Lindgrenjohnston5456
Resistance to apoptosis is a key mechanism underlying how cancer cells evade tumor therapy. Autophagy can prevent anticancer drug-induced apoptosis and promote tumor resistance. The purpose of this study was to improve the sensitivity and efficacy of chemotherapeutic drugs through the inhibition of autophagy. Hydrophobic doxorubicin-hydrazone-caproyl-maleimide (DOX-EMCH) and autophagy-inhibiting si-Beclin1 were simultaneously delivered via the amphiphilic peptide micelle system (Co-PMs) using poly(L-arginine)-poly(L-histidine)-DOX-EMCH as the copolymer building unit. The constructed micelle system promoted the escape of si-Beclin1 from endosomes and the release of DOX into the nucleus. The Co-PMs exhibited 2.7-fold higher cytotoxicity and proapoptotic ability in PC3 cells than DOX treatment alone, demonstrating that si-Beclin1 could inhibit the autophagic activity of prostate cancer (PCa) cells by targeting the type III PI3K pathway and enhance the sensitivity of the cells to the chemotherapeutic drug DOX. In addition, the peptide micelles successfully passively targeted DOX and si-Beclin1 to the tumor tissue. Compared with DOX or si-Beclin1 treatment alone, the Co-PMs showed a 3.4-fold greater tumor inhibitory potential in vivo, indicative of a significant antiproliferative effect. Our results suggested that the Co-PMs developed in this study have the potential to combine autophagy inhibition and chemotherapy in cancer treatment, especially for PCa.The COVID-19 pandemic has resulted in the publishing of a quantity of scientific research. In less than a year, a record of 200,000 scientific articles have been published on COVID-19. Publishing such a massive quantity of scientific research has instigated publishers to accelerate the review process. An upsurge in the publication rate has resulted in an increase in the retraction rate. This paper focuses on the COVID-19 studies originating across the world from 1 January 2020 to 10 October 2021. The data for this study were mined from http//retractiondatabase.org/. A total of 157 withdrawn articles on COVID-19 were retracted, and it was found that the United States of America contributed 31 (19.75%) retracted articles. Also, 16 (51.61%) of the retracted papers from the United States of America emerge in journals having an Impact Factor (IF). The study presents that 31 (19.75%) retracted articles were worked together by two authors, 26 (16.56%) with one author, and 22 (14.01%) by five authors. Furthermore, Elsevier publishers have the highest retraction rate with 80 (50.96%). Half (50%) of the articles were retracted with "no information" as a reason for retraction. Other reasons for retraction include concern/issues about data, duplication, journal error, lack of approval from a third party, plagiarism, etc.
Dry needling (DN) has been shown to be effective for the treatment of upper extremity hypertonia in patients with stroke.
To evaluate the cost-effectiveness of DN in patients with stroke.
A cost-effectiveness analysis was performed in a research study conducted at a Spanish public hospital where patients were classified into two groups with or without DN. Hypertonia was measured using the Modified Modified Ashworth Scale (MMAS), and quality of life (QOL) was assessed using the EuroQoL 5-dimension questionnaire. Data regarding the effects and costs of physiotherapy were presented by calculating the mean and 95% confidence interval. The health outcomes were evaluated considering the rate of responders to the treatment based on the MMAS. Spanish preference weights were used to estimate quality-adjusted life years (QALYs). The incremental cost-effectiveness ratio (ICER) and incremental cost-utility ratio (ICUR) were calculated to determine the economic value of DN.
Eighty patients with stroke in the subacute stage of recovery were selected to participate in this study. Based on the rate of responders, the ICER of the DN group was very low. Despite the sensitivity analysis performed, the results of the ICUR were not encouraging.
Cost-effectiveness with responder rate results were favourable for the DN group and were confirmed by the sensitivity analysis according to levels of care. In addition, our findings revealed that 4 weeks of treatment could be more cost-effective than 8 weeks. DN treatment of the upper extremity appears to be cost-effective based on the rate of responders measured using the MMAS scale.
Cost-effectiveness with responder rate results were favourable for the DN group and were confirmed by the sensitivity analysis according to levels of care. In addition, our findings revealed that 4 weeks of treatment could be more cost-effective than 8 weeks. DN treatment of the upper extremity appears to be cost-effective based on the rate of responders measured using the MMAS scale.The dramatic global consequences of the coronavirus disease 2019 (COVID-19) pandemic soon fueled quests for a suitable model that would facilitate the development and testing of therapies and vaccines. In contrast to other rodents, hamsters are naturally susceptible to infection with severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), and the Syrian hamster (Mesocricetus auratus) rapidly developed into a popular model. It recapitulates many characteristic features as seen in patients with a moderate, self-limiting course of the disease such as specific patterns of respiratory tract inflammation, vascular endothelialitis, and age dependence. Among 4 other hamster species examined, the Roborovski dwarf hamster (Phodopus roborovskii) more closely mimics the disease in highly susceptible patients with frequent lethal outcome, including devastating diffuse alveolar damage and coagulopathy. Thus, different hamster species are available to mimic different courses of the wide spectrum of COVID-19 manifestations in humans. On the other hand, fewer diagnostic tools and information on immune functions and molecular pathways are available than in mice, which limits mechanistic studies and inference to humans in several aspects. Still, under pandemic conditions with high pressure on progress in both basic and clinically oriented research, the Syrian hamster has turned into the leading non-transgenic model at an unprecedented pace, currently used in innumerable studies that all aim to combat the impact of the virus with its new variants of concern. As in other models, its strength rests upon a solid understanding of its similarities to and differences from the human disease, which we review here.The bacterium Listeria monocytogenes (Lm) is widely distributed in the environment as a saprophyte, but may turn into a lethal intracellular pathogen upon ingestion. Invasive infections occur in numerous species worldwide, but most commonly in humans and farmed ruminants, and manifest as distinct forms. Of those, neuroinfection is remarkably threatening due to its high mortality. Lm is widely studied not only as a pathogen but also as an essential model for intracellular infections and host-pathogen interactions. Many aspects of its ecology and pathogenesis, however, remain unclear and are rarely addressed in its natural hosts. U0126 chemical structure This review highlights the heterogeneity and adaptability of Lm by summarizing its association with the environment, farm animals, and disease. It also provides current knowledge on key features of the pathology and (molecular) pathogenesis of various listeriosis forms in naturally susceptible species with a special focus on ruminants and on the neuroinvasive form of the disease. Moreover, knowledge gaps on pathomechanisms of listerial infections and relevant unexplored topics in Lm pathogenesis research are highlighted.Aim We explored the concentrations of urinary neutrophil gelatinase-associated lipocalin (NGAL) in healthy adults in the Jiangsu region in Eastern China and established a reference interval using latex-enhanced immunoturbidimetry to provide important guidelines for the interpretation and application of urinary NGAL in clinical practice. Methods In total, 1970 eligible subjects from four regions were included in this study. The urinary NGAL levels were measured using an AU5800 automatic biochemical analyzer with its matched reagents. The urinary NGAL reference interval was established using the one-sided percentile method (95th percentile). Results The urinary NGAL data were non-normally distributed. The urinary NGAL levels were not significantly different by sex or age. Therefore, the urinary NGAL reference interval in healthy adults in the Jiangsu region in Eastern China was less then 87.5 ng/ml (95th percentile of the upper limit). