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Toft McKenzie opublikował 1 rok, 8 miesięcy temu
lti‑target protective effects. In addition, NBP + edaravone may be a promising combination therapy for ischemic stroke.The aim of the present study was to investigate the effect of hedgehog‑interacting protein antisense RNA 1 (HHIP‑AS1) on epithelial‑mesenchymal transition (EMT) and cellular stemness of human lung cancer cells by regulating the microRNA (miR)‑153‑3p/PCDHGA9 axis. Reverse transcription‑quantitative PCR was used to compare the expression of HHIP‑AS1 in lung cancer and adjacent normal lung tissues. In addition, the correlation of HHIP‑AS1 with E‑cadherin, Vimentin, N‑cadherin and Twist1 was analyzed. HHIP‑AS1 overexpression vector was transfected into lung cancer A549 and NCI‑H1299 cell lines. Cell Counting Kit‑8 and Transwell and clonogenic assays were used to detect the proliferation, invasion and clonogenesis of the lung cancer cells, respectively. The associations among HHIP‑AS1, miR‑153‑3p and PCDHGA9 were predicted by bioinformatics analysis and verified by a dual‑luciferase reporter system. The results showed that the expression of HHIP‑AS1 in lung cancer tissues was significantly lower than that in normal tissues (P less then 0.001). HHIP‑AS1 was positively correlated with E‑cadherin and negatively correlated with Vimentin, N‑cadherin and Twist1. HHIP‑AS1 overexpression inhibited the proliferation, invasion and clonal formation of the A549 and NCI‑H1299 cells. The luciferase reporter system verified that HHIP‑AS1 could adsorb miR‑153‑3p and that PCDHGA9 was the target gene of miR‑153‑3p. A549 cells were transfected with HHIP‑AS1 overexpression vector and miR‑153‑3p mimic, and the miR‑153‑3p mimic had a mitigating effect on HHIP‑AS1 inhibition (P less then 0.001). In conclusion, HHIP‑AS1 inhibits the EMT and stemness of lung cancer cells by regulating the miR‑153‑3p/PCDHGA9 axis. Thus, HHIP‑AS1 may be a new potential target for lung cancer treatment.Rosacea, a chronic condition usually recognized by its visible presentation, can be accompanied by invisible symptoms, such as burning and stinging. This aim of this review is to gather the most recent evidence on burning and stinging, in order to further emphasize the need to address these symptoms. Inflammatory pathways can explain both the signs and symptoms of rosacea, but available treatments are still evaluated primarily on their ability to treat visible signs. Recent evidence also highlights the adverse impact of symptoms, particularly burning and stinging, on quality of life. Despite an increasing understanding of symptoms and their impact, the management of burning and stinging as part of rosacea treatment has not been widely investigated. Clinicians often underestimate the impact of these symptoms and do not routinely include them as part of management. Available therapies for rosacea have the potential to treat beyond signs, and improve burning and stinging symptoms in parallel. Further investigation is needed to better understand these benefits and to optimize the management of rosacea.
To investigate functioning, activity and disability in people with post-COVID syndrome.
Cross-sectional.
Participants were recruited online via Facebook and a stakeholders’ organization for post-COVID syndrome in Sweden.
Sociodemographic data and International Classification of Functioning, Disability and Health (ICF)-based questionnaires were collected via an online platform and analysed.
A total of 100 participants were included (mean age 44.5 years, 82% women, 61% with higher education, and 56% working full- or part-time). For the ICF component Body Functions, the most impaired functions were fatigability and energy drive (98-99%); higher cognitive functions (74-94%); sleep functions (98%); muscle functions (93%); respiratory functions (92%); heart functions (82%); emotional functions (80%); sexual functions (77%); pain problems (56-90%); and thermoregulatory functions (68%). For the component Activity, the most frequent limitations were handling stressful situations (98%); remunerative employment (95%); recreation and leisure (94%); climbing the stairs (94%); doing housework (84%); and informal socializing (64%). The most frequent degrees of impairment/limitations were light and moderate, except for severe-complete for fatigue, higher cognitive functions, multitasking, handling stressful situations; and recreation and leisure activities.
Post-COVID syndrome following a mild COVID-19 infection can result in impaired body functions and activities. These results support the importance of a multidisciplinary rehabilitation approach for these patients.
