Magnolol supplementation alleviates diquat-induced oxidative stress via PI3K-Akt in broiler chickens.

This experiment was conducted to investigate the effects of magnolol on the oxidative parameters and jejunum injury induced by diquat in broiler chickens. This test adopts a 2 × 2 factors design, a total of 288 one-day-old male AA broiler chicks randomly allocated to four groups, consisting of six replicates of 12 birds each, which was then denoted as CON group, diquat (DIQ) group (16 mg/kg BW diquat was injected into birds at the age of 21 days), magnolol (MAG) group (basic bird diet supplemented with 300 mg/kg magnolol), and MAG + DIQ group. At 21 days of age, broilers in the DIQ group and the MAG + DIQ group were intraperitoneally injected with 16 mg/kg BW diquat. Results showed that diet supplementing with MAG could alleviate the decrease of ADG to a certain extent after exposure to DIQ. Addition of magnolol to the diet alleviated the decrease of ADG during injection, antioxidant enzymes, and gene expression and increased the markers of oxidative damage induced by diquat induction. Magnolol supplement reversed the increase of apoptotic cells in the diquat-induced chicken jejunum. RNA sequencing showed that PI3K-Akt, calcium, and NF-kappa B signaling pathways were the main enrichment pathways between the DIQ group and the MAG + DIQ group. Our findings revealed that magnolol may improve antioxidant enzyme activity and expression of related genes through the PI3K-Akt pathway to alleviate oxidative stress.

Omega-3 fatty acids for uremic pruritus: A meta-analysis of randomized controlled trials.

Uremic pruritus (UP) is common in the late stages of chronic kidney disease. Currently, there is a lack of effective treatment for UP. Limited evidence exists on the therapeutic effect of omega-3 fatty acid (O3FA). The aim of this study was to evaluate the efficacy of O3FA supplements in UP patients. We evaluated the efficacy of O3FA supplements in patients with UP through a systematic review and a meta-analysis of randomized control trials retrieved from PubMed, Embase, Cochrane Library, CINAHL, and ClinicalTrials.gov databases. The included studies were summarized and assessed for the risk of bias, and pruritus assessment results were analyzed. To compared with a controlled group, five articles including 164 participants published between 2012 and 2019 using different pruritus scales reported that patients taking O3FA supplement exhibited no significant decrease in the pruritus score (standardized mean difference [SMD] =1.34, 95% confidence interval [CI] = -2.70-0.01, P = 0.05), but three articles using same pruritus scale significant decrease Duo pruritus score (SMD = -0.85, 95% CI = -1.39 to -0.30, P < 0.05). O3FA supplement could be an appealing complementary therapy for UP patients. More rigorously designed studies are needed before recommending the O3FA supplement.

Oncologic feasibility for negative pressure wound therapy application in surgical wounds: A meta-analysis.

Negative pressure wound therapy (NPWT) decreases postoperative complications of various surgeries. However, the use of NPWT for oncological surgical wounds remains controversial. To evaluate the association of NPWT with oncologic recurrence in surgical wounds without residual malignancy, we analysed studies that compared NPWT with conventional non-pressure dressings for cancer surgical wounds without residual tumour by August 12, 2020. We compared tumour recurrence rates and postoperative complications between the two procedures. The six studies included 118 patients who received NPWT, and 149 patients who received conventional non-pressure wound care. The overall quality of the included studies was high based on the Newcastle-Ottawa scale score of 7.5. Tumour recurrence after NPWT was not significantly different compared with conventional non-negative pressure wound care (9.3% versus 11.4%, P = 0.40). There was no significant heterogeneity between the studies (I2  = 3%). Although NTWT was associated with a lower complication rate compared with the control group, the result was non-significant (P = 0.15). Application of NPWT in oncologic resection wounds without residual malignancy revealed no difference in local recurrence and may reduce the risk of postoperative complications compared with conventional non-negative pressure dressings. NPWT can be considered an alternative method for reconstruction in challenging cases.

Plaque-Type Variant of Acquired Rhabdomyomatous Mesenchymal Hamartoma on the Chin: A Case Series.

