Protective Effect of Perilla Seed Meal and Perilla Seed Extract against Dextran Sulfate Sodium-Induced Ulcerative Colitis through Suppressing Inflammatory Cytokines in Mice.

An excessive inflammatory response of the gastrointestinal tract is recognized as one of the major contributors to ulcerative colitis (UC). Despite this, effective preventive approaches for UC remain limited. Rosmarinic acid (RA), an enriched fraction from Perilla frutescens, has been shown to exert beneficial effects on disease-related inflammatory disorders. However, RA-enriched perilla seed meal (RAPSM) and perilla seed (RAPS) extracts have not been investigated in dextran sulfate sodium (DSS)-induced UC in mice. RAPSM and RAPS were extracted using the solvent-partitioning method and analyzed with high-pressure liquid chromatography (HPLC). Mice with UC induced using 2.5% DSS for 7 days were pretreated with RAPSM and RAPS (50, 250, 500 mg/kg). Then, the clinical manifestation, colonic histopathology, and serum proinflammatory cytokines were determined. Indeed, DSS-induced UC mice exhibited colonic pathological defects including an impaired colon structure, colon length shortening, and increased serum proinflammatory cytokines. However, RAPSM and RAPS had a protective effect at all doses by attenuating colonic pathology in DSS-induced UC mice, potentially through the suppression of proinflammatory cytokines. Concentrations of 50 mg/kg of RAPSM and RAPS were sufficient to achieve a beneficial effect in UC mice. This suggests that RAPSM and RAPS have a preventive effect against DSS-induced UC, potentially through alleviating inflammatory responses and relieving severe inflammation in the colon.

Imbalance of mitochondrial fusion in peripheral blood mononuclear cells is associated with liver fibrosis in patients with metabolic dysfunction-associated steatohepatitis.

Mitochondrial dysfunction and inflammation contribute to the pathophysiology of metabolic dysfunction-associated steatohepatitis (MASH). This study aims to evaluate the potential association between mitochondrial dynamics and cell death markers from peripheral blood mononuclear cells (PBMCs) and the presence of MASH with significant liver fibrosis among metabolic dysfunction-associated steatotic liver disease (MASLD) patients. Consecutive patients undergoing bariatric surgery from January to December 2022 were included. Patients with histologic steatosis were classified into MASH with significant fibrosis (F2-4) group or MASLD/MASH without significant fibrosis group (F0-1). Mitochondrial dynamic proteins and cell death markers were extracted from PBMCs. A total of 23 MASLD/MASH patients were included (significant fibrosis group, n = 7; without significant fibrosis group, n = 16). Of the mitochondrial dynamics and cell death markers evaluated, OPA1 protein, a marker of mitochondrial fusion is higher in MASH patients with significant fibrosis compared to those without (0.861 ± 0.100 vs. 0.560 ± 0.260 proportional to total protein, p = 0.001). Mitochondrial fusion/fission (OPA1/DRP1) ratio is significantly higher in MASH patients with significant fibrosis (1.072 ± 0.307 vs. 0.634 ± 0.313, p = 0.009). OPA1 (per 0.01 proportional to total protein) was associated with the presence of significant liver fibrosis with an OR of 1.08 (95%CI, 1.01-1.15, p = 0.035), and adjusted OR of 1.10 (95%CI, 1.00-1.21, p = 0.042). OPA1 from PBMCs is associated with MASH and substantial fibrosis. Future studies should explore if OPA1 could serve as a novel non-invasive liver fibrosis marker.

Mitochondrial dysfunction is associated with the severity of liver fibrosis in patients after the Fontan operation.

The gold standard for determining the severity of liver disease in Fontan patients is now liver biopsy. Since it is an invasive procedure, this study determined the possibility of applying mitochondrial function from isolated peripheral blood mononuclear cells (PBMCs) as a non-invasive indicator of liver fibrosis. Fontan patients (n = 37) without known liver disease were analysed cross-sectionally. Patients were classified according to their histology using the METAVIR score as follows; F0/F1-no/mild fibrosis; F2-moderate fibrosis; and F3/F4-cirrhosis. Peripheral blood mononuclear cells were assessed for mitochondrial activity and apoptosis. This study did not find any significant differences in cardiac function among the groups according to liver histology. Interestingly, our findings indicated a significant decrease in maximal respiration and spare respiratory capacity, in both the moderate (F2) and cirrhosis (F3/F4) groups compared with the group without significant fibrosis (F0/F1). Moreover, the cirrhosis group exhibited higher levels of apoptosis and lower levels of live cells, compared with both the moderate and no significant fibrosis groups. In conclusion, the degree of liver fibrosis in Fontan patients is strongly correlated with mitochondrial dysfunction in PBMCs. Mitochondrial function and apoptosis could potentially serve as novel markers for tracking the progression of liver fibrosis in these patients.

