Publications by authors named "Huazhuang Li"

9 Publications

  • Page 1 of 1

Revisiting bone morphogenetic protein-2 knuckle epitope and redesigning the epitope-derived peptides.

J Pept Sci 2021 Jun 22;27(6):e3309. Epub 2021 Feb 22.

Department of Orthopedics, Yidu Central Hospital Affiliated to Weifang Medical University, Weifang, China.

The bone morphogenetic protein-2 (BMP2) plays a crucial role in bone formation, growth and regeneration, which adopts a conformational wrist epitope and a linear knuckle epitope to interact with its type-I (BRI) and type-II (BRII) receptors, respectively. In this study, we systematically examine the BRII-recognition site of BMP2 at structural, energetic and dynamic levels and accurately locate hotspots of the recognition at BMP2-BRII complex interface. It is revealed that the traditional knuckle epitope (BMP2 residue range 73-92) do fully match the identified hotspots; the BMP2-recognition site includes the C-terminal region of traditional knuckle epitope as well as its flanked β-strands. In addition, the protein context of full-length BMP2 is also responsible for the recognition by addressing conformational constraint on the native epitope segment. Therefore, we herein redefine the knuckle epitope to BMP2 residue range 84-102, which has a similar sequence length but is slid along the protein sequence by ~10 residues as compared to traditional knuckle epitope. The redefined one is also a linear epitope that is natively a double-stranded β-sheet with two asymmetric arms as compared to the natively single β-strand of the traditional version, although their sequences are partially overlapped to each other. It is revealed that the redefined epitope-derived peptide LN exhibits an improved affinity by >3-fold relative to the traditional epitope-derived peptide KL . Even so, the LN peptide still cannot fully represent the BMP2 recognition event by BRII that has been reported to have a nanomolar affinity. We further introduce a disulfide bond across the two arms of double-stranded β-sheet to constrain the free LN peptide conformation, which mimics the conformational constraint addressed by protein context. Consequently, several cyclic peptides are redesigned, in which the LN (cyc89-101) is determined to exhibit a sub-micromolar affinity; this value is ~5-fold higher than its linear counterpart. Structural analysis also reveals that the cyclic peptide can interact with BRII in a similar binding mode with the redefined knuckle epitope region in full-length BMP2 protein.
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http://dx.doi.org/10.1002/psc.3309DOI Listing
June 2021

Lutein Suppresses Oxidative Stress and Inflammation by Nrf2 Activation in an Osteoporosis Rat Model.

Med Sci Monit 2018 Jul 21;24:5071-5075. Epub 2018 Jul 21.

Department of Spine Surgery, Yidu Central Hospital of Weifang, Qingzhou, Shandong, China (mainland).

BACKGROUND Osteoporosis is a major health risk for women worldwide. Osteoporosis is caused by an imbalance between bone resorption and formation. Hormonal imbalance and increased redox signaling cause bone deterioration. MATERIAL AND METHODS Oxidative stress was determined through assessment of ROS, lipid peroxide levels, and antioxidant activity. Inflammatory protein markers and Nrf2-related protein expressions were determined through Western blot analysis. Interleukin expressions were determined using ELSA. RESULTS In the present study, we showed that supplementation of lutein protects the ovariectomized (OVX) rats against oxidative stress through its antioxidant protection. OVX rats showed an increase in oxidative stress markers. Lutein treatment significantly decreased the lipid peroxidation levels and ROS in the OVX rats. OVX rats showed inflammatory responses through NF-κB activation and increased inflammatory cytokines (TNF-α, IL-6, IL-8). Further, there was significant upregulation in osteoclast-specific marker NFATc1 in OVX rats compared to sham rats. Lutein supplementation activated Nrf2 driven antioxidant gene expression (HO-1, NQO1) and protected OVX rats against inflammatory responses. CONCLUSIONS We showed the critical role of Lutein in protection against osteoporosis in OVX rats by downregulation of inflammation and osteoclast-specific marker (NFATc1) expression through Nrf2 activation.
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http://dx.doi.org/10.12659/MSM.908699DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6067024PMC
July 2018

ALK-positive anaplastic large cell lymphoma with soft tissue involvement in a young woman.

Onco Targets Ther 2016 1;9:3993-6. Epub 2016 Jul 1.

Department of Orthopaedics, Yidu Central Hospital, Shandong, People's Republic of China.

Introduction: Anaplastic large cell lymphoma (ALCL) is a type of non-Hodgkin lymphoma that has strong expression of CD30. ALCL can sometimes involve the bone marrow, and in advanced stages, it can produce destructive extranodal lesions. But anaplastic large cell lymphoma kinase (ALK)+ ALCL with soft tissue involvement is very rare.

Case Report: A 35-year-old woman presented with waist pain for over 1 month. The biopsy of soft tissue lesions showed that these cells were positive for ALK-1, CD30, TIA-1, GranzymeB, CD4, CD8, and Ki67 (90%+) and negative for CD3, CD5, CD20, CD10, cytokeratin (CK), TdT, HMB-45, epithelial membrane antigen (EMA), and pan-CK, which identified ALCL. After six cycles of Hyper-CVAD/MA regimen, she achieved partial remission. Three months later, she died due to disease progression.