ABSTRACT: Rhabdomyomatous mesenchymal hamartoma (RMH) is a rare benign tumor composed of skeletal muscle fibers and other mesenchymal-derived cells. The lesions are generally solitary sessile papules or skin tag lesions that occur during childhood. We retrospectively reviewed patients diagnosed with RMH pathologically between January 2001 and June 2020 at a tertiary medical center. A literature review was conducted. Seven plaque-type RMHs on the chin were found, including 6 in adults and one in a 14-year-old boy. The average age was 45.7 years. The onset of the RMH appearance was between several months and years. Pathologically, all patients showed a scattered haphazard arrangement of skeletal muscle bundles in the dermis and/or subcutis. Subcutis replaced by fibrous tissue and skeletal muscle bundles was present in 2 cases. Some skeletal muscles had a periadnexal distribution. This case series demonstrated a distinct clinical presentation of acquired RMH specifically located on the chin.

Spectrum of Hybrid Cysts and Their Clinical Significance.

A hybrid cyst is a cutaneous cyst combining different types of keratinization of those seen in the folliculo-sebaceous-apocrine unit. Previous reports found that it may be occasionally associated with Gardner syndrome. This study aimed to clarify the pathologic findings and clinical significance of hybrid cyst based on case series observations. We retrospectively reviewed patients who fulfilled the pathological criteria of hybrid cyst from 2001 to 2015. The patient profiles, clinical presentations, pathological findings, and associated diseases were analyzed by reviewing the medical records and slides. A total of 71 hybrid cysts were confirmed over the study period. There were 12 pathologic variants. The most frequent variant was combined infundibular cyst and tricholemmal cyst (22 in 71 cases, 30%), followed by infundibular cyst and pilomatricoma (14 in 71 cases, 19%). There was no significant association between sex, age, or site and the pathological type of hybrid cyst. Neither extra-intestinal manifestation nor a family history of Gardner syndrome was found in any case. Hybrid cysts could contain a variety of combinations of components from the folliculo-sebaceous-apocrine unit. No clinical significance was found between demographics and the type of hybrid cyst. No association with Gardner syndrome was identified in this case series.

Concomitant Asymptomatic Intracranial Atherosclerotic Stenosis Increase the 30-Day Risk of Stroke in Patients Undergoing Symptomatic Intracranial Atherosclerotic Stenosis Stenting.

BACKGROUND: In the Stenting and Aggressive Medical Management for Preventing Recurrent Stroke in Intracranial Stenosis (SAMMPRIS) trial, 19.1% of ischemic strokes occurred out of the territory of previously symptomatic stenosis during the mean follow-up period of 23.4 months. However, it is unknown how many ischemic strokes were due to a previously asymptomatic intracranial atherosclerotic stenosis (ICAS). The objective of this study was to investigate whether the concomitant asymptomatic ICAS influences the outcome of patients undergoing symptomatic ICAS stenting. METHODS: We retrospectively reviewed 576 consecutive patients with nondisabling ischemic stroke (modified Rankin scale score of ≤3) who were treated with symptomatic ICAS (≥70% stenosis) stenting with or without concomitant asymptomatic ICAS. The baseline characteristics and the 30-day primary end points (stroke or death after stenting) were compared by bivariate and multivariable logistic analyses. RESULTS: The 30-day rate of primary end points was 5.2%, which was higher in patients with concomitant asymptomatic ICAS (≥50% stenosis) than in those without asymptomatic ICAS (no stenosis or <50% stenosis) (8.9% versus 3.8%, P = .014). In patients with concomitant asymptomatic ICAS, 25% of ischemic strokes occurred out of the territory of the stented artery, whereas in patients without asymptomatic ICAS, no ischemic stroke occurred out of the territory of the stented artery. Multivariable analysis showed that concomitant asymptomatic ICAS was an independent risk factor for 30-day stroke (odds ratio = 2.37, 95% confidence interval, 1.14-5.63; P = .023). CONCLUSIONS: Concomitant asymptomatic ICAS (≥50% stenosis) might increase the 30-day risk of stroke in patients undergoing symptomatic ICAS stenting.