Adenocarcinoma in Intraductal Tubulopapillary Neoplasm of the Pancreas: A Case Report and Literature Review.

Intraductal tubulopapillary neoplasms (ITPNs) are a subgroup of pre-malignant pancreatic epithelial lesions. The histomorphological and immunophenotypical characteristics of ITPN have been described by several authors based on case series; however, the rarity of this tumor subtype and its similarity to other entities makes the identification of ITPN challenging for radiologists and pathologists. Herein, we report a case of ITPN with associated invasive carcinoma along with a literature review that will benefit further studies and help in planning treatments for patients in the future. A pancreatic mass was incidentally discovered in a 40-year-old woman during her annual check-up. Radiological investigation revealed a mass that obstructed the main pancreatic duct and caused ductal dilatation. Endoscopic retrograde cholangiopancreatography with biopsy indicated poorly differentiated adenocarcinoma. Subsequently, total pancreatectomy with splenectomy was performed to remove the tumor. ITPN of the pancreas with associated poorly differentiated adenocarcinoma was diagnosed based on pathological and immunohistological test results. Achieving complete resection of the tumor, the patient did not require chemotherapy during follow-up care. Thus, our study demonstrated the necessity of radiological and histopathological correlation in the definitive diagnosis of pancreatic ITPN. However, the determination of an invasive component is essential because malignant transformation affects the prognosis of patients.

Early Detection of Hepatocarcinogenicity in Rats Using MRI with Ferric-Tannic Nanoparticles.

Herein, we present molecular nanoparticles of ferric-tannic complexes (so called ferric-tannic nanoparticles, FT NPs) used to enhance the MRI signal in the early stage of hepatocarcinoma. FT NPs were found to accumulate in the hepatic parenchyma without tumor nodules of Wistar rats in which hepatocarcinogenicity had been induced using diethylnitrosamine (DEN). The MRI enhancement and accumulation of FT NPs were clearly observed in the early phase of hepatocarcinogenicity, which was possibly modulated by various solute carrier family members present in the entire hepatic parenchyma of the DEN-induced rats. These findings suggest that MRI with FT NPs is promising for the assessment of the early stage of hepatocarcinoma.

Programmed death-ligand 1 expression and overall survival in Thai patients with gastric cancer.

Programmed death-ligand 1 (PD-L1) expression has now been implicated in gastric cancer (GC). This study was conducted to determine the impact of clinicopathological characteristics on PD-L1 expression and its association with survival in GC patients receiving standard-of-care. In total, 268 GC patients receiving upfront surgery were enrolled at Chiang Mai University Hospital. PD-L1 expression was assayed by immunohistochemistry staining using the Dako 22C3 pharmDx. The rates of PD-L1 positivity by combined positive score (CPS) at a cutoff value of 1 and 5 were 22% and 7%. PD-L1 positivity was significantly higher in patients younger than 55 than those older than 55 (32.6% vs. 16.5%, p = 0.003; 11.6% vs. 4.4%, p = 0.027). PD-L1 positivity was observed more frequently in GC with metastases than without (25.2% vs. 17.1%, p = 0.112; 7.2% vs. 6.7%, p = 0.673). Patients with PD-L1 positive had a significantly shorter median overall survival than those with PD-L1 negative (32.7 vs. 41.6 months, p = 0.042, 27.6 vs. 40.8 months, p = 0.038). In conclusion, PD-L1 expression has been associated with young age, short survival, and metastases, although unrelated to the tumor stage. For GC patients, PD-L1 testing is recommended, especially among young patients with metastases.

Protective Effect of Red Rice Extract Rich in Proanthocyanidins in a Murine Colitis Model.

