Renal expression of trefoil factor 3 mRNA in association with tubulointerstitial fibrosis in IgA nephropathy

Aim

Trefoil factor 3 (TFF3) is a small peptide that is involved in mucosal protection. TFF3 is widely expressed in multiple tissues including kidney tissue. Previous studies have reported that the levels of urinary TFF3 are significantly increased in patients with chronic kidney disease. The aim of this study is to detect the TFF3 mRNA in kidney and elucidate the relationship between renal TFF3 mRNA and tubulointerstitial fibrosis in IgA nephropathy (IgAN).

Methods

We investigated the renal mRNA expression of TFF3 by real‐time PCR analysis in biopsy specimens from patients with IgAN, other glomerulonephritis (OGN) and minor glomerular abnormalities (MGA). We also determined the renal localization of TFF3 and the levels of urinary TFF3 by immunostaining and ELISA, respectively.

Results

The renal TFF3 mRNA expression was significantly associated with the urinary TFF3 secretion and the tubulointerstitial fibrosis score in the IgAN group alone. Immunostaining of the renal specimen of IgAN patients revealed that TFF3 is located in the renal tubular epithelial cells. The locations were almost the same as those that showed uromodulin positivity; specifically, the thick ascending limb (TAL) of the loop of Henle and the early portion of the distal tubule. The urinary TFF3 levels were positively correlated with the levels of urinary biomarkers of tubulointerstitial injury in such patients.

Conclusion

Renal TFF3 mRNA is associated with renal tubulointerstitial fibrosis in IgAN patients. The TFF3 located in the renal tubular epithelial cells may play a role in the progression of tubulointerstitial fibrosis in IgAN patients.     

Clinical experience with chemoradiotherapy comprising S-1 plus low-dose cisplatin in a patient with stage IV anal cancer

We report a case of anal cancer in a 58-year-old woman who complained of narrow, bloody stools and anal pain. Physical examination revealed anal stenosis associated with a circular mass arising in the anal canal. Histological examination of biopsy specimens confirmed a diagnosis of moderately differentiated squamous cell carcinoma. Enhanced computed tomography revealed anal cancer invading the levator ani and the vagina, with lymph-node, multiple hepatic, and pulmonary metastases. The patient received two cycle of chemoradiotherapy with S-1 plus low-dose cisplatin with rest for 4 weeks, leading to complete response of the primary lesion and a partial response of the metastatic lesions. Each cycle included oral S-1 (120 mg/body; day 1-21), cisplatin (10 mg/body; day 1-5, 8-12) and radiotherapy (2 Gy/day; day 1-5, 8-12, 15-19). Adverse effects of treatment were mild perineal skin erosion and mild appetite loss, but no hematologic toxicity. Although the patient died 16 months after first admission, chemoradiotherapy with S-1 plus cisplatin is potentially effective for the management of advanced anal cancer.     

Assessment of Cell Cycle and Induction of Apoptosis by Shiga-like Toxin Produced by Escherichia coli O157:H7 in T47D Breast Cancer Cells Using Flow Cytometry

Background: The low general toxicity against tumors expressing globotriaosylceramide (Gb3) and Shiga-like toxins produced by E. coli have been proposed as an anti-cancer therapy because of their specific target. This study aimed to determine the potency of the local strains of E. coli O157:H7 isolated from humans and cattle as a new breast cancer therapy by analyzing the cell cycle’s inhibition and apoptosis induction. Material and Methods: Approximately 10 cultured T47D cells were subjected to Shiga-like toxin produced by four local isolates of E. coli O157:H7, including KL-48 (2) from humans, and SM-25 (1), SM-7 (1), DS-21 (4) from cattle. Using ATCC 43894 as a control, the treatment was observed for 24 h by two replications. In addition, a FITC-Annexin V and PI assay were used to observe apoptosis and necrosis effect, as well as to analyze the cell cycle using propidium iodide (PI) staining. Results: The results showed the toxicity effect of Shiga in the human T47 D cells line. The viability of the cells is subjected to Shiga-like toxins produced by KL-48 (2), SM7 (1), ATCC 43894, SM-25 (1), and DS-21 (4) isolates decreased with 15.20, 16.36, 22.17,  22.64, and 33.86%, in contrary to control of 94.36%. These were supported by the cells entering the late apoptosis of the cell cycle through each isolate with 67.66, 62.60, 63.68, 63.90, and 54.74%, and a control of 0.01%. Also, the necrosis cell for each treatment of 12.73, 19.3, 10.84, 10.53, and 4.86% was higher than the control of 5.51%. These were confirmed by the higher percentage of the cells treated with toxins of KL-48 (2), SM7(1), ATCC 43894, SM-25 (1), and DS-21 (4), which entered G0-G1 of the cell cycle phase with 66.41, 63.37, 61.52, 55.36, and 47.28%, respectively, than control of 40.69%. Additionally, the toxicity effect was supported by an increase in the cells entering the S and the G2-M phase of the cycle for each treatment. Conclusion: It is concluded that the Shiga-like toxin produced by E. coli O157:H7 local isolates can be developed as a drug against breast cancer based on its effect to arrest induction of the cell cycle and inducing apoptosis.     

