Publications by authors named "Tianfu Wu"

89 Publications

One-step removal of harmful algal blooms by dual-functional flocculant based on self-branched chitosan integrated with flotation function.

Carbohydr Polym 2021 May 29;259:117710. Epub 2021 Jan 29.

Key Laboratory for Biobased Materials and Energy of Ministry of Education, College of Materials and Energy, South China Agricultural University, Guangzhou, 510642, China. Electronic address:

Harmful algal blooms induce severe environmental problems. It is challenging to remove algae by the current available treatments involving complicate process and costly instruments. Here, we developed a CaO@PEG-loaded water-soluble self-branched chitosan (CP-SBC) system, which can remove algae from water in one-step without additional instrumentation. This approach utilizes a novel flocculant (self-branched chitosan) integrated with flotation function (induced by CaO@PEG). CP-SBC exhibited better flocculation performance than commercial flocculants, which is attributed to the enhanced bridging and sweeping effect of branched chitosan. CP-SBC demonstrated outstanding biocompatibility, which was verified by zebrafish test and algae activity test. CaO@PEG-loaded self-branched chitosan can serve as an "Air flotation system" to spontaneous float the flocs after flocculation by sustainably released O. Furthermore, CP-SBC can improve water quality through minimizing dissolved oxygen depletion and reducing total phosphorus concentrations.
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http://dx.doi.org/10.1016/j.carbpol.2021.117710DOI Listing
May 2021

In vitro and in vivo synergistic anti-tumor effect of LIN28 inhibitor and metformin in oral squamous cell carcinoma.

Eur J Pharmacol 2021 Jan 26;891:173757. Epub 2020 Nov 26.

The State Key Laboratory Breeding Base of Basic Science of Stomatology (Hubei-MOST) and Key Laboratory of Oral Biomedicine Ministry of Education, School and Hospital of Stomatology, Wuhan University, 237 Luoyu Road, 430079, Wuhan, PR China; Department of Oral and Maxillofacial Surgery, School and Hospital of Stomatology, Wuhan University, 237 Luoyu Road, Wuhan, 430079, PR China. Electronic address:

Cancer stem cell therapy is becoming a focal point for oral squamous cell carcinoma (OSCC). They can be regulated by tumor glucose metabolism, whereas the regulation is not fully investigated in OSCC. Herein, we studied the synergistic anti-tumor effect of a LIN28 inhibitor C1632 and hypoglycemic medication metformin in OSCC. In this study, OSCC cell lines SCC9 and CAL27 were treated with C1632 and metformin respectively or synergistically. First, western blotting was performed to detect the expression level of LIN28 and its downstream molecule HMGA2. Second, MTT assay was conducted to assess cell proliferation. Next, wound healing assay and transwell assay were applied to evaluate cell migration. Then, xenograft mouse experiment was done to explore anti-tumor effect in vivo. Finally, western blotting was used to investigate the pharmacological mechanisms of the synergistic effect oft he two medication. Results showed that LIN28 and HMGA2 expression decreased significantly in SCC9 and CAL27 cells under 240 μM C1632 treatment for 72 h. These effects were synergized under combined treatment for 24 h. Cell proliferation ability and migration ability of both cell lines decreased significantly under respective and combined treatment. In xenograft mouse experiment, tumor weights decreased by 48% under 40 mg/kg/3d C1632 treatment, 53% under 250 mg/kg/d metformin treatment and 91% under combined treatment for 18 days. Tumor volumes decreased by 32%, 57% and 47% under C1632, metformin and combined treatment respectively. These results indicated that C1632 and metformin exerts synergistic anti-tumor effects in OSCC cell lines SCC9 and CAL27, and also inhibits xenograft tumor growth in vivo.
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http://dx.doi.org/10.1016/j.ejphar.2020.173757DOI Listing
January 2021

Vitamin C: A stem cell promoter in cancer metastasis and immunotherapy.

Biomed Pharmacother 2020 Nov 21;131:110588. Epub 2020 Aug 21.

The State Key Laboratory Breeding Base of Basic Science of Stomatology (Hubei-MOST) & Key Laboratory of Oral Biomedicine Ministry of Education, School & Hospital of Stomatology, Wuhan University, People's Republic of China. Electronic address:

Vitamin C is an electron donor and is involved in a variety of biochemical reactions in stem cell and cancer stem cell, as well as collagen synthesis and the regulation of hypoxia-inducible factor synthesis, which two affect extracellular matrix remodelling and hence cancer metastasis. Specific doses of vitamin C can stop cancer cell glycolysis and block nitroso synthesis, indicating the potential of vitamin C in cancer treatment. Recent studies preliminary revealed Vitamin C enhance the cancer's immune response to anti PD-L1 therapy through multiple indirect approaches. Herein we reviewed the recent function of vitamin C for further research in sequential aspects of cancer stem cell, extracellular matrix remodeling, cancer metastasis and cancer immunotherapy.
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http://dx.doi.org/10.1016/j.biopha.2020.110588DOI Listing
November 2020

Recent advance in patient-specific 3D printing templates in mandibular reconstruction.

J Mech Behav Biomed Mater 2020 06 23;106:103725. Epub 2020 Mar 23.