Inflammatory bowel disease (IBD) has become a global concern. Proanthocyanidin-rich red rice extract (PRRE) has been shown to suppress the inflammatory response in cellular cultures. However, the anti-colitis effect of PRRE has never been investigated in animals. This study aimed to examine the protective effect of the PRRE against dextran sulfate sodium (DSS)-induced colitis in mice. Male mice were orally administrated with PRRE of 50, 250 and 500 mg/kg/day for 21 days. Acute colitis was subsequently induced by administrated 2.5% DSS in drinking water for the final seven days. Sulfasalazine-treated mice were the positive group. All doses of PRRE and sulfasalazine significantly ameliorated DSS-induced severity of colitis, as indicated by decreasing daily activity index and restoring colon shortening. Treatments with PRRE, but not sulfasalazine, significantly reduced the histopathological index and infiltration of inflammatory cells. Furthermore, the PRRE treatments effectively improved mucous in colonic goblet cells using PAS staining, and suppressed the production of pro-inflammatory cytokines TNF-α, IL-1ß and IL-6 induced by DSS, while sulfasalazine reduced only IL-1ß and IL-6. This study suggested that PRRE had a greater anti-colitis effect than sulfasalazine. Thus, PRRE has a potential anti-colitis effect, and should be developed in a clinical trial as a natural active pharmaceutical ingredient for IBD.

Prevalence and factors associated with atrophic gastritis and intestinal metaplasia: A multivariate, hospital-based, statistical analysis.

BACKGROUND: Atrophic gastritis (AG) and intestinal metaplasia (IM) play an essential role in gastric carcinogenesis. This study aimed to determine the prevalence of AG and IM and their associated factors. METHODS: Subjects who underwent upper endoscopy at Chiang Mai University Hospital from January 2018 to Dec 2021 were included. All participants were interviewed using a structured questionnaire to collect their personal histories. In addition, clinical and histological data and associated factors of AG and IM were analyzed. RESULTS: A total of 947 subjects (mean age, 53.61 ± 9.73 years; 60% male) were included. The prevalence of AG and IM, diagnosed by histopathology, was 39% and 19%. Prevalence of AG and IM increased from 28% and 9% in those under 50 years to 43% and 30% in those above 60 (p < 0.05). In a multivariate analysis, Helicobacter pylori (H. pylori) infection, age 50-59 and over 60 years were significantly associated with higher odds of AG (odds ratio (OR), 2.07, 2.06, and 1.98) and IM (OR, 2.07, 2.18, and 4.46), respectively. Conversely, ingestion of spicy food was significantly associated with lower odds of AG and IM (OR, 0.75, and 0.62). CONCLUSIONS: This study confirms that age and H. pylori infection are risk factors, whereas spicy food intake is a protective factor against AG and IM, which are common in patients over 50. Therefore, upper endoscopy and gastric mapping sampling are recommended for patients with chronic dyspepsia older than 50 to reduce gastric cancer risk.

Protective Effect of Probiotics Isolated from Traditional Fermented Tea Leaves (Miang) from Northern Thailand and Role of Synbiotics in Ameliorating Experimental Ulcerative Colitis in Mice.

This study aimed to investigate the protective effect of probiotics and synbiotics from traditional Thai fermented tea leaves (Miang) on dextran sulfate sodium (DSS)-induced colitis in mice, in comparison to sulfasalazine. C57BL/6 mice were treated with probiotics L. pentosus A14-6, CMY46 and synbiotics, L. pentosus A14-6 combined with XOS, and L. pentosus CMY46 combined with GOS for 21 days. Colitis was induced with 2% DSS administration for seven days during the last seven days of the experimental period. The positive group was treated with sulfasalazine. At the end of the experiment, clinical symptoms, pathohistological changes, intestinal barrier integrity, and inflammatory markers were analyzed. The probiotics and synbiotics from Miang ameliorated DSS-induced colitis by protecting body weight loss, decreasing disease activity index, restoring the colon length, and reducing pathohistological damages. Furthermore, treatment with probiotics and synbiotics improved intestinal barrier integrity, accompanied by lowing colonic and systemic inflammation. In addition, synbiotics CMY46 combined with GOS remarkedly elevated the expression of IL-10. These results suggested that synbiotics isolated from Miang had more effectiveness than sulfasalazine. Thereby, they could represent a novel potential natural agent against colonic inflammation.

Effects of green tea extract treatment on erythropoiesis and iron parameters in iron-overloaded ß-thalassemic mice.

