Crude extract of Camellia oleifera pomace ameliorates the progression of non-alcoholic fatty liver disease via decreasing fat accumulation, insulin resistance and inflammation.

Consumption of a high-fat diet increases fat accumulation and may further lead to inflammation and hepatic injuries. The aim of the study was to investigate the effects of Camellia oleifera seed extract (CSE) on non-alcoholic fatty liver disease (NAFLD). After a 16-week NAFLD-inducing period, rats were assigned to experimental groups fed an NAFLD diet with or without CSE. At the end of the study, we found that consuming CSE decreased the abdominal fat weight and hepatic fat accumulation and modulated circulating adipokine levels. We also found that CSE groups had lower hepatic cytochrome P450 2E1 and transforming growth factor (TGF)-ß protein expressions. In addition, we found that CSE consumption may have affected the gut microbiota and reduced toll-like receptor (TLR)-4, myeloid differentiation primary response gene 88, toll/IL-1 receptor domain-containing adaptor-inducing interferon-ß (TRIF) expression and proinflammatory cytokine concentrations in the liver. Our results suggest that CSE may alleviate the progression of NAFLD in rats with diet-induced steatosis through reducing fat accumulation and improving lipid metabolism and hepatic inflammation.

Hepatocellular adenoma in Taiwan: Distinct ensemble of male predominance, overweight/obesity, and inflammatory subtype.

BACKGROUND AND AIM: The clinicopathologic features of hepatocellular adenoma in Asian populations have been poorly defined. The study aimed to characterize this rare entity in a single institution in Taiwan. METHODS: In total, 45 hepatocellular adenomas from 1995 to 2018 were included and sent for pathologic review and molecular subtyping. RESULTS: The numbers of patients with hepatocellular adenoma has doubled in the recent decade. Surprisingly, men outnumbered women in our cohort (n = 26, 58% vs N = 19, 42%). A collection of clinical information revealed that overweight/obesity accounts for most of the associated conditions of hepatocellular adenoma. Only three women took oral contraceptives. There were 34 inflammatory (75%), three LFABP-negative (7%), four ß-catenin activated (9%), and four unclassified (9%) hepatocellular adenomas. Ten inflammatory hepatocellular adenomas demonstrated strong and homogeneous glutamine synthetase staining and were thus also ß-catenin activated. Notably, overweight and obesity were significantly associated with inflammatory hepatocellular adenoma than other subtypes (P = .029 and .056, respectively) and were strongly correlated with steatosis in background liver (P = .028 and.007, respectively). Malignant transformation (four borderline tumors and two hepatocellular carcinomas) was identified in six adenomas (two women and four men). All six hepatocellular adenomas with malignancy were ß-catenin activated; ß-catenin activation could serve as a biomarker for malignant progression. CONCLUSIONS: The clinicopathologic features of hepatocellular adenoma in Taiwan are distinct from those reported in Western countries. Rare oral contraceptive usage and an emerging epidemic of overweight/obesity in Taiwan provides new insights into the pathogenesis of hepatocellular adenoma.

Unilateral vs Bilateral Hybrid Approaches for Upper Limb Rehabilitation in Chronic Stroke: A Randomized Controlled Trial.

