The crosstalk between copper-induced oxidative stress and cuproptosis: a novel potential anticancer paradigm.

Copper is a crucial trace element that plays a role in various pathophysiological processes in the human body. Copper also acts as a transition metal involved in redox reactions, contributing to the generation of reactive oxygen species (ROS). Under prolonged and increased ROS levels, oxidative stress occurs, which has been implicated in different types of regulated cell death. The recent discovery of cuproptosis, a copper-dependent regulated cell death pathway that is distinct from other known regulated cell death forms, has raised interest to researchers in the field of cancer therapy. Herein, the present work aims to outline the current understanding of cuproptosis, with an emphasis on its anticancer activities through the interplay with copper-induced oxidative stress, thereby providing new ideas for therapeutic approaches targeting modes of cell death in the future.

PAICS/DYRK3 Multienzyme Interactions as Coregulators of Purinosome Formation and Metabolism on Radioresistance in Oral Squamous Cell Carcinoma.

Oral squamous cell carcinoma (OSCC) is a prevalent type of oral cancer. While therapeutic innovations have made strides, radioresistance persists as a significant hindrance in OSCC treatment. Despite identifying numerous targets that could potentially suppress the oncogenic attributes of OSCC, the exploration of oncogenic protein kinases for cancer therapy remains limited. Consequently, the functions of many kinase proteins in OSCC continue to be largely undetermined. In this research, we aim to disclose protein kinases that target OSCC and elaborate their roles and molecular mechanisms. Through the examination of the kinome library of radiotherapy-resistant/sensitive OSCC cell lines (HN12 and SAS), we identified a key gene, the tyrosine phosphorylation-regulated kinase 3 (DYRK3), a member of the DYRK family. We developed an in vitro cell model, composed of radiation-resistant OSCC, to scrutinize the clinical implications and contributions of DYRK3 and phosphoribosylaminoimidazole carboxylase and phosphoribosylaminoimidazolesuccinocarboxamide synthase (PAICS) signaling in OSCC. This investigation involves bioinformatics and human tissue arrays. We seek to comprehend the role of DYRK3 and PAICS signaling in the development of OSCC and its resistance to radiotherapy. Various in vitro assays are utilized to reveal the essential molecular mechanism behind radiotherapy resistance in connection with the DYRK3 and PAICS interaction. In our study, we quantified the concentrations of DYRK3 and PAICS proteins and tracked the expression levels of key pluripotency markers, particularly PPAT. Furthermore, we extended our investigation to include an analysis of Glut-1, a gene recognized for its linkage to radioresistance in oral squamous cell carcinoma (OSCC). Furthermore, we conducted an in vivo study to affirm the impact of DYRK3 and PAICS on tumor growth and radiotherapy resistance, focusing particularly on the role of DYRK3 in the radiotherapy resistance pathway. This focus leads us to identify new therapeutic agents that can combat radiotherapy resistance by inhibiting DYRK3 (GSK-626616). Our in vitro models showed that inhibiting PAICS disrupts purinosome formation and influences the survival rate of radiation-resistant OSCC cell lines. These outcomes underscore the pivotal role of the DYRK3/PAICS axis in directing OSCC radiotherapy resistance pathways and, as a result, influencing OSCC progression or therapy resistance. Our findings also reveal a significant correlation between DYRK3 expression and the PAICS enzyme in OSCC radiotherapy resistance.

Higher serum homocysteine level and frequency of hyperhomocysteinemia in carcinoembryonic antigen-positive or squamous cell carcinoma-antigen-positive oral leukoplakia patients.

BACKGROUND/PURPOSE: Our previous study found significantly lower serum hematinic levels and higher serum homocysteine level as well as higher frequencies of serum hematinic deficiencies and hyperhomocysteinemia in oral leukoplakia (OL) patients than in healthy control subjects. This study evaluated whether carcinoembryonic antigen (CEA)-positive or squamous cell carcinoma-antigen (SCC-Ag)-positive OL patients had significantly lower serum hematinic levels and higher serum homocysteine level as well as significantly higher frequencies of hematinic deficiencies and hyperhomocysteinemia than CEA-negative or SCC-Ag-negative OL patients or healthy control subjects. METHODS: The complete blood count, serum iron, vitamin B12, folic acid, and homocysteine levels in 184 OL patients including 85 CEA-positive, 99 CEA-negative, 25 SCC-Ag-positive, and 159 SCC-Ag-negative OL patients and in 184 age- and sex-matched healthy control subjects were measured and compared. RESULTS: We found that the 85 CEA-positive or 25 SCC-Ag-positive OL patients had a significantly lower mean serum folic acid level and a significantly higher mean serum homocysteine level as well as significantly higher frequencies of serum folic acid deficiency and hyperhomocysteinemia than 184 healthy control subjects. Moreover, the 25 SCC-Ag-positive OL patients had a significantly higher mean serum homocysteine level than the 159 SCC-Ag-negative OL patients. The 85 CEA-positive OL patients had a higher mean serum homocysteine level and a higher frequency of hyperhomocysteinemia than 99 CEA-negative OL patients (marginally significant, P = 0.060). CONCLUSION: CEA-positive or SCC-Ag-positive OL patients tend to have a higher mean serum homocysteine level and a higher frequency of hyperhomocysteinemia than CEA-negative or SCC-Ag-negative OL patients, respectively.