ß-Thalassemia is characterized by ineffective erythropoiesis leading to chronic anemia. Thus, increased iron absorption from the duodenum and via blood transfusions is required to maintain normal blood hemoglobin (Hb) levels and iron chelators in the removal of excessive iron. Certain agents are also needed for the improvement of stress erythropoiesis and iron dysregulation. Green tea extract (GTE), which is rich in epigallocatechin-3-gallate (EGCG), is known to possess radical scavenging and iron-chelating activities. We aimed to assess the effects of green tea extract on erythroid regulators, iron mobilization and anti-lipid peroxidation in the liver, spleen, and kidneys of iron-loaded ß-globin gene knockout thalassemic (BKO) mice. Our results indicate that treatments of green tea extract and/or deferiprone (DFP) diminished levels of plasma erythropoietin (EPO) and erythroferrone (ERFE), and consistently suppressed kidney Epo and spleen Erfe mRNA expressions (p < .05) in iron- loaded BKO mice when compared with untreated mice. Coincidently, the treatments decreased plasma ferritin (Ft) levels, iron content levels in the liver (p < .05), spleen (p < .05), and kidney tissues of iron-loaded BKO mice. Furthermore, lipid-peroxidation products in the tissues and plasma were also decreased when compared with untreated mice. This is the first evidence of the orchestral role of green tea extract abundant with epigallocatechin-3-gallate in improving ineffective erythropoiesis, iron dysregulation and oxidative stress in iron-overloaded ß-thalassemic mice.

Anti-inflammatory effect of Perilla frutescens seed oil rich in omega-3 fatty acid on dextran sodium sulfate-induced colitis in mice.

BACKGROUND AND PURPOSE: Ulcerative colitis is a chronic inflammatory bowel disease that involves diffused inflammation of the large intestine. Omega-3 fatty acid (FA) has been known to regulate the inflammatory response associated with ulcerative colitis pathogenesis. Perilla frutescens is a valuable source of omega-3 FA and α-linolenic acid (ALA) contained in its seed oil. Therefore, the aim of this study was to evaluate the anti-inflammatory effect of Perilla seed oil (PSO) on colitis induced by dextran sulfate sodium (DSS) in a mouse model. EXPERIMENTAL APPROACH: PSO was extracted using a cold-pressed extractor and FA composition of PSO was analyzed by GC-MS. Acute colitis in mice was induced with 3% DSS in drinking water for 7 days. Some mice were treated with PSO (20, 100, 200 mg/kg BW) for 3 weeks before the DSS administration. Sulfasalazine was used as a positive control. The clinical features, histopathologic, serum, and gene expression of proinflammatory cytokines in the colon were assessed. FINDING/RESULTS: PSO contained the highest proportion of ALA (61.51%). Furthermore, PSO pretreatment evidently reduced body weight loss, diminished diarrhea, gross bleeding, and DSS-induced colon shortening. PSO pretreatment attenuated histopathological changes in response to DSS-induced colitis. PSO pretreatment also markedly decreased inflammatory response in serum and the colon tissue of DSS-induced mice. CONCLUSION AND IMPLICATION: ALA in PSO is suggested to be mainly responsible for the reduction of DSS-induced colitis through suppressing inflammatory markers. PSO could be further developed as a functional health supplement, which would be beneficial for anti-inflammation in the colonic mucosa.

Degos-like lesions as a cutaneous manifestation of cytomegalovirus infection: A rare and serious complication in a patient with drug-induced hypersensitivity syndrome.

Cytomegalovirus causes a myriad of clinical features, potentially affecting any organ system, significantly increasing morbidity and even mortality. Vascular endothelial cell infection by cytomegalovirus has been implicated in the development of vasculopathy, possibly accounting for the clinical association between cytomegalovirus and vascular thrombosis. In contrast with visceral organ involvement, the cutaneous manifestations of cytomegalovirus are variable and rarely described. Malignant atrophic papulosis, commonly known as Degos disease, is an unusual small vessel arteriopathy with a pathognomonic clinical appearance of atrophic porcelain-white central papules surrounded by telangiectatic erythema. As with the arterial occlusive process, Degos disease may be idiopathic or secondary to autoimmune disorders or viral infection. All in all, cytomegalovirus-related Degos-like presentation has never been described. This report describes a case in which disseminated cytomegalovirus disease developed 4 weeks after the onset of drug-induced hypersensitivity syndrome with prominent Degos-like skin lesions. Our case highlights a rare example of Degos-like lesions occurring due to cytomegalovirus disease and emphasizes the importance of early recognition of the characteristic cutaneous eruption as a diagnostic clue leading to the prompt management of this life-threatening infection.

