Publications by authors named "Yi-Ping Wang"

303 Publications

COVID-19 or treatment associated immunosuppression may trigger hepatitis B virus reactivation: A case report.

World J Clin Cases 2021 Jul;9(19):5266-5269

Department of Infectious Diseases, The Affiliated People's Hospital of Ningbo University, Ningbo 315040, Zhejiang Province, China.

Background: Since the initial recognition of coronavirus disease 2019 (COVID-19) in Wuhan, this infectious disease has spread to most areas of the world. The pathogenesis of COVID-19 is yet unclear. Hepatitis B virus (HBV) reactivation occurring in COVID-19 patients has not yet been reported.

Case Summary: A 45-year-old hepatitis B man with long-term use of adefovir dipivoxil and entecavir for antiviral therapy had HBV reactivation after being treated with methylprednisolone for COVID-19 for 6 d.

Conclusion: COVID-19 or treatment associated immunosuppression may trigger HBV reactivation.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.12998/wjcc.v9.i19.5266DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8283611PMC
July 2021

ENO1 Promotes Lung Cancer Metastasis via HGFR and WNT Signaling-Driven Epithelial-to-Mesenchymal Transition.

Cancer Res 2021 Aug 18;81(15):4094-4109. Epub 2021 Jun 18.

Institute of Cellular and Organismic Biology, Academia Sinica, Taipei, Taiwan.

ENO1 (α-enolase) expression is significantly correlated with reduced survival and poor prognosis in many cancer types, including lung cancer. However, the function of ENO1 in carcinogenesis remains elusive. In this study, we found that high expression of ENO1 is present in metastatic lung cancer cell lines and malignant tumors and is associated with poor overall survival of patients with lung cancer. Knockdown of ENO1 decreased cancer cell proliferation and invasiveness, whereas overexpression of ENO1 enhanced these processes. Moreover, ENO1 expression promoted tumor growth in orthotopic models and enhanced lung tumor metastasis in tail-vein injection models. These effects were mediated by upregulation of mesenchymal markers N-cadherin and vimentin and the epithelial-to-mesenchymal transition regulator SLUG, along with concurrent downregulation of E-cadherin. Mechanistically, ENO1 interacted with hepatocyte growth factor receptor (HGFR) and activated HGFR and Wnt signaling via increased phosphorylation of HGFR and the Wnt coreceptor LRP5/6. Activation of these signaling axes decreased GSK3β activity via Src-PI3K-AKT signaling and inactivation of the β-catenin destruction complex to ultimately upregulate SLUG and β-catenin. In addition, we generated a chimeric anti-ENO1 mAb (chENO1-22) that can decrease cancer cell proliferation and invasion. chENO1-22 attenuated cancer cell invasion by inhibiting ENO1-mediated GSK3β inactivation to promote SLUG protein ubiquitination and degradation. Moreover, chENO1-22 prevented lung tumor metastasis and prolonged survival in animal models. Taken together, these findings illuminate the molecular mechanisms underlying the function of ENO1 in lung cancer metastasis and support the therapeutic potential of a novel antibody targeting ENO1 for treating lung cancer. SIGNIFICANCE: This study shows that ENO1 promotes lung cancer metastasis via HGFR and WNT signaling and introduces a novel anti-ENO1 antibody for potential therapeutic use in lung cancer.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1158/0008-5472.CAN-20-3543DOI Listing
August 2021

Disrupting hierarchical control of nitrogen fixation enables carbon-dependent regulation of ammonia excretion in soil diazotrophs.

PLoS Genet 2021 Jun 10;17(6):e1009617. Epub 2021 Jun 10.

Department of Molecular Microbiology, John Innes Centre, Norwich, United Kingdom.

The energetic requirements for biological nitrogen fixation necessitate stringent regulation of this process in response to diverse environmental constraints. To ensure that the nitrogen fixation machinery is expressed only under appropriate physiological conditions, the dedicated NifL-NifA regulatory system, prevalent in Proteobacteria, plays a crucial role in integrating signals of the oxygen, carbon and nitrogen status to control transcription of nitrogen fixation (nif) genes. Greater understanding of the intricate molecular mechanisms driving transcriptional control of nif genes may provide a blueprint for engineering diazotrophs that associate with cereals. In this study, we investigated the properties of a single amino acid substitution in NifA, (NifA-E356K) which disrupts the hierarchy of nif regulation in response to carbon and nitrogen status in Azotobacter vinelandii. The NifA-E356K substitution enabled overexpression of nitrogenase in the presence of excess fixed nitrogen and release of ammonia outside the cell. However, both of these properties were conditional upon the nature of the carbon source. Our studies reveal that the uncoupling of nitrogen fixation from its assimilation is likely to result from feedback regulation of glutamine synthetase, allowing surplus fixed nitrogen to be excreted. Reciprocal substitutions in NifA from other Proteobacteria yielded similar properties to the A. vinelandii counterpart, suggesting that this variant protein may facilitate engineering of carbon source-dependent ammonia excretion amongst diverse members of this family.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1371/journal.pgen.1009617DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8219145PMC
June 2021

FoxP3CD4, IFN-γCD4, and IFN-γCD8 cell levels in erosive and non-erosive types of oral lichen planus patients.

J Dent Sci 2021 Mar 27;16(2):751-756. Epub 2021 Jan 27.

Department of Dentistry, National Taiwan University Hospital, College of Medicine, National Taiwan University, Taipei, Taiwan.

Background/purpose: Oral lichen planus (OLP) is a localized autoimmune oral mucosal disease. This study evaluated whether different types of OLP patients including erosive OLP (EOLP), major EOLP, minor EOLP, and non-erosive OLP (NEOLP) patients had significantly higher percentages of FoxP3CD4 or IFN-γCD4 cells in total CD4 cells, and of IFN-γCD8 cells in total CD8 cells than healthy control subjects and whether the patient's age had significant influences on these cell percentages in OLP patients.

Materials And Methods: Flow cytometry was used to count the FoxP3CD4, IFN-γCD4, or IFN-γCD8 cell levels in 183 OLP patients (67 major EOLP, 81 minor EOLP, and 35 NEOLP patients) and 20 healthy control subjects.

Results: Major EOLP patients had a significantly higher FoxP3CD4 cell percentage than health control subjects ( = 0.049) or minor EOLP patients ( = 0.008). Major EOLP patients had a significantly higher IFN-γCD4 or IFN-γCD8 cell percentage than healthy control subjects, NEOLP patients, or minor EOLP patients (all -values < 0.01). In addition, both 61-80 year and 41-60 year OLP patients had significantly higher IFN-γCD8 cell percentages than healthy control subjects or 20-40 year OLP patients (all -values < 0.005).

Conclusion: Major EOLP patients tend to have significantly higher percentages of FoxP3CD4, IFN-γCD4, and IFN-γCD8 cells than healthy control subjects, NEOLP patients or minor EOLP patients, suggesting that FoxP3CD4 Treg cells are increased to modulate OLP disease activity. Increased number of IFN-γ-producing activated T cell may be involved in oral epithelial cell destruction in OLP patients.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1016/j.jds.2021.01.005DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8025218PMC
March 2021

Malic enzyme 2 connects the Krebs cycle intermediate fumarate to mitochondrial biogenesis.

Cell Metab 2021 May 25;33(5):1027-1041.e8. Epub 2021 Mar 25.

