Background
Obesity increases the risk of colorectal adenoma and colorectal cancer. However, the obesity-related parameters that are best for assessing the risk of colorectal adenoma development ...remain unclear. We analyzed the parameters that may best describe the association between obesity and colorectal adenoma development.
Methods
In this retrospective cohort study, 3405 individuals underwent screening colonoscopy during routine health examinations. We measured body mass index; waist circumference; and metabolic parameters such as high-density lipoprotein-cholesterol, glucose, triglyceride, and systolic blood pressure. We analyzed the risk of developing colorectal adenoma, relative to obesity-related parameters, over a mean interval of 5.8 years from baseline colonoscopy.
Results
In a multivariate analysis, waist circumference was the only obesity-related marker associated with an increased risk of metachronous colorectal adenoma. Men with waist circumferences ≥85 cm and women with waist circumference ≥82 cm had a 31% increased risk of metachronous colorectal adenoma compared to those with smaller waist circumferences odds ratio (OR) 1.31; 95% confidence interval (CI, 1.09–1.57). Other factors associated with metachronous colorectal adenoma were age (OR, 1.03; 95% CI 1.02–1.04), male sex (OR 1.49; 95% CI 1.17–1.88), alcohol consumption ≥3/week (OR 1.33; 95% CI 1.10–1.62), the number of adenoma at baseline (OR 1.21; 95% CI 1.10–1.33), and the presence of advanced adenoma at baseline (OR 1.60; 95% CI 1.24–2.06).
Conclusions
Our findings suggest that central obesity, represented by waist circumference, is a significant predictor of metachronous colorectal adenoma, independent of body mass index and other metabolic variables.
We report the chloroplast (cp) genome sequence of tartary buckwheat (Fagopyrum tataricum) obtained by next-generation sequencing technology and compared this with the previously reported common ...buckwheat (F. esculentum ssp. ancestrale) cp genome. The cp genome of F. tataricum has a total sequence length of 159,272 bp, which is 327 bp shorter than the common buckwheat cp genome. The cp gene content, order, and orientation are similar to those of common buckwheat, but with some structural variation at tandem and palindromic repeat frequencies and junction areas. A total of seven InDels (around 100 bp) were found within the intergenic sequences and the ycf1 gene. Copy number variation of the 21-bp tandem repeat varied in F. tataricum (four repeats) and F. esculentum (one repeat), and the InDel of the ycf1 gene was 63 bp long. Nucleotide and amino acid have highly conserved coding sequence with about 98% homology and four genes--rpoC2, ycf3, accD, and clpP--have high synonymous (Ks) value. PCR based InDel markers were applied to diverse genetic resources of F. tataricum and F. esculentum, and the amplicon size was identical to that expected in silico. Therefore, these InDel markers are informative biomarkers to practically distinguish raw or processed buckwheat products derived from F. tataricum and F. esculentum.
Celotno besedilo
Dostopno za:
DOBA, IZUM, KILJ, NUK, PILJ, PNG, SAZU, SIK, UILJ, UKNU, UL, UM, UPUK
Receptor-interacting protein kinase-3 （RIP3 or RIPK3） is an essential part of the cellular machinery that executes ＂programmed＂ or ＂regulated＂ necrosis. Here we show that programmed necrosis is ...activated in response to many chemotherapeutic agents and contributes to chemotherapy-induced cell death. However, we show that RIP3 expres- sion is often silenced in cancer cells due to genomic methylation near its transcriptional start site, thus RIP3-depen- dent activation of MLKL and downstream programmed necrosis during chemotherapeutic death is largely repressed. Nevertheless, treatment with hypomethylating agents restores RIP3 expression, and thereby promotes sensitivity to chemotherapeutics in a RIP3-dependent manner. RIP3 expression is reduced in tumors compared to normal tissue in 85% of breast cancer patients, suggesting that RIP3 deficiency is positively selected during tumor growth/develop- ment. Since hypomethylating agents are reasonably well-tolerated in patients, we propose that RIP3-deficient cancer patients may benefit from receiving hypomethylating agents to induce RIP3 expression prior to treatment with con- ventional chemotherapeutics.