The State Key Laboratory Breeding Base of Basic Science of Stomatology & Key Laboratory of Oral Biomedicine, Ministry of Education, Wuhan University, Hubei Province, China. Electronic address:

Patient-specific 3D printing template is used in mandibular defect reconstruction with multiple deficiencies. During the operation, the template can accurately transfer the preoperative design, assisting surgeons to complete the surgery with high efficiency and accuracy. The template design has been continuously improved to obtain good application for miscellaneous classification and description. This review attempted to preliminarily analyse and summarise recent advancements in personalized 3D printing templates in mandibular reconstruction from the aspects of functional classification, existing problems, improved strategies and post-surgery evaluation by reviewing studies and through our combined clinical work and experience on hundreds of reconstruction surgeries.
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http://dx.doi.org/10.1016/j.jmbbm.2020.103725DOI Listing
June 2020

Curcumin Attenuates Both Acute and Chronic Immune Nephritis.

Int J Mol Sci 2020 Mar 4;21(5). Epub 2020 Mar 4.

Department of Biomedical Engineering, University of Houston, Houston, TX 77204, USA.

Curcumin is known to have immunomodulatory potential in addition to anti-oxidant, anti-inflammatory and anti-carcinogenic effects. The aim of the present study is to investigate the therapeutic effects of curcumin on immune-mediated renal disease in an anti-glomerular basement membrane (GBM) model (representing acute kidney Injury, AKI) and murine lupus model (representing chronic kidney disease, CKD). In the AKI model, female anti-GBM 129/svj mice were administered with curcumin right before disease induction. In the CKD model, female MRL. mice at the age of 8-10 weeks old were treated with curcumin or placebo via oral gavage daily for two months. After treatment, serum autoantibody levels, splenomegaly and spleen cellularity were reduced in murine lupus. Collectively, curcumin ameliorated kidney disease in the two mouse models with either acute or chronic nephritis, as marked by reduced proteinuria, blood urea nitrogen, glomerulonephritis, crescent formation, tubule-interstitial disease, and renal infiltration by lymphocytes. In addition, curcumin treatment reduced activation of the NFkB, MAPK, AKT and pBAD pathways either systemically, or within the inflamed kidneys. These findings suggest that natural food supplements could become an alternative approach to ameliorating immune-mediated kidney diseases.
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http://dx.doi.org/10.3390/ijms21051745DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7084772PMC
March 2020

Extraskeletal Myxoid Chondrosarcoma of the Parotid Gland.

Ann Maxillofac Surg 2019 Jul-Dec;9(2):439-443

Department of Oral and Maxillofacial Surgery, Teaching Hospital of Kinshasa University, University of Kinshasa, Kinshasa, Democratic Republic of the Congo.

Extraskeletal myxoid chondrosarcoma (EMC) is a rare tumor with an estimated incidence of <3% among of all soft-tissue sarcomas. It is characterized by a multinodular architecture, abundant myxoid matrix, and malignant chondroblast-like cells arranged in cords. The tumor is an entity from chondrosarcomas of bones, commonly found in the soft tissues of the lower extremities at 80%. There are very limited reports of this tumor in the head and neck, especially in the parotid gland. The purpose of this paper is to describe an EMC located at an unusual site in the parotid gland, and briefly, the literature review with special reference to the clinicopathological features and the treatment approach was discussed.
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http://dx.doi.org/10.4103/ams.ams_145_18DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6933961PMC
January 2020

Learning Regional Attraction for Line Segment Detection.

IEEE Trans Pattern Anal Mach Intell 2019 Dec 9. Epub 2019 Dec 9.

This paper presents regional attraction of line segment maps, and hereby poses the problem of line segment detection (LSD) as a problem of region coloring. Given a line segment map, the proposed regional attraction first establishes the relationship between line segments and regions in the image lattice. Based on this, the line segment map is equivalently transformed to an attraction field map (AFM), which can be remapped to a set of line segments without loss of information. Accordingly, we develop an end-to-end framework to learn attraction field maps for raw input images, followed by a squeeze module to detect line segments. Apart from existing works, the proposed detector properly handles the local ambiguity and does not rely on the accurate identification of edge pixels. Comprehensive experiments on the Wireframe dataset and the YorkUrban dataset demonstrate the superiority of our method. In particular, we achieve an F-measure of 0.831 on the Wireframe dataset, advancing the state-of-the-art performance by 10.3 percent.
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http://dx.doi.org/10.1109/TPAMI.2019.2958642DOI Listing
December 2019

Virtual Surgical Planning for Successful Second-Stage Mandibular Defect Reconstruction Using Vascularized Iliac Crest Bone Flap: A Valid and Reliable Method.

Ann Plast Surg 2020 02;84(2):183-187

Glasgow Dental Hospital and School, Glasgow, Scotland, United Kingdom.

Purpose: Second-stage reconstruction of mandibular defects faces problems of anatomic disorder and bone displacement due to tumor resection. As a newer technique, virtual surgical planning (VSP) may help to increase the accuracy and efficiency of the complicated reconstruction. This study aims to evaluate the application of VSP and splint-guided surgery in second-stage mandibular reconstruction using vascularized iliac crest bone flap.

Methods: Between October 2016 and February 2018, 5 patients (3 men and 2 women) with mandibular defects of duration between 8 months and 8 years underwent VSP-aided secondary reconstruction in the School and Hospital of Stomatology of Wuhan University (Wuhan, China). Virtual surgical planning was performed and serial guiding splints were printed to replicate the design into the actual operation. The linear and 3-dimensional deviations after surgery were analyzed. Patient complications and feedback were recorded during follow up.