Serum levels and positive rates of tumor biomarkers in oral precancer patients.

BACKGROUND/PURPOSE: Several previous studies have reported higher serum tumor marker levels in patients with oral or head and neck squamous cell carcinomas. This study evaluated whether 232 patients with oral precancerous lesions (oral precancer patients) had significantly higher serum carcinoembryonic antigen (CEA), squamous cell carcinoma antigen (SCC-Ag), and ferritin levels than healthy control subjects. METHODS: The serum CEA, SCC-Ag, and ferritin levels in 232 oral precancer patients and 187 healthy control subjects were measured and compared. Patients with serum CEA level ≥3 ng/mL, SCC-Ag level ≥2 ng/mL, and ferritin level ≥250 ng/mL were scored as serum positive for CEA, SCC-Ag, and ferritin, respectively. RESULTS: We found significantly higher mean serum CEA, SCC-Ag, and ferritin levels in 232 oral precancer patients than in 187 healthy control subjects (all P-values < 0.05). Moreover, 232 oral precancer patients had significantly higher serum positive rates of CEA (47.4%), SCC-Ag (13.8%), and ferritin (52.2%) than 187 healthy control subjects (all P-values < 0.05). Of the 232 oral precancer patients, 121 (52.1%), 56 (24.1%), and 10 (4.3%) had serum positivities of one, two, or three tumor markers including CEA, SCC-Ag, and ferritin, respectively. CONCLUSION: There are significantly higher mean serum CEA, SCC-Ag, and ferritin levels and significantly higher serum positive rates of CEA, SCC-Ag, and ferritin in oral precancer patients than in healthy control subjects. The serum CEA, SCC-Ag, and ferritin levels are of diagnostic value and may be potential tumor markers for the screening of oral precancer patients.

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

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 (GPCA+BMS) patients had significantly higher frequencies of macrocytosis, anemia, hematinic deficiencies, and hyperhomocysteinemia than healthy control subjects or GPCA-negative BMS (GPCA-BMS) 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 GPCA+BMS patients, 775 GPCA-BMS patients, and 442 healthy control subjects. RESULTS: We found that 109 GPCA+BMS 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 GPCA-BMS patients (all P-values < 0.01). Moreover, 775 GPCA-BMS 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 GPCA+BMS 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 GPCA-BMS patients. CONCLUSION: GPCA+BMS patients have significantly higher frequencies of macrocytosis, blood Hb and serum vitamin B12 deficiencies, and hyperhomocysteinemia than healthy control subjects or GPCA-BMS patients.

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

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.

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

BACKGROUND/PURPOSE: Our previous study found 284 gastric parietal cell antibody (GPCA)-positive atrophic glossitis (AG) patients (so-called GPCA+AG patients in this study) in a group of 1064 AG patients. This study evaluated whether high-titer (GPCA titer ≥ 160) GPCA+AG patients had greater frequencies of anemia, vitamin B12 deficiency, macrocytosis, and hyperhomocysteinemia than low-titer (GPCA titer < 160) GPCA+AG patients. METHODS: Complete blood count, serum iron, vitamin B12, folic acid, homocysteine, and GPCA levels in 117 high-titer GPCA+AG patients, 167 low-titer GPCA+AG 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 GPCA+AG patients and 5.4%, 17.4%, 17.4%, 7.2%, 1.2%, and 14.4% of 167 low-titer GPCA+AG 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 GPCA+AG 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 GPCA+AG 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 GPCA+AG patients. CONCLUSION: For GPCA+AG patients, high-titer GPCA+AG patients have greater frequencies of anemia, serum vitamin B12 deficiency, macrocytosis, and hyperhomocysteinemia than low-titer GPCA+AG patients.