The microRNA‐200 (miR‐200) family plays a major role in specifying epithelial phenotype by preventing expression of the transcription repressors ZEB1 and ZEB2, which are well‐known regulators of the ...epithelial‐to‐mesenchymal transition (EMT) in epithelial tumors including oral squamous cell carcinoma (OSCC). Here, we elucidated whether miR‐200 family members control RNA‐binding protein quaking (QKI), a newly identified tumor suppressor that is regulated during EMT. We predicted that miR‐200a and miR‐200b could recognize QKI 3′‐UTR by analyzing TargetScan and The Cancer Genome Atlas head and neck squamous cell carcinoma (HNSCC) dataset. Forced expression of miR‐200b/a/429 inhibited expression of ZEB1/2 and decreased cell migration in OSCC cell lines CAL27 and HSC3. QKI expression was also suppressed by miR‐200 overexpression, and the 3′‐UTR of QKI mRNA was directly targeted by miR‐200 in luciferase reporter assays. Interestingly, shRNA‐mediated knockdown of QKI led to pronounced EMT and protumor effects in both in vitro and in vivo studies of OSCC. Furthermore, high expression of QKI protein is associated with favorable prognosis in surgically resected HNSCC and lung adenocarcinoma. In conclusion, QKI increases during EMT and is targeted by miR‐200; while, it suppresses EMT and tumorigenesis. We suggest that QKI and miR‐200 form a negative feedback loop to maintain homeostatic responses to EMT‐inducing signals.
What's new?
The epithelial‐mesenchymal transition is controlled by various transcription factors and non‐coding RNAs. The miR‐200 family of microRNAs inhibit the EMT by targeting certain transcription factors. In this study, the authors identified the gene QKI as a novel target of miR‐200 in oral and lung cancer cells. These microRNAs suppressed QKI expression, and QKI knockdown reduced miR‐200 expression, suggesting the two interact in a negative feedback loop. QKI knockdown also promoted cell growth, EMT, and invasion. On the other hand, microarray data from surgical samples showed that high QKI expression correlated with good outcomes for patients with HSNCC and lung cancer.
Introduction/Aims
There are limited studies on the association of COVID‐19 vaccination with neuralgic amyotrophy (NA). Therefore, we evaluated the association between COVID‐19 vaccination and the ...occurrence of NA.
Methods
We explored unexpected safety signals for NA related to COVID‐19 vaccination through disproportionality analysis using VigiBase, the World Health Organization's pharmacovigilance database.
Results
On October 15, 2021, 335 cases of NA were identified in the database. The median time to onset of NA after vaccination was around 2 weeks. A significant signal of disproportionality of NA was observed for the ChAdOx1 nCoV‐19 vaccine (AstraZeneca) (information component IC025 = 0.33, reporting odds ratio ROR025 = 1.30) and two mRNA‐based COVID‐19 vaccines (BNT162b2 Pfizer and BioNTech and mRNA‐1273 Moderna) (IC025 = 1.74, ROR025 = 3.82) compared with the entire database. However, when compared with influenza vaccines, we did not detect any signal of disproportionality of NA for both the ChAdOx1 nCoV‐19 vaccine (IC025 = −2.71, ROR025 = 0.05) and mRNA‐based COVID‐19 vaccines (IC025 = −1.38, ROR025 = 0.13).
Discussion
A weak association was observed between NA and COVID‐19 vaccines. However, the risk did not surpass that of influenza vaccines.
Scrambler therapy is a noninvasive electroanalgesia technique designed to remodulate the pain system. Despite growing evidence of its efficacy in patients with neuropathic pain, little is known about ...the clinical factors associated with treatment outcome. We conducted a prospective, open-label, single-arm trial to assess the efficacy and safety of scrambler therapy in patients with chronic neuropathic pain of various etiologies. A post-hoc analysis was performed to investigate whether cluster analysis of the Neuropathic Pain Symptom Inventory (NPSI) profiles could identify a subgroup of patients regarding neuropathic pain phenotype and treatment outcome. Scrambler therapy resulted in a significant decrease in the pain numerical rating scale (NRS) score over 2 weeks of treatment (least squares mean of percentage change from baseline, - 15%; 95% CI - 28% to - 2.4%; p < 0.001). The mean score of Brief Pain Inventory (BPI) interference subdimension was also significantly improved (p = 0.022), while the BPI pain composite score was not. Hierarchical clustering based on the NPSI profiles partitioned the patients into 3 clusters with distinct neuropathic pain phenotypes. Linear mixed-effects model analyses revealed differential response to scrambler therapy across clusters (p = 0.003, pain NRS; p = 0.072, BPI interference subdimension). Treatment response to scrambler therapy appears different depending on the neuropathic pain phenotypes, with more favorable outcomes in patients with preferentially paroxysmal pain rather than persistent pain. Further studies are warranted to confirm that capturing neuropathic pain phenotypes can optimize the use of scrambler therapy.
Non-traumatic osteonecrosis of the femoral head (ONFH) usually affects adults younger than 50 years and frequently leads to femoral head collapse and subsequent arthritis of the hip. It is becoming ...more prevalent along with increasing use of corticosteroids for the adjuvant therapy of leukemia and other myelogenous diseases as well as management of organ transplantation. This review updated knowledge on the pathogenesis, classification criteria, staging system, and treatment of ONFH.
Idiopathic pulmonary fibrosis (IPF) causes progressive fibrosis and worsening pulmonary function. Prognosis is poor and no effective therapies exist. We show that programmed cell death 5 (PDCD5) ...expression is increased in the lungs of patients with IPF and in mouse models of lung fibrosis. Lung fibrosis is significantly diminished by club cell-specific deletion of Pdcd5 gene. PDCD5 mediates β-catenin/Smad3 complex formation, promoting TGF-β-induced transcriptional activation of matricellular genes. Club cell Pdcd5 knockdown reduces matricellular protein secretion, inhibiting fibroblast proliferation and collagen synthesis. Here, we demonstrate the club cell-specific role of PDCD5 as a mediator of lung fibrosis and potential therapeutic target for IPF.
The electrochemical reduction of carbon dioxide (CO2) to hydrocarbons is a challenging task because of the issues in controlling the efficiency and selectivity of the products. Among the various ...transition metals, copper has attracted attention as it yields more reduced and C2 products even while using mononuclear copper center as catalysts. In addition, it is found that reversible formation of copper nanoparticle acts as the real catalytically active site for the conversion of CO2 to reduced products. Here, it is demonstrated that the dinuclear molecular copper complex immobilized over graphitized mesoporous carbon can act as catalysts for the conversion of CO2 to hydrocarbons (methane and ethylene) up to 60%. Interestingly, high selectivity toward C2 product (40% faradaic efficiency) is achieved by a molecular complex based hybrid material from CO2 in 0.1 m KCl. In addition, the role of local pH, porous structure, and carbon support in limiting the mass transport to achieve the highly reduced products is demonstrated. Although the spectroscopic analysis of the catalysts exhibits molecular nature of the complex after 2 h bulk electrolysis, morphological study reveals that the newly generated copper cluster is the real active site during the catalytic reactions.
Dinuclear copper complex immobilized on graphitized mesoporous carbon exhibits more efficient CO2 reduction activity than that of the mononuclear composite material. Although postcatalytic analysis of the material displays the existence of molecular nature, morphological study shows copper clustering as the real active site. The importance of porous structure, substrate, and controlling the local pH in C2 product selectivity is demonstrated.
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