Results: All 5 patients underwent successful reconstruction using vascularized iliac crest bone flap. No serious donor sites or recipient site complications were observed after 10- to 28-month follow-up. In comparison with the presurgery designs, the linear deviations in coronal plane were 2.7 ± 0.4 mm (range, -2.2 to 3.9 mm) in measurements from the condylar head to the condylar head and 0.70 ± 0.6 mm (range, -0.1 to 1.7 mm) from the gonial angle to the gonial angle, and that in sagittal plane was 2.4 ± 0.88 mm (range, -3 to 4.4 mm) from the anterior inferior mandibular border to the center point on the condylar head to the condylar head line. The whole 3-dimensional deviation was 1.2 ± 1.7 mm in all patients.

Conclusion: Well-designed splints can assist in precise mandibular reconstruction with high efficiency and accuracy, and thus are a reliable method for complicated second-stage mandibular reconstruction. However, to achieve a better outcome, a satisfactory design is required to adapt the complicated and varied defect.
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http://dx.doi.org/10.1097/SAP.0000000000002102DOI Listing
February 2020

A combined nasolabial and infra-nasal bi-lobe flap design with double transposition for reconstruction of the ipsilateral upper and lower lips associated with the commissure defect.

Biomedicine (Taipei) 2019 Dec 14;9(4):29. Epub 2019 Nov 14.

Department of Oral Maxillofacial Head and Neck Oncology Surgery, School, and Hospital of Stomatology, Wuhan University, Wuhan 430079, China - The State Key Laboratory Breeding Base of Basic Science of Stomatology & Key Laboratory of Oral Biomedicine Ministry of Education, School & Hospital of Stomatology, Wuhan University, Wuhan 430079, China.

Several classical flap variations have been designed to reconstruct lip and commissure defects. Although most of these variations maybe the best option for repairing defects, there is an increasing risk of anatomic distortion and functional disability, mostly in older persons. Herein, we present a combined nasolabial and infra-nasal bi-lobe flap design with double transposition, which was used to concomitantly close the upper and lower lips associated with commissure defects.
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http://dx.doi.org/10.1051/bmdcn/2019090429DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6855192PMC
December 2019

Discovery of IgG4 Anti-Gliadin Autoantibody as a Potential Biomarker of Psoriasis Using an Autoantigen Array.

Proteomics Clin Appl 2020 03 11;14(2):e1800114. Epub 2019 Dec 11.

Department of Biomedical Engineering, University of Houston, Houston, TX, 77204-5060, USA.

Purpose: Psoriasis is a complex immunological skin disease. However, whether humoral autoimmunity is involved in the pathogenesis of psoriasis remains unclear. The aim is to determine if there are autoantibodies associated with disease activity of psoriasis.

Experimental Design: A novel autoantigen array harboring 75 antigens is developed to discover autoantibodies in the serum of psoriasis patients (N = 12) compared to healthy controls (N = 12). Validation studies are performed in a larger cohort of psoriasis patients (N = 73) and healthy controls (N = 75) together with atopic dermatitis as disease controls (N = 10).

Results: The screening results demonstrate that immunoglobulin G4 (IgG4) anti-gliadin autoantibodies are significantly elevated in the serum of psoriasis patients, compared to healthy controls. Receiver operating characteristic (ROC) analysis indicates that IgG4 anti-gliadin autoantibody levels can clearly discriminate psoriasis patients from healthy controls with an AUC of 0.98 (p < 0.001). Also, IgG4 anti-gliadin autoantibody can reflect disease severity with the psoriasis area severity index score in a subpopulation of psoriasis patients.

Conclusions And Clinical Relevance: These results suggest that IgG4 anti-gliadin autoantibody may be a disease marker of psoriasis, and it may be useful in clinical diagnostics and disease monitoring of psoriasis.

Clinical Relevance: This work represents a relatively comprehensive screening of autoantibodies, that is, IgG4 autoantibodies in psoriasis using an in-house autoantigen array. This novel proteomic platform may be useful in clinical screening of IgG type or IgG4 subtype autoantibodies in psoriasis patients for disease monitoring or drug responses. Particularly, IgG4 anti-gliadin autoantibody, as a new potential disease marker of psoriasis, may be useful in clinical diagnostics or prognostics of related immunological disorders.
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http://dx.doi.org/10.1002/prca.201800114DOI Listing
March 2020

LIN28: A cancer stem cell promoter for immunotherapy in head and neck squamous cell carcinoma.

Oral Oncol 2019 11 28;98:92-95. Epub 2019 Sep 28.

The State Key Laboratory Breeding Base of Basic Science of Stomatology (Hubei-MOST) & Key Laboratory of Oral Biomedicine Ministry of Education, School & Hospital of Stomatology, Wuhan University, People's Republic of China. Electronic address:

Lin28, a highly conserved RNA-binding protein, plays an important role in differentiation, metabolism, proliferation, pluripotency, and tumourigenicity. Lin28 overexpression promotes tumour-cell proliferation and metastasis in various human cancers, including head and neck cancer. Multiple studies demonstrate that Lin28 critically contributes to anti-tumour immunity and production of cancer stem cells in head and neck squamous cell carcinoma (HNSCC). Thus, Lin28 has potential application in HNSCC treatment.
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http://dx.doi.org/10.1016/j.oraloncology.2019.09.024DOI Listing
November 2019

Comparison of Complicated and Simple Guiding Templates in Mandibular Reconstruction Using Vascularized Iliac Crest Flap.