Department of Stem Cell and Regenerative Biology, Harvard University, Cambridge, MA 02138, USA; Harvard Stem Cell Institute, Cambridge, MA 02138, USA; Center for Regenerative Medicine, Massachusetts General Hospital, Boston, MA 02114, USA. Electronic address:

Mitochondria have an independent genome (mtDNA) and protein synthesis machinery that coordinately activate for mitochondrial generation. Here, we report that the Krebs cycle intermediate fumarate links metabolism to mitobiogenesis through binding to malic enzyme 2 (ME2). Mechanistically, fumarate binds ME2 with two complementary consequences. First, promoting the formation of ME2 dimers, which activate deoxyuridine 5'-triphosphate nucleotidohydrolase (DUT). DUT fosters thymidine generation and an increase of mtDNA. Second, fumarate-induced ME2 dimers abrogate ME2 monomer binding to mitochondrial ribosome protein L45, freeing it for mitoribosome assembly and mtDNA-encoded protein production. Methylation of the ME2-fumarate binding site by protein arginine methyltransferase-1 inhibits fumarate signaling to constrain mitobiogenesis. Notably, acute myeloid leukemia is highly dependent on mitochondrial function and is sensitive to targeting of the fumarate-ME2 axis. Therefore, mitobiogenesis can be manipulated in normal and malignant cells through ME2, an unanticipated governor of mitochondrial biomass production that senses nutrient availability through fumarate.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1016/j.cmet.2021.03.003DOI Listing
May 2021

Genetic Susceptibility and Protein Expression of Extracellular Matrix Turnover-Related Genes in Oral Submucous Fibrosis.

Int J Mol Sci 2020 Oct 30;21(21). Epub 2020 Oct 30.

School of Dentistry, National Taiwan University Medical College, Taipei 100, Taiwan.

Betel quid (BQ) chewing increased the risk of oral cancer and oral submucous fibrosis (OSMF), an oral premalignant disorder (OPMD) with malignant transformation potential. BQ components such as areca nut (AN), trauma by coarse AN fiber, catechin, copper, alkaloids, stimulated reactive oxygen species (ROS), inflammation and cytotoxicity are suggested to be the contributing factors. They may induce tissue inflammation, proliferation of fibroblasts and collagen deposition, myofibroblast differentiation and contraction, collagen cross-links and inhibit collagen phagocytosis, finally leading to the development of OSMF and oral cancer. These events are mediated by BQ components-induced changes of extracellular matrix (ECM) turnover via regulation of TGF-β1, plasminogen activator inhibitor-1 (PAI-1), cystatin, lysyl oxidase (LOX) and tissue inhibitors of metalloproteinases (TIMPs) and metalloproteinases (MMPs). Genetic susceptibility is also involved in these disease processes. Further understanding the molecular mechanisms of BQ-induced OSMF and oral cancer can be helpful for future disease prevention and treatment.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.3390/ijms21218104DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7663238PMC
October 2020

Rh-Catalyzed Decarbonylative Cross-Coupling between o-Carboranes and Twisted Amides: A Regioselective, Additive-Free, and Concise Late-Stage Carboranylation.

Chemistry 2021 Feb 12;27(8):2699-2706. Epub 2021 Jan 12.

State Key Laboratory of Coordination Chemistry, Jiangsu Key, Laboratory of Advanced Organic Materials, School of Chemistry and Chemical Engineering, Nanjing University, Nanjing, 210023, P. R. China.

The convenient cross-coupling of sp or sp carbons with a specific boron vertex on carborane cage represents significant synthetic values and insurmountable challenges. In this work, we report an Rh-catalyzed reaction between o-carborane and N-acyl-glutarimides to construct various B -C bonds. Under the optimized condition, the removable imine directing group (DG) leads to B(3)- or B(3,6)-C couplings, while the pyridyl DG leads to B(3,5)-Ar coupling. In particular, an unexpected rearrangement of amide reagent is observed in pyridyl directed B(4)-C(sp ) formation. This scalable protocol has many advantages, including easy access, the use of cheap and widely available coupling agents, no requirement of an external ligand, base or oxidant, high efficiency, and a broad substrate scope. Leveraging the Rh dimer and twisted amides, this method enables straightforward access to diversely substituted and therapeutically important carborane derivatives at boron site, and provides a highly valuable vista for carborane-based drug screening.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1002/chem.202003634DOI Listing
February 2021

Anemia, hematinic deficiencies, and hyperhomocysteinemia in gastric parietal cell antibody-positive and -negative burning mouth syndrome patients.

J Formos Med Assoc 2021 Feb 2;120(2):819-826. Epub 2020 Sep 2.

Graduate Institute of Clinical Dentistry, School of Dentistry, National Taiwan University, Taipei, Taiwan; Department of Dentistry, National Taiwan University Hospital, College of Medicine, National Taiwan University, Taipei, Taiwan. Electronic address:

Background/purpose: Our previous study found the serum gastric parietal cell antibody (GPCA) positivity in 12.3% of burning mouth syndrome (BMS) patients. This study assessed whether GPCA-positive BMS (GPCABMS) patients had significantly higher frequencies of macrocytosis, anemia, hematinic deficiencies, and hyperhomocysteinemia than healthy control subjects or GPCA-negative BMS (GPCABMS) patients.

Methods: The mean corpuscular volume, blood hemoglobin (Hb), and serum iron, vitamin B12, folic acid, homocysteine, and GPCA levels were measured and compared between any two of three groups of 109 GPCABMS patients, 775 GPCABMS patients, and 442 healthy control subjects.

Results: We found that 109 GPCABMS patients had significantly higher frequencies of macrocytosis, blood Hb and serum iron and vitamin B12 deficiencies, and hyperhomocysteinemia than 442 healthy control subjects (all P-values < 0.001) and significantly higher frequencies of macrocytosis, blood Hb and serum vitamin B12 deficiencies, and hyperhomocysteinemia than 775 GPCABMS patients (all P-values < 0.01). Moreover, 775 GPCABMS patients had significantly higher frequencies of macrocytosis, blood Hb and serum iron, vitamin B12, and folic acid deficiencies, and hyperhomocysteinemia than 442 healthy control subjects (all P-values < 0.005). Pernicious anemia (45.5%) and normocytic anemia (24.2%) were the two most common types of anemia in 33 anemic GPCABMS patients. Moreover, normocytic anemia (61.3%), thalassemia trait-induced anemia (15.5%), and iron deficiency anemia (14.1%) were the three most common types of anemia in 142 anemic GPCABMS patients.

Conclusion: GPCABMS patients have significantly higher frequencies of macrocytosis, blood Hb and serum vitamin B12 deficiencies, and hyperhomocysteinemia than healthy control subjects or GPCABMS patients.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1016/j.jfma.2020.08.032DOI Listing
February 2021

Gastric parietal cell and thyroid autoantibodies in patients with burning mouth syndrome.

J Formos Med Assoc 2020 Dec 1;119(12):1758-1763. Epub 2020 Sep 1.

Graduate Institute of Clinical Dentistry, School of Dentistry, National Taiwan University, Taipei, Taiwan; Department of Dentistry, National Taiwan University Hospital, College of Medicine, National Taiwan University, Taipei, Taiwan. Electronic address:

Background/purpose: Gastric parietal cell antibody (GPCA), thyroglobulin antibody (TGA), and thyroid microsomal antibody (TMA) are organ-specific autoantibodies. This study mainly assessed the frequencies of serum GPCA, TGA, and TMA positivities in burning mouth syndrome (BMS) patients.

