Mcneillriis5801

Atherosclerotic vascular disease (ASVD) is a chronic process, with a progressive course over many years, but it can cause acute clinical events, including acute coronary syndromes (ACS), myocardial infarction (MI) and stroke. In addition to a series of typical risk factors for atherosclerosis, like hyperlipidemia, hypertension, smoking and obesity, emerging evidence suggests that atherosclerosis is a chronic inflammatory disease, suggesting that chronic infection plays an important role in the development of atherosclerosis. Toll-like receptors (TLRs) are the most characteristic members of pattern recognition receptors (PRRs), which play an important role in innate immune mechanism. TLRs play different roles in different stages of infection of atherosclerosis-related pathogens such as Chlamydia pneumoniae (C. pneumoniae), periodontal pathogens including Porphyromonas gingivalis (P. gingivalis), Helicobacter pylori (H. pylori) and human immunodeficiency virus (HIV). Overall, activation of TLR2 and 4 seems to have a profound impact on infection-related atherosclerosis. This article reviews the role of TLRs in the process of atherosclerosis after C. pneumoniae and other infections and the current status of treatment, with a view to providing a new direction and potential therapeutic targets for the study of ASVD.OBJECTIVE AND DESIGN Sepsis, a systemic inflammatory response syndrome, is still a common cause of death even the patients who are in the intensive care unit. Alleviating septic liver damage may be effective in improving sepsis. Necroptosis and miRNAs have been regarded as a potential target in sepsis. MATERIAL OR SUBJECTS The aim of this work is to explain the potential role of miR-425-5p in septic liver damage. LPS was intraperitoneal-injection to C57BL/6 mice for sepsis, and hepatocytes treated with septic serum in vitro. H&E staining for histological evaluation, luciferase reporter assay for target validation, and qRT-PCR, WB, and ELISA analysis for assessment of miR-425-5p, RIP1, inflammatory factors, and LDH levels. RESULTS Down-regulated miR-425-5p and up-regulated RIP1/RIP3 were in LPS-induced sepsis mice. Liver damage, RIP1-mediated necroptosis, IL-1β, and TNF-α were suppressed by miR-425-5p agomiR, but further aggravated by miR-425-5p antagomiR. Furthermore, we demonstrated miR-425-5p targeted the 3'UTR of RIP1 mRNA to inhibit RIP1 expression and activated RIP1 reversed miR-425-5p-induced suppression of necroptosis and inflammation in septic hepatocytes. CONCLUSIONS The data suggest miR-425-5p negatively controls the RIP1-mediated necroptotic signaling cascades and inflammation, and sepsis-related liver damage. miR-425-5p/RIP1 axis is a potential therapeutic strategy for sepsis-related liver damage through necroptosis and inflammation.OBJECTIVE This study aimed to evaluate the protective effect of igalan, a sesquiterpene lactone isolated from Inula helenium (L.), on inhibiting inflammation, regulating the epidermal differentiation gene expression, and reactive oxygen species scavenging in atopic dermatitis (AD)-like inflammatory keratinocytes. METHODS HaCaT human keratinocytes were treated with igalan at indicated concentrations before being activated by a combination of TNF-α and IFN-γ or IL-4 representative for T-helper 1 and T-helper 2 cell cytokines, which are associated with AD pathogenesis. RESULTS By inhibiting the NF-κB pathway as well as the STAT activation, igalan could downregulate several marker inflammatory genes in AD, such as TARC/CCL17, MDC/CCL22, and RANTES/CCL5. In contrast, igalan, acting as JAK inhibitor, could promote the mRNA expression levels of the genes FLG, LOR, KRT10, and DSC1, which encode for essential proteins responsible for keratinocyte differentiation, by inhibiting STAT3 signaling. Furthermore, igalan exerts its antioxidant effect through activating the Nrf2 pathway, triggering the expression of some enzymes that contribute to preventing intracellular ROS generation during inflammation. CONCLUSION These findings indicate that igalan, via suppressing JAK/STAT3 signaling, could impair the production of pro-inflammatory chemokines and enhance expression levels of several genes involved in keratinocyte differentiation in AD-like stimulated keratinocytes.PURPOSE The aim of this study is to provide normative data about the appearances and dimensions of the cavum septi pellucidi and vergae (CSPV) on in utero MR (iuMR) imaging in second and third trimester foetuses. METHODS Two hundred normal foetuses (from a low-risk pregnancy, with normal ante-natal USS findings and no intracranial abnormality of iuMR) had iuMR imaging between 18 and 37 gestational weeks (gw). The anatomical features on those studies were compared with published atlases of post-mortem foetal brains. The length, width and volume of the CSPV were measured in all foetuses. RESULTS The anatomy of the CSPV and its relationship with the corpus callosum and the fornices on iuMR imaging was comparable with post-mortem data at all gestational ages studied. The length of the CSPV increased throughout pregnancy, whereas the width and volume of CSPV reached a maximum between 29 and 31 gw and then showed a reduction later in pregnancy. CONCLUSION The iuMR imaging features of the CSPV and its close anatomical relations closely correspond to post-mortem data. The CSPV was patent in all cases but we have shown that closure commences in the midpart of the third trimester and advances in a posterior to anterior direction.KEY MESSAGE cqSW.A03-2, one of the six identified quantitative trait loci associated with thousand-seed weight in rapeseed, is mapped to a 61.6-kb region on chromosome A03 and corresponds to the candidate gene BnaA03G37960D. Seed weight is an important factor that determines the seed yield of oilseed rape (Brassica napus L.). To elucidate the genetic mechanism of thousand-seed weight (TSW), quantitative trait locus (QTL) mapping was conducted using a double haploid population derived from the cross between an elite line ZY50 and a pol cytoplasmic male sterility restorer line 7-5. The genetic basis of TSW was dissected into six major QTLs. One major QTL denoted as cqSW.A03-2, which explained 8.46-13.70% of the phenotypic variation, was detected across multiple environments. To uncover the genetic basis of cqSW.A03-2, a set of near-isogenic lines were developed. Based on the test of self-pollinated progenies, cqSW.A03-2 was identified as a single Mendelian factor and the ZY50 allele at cqSW.A03-2 showed a positive effect on TSW. Fine mapping delimited the cqSW.A03-2 locus into a 61.6-kb region, and 18 genes within this region were predicted. Candidate gene association analysis and expression analysis indicated that a histidine kinase gene (BnaA03G37960D) is likely to be the candidate gene for the cqSW.A03-2 locus. Our results may contribute to a better understanding of the molecular mechanism of seed weight regulation and promote the breeding program for yield improvement in rapeseed.BACKGROUND Observational studies have demonstrated improved outcomes in TBI patients receiving in-hospital beta-blockers. Selleckchem SMIFH2 The aim of this study is to conduct a randomized controlled trial examining the effect of beta-blockers on outcomes in TBI patients. METHODS Adult patients with severe TBI (intracranial AIS ≥ 3) were included in the study. Hemodynamically stable patients at 24 h after injury were randomized to receive either 20 mg propranolol orally every 12 h up to 10 days or until discharge (BB+) or no propranolol (BB-). Outcomes of interest were in-hospital mortality and Glasgow Outcome Scale-Extended (GOS-E) score on discharge and at 6-month follow-up. Subgroup analysis including only isolated severe TBI (intracranial AIS ≥ 3 with extracranial AIS ≤ 2) was carried out. Poisson regression models were used. RESULTS Two hundred nineteen randomized patients of whom 45% received BB were analyzed. There were no significant demographic or clinical differences between BB+ and BB- cohorts. No significant difference in in-hospital mortality (adj. IRR 0.6 [95% CI 0.3-1.4], p = 0.2) or long-term functional outcome was measured between the cohorts (p = 0.3). One hundred fifty-four patients suffered isolated severe TBI of whom 44% received BB. The BB+ group had significantly lower mortality relative to the BB- group (18.6% vs. 4.4%, p = 0.012). On regression analysis, propranolol had a significant protective effect on in-hospital mortality (adj. IRR 0.32, p = 0.04) and functional outcome at 6-month follow-up (GOS-E ≥ 5 adj. IRR 1.2, p = 0.02). CONCLUSION Propranolol decreases in-hospital mortality and improves long-term functional outcome in isolated severe TBI. This randomized trial speaks in favor of routine administration of beta-blocker therapy as part of a standardized neurointensive care protocol. LEVEL OF EVIDENCE Level II; therapeutic. STUDY TYPE Therapeutic study.BACKGROUND Neoadjuvant chemotherapy (NAC) can improve cosmesis by reducing resection volume. Breast-conserving surgery (BCS) aims to achieve clear excision margins while optimizing cosmesis. However, the influence of NAC on margin re-excision after BCS is unclear. This study examines the rate and determinants of margin re-excision in patients undergoing BCS following NAC in our institution. METHODS From 2011-2015, all patients treated with NAC prior to BCS were identified from a prospectively maintained database. Mann-Whitney and Fisher's exact test tests were used to compare variables in patients who did and did not require re-excision. Patients undergoing primary surgical treatment in 2015 comprised an unmatched comparison group. RESULTS Of 211 patients treated with NAC, 69 initially underwent BCS. The re-excision rate was 32% (n = 22) compared to 17% in the primary operable group (38 of 221, p = 0.02). Re-excision rates were lowest in triple-negative and HER2+ tumors (0% and 10%, respectively). Lobular carcinoma and ER+ tumors had a significantly higher rate of re-excision (100% and 42%, respectively). Of 22 patients undergoing re-excision, 9 had further BCS and 13 had a mastectomy. CONCLUSION The re-excision rate following NAC is almost twice that of patients who underwent primary operative management. Her2+ and triple-negative tumors have lower re-excision rates and may represent a selected cohort most suitable for BCS. Patients with invasive lobular carcinoma or ER+ disease have significantly higher rates of margin positivity, and these patients should be considered for a cavity shave during primary surgery to reduce the rates of re-excision.A selective cortisol sensor based on molecularly imprinted poly(glycidylmethacrylate-co ethylene glycol dimethacrylate) (poly(GMA-co-EGDMA)) has been demonstrated for detection of cortisol in human sweat. The non-enzymatic biomimetric flexible sweat sensor was fabricated inexpensively by layer by layer (LbL) assembly. The sensor layers comprised a stretchable polydimethylsiloxane (PDMS) base with carbon nanotubes-cellulose nanocrystals (CNC/CNT) conductive nanoporous nanofilms. The imprinted (MIP) poly(GMA-co-EGDMA) deposited on the CNC/CNT was the cortisol biomimetric receptor. Rapid in analyte response (3 min), the cortisol MIP sensor demonstrated excellent performance. The sensor has a limit of detection (LOD) of 2.0 ng/mL ± 0.4 ng/mL, dynamic range of 10-66 ng/mL, and a sensor reproducibility of 2.6% relative standard deviation (RSD). The MIP sensor also had high cortisol specificity and was inherently blind to selected interfering species including glucose, epinephrine, β-estradiol, and methoxyprogestrone.