Extracellular microRNAs in Relation to Weight Loss-A Systematic Review and Meta-Analysis.

Obesity is an important risk factor for cardiovascular disease and type 2 diabetes mellitus. Even a modest weight loss of 5-15% improves metabolic health, but circulating markers to indicate weight loss efficiency are lacking. MicroRNAs, small non-coding post-transcriptional regulators of gene expression, are secreted from tissues into the circulation and may be potential biomarkers for metabolic health. However, it is not known which specific microRNA species are reproducibly changed in levels by weight loss. In this study, we performed a systematic review and meta-analysis to investigate the microRNAs associated with weight loss by comparing baseline to follow-up levels following intervention-driven weight loss. This systematic review was performed according to the PRISMA guidelines with searches in PubMed and SCOPUS. The primary search resulted in a total of 697 articles, which were screened according to the prior established inclusion and exclusion criteria. Following the screening of articles, the review was based on the inclusion of 27 full-text articles, which were evaluated for quality and the risk of bias. We performed systematic data extraction, whereafter the relative values for miRNAs were calculated. A meta-analysis was performed for the miRNA species investigated in three or more studies: miR-26a, miR-126, and miR-223 were overall significantly increased following weight loss, while miR-142 was significantly decreased after weight loss. miR-221, miR-140, miR-122, and miR-146 were not significantly changed by intervention-driven weight loss. These results indicate that few miRNAs are significantly changed during weight loss.

Significantly higher use of polypharmacy in elderly with hip fracture treated with psychotropics.

INTRODUCTION: The high prevalence of chronic medical conditions among older adults leads to an increased use of prescription medications and a heightened risk of polypharmacy, raising the risk of falls and fractures. Psychotropic medications influence balance, and therefore our aim was to describe the use of psychotropic medications and the association with polypharmacy in elderly patients with a hip fracture. METHODS: A retrospective study of 200 patients aged 65 years or more admitted consecutively with a hip fracture. RESULTS: In total, 98 of the 200 patients used psychotropic medications. These 98 patients used a higher number of drugs at the time of admission (an average of eight (6-11) versus six (3-10), p less-than0.001), had a higher risk of using five or more medications (odds ratio (OR) = 5.9; 95% confidence interval (CI): 2.75-12.7; p less-than 0.001) and a higher risk of using ten or more medications (OR = 1.9; 95% CI: 1.05-3.5; p = 0.03). Furthermore, they were more likely to use analgesics (65.3% versus 48.0%; p = 0.01) and medications targeting the gastrointestinal tract (59.1% versus 40.2%; p = 0.01). CONCLUSIONS: Psychotropic medication use was frequent in elderly patients with a hip fracture and strongly associated with polypharmacy. Psychotropic medications may potentially be a trigger to perform medication review in elderly patients to prevent re-occurrence hip fractures. FUNDING: none. TRIAL REGISTRATION: not relevant.

Metabolic engineering of Synechocystis sp. PCC 6803 for the production of aromatic amino acids and derived phenylpropanoids.

In light of the climate change challenge, the advantageous trait of using solar energy and carbon dioxide to produce organic molecules has granted cyanobacteria deserved interest as hosts for metabolic engineering. Importantly, these organisms do not directly compete with agricultural resources. Aromatic amino acids and derived phenylpropanoids are of high importance because they are used by the pharmaceutical, food, cosmetic, and agricultural industries as precursors of active ingredients. Amino acids are traditionally produced by extraction from protein hydrolysates, chemical synthesis or fermentation pathways using heterotrophic microorganisms. In this work we demonstrate for the first time the efficient overproduction of phenylalanine and tyrosine from CO2 in a Synechocystis sp. PCC 6803 strain heterologously expressing the feedback-inhibition-resistant AroG and TyrA enzymes from E. coli. Production titers reached 904 ±â€¯53 mg/gDW (580 ±â€¯34 mg/L) of phenylalanine and 64 ±â€¯3.7 mg/gDW (41 ±â€¯2.3 mg/L) of tyrosine after 10 days of photoautotrophic growth. We estimate that the production of the two amino acids corresponds to 56% of the total fixed carbon. Phenylalanine and tyrosine are the precursors for phenylpropanoids, thus, we tested the functionality of several phenylpropanoid biosynthetic enzymes in the generated cyanobacterium strains and successfully achieved the production of 470 ±â€¯70 mg/gDW (207 mg/L) of p-coumaric acid, 267 ±â€¯31 mg/gDW (114 mg/L) of cinnamic acid and 47.4 ±â€¯13.9 mg/gDW (12.6 mg/L) of caffeic acid after 6 days of photoautotrophic growth. All compounds were secreted to the growth medium. Our work enlarges the repertoire and yield of heterologous chemicals produced by Synechocystis and contributes to extend the molecular knowledge about this cyanobacterium.