Methods: Serum GPCA, TGA, and TMA levels were measured in 884 BMS patients and in 442 age- and sex-matched healthy control subjects.

Results: We found that 12.3%, 21.6%, and 22.7% of 884 BMS patients and 1.8%, 2.3%, and 2.9% of 442 healthy control subjects had the serum GPCA, TGA, and TMA positivities, respectively. BMS patients had significantly higher frequencies of GPCA, TGA, and TMA positivities than healthy control subjects (all P-values < 0.001). We also found that 20 (2.3%), 130 (14.7%), and 181 (20.5%) BMS patients and 3 (0.7%), 8 (1.8%), and 6 (1.4%) healthy control subjects had the presence of three (GPCA + TGA + TMA), two (GPCA + TGA, GPCA + TMA, or TGA + TMA), or one (GPCA only, TGA only, or TMA only) organ-specific autoantibody in their sera, respectively. Of 255 TGA/TMA-positive BMS patients whose serum thyroid-stimulating hormone (TSH) levels were measured, 87.8%, 5.1%, and 7.1% of these TGA/TMA-positive BMS patients had normal, lower, and higher serum TSH levels, respectively.

Conclusion: Approximately 37.5% of 884 BMS patients have serum GPCA/TGA/TMA positivity. Moreover, 12.3%, 21.6%, and 22.7% of 884 BMS patients have the serum GPCA, TGA, and TMA positivities, respectively. Only 5.1% and 7.1% of TGA/TMA-positive BMS patients have hyperthyroidism and hypothyroidism, respectively. It needs further studies to know whether GPCA-positive BMS patients may finally become as having autoimmune atrophic gastritis.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1016/j.jfma.2020.08.035DOI Listing
December 2020

Metabolite sensing and signaling in cancer.

J Biol Chem 2020 08 7;295(33):11938-11946. Epub 2020 Jul 7.

Fudan University Shanghai Cancer Center and Institutes of Biomedical Sciences, Cancer Institutes, Key Laboratory of Breast Cancer in Shanghai, Shanghai Key Laboratory of Medical Epigenetics, and Shanghai Medical College, Fudan University, Shanghai, China

Metabolites are not only substrates in metabolic reactions, but also signaling molecules controlling a wide range of cellular processes. Discovery of the oncometabolite 2-hydroxyglutarate provides an important link between metabolic dysfunction and cancer, unveiling the signaling function of metabolites in regulating epigenetic and epitranscriptomic modifications, genome integrity, and signal transduction. It is now known that cancer cells remodel their metabolic network to support biogenesis, caused by or resulting in the dysregulation of various metabolites. Cancer cells can sense alterations in metabolic intermediates to better coordinate multiple biological processes and enhance cell metabolism. Recent studies have demonstrated that metabolite signaling is involved in the regulation of malignant transformation, cell proliferation, epithelial-to-mesenchymal transition, differentiation blockade, and cancer stemness. Additionally, intercellular metabolite signaling modulates inflammatory response and immunosurveillance in the tumor microenvironment. Here, we review recent advances in cancer-associated metabolite signaling. An in depth understanding of metabolite signaling will provide new opportunities for the development of therapeutic interventions that target cancer.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1074/jbc.REV119.007624DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7450124PMC
August 2020

Using synthetic biology to overcome barriers to stable expression of nitrogenase in eukaryotic organelles.

Proc Natl Acad Sci U S A 2020 07 29;117(28):16537-16545. Epub 2020 Jun 29.

State Key Laboratory of Protein and Plant Gene Research, School of Life Sciences & School of Advanced Agricultural Sciences, Peking University, 100871 Beijing, China;

Engineering biological nitrogen fixation in eukaryotic cells by direct introduction of genes requires elegant synthetic biology approaches to ensure that components required for the biosynthesis of active nitrogenase are stable and expressed in the appropriate stoichiometry. Previously, the NifD subunits of nitrogenase MoFe protein from and were found to be unstable in yeast and plant mitochondria, respectively, presenting a bottleneck to the assembly of active MoFe protein in eukaryotic cells. In this study, we have delineated the region and subsequently a key residue, NifD-R98, from that confers susceptibility to protease-mediated degradation in mitochondria. The effect observed is pervasive, as R98 is conserved among all NifD proteins analyzed. NifD proteins from four representative diazotrophs, but not their R98 variants, were observed to be unstable in yeast mitochondria. Furthermore, by reconstituting mitochondrial-processing peptidases (MPPs) from yeast, , , and in , we demonstrated that MPPs are responsible for cleavage of NifD. These results indicate a pervasive effect on the stability of NifD proteins in mitochondria resulting from cleavage by MPPs. NifD-R98 variants that retained high levels of nitrogenase activity were obtained, with the potential to stably target active MoFe protein to mitochondria. This reconstitution approach could help preevaluate the stability of Nif proteins for plant expression and paves the way for engineering active nitrogenase in plant organelles.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1073/pnas.2002307117DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7368281PMC
July 2020

Acetylation promotes BCAT2 degradation to suppress BCAA catabolism and pancreatic cancer growth.

Signal Transduct Target Ther 2020 05 29;5(1):70. Epub 2020 May 29.

Department of Biochemistry and Molecular Biology, School of Basic Medical Sciences, Shanghai Medical College, Fudan University, 131 Dong'an Road, Shanghai, 200032, China.

Pancreatic ductal adenocarcinoma (PDAC) is well-known for inefficient early diagnosis, with most patients diagnosed at advanced stages. Increasing evidence indicates that elevated plasma levels of branched-chain amino acids (BCAAs) are associated with an increased risk of pancreatic cancer. Branched-chain amino acid transaminase 2 (BCAT2) is an important enzyme in BCAA catabolism that reversibly catalyzes the initial step of BCAA degradation to branched-chain acyl-CoA. Here, we show that BCAT2 is acetylated at lysine 44 (K44), an evolutionarily conserved residue. BCAT2 acetylation leads to its degradation through the ubiquitin-proteasome pathway and is stimulated in response to BCAA deprivation. cAMP-responsive element-binding (CREB)-binding protein (CBP) and SIRT4 are the acetyltransferase and deacetylase for BCAT2, respectively. CBP and SIRT4 bind to BCAT2 and control the K44 acetylation level in response to BCAA availability. More importantly, the K44R mutant promotes BCAA catabolism, cell proliferation, and pancreatic tumor growth. Collectively, the data from our study reveal a previously unknown regulatory mechanism of BCAT2 in PDAC and provide a potential therapeutic target for PDAC treatment.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1038/s41392-020-0168-0DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7256045PMC
May 2020

lncRNA Mtss1 promotes inflammatory responses and secondary brain injury after intracerebral hemorrhage by targeting miR-709 in mice.

Brain Res Bull 2020 09 19;162:20-29. Epub 2020 May 19.

