Svendsenkristensen8176

In this review, recent developments and applications with cell-penetrating peptides (CPP) are discussed. CPPs are widely used tools for the delivery of various macromolecular therapeutics, such as proteins and nucleic acids.

The current review focuses on recent important advances and reports that demonstrate high clinical and translational potential. Most important clinical developments have occurred with the CPP-drug conjugate approaches that target various protein-protein interactions, and these have been highlighted subsequently. #link# Most of the applications are targeting cancer, but recently, noteworthy advances have taken place in the field of antisense oligonucleotides and muscular dystrophies, lung targeting, and trans-BBB targeting.

Successful applications and clinical development with the drug conjugate approaches are discussed. On the other hand, the reasons of why the nanoparticle approaches are not as far in development are analyzed.

Successful applications and clinical development with the drug conjugate approaches are discussed. On the other hand, the reasons of why the nanoparticle approaches are not as far in development are analyzed.To characterize atherogenesis functionally, we studied the functional heterogeneity of endotheliocytes in carotid vessels with atherosclerotic plaques and identified several distinct cell clusters. We measured the Ki-67 labeling index (Ki-67 LI), percentage of Bcl-2 cells (CP) and expression of CCL5, IL 6 and VCAM1 in each cell cluster. We also investigated how these indicators change when the plaque becomes unstable and how they affect the risk of adverse cerebrovascular events in patients. We evaluated the inter-cluster gradient of marker activity and its relation to patient prognosis. We identified five endothelial clusters the under plaque cluster (UPC), peripheral cluster (PC), marginal cluster (MC), transient cluster (TC) and outside plaque cluster (OC). The UPC exhibited the greatest proliferative, proinflammatory and adhesive activity, but low anti-apoptotic activity. The PC exhibited the second greatest proliferative, adhesive and proinflammatory activity. Progression of atherosclerosis and transition of a stable atherosclerotic plaque to an unstable one was accompanied by increased expression of nearly all markers. The proliferative activity in the UPC, PC and OC, and the pro-inflammatory activity in UPC and anti-apoptotic activity in the PC, were correlated with prognosis. Also, two gradients of proliferative activity and a gradient of pro-inflammatory activity were associated with risk of adverse events.

The widespread use of probiotics globally has established an argument against their safety profile. Recent studies investigated the gastrointestinal tract (GIT) as a reservoir for antibiotic resistance genes and horizontal gene transfer (HGT) amongst opportunistic pathogens, probiotics, and the normal microbiota which might cause severe clinical implications.

In this review, we aimed to discuss the potential role of probiotics in spreading antibiotic resistance. All relevant data were found through online/updated databases such as PubMed, Google Scholar, and Clinicaltrials.gov. This review is based on the studies undertaken over the past two decades (2000-2020).

Microorganisms are capable of transferring resistance genes to survive against antimicrobial medications. Transference of resistance genes among pathogens, probiotics, and gut microbiota in the GIT through HGT endow probiotics as a possible source for antimicrobial resistance genes, which is responsible for the development of the antibiotic resistance crisis. According to the expression of genes in mechanisms of antibiotics resistance and probiotics HGT, the hypothesis of the role of these microorganisms in personalized medicine and gene therapy could also be considered.

Microorganisms are capable of transferring resistance genes to survive against antimicrobial medications. link2 Transference of resistance genes among pathogens, probiotics, and gut microbiota in the GIT through HGT endow probiotics as a possible source for antimicrobial resistance genes, which is responsible for the development of the antibiotic resistance crisis. According to the expression of genes in mechanisms of antibiotics resistance and probiotics HGT, the hypothesis of the role of these microorganisms in personalized medicine and gene therapy could also be considered.

Induced abortion is an occupational hazard for female sex workers (FSWs). This study aimed to examine the prevalence and factors associated with induced abortion among FSWs in Iran.

1337 FSWs aged ≥18 years who reported selling sex to more than one male client in the past 12 months were recruited in 13 major cities in Iran between January and August 2015. Bivariable and multivariable modified Poisson regression models were constructed to examine the correlates of induced abortion. Adjusted prevalence ratios (APRs) with 95% confidence intervals (CIs) were reported.

Lifetime induced abortion was reported by 621 of 1335 participants (46.5%; 95% CI 43.8, 49.2). Older age (APR for ≥ 35 vs. < 25 years, 1.46; 95% CI 1.03, 2.07), having ever been married (APR 1.58; 95% CI 1.05, 2.39), having ever worked in a brothel (APR 1.19; 95% CI 1.02, 1.38) and a lifetime history of being raped (APR 1.19; 95% CI 1.03, 1.38) were significantly associated with lifetime induced abortion (all

 < 0.05).

The high prevalence of induced abortion among FSWs in Iran is concerning. link3 Evidence-informed programmes targeting FSWs in Iran would improve their knowledge and encourage contraceptive use as well as promote pregnancy prevention and post-abortion care.

The high prevalence of induced abortion among FSWs in Iran is concerning. Evidence-informed programmes targeting FSWs in Iran would improve their knowledge and encourage contraceptive use as well as promote pregnancy prevention and post-abortion care.

Trauma can lead to trauma centrality and affect levels of interpersonal sensitivity and psychiatric co-morbidity. Whether a coexisting relationship between posttraumatic stress disorder (PTSD) and trauma centrality can influence levels of interpersonal sensitivity and psychiatric co-morbidity among university students from Kazakhstan is unknown.

