Hoffmannhahn0867

This review provides an overview of the current and emerging techniques for sickle cell disease detection and highlights the different potential methods that could be applied to help the early diagnosis of SCD.The multistep development of cancer involves the cooperation between multiple molecular lesions, as well as complex interactions between cancer cells and the surrounding tumour microenvironment. The search for these synergistic interactions using experimental models made tremendous contributions to our understanding of oncogenesis. Yet, these approaches remain labour-intensive and challenging. To tackle such a hurdle, an integrative, multidisciplinary effort is required. In this article, we highlight the use of logical computational models, combined with experimental validations, as an effective approach to identify cooperative mechanisms and therapeutic strategies in the context of cancer biology. In silico models overcome limitations of reductionist approaches by capturing tumour complexity and by generating powerful testable hypotheses. We review representative examples of logical models reported in the literature and their validation. We then provide further analyses of our logical model of Epithelium to Mesenchymal Transition (EMT), searching for additional cooperative interactions involving inputs from the tumour microenvironment and gain of function mutations in NOTCH.Postprandial hyperglycemia (PPHG) is strongly linked with the future development of cardiovascular complications in type 2 diabetes (T2D). Hence, reducing postprandial glycemic excursions is essential in T2D treatment to slow progressive deficiency of β-cell function and prevent cardiovascular complications. Most of the metabolic processes involved in PPHG, i.e., β-cell secretory function, GLP-1 secretion, insulin sensitivity, muscular glucose uptake, and hepatic glucose production, are controlled by the circadian clock and display daily oscillation. Consequently, postprandial glycemia displays diurnal variation with a higher glycemic response after meals with the same carbohydrate content, consumed at dusk compared to the morning. T2D and meal timing schedule not synchronized with the circadian clock (i.e., skipping breakfast) are associated with disrupted clock gene expression and is linked to PPHG. In contrast, greater intake in the morning (i.e., high energy breakfast) than in the evening has a resetting effect on clock gene oscillations and beneficial effects on weight loss, appetite, and reduction of PPHG, independently of total energy intake. Therefore, resetting clock gene expression through a diet intervention consisting of meal timing aligned to the circadian clock, i.e., shifting most calories and carbohydrates to the early hours of the day, is a promising therapeutic approach to improve PPHG in T2D. This review will focus on recent studies, showing how a high-energy breakfast diet (Bdiet) has resetting and synchronizing actions on circadian clock genes expression, improving glucose metabolism, postprandial glycemic excursions along with weight loss in T2D.The gut microbiota is crucial for physiological development and immunological homeostasis. Alterations of this microbial community called dysbiosis, have been associated with cancers such colorectal cancers (CRC). The pro-carcinogenic potential of this dysbiotic microbiota has been demonstrated in the colon. Recently the role of the microbiota in the efficacy of anti-tumor therapeutic strategies has been described in digestive cancers and in other cancers (e.g., melanoma and sarcoma). Different bacterial species seem to be implicated in these mechanisms F. nucleatum, B. fragilis, and colibactin-associated E. coli (CoPEC). CoPEC bacteria are prevalent in the colonic mucosa of patients with CRC and they promote colorectal carcinogenesis in susceptible mouse models of CRC. In this review, we report preclinical and clinical data that suggest that CoPEC could be a new factor predictive of poor outcomes that could be used to improve cancer management. Moreover, we describe the possibility of using these bacteria as new therapeutic targets.Untargeted metabolomics based on liquid chromatography coupled with mass spectrometry (LC-MS) can detect thousands of features in samples and produce highly complex datasets. The accurate extraction of meaningful features and the building of discriminant models are two crucial steps in the data analysis pipeline of untargeted metabolomics. In this study, pure ion chromatograms were extracted from a liquor dataset and left-sided colon cancer (LCC) dataset by K-means-clustering-based Pure Ion Chromatogram extraction method version 2.0 (KPIC2). Then, the nonlinear low-dimensional embedding by uniform manifold approximation and projection (UMAP) showed the separation of samples from different groups in reduced dimensions. The discriminant models were established by extreme gradient boosting (XGBoost) based on the features extracted by KPIC2. Results showed that features extracted by KPIC2 achieved 100% classification accuracy on the test sets of the liquor dataset and the LCC dataset, which demonstrated the rationality of the XGBoost model based on KPIC2 compared with the results of XCMS (92% and 96% for liquor and LCC datasets respectively). Finally, XGBoost can achieve better performance than the linear method and traditional nonlinear modeling methods on these datasets. UMAP and XGBoost are integrated into KPIC2 package to extend its performance in complex situations, which are not only able to effectively process nonlinear dataset but also can greatly improve the accuracy of data analysis in non-target metabolomics.The COVID-19 pandemic has greatly affected the personal and academic lives of undergraduates in Saudi Arabia. Although studies have suggested that COVID-19 increased the prevalence of psychological health problems among undergraduates, the associations between