IL-17A,IL-17E and IL-17F as Potential Biomarkers for the Intensity of Low-Grade Inflammation and the Risk of Cardiovascular Diseases in Obese People

Low-grade inflammation is a factor that predisposes to many obesity-related comorbidities. The immune mechanisms controlling the inflammatory response related to the secretory activity of adipocytes and its consequences for the organism are still under investigation. Methods: 84 obese adult volunteers (BMI ≥ 30 kg/m²) were tested by BIA. Serum samples were collected to analyze the concentrations of interleukins IL-17A, IL-17E and IL-17F. The subjects completed the original questionnaire, the FFQ-6 food consumption frequency questionnaire and the food diary. Results: The level of IL-17E and IL-17F was positively correlated with the BMI value and the level of IL-17E increased with the content of subcutaneous fat. Its increased blood concentration was also observed in individuals who declared that they were diagnosed with atherosclerosis and/or were taking beta-blockers. Products that were related with a low level of the above-mentioned interleukins were vegetables, groats, eggs, red meat, fast-food and alcohol. The level of these interleukins was positively correlated with the frequent consumption of confectionery and breakfast cereals. Nutrients that decreased the concentrations of IL-17 isoforms were potassium, iron, vitamins B6 and C, and folic acid. Conclusions: Both IL-17E and IL-17F may be closely related to the intensity of low-grade inflammation and be biomarkers of cardiovascular disease risk. Food products or the nutrients they contain may affect the levels of the above-mentioned interleukins as well as IL-17A.     

COVID-19 Mortality and Social Inequalities: Escherichia coli O103 outbreak associated with minced celery among hospitalized individuals in Victoria,British Columbia, 2021

BackgroundIn April 2021, a Shiga toxin-producing Escherichia coli (E. coli) (STEC) O103 outbreak was identified among patients at two hospitals in Victoria, British Columbia (BC). The objective of this study is to describe this outbreak investigation and identify issues of food safety for high-risk products prepared for vulnerable populations.MethodsConfirmed cases of E. coli O103 were reported to the Island Health communicable disease unit. The provincial public health laboratory conducted whole genome sequencing on confirmed case isolates, as per routine practice for STEC in BC. Exposure information was obtained through case interviews and review of hospital menus. Federal and local public health authorities conducted an inspection of the processing plant for the suspect source.ResultsSix confirmed cases of E. coli O103 were identified, all related by whole genome sequencing. The majority of cases were female (67%) and the median age was 61 years (range 24–87 years). All confirmed cases were inpatients or outpatients at two hospitals and were exposed to raw minced celery within prepared sandwiches provided by hospital food services. A local processor supplied the minced celery exclusively to the two hospitals. Testing of product at the processor was infrequent, and chlorine rinse occurred before mincing. The spread of residual E. coli contamination through the mincing process, in addition to temperature abuse at the hospitals, are thought to have contributed to this outbreak.ConclusionRaw vegetables, such as celery, are a potential source of STEC and present a risk to vulnerable populations. Recommendations from this outbreak include more frequent testing at the processor, a review of the chlorination and mincing process and a review of hospital food services practices to mitigate temperature abuse.     

阻断NHE1抑制人胶质母细胞瘤细胞增殖和侵袭的研究

目的分析Na⁺/H⁺交换蛋白1（NHE1）抑制剂对癌基因BRAF野生型（BRAF^WT）和激活型BRAF^V600E突变的胶质母细胞瘤（GBM）细胞生长和侵袭能力的影响。 方法NHE1抑制剂Cariporide分别处理U251（BRAF^WT）和AM38（BRAF^V600E）GBM细胞系,乙酰甲酯化的2’,7’-双（2-羧乙基）-5（6）-羧荧光素荧光探针处理细胞并采用紫外分光光度计检测细胞在440 nm与490 nm的荧光强度,计算荧光强度比值以反映NHE1的活性,MTT法检测细胞增殖活性,基质胶-Transwell实验检测细胞侵袭能力。 结果AM38细胞的NHE1活性、增殖和侵袭能力均显著高于U251细胞,差异均有统计学意义（P=0.006、0.010、0.047）;Cariporide处理的U251和AM38细胞的NHE1活性、增殖和侵袭能力均显著低于溶剂二甲基亚砜处理的U251和AM38细胞,差异均有统计学意义（U251：P=0.012、0.023、0.044;AM38：P=0.006、0.001、0.038）。 结论采用Cariporide阻断NHE1活性可有效抑制BRAF^WT和BRAF^V600E突变型GBM细胞的增殖和侵袭。     

Vitamin E and cancer prevention: Studies with different forms of tocopherols and tocotrienols

α-Tocopherol (α-T) is the major form of vitamin E (VE) in animals and has the highest activity in carrying out the essential antioxidant functions of VE. Because of the involvement of oxidative stress in carcinogenesis, the cancer prevention activity of α-T has been studied extensively. Lower VE intake or nutritional status has been shown to be associated with increased cancer risk, and supplementation of α-T to populations with VE insufficiency has shown beneficial effects in lowering the cancer risk in some intervention studies. However, several large intervention studies with α-T conducted in North America have not demonstrated a cancer prevention effect. More recent studies have centered on the γ- and δ-forms of tocopherols and tocotrienols (T3). In comparison with α-T, these forms have much lower systemic bioavailability but have shown stronger cancer-preventive activities in many studies in animal models and cell lines. γ-T3 and δ-T3 generally have even higher activities than γ-T and δ-T. In this article, we review recent results from human and laboratory studies on the cancer-preventive activities of different forms of tocopherols and tocotrienols, at nutritional and pharmacological levels. We aim to elucidate the possible mechanisms of the preventive actions and discuss the possible application of the available information for human cancer prevention by different VE forms.     

早期宫颈癌组织中ATG-12表达与HPV16-E6/E7-DNA病毒载量及预后的关系

目的探讨早期宫颈癌组织中自噬相关蛋白-12(ATG-12)与人乳头瘤病毒(HPV)16-E6/E7-DNA病毒载量及预后的关系。方法选取2015年1月至2017年12月期间在安徽皖北煤电集团总医院保存的宫颈活检或手术切除宫颈组织203例,包括30例慢性宫颈炎、18例宫颈上皮内瘤变(CIN)Ⅰ、23例CINⅡ、26例CINⅢ和106例早期(ⅠA2~ⅡB期)宫颈鳞状上皮癌(CSCC)。采用巢式多重聚合酶链式反应(NM-PCR)和免疫组化染色SP法检测组织中HPV 16-E6/E7-DNA病毒载量和ATG-12蛋白表达。分析ATG-12蛋白表达与早期CSCC临床病理特征的关系。随访CSCC患者无瘤生存时间(DFS)。采用Cox风险比例回归模型分析影响CSCC预后的因素。结果CSCC组织ATG-12蛋白阳性表达率为26.42%(28/106),低于慢性宫颈炎和CIN组织(P<0.05)。ATG-12蛋白表达与HPV16-E6/E7-DNA病毒载量呈负相关(r=-0.306,P=0.001;r=-0.436,P=0.001)。ATG-12蛋白表达与FIGO分期、间质浸润、淋巴脉管间隙浸润、淋巴结转移有关(P<0.05)。随访11~64个月,ATG-12蛋白阳性表达患者5年无瘤生存率为78.57%(22/28),ATG-12蛋白表达阴性患者5年无瘤生存率为60.26%(47/78)。多因素Cox风险回归模型结果显示,HPV16-E6/E7-DNA病毒载量和ATG-12蛋白表达是影响患者DFS的独立预后因素(P<0.05)。结论早期宫颈鳞状上皮癌组织中ATG-12阳性表达率低,与HPV16-E6/E7-DNA病毒载量呈负相关,有望成为评估HPV阳性早期宫颈癌患者预后的重要指标。     

Suppression of KIF3A inhibits triple negative breast cancer growth and metastasis by repressing Rb‐E2F signaling and epithelial‐mesenchymal transition

Triple negative breast cancer (TNBC) displays higher heterogeneity, stronger invasiveness, higher risk of metastasis and poorer prognosis compared with major breast cancer subtypes. KIF3A, a member of the kinesin family of motor proteins, serves as a microtubule‐directed motor subunit and has been found to regulate early development, ciliogenesis and tumorigenesis. To explore the expression, regulation and mechanism of KIF3A in TNBC, 3 TNBC cell lines, 98 cases of primary TNBC and paired adjacent tissues were examined. Immunohistochemistry, real‐time PCR, western blot, flow cytometry, short hairpin RNA (shRNA) interference, 3‐(4,5‐dimethylthiazol‐2‐yl)‐2,5‐diphenyltetrazolium bromide (MTT), colony formation techniques, transwell assays, scratch tests, and xenograft mice models were used. We found that KIF3A was overexpressed in TNBC and such high KIF3A expression was also associated with tumor recurrence and lymph node metastasis. Silencing of KIF3A suppressed TNBC cell proliferation by repressing the Rb‐E2F signaling pathway and inhibited migration and invasion by repressing epithelial‐mesenchymal transition. The tumor size was smaller and the number of lung metastatic nodules was lower in KIF3A depletion MDA‐MB‐231 cell xenograft mice than in the negative control group. In addition, KIF3A overexpression correlated with chemoresistance. These results suggested that high expression of KIF3A in TNBC was associated with the tumor progression and metastasis.     

Anesthesia and ventilation options for flex robotic assisted laryngopharyngeal surgery

BackgroundTransoral treatment of benign and malignant lesions of laryngopharynx has limitations in exposure and access, partially due to the endotracheal tube (ETT). With a proper airway control to tailor ventilation and maximize exposure, transoral Flex robotic surgery (FLEX), using its 3D camera and instruments, can expand its ability. Choosing the right ETT, including a novel concept of using jet ventilation (JV) in FLEX, and placement technique can allow augmentation of the advantages that robotic surgery offers.MethodsChart review of FLEX assisted procedures was performed. Attention was given to demographics, all events of airway manipulation and ventilation type, procedures performed and outcomes including adverse effects.ResultsFifty-two patients underwent eighty procedures. The airway was manipulated sixty-four times to include 8 JV. All possible FLEX instruments including CO2 laser were used. Three novel possible indications for trans-oral robotic surgery including the feasibility of JV in FLEX procedures were shown.ConclusionsLesions of the tongue base, hypopharynx, larynx and trachea have the possibility to be managed with adequate exposure with minimal obstruction from ETT. Robotic HD camera permits both the surgeon and anesthesiologist to observe surgery and safely monitor the airway. An algorithm was developed for selecting ideal ventilation method for different procedures. The FLEX and the utilization of JV allows flexibility of two instruments without obstruction.