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Rheumatoid arthritis (RA) is an autoimmune disease characterized by chronic systemic inflammation causing progressive joint damage that can lead to lifelong disability. The pathogenesis of RA involves a complex network of various cytokines and cells that trigger synovial cell proliferation and cause damage to both cartilage and bone. Involvement of the cytokines tumor necrosis factor (TNF)-α and interleukin (IL)-6 is central to the pathogenesis of RA, but recent research has revealed that other cytokines such as IL-7, IL-17, IL-21, IL-23, granulocyte macrophage colony-stimulating factor (GM-CSF), IL-1β, IL-18, IL-33, and IL-2 also play a role. Clarification of RA pathology has led to the development of therapeutic agents such as biological disease-modifying anti-rheumatic drugs (DMARDs) and Janus kinase (JAK) inhibitors, and further details of the immunological background to RA are emerging. This review covers existing knowledge regarding the roles of cytokines, related immune cells and the immune system in RA, manipulation of which may offer the potential for even safer and more effective treatments in the future.

COVID-19 is spreading worldwide, causing various social problems. The aim of the present study was to verify the reliability and validity of the Japanese version of the Fear of COVID-19 Scale (FCV-19S) and to ascertain FCV-19S effects on assessment of Japanese people's coping behavior. After back-translation of the scale, 450 Japanese participants were recruited from a crowdsourcing platform. These participants responded to the Japanese FCV-19S, the Japanese versions of the Hospital Anxiety and Depression scale (HADS) and the Japanese versions of the Perceived Vulnerability to Disease (PVD), which assesses coping behaviors such as stockpiling and health monitoring, reasons for coping behaviors, and socio-demographic variables. Results indicated the factor structure of the Japanese FCV-19S as including seven items and one factor that were equivalent to those of the original FCV-19S. The scale showed adequate internal reliability (α = .87; ω = .92) and concurrent validity, as indicated by significantly positive correlations with the Hospital Anxiety and Depression Scale (HADS; anxiety, r = .56; depression, r = .29) and Perceived Vulnerability to Disease (PVD; perceived infectability, r = .32; germ aversion, r = .29). Additionally, the FCV-19S not only directly increased all coping behaviors (β = .21 - .36); it also indirectly increased stockpiling through conformity reason (indirect effect, β = .04; total effect, β = .31). These results suggest that the Japanese FCV-19S psychometric scale has equal reliability and validity to those of the original FCV-19S. These findings will contribute further to the investigation of various difficulties arising from fear about COVID-19 in Japan.

BackgroundAlthough peritoneal lavage cytology often serves as a sensitive method to detect free cancer cells in the abdominal cavity, some patients experience peritoneal recurrence despite negative cytology. The aim of this study was to evaluate mRNAs in peritoneal lavage fluid as potential markers for predicting the peritoneal recurrence of gastric cancer (GC).MethodsPeritoneal lavage fluid samples were obtained during surgery conducted on 187 patients with GC and from 30 patients with non-malignant disease (controls). The mRNA levels of nine candidate markers were quantified, and analysis of a receiver-operating characteristic curve compared their accuracies. The cutoff was defined as the highest value of the controls.ResultsSynaptotagmin XIII (SYT13) and carcinoembryonic antigen (CEA) mRNA levels were analyzed further. SYT13 levels were significantly associated with shorter peritoneal recurrence-free survival (PRFS) and overall survival. Among patients with negative peritoneal lavage cytology, those positive for either SYT13 or CEA mRNA experienced significantly shorter peritoneal recurrence-free survival compared with those with negative fluid (hazards ratio [HR] 4.21, P = 0.0114; HR 3.53; P = 0.0426, respectively). Univariate analysis revealed that SYT13 and CEA mRNA levels were significant predictors of peritoneal recurrence. Positive levels of both SYT13 and CEA mRNA demonstrated the highest HR for peritoneal recurrence (HR 12.27, P = 0.0064). Multivariable analysis revealed that SYT13 positivity was a significant independent prognostic factor (HR 3.69; 95% confidence interval, 1.18–12.74; P = 0.0246).ConclusionsCombined measurement of SYT13 and CEA mRNA levels in peritoneal lavage fluid could serve as a promising approach to predict peritoneal recurrence of GC.