Effect of Insurance Type on Stage at Presentation, Surgical Approach, Tumor Recurrence and Cancer-Specific Survival in Resectable Non-Small Lung Cancer Patients.

PURPOSE: The aim of this study was to identify the association between Thailand's insurance types and stage at presentation, surgical approach, tumor recurrence and cancer-specific survival in resectable non-small cell lung cancer (NSCLC) patients in northern Thailand. PATIENTS AND METHODS: Medical records of patients with NSCLC who underwent pulmonary resection at Chiang Mai University Hospital from January 2007 through December 2015 were retrospectively reviewed. Patients were divided into two groups: patients with the Universal Coverage Scheme (UCS) or Social Security Scheme (SSS) and patients with the Civil Servant Medical Benefit Scheme (CSMBS) or private insurance (PI). Patient characteristics were assessed. The primary outcome was cancer-specific survival while the secondary outcome was tumor recurrence. Cox's regression and matching propensity score analysis was used to analyze data. RESULTS: This study included 583 patients: 344 with UCS or SSS and 239 with CSMBS or PI. Patients with UCS or SSS were more likely to be active smokers, have a lower percent predicted FEV1, present with higher-stage tumors and worse differentiated tumors, present with tumor necrosis, and undergo an open surgical approach than those with CSMBS or PI. At multivariable analysis of all patients cohort, there were no significant differences in terms of early stage at presentation (adjusted odds ratio (ORadj) = 0.94, 95% confidence interval (CI) = 0.65-1.37), undergoing lobectomy (ORadj = 0.59, 95% CI = 0.24-1.46), and recurrent-free survival (adjusted hazard ratio (HRadj) =1.20, 95% CI = 0.88-1.65) between groups (UCS/SSS versus CSMBS/PI). However, patients with UCS or SSS had shorter cancer-specific survival (HRadj = 1.61, 95% CI = 1.22-2.15). The results from the propensity score matched patient cohort were not different from those analyses on the full patient cohort. CONCLUSION: Thai insurance types have an effect on cancer-specific survival. The Thai government should recognize the importance of these differences, and further multi-center studies with a larger sample size are warranted to confirm this result.

Pheochromocytoma and gastrointestinal stromal tumours in an adult neurofibromatosis type 1 patient: a rare co-occurrence.

The risk of tumours including pheochromocytoma and gastrointestinal stromal tumour (GIST) has been reported to be higher in neurofibromatosis type 1 (NF1) patients. The concomitant occurrence of these two tumours was rare in NF1 patient and most were symptomatic. In this case report, we describe the case of a 47-year-old man with NF1 who presented with microscopic haematuria. Neither hypertension nor any gastrointestinal symptoms were reported by the patient. While investigating for haematuria, left adrenal mass and arterial enhancing lesions in the small bowel were incidentally documented during computerised urography. The patient subsequently underwent a left adrenalectomy and small bowel resection. The pheochromocytoma and multiple GIST tumours were diagnosed based on pathology. Here, we discuss the rare association of pheochromocytoma and GIST and the asymptomatic presentation of those tumours in an NF1 patient. We further suggest that in NF1 patients a heightened level of vigilance can help identify this infrequent combination.

Outcomes of pulmonary resection in non-small cell lung cancer patients older than 70 years old.

BACKGROUND: An appropriate treatment of older lung cancer patients has become an important issue. The aim of this study is to evaluate the short and long-term surgical outcomes in lung cancer patients using 70 years as a cut-point, and to identify prognostic factors of cancer-specific mortality in patients older than 70 years. METHODS: Medical records of non-small cell lung cancer (NSCLC) patients who underwent pulmonary resection at Chiang Mai University Hospital from January 2002 through December 2016 were retrospectively reviewed. Patients were divided into age less than 70 years (control group) and 70 years or more (study group). Primary outcomes were major post-operative complications and in-hospital death (POM); secondary outcome was long-term survival. Multivariable regression analysis was used. RESULTS: This study included 583 patients, 167 for study group, and 416 for control group. There were no differences in POM, both at univariable and multivariable analyses, however, for long-term cancer-specific mortality, the study group was more likely to die (HRadj = 1.40, 95%CI = 1.03-1.89). Adverse prognostic factors for long-term mortality in study group were having universal coverage scheme (HRadj = 1.70, 95%CI = 1.03-2.79), the presence of intratumoral lymphatic invasion (HRadj = 2.83, 95%CI = 1.28-6.29), perineural invasion (HRadj = 2.80, 95%CI = 1.13-6.94), underwent lymph node sampling (HRadj = 2.23, 95%CI = 1.16-4.30) and higher stage of disease (HRadj = 2.02, 95%CI = 1.06-3.85 for stage III, HRadj = 3.40, 95%CI = 1.29-8.94 for stage IV). CONCLUSIONS: In-hospital mortality and composite post-operative complications are acceptable in pulmonary resection for NSCLC patients older than 70 years. However, these patients had shorter long-term survival, especially who have some adverse prognostic factors. Further studies with larger sample size are warranted.