Biomed Res Int 2019 26;2019:7496538. Epub 2019 Jun 26.

The State Key Laboratory Breeding Base of Basic Science of Stomatology (Hubei-MOST) & Key Laboratory of Oral Biomedicine Ministry of Education, School & Hospital of Stomatology, Wuhan University, China.

Objective: This study aims to compare the degree of accuracy achieved in mandibular reconstruction between complicated guiding templates (CGT) and simple guiding templates (SGT), to evaluate the necessity to spend more time to design complicated templates prior to surgery.

Methods: The preoperative virtual surgery plan (VSP) was used to simulate the osteotomy and accurate mandibular reconstruction strategy. Then the guiding templates were designed and printed to transfer the VSP into the real operation. Between July 2013 and November 2014, we used the SGT in 13 L-type mandibular defect reconstructions utilising vascularized iliac crest bone (VICB). From March 2015 to March 2018, we used CGT in 14 L-type mandibular defects, also reconstructing with VICB. The indicators of mandibular symmetry, midline deviation, alveolar height loss, bone conjunction gap, and operation time were analyzed and compared between the two groups.

Results: The overall bone graft success rate was 100% (27/27) between all patients. The SGT and CGT groups showed similar symmetry (1.01 ± 0.03 vs. 1.03 ± 0.04, = 0.11) and mandibular midline displacement (1.0 ± 0.7 mm vs. 1.2 ± 0.8 mm, =0.29). The CGT group showed less alveolar height deficiency than the SGT group (3.0 ± 2.4 mm vs. 7.8 ± 6.8 mm, =0.01) and lesser bony conjunction gap between the graft and the mandible (1.6 ± 0.7 mm vs. 2.4 ± 1.2 mm, = 0.02). The average operation time was significantly lower in the CGT group than in the SGT group (340.5 ± 74 min vs. 391.9 ± 41.7 min, = 0.02).

Conclusion: In the simple mandibular reconstruction, the time-consuming CGT did not significantly improve the symmetry and midline displacement compared to SGT, but it demonstrated less reduction (increased preservation) in alveolar height and decreased the size of the bone conjunction gap. And in addition, CGT also reduced the average operation time and simplified intraoperative procedures compared with SGT.
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http://dx.doi.org/10.1155/2019/7496538DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6617867PMC
December 2019

Management of mandibular odontogenic keratocyst through radical resection: Report of 35 cases.

Oncol Lett 2019 Jul 17;18(1):733-741. Epub 2019 May 17.

Department of Oral Maxillofacial Head and Neck Oncology Surgery, School and Hospital of Stomatology, Wuhan University, Wuhan, Hubei 430079, P.R. China.

The present study reported the clinical outcomes of 35 patients with mandibular odontogenic keratocysts (OKCs) following treatment by radical resection and immediate defect reconstruction. Amongst 565 patients with OKCs that were treated between April 2003 and May 2015, 35 patients underwent segmental or marginal mandibulectomy. The use of radical resection was based on clinical and/or radiographic evidence of size, cortical perforation and subsequent soft tissue involvement, and on the history of previous recurrence of the same lesion. Recurrence, justifications of the main major factor for resection, and functional and cosmetic results of the patients following mandibular reconstruction were systematically evaluated. There were 26 OKCs in the mandibular molar-ramus region, eight in the mandibular anterior-premolar region and one in the mandibular molar-ramus and anterior-molar regions. Among the 35 patients, 20 had primary OKCs and 15 had recurrent OKCs. A total of 31 patients underwent segmental mandibulectomy, of which 28 were immediately reconstructed with a vascularized flap, whereas four patients underwent marginal mandibulectomy. The functional and cosmetic outcomes of patients were evaluated as satisfactory. The length of the follow-up period ranged from 2 to 17 years following operation (average, 5.82 years). Recurrence was identified in one patient who had been treated with marginal mandibulectomy. In conclusion, the findings from the present study suggested that radical resection may be recommended for patients with OKCs and locally aggressive features. Immediate mandibular reconstruction with a vascularized flap may be a crucial part of this aggressive treatment method that may reduce OKCs-associated morbidity.
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http://dx.doi.org/10.3892/ol.2019.10367DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6540166PMC
July 2019

Treatment of Multiple Odontogenic Keratocysts Involving Chinese Patients.

J Oral Maxillofac Surg 2019 Oct 8;77(10):2044-2054. Epub 2019 Jun 8.

Associate Professor, Department of Oral Maxillofacial Head and Neck Oncology Surgery; and State Key Laboratory Breeding Base of Basic Science of Stomatology and Key Laboratory of Oral Biomedicine Ministry of Education, School and Hospital of Stomatology, Wuhan University, Wuhan, China. Electronic address:

Purpose: The optimal treatment of odontogenic keratocysts (OKCs) remains a matter of debate in reported studies. The present study aimed to estimate the postoperative recurrence rates of multiple OKCs (MOKCs) in Chinese patients.

