmenopausal females with osteoporotic vertebral compression fractures, a retrospective cohort study.

Ann Palliat Med 2021 Apr 1;10(4):4000-4007. Epub 2021 Mar 1.

Department of Spine Surgery, The First Affiliated Hospital of Sun Yat-sen University, Guangzhou, China; Guangdong Provincial Key Laboratory of Orthopedics and Traumatology, The First Affiliated Hospital of Sun Yat-sen University, Guangzhou, China.

Background: Osteoporotic vertebral compression fracture (OVCF) is a common disease in elderly population, which could cause serious back pain and has a substantial impact on patients' health-related quality of life (HRQoL). The aim of this study was to identify the effect of Teriparatide as a conservative treatment on reducing back pain, and improving quality of life for postmenopausal women with osteoporotic vertebral fractures.

Methods: In a 12-month, retrospective study, 112 postmenopausal women with OVCFs were assigned to Teriparatide group (20 µg Teriparatide, subcutaneous, once daily, n=38) or control group (500 mg calcium and 400-800 IU Vitamin D per day, oral administration, n=74) according to patients' choices between January 2016 and October 2018. Patient-reported outcomes scores including the visual analogue score (VAS), Oswestry disability index (ODI), and short form 36 questionnaire (SF-36) were assessed at baseline, the 3rd months, the 6th months and 1 year after treatment.

Results: Treatments with Teriparatide or calcium plus vitamin D supplements had significant effect on improvement of patients' back pain as well as HRQoL, with significantly reduced VAS and ODI and increased SF-36 physical component summary (PCS) and mental component summary (MCS) scores. At the endpoint, Teriparatide showed better therapeutic effect, with greater reductions in VAS and ODI and more increases in SF-36 PCS and MCS scores. However, more adverse events (AEs) were found in Teriparatide group, but symptoms were relatively mild and of short duration.

Conclusions: In postmenopausal women with OVCFs, the consequent persistent back pain and impaired HRQoL, treatment with Teriparatide was associated with more profound therapeutic effects and more AEs compared with calcium plus vitamin D supplements.
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http://dx.doi.org/10.21037/apm-20-2333DOI Listing
April 2021

Structure of Lumbar Intervertebral Foraminal Ligaments Based on 3-Dimensional Reconstruction Through Ultrathin Cryomilling of a Human Cadaver.

World Neurosurg 2021 04 19;148:e609-e616. Epub 2021 Jan 19.

Department of Spine Surgery, Zhujiang Hospital, Southern Medical University, Guangzhou, China. Electronic address:

Background: This study aimed to assess the feasibility of using the 3-dimensional (3-D) reconstruction technique based on ultrathin cryomilling to show the lumbar intervertebral foraminal ligaments in situ.

Methods: Cryomilling was performed on an embalmed human cadaver to acquire successive cross-sectional images. In each of the images, the boundaries of lumbar intervertebral foraminal ligaments and their adjacent structures were outlined, labeled, and reconstructed for 3-D modeling. The morphology, attachments, and spatial orientation of ligaments were described.

Results: A total of 9 ligaments in 10 lumbar intervertebral foramina (IVFs) were identified and reconstructed. These ligaments can be divided into 5 types. The IVFs were divided into 2 or 3 main portions by the first 4 types of ligaments (transforaminal ligaments, corporotransverse ligaments, "reticular" ligaments, and "Y-shaped" ligaments). The radiating ligaments (the fifth type of ligaments) attached to the surrounding structures of the IVF and were connected directly to the nerve root sleeves. Although there was no indication of neurovascular compromise in this normal specimen, these ligaments limit the space within the bony IVF such that under certain pathologic conditions (e.g., inflammation), their presence would make neurovascular compression more likely than if they were absent.

Conclusions: The 3-D reconstruction technique based on ultrathin cryomilling can effectively show the lumbar intervertebral foraminal ligaments and their anatomical characteristics in situ, providing a new way to clarify the relationships between these ligaments and their adjacent structures.
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http://dx.doi.org/10.1016/j.wneu.2021.01.032DOI Listing
April 2021

PTH(1‑34) activates the migration and adhesion of BMSCs through the rictor/mTORC2 pathway.

Int J Mol Med 2020 Dec 13;46(6):2089-2101. Epub 2020 Oct 13.

Guangdong Provincial Key Laboratory of Orthopedics and Traumatology, The First Affiliated Hospital of Sun Yat‑sen University, Guangzhou, Guangdong 510080, P.R. China.

The ability of intermittent parathyroid hormone (1‑34) [PTH(1‑34)] treatment to enhance bone‑implant osseointegration was recently demonstrated in vivo. However, the mechanisms through which PTH (1‑34) regulates bone marrow‑derived stromal cells (BMSCs) remain unclear. The present study thus aimed to investigate the effects of PTH(1‑34) on the migration and adhesion of, and rictor/mammalian target of rapamycin complex 2 (mTORC2) signaling in BMSCs. In the present study, BMSCs were isolated from Sprague‑Dawley rats treated with various concentrations of PTH(1‑34) for different periods of time. PTH(1‑34) treatment was performed with or without an mTORC1 inhibitor (20 nM rapamycin) and mTORC1/2 inhibitor (10 µM PP242). Cell migration was assessed by Transwell cell migration assays and wound healing assays. Cell adhesion and related mRNA expression were investigated through adhesion assays and reverse transcription‑quantitative polymerase chain reaction (RT‑qPCR), respectively. The protein expression of chemokine receptors (CXCR4 and CCR2) and adhesion factors [intercellular adhesion molecule 1 (ICAM‑1), fibronectin and integrin β1] was examined by western blot analysis. The results revealed that various concentrations (1, 10, 20, 50 and 100 nM) of PTH(1‑34) significantly increased the migration and adhesion of BMSCs, as well as the expression of CXCR4, CCR2, ICAM‑1, fibronectin and integrin β1. In addition, the p‑Akt and p‑S6 levels were also upregulated by PTH(1‑34). BMSCs subjected to mTORC1/2 signaling pathway inhibition or rictor silencing exhibited a markedly reduced PTH‑induced migration and adhesion, while no such effect was observed for the BMSCs subjected to mTORC1 pathway inhibition or raptor silencing. These results indicate that PTH(1‑34) promotes BMSC migration and adhesion through rictor/mTORC2 signaling in vitro. Taken together, the results of the present study reveal an important mechanism for the therapeutic effects of PTH(1‑34) on bone‑implant osseointegration and suggest a potential treatment strategy based on the effect of PTH(1‑34) on BMSCs.
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http://dx.doi.org/10.3892/ijmm.2020.4754DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7595657PMC
December 2020

Discovery of a series of benzopyrimidodiazepinone TNK2 inhibitors via scaffold morphing.