Blocking of stromal interaction molecule 1 expression influence cell proliferation and promote cell apoptosis in vitro and inhibit tumor growth in vivo in head and neck squamous cell carcinoma.

Calcium signal plays an important role in a variety of cancer cell metabolism, but knowledge on its role in head and neck squamous cell carcinoma (HNSCC) is limited. Store-operated calcium entry (SOCE) is the principal Ca2+ entry mechanism that maintains calcium concentration and produces calcium signal in non-excitable cells. SOCE is triggered by stromal interaction molecule 1 (STIM1), which is located in endoplasmic reticulum (ER) as Ca2+ sensor. Although, many studies demonstrated that STIM1 and SOCE play important functions in the regulation of many cancer progressions, their clinical relevance in HNSCC remains unclear. In this study, STIM1 expression levels notably increased in 89% HNSCC tissues compared with those in adjacent normal tissues. Meanwhile, this overexpression was close associated with tumor size but not with neck lymph node metastasis. Thus, this study mainly focuses on STIM1 function in HNSCC tumor growth. Three HNSCC cell lines, namely, TSCCA (oral cancer cell line) and Hep2 (laryngeal cell line) with high STIM1 expression levels and Tb3.1 (oral cancer cell line) with STIM1 expression level lower than previous two cell lines, were selected for in vitro study. Downregulated STIM1 expression levels in TSCCA and Hep2 arrested cells in G0/G1 stages, promoted cell apoptosis, and inhibited cell proliferation. By contrast, upregulated STIM1 expression in Tb3.1 inhibited cell apoptosis and promoted cell proliferation. Induced by thapsigargin (TG), ER stress was amplified when STIM1 expression was downregulated but was attenuated as STIM1 expression was upregulated. Furthermore, TSCCA cell xenograft models confirmed that STIM1 could promote HNSCC tumor growth in vivo. The present study provides new insight into HNSCC molecular mechanism and potential therapeutic target through targeting SOCE-dependent process. However, whether STIM1 participates in HNSCC metastasis requires further study.

Low-level sodium arsenite induces apoptosis through inhibiting TrxR activity in pancreatic ß-cells.

In our previous study, we reported that sodium arsenite induced ROS-dependent apoptosis through lysosomal-mitochondrial pathway in pancreatic ß-cells. Since the thioredoxin (Trx) system is the key antioxidant factor in mammalian cells, we investigate whether the inhibition of Trx system contributes to sodium arsenite-induced apoptosis in this study. After treatment with low-level (0.25-1µM) sodium arsenite for 96h, the thioredoxin reductase (TrxR) activity was decreased significantly in pancreatic INS-1 cells. Following with the inactivation of TrxR, ASK1 was released from combining with Trx, which was evidenced by increased levels of ASK1 in sodium arsenite-treated INS-1 cells. Subsequently, activated ASK1 accelerated the expression of proapoptotic protein Bax and reduced the expression of anti-apoptic protein Bcl-2. Finally, low-level sodium arsenite induced apoptosis via caspase-3 in INS-1 cells. Knockdown of ASK1 alleviated sodium arsenite-induced apoptosis. In summary, the precise molecular mechanisms through which arsenic is related to diabetes have not been completely elucidated, inactivation of Trx system might provide insights into the underlying mechanisms at the environmental exposure levels.

Citreoviridin induces ROS-dependent autophagic cell death in human liver HepG2 cells.

Citreoviridin (CIT) is one of toxic mycotoxins derived from fungal species in moldy cereals. Whether CIT exerts hepatotoxicity and the precise molecular mechanisms of CIT hepatotoxicity are not completely elucidated. In this study, the inhibitor of autophagosome formation, 3-methyladenine, protected the cells against CIT cytotoxicity, and the autophagy stimulator rapamycin further decreased the cell viability of CIT-treated HepG2 cells. Knockdown of Atg5 with Atg5 siRNA alleviated CIT-induced cell death. These finding suggested the hypothesis that autophagic cell death contributed to CIT-induced cytotoxicity in HepG2 cells. CIT increased the autophagosome number in HepG2 cells observed under a transmission electron microscope, and this effect was confirmed by the elevated LC3-II levels detected through Western blot. Reduction of P62 protein levels and the result of LC3 turnover assay indicated that the accumulation of autophagosomes in the CIT-treated HepG2 cells was due to increased formation rather than impaired degradation. The pretreatment of HepG2 cells with the ROS inhibitor NAC reduced autophagosome formation and reversed the CIT cytotoxicity, indicating that CIT-induced autophagic cell death was ROS-dependent. In summary, ROS-dependent autophagic cell death of HpeG2 cells described in this study may help to elucidate the underlying mechanism of CIT cytotoxicity.