OBJECTIVE: To investigate the effects of unilateral hybrid therapy (UHT) and bilateral hybrid therapy (BHT) compared with robot-assisted therapy (RT) alone in patients with chronic stroke. DESIGN: A single-blind, randomized controlled trial. SETTING: Four hospitals. PARTICIPANTS: Outpatients with chronic stroke and mild to moderate motor impairment (N=44). INTERVENTION: UHT combined unilateral RT (URT) and modified constraint-induced therapy. BHT combined bilateral RT (BRT) and bilateral arm training. The RT group received URT and BRT. The intervention frequency for the 3 groups was 90 min/d 3 d/wk for 6 weeks. MAIN OUTCOME MEASURES: Fugl-Meyer Assessment (FMA, divided into the proximal and distal subscale) and Stroke Impact Scale (SIS) version 3.0 scores before, immediately after, and 3 months after treatment and Wolf Motor Function Test (WMFT) and Nottingham Extended Activities of Daily Living (NEADL) scale scores before and immediately after treatment. RESULTS: The results favored BHT over UHT on the FMA total score and distal score at the posttest (P=.03 and .04) and follow-up (P=.01 and .047) assessment and BHT over RT on the follow-up FMA distal scores (P=.03). At the posttest assessment, the WMFT and SIS scores of the 3 groups improved significantly without between-group differences, and the RT group showed significantly greater improvement in the mobility domain of NEADL compared with the BHT group (P<.01). CONCLUSIONS: BHT was more effective for improving upper extremity motor function, particularly distal motor function at follow-up, and individuals in the RT group demonstrated improved functional ambulation post intervention.

CTNNB1 mutations in basal cell adenoma of the salivary gland.

BACKGROUND/PURPOSE: Basal cell adenoma (BCA) and basal cell adenocarcinoma (BCAC) are uncommon salivary gland tumors comprising proliferation of basaloid cells. Nuclear ß-catenin expression and mutations in its encoding gene (CTNNB1) are reported to be specific to BCA. PIK3CA mutations are only found in BCAC not in BCA. However, in previous studies the number of cases was relatively small. The present study analyzed 44 cases of basal cell neoplasms to identify the CTNNB1 and PIK3CA mutation profiles in this rare salivary gland tumor. METHODS: The basic clinical features and detailed histological patterns of 41 BCA and three BCAC cases were analyzed. All basal cell neoplasms and a tissue microarray of adenoid cystic carcinoma (AdCC) were tested for ß-catenin immunohistochemistry. CTNNB1, PIK3CA, and CYLD mutations were detected by PCR and Sanger sequencing in each case. RESULTS: Nuclear ß-catenin expression was present in 97.6% of BCA and 66.7% of BCAC cases but not in AdCC cases. CTNNB1 mutations were found in 60% of BCA but not in BCAC. None of the tested cases had PIK3CA mutations. CTNNB1 mutation trended to be more common in those cases having a predominant tubular or tubulotrabecular patterns (p = 0.059). CONCLUSION: ß-catenin immunohistochemistry is very useful for the differential diagnosis between BCA/BCAC and AdCC. CTNNB1 mutations are common in BCA, especially those with tubular or tubulotrabecular patterns.

Comprehensive screening for MED12 mutations in gynaecological mesenchymal tumours identified morphologically distinctive mixed epithelial and stromal tumours.

AIMS: MED12 exon 2 mutations have been identified in most uterine leiomyomas and mammary fibroepithelial tumours. MED12 has not been genotyped in most other gynaecological mesenchymal tumours. The purpose of this study was to determine the prevalence of MED12 mutations in uncommon gynaecological mesenchymal tumours. METHODS AND RESULTS: Sixty-eight uncommon gynaecological mesenchymal tumours were genotyped for MED12 exon 2, including 27 Müllerian adenosarcomas (including three tentatively diagnosed as 'variant adenosarcomas'), six cellular angiofibromas, six aggressive angiomyxomas, five angiomyofibroblastomas, five superficial myofibroblastomas, five atypical polypoid adenomyomas, and 14 endometrial stromal sarcomas. Immunohistochemistry for CD10, myogenic markers, hormone receptors, MDM2, and CDK4, and fluorescence in-situ hybridization (FISH) for JAZF1, PHF1 and YWHAE rearrangement, were performed on selected cases. The three 'variant adenosarcomas' harboured MED12 exon 2 mutations (including p.L36R hotspot mutation, recurrent p.L39_A50del, and a novel splice site mutation). Three endometrial stromal sarcomas with JAZF1-SUZ12 or JAZF1-PHF1 fusion harboured unprecedented mutations (p.D54G in two, and p.Q48* in one). All remaining tumours were wild-type. The three MED12-mutated 'variant adenosarcomas' showed distinctive morphological features, including 'fibromyomatous' cytomorphology, a close association with adenomyosis, clustered thick-walled vessels, focal conspicuous hyalinization, and intralymphovascular tumour growth. Features of conventional adenosarcomas, including nuclear atypia, mitotic activity, periglandular condensation, and phyllodes-like architecture, were inconspicuous. All three cases showed immunoreactivity for desmin and hormone receptors, while being negative for MDM2 and CDK4; they showed no JAZF1, PHF1 or YWHAE rearrangement. Despite deep myoinvasion, these tumours followed an indolent clinical course. CONCLUSIONS: These MED12-mutated adenosarcoma-like tumours might represent a distinct entity that requires more studies for its identification. MED12 exon 2 mutations seemed to have no significant role in other uncommon gynaecological mesenchymal tumours.