Bioorg Med Chem Lett 2020 10 31;30(19):127456. Epub 2020 Jul 31.

Department of Cancer Biology, Dana-Farber Cancer Institute, Boston, MA 02115, USA; Department of Biological Chemistry & Molecular Pharmacology, Harvard Medical School, 360 Longwood Ave, Boston, MA 02115, USA. Electronic address:

The protein kinase TNK2 (ACK1) is an emerging drug target for a variety of indications, in particular for cancer where it plays a key role transmitting cell survival, growth and proliferative signals via modification of multiple downstream effectors by unique tyrosine phosphorylation events. Scaffold morphing based on our previous TNK2 inhibitor XMD8-87 identified urea 17 from which we developed the potent and selective compound 32. A co-crystal structure was obtained showing 32 interacting primarily with the main chain atoms of an alanine residue of the hinge region. Additional H-bonds exist between the urea NHs and the Thr205 and Asp270 residues.
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http://dx.doi.org/10.1016/j.bmcl.2020.127456DOI Listing
October 2020

Effect of whole soy and isoflavones daidzein on bone turnover and inflammatory markers: a 6-month double-blind, randomized controlled trial in Chinese postmenopausal women who are equol producers.

Ther Adv Endocrinol Metab 2020 18;11:2042018820920555. Epub 2020 Jun 18.

Department of Nutrition, School of Public Health, Sun Yat-sen University (North Campus), Guangzhou, Guangdong, PR China.

Background: Human studies have demonstrated the beneficial effects of soy or isoflavones on bone metabolism. However, conflicting data remain. Equol is the intestinal metabolite of the isoflavone daidzein. The health benefits of soy are more pronounced in equol producers than those not producing equol. This 6-month randomized controlled trial aimed to examine the effect of whole soy (soy flour) and purified daidzein on bone turnover markers (BTMs) in Chinese postmenopausal women who are equol producers.

Methods: A total of 270 eligible women were randomized to either one of the three isocaloric supplements as follows: 40 g soy flour (whole soy group), 40 g low-fat milk powder + 63 mg daidzein (daidzein group), or 40 g low-fat milk powder (placebo group) given as a solid beverage daily for 6 months. The following fasting venous samples were collected at the baseline and end of the trial to analyze BTMs: serum cross-linked C-telopeptides of type I collagen, bone-specific alkaline phosphatase, osteocalcin, procollagen type I N-terminal propeptide, and 25(OH)D. Inflammation-related biomarkers, such as serum interleukin-6, tumor necrosis factor-alpha, C-reactive protein, transferrin, and homocysteine, were also tested to explore potential mechanisms.

Results: A total of 253 subjects validly completed the study protocol. Urinary isoflavones suggested a good compliance to the treatments. Intention-to-treat and per-protocol analyses indicated no significant difference in the 6-month or percentage changes in the parameters of bone metabolism and inflammatory markers among the three treatment groups.

Conclusions: Whole soy and purified daidzein at provided dosages exhibited no significant effect on the bone metabolism and inflammation levels among Chinese equol-producing postmenopausal women.

Trial Registration: ClinicalTrials.gov identifier NCT01270737.
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http://dx.doi.org/10.1177/2042018820920555DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7303504PMC
June 2020

Short-term predictive potential of quantitative assessment of spinal cord impairment in patients undergoing French-door Laminoplasty for degenerative cervical myelopathy: preliminary results of an exploratory study exploiting intraoperative ultrasound data.

BMC Musculoskelet Disord 2020 May 30;21(1):336. Epub 2020 May 30.

Department of Orthopedic Surgery, The Seventh Affiliated Hospital, Sun Yat-sen University, Shenzhen, P.R. China.

Background: To study the correlation of neurological function in degenerative cervical myelopathy (DCM) patients with quantitative assessment of spinal cord compression and impairment by intraoperative ultrasound imaging (IOUSI).

Methods: Twenty-three patients who underwent French-Door laminoplasty for multilevel DCM were followed for 6 months. Modified Japanese Orthopaedic Association (mJOA) score and cervical MRI were assessed before surgery and at postoperative 6 months. IOUS, used to guide decompression, were recorded. The anteroposterior diameter (APD) and the gray values of the IOUSI hyperechogenicity of the midsagittal IOUSI at the narrowest level and at the lesion-free level, and the APD and traverse diameter at the traverse maximum compression level of IOUSI were measured. Maximum spinal cord compression (MSCC), compression rate (CR), and IOUSI gray value ratio (R) were calculated. The appearance of preoperative T2W MRI increased signal intensity (ISI), and the signal change rate (SCR) on postoperative T2W MRI of 9 patients were also measured and calculated, and compared with that of IOUSI hyperechogenicity.

Results: Average mJOA score increased significantly from 11.57 ± 2.67 before surgery to 15.39 ± 1.50 at 6 months after surgery, with an average recovery rate (RR) of 71.11 ± 22.81%. The difference between the appearance of preoperative T2W MRI ISI and IOUSI hyperechogenicity was not significant. Spearman correlation analysis found that the IOUSI R were negatively correlated with the RR of mJOA score with a coefficient of - 0.77, and the IOUSI R was not correlated with the postoperative MRI SCR.

Conclusions: In DCM patients, the gray values of IOUSI can be measured accurately. The IOUSI R correlated with postoperative neurological recovery significantly.
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http://dx.doi.org/10.1186/s12891-020-03319-wDOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7261379PMC
May 2020

Ten-Year Surgical Outcomes and Prognostic Factors for French-Door Laminoplasty in the Treatment of Multilevel Cervical Spondylotic Myelopathy.

Biomed Res Int 2020 6;2020:3627071. Epub 2020 May 6.

Department of Orthopedic Surgery, The Seventh Affiliated Hospital, Sun Yat-sen University, Shenzhen, China.

Objective: To analyze the ten-year surgical outcomes and postoperative complications of French-Door laminoplasty (FDL) in the management of multilevel cervical spondylotic myelopathy (MCSM) and analyze the prognostic factors for FDL in treating MCSM.