Sodium arsenite induces ROS-dependent autophagic cell death in pancreatic ß-cells.

Inorganic arsenic is a worldwide environmental pollutant. Inorganic arsenic's positive relationship with the incidence of type 2 diabetes mellitus arouses concerns associated with its etiology in diabetes among the general human population. In this study, the inhibitor of autophagosome formation, 3-methyladenine, protected the cells against sodium arsenite cytotoxicity, and the autophagy stimulator rapamycin further decreased the cell viability of sodium arsenite-treated INS-1 cells. These finding suggested the hypothesis that autophagic cell death contributed to sodium arsenite-induced cytotoxicity in INS-1 cells. Sodium arsenite increased the autophagosome-positive puncta in INS-1 cells observed under a fluorescence microscope, and this effect was confirmed by the elevated LC3-II levels detected through Western blot. The LC3 turnover assay indicated that the accumulation of autophagosomes in the arsenite-treated INS-1 cells was due to increased formation rather than impaired degradation. The pretreatment of INS-1 cells with the ROS inhibitor NAC reduced autophagosome formation and reversed the sodium arsenite cytotoxicity, indicating that sodium arsenite-induced autophagic cell death was ROS-dependent. In summary, the precise molecular mechanisms through which arsenic is related to diabetes have not been completely elucidated, but the ROS-dependent autophagic cell death of pancreatic ß-cells described in this study may help to elucidate the underlying mechanism.

Perfluorooctane sulfonate blocked autophagy flux and induced lysosome membrane permeabilization in HepG2 cells.

Perfluorooctane sulfonate (PFOS) is an emerging persistent organic pollutant widely distributed in the environment, wildlife and human. In this study, as observed under the transmission electron microscope, PFOS increased autophagosome numbers in HepG2 cells, and it was confirmed by elevated LC3-II levels in Western blot analysis. PFOS increased P62 level and chloroquine failed to further increase the expression of LC3-II after PFOS treatment, indicating that the accumulation of autophagosome was due to impaired degradation rather than increased formation. With acridine orange staining, we found PFOS caused lysosomal membrane permeabilization (LMP). In this study, autophasome formation inhibitor 3-methyladenine protected cells against PFOS toxicity, autophagy stimulator rapamycin further decreased cell viability and increased LDH release, cathepsin inhibitor did not influence cell viability of PFOS-treated HepG2 cells significantly. These further supported the notion that autophagic cell death contributed to PFOS-induced hepatotoxicity. In summary, the data of the present study revealed that PFOS induced LMP and consequent blockage of autophagy flux, leading to an excessive accumulation of the autophagosomes and turning autophagy into a destructive process eventually. This finding will provide clues for effective prevention and treatment of PFOS-induced hepatic disease.

[Clinical analysis of level II occult metastasis of papillary thyroid carcinoma].

OBJECTIVE: To analyze the relevant factors occult II lymph node metastases in papillary thyroid carcinoma (PTC) with clinical factors. METHODS: The medical records of 213 PTC patients with clinically positive neck lymph nodes in level III and IV, and/or V based on preoperative ultrasonography, treated between January 2003 and December 2009 were retrospectively reviewed. All patients had no suspicion of clinical positive neck nodes in level II. Univariate and Multivariate analysis were performed using the Pearson chi-square test or Fisher's exact test and a binary logistic regression test, respectively. RESULTS: The rate of metastasis at levels III, IV, V and VI was 83.6% (178/213), 75.1% (160/213), 13.1% (28/213) and 79.3% (169/213), respectively. The rate of occult metastasis at level II were observed in 16.0% (34/213). In univariate analysis, lymph node metastasis in level II was statistically significantly more frequent in patients with positive level III lymph node and positive lymph node throughout the lateral neck (level III + IV, χ(2) were 11.120 and 5.614 respectively, P < 0.05). Multivariate analysis showed that positive lymph node involvement in all lateral neck (level III + IV) was an independent predictive factor of level II lymph node metastasis (P = 0.033, OR = 3.846). CONCLUSION: In PTC patients without suspicious lymph node in neck level II and III by preoperative US, prophylactic level II lymph node dissection may not be considered.