Mutation analysis and copy number changes of KRAS and BRAF genes in Taiwanese cases of biliary tract cholangiocarcinoma.

BACKGROUND/PURPOSE: Cholangiocarcinoma (CC) is a fatal malignancy originating from biliary tracts and constitutes approximately 10-20% of hepatobiliary cancers. CC is characterized by a very poor prognosis. The definite molecular mechanisms leading to oncogenesis remain unclear. This study aimed to perform mutation analysis and copy number changes of KRAS and BRAF genes of CC in Taiwan. METHODS: A total of 182 cases of biliary tact CC were studied for point mutation and quantitative real-time polymerase chain reaction analysis of KRAS and BRAF genes. The obtained data were analyzed with clinical and histopathological variables and survival. RESULTS: KRAS point mutations were detected in intrahepatic CC (7.6%), common bile duct cancer (13.3%), and gallbladder carcinoma (3.3%). BRAF gene amplifications were demonstrated in intrahepatic CC (4.3%), common bile duct cancer (3.3%), and gallbladder cancer (5%). No association was observed between mutation patterns and histopathological features. The analyses of risk factors for overall survival in patients with CC revealed no significant association in age, tumor site, genetic mutation, or amplifications. The tumor stage was the significant prognostic factor. CONCLUSION: Unlike other studies from American, European, or Japanese groups which showed certain levels of gene mutations in CC, our data revealed a rather low frequency of KRAS mutations and BRAF gene amplifications in CC in Taiwan. Tumor TNM stage was the only significant prognostic parameter in this analysis. It is crucial to gain more information of carcinogenesis, molecular mechanisms and therapeutic strategy in biliary tract cholangiocarcinoma.

Loss of ARID1A expression and its relationship with PI3K-Akt pathway alterations and ZNF217 amplification in ovarian clear cell carcinoma.

AT-rich interactive domain 1A (ARID1A) is a subunit of switch/sucrose non-fermentable (SWI/SNF) complex. Recently, alterations of ARID1A gene, phosphatidylinositol 3-kinase-protein kinase B (PI3K-Akt) pathway and zinc-finger protein 217 (ZNF217) gene have been identified as frequent molecular genetic changes in ovarian clear cell carcinoma. The relationships between these events have not been studied and integrated in the same cohort. This study was aimed at determining the correlation between these molecular events and other clinicopathological factors, including the prognostic impacts of these clinicopathological factors. A total of 68 ovarian clear cell carcinoma cases were collected and subjected to immunohistochemistry testing for ARID1A, SMARCA2, SMARCA4, SMARCB1 and phosphatase and tensin homolog (PTEN), mutation analysis for phosphatidylinositol-4,5-bisphosphate 3-kinase, catalytic subunit alpha (PIK3CA) gene and fluorescence in situ hybridization for ZNF217 amplification. The correlations between ARID1A expression, PI3K-Akt pathway, ZNF217 amplification and other clinicopathological factors were analyzed. Loss of ARID1A expression was present in 35 cases (52%) and loss of SMARCA2 expression occurred in 1 case. SMARCA4 and SMARCB1 expressions were preserved in all cases. PIK3CA mutations were present in 23 cases (34%) and loss of PTEN expression occurred in 8 cases (12%). Alterations in the PI3K-Akt pathway (PIK3CA mutations or loss of PTEN expression) were found in 42 cases (62%). ZNF217 amplification was detected in 21 cases (31%). Loss of ARID1A expression was significantly related to younger patient age (P=0.048), PI3K-Akt pathway activation (P=0.046) and ZNF217 amplification (P=0.028). All of the clinicopathological factors were not prognostic factors for ovarian clear cell carcinoma after multivariate analysis, except International Federation of Gynecology and Obstetrics staging (P=0.001). Our results showed that loss of ARID1A expression usually coexisted with PI3K-Akt pathway activation and/or ZNF217 amplification. Synergic effects of loss of ARID1A and PI3K-Akt pathway activation as well as ZNF217 amplification may be related to the development of ovarian clear cell carcinoma.