Methods: 64 patients with MCSM, who were operated by FDL, were included in this study and followed up for at least 10 years. Clinical assessments including modified Japanese Orthopaedic Association (mJOA) score, age at surgery, preoperative symptom duration, operative time, blood loss and postoperative complications, radiological assessments including Cobb angle, cervical range of motion (ROM), intramedullary signal intensity on T2W MRI, canal narrowing ratio (CNR), and maximum spinal cord compression (MSCC). mJOA score, Cobb angle, cervical ROM, intramedullary signal intensity on T2W MRI, and CNR were assessed before surgery and at the final follow-up.

Results: The average mJOA score was significantly improved from preoperative 10.32 ± 1.63 points to 15.10 ± 0.62 points at the final follow-up ( < 0.05). The average RR of the mJOA score at the final follow-up was 69.10 ± 7.32%. The cervical Cobb angle and ROM decreased significantly at the final follow-up. Patients with high intramedullary signal intensity of T2W MRI or CNR more than 50% showed a lower RR of the mJOA score. Correlation analysis revealed that preoperative symptom duration and intramedullary signal intensity of T2W MRI, CNR, MSCC, and blood loss were significantly correlated with the RR of the mJOA score. Gender, operative method, and age at surgery were significantly correlated with the preservation rate of ROM. Operative time was significantly correlated with the incidence of axial symptoms.

Conclusions: The ten-year clinical outcomes of FDL were satisfactory. Higher intramedullary signal intensity of T2W MRI and a greater CNR predicted poorer prognoses.
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http://dx.doi.org/10.1155/2020/3627071DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7229559PMC
February 2021

Benzopyrimidodiazepinone inhibitors of TNK2.

Bioorg Med Chem Lett 2020 02 7;30(4):126948. Epub 2020 Jan 7.

Department of Cancer Biology, Dana-Farber Cancer Institute, Boston, MA 02115, USA; Department of Biological Chemistry & Molecular Pharmacology, Harvard Medical School, 360 Longwood Ave, Boston, MA 02115, USA.

The SAR of a series of benzopyrimidodiazepinone inhibitors of TNK2 was developed, starting from the potent and selective compound XMD8-87. A diverse set of anilines was introduced in an effort to improve the in vivo PK profile and minimize the risk of quinone diimine formation.
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http://dx.doi.org/10.1016/j.bmcl.2020.126948DOI Listing
February 2020

Targeting prostate cancer cells with enzalutamide-HDAC inhibitor hybrid drug 2-75.

Prostate 2019 07 28;79(10):1166-1179. Epub 2019 May 28.

Department of Pharmaceutical Sciences, Eugene Applebaum College of Pharmacy and Health Sciences, Wayne State University, Detroit, Michigan.

Background: The progression of castration-resistant prostate cancer (CRPC) still relies on the function of androgen receptor (AR), achieved by evolving mechanisms to reactivate AR signaling under hormonal therapy. Histone deacetylase inhibitors (HDACis) disrupt cytoplasmic AR chaperone heat shock protein 90 (Hsp90) via HDAC6 inhibition, leading to AR degradation and growth suppression of prostate cancer (PCa) cells. However, current HDACis are not effective in clinical trials treating CRPC.

Methods: We designed hybrid molecules containing partial chemical scaffolds of AR antagonist enzalutamide (Enz) and HDACi suberoylanilide hydroxamic acid (SAHA) as new anti-PCa agents. We previously demonstrated that Enz-HDACi hybrid drug 2-75 targets both AR and Hsp90, which inhibits the growth of Enz-resistant C4-2 cells. In the current study, we further investigate the molecular and cellular actions of 2-75 and test its anti-PCa effects in vivo.

Results: Compared with Enz, 2-75 had greater AR antagonistic effects by decreasing the stability, transcriptional activity, and nuclear translocation of intracellular AR. In addition to inhibition of full-length AR (FL AR), 2-75 downregulated the AR-V7 variant in multiple PCa cell lines. Mechanistic studies indicated that the AR affinity of 2-75 retains the drug in the cytoplasm of AR + PCa cells and further directs 2-75 to the AR-associated protein complex, which permits localized effects on AR-associated Hsp90. Further, unlike pan-HDACi SAHA, the cytoplasm-retaining property allows 2-75 to significantly inhibit cytoplasmic HDAC6 with limited impact on nuclear HDACs. These selective cytoplasmic actions of 2-75 overcome the unfavorable resistance and toxicity properties associated with classical AR antagonists, HDACis, and Hsp90 inhibitors. Finally, 2-75 showed greater antitumor activities than Enz in vivo on SQ xenografts derived from LNCaP cells.

Conclusions: Novel therapeutic strategy using newly designed 2-75 and related AR antagonist-HDACi hybrid drugs has great potential for effective treatment of CRPC.
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http://dx.doi.org/10.1002/pros.23832DOI Listing
July 2019

Loss of mdig expression enhances DNA and histone methylation and metastasis of aggressive breast cancer.

Signal Transduct Target Ther 2018;3:25. Epub 2018 Sep 21.

1Department of Pharmaceutical Sciences, Eugene Applebaum College of Pharmacy and Health Sciences, Wayne State University, Detroit, MI 48201 USA.

We previously reported that expression of an environmentally induced gene, mineral dust-induced gene (), predicts overall survival in breast cancer patients. In the present report, we further demonstrate the differential roles of mdig between earlier- and later-stage breast cancers. In noncancerous breast, mdig is a proliferation factor for cell growth and cell motility. In breast cancer, however, higher levels of mdig negatively regulate the migration and invasion of cancer cells. Assessment of global DNA methylation, chromatin accessibility and H3K9me3 heterochromatin signature suggests that silencing mdig enhances DNA and histone methylation. Through immunostaining and data mining, we found that mdig is significantly upregulated in noninvasive and/or earlier-stage breast cancers. In contrast, in triple-negative and other invasive breast cancers, diminished mdig expression was noted, indicating that the loss of mdig expression could be an important feature of aggressive breast cancers. Taken together, our data suggest that mdig is a new biomarker that likely promotes tumor growth in the early stages of breast cancer while acting as a tumor suppressor to inhibit invasion and metastasis in later-stage tumors.
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http://dx.doi.org/10.1038/s41392-018-0027-4DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6147911PMC
February 2021

Dietary sugar intake does not pose any risk of bone loss and non-traumatic fracture and is associated with a decrease in all-cause mortality among Chinese elderly: Finding from an 11-year longitudinal study of Mr. and Ms. OS Hong Kong.

Bone 2018 11 3;116:154-161. Epub 2018 Aug 3.

