In contrast to selenoprotein Ps (SeIPs) from other animal species, bovine selenoprotein P-like-protein (SeIPLP) was found to contain a tandem repeat of (CAYYCC)(11). During an investigation into whether SeIPLP was a bovine substitute for SeIP or uniquely bovine, its mRNA was found to consist of multiple variants with different length tandem repeat, namely p(0) with (CAYYCC)(11), p(-4) lacking (CAYYCC)(4), p(-8) lacking (CAYYCC)(8), and p(-9) lacking (CAYYCC)(9). Although they were encoded on a single gene locus, neither classicalGT-AG: nor minor classAT-AC: donator-acceptor sequences for alternative splicing were identified. A subsequent S1 protection assay using oligonucleotides, whose sequence may occur as variants, performed against bovine poly(A)(+)RNA identified a total of nine variants. Judging from the sequence of these variants and the branch point mapping, the consensus sequence for recognition of the donator was CACCCCCAC: and of the acceptor and the branch point A nucleotide,ACCCC: CAT orACCCC: CATCCCCAT. Furthermore, when the p(0) insert mRNA was expressed in COS-7 cells derived from an African green monkey kidney, cDNAs corresponding to p(-8) and p(-9) could be isolated. Therefore, the bovine SeIPLP mRNAs consisted of multiple variants probably due to a novel splicing mechanism which was not bovine-specific but common to other mammals.

Reactive oxygen species (ROS) are produced under oxidative stress, such as high oxygen concentration and during the metabolic consumption of oxygen molecules. Male reproductive tissues appear to be continuously exposed to ROS produced by active metabolism. In addition, spermatozoa must pass through a high oxygen environment during the mating process. Thus, to maintain viable reproductive ability, a protective mechanism against oxidative stress is of importance. Here, we overview our current understanding of the cooperative function of antioxidative and redox systems that are involved in male fertility. Superoxide dismutase and glutathione peroxidase are major enzymes that scavenge harmful ROS in male reproductive organs. In turn, glutathione and thioredoxin systems constitute the main redox systems that repair oxidized and damaged molecules and also play a role in regulating a variety of cellular functions. While glutathione functions as an antioxidant by donating electrons to glutathione peroxidase and thioredoxin donates electrons to peroxiredoxin as a counterpart of glutathione peroxidase. In addition, aldo-keto reductases, which detoxify carbonyl compounds produced by oxidative stress, are present at high levels in the epithelia of the genital tract and Sertoli cells of the testis. Since these systems are involved in cross-talk, a comprehensive understanding will be required to maintain the physiological functions of male reproductive system.
Animals ; Antioxidants ; metabolism ; Catalase ; metabolism ; Genitalia, Male ; enzymology ; metabolism ; Glutathione ; biosynthesis ; Glutathione Peroxidase ; metabolism ; Humans ; Male ; Oxidation-Reduction ; Oxidative Stress ; physiology ; Oxidoreductases ; metabolism ; Superoxide Dismutase ; metabolism ; Thioredoxins ; metabolism

BACKGROUNDEstrogen receptor alpha (ER alpha) is the most important endocrine therapy responsiveness predictor for women with breast cancer. The accuracy of the prediction of the response to endocrine therapy was thought to be affected by involving the estrogen receptor coregulatory proteins and cross-talk between ER and other growth factor-signaling networks. Nuclear corepressor 1 (NCOR1) is one of the ER a transcription repressor. The objective of the study is to investigate the expression of NCOR1 at the protein level and pursue its predictive value for breast cancer endocrine therapy.

METHODSIn the present study, the level of expression of NCOR1 protein has been assessed by immunohistochemistry in 104 cases of invasive carcinoma of the breast. Associations between NCOR1 protein expression and different clinicopathological factors and survival were sought.

RESULTSIt was found that NCOR1 was expressed at significantly higher levels in responsive patients treated with endocrine therapy as first-line treatment on relapse. Responsive patients also had a significantly longer post-relapse survival and overall survival. No NCOR1 expression difference was found between patient by age, tumor size, lymph node status, different histological grade groups and human epidermal growth factor receptor 2 (HER2) status. Multivariate analysis showed that NCOR1 is an independent prognostic factor for over-all survival.

CONCLUSIONSIn breast cancer, NCOR1 protein expression level predicts response to endocrine therapy as first-line treatment for breast cancer patients on relapse and NCOR1 protein level assay may increase the accuracy in the endocrine treatment determination and, therefore, improving the patients survival.