Very low-carbohydrate diet with higher protein ratio improves lipid metabolism and inflammation in rats with diet-induced nonalcoholic fatty liver disease.

Non-alcoholic fatty liver disease (NAFLD) is commonly associated with obesity, and it is mainly treated through lifestyle modifications. The very low-carbohydrate diet (VLCD) can help lose weight rapidly but the possible effects of extreme dietary patterns on lipid metabolism and inflammatory responses in individuals with NAFLD remain debatable. Moreover, VLCD protein content may affect its effectiveness in weight loss, steatosis, and inflammatory responses. Therefore, we investigated the effects of VLCDs with different protein contents in NAFLD rats and the mechanisms underlying these effects. After a 16-week inducing period, the rats received an isocaloric normal diet (NC group) or a VLCD with high or low protein content (NVLH vs. NVLL group, energy ratio:protein/carbohydrate/lipid=20/1/79 vs. 6/1/93) for the next 8 weeks experimental period. We noted that the body weight decreased in both the NVLH and NVLL groups; nevertheless, the NVLH group demonstrated improvements in ketosis. The NVLL group led to hepatic lipid accumulation, possibly by increasing very-low-density lipoprotein receptor (VLDLR) expression and elevating liver oxidative stress, subsequently activating the expression of Nrf2, and inflammation through the TLR4/TRIF/NLRP3 and TLR4/MyD88/NF-κB pathway. The NVLH was noted to prevent the changes in VLDLR and the TLR4-inflammasome pathway partially. The VLCD also reduced the diversity of gut microbiota and changed their composition. In conclusion, although low-protein VLCD consumption reduces BW, it may also lead to metabolic disorders and changes in microbiota composition; nevertheless, a VLCD with high protein content may partially alleviate these limitations.

Mutation analysis of papillary tubal hyperplasia associated with ovarian atypical proliferative serous tumor and low-grade serous carcinoma.

We present a patient with ovarian atypical proliferative serous tumor and low-grade serous carcinoma, related to KRAS mutation. Bilateral fallopian tubes had papillary tubal hyperplasia, providing additional evidence that it is the putative precursor of low-grade serous tumors. Mutation analysis of papillary tubal hyperplasia has not been done in previous literature.

Partial Replacement of Diet with Dehulled Adlay Ameliorates Hepatic Steatosis, Inflammation, Oxidative Stress, and Gut Dysbiosis in Rats with Nonalcoholic Fatty Liver Disease.