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

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.

Atrophic glossitis: Etiology, serum autoantibodies, anemia, hematinic deficiencies, hyperhomocysteinemia, and management.

Atrophic glossitis (AG) is characterized by the partial or complete absence of filiform papillae on the dorsal surface of the tongue. AG may reflect the significant deficiencies of some major nutrients including riboflavin, niacin, pyridoxine, vitamin B12, folic acid, iron, zinc, and vitamin E. Moreover, protein-calorie malnutrition, candidiasis, Helicobacter pylori colonization, xerostomia, and diabetes mellitus are also the etiologies of AG. Our previous study found the serum gastric parietal cell antibody (GPCA), thyroglobulin antibody (TGA), and thyroid microsomal antibody (TMA) positivities in 26.7%, 28.4%, and 29.8% of 1064 AG patients, respectively. We also found anemia, serum iron, vitamin B12, and folic acid deficiencies, and hyperhomocysteinemia in 19.0%, 16.9%, 5.3%, 2.3%, and 11.9% of 1064 AG patients, respectively. Moreover, GPCA-positive AG patients tended to have relatively higher frequencies of hemoglobin, iron, and vitamin B12 deficiencies and hyperhomocysteinemia than GPCA-negative AG patients. Supplementations with vitamin BC capsules plus corresponding deficient hematinics for those AG patients with hematinic deficiencies can achieve complete remission of oral symptoms and AG in some AG patients. Therefore, it is very important to examine the complete blood count, serum hematinic, homocysteine, and autoantibody levels in AG patients before we start to offer treatments for AG patients.

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

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.

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

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.

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

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.

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

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.

Hematinic deficiencies and hyperhomocysteinemia in gastric parietal cell antibody-positive or gastric and thyroid autoantibodies-negative Behcet's disease patients.

BACKGROUND/PURPOSE: Our previous study found that 9 of 63 recurrent aphthous stomatitis (RAS)/Behcet's disease (BD) patients have serum gastric parietal cell antibody (GPCA) positivity. This study assessed whether serum GPCA positivity or RAS/BD itself was a significant factor causing hematinic deficiencies and hyperhomocysteinemia in GPCA-positive RAS/BD (GPCA+RAS/BD) or gastric and thyroid autoantibodies-negative RAS/BD (Abs-RAS/BD) patients. METHODS: The mean blood hemoglobin (Hb), iron, vitamin B12, folic acid, and homocysteine levels were measured and compared between any two of three groups of 9 GPCA+RAS/BD patients, 41 Abs-RAS/BD patients, and 126 healthy control subjects. RESULTS: GPCA+RAS/BD patients had significantly lower mean blood Hb (for men only), iron (for men only), and vitamin B12 levels as well as a significantly higher mean serum homocysteine level than 126 healthy control subjects. Moreover, GPCA+RAS/BD patients had significantly greater frequencies of blood Hb, iron, and vitamin B12 deficiencies and of hyperhomocysteinemia than healthy control subjects. GPCA+RAS/BD patients did have a significantly lower mean serum vitamin B12 level and a significantly higher mean serum homocysteine level as well as significantly greater frequencies of vitamin B12 deficiency and of hyperhomocysteinemia than Abs-RAS/BD patients. Moreover, Abs-RAS/BD patients did have significantly lower mean blood Hb, iron, and folic acid levels and significantly greater frequencies of blood Hb and iron deficiencies than healthy control subjects. CONCLUSION: The GPCA is a major factor causing vitamin B12 deficiency and hyperhomocyteinemia in GPCA+RAS/BD patients. RAS/BD itself does play a significant role in causing anemia and hematinic deficiencies in both GPCA+RAS/BD and Abs-RAS/BD patients.

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

BACKGROUND/PURPOSE: Macrocytosis is defined as having the mean corpuscular volume (MCV) â‰§ 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.

Hematinic deficiencies and hyperhomocysteinemia in gastric parietal cell antibody-positive or gastric and thyroid autoantibodies-negative atrophic glossitis patients.