Antineoplastic Agents, Hormonal ; therapeutic use ; Breast Neoplasms ; drug therapy ; metabolism ; Estrogen Receptor alpha ; metabolism ; Female ; Gene Expression Regulation ; Humans ; Immunohistochemistry ; Middle Aged ; Nuclear Receptor Co-Repressor 1 ; metabolism ; Receptor, ErbB-2 ; metabolism ; Receptors, Progesterone ; metabolism ; Tamoxifen ; therapeutic use

BACKGROUND/AIMS: Noninvasive liver fibrosis evaluation was performed in patients with nonalcoholic fatty liver disease (NAFLD). We used a quantitative method based on the hepatic volume acquired from gadoxetate disodium-enhanced (Gd-EOB-DTPA-enhanced) magnetic resonance imaging (MRI) for diagnosing advanced fibrosis in patients with NAFLD. METHODS: A total of 130 patients who were diagnosed with NAFLD and underwent Gd-EOB-DTPA-enhanced MRI were retrospectively included. Histological data were available for 118 patients. Hepatic volumetric parameters, including the left hepatic lobe to right hepatic lobe volume ratio (L/R ratio), were measured. The usefulness of the L/R ratio for diagnosing fibrosis ≥F3–4 and F4 was assessed using the area under the receiver operating characteristic (AUROC) curve. Multiple regression analysis was performed to identify variables (age, body mass index, serum fibrosis markers, and histological features) that were associated with the L/R ratio. RESULTS: The L/R ratio demonstrated good performance in differentiating advanced fibrosis (AUROC, 0.80; 95% confidence interval, 0.72 to 0.88) from cirrhosis (AUROC, 0.87; 95% confidence interval, 0.75 to 0.99). Multiple regression analysis showed that only fibrosis was significantly associated with the L/R ratio (coefficient, 0.121; p<0.0001). CONCLUSIONS: The L/R ratio, which is not influenced by pathological parameters other than fibrosis, is useful for diagnosing cirrhosis in patients with NAFLD.
Body Mass Index ; Fibrosis* ; Humans ; Liver Cirrhosis ; Magnetic Resonance Imaging ; Methods ; Non-alcoholic Fatty Liver Disease* ; Retrospective Studies ; ROC Curve

We developed a virtual career thinking game and provided third-year medical students with workshop-type career instruction to identify "transition" in a career and their own values. The game is a group work activity based on the assumption that the virtual character will respond to a turning point during undergraduate school and after graduation, and experience the story of a doctor's life. After playing the game and sharing the story of each group, participants were asked to think about what they would do at a possible turning point. Although favorable response were observed in the first year, problems were found, and improvements were made in the second year, and further effects were observed. The results show that career education using games increases students' ability to respond to turning points and is an effective technique in career education.

In career education, devising ways to elicit proactive participation is vital, thus we conducted face-to-face workshops to drive learners’ participation. However, the COVID-19 pandemic forced us to teach classes online. Therefore, to motivate more than 100 students to participate actively in the online format, we conducted career education using Active Book Dialogue® where several students read a book together in a short period of time. Each student read a specific part of the book they were assigned and summarized it in collaboration with their group members. This enabled them to learn career theory. Additionally, the online format allowed several lectures to be held within a remote and interactive environment. We will reflect on this experience and report on how this can be applied in other schools.

PURPOSE: Opioids improve pain from knee and hip osteoarthritis (OA) and decrease the functional impairment of patients. However, there is a possibility that opioids induce analgesia and suppress the physiological pain of OA in patients, thereby inducing the progression of OA changes in these patients. The purpose of the current study was to investigate the possibility of progressive changes in OA among patients using opioids. MATERIALS AND METHODS: Two hundred knee or hip OA patients were evaluated in the current prospective, randomized, active-controlled study. Patients were randomized 1:1:1 into three parallel treatment groups: loxoprofen, tramadol/acetaminophen, and transdermal fentanyl groups. Medication was administered for 12 weeks. Pain scores and progressive OA changes on X-ray films were evaluated. RESULTS: Overall, pain relief was obtained by all three groups. Most patients did not show progressive OA changes; however, 3 patients in the transdermal fentanyl group showed progressive OA changes during the 12 weeks of treatment. These 3 patients used significantly higher doses than others in the transdermal fentanyl group. Additionally, the average pain score for these 3 patients was significantly lower than the average pain score for the other patients in the transdermal fentanyl group. CONCLUSION: Fentanyl may induce progressive changes in knee or hip OA during a relatively short period, compared with oral Non-Steroidal Anti-Inflammatory Drugs or tramadol.
Aged ; Aged, 80 and over ; Analgesics, Opioid/*adverse effects/therapeutic use ; Disease Progression ; Female ; Fentanyl/*adverse effects/therapeutic use ; Humans ; Male ; Middle Aged ; Osteoarthritis, Hip/*drug therapy/radiography ; Osteoarthritis, Knee/*drug therapy/radiography ; Pain/drug therapy