Materials And Methods: A retrospective cohort study of histologically confirmed MOKCs treated from 2003 to 2017 using enucleation, marsupialization alone, enucleation and peripheral ostectomy, or marsupialization followed by secondary enucleation was performed. Patients with MOKCs who had undergone follow-up for 12 or more months with panoramic radiographs and radiographs of the chest and skull available from the first visit and had been treated by the same team using the same treatment protocol were included in the study. Patients were excluded if the lesion had been treated previously, they had a solitary OKC, or their medical records were not available for review. The treatment methods, recurrence rate, and interval to recurrence were evaluated. The Kaplan-Meier method was used to estimate the survival rate and median time to recurrence. Univariate analysis was used to identify the risk factors associated with recurrence. Significant differences were determined at an α level of 5%.

Results: The sample included 81 patients with MOKCs; 21 (25.6%) were male and 60 (74.07%) were female. The age range was 7 to 63 years (mean ± standard deviation, 18.4 ± 4). The overall recurrence rate was 26.63%, with an overall recurrence-free interval of 26.85 months. The average length of follow-up was 55.68 months. No association was found between the treatment method used and the risk of recurrence (P = .178). Although the interval to recurrence was not affected by any of the study variables, the average interval to the recurrence of MOKCs involving the maxilla was short compared with that of MOKCs involving the mandible.

Conclusions: The surgical treatment method did not influence the risk of recurrence in patients with MOKCs, and the interval to recurrence was not associated with any of the study variables.
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http://dx.doi.org/10.1016/j.joms.2019.05.022DOI Listing
October 2019

A BODIPY biosensor to detect and drive self-assembly of diphenylalanine.

Chem Commun (Camb) 2019 Jul;55(59):8564-8566

Department of Biomedical Engineering, University of Houston, Houston, Texas 77204, USA.

Diphenylalanine (FF), as the smallest unit and core recognition motif of β-amyloid (Aβ), could self-assemble into nanofibers, which induces an early onset of Alzheimer's disease (AD). Green/near-infrared fluorescent BODIPY probes were designed and synthesized to detect FF-assembly, providing unique insights into the chemical and molecular mechanism of Aβ aggregation and drug development for AD.
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http://dx.doi.org/10.1039/c9cc03810hDOI Listing
July 2019

Elevated oxidized lipids, anti-lipid autoantibodies and oxidized lipid immune complexes in active SLE.

Clin Immunol 2019 08 7;205:43-48. Epub 2019 May 7.

Department of Biomedical Engineering, University of Houston, Houston, TX, USA. Electronic address:

Background: Here, we explore the serum levels of anti-oxidized lipid autoantibodies as well as immune complexes in patients with SLE and determine their correlation with disease.

Methods: Serum levels of oxidized-LDL immune complexes, autoantibodies to dsDNA, ox-LDL, MDA-LDL, 9-HODE, 13-HODE and POVPC were detected by ELISA in 64 SLE patients and 9 healthy controls.

Results: Active SLE patients exhibited increased serum levels of autoantibodies compared to healthy controls, including anti-MDA-LDL-IgG (p = .003), anti-ox-LDL-IgG (p = .004), anti-9-HODE-IgG (p = .001), anti-13-HODE-IgG (p = .0003), anti-POVPC-IgG (p = .001) and ox-LDL-IC (p = .003). Serum anti-ox-LDL-IgG was positively correlated with SLEDAI (r = 0.34; p = .01), and negatively with C3 (r = -0.40; p = .01). Anti-9-HODE-IgG and anti-POVPC-IgG were positively correlated with SLEDAI and negatively with C4.

Conclusions: Active SLE patients exhibit significantly increased serum levels of IgG anti-oxidized-lipid autoantibodies. Coordinated elevation of oxidized lipids, autoantibodies to these lipids, and immune complexes of these lipid-antibody components could potentially serve as pathogenic drivers and serum markers of SLE disease activity.
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http://dx.doi.org/10.1016/j.clim.2019.05.004DOI Listing
August 2019

Identification of Novel Autoantibodies Associated With Psoriatic Arthritis.

Arthritis Rheumatol 2019 06 6;71(6):941-951. Epub 2019 Apr 6.

University of Houston, Houston, Texas.

Objective: The autoimmune etiology in psoriasis remains to be clarified. We therefore undertook this study to identify novel pathogenic autoantigens and autoantibodies in patients with psoriasis, with the aim of shedding light on the molecular and cellular basis of the pathogenesis of psoriasis and psoriatic arthritis (PsA).

Methods: In this study, we developed an autoantigen array system that harbors a variety of antigens, including typical autoantigens in rheumatic diseases as well as skin antigens, inflammatory mediators, and putative autoantigens in psoriasis. Serum samples from patients with psoriasis (n = 73) were used to interrogate the antigens on the array. In addition, enzyme-linked immunosorbent assays of individual autoantibodies were used in validation studies.

Results: Levels of several autoantibodies were found to be elevated in the serum of patients with psoriasis compared to healthy controls; in particular, IgG autoantibodies against 2 novel antigens, LL-37 and ADAMTS-L5, were significantly increased in patients with psoriasis. Importantly, serum levels of IgG autoantibodies against LL-37 and ADAMTS-L5 were correlated with the Psoriasis Area and Severity Index, and reflected disease progression in longitudinally collected serum samples from patients with psoriasis. Importantly, both anti-ADAMTS-L5 and anti-LL-37 autoantibody levels were also significantly elevated in psoriasis patients with PsA compared to those without PsA, suggesting that these molecules may be involved in the pathogenesis of PsA.

