Perianal rhabdomyosarcoma in an adult: A case report and review of the literature.

Perianal/perineal rhabdomyosarcomas (PRMS) is rare, and the outcome is poor. A 29-year-old female presented with perineal rhabdomyosarcomas revealed metastases to inguinal lymph nodes on the bilateral side. Disease progression was discovered when the patient got adjuvant epirubicin, ifosfamide, and bevacizumab for 2 cycles. After 3 cycles of nivolumab, dacarbazine, cisplatin, and vinblastine therapy, a partial response was identified in the patient. The surgical resection was performed. The patient received neoadjuvant chemotherapy before surgery and was weak after surgery, so he did not receive chemoradiotherapy. The patient succumbed after 11 months postoperatively due to widespread intraabdominal metastasis.

Reverse relationship between autophagy and apoptosis in an in vitro model of cortical neuronal injury.

Autophagy and apoptosis are intertwined, and their relationship involves complex cross-talk. Whether the activation and inhibition of autophagy protect or damage neurons in the central nervous system has been a matter of longstanding controversy. We investigated the effect of autophagy on the apoptosis of cortical neurons after oxygen- and glucose-deprivation/reoxygenation (OGD/R) injury in vitro and found that protective mechanism activation was the predominant response to enhanced autophagy activation and increased autophagic flux. After successful establishment of an OGD/R model with cortical neurons, the autophagy activator rapamycin (Rap) or the late-autophagy inhibitor bafilomycin A1 (BafA1) was added to cell groups according to the experimental design. Cell viability was determined by Cell Counting Kit-8 (CCK-8) and lactate dehydrogenase (LDH) assays, and the apoptosis rate was measured by analysing Annexin V-FITC/PI-stained cells. The protein and mRNA expression levels of the apoptosis factors Caspase8 and Caspase3 and autophagy-associated proteins LC3 and p62 were measured by Western blotting and RT-qPCR. The extent of autophagic flux was determined by measuring the intensity of double immunofluorescence labelled protein after cells were transfected with RFP-GFP-LC3-expressing virus, and the ultrastructures of autophagosomes were observed by transmission electron microscopy (TEM). The results showed that cell viability decreased and that cells underwent autophagy and apoptosis after OGD/R. After the addition of Rap, cell viability was increased, and the apoptosis rate was decreased significantly. In addition, the level of the autophagic flux protein LC3II was increased, and the level of p62 was decreased. The number of autophagosomes and the ratio of autophagosomes to lysosomes were increased significantly. After BafA1 intervention, however, these results were reversed, with decreased cell viability, a significantly increased apoptosis rate, and disrupted autophagic flux. In conclusion, enhanced autophagy activation or autophagic flux exerted a significant protective effect on neurons after OGD/R injury in vitro.

Neuritin attenuates oxygen-glucose deprivation/reoxygenation (OGD/R)-induced neuronal injury by promoting autophagic flux.

The autophagy/apoptosis interaction has always been a focus of study in pathogenicity models. Neuritin is a neurotrophic factor that is highly expressed primarily in the central nervous system. Our previous study revealed that it protects against apoptosis in cortical neurons subjected to oxygen-glucose deprivation (OGD)/reoxygenation (OGD/R), and later animal experiments revealed that it can increase the expression of the autophagy-related protein LC3. Whether this neuroprotective effect is closely related to autophagy is still unclear. In this study, we hypothesized that neuritin can promote autophagic flux to protect nerve cells after OGD/R. To verify this hypothesis, we induced OGD/R in primary cortical neurons and assessed cell viability by the CCK8 and LDH assays. Cell apoptosis was assessed by Annexin V-FITC/PI, staining, and the contents and mRNA abundances of the autophagy-related proteins LC3 and p62, the apoptotic protein Caspase3 were quantified by Western blotting and RT-PCR. Autophagic flux was assessed by immunofluorescence after RFP-GFP-LC3 virus transfection, and ultrastructural changes in autophagosomes were observed by transmission electron microscopy (TEM). The results showed that cell viability was decreased, apoptosis was increased and autophagy was enhanced after OGD/R. Neuritin significantly increased cell viability, decreased apoptosis, further increased the expression of the autophagic flux-related protein LC3, further decreased p62 expression, and significantly increased the autophagosome number and autophagosome to lysosome ratio. Bafilomycin A1 (BafA1) is a late autophagy inhibitor, aggravated cell damage and apoptosis and counteracted the enhancement of autophagy activation and protective effects of neuritin. In conclusion, neuritin may promote the completion of autophagic flux by ameliorating neuronal damage after OGD/R.