Hand-foot syndrome (HFS), also known as palmar-plantar erythrodysesthesia (PPE), is a major side effect of capecitabine. Although the pathogenesis of HFS remains unknown, some studies suggested a potential involvement of inflammation in its pathogenesis. Proton pump inhibitors (PPIs) have been reported to have anti-inflammatory effects. In this study, we investigated the ameliorative effects of omeprazole, a PPI on capecitabine-related HFS in mice model, and a real-world database. Repeated administration of capecitabine (200 mg/kg, p.o., five times a week for 3 weeks) increased fluid content, redness, and tumor necrosis factor (TNF)-α substance of the mice hind paw. Co-administration of omeprazole (20 mg/kg, p.o., at the same schedule) significantly inhibited these changes induced by capecitabine. Moreover, based on the clinical database analysis of the Food and Drug Administration Adverse Event Reporting System, the group that has used any PPIs had a lower reporting rate of capecitabine-related PPE than the group that has not used any PPIs. (6.25% vs. 8.31%, p  < 0.0001, reporting odds ratio (ROR) 0.74, 95% confidence interval (CI) 0.65–0.83). Our results suggest that omeprazole may be a potential prophylactic agent for capecitabine-induced HFS.

Hepcidin, a major regulator of iron metabolism and homeostasis, is regulated by inflammation. Recent studies have suggested that hepcidin and iron metabolism are involved in osteoporosis, and the aim of this study was to determine whether serum hepcidin levels are correlated with the degree of osteoporosis in patients with rheumatoid arthritis (RA). A total of 262 patients with RA (67.5 ± 11.4 years; 77.5% female) were enrolled. Serum iron, ferritin, and hepcidin levels were positively correlated each other. Multiple regression analyses revealed that the serum iron level was positively correlated with femoral T and Z scores, whereas the serum hepcidin level was not. Serum hepcidin level was correlated with the serum 25-hydroxy vitamin D level, which was in turn positively related to the femoral Z score. Serum hepcidin and serum iron were indirectly and directly related to osteoporosis in patients with RA.

Oxaliplatin frequently causes severe peripheral neuropathy as a dose-limiting toxicity. However, this toxicity lacks a strategy for prevention. Cystine/Theanine is a supplement, which includes precursors for the biosynthesis of glutathione. In this study, we investigated the effects of Cystine/Theanine on oxaliplatin-induced peripheral neuropathy using an in vivo model. Repeated injection of oxaliplatin (4 mg/kg intraperitoneally twice a week for 2 weeks) caused mechanical allodynia, cold hyperalgesia and axonal degeneration of the sciatic nerve in rats. Mechanical allodynia and axonal degeneration, but not cold hyperalgesia, were ameliorated by daily co-administration of Cystine [200 mg/kg orally (p.o.)] and Theanine (80 mg/kg p.o.). Moreover, co-administration of Cystine and Theanine to rats significantly increased the glutathione level in the sciatic nerve compared with the oxaliplatin group. Furthermore, Cystine and Theanine did not attenuate the tumour cytotoxicity of oxaliplatin in C-26 tumour cell-bearing mice. These findings suggest that Cystine and Theanine may be beneficial for preventing oxaliplatin-induced peripheral neuropathy.

BackgroundLiver metastasis of gastric cancer (GC) is highly associated with poor prognosis. The development of sensitive biomarkers for detecting and predicting liver metastasis is required for better clinical outcome.ObjectiveIn this study, we aimed to identify novel genes associated with liver metastasis of GC.MethodsGlobal expression profiling of 57,749 genes was performed using surgically resected gastric tissues from four patients with liver metastasis to identify candidate genes. The mRNA expression levels of the selected candidate gene were analyzed in the resected gastric tissues of 300 GC patients and correlated with clinicopathological parameters. Fourteen GC cell lines were subjected to mRNA expression and polymerase chain reaction (PCR) array analysis.ResultsAmong 25 candidate genes identified by transcriptome analysis, preferentially expressed antigen of melanoma (PRAME) was selected for subsequent analyses. mRNA expression analysis of clinical samples revealed the aberrant expression of PRAME in GC tissues, and its high expression was significantly related to differentiated phenotype and vessel invasion, as well as liver metastasis. High PRAME expression was significantly associated with hepatic recurrence after curative surgery, and cumulative incidences of hepatic recurrence were significantly greater in patients with high PRAME expression compared with patients with low PRAME expression. In an in vitro analysis, overexpression was observed in all GC cell lines compared with a normal epithelial cell line. PCR array analysis revealed the coordinate expression of MMP9, OCLN, IL1RN, and MST1R.ConclusionsPRAME is related to the malignant potential of GC and could serve as a novel biomarker for the detection and prediction of liver metastasis.