Conclusion: Our findings indicate that these identified autoantibodies may be useful biomarkers and may serve as therapeutic targets in psoriasis and PsA.
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http://dx.doi.org/10.1002/art.40830DOI Listing
June 2019

Insulin-Like Growth Factor Binding Proteins in Autoimmune Diseases.

Front Endocrinol (Lausanne) 2018 30;9:499. Epub 2018 Aug 30.

Department of Biomedical Engineering, University of Houston, Houston, TX, United States.

Insulin-like growth factor binding proteins (IGFBPs) are a family of proteins binding to Insulin-like growth factors (IGFs), generally including IGFBP1, IGFBP2, IGFBP3, IGFBP4, IGFBP5, and IGFBP6. The biological functions of IGFBPs can be classified as IGFs-dependent actions and IGFs-independent effects. In this review, we will discuss the structure and function of various IGFBPs, particularly IGFBPs as potential emerging biomarkers and therapeutic targets in various autoimmune diseases, and the possible mechanisms by which IGFBPs act on the pathogenesis of autoimmune diseases.
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http://dx.doi.org/10.3389/fendo.2018.00499DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6125368PMC
August 2018

SERS substrate based on the flexible hybrid of polydimethylsiloxane and silver colloid decorated with silver nanoparticles.

Opt Express 2018 Aug;26(17):21784-21796

Various flexible SERS sensors have attracted widespread concern in performing the direct identification of the analytes adsorbed on arbitrary surfaces. Here, a sample method was proposed to integrate plasmonic nanoparticles into polydimethylsiloxane (PDMS) to fabricate flexible substrate for the decoration of silver nanoparticles (AgNPs). The flexible SERS sensor based on AgNPs/AgNPs-PDMS offers highly sensitive Raman detection with enhancement factor up to 8.3 × 10, which can be attributed to the integrative effects from both the increase of the light absorption of the embedded AgNPs in PDMS substrate and the EM enhancement from the adjacent top-top, bottom-bottom and top-bottom AgNPs. After undergoing the cyclic mechanical deformation, the SERS substrate still maintains high mechanical stability and stable SERS signals. However, upon stretching the flexible substrate, there was an amusing phenomenon that SERS signals can be highly increased, which results from that the reduction of lateral nanogaps between top and bottom of the PDMS boundary strengthens the trigger of the plasmon coupling as demonstrated by the simulated result. This result reveals that the tuning and the coupling of the electromagnetic fields can be effectively controlled by the macroscopic mechanical solicitation. That will have an important significance for practical applications in strain-dependent sensors and detectors.
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http://dx.doi.org/10.1364/OE.26.021784DOI Listing
August 2018

Relationship between serum bilirubin levels s and the progression of renal function in patients with chronic kidney disease and hyperuricemia.

Clin Chim Acta 2018 Nov 1;486:156-161. Epub 2018 Aug 1.

Department of Nephrology & Rheumatology, Shanghai Tenth People's Hospital, Tongji University School of Medicine, 301, Middle Yanchang Road, Shanghai 200072, China. Electronic address:

It is known that inflammation and oxidative stress have strong influences on chronic kidney disease (CKD). As an antioxidant, bilirubin is currently under extensive scrutiny. However, there are disagreements with regard to the oxidative and antioxidative roles of serum uric acid (SUA). This study aimed to investigate the relationship between serum bilirubin and the progression of renal function in CKD patients with hyperuricemia (HUA). This retrospective longitudinal study included 427 CKD patients. The endpoint was renal replacement therapy or death. Patients were divided into the following two groups according to the SUA level: HUA group (SUA ≥ 420 μmol/L for men; SUA ≥ 360 μmol/L for women) and normal uric acid level (NUA) group. A Cox proportional hazards model was used to evaluate the risk factors for renal outcomes in the two patient groups. The median follow-up time was 36 months. In the Cox regression analysis, the risk of renal outcomes in patients with serum indirect bilirubin (IBIL) levels >4.55 μmol/L was 0.15 times the risk in patients with serum IBIL levels ≤4.55 μmol/L (hazard ratio = 0.15, p = .013). Our findings suggest that a high serum IBIL level might be a protective factor for the progression of renal function in CKD patients with HUA.
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http://dx.doi.org/10.1016/j.cca.2018.07.045DOI Listing
November 2018

Autoantibodies as Potential Biomarkers in Breast Cancer.

Biosensors (Basel) 2018 Jul 13;8(3). Epub 2018 Jul 13.

Department of Biomedical Engineering, University of Houston, 3517 Cullen BLVD, SERC 2008, Houston, TX 77204, USA.

Breast cancer is a major cause of mortality in women; however, technologies for early stage screening and diagnosis (e.g., mammography and other imaging technologies) are not optimal for the accurate detection of cancer. This creates demand for a more effective diagnostic means to replace or be complementary to existing technologies for early discovery of breast cancer. Cancer neoantigens could reflect tumorigenesis, but they are hardly detectable at the early stage. Autoantibodies, however, are biologically amplified and hence may be measurable early on, making them promising biomarkers to discriminate breast cancer from healthy tissue accurately. In this review, we summarized the recent findings of breast cancer specific antigens and autoantibodies, which may be useful in early detection, disease stratification, and monitoring of treatment responses of breast cancer.
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http://dx.doi.org/10.3390/bios8030067DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6163859PMC
July 2018

Serum vascular endothelial growth factor receptor 3 as a potential biomarker in psoriasis.

