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Moreover, it was also observed that addition of polymyxin B in the curcumin-mediated aPDT led to the apparent bacterial membrane damage with increased leakage of cytoplasmic contents and extensive DNA and protein degradation.

The photodynamic action of curcumin against P. aeruginosa could be significantly enhanced by the FDA-approved drug polymyxin B. Our results highlight the potential of introducing polymyxin B to enhance the effects of aPDT treatment against gram-negative skin infections, in particular, P. aeruginosa.

The photodynamic action of curcumin against P. aeruginosa could be significantly enhanced by the FDA-approved drug polymyxin B. Our results highlight the potential of introducing polymyxin B to enhance the effects of aPDT treatment against gram-negative skin infections, in particular, P. aeruginosa.Opportunistic infections are widely described in patients with novel coronavirus disease 2019 (COVID-19); however, very few studies have addressed those affecting the oral cavity. Given the lack of information on the clinical presentations and the available treatment options, the present study aimed to show a case in which a combination of antimicrobial photodynamic therapy (aPDT) and photobiomodulation therapy (PBMT) was used for the management of two concomitant COVID-19-associated opportunistic oral infections (oral pseudomembranous candidiasis and recurrent herpes labialis). Within 7 days and without any systemic drug administration, all the lesions resolved completely, and the patient no longer reported oral pain or discomfort. According to the current case report and taking into consideration the significant gaps in the knowledge and understanding of COVID-19, this combination of phototherapy modalities seems to be a promising tool for managing viral and fungal opportunistic oral infections.We analyzed the effects of selective knockdown of either HIF-1α or HIF-2α on the transcriptional response to hypoxia of human umbilical endothelial cells at two time-points (2 h and 8 h) of hypoxia. We focused on 13 previously identified hypoxia-responsive genes, pre-selected to have different activation kinetics and different proportions of HRE motifs annotated to either HIF-1 or HIF-2 in open promoters - open chromatin DNase-hypersensitive sites (DHS) regions within ±1 kb of the gene start. We report that genes activated by both HIF-1 and 2 tend to be activated earlier than genes activated by HIF-1 only, which, in turn, tend to be activated earlier than genes activated by HIF-2 only. Moreover, for the 13 analyzed genes, we found that the effect of silencing HIF1A on the gene induction by hypoxia is greater for the genes with more HRE motifs annotated to HIF-1 in their promoter open chromatin DHS regions within ±1 kb and also within ±10 kb of the gene start. We corroborated and extended this finding by showing that among 232 genes previously identified as activated by hypoxia, the genes with ChIP-seq peak(s) for HIF-1α within a ±10 kb flank of the gene start contain more HRE motifs annotated to HIF-1 in the DHS regions within this flank than the genes with no ChIP-seq peaks. Also in the whole genome, the DHS regions intersecting ChIP-seq peaks for HIF-1α contain more HRE motifs annotated to HIF-1 than the DHS regions not intersecting the ChIP-seq peaks. This suggests a mechanism, by which higher promoter content of HRE motifs in DHS regions increases HIF-1 binding, which in turn increases gene induction by hypoxia.The dual-target stool DNA test, iColocomf, has potential utility for colorectal cancer (CRC) detection, but its clinical accuracy has not been validated on larger groups. We therefore evaluated the performance of iColocomf in a multicenter clinical trial. In this double-blinded case-control study, 1164 participants from three independent hospitals, including 320 CRC patients, 148 adenomas, 396 interfering diseases, and 300 healthy controls were enrolled. The primary indicators of sensitivity, specificity, and accuracy were estimated. Stool samples of participants were collected and tested by the assay. The test results were then verified by Sanger sequencing and retesting of resected participants. The sensitivity and specificity for CRC detection were 95.31% and 96.67%, respectively, with an accuracy of 90.29%. When combining the interfering diseases, the specificity was 88.39%. No statistically significant variations of positive detection rates were observed for the test in different patients' clinical features. For advanced adenomas (n = 38) and nonadvanced adenomas (n = 110), the sensitivities were 63.16% and 33.64%, respectively. Selleck LGK-974 The average accuracy was 99.62% for the methylation status of 375 samples verified by Sanger sequencing, and 94.12% for 34 participants who received the test after surgical resection. The iColocomf test showed robust performance for the early detection of colorectal cancer and potential monitoring ability in clinical practice.

Beta-lactam antibiotic allergy labels are highly prevalent but rarely indicate an allergic intolerance. These patient-reported allergies lead to broad-spectrum antibiotic use, conferred resistance, increased expense, and adverse effects.

To implement and assess the impact of a history-based clinical guideline that directs antibiotic management and beta-lactam allergy relabeling for patients reporting beta-lactam allergies.

Patients with beta-lactam allergy labels were identified by our trained multidisciplinary team in diverse clinical settings. This quality improvement project was conducted to evaluate the safety and impact of the guideline on antibiotic use by comparing prescribing practices before and after guideline implementation.

