Overexpression of carbonyl reductase 1 in ovarian cancer cells suppresses proliferation and activates the eIF2 signaling pathway.

High expression of carbonyl reductase 1 (CBR1) protein in ovarian cancer cells inhibits tumor growth and metastasis. However, the underlying mechanism is unknown. To investigate the mechanism by which CBR1 suppresses tumor growth, the present study generated ovarian cancer cells that constitutively overexpress human CBR1 (hCBR1) protein. Ovarian cancer cell lines (OVCAR-3 and SK-OV-3) were transfected with a plasmid encoding hCBR1, followed by selection with G418 to isolate hCBR1-overexpressing lines. The proliferation rates of hCBR1-overexpressing cells were then compared with those of negative control and wild-type cells. Overexpression of hCBR1 led to significant inhibition of proliferation (P<0.05). Subsequently, to investigate changes in intracellular signaling pathways, cellular proteins were extracted and subjected to proteome analysis using liquid chromatography followed by mass spectrometry. There was an inverse correlation between CBR1 protein expression and cell proliferation. In addition, Ingenuity Pathway Analysis of hCBR1-overexpressing cell lines was performed, which revealed changes in the expression of proteins involved in signaling pathways related to growth regulation. Of these, the eukaryotic translation initiation factor 2 (eIF2) signaling pathway was upregulated most prominently. Thus, alterations in multiple tumor-related signaling pathways, including eIF2 signaling, may lead to growth suppression. Taken together, the present data may lead to the development of new drugs that target CBR1 and related signaling pathways, thereby improving outcomes for patients with ovarian cancer.

Survey on the Awareness of Menstruation and Menstruation-Related Problems in Athletes among Public High School Physical Education Teachers.

Introduction: In recent years, the activities of female athletes have attracted increasing attention, especially regarding the effect of menstruation on athletic performance. Nevertheless, there are no surveys of these practices among coaches who train non-top-level athletes for general competition. This study aimed to investigate how high school physical education teachers approach the issue of menstruation and the awareness of menstruation-related problems. Methods: This was a questionnaire-based cross-sectional study. The participants were 225 health and physical education teachers from 50 public high schools in the Aomori Prefecture. Participants were asked to answer a questionnaire regarding whether they talk to their female athletes about menstruation, keep track of their menstrual status, or make adjustments for menstruating students. Additionally, we asked for their views on painkiller use and their knowledge of menstruation. Results: The participants included 183 men (81.3%) and 42 women (18.7%); data from 221 participants were analyzed after four teachers were excluded. Teachers of female athletes who communicated with students regarding their menstrual conditions and physical changes were predominantly female (p < 0.01). Regarding the use of painkillers for menstrual pain, more than 70% of respondents said that they recommended their active use. Few respondents reported that they would adjust a game because of athletes with menstrual problems. More than 90% of the respondents knew that there was a change in performance due to the menstrual cycle, and 57% of the respondents understood the relationship between amenorrhea and osteoporosis. Conclusions: Menstruation-related problems are not only issues for top athletes but also important for general competition level athletes. Hence, even in high school clubs, teachers should be educated on how to deal with menstruation-related problems to prevent withdrawal from sports, maximize athletes' abilities, prevent future diseases, and preserve fertility.

Development of transgenic mice overexpressing mouse carbonyl reductase 1.

BACKGROUND: Carbonyl reductase 1 (CBR1) is a nicotinamide adenine dinucleotide phosphate (NADPH)-dependent reductase with broad substrate specificity. CBR1 catalyzes the reduction of numerous carbonyl compounds, including quinones, prostaglandins, menadione, and multiple xenobiotics, while also participating in various cellular processes, such as carcinogenesis, apoptosis, signal transduction, and drug resistance. In this study, we aimed to generate transgenic mice overexpressing mouse Cbr1 (mCbr1), characterize the mCbr1 expression in different organs, and identify changes in protein expression patterns. METHODS AND RESULTS: To facilitate a deeper understanding of the functions of CBR1, we generated transgenic mice overexpressing CBR1 throughout the body. These transgenic mice overexpress 3xFLAG-tagged mCbr1 (3xFLAG-mCbr1) under the CAG promoter. Two lines of transgenic mice were generated, one with 3xFLAG-mCbr1 expression in multiple tissues, and the other, with specific expression of 3xFLAG-mCbr1 in the heart. Pathway and network analysis using transgenic mouse hearts identified 73 proteins with levels of expression correlating with mCbr1 overexpression. The expression of voltage-gated anion channels, which may be directly related to calcium ion-related myocardial contraction, was also upregulated. CONCLUSION: mCbr1 transgenic mice may be useful for further in vivo analyses of the molecular mechanisms regulated by Cbr1; such analyses will provide a better understanding of its effects on carcinogenesis and cardiotoxicity of certain cancer drugs.