Department of Neurosurgery, Zhujiang Hospital, Southern Medical University, Guangzhou, China; The National Key Clinical Specialty, Engineering Technology Research Center of Education Ministry of China, Guangdong Provincial Key Laboratory on Brain Function Repair and Regeneration, Guangzhou, China. Electronic address:

Secondary brain injuries following intracerebral hemorrhage (ICH) are mediated by inflammatory pathway activation. The present study aimed to characterize long noncoding RNAs (lncRNAs) that are differentially expressed in cerebral tissues during ICH pathogenesis and to investigate their pathogenic functions. An ICH mouse model established by collagenase injection was used to obtain differentially expressed lncRNAs for deep sequencing. A cellular inflammation model was established by treating mouse microglia with lipopolysaccharide. Expression of lncRNA and miRNA was assessed by quantitative RT-PCR, and protein abundance was measured by western blot. Cytokine levels in mouse serum and cell culture supernatants were analyzed using enzyme-linked immunosorbent assay. Cerebral injury was evaluated by hematoxylin-eosin and Nissl staining, the ratio of brain dry weight/brain wet weight, and neurobehavior scoring. Ionized calcium-binding adaptor molecule 1 (IBA1) expression in the brain sections was assessed using immunohistochemistry. A total of 3681 lncRNAs were differentially expressed in the brain tissue of the ICH mice group compared with the Sham group. Of these, lncRNA metastasis suppressor-1 (Mtss1) expression was increased. Mtss1 knockdown by siRNA in the cellular model strongly suppressed TIR-domain-containing adapter-inducing interferon-β (TRIF) expression, P65 phosphorylation, and tumor necrosis factor (TNF)-α and interleukin (IL)-1β secretion. Mtss1 knockdown in ICH mice inhibited secondary brain injury and decreased IBA1, TNF-α, and IL-1β. Mtss1 was predicted to bind miR-709, and Mtss1 knockdown elevated miR-709 expression in the cellular inflammation model and ICH mice. High expression of Mtss1 promoted inflammatory brain injuries after ICH by enhancing inflammatory cytokine secretion and targeting miR-709 expression.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1016/j.brainresbull.2020.04.017DOI Listing
September 2020

Novel anti-EGFR scFv human antibody-conjugated immunoliposomes enhance chemotherapeutic efficacy in squamous cell carcinoma of head and neck.

Oral Oncol 2020 07 21;106:104689. Epub 2020 Apr 21.

Institute of Cellular and Organismic Biology, Academia Sinica, Taipei, Taiwan; Graduate Institute of Oral Biology, School of Dentistry, National Taiwan University, Taipei, Taiwan. Electronic address:

Background And Objectives: Squamous cell carcinoma of head and neck (SCCHN) is the fifth most prevalent cancer worldwide. Because the anatomical complexity of this region, complete surgical resection is often not achievable and conventional chemotherapy would aid locoregional control and mitigate distant metastasis. Nonetheless, the nonspecific cytotoxicity and short in vivo half-life of conventional chemotherapeutic drugs limit their effects. Given the high frequency of overexpression of wild type epidermal growth factor receptor (EGFR), we exploit EGFR as a homing beacon for drug delivery system with cytotoxic payloads.

Materials And Methods: We generated fully human anti-EGFR single chain variable fragment (scFv)-conjugated immunoliposomes (IL) containing doxorubicin and vinorelbine and tested their anti-neoplastic efficacy in vitro and in vivo.

Result: Our IL enhanced endocytosis and significantly reduced the half maximal inhibitory concentrations of the therapeutic payloads when compared to non-targeting liposomal counterparts in various cell lines of SCCHN. Furthermore, median survival time was significantly prolonged in subcutaneous and orthotopic SCCHN xenograft murine models treated with our IL formulations than those treated with non-targeting counterparts (94 days versus 60 days and 72 days versus 56 days, respectively) without evident increased systemic toxicity.

Conclusion: The therapeutic index of the chemotherapeutic payloads was augmented by our EFGR-targeting IL formulation and they are warranted for further development and preclinical trial.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1016/j.oraloncology.2020.104689DOI Listing
July 2020

Anemia, hematinic deficiencies, hyperhomocysteinemia, and gastric parietal cell antibody positivity in burning mouth syndrome patients with iron deficiency.

J Dent Sci 2020 Mar 9;15(1):42-49. Epub 2019 Dec 9.

Graduate Institute of Clinical Dentistry, School of Dentistry, National Taiwan University, Taipei, Taiwan.

Background/purpose: Our previous study found that 143 of 884 burning mouth syndrome (BMS) patients have iron deficiency (ID). This study assessed whether all BMS patients with ID (so-called ID/BMS patients) had iron deficiency anemia (IDA) and evaluated whether the ID/BMS patients had significantly higher frequencies of anemia, hematinic deficiencies, hyperhomocysteinemia, and serum gastric parietal cell antibody (GPCA) positivity than healthy control subjects.

Materials And Methods: The blood hemoglobin (Hb) and serum iron, vitamin B12, folic acid, homocysteine, and GPCA levels in 143 ID/BMS patients and 442 healthy control subjects were measured and compared.

Results: We found that 143 ID/BMS patients had significantly lower mean blood Hb and serum iron, vitamin B12, folic acid levels as well as significantly higher mean serum homocysteine level than healthy control subjects (all -values < 0.01). Moreover, 143 ID/BMS patients had significantly higher frequencies of blood Hb (55.9%) and serum iron (100.0%), vitamin B12 (7.7%), and folic acid (2.1%) deficiencies, hyperhomocysteinemia (27.3%), and serum GPCA positivity (12.6%) than 442 healthy control subjects (all -values < 0.001). Furthermore, of 80 anemic ID/BMS patients, 5 (6.3%) had pernicious anemia, 5 (6.3%) had macrocytic anemia other than pernicious anemia, 42 (52.5%) had normocytic anemia, 21 (26.3%) had IDA, and 7 (8.8%) had thalassemia trait-induced anemia.

Conclusion: ID/BMS patients had significantly higher frequencies of blood Hb and serum iron, vitamin B12, and folic acid deficiencies, hyperhomocysteinemia, and serum GPCA positivity than healthy control subjects. Normocytic anemia is the most common type of anemia in ID/BMS patients.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1016/j.jds.2019.11.001DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7109489PMC
March 2020

Preventing Hypoxemia During Nonintubated Thoracoscopic Surgery.

Ann Thorac Surg 2020 08 16;110(2):747-748. Epub 2020 Feb 16.

Department of Anesthesiology, National Taiwan University Hospital Hsinchu Branch, 25, Lane 442, Section 1, Jingguo Rd, Hsinchu, 300195, Taiwan.

View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1016/j.athoracsur.2019.12.076DOI Listing
August 2020

BCAT2-mediated BCAA catabolism is critical for development of pancreatic ductal adenocarcinoma.

Nat Cell Biol 2020 02 6;22(2):167-174. Epub 2020 Feb 6.

Fudan University Shanghai Cancer Center and Cancer Metabolism Laboratory, Institutes of Biomedical Sciences, Shanghai Medical College, Fudan University, Shanghai, China.

Branched-chain amino acid (BCAA) metabolism is potentially linked with development of pancreatic ductal adenocarcinoma (PDAC). BCAA transaminase 2 (BCAT2) was essential for the collateral lethality conferred by deletion of malic enzymes in PDAC and the BCAA-BCAT metabolic pathway contributed to non-small-cell lung carcinomas (NSCLCs) other than PDAC. However, the underlying mechanism remains undefined. Here we reveal that BCAT2 is elevated in mouse models and in human PDAC. Furthermore, pancreatic tissue-specific knockout of Bcat2 impedes progression of pancreatic intraepithelial neoplasia (PanIN) in LSL-Kras; Pdx1-Cre (KC) mice. Functionally, BCAT2 enhances BCAA uptake to sustain BCAA catabolism and mitochondrial respiration. Notably, BCAA enhances growth of pancreatic ductal organoids from KC mice in a dose-dependent manner, whereas addition of branched-chain α-keto acid (BCKA) and nucleobases rescues growth of KC organoids that is suppressed by BCAT2 inhibitor. Moreover, KRAS stabilizes BCAT2, which is mediated by spleen tyrosine kinase (SYK) and E3 ligase tripartite-motif-containing protein 21 (TRIM21). In addition, BCAT2 inhibitor ameliorates PanIN formation in KC mice. Of note, a lower-BCAA diet also impedes PDAC development in mouse models of PDAC. Thus, BCAT2-mediated BCAA catabolism is critical for development of PDAC harbouring KRAS mutations. Targeting BCAT2 or lowering dietary BCAA may have translational significance.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1038/s41556-019-0455-6DOI Listing
February 2020

Stafne bone defect of the molar region of the mandible.

J Dent Sci 2019 Dec 13;14(4):378-382. Epub 2019 Jun 13.

Department of Dentistry, National Taiwan University Hospital, College of Medicine, National Taiwan University, Taipei, Taiwan.

Background/purpose: The classic Stafne bone defect (SBD) is a rare small well-demarcated radiolucent lesion in the molar region of the mandible near the mandibular angle. This study reported a series of 5 SBD cases.

Materials And Methods: This study reviewed 4000 consecutive panoramic radiographs from February 2017 to May 2017 and found 5 classic SBD cases. The clinical and radiographic findings of these 5 SBD cases were reported.

Results: We found 5 SBD cases presenting as small, well-defined, and radiolucent lesions at the typical first molar to third molar region of the mandible near the mandibular angle and below the mandibular canal. The mean age of the 5 patients at the time of diagnosis was 53.4 years (range, 45-69 years). All the 5 SBD cases occurred in male patients, 3 were on the right side and 2 were on the left side of the mandible. The mean greatest dimension of the 5 SBDs was 1.5 cm (range, 1.2-1.9 cm). All the 5 SBD cases were found incidentally on the panoramic radiographs and two of them were confirmed by cone-beam computed tomography. No surgical intervention was performed for these 5 SBD cases.

Conclusion: The classic SBDs occur most frequently in male patients in the age group between 40 years and 60 years. For the SBDs at the typical site of the molar region of the mandible near the mandibular angle and below the mandibular canal, these lesions can be monitored by panoramic radiography once per one or two years.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1016/j.jds.2019.05.002DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6921125PMC
December 2019

Metabolism remodeling in pancreatic ductal adenocarcinoma.

Cell Stress 2019 Nov 4;3(12):361-368. Epub 2019 Nov 4.

Fudan University Shanghai Cancer Center and Cancer Metabolism Laboratory, Institutes of Biomedical Sciences, Shanghai Medical College, Fudan University; Department of Oncology, Shanghai Medical College, Fudan University, Shanghai 200032, People's Republic of China.

Pancreatic ductal adenocarcinoma (PDAC) is predicted to become the second leading cause of death of patients with malignant cancers by 2030. Current options of PDAC treatment are limited and the five-year survival rate is less than 8%, leading to an urgent need to explore innovatively therapeutic strategies. PDAC cells exhibit extensively reprogrammed metabolism to meet their energetic and biomass demands under extremely harsh conditions. The metabolic changes are closely linked to signaling triggered by activation of oncogenes like as well as inactivation of tumor suppressors. Furthermore, tumor microenvironmental factors including extensive desmoplastic stroma reaction result in series of metabolism remodeling to facilitate PDAC development. In this review, we focus on the dysregulation of metabolism in PDAC and its surrounding microenvironment to explore potential metabolic targets in PDAC therapy.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.15698/cst2019.12.205DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6883744PMC
November 2019

Anemia, hematinic deficiencies, hyperhomocysteinemia, and serum gastric parietal cell antibody positivity in 884 patients with burning mouth syndrome.

J Formos Med Assoc 2020 Apr 1;119(4):813-820. Epub 2019 Nov 1.

Graduate Institute of Clinical Dentistry, School of Dentistry, National Taiwan University, Taipei, Taiwan; Department of Dentistry, National Taiwan University Hospital, College of Medicine, National Taiwan University, Taipei, Taiwan. Electronic address:

Background/purpose: Burning mouth syndrome (BMS) is characterized by burning sensation of the oral mucosa in the absence of clinically apparent oral mucosal alterations. This study evaluated the anemia, hematinic deficiencies, hyperhomocysteinemia, and serum gastric parietal cell antibody (GPCA) positivity in 884 BMS patients.

Methods: The blood hemoglobin (Hb) and serum iron, vitamin B12, folic acid, homocysteine, GPCA levels in 884 BMS patients were measured and compared with the corresponding levels in 442 age- and sex-matched healthy control subjects.

Results: We found that 175 (19.8%), 143 (16.2%), 42 (4.8%), 20 (2.3%), 170 (19.2%), and 109 (12.3%) BMS patients had blood Hb, serum iron, vitamin B12, and folic acid deficiencies, hyperhomocysteinemia, and serum GPCA positivity, respectively. Moreover, 884 BMS patients had significantly higher frequencies of blood Hb and serum iron, vitamin B12, and folic acid deficiencies, hyperhomocysteinemia, and serum GPCA positivity than 442 healthy control subjects (all P-values < 0.005). Of 175 anemic BMS patients, 95 had normocytic anemia, 27 had thalassemia trait-induced anemia, 21 had iron deficiency anemia, 15 had pernicious anemia, 15 had macrocytic anemia other than pernicious anemia, and 2 had microcytic anemia other than iron deficiency anemia and thalassemia trait-induced anemia. Burning sensation of oral mucosa (100.0%), dry mouth (48.1%), numbness of oral mucosa (30.7%), and dysfunction of taste (16.7%) were the four common symptoms in 884 BMS patients.

Conclusion: BMS patients have significantly higher frequencies of blood Hb and serum iron, vitamin B12, and folic acid deficiencies, hyperhomocysteinemia, and serum GPCA positivity than healthy control subjects.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1016/j.jfma.2019.10.013DOI Listing
April 2020

Anemia, hematinic deficiencies, hyperhomocysteinemia, and gastric parietal cell antibody positivity in atrophic glossitis patients with vitamin B12 deficiency.

J Formos Med Assoc 2020 Mar 18;119(3):720-727. Epub 2019 Oct 18.

Graduate Institute of Clinical Dentistry, School of Dentistry, National Taiwan University, Taipei, Taiwan; Department of Dentistry, National Taiwan University Hospital, College of Medicine, National Taiwan University, Taipei, Taiwan. Electronic address:

Background/purpose: Our previous study found that 56 of 1064 atrophic glossitis (AG) patients have vitamin B12 deficiency. This study assessed whether the AG patients with vitamin B12 deficiency (B12D/AG patients) had significantly higher frequencies of anemia, hematinic deficiencies, hyperhomocysteinemia, and serum gastric parietal cell antibody (GPCA) positivity than healthy control subjects.