A total of 79 patients with beta-lactam allergies were identified (penicillins-90%, cephalosporins-10%). After guideline implementation, outcomes of allergy relabeling included the following (1) complete removal, indicating an unlikely true allergy (27%); (2) updated tosulted in most patients' allergy labels being removed or advantageously updated. These allergy label changes correlated with a substantial increase in the percentage of beta-lactam antibiotics prescribed. After guideline implementation, beta-lactam antibiotics had a 3-fold increased odds of being prescribed independent of allergy label outcome.Infectious hematopoietic necrosis virus (IHNV) is the vital pathogen that has caused the great economic loss in salmonid fisheries. To date, there is limited information concerning the changes of lncRNAs in RTG-2 cells infected by IHNV. In this study, a comparative transcriptome analysis of lncRNAs was performed in RTG-2 cells with and without IHNV infection to determine their changes and the effects on IHNV infection. The results showed that IHNV infection significantly changed the expression levels of lncRNAs and mRNAs, including 3693 differentially expressed lncRNAs (DE-lncRNAs) and 3503 differentially expressed mRNAs (DE-mRNAs) respectively. These DE-lncRNAs and DE-mRNAs induced by IHNV were mostly associated with immune response, RNA processing, and viral diseases related pathways. Further analysis found that some DE-lncRNAs might participate in the regulation of extracellular matrix metabolism, apoptosis, lipid synthesis, autophagy, and immune responses referring to the functions of their target genes. Afterwards, 349 co-expression relationships were constructed by 223 DE-lncRNAs and 271 DE-mRNAs, of which LTCONS_00146935 was the pivotal node in the interaction networks, and was together with its target genes modulated the immune responses under the IHNV infection. RT-qPCR results showed that the changes of the selected immune-related DEGs were in consistent with the RNA-seq data, suggesting that the sequencing data was relatively reliable. In summary, this is the first study to determine the changes and interactions of lncRNA-mRNA in RTG-2 cells under the IHNV infection. The results provided the valuable information concerning the lncRNAs in salmonid fish, which will benefit for future study on uncovering the roles of lncRNAs-mRNAs during the viral infection.The growing incidence of skin cancer (SC) has prompted the search for additional preventive strategies to counteract this global health concern. Mutant p53 (mutp53), particularly with ultraviolet radiation (UVR) signature, has emerged as a promising target for SC prevention based on its key role in skin carcinogenesis. Herein, the preventive activity of our previously disclosed mutp53 reactivator SLMP53-2 against UVR-induced SC was investigated. The pre-treatment of keratinocyte HaCaT cells with SLMP53-2, before UVB exposure, depleted mutp53 protein levels with restoration of wild-type-like p53 DNA-binding ability and subsequent transcriptional activity. SLMP53-2 increased cell survival by promoting G1-phase cell cycle arrest, while reducing UVB-induced apoptosis through inhibition of c-Jun N-terminal kinase (JNK) activity. SLMP53-2 also protected cells from reactive oxygen species and oxidative damage induced by UVB. Moreover, it enhanced DNA repair through upregulation of nucleotide excision repair pathway and depletion of UVB-induced DNA damage, as evidenced by a reduction of DNA in comet tails, γH2AX staining and cyclobutane pyrimidine dimers (CPD) levels. SLMP53-2 further suppressed UVB-induced inflammation by inhibiting the nuclear translocation and DNA-binding ability of NF-κB, and promoted the expression of key players involved in keratinocytes differentiation. Consistently, the topical application of SLMP53-2 in mice skin, prior to UVB irradiation, reduced cell death and DNA damage. It also decreased the expression of inflammatory-related proteins and promoted cell differentiation, in UVB-exposed mice skin. Notably, SLMP53-2 did not show signs of skin toxicity for cumulative topical use. Overall, these results support a promising protective activity of SLMP53-2 against UVB-induced SC.Cardiac arrhythmia occurs frequently worldwide, and in severe cases can be fatal. Mitochondria are the power plants of cardiomyocytes. In recent studies, mitochondria under certain stimuli produced excessive reactive oxygen species (ROS), which affect the normal function of cardiomyocytes through ion channels and related proteins. Mitochondrial oxidative stress (MOS) plays a key role in diseases with multifactorial etiopathogenesis, such as arrhythmia; MOS can lead to arrhythmias such as atrial fibrillation and ventricular tachycardia. This review discusses the mechanisms of arrhythmias caused by MOS, particularly of ROS produced by mitochondria. MOS can cause arrhythmias by affecting the activities of Ca2+-related proteins, the mitochondrial permeability transition pore protein, connexin 43, hyperpolarization-activated cyclic nucleotide-gated potassium channel 4, and ion channels. Based on these mechanisms, we discuss possible new treatments for arrhythmia. Targeted treatments focusing on mitochondria may reduce the progression of arrhythmias, as well as the occurrence of severe arrhythmias, and may be effective for personalized disease prevention.This study aimed to investigate the association between cardiovascular drugs and depression/anxiety in patients with cardiovascular disease (CVD). This meta-analysis was registered in PROSPERO (International Prospective Register of Systematic Reviews; CRD42020197839) and conducted in accordance with the MOOSE (Meta-analysis of Observational Studies in Epidemiology) guidelines. The PubMed, EMBASE, Web of Science, China National Knowledge Infrastructure, Wanfang, and VIP databases were systematically searched to identify all available studies on this topic. Random-effects multivariate meta-regression was performed to investigate the sources of study heterogeneity. Review Manager version 5.3 and Stata 12.0 were used for data analyses. This meta-analysis included 54 studies with a total number of 212,640 patients. Overall, in patients with CVD, aspirin (odds ratio [OR]0.91, 95% confidence interval [CI]0.86-0.96, P = 0.02) was associated with a lower risk of depression, while calcium channel blockers (CCB) (OR1.21, 95%CI1.