Significance of IL36RN mutation analyses in the management of impetigo herpetiformis: A case report and review of published cases.

Impetigo herpetiformis (IH) is a rare variant of generalized pustular psoriasis (GPP), which develops during pregnancy. GPP is associated with mutations of IL36RN, but it is still unclear whether the same is true of IH. A 20-year-old Japanese woman developed erythema and pustules on her trunk during the 27th week of her first pregnancy. Within 1 month, the skin lesions spread over her whole body, accompanied by fever. Skin biopsy revealed Kogoj's spongiform pustules in the epidermis and she was diagnosed with IH. Systemic administration of prednisolone failed to resolve the skin eruption, but it was partially improved by the addition of cyclosporin. The patient gave birth to a healthy female infant. After delivery, her erythema relapsed and the effect of granulocyte and monocyte adsorption apheresis was limited. Thus, secukinumab was administrated, and since then, she has maintained complete remission. Mutation analysis revealed a homozygous c.28C>T (p.Arg10X) mutation in IL36RN. Twelve cases of IH, including that presented here, have been reported together with the results of IL36RN genetic analyses, and 10 of the 12 cases occurred in East Asia (Japan and China) despite the fact that IL36RN mutations in GPP have been reported worldwide. Among 10 IH patients of East Asian descent, seven had IL36RN mutations, all of which were founder mutations causing GPP in East Asia: c.28C>T (p.Arg10X) or c.115+6T>C (p.Arg10ArgfsX1). Thus, East Asian founder mutations may play an important role in the pathogenesis of IH. IH patients with IL36RN mutations have a tendency to require biologics to resolve postpartum flare-ups or sustained psoriatic skin lesions. Because IL36RN mutation status may help predict postpartum flare-ups in IH patients, mutation analysis should be considered to enable preparation for biologic therapy of intractable flare-ups.

Preventive effect of daikenchuto, a traditional Japanese herbal medicine, on onset of ileus after gynecological surgery for malignant tumors.

BACKGROUND: Postoperative ileus is a major complication of abdominal surgical procedures. The purpose of this study was to investigate preventive effect of daikenchuto (DKT) on onset of ileus in patients who received gynecological surgery for malignant tumors. METHODS: A total of 904 patients who received gynecological surgery for malignant tumors by opening retroperitoneum along with retroperitoneal lymph node dissection during a period between 2004 and 2018 were included in this retrospective study. The retroperitoneum was not sutured in all patients. Comparisons were made for proportion of patients developing ileus (frequency of postoperative ileus onset), timing of ileus onset, and treatment types for ileus among following three groups: a group treated with enema or laxatives to release gas if they did not pass the intestinal gas for 3 days postoperatively (Group A, n = 152); a group treated with adhesion-inhibitory absorptive barrier at the opening to the retroperitoneum (Group B, n = 188); and a group treated with adhesion-inhibitory absorptive barrier and oral intake of DKT 7.5 g per day (Group C, n = 564). RESULTS: The frequency of ileus onset significantly decreased in both Groups B (4.8%) and C (3.5%) compared to Group A (16.4%). Furthermore, the frequency of ileus onset was significantly less in Group C compared to Group B. For the treatment types, frequency of ileus, which was successfully treated only with conservative therapy, was the same for Groups B and C. However, incidence of serious ileus that required surgery decreased by 45% in Group C (2/564) compared to Groups A (2/152) and B (3/188). CONCLUSIONS: Results suggest that DKT prevents development of serious ileus after gynecological surgery for malignant tumors and therefore contributes to improvement in patients' QOL.

Streptococcal Toxic Shock Syndrome: Life Saving Role of Peritoneal Lavage and Drainage.

PURPOSE: We encountered a case where an infection with group A streptococcus (GAS; ie, Streptococcus pyogenes) initially caused primary peritonitis and then subsequently caused streptococcal toxic shock syndrome. The patient's life was likely saved by an emergency laparotomy followed by extensive peritoneal lavage and drainage. CASE PRESENTATION: A 40-year-old woman was admitted to the Emergency Department for lower abdominal pain and numbness in the extremities. She presented with systemic inflammatory response syndrome. An emergency laparotomy was performed, and ascites that resembled pus and general peritonitis were noted. Peritoneal lavage and drainage were performed, and GAS was isolated from peritoneal fluid. Gram staining of cervical polyp specimens revealed Gram-positive bacteria. CONCLUSIONS: The patient was diagnosed with streptococcal toxic shock syndrome due to an ascending GAS infection originating from vagina.