[Treatment and prognosis analysis of primary parotid squamous cell carcinoma].

OBJECTIVE: To investigate the prognosis-related factors and treatment strategy of primary parotid squamous cell carcinoma. METHODS: Forty-nine primary parotid squamous cell carcinoma treated from 1970 to 2005 were retrospectively analyzed. The follow up data were analyzed by SPSS 13.0 software. RESULTS: Integrated follow up data were obtained from 44 patients with a median follow up time of 38 months (5 - 215 months). Recurrence or distant metastasis of the carcinoma occurred in 21 patients, including 13 local recurrence in parotid or neck and 8 distant metastasis. Local recurrence was the main reason of treatment failure. The 3-year and 5-year survival rate and disease-free survival rate was 52%, 27% and 34%, 16%. Kaplan-Meier and log-rank analysis indicated that age, tumor size, distant metastasis, postoperative radiotherapy, facial nerve dysfunction, neck dissection, skin invasion, and surgical margins were prognosis-related factors. Cox analysis showed that age, facial nerve dysfunction, distant metastasis and surgical margins were the important factors that influenced the prognosis. CONCLUSIONS: Primary parotid gland squamous cell carcinoma is an uncommon tumor, surgery and postoperative radiotherapy are the optimal treatment, which can improve the prognosis of the patients and decrease recurrence of the tumor.

Curcumin attenuates acrylamide-induced cytotoxicity and genotoxicity in HepG2 cells by ROS scavenging.

Acrylamide (AA), a proven rodent carcinogen, has recently been discovered in foods heated at high temperatures. This finding raises public health concerns. In our previous study, we found that AA caused DNA fragments and increase of reactive oxygen species (ROS) formation and induced genotoxicity and weak cytotoxicity in HepG2 cells. Presently, curcumin, a natural antioxidant compound present in turmeric was evaluated for its protective effects. The results showed that curcumin at the concentration of 2.5 microg/mL significantly reduced AA-induced ROS production, DNA fragments, micronuclei formation, and cytotoxicity in HepG2 cells. The effect of PEG-catalase on protecting against AA-induced cytotoxicity suggests that AA-induced cytotoxicity is directly dependent on hydrogen peroxide production. These data suggest that curcumin could attenuate the cytotoxicity and genotoxicity induced by AA in HepG2 cells. The protection is probably mediated by an antioxidant protective mechanism. Consumption of curcumin may be a plausible way to prevent AA-mediated genotoxicity.

Curcumin-induced genotoxicity and antigenotoxicity in HepG2 cells.

Curcumin, a polyphenolic yellow pigment found in turmeric, is commonly used as a coloring agent in foods, drugs, and cosmetics. In our previous study, we found that low levels of curcumin did not increase the reactive oxygen species (ROS) formation and caused no damage to DNA in human hepatoma G2 (HepG2) cells, but at high doses, curcumin imposed oxidative stress and damaged DNA. In the present study, we are determined to investigate the genotoxic and antigenotoxic effects of curcumin using HepG2 cell line, a relevant in vitro model to detect the cytoprotective, antigenotoxic, and cogenotoxic agents. The results of micronucleus (MN) assays showed that, on one hand, curcumin at the high tested concentrations (8 and 16 microg/ml) displayed a small but significant increase in the frequency of MN, and on the other hand, it was observed that the low tested concentration (2 microg/ml) significantly reduced the MN formation induced by the chemotherapeutic agent cyclophosphamide. The present results indicate that curcumin shows both genotoxicity and antigenotoxicity depending on its concentration.