The prevalence of nonalcoholic fatty liver disease (NAFLD) has been increasing worldwide, and the average age at NAFLD diagnosis has been decreasing. Although some components of adlay can ameliorate lipid metabolism, oxidative stress, inflammatory response, and gut microbiota, few studies have explored the effects of the dietary intake of intact dehulled adlay on liver diseases. Therefore, in this study, we investigated the effects of the dietary intake of dehulled adlay on NAFLD progression and explored the potential underlying mechanisms. Rats were randomized into a control group; a high-fat, high-sucrose diet (60% total energy derived from fat and 9.4% from sucrose)-induced NAFLD group (N); or a high-fat, high-sucrose diet with dehulled adlay group (received the same amounts of dietary fiber and total energy as did the N group). The experimental duration was 16 weeks. The diet containing dehulled adlay mitigated hepatic fat accumulation, proinflammatory cytokine levels, and oxidative stress by regulating the AMPK-Nrf2-NLRP3 inflammasome pathway and ferroptosis. Additionally, the dietary intake of dehulled adlay modulated the composition of the gut microbiota. In conclusion, a diet containing dehulled adlay may decelerate the progression of NAFLD by ameliorating hepatic steatosis, inflammation, oxidative stress, and gut dysbiosis.

S100P immunostaining identifies a subset of peripheral-type intrahepatic cholangiocarcinomas with morphological and molecular features similar to those of perihilar and extrahepatic cholangiocarcinomas.

AIMS: S100P is a calcium-binding protein that is frequently expressed in pancreatic adenocarcinoma and perihilar cholangiocarcinoma. The aim of this study was to investigate the pathological significance of the expression of S100P in peripheral intrahepatic cholangiocarcinoma (ICC). METHODS AND RESULTS: Immunohistochemical staining was used to investigate S100P expression in 112 cases of peripheral ICC. The results were compared with those for perihilar and extrahepatic cholangiocarcinomas. Patients with S100P-positive peripheral ICC were more likely to have elevated serum levels of carcinoembryonic antigen (CEA) and CA19-9 than those with S100P-negative peripheral ICCs. All cases of peripheral ICC associated with intrahepatic lithiasis and all cases with intraductal/periductal growth patterns were positive for S100P. S100P-positive peripheral ICCs were highly associated with 'bile duct' morphology rather than cholangiolar differentiation. Nearly all cases of perihilar and extrahepatic cholangiocarcinoma were positive for S100P. Similarly to perihilar and extrahepatic cholangiocarcinomas, S100P-positive peripheral ICCs showed more frequent expression of CEA and MUC2, and were more likely to be N-cadherin-negative, than S100P-negative cases. Notably, K-RAS mutations were only detected in S100P-positive peripheral ICCs, with a frequency similar to that in perihilar and extrahepatic cholangiocarcinomas. Patients with S100P-positive peripheral ICC were more likely to have poor prognoses than those with S100P-negative tumours. CONCLUSIONS: S100P immunostaining identifies a subset of peripheral ICC that probably originates from larger bile ducts. This subset of peripheral ICCs shares common morphological and molecular features with perihilar and extrahepatic cholangiocarcinomas.

Capsaicin attenuates imiquimod-induced epidermal hyperplasia and cutaneous inflammation in a murine model of psoriasis.

Psoriasis is one of the most common chronic inflammatory diseases that is characterized by well-defined erythematous plaques, with typical histopathological findings of lymphocytic infiltration and epidermal hyperplasia. Topical treatments of psoriasis are either associated with limited response or with side effects. Up to date, topicals targeting neuroimmune axis in psoriasis or psoriasiform dermatitis have not been explored. Here, we investigated whether percutaneous delivery of capsaicin could attenuate the pathological change of psoriasiform inflammation. Imiquimod-induced psoriasis-like murine model was used to evaluate therapeutic effects from topical application of capsaicin. An additional model of psoriasiform dermatitis induced by direct IL-23 injection was used to identify the level of action from capsaicin in this neuroimmune axis. Cutaneous inflammation was assessed by erythema level and ear thickness change. Key cytokines, infiltrating cells in the skin, and draining lymph node cells were investigated. The results showed that capsaicin administration obstructed the activation of IL-23/IL-17 pathway induced by imiquimod, presenting with significantly reduced psoriasiform dermatitis both in gross appearance and microscopic features. Tissue gene expression of psoriatic core cytokines induced by imiquimod (including IL-23, IL-17A, IL-22, TNF-α, and IL-6) were greatly decreased by capsaicin application. This protective effect from capsaicin could be hampered by direct intradermal injection of IL-23. CONCLUSION: Epicutaneous delivery of capsaicin on imiquimod-treated murine skin could significantly decrease expression of multiple inflammatory cytokines and the severity of prototypic change of psoriasiform inflammation. The beneficial effect imposed by capsaicin reinforces the neuroimmune contribution towards psoriasiform inflammation and provides a potential non-steroidal therapeutic alternative for topical treatment of psoriasiform dermatitis.