the risk of depression and safety practices and the influence of gender on these associations have not been studied in detail. A cross-sectional online survey was conducted among preparatory-year undergraduates in a large public university in Saudi Arabia during the outbreak. Depressive symptoms were assessed using the Center for Epidemiological Studies Depression (CES-D) Scale, and the practice of eight precautionary behaviors was also assessed. Data analysis was performed using the chi-square test, multiple linear regression and Spearman's correlation coefficient. In total, 3044 undergraduates were surveyed. The mean age was 18.6 years (SD = 0.84), and 61.9% (n = 1883) of the participants were female. Overall, 47.7% of the participants reported havingndergraduates seemed to be more vulnerable to developing such symptoms. Results also indicated that female undergraduates were more likely to implement the protective measures for COVID-19. The promotion of precautionary measures seems to be effective in reducing distress in this target population, but further research is needed to confirm our assertions.Our aim was to describe the main features of amyloid goiter in adults with amyloidosis secondary to familial Mediterranean fever. check details Therefore, we analyzed cases from a French cohort of familial Mediterranean fever patients with amyloidosis and from literature review. Forty-two cases were identified 9 from the French cohort and 33 from literature review. Ninety percent of patients were on hemodialysis for renal amyloidosis before the development of goiter. The goiter grew up rapidly in 88% of cases; 75.6% of patients were euthyroid, 58% displayed dyspnea, and 44.8% dysphagia. Various features were seen on ultrasound, from diffuse to multinodular goiter. When it was performed, fine-needle aspiration biopsy almost always revealed amyloidosis. Thirty-one patients underwent thyroidectomy to manage compressive symptoms (72%) or rule out malignancy (27%). Histology showed mature adipose tissue in 64% of cases and lymphocytic infiltration in 21.4%. In conclusion, amyloid goiter in familial Mediterranean fever preferentially occurs in patients with end stage renal failure. Fine-needle aspiration biopsy seems to be a sensitive exam for diagnosis, but thyroidectomy remains sometimes necessary to rule out malignancy or release compressive symptoms.Antisense oligonucleotides (ASOs), siRNA and splice switching oligonucleotides (SSOs) all have immense potential as therapeutic agents, potential that is now being validated as oligonucleotides enter the clinic. However, progress in oligonucleotide-based therapeutics has been limited by the difficulty in delivering these complex molecules to their sites of action in the cytosol or nucleus of cells within specific tissues. There are two aspects to the delivery problem. The first is that most types of oligonucleotides have poor uptake into non-hepatic tissues. The second is that much of the oligonucleotide that is taken up by cells is entrapped in endosomes where it is pharmacologically inert. It has become increasingly recognized that endosomal trapping is a key constraint on oligonucleotide therapeutics. Thus, many approaches have been devised to address this problem, primarily ones based on various nanoparticle technologies. However, recently an alternative approach has emerged that employs small molecules to manipulate intracellular trafficking processes so as to enhance oligonucleotide actions. This review presents the current status of this chemical biology approach to oligonucleotide delivery and seeks to point out possible paths for future development.This study was aimed at disclosing the influence of intravesically instilled guanethidine (GUA) on the distribution, relative frequency and chemical coding of both the urinary bladder intramural sympathetic nerve fibers and their parent cell bodies in the caudal mesenteric ganglion (CaMG) in juvenile female pigs. GUA instillation led to a profound decrease in the number of perivascular nerve terminals. Furthermore, the chemical profile of the perivascular innervation within the treated bladder also distinctly changed, as most of axons became somatostatin-immunoreactive (SOM-IR), while in the control animals they were found to be neuropeptide Y (NPY)-positive. Intravesical treatment with GUA led not only to a significant decrease in the number of bladder-projecting tyrosine hydroxylase (TH) CaMG somata (94.3 ± 1.8% vs. 73.3 ± 1.4%; control vs. GUA-treated pigs), but simultaneously resulted in the rearrangement of their co-transmitters repertoire, causing a distinct decrease in the number of TH+/NPY+ (89.6 ± 0.7% vs. 27.8 ± 0.9%) cell bodies and an increase in the number of SOM-(3.6 ± 0.4% vs. 68.7 ± 1.9%), calbindin-(CB; 2.06 ± 0.2% vs. 9.1 ± 1.2%) or galanin-containing (GAL; 1.6 ± 0.3% vs. 28.2 ± 1.3%) somata. The present study provides evidence that GUA significantly modifies the sympathetic innervation of the porcine urinary bladder wall, and thus may be considered a potential tool for studying the plasticity of this subdivision of the bladder innervation.Hydrogen sulfide and carbon monoxide share the ability to be beneficial or harmful molecules depending on the concentrations to which organisms are exposed. Interestingly, humans and some bacteria produce small amounts of these compounds. Since several publications have summarized the recent knowledge of its effects in humans, here we have chosen to focus on the role of H2S and CO on microbial physiology. We briefly review the current knowledge on how bacteria produce and use H2S and CO. We address their potential antimicrobial properties when used at higher concentrations, and describe how microbial systems detect and survive toxic levels of H2S and CO. Finally, we highlight their antimicrobial properties against human pathogens when endogenously produced by the host and when released by external chemical donors.