Methods: The blood hemoglobin (Hb) and serum iron, vitamin B12, folic acid, homocysteine, and GPCA levels in 56 B12D/AG patients and 532 healthy control subjects were measured and compared.

Results: We found that 56 B12D/AG patients had significantly lower mean blood Hb and serum iron levels as well as significantly higher mean corpuscular volume (MCV) and mean serum homocysteine level than healthy control subjects (all P-values < 0.05). Moreover, 56 B12D/AG patients had significantly higher frequencies of macrocytosis (53.6%), blood Hb (64.3%), iron (26.8%), and folic acid (3.6%) deficiencies, hyperhomocysteinemia (89.3%), and serum GPCA positivity (55.4%) than 532 healthy control subjects (all P-values < 0.005). In addition, of 36 anemic B12D/AG patients, 22 (61.1%) had pernicious anemia (PA), 6 (16.7%) had macrocytic anemia other than PA, 4 (11.1%) had normocytic anemia, 3 (8.3%) had iron deficiency anemia (IDA), and one (2.8%) had microcytic anemia other than IDA and thalassemia trait-induced anemia.

Conclusion: We conclude that B12D/AG patients have significantly higher frequencies of macrocytosis, blood Hb, iron, and folic acid deficiencies, hyperhomocysteinemia, and serum GPCA positivity than healthy control subjects. PA is the most common type of anemia in our B12D/AG patients.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1016/j.jfma.2019.10.002DOI Listing
March 2020

Anemia, hematinic deficiencies, hyperhomocysteinemia, and gastric parietal cell antibody positivity in atrophic glossitis patients with iron deficiency.

J Formos Med Assoc 2020 Feb 10;119(2):587-594. Epub 2019 Oct 10.

Graduate Institute of Clinical Dentistry, School of Dentistry, National Taiwan University, Taipei, Taiwan; Department of Dentistry, National Taiwan University Hospital, College of Medicine, National Taiwan University, Taipei, Taiwan. Electronic address:

Background/purpose: Our previous study found that 180 of 1064 atrophic glossitis (AG) patients have iron deficiency. This study assessed whether all AG patients with iron deficiency (so-called ID/AG patients) had iron deficiency anemia (IDA) and evaluated whether the ID/AG patients had significantly higher frequencies of anemia, hematinic deficiencies, hyperhomocysteinemia, and serum gastric parietal cell antibody (GPCA) positivity than healthy control subjects.

Methods: The blood hemoglobin (Hb) and serum iron, vitamin B12, folic acid, homocysteine, and GPCA levels in 180 ID/AG patients and 532 healthy control subjects were measured and compared.

Results: We found that 180 ID/AG patients had significantly lower mean corpuscular volume (MCV) and lower mean blood Hb and serum iron levels as well as significantly higher mean serum homocysteine level than healthy control subjects (all P-values < 0.001). Moreover, 180 ID/AG patients had significantly higher frequencies of blood Hb (46.1%), serum iron (100.0%), vitamin B12 (8.3%), and folic acid (4.4%) deficiencies, hyperhomocysteinemia (16.1%), and serum GPCA positivity (31.1%) than 532 healthy control subjects (all P-values < 0.001). In addition, of 83 anemic ID/AG patients, 9 (10.8%) had pernicious anemia, 40 (48.2%) had normocytic anemia, 30 (36.2%) had IDA, and 4 (4.8%) had thalassemia trait-induced anemia.

Conclusion: We conclude that ID/AG patients had significantly higher frequencies of blood Hb, serum iron, vitamin B12, and folic acid deficiencies, hyperhomocysteinemia, and serum GPCA positivity than 532 healthy control subjects. Normocytic anemia is the most common type of anemia in ID/AG patients, followed by IDA, pernicious anemia, and thalassemia trait-induced anemia.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1016/j.jfma.2019.09.014DOI Listing
February 2020

Upregulated NPM1 is an independent biomarker to predict progression and prognosis of oral squamous cell carcinomas in Taiwan.

Head Neck 2020 01 1;42(1):5-13. Epub 2019 Oct 1.

Graduate Institute of Clinical Dentistry, School of Dentistry, National Taiwan University, Taipei, Taiwan.

Background: Nucleophosmin/nucleoplasmin family 1 (NPM1) has broad physiological functions, such as DNA replication, transcription, ribosome biogenesis, and centrosome replication. This study explored the clinicopathological importance of NPM1 as a prognostic marker for oral squamous cell carcinoma (OSCC).

Methods: We collected specimens from 96 OSCC, 45 oral epithelial dysplasia (OED), and 29 normal oral mucosa (NOM). NPM1 expression was analyzed via immunohistochemistry. Correlations between NPM1and clinical parameters were analyzed using Student t test, chi-squared test, and Kaplan-Meier product-limit method.

Results: The NPM1 labeling indices (LIs) were significantly higher in OSCCs than in NOM and oral OED. Higher NPM1 expression was significantly correlated with larger tumor size, nodal metastasis, and advanced clinical stage. Multivariate analysis revealed that higher NPM1 LIs were an unfavorable independent factor for survival.

Conclusions: Upregulated NPM1 is an independent biomarker of poor prognosis and NPM1 inhibitors may be promising in molecular targeted therapy against OSCC.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1002/hed.25971DOI Listing
January 2020

Salivary Sialadenoma Papilliferum Consists of Two Morphologically, Immunophenotypically, and Genetically Distinct Subtypes.

Head Neck Pathol 2020 Jun 31;14(2):489-496. Epub 2019 Aug 31.

Department of Dentistry, National Taiwan University Hospital, No. 1, Changde St., Zhongzheng Dist., Taipei City, 100, Taiwan, ROC.

Papillary salivary gland neoplasms are rare tumors usually arising in the minor salivary glands of the oral cavity. Their classification has been historically confusing due to overlapping histologic features, but molecular analysis may clarify these entities. Sialadenoma papilliferum (SP) is a peculiar member of this group that demonstrates both an endophytic ductal and an exophytic squamous component. SP closely resembles syringocystadenoma papilliferum of the skin, a tumor which has recently been shown to harbor BRAF V600E or HRAS mutations. We sought to perform histologic and immunophenotypic analysis of a group of SP, along with BRAF and HRAS mutational analysis. We collected 13 SP cases from 7 females and 6 males ranging from 2 to 91 years (mean 62.8). Five exophytic ductal papillomas were also analyzed as controls. Histological analysis was performed along with immunohistochemistry for CK7, p63, and SOX10. BRAF VE1 immunohistochemistry was done in all tumors, and BRAF V600E and HRAS Sanger sequencing was successfully performed in all but two cases. Histologic analysis revealed that SP consisted not only of classic SP (9 of 13 cases) but also an oncocytic variant (4 of 13 cases) characterized by a glandular component that uniformly exhibited abundant granular cytoplasm and prominent nucleoli. By immunohistochemistry, all SP demonstrated luminal CK7 and basal p63 expression, but SOX10 was expressed only in conventional SP (9 of 9 cases). BRAF VE1 immunohistochemistry was positive in 9 of 9 conventional SP but 0 of 4 oncocytic SP; staining was present in both the exophytic and endophytic components. BRAF V600E mutational status was confirmed by Sanger sequencing in 11 cases (7 conventional and 4 oncocytic). The exophytic ductal papillomas were negative for BRAF mutations, and all tumors tested were negative for HRAS mutations. In summary, we demonstrated that SP consists of two variants: (1) conventional SP which is SOX10-positive and harbors BRAF V600E mutations similar to syringocystadenoma papilliferum of the skin; and (2) an oncocytic variant which is SOX10-negative and negative for BRAF mutations. We also demonstrated that both the endophytic glandular component and exophytic squamous components of conventional SP harbor BRAF V600E mutations and are therefore neoplastic.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1007/s12105-019-01068-4DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7235136PMC
June 2020

Anemia, hematinic deficiencies, and gastric parietal cell antibody positivity in atrophic glossitis patients with or without hyperhomocysteinemia.