Polyphenol-Rich Loquat Fruit Extract Prevents Fructose-Induced Nonalcoholic Fatty Liver Disease by Modulating Glycometabolism, Lipometabolism, Oxidative Stress, Inflammation, Intestinal Barrier, and Gut Microbiota in Mice.

Fructose as a daily sweetener is widely recognized as a risk catalyst for nonalcoholic fatty liver disease (NAFLD). The aim of current study is to evaluate the effects and molecular mechanism by which polyphenol-rich loquat fruit extract (LFP) prevents NAFLD in mice fed 30% fructose water (HF) for 8 weeks. Administration of LFP to HF-fed mice mitigated abnormal body weight, disordered lipid metabolism, oxidative stress, and inflammation through a mechanism regulated by the AKT, ChREBP/SREBP-1c, Nrf2, and TLR4/MyD88/TRIF pathways. LFP caused a significant decrease in the endotoxin content (16.67-12.7 EU/mL) in the liver of HF-fed mice. LFP not only improved HF-induced breakage of the intestinal barrier via interacting with tight junction proteins (ZO-1, occludin), mucin, and immunoreaction in the colon but also maintained normal colonic Firmicutes/Bacteroidetes ratios and the relative abundance of Veillonella in HF-fed mice. Our results suggest that LFP may serve as a nutritional agent for protecting liver in HF-fed mice.

Multivariate Analysis Illuminates the Effects of Vacuum Drying on the Extractable and Nonextractable Polyphenols Profile of Loquat Fruit.

The current study evaluated the effects of vacuum drying on the whole polyphenol profile of loquat fruit, including extractive and nonextractive polyphenols. Absorbance analysis determined that total polyphenol content and antioxidant levels were higher in loquat fruit vacuum dried at 140 °C than in loquat fruit vacuum dried at 70 °C. The results of ultra-HPLC-triple quadruple mass spectrum analysis showed that 15 phenolic acids and 17 flavonoids were found in dried loquat fruit. Multivariate integrative (MINT) sparse partial least square-discriminant analysis showed that vacuum drying affects the polyphenol profile of loquat fruit. Co-analysis of principal component analysis, partial least square-discriminant analysis, and orthometric partial least square-discriminant analysis revealed that vacuum drying mainly changed the content of chlorogenic acid, cryptochlorogenic acid, protocatechuic acid, phloretin, and hesperidin in loquat fruit. Chlorogenic acid (12.020 to 39.153 µg/g d.b. [dried base weight]), the main polyphenol in dried loquat fruit, was degraded to caffeic acid (0.028 to 2.365 µg/g d.b.) and protocatechuic acid (0.014 to 18.285 µg/g d.b.) during vacuum drying. Moreover, vacuum drying also induced the isomerization of chlorogenic acid into cryptochlorogenic acid (1.628 to 12.737 µg/g d.b.). These results might be used to develop dried loquat fruit with high levels of polyphenols and antioxidant activity. PRACTICAL APPLICATION: Interests in polyphenols of loquat fruit had increased greatly because of their possible role in health benefits. This work provided a holistic insight in the effects of vacuum drying on polyphenols profile of loquat fruit. Current results have contributed to the development of vacuum-drying method, which produced loquat fruit rich in polyphenols. Furthermore, it also suggested that multivariate analysis was a feasible method to reveal the important changes of polyphenols profile during food processing.

PAK4 enhances TGF-ß1-induced epithelial-mesenchymal transition through activating ß-catenin signaling pathway in renal tubular epithelial cells.