Thai Perilla frutescens fruit oil alleviates carbon tetrachloride-induced hepatotoxicities in rats

Objective: To study the effect of perilla fruit oil against carbon tetrachloride (CCl4)-induced liver damage in rats. Methods: Perilla fruit oil was analyzed in terms of fatty acids, tocopherols and tocotrienols using chromatography. Sub-chronic toxicity of perilla fruit oil was investigated in rats for 90 d followed by a 28 d recovery period. Hematological, biochemical and pathological parameters were determined. To evaluate hepatoprotection, rats were divided into five groups and orally administered with Tween 80 for 10 d; Tween 80, silymarin, perilla fruit oil (0.1 mL/200 g) and perilla fruit oil (1 mL/200 g) for 10 d together with subcutaneous injection of CCl4 (2 mL/200 g) on days 9 and 10. Liver enzymes and pathological parameters were determined. Results: Perilla fruit oil contained α-linolenic acid (56.55％ of total fatty acid), β-tocopherol (49.50 mg/kg) and γ-tocotrienol (43.65 mg/kg). Rats showed significant changes in the percentage of monocytes and platelet indices following perilla fruit oil consumption for 90 d; in the percentage of neutrophils and lymphocytes, and RBC indices in the recovery period when compared with the deionized water group. Total protein and creatinine levels were increased while alkaline phosphatase and aspartate aminotransferase levels were decreased (P < 0.05). Organ weight index and pathological indicators did not change significantly. The liver of CCl4-induced rats showed remarkable centrilobular fatty changes, which was ameliorated by perilla fruit oil pretreatment. Aspartate aminotransferase, alanine aminotransferase and alkaline phosphatase levels were decreased (P < 0.05) in rats given perilla fruit oil. Conclusions: Perilla fruit oil is rich in α-linolenic acid, β-tocopherol and γ-tocotrienol and improves blood biomarker levels and protects against CCl4-induced hepatotoxicity. Further studies are required before supporting its use for the treatment of hepatitis.

Downregulation of Friend Leukemia Integration 1 (FLI1) follows the stepwise progression to gastric adenocarcinoma.

Gastric adenocarcinoma (GC) is a leading cause of cancer-related deaths worldwide. The transcription factor gene Friend Leukemia Integration 1 (FLI1) is methylated and downregulated in human GC tissues. Using human GC samples, we determined which cells downregulate FLI1, when FLI1 downregulation occurs, if FLI1 downregulation correlates with clinical-pathologic characteristics, and whether FLI1 plays a role in invasion and/or proliferation of cultured cells. We analyzed stomach tissues from 98 patients [8 normal mucosa, 8 intestinal metaplasia (IM), 7 dysplasia, 91 GC] by immunohistochemistry for FLI1. Epithelial cells from normal, IM, and low-grade dysplasia (LGD) showed strong nuclear FLI1 staining. GC epithelial cells showed significantly less nuclear FLI1 staining as compared to normal epithelium, IM and LGD (P=1.2×10-5, P=1.4×10-6 and P=0.006, respectively). FLI1 expression did not correlate with tumor stage or differentiation, but was associated with patient survival, depending on tumor differentiation. We tested the functional role of FLI1 by assaying proliferation and invasion in cultured GC cells. Lentiviral-transduced FLI1 overexpression in GC AGS cells inhibited invasion by 73.5% (P = 0.001) and proliferation by 31.5% (P = 0.002), as compared to controls. Our results support a combined role for FLI1 as a suppressor of invasiveness and proliferation in gastric adenocarcinoma, specifically in the transition from pre-cancer lesions and dysplasia to invasive adenocarcinoma, and suggest that FLI1 may be a prognostic biomarker of survival in gastric cancers.