Jockey Club School of Public Health and Primary Care, The Chinese University of Hong Kong, Hong Kong Special Administrative Region. Electronic address:

Background: The association of dietary sugar intake and skeletal health remains uncertain in the elderly. We aimed to investigate the association of sugar intake with the bone health and mortality of Chinese elderly.

Methods: An analysis was conducted through an 11-year longitudinal study (Mr. and Ms. OS Hong Kong). Four thousand Chinese elderly aged 65 and older were recruited from the local community between 2001 and 2003. Sugar intake was assessed at baseline by a validated 329-item Food Frequency Questionnaire and a local sugar database. The bone mineral density (BMD) was examined at baseline and the fourth year follow-up by a dual-energy X-ray absorptiometry. Data on the incidence of non-traumatic fractures (total, hip and osteoporotic sites) and all-cause mortality were collected. The multivariable logistic and Cox regression models were used to test the associations of sugar intake with bone health and all-cause mortality.

Results: No significant association was observed between sugar intakes and BMD changes in the fourth year's follow-up. During a total 34,483 person years' follow-up, we documented 433 non-traumatic fractures and 769 deaths. Although lack of significant association with the incidence of non-traumatic fractures, high added sugar intakes were significantly associated with a low risk of all-cause mortality among the elderly with a hazard ratio of 0.750 (95% CI: 0.590-0.954, P for trend = 0.007) in the highest quintile compared with that in the lowest quintile.

Conclusion: The amount of sugar consumed by the Chinese elderly did not pose any risk of bone loss and fracture. Moreover, high sugar intake of the elderly was associated with a low rate of all-cause mortality.
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http://dx.doi.org/10.1016/j.bone.2018.07.011DOI Listing
November 2018

Dietary acrylamide exposure was associated with mild cognition decline among non-smoking Chinese elderly men.

Sci Rep 2017 07 25;7(1):6395. Epub 2017 Jul 25.

Division of Family Medicine and Primary Care, Jockey Club School of Public Health and Primary Care, the Chinese University of Hong Kong, Hong Kong SAR, China.

The aim of the study is to explore the longitudinal association of dietary acrylamide exposure with cognitive performance in Chinese elderly. The analysis was conducted among 2534 non-smoking elderly men and women based on a prospective study, Mr. and Ms. OS Hong Kong. Dietary acrylamide intake was assessed by food frequency questionnaires with data on local food contamination, derived from the first Hong Kong Total Diet Study. Global cognitive function was assessed by Cantonese version of Mini-Mental State Exam (MMSE) at the baseline and the 4 year of follow-up. Multivariable-adjusted linear and logistic regression models were used to assess the associations of dietary acrylamide with MMSE score changes or risk of poor cognition. The results indicated that among men with MMSE ≥ 18, each one SD increase of acrylamide decreased MMSE score by 7.698% (95%CI: -14.943%, -0.452%; p = 0.037). Logistic regression revealed an increased risk of poor cognition (MMSE ≤ 26) in men with HR of 3.356 (1.064~10.591, p = 0.039). The association became non-significance after further adjustment for telomere length. No significant association was observed in women. Dietary acrylamide exposure was associated with a mild cognitive decline or increased risk of poor cognition over a 4-year period in non-smoking Chinese elderly men.
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http://dx.doi.org/10.1038/s41598-017-06813-9DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC5527102PMC
July 2017

Dietary acrylamide exposure was associated with increased cancer mortality in Chinese elderly men and women: a 11-year prospective study of Mr. and Ms. OS Hong Kong.

J Cancer Res Clin Oncol 2017 Nov 19;143(11):2317-2326. Epub 2017 Jul 19.

Division of Occupational and Environmental Health, Jockey Club School of Public Health and Primary Care, The Chinese University of Hong Kong, Hong Kong SAR, People's Republic of China.

Aim: Our study aims to investigate the association between dietary acrylamide exposure and cancer mortality among Chinese elderly.

Methods: A prospective cohort of 4000 elderly men and women aged 65 years and above (Mr. and Ms. OS Hong Kong study) was recruited from local communities from 2001 to 2003. Dietary exposure to acrylamide was evaluated at baseline based on a validated food frequency questionnaire and an acrylamide database from the 1st Hong Kong Total Diet Study. Data on mortality statistics through March 2014 were obtained from the Death Registry of the Department of Health of Hong Kong with a median follow-up of 11.1 years. Cox proportional hazards models were used to examine the association between the acrylamide exposure and cancer mortality. Sex hormones were assessed in men.

Results: During a median follow-up of 11.1 years (39,271 person-years), we ascertained 330 cancer deaths. Vegetables (43.7%) and cereals (28.9%) products were the major contributors to dietary acrylamide. Compared with the lowest quartile of acrylamide intake (<9.9 µg/day), the multivariable hazard ratios for the highest quartile (>17.1 µg/day) were 1.9 (95% CI 1.3-2.8; P  < 0.01), 1.9 (95% CI 1.0-3.6; P  = 0.05), and 2.0 (95% CI 1.0-4.0; P  = 0.06) for the cancer mortality from overall, digestive and respiratory system, respectively. The associations were attenuated to null after further adjustment for circulating free estradiol in men. No statistically significant interactions were observed between acrylamide exposure and sex, obesity and overall lifestyle pattern scores.

Conclusions: The longitudinal data provided evidence that dietary acrylamide, in amounts that Chinese elderly are typically exposed to, was associated with increased cancer mortality. Circulating free estradiol may mediate the association in men.
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http://dx.doi.org/10.1007/s00432-017-2477-4DOI Listing
November 2017

Manipulating environmental stresses and stress tolerance of microalgae for enhanced production of lipids and value-added products-A review.

Bioresour Technol 2017 Nov 31;244(Pt 2):1198-1206. Epub 2017 May 31.

State Key Laboratory of Microbial Metabolism and School of Life Science and Biotechnology, Shanghai Jiao Tong University, Shanghai 200240, China. Electronic address:

Microalgae have promising potential to produce lipids and a variety of high-value chemicals. Suitable stress conditions such as nitrogen starvation and high salinity could stimulate synthesis and accumulation of lipids and high-value products by microalgae, therefore, various stress-modification strategies were developed to manipulate and optimize cultivation processes to enhance bioproduction efficiency. On the other hand, advancements in omics-based technologies have boosted the research to globally understand microalgal gene regulation under stress conditions, which enable further improvement of production efficiency via genetic engineering. Moreover, integration of multi-omics data, synthetic biology design, and genetic engineering manipulations exhibits a tremendous potential in the betterment of microalgal biorefinery. This review discusses the process manipulation strategies and omics studies on understanding the regulation of metabolite biosynthesis under various stressful conditions, and proposes genetic engineering of microalgae to improve bioproduction via manipulating stress tolerance.
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http://dx.doi.org/10.1016/j.biortech.2017.05.170DOI Listing
November 2017

Low-magnitude, high-frequency vibration promotes the adhesion and the osteogenic differentiation of bone marrow-derived mesenchymal stem cells cultured on a hydroxyapatite-coated surface: The direct role of Wnt/β-catenin signaling pathway activation.