BackgroundSquamous cell carcinoma antigen (SCC-Ag) and carcinoembryonic antigen (CEA) are widely used in clinical practice to predict the prognosis of patients with esophageal squamous cell carcinoma (ESCC). However, their predictive values for prognosis are controversial. This study determined optimal cutoff values of serum SCC-Ag and CEA concentrations for predicting postoperative recurrence of ESCC, which enabled selection of high-risk patients.MethodsThe study retrospectively analyzed 427 patients who underwent curative resection for ESCC. The optimal cutoff values of preoperative SCC-Ag and CEA concentrations for predicting postoperative recurrence were determined using combined analysis of hazard ratios and sensitivities for recurrence. Using the optimal cutoff value, the study evaluated survival, recurrence patterns, and temporal changes in marker concentrations.ResultsThe preoperative SCC-Ag concentration of 1.1 ng/ml was the optimal cutoff value for predicting postoperative recurrence, whereas precise cutoff values could not be determined for preoperative CEA concentrations. High preoperative SCC-Ag concentrations (> 1.1 ng/ml), which were significantly associated with more aggressive tumor phenotypes and shorter disease-free survival, were identified as an independent prognostic factor in the multivariable analysis. High preoperative SCC-Ag concentrations were significantly associated with greater prevalence of lung/pleura and local recurrences. Normalization of serum SCC-Ag concentrations after neoadjuvant treatment or esophagectomy was not associated with a decreased risk of postoperative recurrence.ConclusionsThe optimal cutoff value of preoperative SCC-Ag concentrations that predicted recurrence of ESCC was 1.1 ng/ml, illuminating the utility of serum SCC-Ag concentrations as an easily measurable tool for selecting a perioperative management strategy.

BackgroundNutritional and immunological statuses are attracting increasing attention for their ability to predict surgical outcomes in various cancers. The Naples prognostic score (NPS) consists of the serum albumin level, total cholesterol level, neutrophil-to-lymphocyte ratio, and lymphocyte-to-monocyte ratio and could be useful for predicting survival.Patients and MethodsWe retrospectively analyzed 196 patients with pancreatic cancer who underwent curative R0/R1 resection with a surgery-first strategy between June 2003 and August 2016. The NPS of the patients was calculated from preoperative data, and the patients were then divided into three groups based on their NPS. Clinicopathological characteristics, surgical outcomes, and long-term survival were compared, and multivariate analysis of overall survival was conducted.ResultsOf a total of 196 patients, 22 were classified into group 0 (NPS 0), 113 into group 1 (NPS 1 or 2), and 61 into group 2 (NPS 3 or 4). Median survival time was 103.4 months in group 0, 33.3 months in group 1, and 21.3 months in group 2. Significant survival differences were observed among the 3 groups (group 1 vs. 2, group 0 vs. 2, P = 0.0380, P = 0.0022, respectively). On multivariate analysis, NPS was identified as an independent prognostic factor [hazard ratio (HR) = 1.78; P = 0.0131]; however, there were no significant differences in the incidence of postoperative morbidity among the NPS groups.ConclusionsThe NPS could be an easy scoring system and an independent preoperative predictor of survival.

Hydrogen produced by electrolysis using electricity derived from renewable energy sources has a fluctuating supply. However, conventional catalyst evaluation methods cannot evaluate catalyst synthesis assuming a fluctuating feedstock. This paper investigates a simple screening method for catalysts that can be used for renewable energy by using a combination of three catalyst evaluation methods: Light-off Performance, equilibrium achievement degree, and maximum ammonia concentration. We examined the combination of evaluation methods and trends for each element, and finally concluded that a three-axis graph combining the three is the easiest graph to obtain the information necessary for catalyst screening intuitively rather than quantitatively.