Exp Dermatol 2018 09 29;27(9):1053-1057. Epub 2018 Jul 29.

Department of Biomedical Engineering, University of Houston, Houston, Texas.

To discover novel biomarkers of psoriasis, a target-specific antibody array screening of serum samples from psoriasis patients was initially performed. The results revealed that vascular endothelial growth factor receptor 3 (VEGFR-3) was significantly elevated in the sera of psoriasis patients, compared to healthy controls. Next, ELISA validation studies in a larger cohort of psoriasis patients (N = 73) were conducted, which confirmed that serum VEGFR-3 was indeed significantly increased in patients with psoriasis compared to healthy controls (P < 0.001). Furthermore, receiver operating characteristic curve analysis demonstrated that serum VEGFR-3 exhibited potential in distinguishing healthy controls from psoriasis patients: area under the curve = 0.85, P < 0.001. In addition, serum levels of VEGFR-3 were correlated with Psoriasis Area Severity Index scores (R = 0.32, P = 0.008) in psoriasis patients. Interestingly, serum VEGFR-3 levels were significantly elevated in psoriatic arthritis compared to non-psoriatic arthritis (P = 0.026). A pilot longitudinal study demonstrated that serum levels of VEGFR-3 could reflect disease progression in psoriasis. Collectively, serum VEGFR-3 may have a clinical value in monitoring disease activity of psoriasis.
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http://dx.doi.org/10.1111/exd.13727DOI Listing
September 2018

Proteomic approaches for novel systemic lupus erythematosus (SLE) drug discovery.

Authors:
Yaxi Li Tianfu Wu

Expert Opin Drug Discov 2018 08 4;13(8):765-777. Epub 2018 Jun 4.

a Department of Biomedical Engineering , University of Houston , Houston , TX , USA.

Introduction: Systemic lupus erythematosus (SLE) is a complex autoimmune disease with a high risk of morbidity and mortality; however, there is no cure and the current medications are far from optimal in addressing efficacy and safety concerns. Over the past decade, various emerging technologies have been used in the search for novel drug targets of SLE which have resulted in numerous promising data. However, the systematic review and careful digestion of this information have been lacking. Areas covered: In this review, the authors summarize promising biomarkers and drug targets which have been identified via various multiplexing and high-throughput proteomic strategies. The authors also introduce emerging technologies which are hopeful to be used for the discovery of novel biomarkers and therapeutic targets of SLE in the near future. Expert opinion: Emerging proteomic technologies and genome-wide association studies (GWAS) have been the new driving forces in the discovery of novel biomarkers and promising therapeutic targets of SLE. Careful validation of these potential targets in lupus mouse models and clinical trials are urgently needed so that the next generation of target-specific medications can be developed for SLE patients.
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http://dx.doi.org/10.1080/17460441.2018.1480718DOI Listing
August 2018

Three-Dimensional Printed Plate-Guided I Brachytherapy for Malignant Parotid Tumors.

J Oral Maxillofac Surg 2018 10 10;76(10):2113-2121. Epub 2018 May 10.

Associate Professor, Department of Oral and Maxillofacial Surgery and State Key Laboratory Breeding Base of Basic Science of Stomatology and Key Laboratory of Oral Biomedicine Ministry of Education, School and Hospital of Stomatology, Wuhan University, Wuhan, China. Electronic address:

Purpose: The treatment of malignant parotid tumors with I brachytherapy is rarely reported. This study evaluated the efficacy and dose and response of I brachytherapy in patients with malignant tumors.

Materials And Methods: From July 2014 through August 2017, 39 patients with malignant parotid tumors were treated with I brachytherapy. Thirty-five patients were treated with conservative surgical resection before brachytherapy. Four patients were treated with brachytherapy alone. Clinical outcomes and side effects were evaluated. Clinical factors were investigated to determine correlations with local control (LC) and side effects.

Results: Mean follow-up was 25 months (range, 7 to 47 months). The LC rate was 87.2% and the overall survival rate was 97.4%. High tumor grade and large tumor showed a propensity for local recurrence. Acute skin toxicity occurred in 87.2% of patients and grade 3 and 4 radioepidermitis was found in 20.5% of patients. In total, 89.7% of patients with facial nerve dysfunction recovered within 12 months.

Conclusions: I brachytherapy was a feasible treatment option for patients with malignant parotid tumors. Although side effects were minimal, strict follow-up was necessary for patients treated with a high dose.
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http://dx.doi.org/10.1016/j.joms.2018.05.001DOI Listing
October 2018

Kissing Nevus of the Penis.

J Coll Physicians Surg Pak 2018 Mar;28(3):S19-S20

Center for Clinical Studies, Houston 77004, USA.

Kissing nevus is a very rare congenital melanocytic nevus. Here, we describe one case of kissing nevus on the penis. A 15-year boy presented with asymptomatic black to dark brown color patches on his penis. Histopathological findings showed that there were nests and cords of nevus cells in upper dermis. No significant cytologic atypia and mitoses were noted. Immunohistochemical stains revealed a partial positive for HMB-45 only in upper dermis and a stronger positivity for S-100 in almost all nevus cells. We diagnosed the lesion as kissing nevus of penis. The patient and his parents refused further treatment, and the patient is being followed in our clinic.
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http://dx.doi.org/10.29271/jcpsp.2018.03.S19DOI Listing
March 2018

Protein Arrays III: Reverse-Phase Protein Arrays.

