Endometriosis, a disease in which endometrial tissue proliferates outside the uterus, is a progressive disease that affects women in reproductive age. It causes abdominal pain and infertility that severely affects the quality of life in young women. The mechanism of the onset and development of endometriosis has not been fully elucidated because of the complex mechanism involved in the disease. Nonhuman primates have been used to study the pathogenesis of spontaneous endometriosis because of their gynecological and anatomical similarities to humans. To reveal the natural history of endometriosis in cynomolgus monkeys, we selected 11 female cynomolgus monkeys with spontaneous endometriosis and performed monthly laparoscopies, mapping endometriotic lesions and adhesions up to two years. At the initial laparoscopy, endometriotic lesions were exclusively found in the vesicouterine pouch in 45.4% (5/11) of the monkeys and spread to the Douglas’ pouch over time. Appearance of small de novo lesions and disappearance of some of the small lesions were observed in 100% (11/11) and 18.2% (2/11) of the monkeys, respectively. Endometriosis developed in all monkeys, and the speed of progression varied greatly among individuals that could be attributed to the degree or frequency of retrograde menstruation and genetic factors; these findings support the similarities between humans and monkeys, thus verifying the value of this nonhuman primate model. Finding reliable quantification markers and unravelling the underlying factors in correlation with the spatiotemporal development of the disease using a nonhuman primate model would be useful for the better management of endometriosis in humans.
The apelinergic system plays an important role in the modulation of the cardiovascular system via the apelin peptide and the apelin receptor (APJ receptor). Apelin and elabela, also known toddler, are peptide ligands for the apelin receptor. These two peptides show similar biological actions, such as vasodilatation, increased myocardial contractility, angiogenesis, and energy metabolism. However, the serum levels of elabela in patients with hyperthyroidism are not well known. The aim of this study was to investigate the changes in serum elabela levels in patients with hyperthyroidism and its association with hypertension. This cross-sectional study included 74 patients with newly diagnosed hyperthyroidism due to Graves’ disease and 20 healthy individuals. Serum elabela levels were measured by enzyme-linked immunosorbent assay. The patients were divided into two groups: hyperthyroid patients without hypertension (n = 51) and those with hypertension (n = 23). Basal heart rate, serum glucose and high-sensitive C reactive protein were significantly higher in hyperthyroid patients with and those without hypertension than in healthy controls (p < 0.05 for each). Serum elabela levels were significantly elevated in hyperthyroid patients compared with healthy controls, with higher serum elabela levels found in hyperthyroid patients with hypertension than those without hypertension. Linear regression analysis showed that serum elabela levels were correlated with systolic blood pressure (p < 0.001). In conclusion, serum elabela levels were significantly increased in patients with hyperthyroidism, especially in hyperthyroid patients with hypertension. Elevation in serum elabela levels may contribute to alleviation of cardiovascular complications of hyperthyroidism and hypertension.
The incidence of endometrial cancer has rapidly risen over recent years. Paclitaxel, a key drug for endometrial cancer treatment, inhibits microtubule depolymerization and induces apoptosis in cancer cells. Endometrial serous carcinoma (ESC) accounts for < 10% of all endometrial carcinomas, but its aggressive nature makes it responsible for close to 40% of cancer deaths. Thus, novel therapeutic targets are required for ESC. To identify microRNAs that promote paclitaxel resistance, we established two paclitaxel-resistant cell lines from USPC1 human ESC cells by exposing paclitaxel to parental cells for 12 weeks. Paclitaxel concentrations were increased every 2 weeks, and after 12 weeks of paclitaxel exposure, two replicate paclitaxel-resistant cell lines were established (USPC1-PTSR1 and USPC1-PTXR2). The microarray analysis was performed using USPC1 cells and USPC1-PTXR1 cells, and eight candidate microRNAs were thus selected as potential mediators of paclitaxel sensitivity. Among these candidate microRNAs, let-7c precursor treatment of paclitaxel-resistant USPC1-PTXR1 cells caused the greatest increase in paclitaxel-mediated cytotoxicity. Let-7c inhibition conversely decreased paclitaxel-induced apoptosis. It is known that let-7a microRNA, a member of the let-7 family, inhibits growth of endometrial carcinoma cells targeting Aurora-B that controls progression through each phase of mitosis. We thus studied whether let-7c mediates Aurora-B expression in ESC cells. The expression levels of Aurora-B mRNA and protein were higher in USPC-PTXR1 cells compared with USPC1 cells. Let-7c inhibition increased Aurora-B expression in USPC1 cells but decreased Aurora-B expression in USPC1-PTXR1 cells. These results indicate that let-7c mediates paclitaxel resistance via inhibition of Aurora-B expression in ESC cells.