In‐depth assessment of snacking behaviour in unmarried adolescent girls 16–19 years of age living in urban centres of Java,Indonesia

Adolescence is a critical period characterized by physical, social, and developmental changes that impact on health and eating behaviour. Indonesia is experiencing dramatic economic and infrastructural changes, causing greater access to the global food industry and media. This transition is influencing food intake trends, leading to new nutritional challenges in adolescent girls. Qualitative research was conducted between November 2016 and January 2017 in five urban sites in Java, Indonesia, to examine individual, social, environmental, and macrosystem factors affecting snacking behaviours in unmarried adolescent girls 16–19 years of age. Methods entailed 30 freelisting exercises, nine key informant interviews, and 16 in‐depth interviews. Freelisting results identified over 200 snack foods, with the most salient processed convenience foods such as chips and cookies. Respondents typically snacked multiple times daily. Widespread availability of affordable and “tasty” snacks makes snack foods appealing meal substitutes. Snacks provide a distraction to boredom and loneliness and an enhancement to social gatherings. Girls exhibited limited understanding or concern about potential negative effects of snacking. Parents facilitate acquisition of nutrient‐poor snacks, whereas friends exert pressure for routine consumption of snack foods. Social media infiltrated with promotions of eateries and snack foods is likely contributing to the preponderance of snack food consumption. Routine consumption of snack foods high in sugar, salt, and fat and skipping meals will likely have long‐term consequences on the nutritional status and health of Indonesian adolescent girls. Findings underline the urgent need to develop contextually relevant, targeted behavioural change strategies to modify the potentially harmful eating and activity patterns of adolescent girls identified in this study and to curb the trajectory of overweight in urban Indonesia.     

Correlation of arterial stiffness to left ventricular function in patients with reduced ejection fraction

Heart failure has been divided into heart failure with preserved left ventricular (LV) ejection fraction (EF) and heart failure with reduced EF, because the pathophysiologies of the two conditions are different. Cardio-ankle vascular index (CAVI) is a new indicator of arterial stiffness, and the most conspicuous feature of CAVI is its independence of blood pressure at the time of measurement. Arterial stiffness has been considered to increase LV afterload, which requires special care to avoid the onset of heart failure. We compared the correlation of arterial stiffness as assessed by CAVI to LV function in 44 hypertensive patients with preserved EF (EF: 71 ± 7%) and 31 patients with reduced EF (48 ± 8%). All of patients with reduced EF had history of both hypertension and myocardial infarction. Using Doppler echocardiography, LV diastolic and systolic function was evaluated by measuring peak early diastolic mitral annular velocity (e') and global LV peak systolic longitudinal strain (GPSLS), respectively. In patients with preserved EF, CAVI was correlated with e' (r = -0.313, p = 0.038), but not with GPSLS (r = 0.207). By contrast, CAVI was correlated with GPSLS (r = 0.604, p < 0.001) as well as e' (r = -0.393, p = 0.029) in patients with reduced EF. Thus, patients with reduced EF showed a closer correlation of arterial stiffness to LV function compared with patients with preserved EF. Therefore, hypertensive patients with reduced EF require a stricter regimen for treating arterial stiffness than their counterparts with preserved EF.