J Formos Med Assoc 2020 Jan 20;119(1 Pt 3):544-552. Epub 2019 Aug 20.

Graduate Institute of Clinical Dentistry, School of Dentistry, National Taiwan University, Taipei, Taiwan; Department of Dentistry, National Taiwan University Hospital, College of Medicine, National Taiwan University, Taipei, Taiwan. Electronic address:

Background/purpose: Our previous study found that 127 of 1064 atrophic glossitis (AG) patients have hyperhomocysteinemia. This study assessed whether the AG patients with hyperhomocysteinemia had significantly higher frequencies of anemia, hematinic deficiencies, and serum gastric parietal cell antibody (GPCA) positivity than AG patients without hyperhomocysteinemia or healthy control subjects.

Methods: The blood hemoglobin (Hb) and serum iron, vitamin B12, folic acid, homocysteine, and GPCA levels in 127 AG patients with hyperhomocysteinemia, 937 AG patients without hyperhomocysteinemia, and 532 healthy control subjects were measured and compared.

Results: We found that 127 AG patients with hyperhomocysteinemia had significantly higher frequencies of blood Hb and serum iron, vitamin B12, and folic acid deficiencies and serum GPCA positivity than 532 healthy control subjects (all P-values < 0.001) and significantly higher frequencies of blood Hb and serum vitamin B12 and folic acid deficiencies and serum GPCA positivity than 937 AG patients without hyperhomocysteinemia (all P-values < 0.001). Moreover, 127 AG patients with hyperhomocysteinemia had significantly higher frequencies of macrocytic anemia and significantly lower frequencies of normocytic anemia than 937 AG patients without hyperhomocysteinemia (both P-values < 0.001). Pernicious anemia (22 cases) was found only in AG patients with hyperhomocysteinemia but not in AG patients without hyperhomocysteinemia.

Conclusion: AG patients with hyperhomocysteinemia had significantly higher frequencies of anemia, serum iron, vitamin B12, and folic acid deficiencies, and serum GPCA positivity than healthy control subjects and significantly higher frequencies of anemia, serum vitamin B12 and folic acid deficiencies, and serum GPCA positivity than AG patients without hyperhomocysteinemia.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1016/j.jfma.2019.08.002DOI Listing
January 2020

Hematinic deficiencies, hyperhomocysteinemia, and gastric parietal cell antibody positivity in atrophic glossitis patients with normocytosis.

J Formos Med Assoc 2020 Jun 27;119(6):1109-1115. Epub 2019 Jul 27.

Graduate Institute of Clinical Dentistry, School of Dentistry, National Taiwan University, Taipei, Taiwan; Department of Dentistry, National Taiwan University Hospital, College of Medicine, National Taiwan University, Taipei, Taiwan. Electronic address:

Background/purpose: Normocytosis is defined as having the mean corpuscular volume (MCV) between 80 fL and 99.9 fL. This study evaluated whether 944 atrophic glossitis (AG) patients with normocytosis had significantly higher frequencies of anemia, hematinic deficiencies, hyperhomocysteinemia, and serum gastric parietal cell antibody (GPCA) positivity than 532 healthy control subjects or 1064 AG patients.

Methods: Complete blood count, serum iron, vitamin B12, folic acid, homocysteine, and GPCA levels in 944 AG patients with normocytosis, 1064 AG patients, and 532 healthy control subjects were measured and compared.

Results: We found that 12.4%, 14.5%, 2.3%, 2.0%, 9.0%, and 25.7% of 944 AG patients with normocytosis had blood hemoglobin (Hb), iron, vitamin B12, and folic acid deficiencies, hyperhomocysteinemia, and serum GPCA positivity, respectively. Furthermore, 944 AG patients with normocytosis had significantly higher frequencies of blood Hb, iron, vitamin B12, folic acid deficiencies, hyperhomocysteinemia, and serum GPCA positivity than 532 healthy control subjects (all P-values < 0.01). On the contrary, 944 AG patients with normocytosis had significantly lower frequencies of blood Hb and vitamin B12 deficiencies and hyperhomocysteinemia than overall 1064 AG patients (all P-values < 0.05).

Conclusion: We conclude that there are significantly higher frequencies of anemia and serum iron, vitamin B12, and folic acid deficiencies, hyperhomocysteinemia, and serum GPCA positivity in AG patients with normocytosis than in healthy control subjects. On the contrary, AG patients with normocytosis have significantly lower frequencies of blood Hb and vitamin B12 deficiencies and hyperhomocysteinemia than overall AG patients.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1016/j.jfma.2019.07.020DOI Listing
June 2020

Hematinic deficiencies, hyperhomocysteinemia, and gastric parietal cell antibody positivity in atrophic glossitis patients with macrocytosis.

J Formos Med Assoc 2019 Nov 16;118(11):1515-1521. Epub 2019 Jul 16.

Graduate Institute of Clinical Dentistry, School of Dentistry, National Taiwan University, Taipei, Taiwan; Department of Dentistry, National Taiwan University Hospital, College of Medicine, National Taiwan University, Taipei, Taiwan. Electronic address:

Background/purpose: Macrocytosis is defined as having the mean corpuscular volume (MCV) ≧ 100 fL. This study evaluated whether 41 atrophic glossitis (AG) patients with macrocytosis had significantly higher frequencies of anemia, hematinic deficiencies, hyperhomocysteinemia, and serum gastric parietal cell antibody (GPCA) positivity than 532 healthy control subjects or 1064 AG patients.

Methods: Complete blood count, serum iron, vitamin B12, folic acid, homocysteine, and GPCA levels in 41 AG patients with macrocytosis, 1064 AG patients, and 532 healthy control subjects were measured and compared.

Results: We found that 73.2%, 22.0%, 73.2%, 4.9%, 80.5%, and 56.1% of 41 AG patients with macrocytosis were diagnosed as having blood hemoglobin, iron, vitamin B12, and folic acid deficiencies, hyperhomocysteinemia, and serum GPCA positivity, respectively. Moreover, 41 AG patients with macrocytosis had significantly higher frequencies of blood hemoglobin and serum vitamin B12 deficiencies, hyperhomocysteinemia, and serum GPCA positivity than 532 healthy control subjects or 1064 AG patients (all P-values < 0.001). In addition, 41 AG patients with macrocytosis also had significantly higher frequencies of serum iron and folic acid deficiencies than 532 healthy control subjects (both P-values < 0.001). Pernicious anemia was found in 22 AG patients with macrocytosis.