To investigate the impact of the aforementioned co-existing relationship on interpersonal sensitivity and psychiatric co-morbidity among Kazakh university students.

597 students (F = 428, M = 169) completed questionnaires measuring PTSD, psychiatric co-morbidity, interpersonal sensitivity, and trauma centrality.

28%, 32% and 40% met the criteria for full, partial and no-PTSD, respectively. Latent Class Analysis revealed a three-class solution Class 1 (the altered-self group) with a low level of PTSD but a high level of trauma centrality, Class 2 (the traumatized-self group) with high levels of PTSD and trauma centrality and Class 3 (the low symptom group) with low levels of PTSD and trauma centrality. There were significant differences in the levels of interpersonal sensitivity and psychiatric co-morbidity across three classes.

There are individual differences in the display of posttraumatic stress disorder symptoms, and trauma centrality. These differences can influence interaction with others and psychological distress.

There are individual differences in the display of posttraumatic stress disorder symptoms, and trauma centrality. These differences can influence interaction with others and psychological distress.Many cholesterol-laden foam cells in atherosclerotic lesions are macrophages and much of their cholesterol is present in their lysosomes and derived from low density lipoprotein (LDL). LDL oxidation has been proposed to be involved in the pathogenesis of atherosclerosis. We have shown previously that LDL can be oxidised in the lysosomes of macrophages. α-Tocopherol has been shown to inhibit LDL oxidation in vitro, but did not protect against cardiovascular disease in large clinical trials. We have therefore investigated the effect of α-tocopherol on LDL oxidation at lysosomal pH (about pH 4.5). LDL was enriched with α-tocopherol by incubating human plasma with α-tocopherol followed by LDL isolation by ultracentrifugation. The α-tocopherol content of LDL was increased from 14.4 ± 0.2 to 24.3 ± 0.3 nmol/mg protein. LDL oxidation was assessed by measuring the formation of conjugated dienes at 234 nm and oxidised lipids (cholesteryl linoleate hydroperoxide and 7-ketocholesterol) by HPLC. As expected, LDL enriched with α-tocopherol was oxidised more slowly than control LDL by Cu2+ at pH 7.4, but was not protected against oxidation by Cu2+ or Fe3+ or a low concentration of Fe2+ at pH 4.5 (it was sometimes oxidised faster by α-tocopherol with Cu2+ or Fe3+ at pH 4.5). α-Tocopherol-enriched LDL reduced Cu2+ and Fe3+ into the more pro-oxidant Cu+ and Fe2+ faster than did control LDL at pH 4.5. These findings might help to explain why the large clinical trials of α-tocopherol did not protect against cardiovascular disease.The symptoms of Alzheimer's disease (AD) do not include only memory loss and cognitive decline but also neuropsychiatric manifestation. These AD-related symptoms are usually treated with the aid of antipsychotics; however, their effects on cognition and safety remain unexplored. The present study determines the effects of quetiapine, an atypical antipsychotic, and two imidazo[1,2-a]pyrimidine-based inhibitors of PDE10A on the activity of human cholinesterases. Quetiapine moderately inhibited BuChE (IC50 = 6.08 ± 1.64 µmol/L) but improved the anti-BuChE properties of donepezil by decreasing its IC50 value. Both PDE10A inhibitors were found to possess moderate anti-AChE properties. The combined mixtures of donepezil and imidazo[1,2-a]pyrimidine analogues produce a synergistic anti-BuChE effect which was greater than either compound alone, improving the IC50 value by approximately six times. These favourable interactions between quetiapine, PDE10A inhibitors and clinically approved donepezil, resulting in improved anti-BuChE activity, can lead to a wider variety of potent AD treatment options.

To examine the biochemical and histopathological effects of ischemia/reperfusion (I/R) injury in a ruptured abdominal aortic aneurysm (RAAA) model in rats, and to investigate the potential protective role of resveratrol.

Thirty-two male Sprague-Dawley rats were randomly assigned into four groups-control, I/R, sham (I/R + solvent/dimethyl sulfoxide), and I/R + resveratrol. read more underwent midline laparotomy only. In the other groups, infrarenal vascular clamps were attached following 60-min shock to the abdominal aorta. Ischemia was applied for 60 min followed by reperfusion for 120 min. In the I/R + resveratrol group, intraperitoneal 10 mg/kg resveratrol was administered 15 min prior to ischemia and immediately before reperfusion. The I/R + dimethyl sulfoxide group received dimethyl sulfoxide, and the I/R group was given saline solution. All animals were sacrificed by exsanguination from the carotid artery at the end of the experiment. In addition to histopathological examination of the rat kidney tissues, malondialdehyde, glutathione, catalase, and nitric oxide levels were also investigated.

A decrease in glutathione, catalase and nitric oxide levels, together with increases in malondialdehyde levels, numbers of apoptotic renal tubular cells, caspase-3 levels, and tubular necrosis scores, were observed in the IR and I/R + dimethyl sulfoxide groups. In contrast, resveratrol increased glutathione, catalase and nitric oxide levels in renal tissues exposed to I/R, while reducing malondialdehyde levels, apoptotic renal tubular cell numbers, caspase-3 levels, and tubular necrosis scores.

Our findings suggest that resveratrol can be effective against I/R-related acute kidney damage developing during RAAA surgery by reducing oxidative stress and apoptosis.

Our findings suggest that resveratrol can be effective against I/R-related acute kidney damage developing during RAAA surgery by reducing oxidative stress and apoptosis.