BACKGROUND/PURPOSE: Our previous study found that 177 of 1064 atrophic glossitis (AG) patients have serum gastric parietal cell antibody (GPCA) positivity only (so-called GPCA+AG patients). This study assessed whether serum GPCA positivity or AG itself was a significant factor causing hematinic deficiencies and hyperhomocysteinemia in GPCA+AG or GPCA-negative, thyroglobulin antibody (TGA)-negative, and thyroid microsomal antibody (TMA)-negative AG (GPCAÖ¾TGAÖ¾TMAÖ¾AG) patients. METHODS: The mean blood hemoglobin (Hb), iron, vitamin B12, folic acid, and homocysteine levels were measured and compared between any two of three groups of 177 GPCA+AG patients, 476 GPCAÖ¾TGAÖ¾TMAÖ¾AG patients, and 532 healthy control subjects. RESULTS: GPCA+AG patients had significantly lower mean blood Hb and iron (for women only) levels and a significantly higher mean serum homocysteine level than healthy control subjects. Moreover, GPCA+AG patients had significantly greater frequencies of blood Hb, iron, and vitamin B12 deficiencies and hyperhomocysteinemia than healthy control subjects. GPCA+AG patients have a lower mean serum vitamin B12 level and a significantly higher mean serum homocysteine level as well as significantly greater frequencies of vitamin B12 deficiency and hyperhomocysteinemia than GPCAÖ¾TGAÖ¾TMAÖ¾AG patients. Moreover, GPCAÖ¾TGAÖ¾TMAÖ¾AG patients did have significantly lower mean blood Hb and iron levels and significantly greater frequencies of blood Hb, iron, vitamin B12, and folic acid deficiencies and hyperhomocysteinemia than healthy control subjects. CONCLUSION: The GPCA is a major factor causing vitamin B12 deficiency and hyperhomocyteinemia in GPCA+AG patients. AG itself does play a significant role in causing anemia, hematinic deficiencies, and hyperhomocysteinemia in both GPCA+AG and GPCAÖ¾TGAÖ¾TMAÖ¾AG patients.

Blood profile of atrophic glossitis patients with thyroglobulin antibody/thyroid microsomal antibody positivity but without gastric parietal cell antibody positivity.

BACKGROUND/PURPOSE: Our previous study found that 304 of 1064 atrophic glossitis (AG) patients have thyroglobulin antibody (TGA) positivity and/or thyroid microsomal antibody (TMA) positivity but without gastric parietal cell antibody positivity (GPCAÖ¾TGA+/TMA+AG patients). This study mainly assessed whether the serum TGA/TMA positivity was significantly associated with anemia, hematinic deficiencies, and hyperhomocysteinemia in GPCAÖ¾TGA+/TMA+AG patients. METHODS: The mean blood hemoglobin (Hb), iron, vitamin B12, folic acid, and homocysteine levels were measured and compared between 304 GPCAÖ¾TGA+/TMA+AG patients and 476 GPCA-negative, TGA-negative, and TMA-negative AG patients (GPCAÖ¾TGAÖ¾TMAÖ¾AG patients) or 532 healthy control subjects. RESULTS: We found significantly lower MCV and lower mean blood Hb and iron levels as well as significantly greater frquencies of microcytosis, macrocytosis, blood Hb, iron, vitamin B12, and folic acid deficiencies and hyperhomocysteinemia in 304 GPCAÖ¾TGA+/TMA+AG patients than in 532 healthy control subjects. However, no significant differences in the MCV and mean blood Hb, iron, vitamin B12, folic acid, and homocysteine leve1s as well as no significant differences in the frequencies of microcytosis, macrocytosis, blood Hb, iron, and folic acid deficiencies, and hyperhomocysteinemia were discovered between 304 GPCAÖ¾TGA+/TMA+AG patients and 476 GPCAÖ¾TGAÖ¾TMAÖ¾AG patients. The 304 GPCAÖ¾TGA+/TMA+AG patients had a significantly greater frquency of serum vitamin B12 deficiency than 476 GPCAÖ¾TGAÖ¾TMAÖ¾AG patients. CONCLUSION: The disease of AG itself plays a significant role in causing anemia, hematinic deficiencies, and hyperhomocysteinemia in GPCAÖ¾TGA+/TMA+AG patients. However, the serum TGA/TMA-positivity is not significantly associated with anemia, serum iron and folic acid deficiencies, and hyperhomocysteinemia in GPCAÖ¾TGA+/TMA+AG patients.

Gastric parietal cell and thyroid autoantibodies in patients with atrophic glossitis.