Post-COVID syndrome following a mild COVID-19 infection can result in impaired body functions and activities. These results support the importance of a multidisciplinary rehabilitation approach for these patients.In the skin fragility disorder epidermolysis bullosa simplex (EBS), mutations in keratin 14 (K14, also known as KRT14) or keratin 5 (K5, also known as KRT5) lead to keratinocyte rupture and skin blistering. Severe forms of EBS are associated with cytoplasmic protein aggregates, with elevated kinase activation of ERK1 and ERK2 (ERK1/2; also known as MAPK3 and MAPK1, respectively), suggesting intrinsic stress caused by misfolded keratin protein. Human keratinocyte EBS reporter cells stably expressing GFP-tagged EBS-mimetic mutant K14 were used to optimize a semi-automated system to quantify the effects of test compounds on keratin aggregates. Screening of a protein kinase inhibitor library identified several candidates that reduced aggregates and impacted on epidermal growth factor receptor (EGFR) signalling. EGF ligand exposure induced keratin aggregates in EBS reporter keratinocytes, which was reversible by EGFR inhibition. EBS keratinocytes treated with a known EGFR inhibitor, afatinib, were driven out of activation and towards quiescence with minimal cell death. Aggregate reduction was accompanied by denser keratin filament networks with enhanced intercellular cohesion and resilience, which when extrapolated to a whole tissue context would predict reduced epidermal fragility in EBS patients. This assay system provides a powerful tool for discovery and development of new pathway intervention therapeutic avenues for EBS.At nine US hospitals that enrolled children hospitalized with acute respiratory illness (ARI) during 2015-2016 through 2017-2018 influenza seasons, 50% of children with ARI received clinician-initiated testing for influenza and 35% of cases went undiagnosed due to lack of clinician-initiated testing. Marked heterogeneity in testing practice was observed across sites.
Amorphous urate crystals can obscure significant findings during a routine urinalysis. There is no standardized protocol to minimize their effect.
We tested 210 urine specimens. Three specimens had high red blood cell (RBC) or white blood cell (WBC) counts. Fifty-six specimens formed amorphous urates. Sediment from these specimens was treated with 50 mM sodium hydroxide (NaOH) at a 12 and/or 14 dilution. We warmed 22 specimens with crystals at various temperatures.
Amorphous urate crystals formed in concentrated urine with an acidic pH. Adding 50 mM NaOH dissolved amorphous urates, revealing the presence of underlying bacteria and yeast, but WBC and RBC counts were grossly decreased. Prewarming unspun specimens to 60°C for 90 seconds dissolved most amorphous urates.
The protocol to eliminate amorphous urate crystals is to prewarm the specimen before testing. Adding 50 mM NaOH to sediment dissolves amorphous urates to enhance the visibility of bacteria and yeast but has a deleterious effect on WBC and RBC.
The protocol to eliminate amorphous urate crystals is to prewarm the specimen before testing. Adding 50 mM NaOH to sediment dissolves amorphous urates to enhance the visibility of bacteria and yeast but has a deleterious effect on WBC and RBC.Indirect genetic effects (IGE) occur when an individual’s phenotype is influenced by genetic variation in conspecifics. Opportunities for IGE are ubiquitous, and, when present, IGE have profound implications for behavioral, evolutionary, agricultural, and biomedical genetics. Despite their importance, the empirical study of IGE lags behind the development of theory. In large part, this lag can be attributed to the fact that measuring IGE, and deconvoluting them from the direct genetic effects of an individual’s own genotype, is subject to many potential pitfalls. In this Perspective, we describe current challenges that empiricists across all disciplines will encounter in measuring and understanding IGE. Using ideas and examples spanning evolutionary, agricultural, and biomedical genetics, we also describe potential solutions to these challenges, focusing on opportunities provided by recent advances in genomic, monitoring, and phenotyping technologies. We hope that this cross-disciplinary assessment will advance the goal of understanding the pervasive effects of conspecific interactions in biology.Growth rate is regulated by hormonal pathways that might affect early cancer development. We explored the association between rate of growth in height from age 8 to 13 (childhood) years and from age 13 to height at study entry (adolescence), and risk of breast and prostate cancer. Participants were 2,037 Icelanders born 1915 – 1935, who took part in the Reykjavik Study established 1967. Height measures were obtained from school records and at study entry. We used multivariable Cox regression models to calculate hazard ratios with 95% confidence intervals of breast and prostate cancer by rates of growth in tertiles. During a mean follow-up of 66 years (women) and 64 years (men), 117 women were diagnosed with breast cancer and 118 men with prostate cancer (45 w/advanced). Women in the highest tertile of growth rate in adolescence had increased risk of breast cancer, hazard ratio 2.4, 95% confidence interval 1.3, 4.3, compared with women in the lowest tertile. A suggestive inverse association was observed for highest adolescent rate of growth in men and advanced prostate cancer, hazard ratio 0.4, 95% confidence interval 0.2, 1.0. Rapid growth, particularly in adolescence may affect cancer risk later in life.Sauchinone, a lignan isolated from Saururus chinenesis, is known to exhibit anti-inflammatory and anti-oxidant effects. Recently, sauchinone has been reported to inhibit the growth of various cancer cells, but its effects on breast cancer cells remain poorly understood. In the present study, we investigated the effects of sauchinone on the growth of breast cancer cells along with the underlying molecular mechanisms. Our results show that sauchinone treatment markedly inhibited the proliferation, migration, and invasion of breast cancer cells. Sauchinone reduced the phosphorylation of Akt, ERK, and CREB increased by transforming growth factor-β (TGF-β). In particular, sauchinone treatment suppressed the expression of matrix metalloproteinase (MMP)-13 (MMP13) by regulating the Akt-CREB signaling pathway. Sauchinone was less effective in inhibiting cell migration in Mmp13-knockdown cells than in control cells, suggesting that MMP13 may be a novel target for sauchinone. Our study suggests that sauchinone inhibits the growth of breast cancer cells by attenuating the Akt-CREB-MMP13 pathway.