Int J Mol Med 2016 Nov 28;38(5):1531-1540. Epub 2016 Sep 28.

Department of Rehabilitation, General Hospital of Guangzhou Military Command of PLA, Guangzhou, Guangdong 510000, P.R. China.

The positive effect of low-magnitude, high‑frequency (LMHF) vibration on implant osseointegration has been demonstrated; however, the underlying cellular and molecular mechanisms remain unknown. The aim of this study was to explore the effect of LMHF vibration on the adhesion and the osteogenic differentiation of bone marrow-derived mesenchymal stem cells (BMSCs) cultured on hydroxyapatite (HA)-coated surfaces in an in vitro model as well as to elucidate the molecular mechanism responsible for the effects of LMHF vibration on osteogenesis. LMHF vibration resulted in the increased expression of fibronectin, which was measured by immunostaining and RT-qPCR. Stimulation of BMSCs by LMHF vibration resulted in the rearrangement of the actin cytoskeleton with more prominent F-actin. Moreover, the expression of β1 integrin, vinculin and paxillin was notably increased following LMHF stimulation. Scanning electron microscope observations revealed that there were higher cell numbers and more extracellular matrix attached to the HA-coated surface in the LMHF group. Alkaline phosphatase activity as well as the expression of osteogenic-specific genes, namely Runx2, osterix, collagen I and osteocalcin, were significantly elevated in the LMHF group. In addition, the protein expression of Wnt10B, β-catenin, Runx2 and osterix was increased following exposure to LMHF vibration. Taken together, the findings of this study indicate that LMHF vibration promotes the adhesion and the osteogenic differentiation of BMSCs on HA-coated surfaces in vitro, and LMHF vibration may directly induce osteogenesis by activating the Wnt/β‑catenin signaling pathway. These data suggest that LMHF vibration enhances the osseointegration of bone to a HA-coated implant, and provide a scientific foundation for improving bone-implant osseointegration through the application of LMHF vibration.
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http://dx.doi.org/10.3892/ijmm.2016.2757DOI Listing
November 2016

Randomised controlled trial of effect of whole soy replacement diet on features of metabolic syndrome in postmenopausal women: study protocol.

BMJ Open 2016 Sep 27;6(9):e012741. Epub 2016 Sep 27.

School of Public Health, Sun Yat-Sen University, Guangzhou, People's Republic of China.

Introduction: Metabolic syndrome (MetS) is a public health problem in postmenopausal women. Whole soy foods are rich in unsaturated fats, high quality plant protein and various bioactive phytochemicals that may have a beneficial role in the management of MetS. The aim of the study is to examine the effect of whole soy replacement diet on the features of MetS among postmenopausal women.

Methods And Analysis: This will be a 12-month, randomised, single-blind, parallel controlled trial among 208 postmenopausal women at risk of MetS or with early MetS. After 4 weeks' run-in, subjects will be randomly allocated to one of two intervention groups, whole soy replacement group or control group, each for 12 months. Subjects in the whole soy group will be required to include four servings of whole soy foods (containing 25 g soy protein) into their daily diet iso-calorically, replacing red or processed meat and high fat dairy products. Subjects in the control group will remain on a usual diet. The outcome measures will include metabolic parameters as well as a 10-year risk for ischaemic cardiovascular disease. We hypothesise that the whole soy substitution diet will notably improve features of MetS in postmenopausal women at risk of MetS or with early MetS. The study will have both theoretical and practical significance. If proven effective, the application of the whole soy replacement diet model will be a safe, practical and economical strategy for MetS prevention and treatment.

Ethics And Dissemination: Ethics approval has been obtained from the Ethics Committee of the Chinese University of Hong Kong. The results will be disseminated via conference presentations and papers in academic peer reviewed journals. Data files will be deposited in an accessible repository.

Trial Registration Number: NCT02610322.
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http://dx.doi.org/10.1136/bmjopen-2016-012741DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC5051416PMC
September 2016

Synthesis and Antileukemic Activities of Piperlongumine and HDAC Inhibitor Hybrids against Acute Myeloid Leukemia Cells.

J Med Chem 2016 09 24;59(17):7974-90. Epub 2016 Aug 24.

Department of Pharmaceutical Sciences, Eugene Applebaum College of Pharmacy and Health Sciences, Wayne State University , Detroit, Michigan 48201, United States.

Synergistic-to-additive antileukemic interactions of piperlongumine (PL) and HDAC inhibitor (HDACi) SAHA (Vorinostat) provide a compelling rationale to construct PL-HDACi hybrids, such as 1-58, which recapitulated the synergism between the parental compounds in high-risk and chemoresistant AML cells. Both PL and HDACi components, either in combination or in hybrid molecules, are essential for inducing significant DNA damage and apoptosis. Introducing C2-chloro substituent to 1-58 yielded 3-35 with increased cytotoxicity but decreased selectivity in noncancerous MCF-10A cells; eliminating C7-C8 olefin of PL obtained 3-31/3-98 scaffolds which were still more active than PL or SAHA in AML and were well-tolerated by MCF-10A cells. The HDACi function was crucial for modulating expression of DNA repair and apoptosis-related proteins. Collectively, PL and SAHA hybrids are potent, multifunctional anti-AML agents, acting in part, by interfering cellular GSH defense, suppressing expression of DNA repair and pro-survival proteins, and inducing expression of pro-apoptotic proteins.
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http://dx.doi.org/10.1021/acs.jmedchem.6b00772DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6878111PMC
September 2016

Associations between dietary patterns and psychological factors: a cross-sectional study among Chinese postmenopausal women.