Conclusion: This case illustrates the unusual presentation of ALCL in soft tissue with a bad response to chemotherapy. Because of the tendency for rapid progression, ALCL in young adults with extra-nodal lesions are often treated with high-grade chemotherapy, such as Hyper-CVAD/MA.
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http://dx.doi.org/10.2147/OTT.S109746DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC4936818PMC
July 2016

microRNA-363 plays a tumor suppressive role in osteosarcoma by directly targeting MAP2K4.

Int J Clin Exp Med 2015 15;8(11):20157-67. Epub 2015 Nov 15.

Department of Orthopaedic Surgery, Yidu Central Hospital of Weifang, Weifang Medical University Qingzhou 262500, Shandong, China.

Abnormal expression of microRNAs plays important functions in osteosarcoma. The aim of this study was to investigate expression, functions and molecular mechanisms of microRNA-363 in osteosarcoma. Quantitative Real-time PCR was used to detect the expression level of microRNA-363 in osteosarcoma tissue samples and cell lines. After transfection, CCK8 assay, cell migration and invasion assay, western blot and Dual-Luciferase report assay were performed in human osteosarcoma cells. According to the results, we found that microRNA-363 was down-regulated in osteosarcoma tissues and cell lines. In addition, low expression level of microRNA-363 was associated with tumor size, clinical stage and distant metastasis. Moreover, microRNA-363 targeted MAP2K4 to inhibit osteosarcoma cell growth, migration and invasion. In conclusion, microRNA-363 played a tumor suppressive role in osteosarcoma by directly targeting MAP2K4. These findings indicated that microRNA-363 may have therapeutic value in treating osteosarcoma.
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http://www.ncbi.nlm.nih.gov/pmc/articles/PMC4723773PMC
February 2016

MicroRNA-128 inhibits EMT of human osteosarcoma cells by directly targeting integrin α2.

Tumour Biol 2016 Jun 24;37(6):7951-7. Epub 2015 Dec 24.

Department of Orthopaedics, Yidu Central Hospital of Weifang, Qingzhou, 262500, Shandong, People's Republic of China.

Deregulated expression of miRNAs contributes to the development of osteosarcoma. The present study was to evaluate the level of miR-128 and integrin α2 (ITGA2) in osteosarcoma tissues and cells. We further investigated the molecular mechanisms of miR-128 and ITGA2 in osteosarcoma cell lines. In the present study, we found that miR-128 expression was down-regulated in osteosarcoma tissues and MG-63, U2OS, and SAOS-2 cells (all p < 0.001). By contrast, ITGA2 was up-regulated. Furthermore, we found that miR-128 overexpression suppressed cell migration and invasion of MG-63 cells. Mechanically, miR-128 overexpression inhibited epithelial-mesenchymal transition (EMT) of MG-63 cells. Importantly, we identified that the 3'-untranslated region (3'-UTR) of ITGA2 was a direct target of miR-128. Luciferase reporter assays confirmed that miR-128 binding to the 3'-UTR regions of ITGA2 inhibited the expression of ITGA2 in MG-63 cells. At the same time, overexpressed ITGA2 also reversed EMT inhibited by miR-128. In conclusion, this study suggested that high miR-128 expression suppressed osteosarcoma cell migration, invasion, and EMT development through targeting ITGA2, which may be recommended as a therapeutic target for osteosarcoma.
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http://dx.doi.org/10.1007/s13277-015-4696-0DOI Listing
June 2016

miR‑542‑3p overexpression is associated with enhanced osteosarcoma cell proliferation and migration ability by targeting Van Gogh‑like 2.

Mol Med Rep 2015 Feb 27;11(2):851-6. Epub 2014 Oct 27.

Department of Spinal Orthopedics, Yantai Yuhuangding Hospital, Medical College of Qingdao University, Yantai, Shandong 264000, P.R. China.

Osteosarcoma is the most common histological form of primary bone cancer, which arises from osteoid tissue. It occurs predominantly in infants and adolescents, with an incidence of 4‑5 cases/100,000,000. The 5-year survival rate of patients with osteosarcoma has significantly improved over time; however, there remains a significant proportion of patients that respond poorly to chemotherapy. An improved understanding of the pathology of osteosarcoma is required to provide more effective treatment strategies, identify biomarkers and develop novel chemotherapeutic agents. Disturbance in microRNA (miRNA) expression has been identified in osteosarcoma tissues and cell lines; however, the roles of miRNA during osteosarcoma pathogenesis remain to be elucidated. In the present study, the expression levels of eight selected miRNAs were investigated in osteosarcoma tissues and the results revealed that the expression levels of miR‑542‑3p and miR‑542‑5p were significantly upregulated and the expression of miR‑199‑3p was significantly downregulated. Using a dual luciferase assay and western blot analysis, the present study confirmed that Van Gogh‑like 2, which is a non‑canonical Wnt pathway suppressor, was a target gene of miR‑542‑3p. Subsequently, the biological function of miR‑542‑3p in U2OS cells was examined, which revealed that overexpression of miR‑542‑3p can enhance the cell proliferation and migration ability of U2OS cells. This indicated that miR‑542‑3p may act as an oncogene in osteosarcoma pathogenesis. The findings of the present study may provide assistance in understanding the development of osteosarcoma and aid in the development of strategies for the diagnosis and treatment of osteosarcoma.
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http://dx.doi.org/10.3892/mmr.2014.2777DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC4262515PMC
February 2015

Dimethyl fumarate inhibits the expression and function of hypoxia-inducible factor-1α (HIF-1α).