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 presence of serum GPCA, TGA, and TMA in atrophic glossitis (AG) patients. METHODS: Serum GPCA, TGA, and TMA levels were measured in 1064 AG patients and in 532 age- and sex-matched healthy control subjects. RESULTS: We found that 26.7%, 28.4%, and 29.8% of 1064 AG patients and 2.3%, 2.1%, and 2.6% of 532 healthy control subjects had the serum GPCA, TGA, and TMA positivities, respectively. AG patients had a significantly higher frequency of GPCA, TGA, or TMA positivity than healthy control subjects (all P-values < 0.001). We also found that 67 (6.3%), 181 (17.0%), and 340 (32.0%) AG patients and 3 (0.6%), 10 (1.9%), and 8 (1.5%) 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 373 TGA/TMA-positive AG patients whose serum thyroid-stimulating hormone (TSH) levels were measured, 78.6%, 8.0%, and 13.4% of these TGA/TMA-positive AG patients had normal, lower, and higher serum TSH levels, respectively. CONCLUSION: Approximately 55.3% of 1064 AG patients have serum GPCA/TGA/TMA positivity. Because part of GPCA-positive AG patients may develop pernicious anemia, autoimmune atrophic gastritis, and gastric carcinoma, and part of TGA/TMA-positive AG patients may have thyroid dysfunction such as hyperthyroidism and hypothyroidism, these autoantibody-positive AG patients should be referred to medical doctors for further management.

Recurrent aphthous stomatitis - Etiology, serum autoantibodies, anemia, hematinic deficiencies, and management.

Recurrent aphthous stomatitis (RAS) is one of the most common oral mucosal diseases characterized by recurrent and painful ulcerations on the movable or nonkeratinized oral mucosae. Clinically, three types of RAS, namely minor, major, and herpetiform types, can be identified. RAS more commonly affects labial mucosa, buccal mucosa, and tongue. Previous studies indicate that RAS is a multifactorial T cell-mediated immune-dysregulated disease. Factors that modify the immunologic responses in RAS include genetic predisposition, viral and bacterial infections, food allergies, vitamin and microelement deficiencies, systemic diseases, hormonal imbalance, mechanical injuries, and stress. Our previous study found the presence of serum gastric parietal cell antibody, thyroglobulin antibody, and thyroid microsomal antibody in 13.0%, 19.4%, and 19.7% of 355 RAS patients, respectively. We also found anemia, serum iron, vitamin B12, and folic acid deficiencies, and hyperhomocysteinemia in 20.9%, 20.1%, 4.8%, 2.6%, and 7.7% of 273 RAS patients, respectively. Therefore, it is very important to examine the complete blood count, serum autoantibody, hematinic, and homocysteine levels in RAS patients before we start to offer treatments for RAS. Because RAS is an immunologically-mediated disease, topical and systemic corticosteroid therapies are the main treatments of choice for RAS.

Anemia, hematinic deficiencies, and hyperhomocysteinemia in gastric parietal cell antibody-positive and -negative atrophic glossitis patients.

BACKGROUND/PURPOSE: Approximately 27% of atrophic glossitis (AG) patients have the serum gastric parietal cell antibody (GPCA) positivity. This study assessed whether the serum GPCA or AG itself was a significant factor causing anemia, hematinic deficiencies, and hyperhomocysteinemia in GPCA-positive AG (GPCA+AG) and GPCA-negative AG (GPCA-AG) patients. METHODS: The mean corpuscular volume (MCV) and mean blood hemoglobin (Hb), iron, vitamin B12, folic acid, and homocysteine levels were measured and compared between any two of three groups of 284 GPCA+AG, 780 GPCA-AG patients, and 532 healthy control subjects. RESULTS: Both 284 GPCA+AG and 780 GPCA-AG patients had significantly higher frequencies of microcytosis, macrocytosis, blood Hb, iron, vitamin B12, and folic acid deficiencies, and hyperhomocysteinemia than 532 healthy control subjects. Moreover, 284 GPCA+AG patients had significantly higher frequencies of macrocytosis, vitamin B12 deficiency, and hyperhomocysteinemia than 780 GPCA-AG patients. Sixty-three (22.2%) of 284 GPCA+AG patients and 139 (17.8%) of 780 GPCA-AG patients had anemia. The normocytic anemia (42.9%), pernicious anemia (34.9%), and iron deficiency anemia (15.9%) were the three most common types of anemia in the 63 anemic GPCA+AG patients. Moreover, the normocytic anemia (64.8%), iron deficiency anemia (14.4%), and thalassemia trait-induced anemia (13.7%) were the three most common types of anemia in 139 anemic GPCA-AG patients. CONCLUSION: The disease of AG itself is a significant factor causing anemia, hematinic deficiencies, and hyperhomocysteinemia in both GPCA+AG and GPCA-AG patients. The serum GPCA also plays a significant role in causing macrocytosis, vitamin B12 deficiency, and hyperhomocysteinemia in GPCA+AG patients.