Menopause 2016 12;23(12):1294-1302

1The Jockey Club School of Public Health and Primary Care, The Chinese University of Hong Kong, Hong Kong SAR, P.R. China 2School of Nursing, Faculty of Health and Social Sciences, The Hong Kong Polytechnic University, Hong Kong SAR, P.R. China 3School of Public Health, Sun Yat-sen University, Guangzhou, P.R. China 4Department of Spine Surgery, The First Affiliated Hospital of Sun Yat-sen University, Guangzhou, P.R. China 5School of Public Health, Wuhan University, Wuhan, P.R. China 6Department of Medicine & Therapeutics, The Chinese University of Hong Kong, Hong Kong SAR, P.R. China.

Objective: The aim of this study is to explore the association of dietary patterns with depression, perceived stress, and self-esteem among postmenopausal Chinese women.

Methods: A cross-sectional study was conducted among 906 participants who attended the screening visits for two soy trials. Dietary data were collected using a validated food frequency questionnaire containing 85 food items. Principal component factor analysis was used to derive dietary patterns based on 11 food groups. Psychological factors were assessed by the Center for Epidemiologic Studies Depression Scale, Perceived Stress Scale, and Rosenberg Self-esteem Scale.

Results: We identified three dietary patterns as follows: processed foods (refined grains, preserved foods, fat meat, fried foods, and sweets), whole plant foods (whole grains, vegetables, and fruits), and animal foods (fish, lean meat, and milk products). Multivariable linear regression analyses indicated that whole plant food intake was negatively associated with depression score (P = 0.030). Processed food intake was positively associated with perceived stress (P = 0.025) and depression (P = 0.073), and negatively associated with scores of self-esteem (P = 0.046). The highest tertile of processed foods score was associated with 79.3% increased risk of depression (P for trend = 0.006), whereas the highest tertile of whole plant food score was associated with 26% reduction of depression (P for trend = 0.023) relative to the lowest tertile.

Conclusions: Dietary patterns featuring a low intake of processed foods and/or a high intake of whole plant foods were associated with a reduced risk of depression and perceived stress.
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http://dx.doi.org/10.1097/GME.0000000000000701DOI Listing
December 2016

Hybrid Enzalutamide Derivatives with Histone Deacetylase Inhibitor Activity Decrease Heat Shock Protein 90 and Androgen Receptor Levels and Inhibit Viability in Enzalutamide-Resistant C4-2 Prostate Cancer Cells.

Mol Pharmacol 2016 09 5;90(3):225-37. Epub 2016 Jul 5.

Barbara Ann Karmanos Cancer Institute, Departments of Oncology (R.R., M.P., T.M., E.H., M.R.) and Pharmaceutical Sciences (B.C., S.O., Z.Q.), Wayne State University, Detroit, Michigan

Histone deacetylase inhibitors (HDACIs) can disrupt the viability of prostate cancer (PCa) cells through modulation of the cytosolic androgen receptor (AR) chaperone protein heat shock protein 90 (HSP90). However, toxicities associated with their pleiotropic effects could contribute to the ineffectiveness of HDACIs in PCa treatment. We designed hybrid molecules containing partial chemical scaffolds of enzalutamide and suberoylanilide hydroxamic acid (SAHA), with weakened intrinsic pan-HDACI activities, to target HSP90 and AR in enzalutamide-resistant PCa cells. The potency of the new molecules, compounds 2-75 [4-(3-(4-cyano-3-(trifluoromethyl)phenyl)-5,5-dimethyl-4-oxo-2-thioxoimidazolidin-1-yl)-2-fluoro-N-(7-(hydroxyamino)-7-oxoheptyl)benzamide] and 1005 [(E)-3-(4-(3-(4-cyano-3-(trifluoromethyl)phenyl)-5,5-dimethyl-4-oxo-2-thioxoimidazolidin-1-yl)-2-fluorophenyl)-N-hydroxyacrylamide], as inhibitors of nuclear and cytosolic histone deacetylases was substantially lower than that of SAHA in cell-free and in situ assays. Compounds 2-75 and 1005 antagonized gene activation by androgen without inducing chromatin association of AR. Enzalutamide had no effect on the levels of AR or HSP90, whereas the hybrid compounds induced degradation of both AR and HSP90, similar to (compound 1005) or more potently than (compound 2-75) SAHA. Similar to SAHA, compounds 2-75 and 1005 decreased the level of HSP90 and induced acetylation in a predicted approximately 55 kDa HSP90 fragment. Compared with SAHA, compound 2-75 induced greater hyperacetylation of the HDAC6 substrate α-tubulin. In contrast with SAHA, neither hybrid molecule caused substantial hyperacetylation of histones H3 and H4. Compounds 2-75 and 1005 induced p21 and caused loss of viability in the enzalutamide-resistant C4-2 cells, with efficacies that were comparable to or better than SAHA. The results suggest the potential of the new compounds as prototype antitumor drugs that would downregulate HSP90 and AR in enzalutamide-resistant PCa cells with weakened effects on nuclear HDACI targets.
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http://dx.doi.org/10.1124/mol.116.103416DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC4998664PMC
September 2016

Intermittent parathyroid hormone (1-34) application regulates cAMP-response element binding protein activity to promote the proliferation and osteogenic differentiation of bone mesenchymal stromal cells, via the cAMP/PKA signaling pathway.

Exp Ther Med 2016 Jun 22;11(6):2399-2406. Epub 2016 Mar 22.

Department of Spine Surgery, The First Affiliated Hospital of Sun Yat-sen University, Guangzhou, Guangdong 510080, P.R. China.

The potential effects of intermittent parathyroid hormone (1-34) [PTH (1-34)] administration on bone formation have previously been investigated. A number of studies have suggested that the cyclic adenosine monophosphate/protein kinase A (cAMP/PKA) pathway is associated with PTH-induced osteogenic differentiation. However, the precise signaling pathways and molecular mechanism by which PTH (1-34) induces the osteogenic differentiation of bone mesenchymal stromal cells (BMSCs) remain elusive. The purpose of the present study was to investigate the mechanism underlying the effect of intermittent PTH (1-34) application on the proliferation and osteogenic differentiation of BMSCs. BMSCs were randomly divided into four groups, as follows: Osteogenic medium (control group); osteogenic medium and intermittent PTH (1-34); osteogenic medium and intermittent PTH (1-34) plus the adenylyl cyclase activator forskolin; and osteogenic medium and intermittent PTH (1-34) plus the PKA inhibitor H-89. A cell proliferation assay revealed that PTH (1-34) stimulates BMSC proliferation via the cAMP/PKA pathway. Furthermore, reverse transcription-quantitative polymerase chain reaction, alkaline phosphatase activity testing and cell examination using Alizarin Red S staining demonstrated that PTH (1-34) administration promotes osteogenic differentiation and mineralization, mediated by the cAMP/PKA pathway. Crucially, the results of western blot analyses suggested that PTH (1-34) treatment and, to a greater degree, PTH (1-34) plus forskolin treatment caused an increase in phosphorylated cAMP response element binding protein (p-CREB) expression, but the effect of PTH on p-CREB expression was blocked by H-89. In conclusion, the current study demonstrated that intermittent PTH (1-34) administration regulates downstream proteins, particularly p-CREB, in the cAMP/PKA signaling pathway, to enhance the proliferation, osteogenic differentiation and mineralization of BMSCs.
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http://dx.doi.org/10.3892/etm.2016.3177DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC4887846PMC
June 2016

Association of Circulating 25(OH)D and Lower Urinary Tract Symptoms: A Four-Year Prospective Study among Elderly Chinese Men.