High-resolution genomic alterations in Barrett's metaplasia of patients who progress to esophageal dysplasia and adenocarcinoma.

The main risk factor for esophageal dysplasia and adenocarcinoma (DAC) is Barrett's esophagus (BE), characterized by intestinal metaplasia. The critical genomic mechanisms that lead to progression of nondysplastic BE to DAC remain poorly understood and require analyses of longitudinal patient cohorts and high-resolution assays. We tested BE tissues from 74 patients, including 42 nonprogressors from two separate groups of 21 patients each and 32 progressors (16 in a longitudinal cohort before DAC/preprogression-BE and 16 with temporally concurrent but spatially separate DAC/concurrent-BE). We interrogated genome-wide somatic copy number alterations (SCNAs) at the exon level with high-resolution SNP arrays in DNA from formalin-fixed samples histologically confirmed as nondysplastic BE. The most frequent abnormalities were SCNAs involving FHIT exon 5, CDKN2A/B or both in 88% longitudinal BE progressors to DAC vs. 24% in both nonprogressor groups (p = 0.0004). Deletions in other genomic regions were found in 56% of preprogression-BE but only in one nonprogressor-BE (p = 0.0004). SCNAs involving FHIT exon 5 and CDKN2A/B were also frequently detected in BE temporally concurrent with DAC. TP53 losses were detected in concurrent-BE but not earlier in preprogression-BE tissues of patients who developed DAC. CDKN2A/p16 immunohistochemistry showed significant loss of expression in BE of progressors vs. nonprogressors, supporting the genomic data. Our data suggest a role for CDKN2A/B and FHIT in early progression of BE to dysplasia and adenocarcinoma that warrants future mechanistic research. Alterations in CDKN2A/B and FHIT by high-resolution assays may serve as biomarkers of increased risk of progression to DAC when detected in BE tissues.

Green tea extract modulates oxidative tissue injury in beta-thalassemic mice by chelation of redox iron and inhibition of lipid peroxidation.

Iron overload in patients with ß-thalassemia can cause oxidative organ dysfunction. Iron chelation along with antioxidant supplementation can ameliorate such complications and prolong lives. Green tea extract (GTE) rich in epigallocatechin-3-gallate (EGCG) exhibits anti-oxidation and iron chelation properties in ß-knockout thalassemic (BKO) mice diagnosed with iron overload. We investigated the effects of GTE and deferiprone (DFP) alone in combination with one another, and upon the levels of redox-active iron, lipid-peroxidation product, insulin and hepcidin in BKO mice. A state of iron overload was induced in the mice via a trimethylhexanoyl-ferrocene supplemented (Fe) diet for 3 months, and the mice were treated daily with either: DFP (50 mg/kg), DFP (50 mg/kg) plus GTE (50 mg EGCG equivalent/kg), or GTE alone for 2 months. Plasma non-transferrin bound iron (NTBI), malondialdehyde (MDA), alanine aminotransferase (ALT), aspartate aminotransferase (AST), hepcidin and insulin; tissue iron and MDA were measured. DFP, GTE and GTE + DFP effectively decreased plasma MDA (p < 0.05), NTBI and ALT, and increased plasma hepcidin and insulin. All the treatments also reduced iron accumulation and MDA production in both the pancreas and liver in the mice. However, the combination therapy demonstrated no advantages over monotherapy. The findings suggest GTE improved liver and pancreatic ß-cell functions in iron-overloaded ß-thalassemia mice by diminishing redox iron and free radicals, while inhibiting lipid peroxidation. Consequently, there are indications that GTE holds significant potential for clinical use.

Nail Matrix Pathology in Cronkhite-Canada Syndrome: The First Case Report.

Cronkhite-Canada Syndrome (CCS) presents with gastrointestinal polyposis and the triad of cutaneous abnormalities including nail dystrophy, alopecia, and hyperpigmentation of the skin. The etiology is not well understood. The histology of skin lesion in CCS has not been routinely described. Especially, the nail matrix pathology has not been reported. In this study, the authors report the nail matrix pathology in a patient with CCS. Interestingly, the histologic evaluation revealed matrix hypergranulosis. Because matrix hypergranulosis is commonly found in several inflammatory nail diseases, this discovery points out that an inflammatory process is probably one of the important pathogeneses in CCS.