Imprint cytology in diagnosing-primary non-Hodgkin's lymphoma of the breast during intraoperative frozen consultation: a case report.

UNLABELLED: BACKGROUND; Primary non-Hodgkin's lymphoma of the breast is uncommon among primary malignant breast tumors. Here we present a case diagnosed as primary breast lymphoma with imprint cytology during intraoperative frozen consultation. CASE: A 67-year-old woman presented with a palpable, non-tender mass in her left breast that she had had for 2 weeks. The mammogram and ultrasound studies revealed 1 lobular mass in the left breast without axillary lymphadenopathy. Imprint cytology helped diagnose malignant lymphoma of the breast, preventing radical surgery. CONCLUSION: Frozen artifact may obscure the evaluation of cytomorphology during intraoperative consultation. Imprint cytology may help due to less artifact with the cytologic details. Primary breast lymphomas should be considered in the differential diagnosis of breast tumors. The current literature recommendation of intermediate to high grade lymphoma is combined partial mastectomy followed by chemotherapy with local radiotherapy.

Prolonged cholestasis following endoscopic retrograde cholangiopancreatography, a rare complication of contrast agent induced liver injury: A case report and literature review.

RATIONALE: Prolonged cholestasis is a rare complication associated with endoscopic retrograde cholangiopancreatography (ERCP). PATIENT CONCERNS: A 68-year-old man who presented with worsening cholestasis after ERCP for the removal of a common bile duct stone. DIAGNOSIS: Total bilirubin increased up to 35.2 mg/dL after the 21st day post-ERCP. A percutaneous liver biopsy was performed and drug-related cholestasis was suspected as occurring as a result of the contrast agent. INTERVENTIONS: Oral ursodeoxycholic acid and cholestyramine were prescribed to the patient. OUTCOMES: By the 7th week post-ERCP, the patient's symptoms and markers of physiological health began to resolve. The bilirubin returned to normal levels on the 106th day post-ERCP. We reviewed the literature for studies of 9 patients with jaundice more than 30 days post-ERCP, the peak of total serum bilirubin occurred on 16th ±â€Š7th days and the recovery followed after mean time of 54th ±â€Š22th days. LESSONS: Although the cholestasis was prolonged, the outcome was favorable after medical therapy. There were no long-term consequences for the patient.

Camellia Oleifera Seed Extract Mildly Ameliorates Carbon Tetrachloride-Induced Hepatotoxicity in Rats by Suppressing Inflammation.

The objective of this study was to evaluate the effects of a hot-water extract of defatted Camellia oleifera seeds (CSE) in carbon tetrachloride (CCl4 )-induced liver damage in rats. Wistar rats were separated into four groups including the normal (N) and CCl4 control (C) groups, which are fed a control diet, and the CCL (low-dose CSE) and CCH (high-dose CSE) groups, which are fed with a control diet plus different amount of CSE for an 8-week experimental period. Liver injury in the C, CCL, and CCH groups was induced by injecting CCl4 (i.p.) twice a week from the 5th week to the end of the study. In CCl4 -treated rats, the alanine transaminase (ALT) and aspartate transaminase (AST) activities and malondialdehyde (MDA) concentration significantly increased compared to the normal group. Lower antioxidative enzyme activities and higher proinflammatory cytokines, transforming growth factor-ß (TGF-ß) and hydroxyproline concentrations in the liver were also found in the CCl4 -treated group compared to the normal group. In contrast, the administration of CSE alleviated the biochemical and histopathological changes including inflammation, liver cell damage, and fibrosis caused by CCl4 in rats. Our results indicated that CSE exhibited hepatoprotective effects in CCl4 -induced liver hepatotoxicity through alleviating hepatic inflammation and fibrosis in rats. PRACTICAL APPLICATION: Camellia oleifera are widely used for edible oil production while the defatted seeds pomace is often discarded. We found that extract of C. oleifera pomace containing phenolic compounds, saponins, and polysaccharides showed protective effects chemical-driven liver damage and, therefore, may be used in further studies and developing functional foods.