Epithelial-mesenchymal transition (EMT) of renal tubular epithelial cells contributes to development and progression of renal interstitial fibrosis in CKD. p21-activated kinase 4 (PAK4) is a member of serine/threonine protein kinases but the role of PAK4 in renal fibrosis remains unknown. In this study, we investigated the effects of PAK4 on transforming growth factor-ß1 (TGF-ß1)-treated human renal tubular epithelial cells (HK-2 cells) and aimed to elucidate probable mechanisms for its fibrogenic effects. Our results revealed that PAK4 was highly expressed in TGF-ß1-treated HK-2 cells. Overexpressing PAK4 could further decrease TGF-ß1-induced E-cadherin expression and increase TGF-ß1-induced fibronectin and vimentin expression in HK-2 cells. In addition, overexpressing PAK4 could promote the translocation of ß-catenin from cell membranes into the nucleus in TGF-ß1-treated HK-2 cells. These results indicate that PAK4 could enhance TGF-ß1-induced EMT in renal tubular epithelial cells. Our findings indicate that PAK4 may promote renal interstitial fibrosis by activating ß-catenin signaling pathway. Thus, we suggest that PAK4 might be a potential therapeutic target for ameliorating renal interstitial fibrosis.

A practical guide to treatment of infantile hemangiomas of the head and neck.

Infantile hemangiomas are the most common benign vascular tumors in infancy and childhood. As hemangioma could regress spontaneously, it generally does not require treatment unless proliferation interferes with normal function or gives rise to risk of serious disfigurement and complications unlikely to resolve without treatment. Various methods for treating infant hemangiomas have been documented, including wait and see policy, laser therapy, drug therapy, sclerotherapy, radiotherapy, surgery and so on, but none of these therapies can be used for all hemangiomas. To obtain the best treatment outcomes, the treatment protocol should be individualized and comprehensive as well as sequential. Based on published literature and clinical experiences, we established a treatment guideline in order to provide criteria for the management of head and neck hemangiomas. This protocol will be renewed and updated to include and reflect any cutting-edge medical knowledge, and provide the newest treatment modalities which will benefit our patients.

Curcumin attenuates insulin resistance in hepatocytes by inducing Nrf2 nuclear translocation.

BACKGROUND/AIMS: NF-E2-Related Factor-2 (Nrf2) is a transcription factor that plays a crucial role in the cellular protection against oxidative stress. Curcumin has been reported to induce Nrf2 nuclear translocation and upregulate the expression of numerous reactive oxygen species (ROS) detoxifying and antioxidant genes in hepatocytes. This study was designed to investigate whether curcumin-induced Nrf2 nuclear translocation could reduce ROS-mediated insulin resistance in cultured LO2 hepatocytes. METHODOLOGY: Human LO2 hepatocytes were incubated with curcumine and glucose oxidase (GO) in the presence/absence of wortmannin (a phosphatidyinositol 3-kinase (PI3K) inhibitor), oxidative stress, cellular damage, Nrf2 nuclear translocation and insulin resistance were measured. RESULTS: GO exposure significantly increased intracellular ROS, glutathione (GSH) depletion, malondialdehyde (MDA) formation, and increased activities of cellular lactate dehydrogenase (LDH) and aspartate amino transferase (AST), as well as causing insulin resistance. Curcumin pretreatment significantly attenuated these disturbances in intracellular ROS, liver enzyme activity and significantly antagonized the lipid peroxidation, GSH depletion and insulin resistance induced by GO in LO2 hepatocytes. These effects paralleled Nrf2 nuclear translocation induced by curcumin. Wortmannin partially blocked curcumin-induced Nrf2 nuclear translocation. In addition, wortmannin prevented curcumin-induced improvements in intracellular ROS, MDA formation, GSH depletion, liver enzyme activity and insulin resistance in cultured LO2 hepatocytes. CONCLUSIONS: These findings suggest that curcumin could reduce ROS-mediated insulin resistance in hepatocytes, at least in part through nuclear translocation of Nrf2.