Methods Mol Biol 2017 ;1654:279-289

Department of Biomedical Engineering, University of Houston, 3605 Cullen Blvd, Houston, TX, 77204-5060, USA.

The reverse-phase protein array (RPPA) is to use highly specific antibodies to interrogate pan or posttranslationally modified protein targets, such as phosphorylated proteins, particularly the proteins involved in cell signaling pathways. In this protocol we will cover the preparation of cell (or tissue) lysates, sample printing, antibody validation, antibody interrogation, signal amplification steps, imaging and data analysis. In this protocol, colorimetric catalyzed signal amplification (CSA) chemistry, fluorescence and near-infrared (NIR) based detection methods will be described.
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http://dx.doi.org/10.1007/978-1-4939-7231-9_21DOI Listing
June 2018

Protein Arrays II: Antigen Arrays.

Methods Mol Biol 2017 ;1654:271-277

Department of Biomedical Engineering, University of Houston, 3605 Cullen Blvd, Houston, TX, 77204-5060, USA.

Antigen arrays are fabricated using various antigens such as DNA, histones, synthetic peptides, recombinant proteins, or cell extracts to detect autoantibodies in autoimmune diseases, alloantibodies in transplantation, drug-induced antibodies or cancer-induced antibodies in blood or cell culture supernatant. In this protocol, we will provide a step-by-step executable procedure to perform antigen arrays, including antigen preparation and printing, blocking, sample loading, array detection, imaging, and data analysis.
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http://dx.doi.org/10.1007/978-1-4939-7231-9_20DOI Listing
June 2018

Protein Arrays I: Antibody Arrays.

Methods Mol Biol 2017 ;1654:261-269

Department of Biomedical Engineering, University of Houston, 3605 Cullen Blvd, Houston, TX, 77204-5060, USA.

Antibody arrays represent one of the very early protein array systems where antibodies are used to capture and detect target proteins in a high-throughput platform. The development of high-quality antibodies, nanomaterial-based novel detection probes, as well as innovative imaging technologies and computational tools has tremendously improved the sensitivity, specificity, and robustness of antibody arrays during the past decade. In this protocol we will incorporate the most updated innovations and developments of antibody arrays into the step-by-step experimental procedures. This includes antibody printing, sample preparation, array detection, as well as imaging and data analysis. Antibody array could be used for cytokine profiling or mapping of phosphorylation, glycosylation, or other post-translational modifications of target proteins.
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http://dx.doi.org/10.1007/978-1-4939-7231-9_19DOI Listing
June 2018

Development and validation of an impedance biosensor for point-of-care detection of vascular cell adhesion molecule-1 toward lupus diagnostics.

Future Sci OA 2017 08 7;3(3):FSO224. Epub 2017 Jul 7.

Department of Bioengineering, University of Texas at Dallas, Richardson, TX 75080, USA.

Aim: Systemic lupus erythematosus is an autoimmune disease that requires chronic monitoring. In this study, we demonstrate a proof-of-concept study of a highly attractive noninvasive strategy for monitoring systemic lupus erythematosus through biomarker quantification.

Results: This sensor technology requires 50 μl of urine to detect and quantify vascular cell adhesion molecule-1 in 15 min. The sensor used nonfaradaic detection to demonstrate performance with and without detection antibody. Binding of immunoassay and target biomarkers were quantified with an impedance electrical immunoassay and correlated with an equivalent circuit.

Conclusion: The novel sensor technology demonstrates detection in the range of 8 fg/ml to 800 pg/ml and comparative analysis with ELISA platforms was performed for 12 patient urine samples.
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http://dx.doi.org/10.4155/fsoa-2017-0047DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC5583674PMC
August 2017

A Nanoparticle-Decorated Biomolecule-Responsive Polymer Enables Robust Signaling Cascade for Biosensing.

Adv Mater 2017 Aug 14;29(31). Epub 2017 Jun 14.

Department of Biomedical Engineering, University of Houston, Houston, TX, 77204, USA.

To meet the increasing demands for ultrasensitivity in monitoring trace amounts of low-abundance early biomarkers or environmental toxins, the development of a robust sensing system is urgently needed. Here, a novel signal cascade strategy is reported via an ultrasensitive polymeric sensing system (UPSS) composed of gold nanoparticle (gNP)-decorated polymer, which enables gNP aggregation in polymeric network and electrical conductance change upon specific aptamer-based biomolecular recognition. Ultralow concentrations of thrombin (10 m) as well as a low molecular weight anatoxin (165 Da, 10 m) are detected selectively and reproducibly. The biomolecular recognition induced polymeric network shrinkage responses as well as dose-dependent responses of the UPSS are validated using in situ real-time atomic-force microscopy, representing the first instance of real-time detection of biomolecular binding-induced polymer shrinkage in soft matter. Furthermore, in situ real-time confocal laser scanning microscopy imaging reveals the dynamic process of gNP aggregation responses upon biomolecular binding.
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http://dx.doi.org/10.1002/adma.201702090DOI Listing
August 2017