Nutrients 2016 May 7;8(5). Epub 2016 May 7.

Division of Family Medicine and Primary Care, Jockey Club School of Public Health and Primary Care, the Chinese University of Hong Kong, Hong Kong 99977, China.

The role of vitamin D in relation to lower urinary tract symptoms (LUTS) remains inconclusive. This four-year longitudinal study aims to explore the association of circulating 25(OH)D and LUTS in elderly Chinese men. Two thousand Chinese men aged 65 and older were recruited from a local community, of which 1998 (99.9%) at baseline and 1564 (78.2%) at four-year follow-up reported data on LUTS, and 988 of the randomly chosen subpopulation were assayed for serum 25(OH)D by radioimmunoassay at baseline. LUTS were evaluated by a validated International Prostate Symptoms Scale (IPSS). Data on demographic characteristics, lifestyle factors, health, and medications were collected. Serum parathyroid and sex steroid hormones and genotypes of vitamin D receptors were assayed. The association of serum 25(OH)D and LUTS was examined by using multivariable regression models. Serum 25(OH)D was not significantly associated with the changes of IPSS or the risk of LUTS in overall participants. However, among men with 25(OH)D ≤ 60 nmol/L, each 10 nmol/L increase of 25(OH)D over 0 nmol/L was significantly associated with 1.3 lower points of IPSS or a 51.6% decreased risk for moderate/severe LUTS four years later. Adjustment for serum androstenedione (p = 0.019) and dehydropiandrosterone (p = 0.037) attenuated the associations. Our study suggested that among individuals with low vitamin D status, the increase of the 25(OH)D level may be associated with a lowered risk of LUTS.
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http://dx.doi.org/10.3390/nu8050273DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC4882686PMC
May 2016

[Right ventricular systolic function of patients with pneumoconiosis based on the evaluation of systolic displacement of tricuspid annulus].

Zhonghua Lao Dong Wei Sheng Zhi Ye Bing Za Zhi 2015 May;33(5):382-4

Heilongjiang Institute of Labor Health and Occupational Diseases, Heilongjiang, Harbin 150010, China; E-mail:

Objective: To determine the tricuspid annular plane systolic excursion (TAPSE) using M-mode echocardiography, and to evaluate the right ventricular systolic function in patients with pneumoconiosis.

Methods: One hundred and eighty-three patients with pneumoconiosis were enrolled as subjects, and one hundred and ninety-nine healthy volunteers were used as controls. According to the types of ventilation dysfunction, patients were divided into four groups: normal type, obstructive type, restrictive type, and mixed type. In the apex four-chamber sections, the displacement of tricuspid annular plane on the right ventricular free wall side was measured from end-diastole to end-systole using M-mode echocardiography.

Results: The average TAPSE in the pneumoconiosis group was significantly lower than that in the control group (18.61 ± 3.08 vs 22.38 ± 3.03 mm, P < 0.01). Along with the progression of pneumoconiosis, the TAPSE values in patients with stage I, II, and III pneumoconiosis were significantly decreased compared with those in the control group (P < 0.01). The TAPSE values in patients diagnosed with normal, obstructive, restrictive, and mixed types of pneumoconiosis in pulmonary function tests were all significantly lower than those in the control group (P < 0.01). Among all patients, patients with mixed type of pneumoconiosis had the most significant reduction in the TAPSE.

Conclusion: The TAPSE is substantially decreased in patients with pneumoconiosis and further decreased along with the progression of pneumoconiosis. Measurement of the TAPSE is an easy way to evaluate the right ventricular systolic function in patients with pneumoconiosis.
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May 2015

Assessment of bilateral cerebral peduncular infarction: Magnetic resonance imaging, clinical features, and prognosis.

J Neurol Sci 2015 Oct 15;357(1-2):131-5. Epub 2015 Jul 15.

Department of Neurology, Zhangzhou Affiliated Hospital of Fujian Medical University, Fujian, China.

Background: Bilateral cerebral peduncular infarction (BCPI) is an extremely rare neurological disorder, and related literature is scarce. This study investigated the clinical manifestations, magnetic resonance imaging (MRI) features and prognosis of BCPI.

Method: We retrospectively reviewed the clinical features, MRI and magnetic resonance angiography manifestations, and prognosis of 14 patients with BCPI, confirmed by diffusion-weighted MRI from 5050 cerebral infarction patients at our medical center from January 2007 to June 2013.

Result: Eleven of the 14 (78.6%) patients had quadriplegia and 9 (64.3%) had decreased consciousness. At the most severe stage, the National Institutes of Health Stroke Scale scores ranged from grades 4 to 26 (mean grade, 18.9). Eleven (78.6%) cases were caused by large artery atherosclerosis. Besides the bilateral cerebral peduncle, the pons (85.7%) and cerebellum (42.9%) were the other infarct locations. Twelve (85.7%) patients had vertebrobasilar artery occlusion or severe stenosis, and 12 (85.7%) did not have collateral patency of the posterior cerebral artery. Thirteen (92.9%) patients had poor prognosis and 9 of them died.

Occlusion: BCPI is a very rare disorder and associated with severe vertebrobasilar artery stenosis or occlusion without collateral patency of the posterior communicating artery. It has a very poor prognosis.
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http://dx.doi.org/10.1016/j.jns.2015.07.016DOI Listing
October 2015

Arsenic-induced sub-lethal stress reprograms human bronchial epithelial cells to CD61¯ cancer stem cells.

Oncotarget 2014 Mar;5(5):1290-303

Department of Pharmaceutical Sciences, Eugene Applebaum College of Pharmacy and Health Sciences, Wayne State University, Detroit, MI, USA.