Correction: Metformin sensitizes anticancer effect of dasatinib in head and neck squamous cell carcinoma cells through AMPK-dependent ER stress.

[This corrects the article DOI: 10.18632/oncotarget.1628.].

Correction: Metformin sensitizes anticancer effect of dasatinib in head and neck squamous cell carcinoma cells through AMPK-dependent ER stress.

[This corrects the article DOI: 10.18632/oncotarget.1628.].

Strong SOX10 expression in human papillomavirus-related multiphenotypic sinonasal carcinoma: report of 6 new cases validated by high-risk human papillomavirus mRNA in situ hybridization test.

Human papillomavirus (HPV)-related multiphenotypic sinonasal carcinoma (HMSC) is associated with high-risk HPV (HR-HPV) infection. Using HR-HPV messenger RNA (mRNA) in situ hybridization (ISH), we reported 6 new HMSC cases and compared their histopathology with that of sinonasal adenoid cystic carcinoma. Using p16 immunohistochemistry (IHC) and HR-HPV ISH, we retrospectively identified 6 HMSC cases. All HMSC cases were positive for HR-HPV mRNA ISH and p16 IHC. Two HMSC cases had overlying atypical squamous epithelium, and 1 had invasive squamous cell carcinoma (SCC). All HMSC cases were SOX10 positive, whereas the overlying atypical squamous epithelium and the SCC were SOX10 negative. One atypical HMSC-like case was also identified, which was positive for HR-HPV mRNA ISH, HR-HPV DNA ISH, and SOX10 IHC, but negative for p16 IHC. This study showed that HR-HPV mRNA ISH was a useful tool to diagnose HMSC and had stronger signals compared with HR-HPV DNA ISH. HR-HPV E6/E7 mRNA could be identified in the overlying atypical squamous epithelium and the invasive SCC. A combination of p16 and SOX10 IHC will be a useful screening panel for HMSC followed by confirmatory HR-HPV mRNA ISH test.

Renoprotective Effects of Antroquinonol in Rats with Nω-Nitro-l-Arginine Methyl Ester-Induced Hypertension.

Endothelial dysfunction leads to elevation of blood pressure and vascular remodeling, which may result in tissue injuries. The aim of this study was to investigate the mechanisms and effects of antroquinonol on hypertension and related renal injuries. Rats were fed water containing 25 mg/kg/day Nω-nitro-l-arginine methyl ester (L-NAME) to induce hypertension, and a diet with or without antroquinonol (20 or 40 mg/kg/day) for a 9-week experiment. During the experimental period, antroquinonol reduced the elevation of systolic and diastolic blood pressure. At the end of the study, we found that the antroquinonol groups had lower serum creatinine, renal endothelin-1, angiotensin II, and malondialdehyde levels and arteriole thickening. We found that the 40 mg/kg/day antroquinonol group had lower renal nicotinamide adenine dinucleotide phosphate (NADPH) oxidase activities, greater nuclear factor erythroid-2, and heme oxygenase-1 expressions. Moreover, we also found that antroquinonol decreased proinflammatory cytokine concentrations in the kidney by modulating the nuclear factor-κB pathway. These results suggest that antroquinonol may ameliorate hypertension and improve renal function by reducing oxidative stress and inflammation in rats with endothelial dysfunction.