Systematic proteome-wide Mendelian randomization to prioritize causal plasma proteins for skin cancers.

Skin cancer is one of the most common cancers worldwide. Some risk factors including sun exposure and MC1R variants are recognized; however, the identification of additional genetic factors is essential for the development of novel therapeutic strategies. Here, we conducted a proteome-wide Mendelian randomization (MR) using plasma protein quantitative trait loci (pQTLs) from a published study and the UK Biobank genome-wide association study (GWAS) of skin cancers.

Prioritization of nasal polyp-associated genes by integrating GWAS and eQTL summary data.

Nasal polyps (NP) are benign inflammatory growths of nasal and paranasal sinus mucosa that can substantially impair patients' quality of life by various symptoms such as nasal obstruction, insomnia, and anosmia. NP often relapse even after surgical treatment, and the curative therapy would be challenging without understanding the underlying mechanisms. Genome wide association studies (GWASs) on NP have been conducted; however, few genes that are causally associated with NP have been identified.

Estimating causal effects of genetically predicted type 2 diabetes on COVID-19 in the East Asian population.

Background: Observational studies suggested that type 2 diabetes mellitus (T2DM) was associated with an increased risk of coronavirus disease 2019 (COVID-19). However, Mendelian randomization (MR) studies in the European population failed to find causal associations, partly because T2DM was pleiotropically associated with body mass index (BMI). We aimed to estimate the causal effects of T2DM on COVID-19 outcomes in the East Asian (EAS) population using a two-sample MR approach.

Causal effect of atrial fibrillation/flutter on chronic kidney disease: A bidirectional two-sample Mendelian randomization study.

Chronic kidney disease (CKD) and atrial fibrillation are both major burdens on the health care system worldwide. Several observational studies have reported clinical associations between CKD and atrial fibrillation; however, causal relationships between these conditions remain to be elucidated due to possible bias by confounders and reverse causations. Here, we conducted bidirectional two-sample Mendelian randomization analyses using publicly available summary statistics of genome-wide association studies (the CKDGen consortium and the UK Biobank) to investigate causal associations between CKD and atrial fibrillation/flutter in the European population.

Estimating causal effects of atherogenic lipid-related traits on COVID-19 susceptibility and severity using a two-sample Mendelian randomization approach.

Background: As the number of COVID-19 deaths continues to rise worldwide, the identification of risk factors for the disease is an urgent issue, and it remains controversial whether atherogenic lipid-related traits including serum apolipoprotein B, low-density lipoprotein (LDL)-cholesterol, and triglyceride levels, are risk factors. The aim of this study was to estimate causal effects of lipid-related traits on COVID-19 risk in the European population using a two-sample Mendelian randomization (MR) approach.

Methods: We used summary statistics from a genome-wide association study (GWAS) that included 441,016 participants from the UK Biobank as the exposure dataset of lipid-related traits and from COVID-19 Host Genetics Initiative GWAS meta-analyses of European ancestry as the outcome dataset for COVID-19 susceptibility (32,494 cases and 1,316,207 controls), hospitalization (8316 cases and 1,549,095 controls), and severity (4792 cases and 1,054,664 controls).

Educational Attainment Decreases the Risk of COVID-19 Severity in the European Population: A Two-Sample Mendelian Randomization Study.

Observational studies have reported that the severity of COVID-19 depends not only on physical conditions but also on socioeconomic status, including educational level. Because educational attainment (EA), which measures the number of years of schooling, is moderately heritable, we investigated the causal association of EA on the risk of COVID-19 severity using the Mendelian randomization (MR) approach. A two-sample MR analysis was performed using publicly available summary-level data sets of genome-wide association studies (GWASs).

Structure-activity relationship studies of 3-substituted pyrazoles as novel allosteric inhibitors of MALT1 protease.

We report the discovery of a novel series of 1,5-bisphenylpyrazoles as potent MALT1 inhibitors. Structure-activity relationship exploration of a hit compound led to a potent MALT1 inhibitor. Compound 33 showed strong activity against MALT1 (IC: 0.

Moderating effect of sense of coherence on the relationship between symptom distress and health-related quality of life in patients receiving cancer chemotherapy.

Purpose: This study is aimed at examining the buffering effect of sense of coherence (SOC) on symptom distress during cancer drug therapy, which thereby affects health-related quality of life (QoL), and obtaining suggestions for promoting supportive care.

Methods: We investigated health-related QoL (SF-8), symptom distress (using the Symptom Distress Scale (SDS)), and SOC (the SOC 13-item Scale) in 66 patients receiving adjuvant chemotherapy for non-small cell lung cancer. We employed descriptive statistics to seek the correlation of each variable; then, a hierarchical multiple regression analysis was conducted with SF-8 score as the dependent variable.

The APLNR gene polymorphism rs7119375 is associated with an increased risk of development of essential hypertension in the Chinese population: A meta-analysis.

Hypertension (HT) has recently been defined as a systolic blood pressure (BP) of ≥130 mm Hg and/or a diastolic BP of ≥80 mm Hg. It is important to further understand the pathophysiology of essential HT as its proportion is larger among most of the diagnosed HT cases. The apelin and apelin receptor (APLNR) are known to play roles in regulating BP, but the putative associations of single nucleotide polymorphisms in the APLNR gene with the risk of development of essential HT have not yet been fully investigated.

Single-nucleotide polymorphism rs4664308 in PLA2R1 gene is associated with the risk of idiopathic membranous nephropathy: a meta-analysis.