In the present report, we demonstrate that sub-lethal stress induced by consecutive exposure to 0.25 µM arsenic (As3+) for six months can trigger reprogramming of the human bronchial epithelial cell (BEAS-2B) to form cancer stem cells (CSCs) without forced introduction of the stemness transcription factors. These CSCs formed from As3+-induced sub-lethal stress featured with an increased expression of the endogenous stemness genes, including Oct4, Sox2, Klf4, Myc, and others that are associated with the pluripotency and self-renewal of the CSCs. Flow cytometry analysis indicated that 90% of the CSC cells are CD61¯, whereas 100% of the parental cells are CD61+. These CD61¯ CSCs are highly tumorigenic and metastatic to the lung in xenotransplantation tests in NOD/SCID Il2rγ-/- mice. Additional tests also revealed that the CD61¯ CSCs showed a significant decrease in the expression of the genes important for DNA repair and oxidative phosphorylation. To determine the clinical relevance of the above findings, we stratified human lung cancers based on the level of CD61 protein and found that CD61low cancer correlates with poorer survival of the patients. Such a correlation was also observed in human breast cancer and ovarian cancer. Taken together, our findings suggest that in addition to the traditional approaches of enforced introduction of the exogenous stemness circuit transcription factors, sub-lethal stress induced by consecutive low dose As3+ is also able to convert non-stem cells to the CSCs.
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http://www.ncbi.nlm.nih.gov/pmc/articles/PMC4012730PMC
http://dx.doi.org/10.18632/oncotarget.1789DOI Listing
March 2014

Reactive oxygen species contribute to arsenic-induced EZH2 phosphorylation in human bronchial epithelial cells and lung cancer cells.

Toxicol Appl Pharmacol 2014 May 25;276(3):165-70. Epub 2014 Feb 25.

Department of Pharmaceutical Sciences, Eugene Applebaum College of Pharmacy and Health Sciences, Wayne State University, 259 Mack Avenue, Detroit, MI 48201, USA,. Electronic address:

Our previous studies suggested that arsenic is able to induce serine 21 phosphorylation of the EZH2 protein through activation of JNK, STAT3, and Akt signaling pathways in the bronchial epithelial cell line, BEAS-2B. In the present report, we further demonstrated that reactive oxygen species (ROS) were involved in the arsenic-induced protein kinase activation that leads to EZH2 phosphorylation. Several lines of evidence supported this notion. First, the pretreatment of the cells with N-acetyl-l-cysteine (NAC), a potent antioxidant, abolishes arsenic-induced EZH2 phosphorylation along with the inhibition of JNK, STAT3, and Akt. Second, H2O2, the most important form of ROS in the cells in response to extracellular stress signals, can induce phosphorylation of the EZH2 protein and the activation of JNK, STAT3, and Akt. By ectopic expression of the myc-tagged EZH2, we additionally identified direct interaction and phosphorylation of the EZH2 protein by Akt in response to arsenic and H2O2. Furthermore, both arsenic and H2O2 were able to induce the translocation of ectopically expressed or endogenous EZH2 from nucleus to cytoplasm. In summary, the data presented in this report indicate that oxidative stress due to ROS generation plays an important role in the arsenic-induced EZH2 phosphorylation.
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http://dx.doi.org/10.1016/j.taap.2014.02.005DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC4401465PMC
May 2014

Paradoxical roles of mineral dust induced gene on cell proliferation and migration/invasion.

PLoS One 2014 4;9(2):e87998. Epub 2014 Feb 4.

Department of Pharmaceutical Sciences, Eugene Applebaum College of Pharmacy, Wayne State University, Detroit, Michigan, United States of America.

Increased expression of mineral dust-induced gene (mdig, also named as mina53, MINA, or NO52) has been observed in a number of human cancers. The mechanism of how mdig contribute to the pathogenesis of cancer remains to be fully elucidated. In this report, we demonstrated that overexpression of mdig decreased the nuclear staining signal by 4',6-diamidino-2-phenylindole (DAPI), along with a considerable enhancement in cell proliferation. Silencing mdig by shRNA resulted in a statistically significant decrease of cell proliferation. Intriguingly, mdig overexpression reduced the capacity of the cells in migration and invasion in vitro, whereas silencing mdig by shRNA/siRNA enhanced migration and invasion. Clinically, we found that increased expression of mdig in cancer tissues correlates with poorer overall survival of the lung cancer patients, esp., for those without lymph node metastasis. Taken together, our results suggest that mdig plays opposite roles on cell growth and motility, which possibly indicates the paradoxical effect of mdig at the different stages of carcinogenesis.
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http://journals.plos.org/plosone/article?id=10.1371/journal.pone.0087998PLOS
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC3913710PMC
September 2014

Carcinogenic metalloid arsenic induces expression of mdig oncogene through JNK and STAT3 activation.

Cancer Lett 2014 May 14;346(2):257-63. Epub 2014 Jan 14.

Department of Pharmaceutical Sciences, Eugene Applebaum College of Pharmacy, Wayne State University, 259 Mack Avenue, Detroit, MI 48201, USA. Electronic address:

Environmental or occupational exposure to arsenic, a chemical element classified as metalloid, has been associated with cancer of the lung, skin, bladder, liver, etc. Mdig (mineral dust-induced gene) is a newly identified oncogene linked to occupational lung diseases and lung cancer. It is unclear whether mdig is also involved in arsenic-induced malignant transformation of the lung cells. By using human bronchial epithelial cells and human lung cancer cell lines, we showed that arsenic was able to induce expression of mdig. We further demonstrated that this mdig induction by arsenic was partially dependent on the JNK and STAT3 signaling pathways. Disruption of the JNK or STAT3 by either chemical inhibitors or siRNAs diminished arsenic-induced accumulation of mdig mRNA and protein. Furthermore, we also showed that microRNA-21 (miR-21) and Akt were down-stream effectors of the JNK and STAT3 signaling pathways in arsenic-induced mdig expression. Transfection of the cells with anti-miR-21 or pre-treatment of the cells with Akt inhibitor blunted mdig induction by arsenic. Clinically, the levels of mdig can be applied to predict the disease progression, the first progression (FP), in non-small cell lung cancer (NSCLC) patients. Taken together, our data suggest that mdig may play important roles on the pathogenesis of arsenic-induced lung cancer and that JNK and STAT3 signaling pathways are essential in mediating arsenic-induced mdig expression.
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http://dx.doi.org/10.1016/j.canlet.2014.01.002DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC3976992PMC
May 2014
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