Biochem Biophys Res Commun 2014 Jun 22;448(3):303-7. Epub 2014 Feb 22.

Department of Orthopaedics, Yidu Central Hospital of Weifang, China.

Osteocyte hypoxia has been induced by skeletal unloading and fracture. Hypoxia-dependent regulation of gene expression is mediated by hypoxia-sensitive transcription factors such as hypoxia-inducible factor-1α (HIF-1α). Dimethyl fumarate (DMF) is a recently approved first-line therapy for multiple sclerosis. However, the role of DMF in regulating HIF-1α expression and function has not been evaluated. In this study, we found that DMF inhibited hypoxia-induced expression of HIF-1α and its target genes such as interleukin 8 (IL-8) and vascular endothelial growth factor (VEGF) in MC3T3 E1 cells. Mechanistically, DMF promoted HIF-1α degradation in a proteasome-dependent but von Hippel-Lindau (VHL) protein-independent manner. Importantly, we found that DMF disrupted the interaction between HIF-1α and its chaperone heat shock protein 90 (Hsp90) but promoted the interaction between HIF-1α and the receptor of activated protein kinase C (RACK1). These data suggest that DMF might promote degradation of HIF-1α by affecting its folding and maturation. Based on these observations, we conclude that DMF is a novel inhibitor of HIF-1α.
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http://dx.doi.org/10.1016/j.bbrc.2014.02.062DOI Listing
June 2014

Crossover replantation after bilateral traumatic lower limb amputations: a case report.

J Med Case Rep 2012 Jul 24;6:218. Epub 2012 Jul 24.

Department of Oral and Maxillofacial Surgery, Yidu Central Hospital, Weifang Medical University, Shandong Province, 262500, PR China.

Introduction: Replantation of a limb to the contralateral stump after bilateral traumatic amputations is rare. To the best of our knowledge, there are only a few reports of crossover lower limb replantation in the literature.

Case Presentation: We treated a 37-year-old Chinese woman with bilateral lower limb crush injuries sustained in a traffic accident. Her lower limb injuries were at different anatomic levels. We performed emergency bilateral amputations followed by crossover replantation. Five years later, the woman had recovered well, and had perfect movement and stability in her replanted leg. After reviewing the literature, we thought that presentation of our patient's case might provide useful information for clinicians.

Conclusions: Crossover replantation should be considered when evaluating a patient with bilateral lower limb injuries, thus allowing the patient to touch the ground and stand using their own foot.
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http://dx.doi.org/10.1186/1752-1947-6-218DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC3419122PMC
July 2012

[Effects of core binding factor alpha1 on promotion of osteoblastic differentiation from marrow mesenchymal stem cells].

Zhongguo Xiu Fu Chong Jian Wai Ke Za Zhi 2006 Feb;20(2):121-4

Third Military Medical University, Chongqing 400037, P. R. China.

Objective: To observe effects of the core binding factor alpha1 (Cbfalpha1) in its promoting differentiation of the rabbit marrow mesenchymal stem cells (MSCs) into osteoblasts.

Methods: The rabbit marrow MSCs were isolated and cultured in vitro and were divided into 3 groups. In the control group, the marrow MSCs were cultured by DMEM; in the single inducement group, they were cultured by the condition medium (DMEM, 10% fetal bovine serum, dexamethasone 10 mmol/L, vitamin C 50 mg/L, and beta-GP 10 mmol/L); and in the experimental group, they were transfected with AdEasyl/Cbfalpha1, and then were cultured by the condition medium. The alkaline phosphatase (ALP) activity and the expression of osteocalcin as the osteoblast markers were measured with the chemohistological and immunohistochemical methods at 3 days, 1, 2, 3, and 4 weeks after inducement.

Results: More than 90% MSCs were grown well in vitro. The GFP was positive in MSCs after their being transfected with AdEasyl/Cbfalpha1. The ALP activity and the expression of osteocalcin were significantly upregulated in the transfection group compared with those in the single inducement group and the control group at 1, 2, 3, and 4 weeks (P < 0.05). The mineralized node began to appear at 2 weeks in the experimental group and the single induction group, but did not appear in control group.

Conclusion: Cbfalpha1 can obviously promote differentiation of the rabbit marrow mesenchymal stem cells into the osteoblasts.
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February 2006
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