Salmonella infection predominantly causes four clinical syndromes: enteric fever, gastroenteritis, bacteremia, and asymptomatic carrier state. Salmonella osteomyelitis is an extremely rare manifestation of salmonella infection except in children with hemoglobinopathies. Salmonella osteomyelitis has been reported to mostly affect the diaphysis of long bones and lumbar spine. Here, we describe a case of salmonella osteomyelitis of the right 6th rib in a 74-year-old woman who presented with breast pain, swelling, high fever and local heat. Her medical history showed myocardial infarction; namely, at the age of 71, the patient had undergone the drug-eluting stent placement in the left anterior descending artery. A computed tomography (CT) scan at the first visit to another hospital showed a mass in the chest that invaded the ribs. 18F-fluorodeoxyglucose-positron emission tomography-computed tomography imaging showed a lesion suspected to be a mammary malignant tumor. A needle biopsy revealed mesenchymal cells and suspected mammary sarcoma. However, the osteomyelitis of the rib was diagnosed when pyogenic tissue was observed during an open biopsy. The bacterial culture examination identified Salmonella enterica. Surgical drainage and antibiotic treatment were performed. Importantly, there was no evidence for any underlying disease that could lead to an immunocompromised status of the patient. To our knowledge, this is the first report of salmonella osteomyelitis of the rib presenting in an older female that required differentiation from a mammary tumor. Clinicians should consider rib osteomyelitis when they find swelling and local heat in the female’s breast tissue and detect no cancerous tissue.
Low preoperative physical function in cancer patients is associated with postoperative complications; however, there have been no reports on the benefits of in-hospital preoperative rehabilitation on preoperative physical function in patients with pancreatic cancer. Therefore, the aim of this study was to quantitatively determine the effects of preoperative in-hospital rehabilitation provided under the supervision of a physiotherapist, on preoperative physical function in patients with pancreatic cancer. The study subjects were 26 patients (15 males, 11 females; age 71.2 ± 8.5 years, range: 51-87 years), including four patients with preoperative chemotherapy, scheduled for surgery for pancreatic cancer. Muscle strengthening exercises and aerobic exercises were conducted 11.9 ± 5.1 days prior to surgery. Cardiopulmonary exercise testing, 6-minute walk distance, and the Functional Independence Measure score were measured before and after the rehabilitation program. We also investigated the relation between the rehabilitation program and incidence of postoperative complications. All 26 study patients completed the preoperative rehabilitation program and no adverse events were noted. Peak oxygen uptake during cardiopulmonary exercise testing and 6-minute walk distance increased significantly after the rehabilitation program. The Functional Independence Measure score remained constant throughout the intervention. No wound infection, delirium, deep vein thrombosis, or respiratory complications were encountered postoperatively. In-hospital preoperative rehabilitation under the supervision of a physiotherapist significantly improved physical function and maintained physical activity in patients with pancreatic cancer. Such improvements may contribute toward preventing serious postoperative complications, resulting in better outcomes.
In Japan, a bivalent human papillomavirus (HPV) vaccine against carcinogenic HPV16/18 was licensed in 2009, and a quadrivalent vaccines against HPV16/18 and non-carcinogenic HPV6/11 was licensed in 2011. Recently, the next-generation 9-valent vaccine targeting HPV6/11/16/18/31/33/45/52/58 has been approved. Accurate HPV genotyping is essential for HPV vaccine research and surveillance. The Roche Linear Array (LA) has long been a standard assay for HPV genotyping, but its recent product discontinuation notice has urged us to introduce an alternative assay with comparable performance. In the present study, an in-house HPV genotyping assay that employs PCR with PGMY09/11 primers and reverse blotting hybridization (PGMY-CHUV) was compared with LA to assess genotype-specific agreement. A total of 100 cervical precancer specimens were subjected to both PGMY-CHUV and LA. For detection of genotypes included in the 9-valent vaccine, PGMY-CHUV completely agreed with LA for detection of HPV6, HPV11, HPV16, HPV18, HPV33 and HPV45, and showed near-complete agreement for HPV31 and HPV58 (98% and 99%, respectively). Moreover, PGMY-CHUV detected a significantly higher prevalence of HPV52 than LA (22% vs. 14%, P = 0.008 by McNemar’s exact test), with 92.0% overall agreement, 63.6% positive agreement and a kappa value of 0.73. Most (87.5%) of HPV52 discordant cases involved mixed infections with HPV35 or HPV58. In conclusion, while the two assays present equivalent data for assessing the effectiveness of the bivalent and quadrivalent vaccines, PGMY-CHUV is more suitable for evaluating the impact of the current 9-valent vaccine because of its superior detection of HPV52 in co-infection cases.