Although many studies investigated the associations between single-nucleotide polymorphisms (SNPs) in the M-type phospholipase A2 receptor-1 (PLA2R1) gene and susceptibility to idiopathic membranous nephropathy (IMN), some showed inconsistent results. Here, we conducted a meta-analysis examining the associations between PLA2R1 SNPs and IMN susceptibility after systematic searches in the PubMed and Web of Science databases. Our meta-analysis for rs4664308 A>G including 2,542 IMN patients and 4,396 controls in seven studies showed a significant association between the G allele and a lower risk of IMN, as determined using an allelic model (odds ratio, 0.

Controllable Monobromination of Perylene Ring System: Synthesis of Bay-Functionalized Perylene Dyes.

Practical synthesis of bay-monofunctionalized perylene dyes has been developed based on controllable NBS bromination of tetrabenzyl perylene-3,4,9,10-tetracarboxylate. The ability to perform the convenient and high-yielding synthesis highlights the potential utility of our multifunctional approach to access a diverse range of new perylene systems.

Mechanisms of Fatal Cardiotoxicity following High-Dose Cyclophosphamide Therapy and a Method for Its Prevention.

Observed only after administration of high doses, cardiotoxicity is the dose-limiting effect of cyclophosphamide (CY). We investigated the poorly understood cardiotoxic mechanisms of high-dose CY. A rat cardiac myocardial cell line, H9c2, was exposed to CY metabolized by S9 fraction of rat liver homogenate mixed with co-factors (CYS9).

The resistive index is a marker of renal function, pathology, prognosis, and responsiveness to steroid therapy in chronic kidney disease patients.

To evaluate the significance of the renal resistive index (RI) as a noninvasive marker of renal histological damage and a prognostic indicator, we examined RI by Doppler ultrasonography in 202 chronic kidney disease (CKD) patients who underwent renal biopsy. RI increased as the CKD stage progressed and correlated with age, systolic blood pressure, estimated glomerular filtration rate (eGFR), and renal histological changes, including glomerulosclerosis, arteriolosclerosis, and tubulointerstitial damage. Prognostic evaluation with a median follow-up period of 38.

Asymmetric total synthesis of an iboga-type indole alkaloid, voacangalactone, newly isolated from Voacanga africana.

A new hexacyclic iboga-type indole alkaloid, voacangalactone (1), was isolated from Voacanga africana , and its structure including the absolute configuration was established by asymmetric total synthesis involving such key steps as the asymmetric Diels-Alder reaction using an aminodiene and the construction of an isoquinuclidine ring and an indole skeleton.

Laser fabrication of Au nanorod aggregates microstructures assisted by two-photon polymerization.

We demonstrate fabrication of Au nanorod aggregates microstructures by means of a femtosecond near-infrared laser. The laser light was tightly focused into colloidal Au nanorods dispersed in photopolymerizable metyl-methacrylate (MMA) compound to induce two-photon polymerization (TPP). TPP of MMA glued the nanorods together to form solid microstrucures of aggregates.

Detection of myeloperoxidase in membranous nephropathy-like deposits in patients with anti-neutrophil cytoplasmic antibody-associated glomerulonephritis.

Anti-neutrophil cytoplasmic antibody-associated glomerulonephritis is usually classified as a pauci-immune type. However, it sometimes shows immune complex deposition of unknown origin. We examined the glomerular localization of myeloperoxidase by double immunofluorescence and immunoelectron microscopy in cases of anti-neutrophil cytoplasmic antibody-associated glomerulonephritis with membranous nephropathy-like immunoglobulin G deposition to investigate the immune complex antigens in these cases.

[The outpatient palliative care conference for the home palliative care shift (the second report)--the conference was used to look back on the case where the patient's QOL was kept and improved].

The patient was a 30-year-old woman with right tongue cancer and SCC (T4N2bM0). After it had relapsed, the outpatient palliative care conference intervened. The purpose of intervention was as follows: pain control, nutrition management, home recuperation support, and relief of a spiritual pain.

Long-term renal prognosis of IgA nephropathy with therapeutic trend shifts.

Objective: We compared the effect of treatments in the long-term renal survival of IgA nephropathy.

Methods: One hundred and fourteen patients with biopsy-proven IgA nephropathy were retrospectively divided into 4 groups, reflecting shifts in treatment trends from 1985 to 2005: patients without treatment (no treatment group; n=36), patients treated only with anti-platelet drugs (anti-platelet group; n=12), those treated mainly with angiotensin-converting enzyme (ACE) inhibitors or angiotensin receptor blockers (ARBs) (ACEI/ARB group; n =29), and prednisolone-treated patients (PSL group; n =37).

Results: Baseline blood pressure, serum creatinine and renal histological findings were similar among the 4 groups; however, the urinary protein level was significantly severer in the PSL group.

CRH mRNA expression in the hypothalamic paraventricular nucleus is inhibited despite the activation of the hypothalamo-pituitary-adrenal axis during starvation.

Corticotropin-releasing hormone (CRH) is one of the anorexigenic neuropeptides, and indeed the expression of hypothalamic CRH is known to be inhibited by starvation. To clarify whether elevated plasma glucocorticoid during starvation is responsible for the CRH suppression, we examined the expression level of hypothalamic CRH mRNA after food deprivation in adrenalectomized, plasma corticosterone (B)-clamped animals. Male Wistar rats were divided into 2 groups: one group had adrenalectomy (ADX) and B pellet implantation (ADX+B, n=42), and the other group had only sham operation (sham, n=42).