Conclusion: There are significantly higher frequencies of anemia and serum iron, vitamin B12, and folic acid deficiencies, hyperhomocysteinemia, and serum GPCA positivity in AG patients with macrocytosis than in healthy control subjects. AG patients with macrocytosis also have significantly higher frequencies of blood hemoglobin and serum vitamin B12 deficiencies, hyperhomocysteinemia, and serum GPCA positivity than AG patients.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1016/j.jfma.2019.07.001DOI Listing
November 2019

Does serum gastric parietal cell antibody titer have influence on anemia and vitamin B12 deficiency in atrophic glossitis patients?

J Formos Med Assoc 2020 Jan 2;119(1 Pt 2):377-383. Epub 2019 Jul 2.

Graduate Institute of Clinical Dentistry, School of Dentistry, National Taiwan University, Taipei, Taiwan; Department of Dentistry, National Taiwan University Hospital, College of Medicine, National Taiwan University, Taipei, Taiwan. Electronic address:

Background/purpose: Our previous study found 284 gastric parietal cell antibody (GPCA)-positive atrophic glossitis (AG) patients (so-called GPCAAG patients in this study) in a group of 1064 AG patients. This study evaluated whether high-titer (GPCA titer ≥ 160) GPCAAG patients had greater frequencies of anemia, vitamin B12 deficiency, macrocytosis, and hyperhomocysteinemia than low-titer (GPCA titer < 160) GPCAAG patients.

Methods: Complete blood count, serum iron, vitamin B12, folic acid, homocysteine, and GPCA levels in 117 high-titer GPCAAG patients, 167 low-titer GPCAAG patients, and 532 healthy control subjects were measured and compared.

Results: We found that 12.0%, 29.1%, 23.1%, 16.2%, 1.7%, and 23.1% of 117 high-titer GPCAAG patients and 5.4%, 17.4%, 17.4%, 7.2%, 1.2%, and 14.4% of 167 low-titer GPCAAG patients were diagnosed as having macrocytosis, blood hemoglobin, iron, vitamin B12, and folic acid deficiencies, and hyperhomocysteinemia, respectively. Moreover, both 117 high-titer and 167 low-titer GPCAAG patients had significantly greater frequencies of macrocytosis, blood hemoglobin, serum iron and vitamin B12 deficiencies, and hyperhomocysteinemia than 532 healthy control subjects (all P-values < 0.05). In addition, 117 high-titer GPCAAG patients also had greater frequencies of anemia (P = 0.029, statistically significant), serum vitamin B12 deficiency (P = 0.027, statistically significant), macrocytosis (P = 0.075, marginal significance), and hyperhomocysteinemia (P = 0.085, marginal significance) than 167 low-titer GPCAAG patients.

Conclusion: For GPCAAG patients, high-titer GPCAAG patients have greater frequencies of anemia, serum vitamin B12 deficiency, macrocytosis, and hyperhomocysteinemia than low-titer GPCAAG patients.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1016/j.jfma.2019.06.009DOI Listing
January 2020

Anemia, hematinic deficiencies, hyperhomocysteinemia, and serum gastric parietal cell antibody positivity in atrophic glossitis patients with or without microcytosis.

J Formos Med Assoc 2019 Oct 24;118(10):1401-1407. Epub 2019 Jun 24.

Department of Dentistry, National Taiwan University Hospital, College of Medicine, National Taiwan University, Taipei, Taiwan; Graduate Institute of Clinical Dentistry, School of Dentistry, National Taiwan University, Taipei, Taiwan. Electronic address:

Background/purpose: Microcytosis is defined as having mean corpuscular volume (MCV) < 80 fL. This study evaluated whether 79 atrophic glossitis (AG) patients with microcytosis and 985 AG patient without microcytosis had higher frequencies of anemia, hematinic deficiencies, hyperhomocysteinemia, and serum gastric parietal cell antibody (GPCA) positivity than 532 healthy control subjects.

Methods: Complete blood count, serum iron, vitamin B12, folic acid, homocysteine, and serum GPCA levels in 79 AG patients with microcytosis, 985 AG patient without microcytosis, and 532 healthy control subjects were measured and compared.

Results: We found that 69.6%, 43.0%, 5.1%, 3.8%, 11.4%, and 22.8% of 79 AG patients with microcytosis and 14.9%, 14.8%, 5.3%, 2.1%, 12.0%, and 27.0% of 985 AG patients without microcytosis were diagnosed as having blood hemoglobin, iron, vitamin B12, and folic acid deficiencies, hyperhomocysteinemia, and serum GPCA positivity, respectively. Both 79 AG patients with microcytosis and 985 AG patients without microcytosis had significantly higher frequencies of blood hemoglobin, iron, vitamin B12, and folic acid deficiencies, hyperhomocysteinemia, and serum GPCA positivity than 532 healthy control subjects (all P-values < 0.01). Moreover, 79 AG patients with microcytosis had significantly higher frequencies of blood hemoglobin and iron deficiencies than 985 AG patients without microcytosis.

Conclusion: There are significantly higher frequencies of anemia, serum iron, vitamin B12, and folic acid deficiencies, hyperhomocysteinemia, and serum GPCA positivity in AG patients with or without microcytosis than in healthy control subjects. AG patients with microcytosis have significantly higher frequencies of blood hemoglobin and iron deficiencies than AG patients without microcytosis.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1016/j.jfma.2019.06.004DOI Listing
October 2019

Can we predict who will develop postoperative hyperkalaemia after parathyroidectomy in dialysis patients with secondary hyperparathyroidism?

BMC Nephrol 2019 06 20;20(1):225. Epub 2019 Jun 20.

Department of Nephrology, National Clinical Research Center for Kidney Diseases, Chinese PLA General Hospital, Chinese PLA Institute of Nephrology, State Key Laboratory of Kidney Diseases, 28 Fuxing Road, Beijing, 100853, China.

Background: Hyperkalaemia occurs frequently in many maintenance haemodialysis (MHD) patients after parathyroidectomy (PTX) with secondary hyperparathyroidism (SHPT). However, the clinical risk factors that predict postoperative hyperkalaemia are uncertain.

Methods: This retrospective cohort study included 90 maintenance haemodialysis patients aged ≥18 years who underwent PTX between April 2011 and April 2016 at Aerospace Center Hospital (Peking University Aerospace School of Clinical Medicine). Pre- and post-PTX surgery venous samples were measured in quadruplicate. We examined univariate associations with demographics, dialysis characteristics, laboratory values and medications. Hyperkalaemia was defined as serum potassium >5.3 mmol/L.

Results: Out of nighty patients, twenty-two (24.4%) developed postoperative hyperkalaemia, of whom sixteen (18.1%) developed hyperkalaemia on postoperative day 3. The univariate analysis showed that weight, dialysis duration, preoperative serum potassium, alkaline phosphate, triglyceride, and postoperative alkaline phosphate were independently associated with hyperkalaemia after parathyroidectomy. The univariate logistic regression model showed that preoperative serum potassium was the only independent factor that could predict hyperkalaemia after parathyroidectomy (odds ratio, 1.59; 95% confidence interval, 1.24-2.05). The optimal cut-off for pre-operative K was 3.9 mmol/L according to the receiver operating characteristic (ROC) curve. A higher incidence of postoperative hyperkalaemia was found in male and younger patients, but the difference was not statistically significant (p>0.05).

Conclusions: Pre-operative serum potassium less than 3.9 mmol/L was associated with less hyperkalaemia post-operatively in end-stage renal disease (ESRD) patients undergoing PTX.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1186/s12882-019-1416-9DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6585140PMC
June 2019
-->