Martial arts, such as judo, kendo, and karate, are popular worldwide, not only among adults but also among children and adolescents. Although low back pain (LBP) is considered to be a common problem in these sports, it has been scarcely studied, especially in young athletes. The purpose of this study was to elucidate the point prevalence of and factors related to LBP among school-aged athletes in judo, kendo, and karate. A cross-sectional study was conducted in school-aged athletes (age, 6-15 years; n = 896) using a self-reported questionnaire. Multiple logistic regression models were used to assess the factors related to LBP along with the odds ratio (OR) and 95% confidence interval (95% CI). Variables included in the analysis were sex, age, body mass index, team level, number of days and hours of training, frequency of participation in games, practice intensity, and lower extremity pain. The prevalence of LBP was 6.9% in judo, 4.7% in kendo, and 2.9% in karate. Older age was significantly associated with LBP in judo (adjusted OR, 2.12 [95% CI, 1.24-3.61]), kendo (1.77 [1.27-2.47]), and karate (2.22 [1.14-4.33]). Lower extremity pain was significantly associated with LBP in judo (6.56 [1.57-27.34]) and kendo (21.66 [6.96-67.41]). Coaches should understand the characteristics of LBP in each martial art to develop strategies to prevent LBP among school-aged martial arts athletes.
Colorectal cancer is the fourth most common malignancy across the world, and over 50% of patients had colorectal liver metastases (CLM). Activated neutrophils and tumor-infiltrating lymphocytes (TILs) are considered to interrupt progression of primary colorectal cancer; however, immunological host reactions to CLM have not been fully elucidated. We thus aimed to explore the prognostic implication of neutrophil-to-lymphocyte ratio (NLR) in peripheral blood and TILs in resected metastatic cancer tissues of 29 patients with CLM who underwent hepatectomy. To evaluate local immunological responses in CLM, we examined the infiltration of CD66b+ neutrophils and TILs, such as CD8+ T cells, CD45RO+ T cells, and forkhead box P3+ (FOXP3+) T cells. The presence of fewer than 4 tumors (p = 0.0005), the absence of distant metastasis (p = 0.018), adjuvant anti-cancer chemotherapy (p = 0.0013), and elevated NLR over 4.1 (p = 0.026) were found to be significant parameters related to longer survival after hepatectomy. Further, high numbers of infiltrated CD45RO+ T cells in CLM were significantly associated with longer patient survival (p = 0.020). The numbers of CD45RO+ T cells were correlated with those of CD8+ T cells (p = 0.008). The numbers of peripheral blood neutrophils were negatively correlated with those of CD45RO+ T cells (p = 0.038) and of CD66b+ neutrophils (p = 0.008) in CLM. The present data indicate that elevated peripheral blood NLR and high numbers of intratumoral CD45RO+ T cells are predictive of longer CLM patient survival after hepatectomy among current biomarkers.
The lungs are the organs that work for gas exchange. The basic structure of the lungs is an alveolus, which consists of various types of parenchymal cells and bone marrow-derived cells. Therefore, because the lungs consist of various types of cells with various functions, communication among the different types of the cells should play important roles for the homeostasis and response to disease pathogens. In the past decades, researchers have focused on cytokines or adhesion molecules to reveal the intercellular communication for understanding the homeostasis and pathogenesis in the lungs. Recent investigations have revealed that an extracellular vesicle can move among cells for transferring substances including microRNAs in the vesicles as an intercellular messenger. MicroRNAs and extracellular vesicles are therefore attracting increasing attention from both translational and clinical researchers because these emerging intercellular communication tools seem to be useful for further understanding of the disease pathogenesis as well as the biomarkers for diagnosis and prognosis of the diseases including cancer and inflammatory diseases. This review article is an attempt to review studies about microRNAs and extracellular vesicles in terms of their roles in normal conditions and refractory diseases of the lungs such as idiopathic pulmonary fibrosis and acute respiratory distress syndrome including our recent study about pulmonary microvascular endothelial microparticles particles as the biomarker for diagnosis and prognosis of acute respiratory distress syndrome. This review also addresses the possibility of microRNAs and extracellular vesicles as new clinical tools for the diagnosis or treatment for these refractory respiratory diseases.
After the first cases of COVID-19 appeared in Wuhan, China at the end of 2019, the disease quickly become a pandemic that has seriously affected the economic and health systems in more than 200 countries and territories around the world. Although most patients have mild symptoms or are even asymptomatic, there are patients who can develop serious complications such as acute respiratory distress syndrome or venous thromboembolism requiring mechanical ventilation and intensive care. Hence, it is important to identify patients with a higher risk of complications in a timely manner. Thus, the objective of this paper is to review the hematological laboratory parameters that consistently are altered in COVID-19 and to identify their relationship with the severity of the disease. According to 11 selected reports, the frequency of patients aged > 65 years is higher among subjects severely affected or deceased; likewise, males predominantly suffer from comorbidities such as hypertension, diabetes or obesity. Retrospective studies have identified alterations in various hematological and inflammatory parameters as part of the host’s response to infection and a secondary increased risk of different thrombotic events. Among these altered parameters, D-dimer, C-reactive protein, and interleukin-6 have been tested as prognostic biomarkers due to their close relationship with the severity of the disease. Actually, they can reliably indicate the use of antithrombotic therapy at prophylactic or therapeutic doses (mainly D-dimer), as has already been established in those patients who, after an individualized assessment, appear to be at high risk for thrombotic events.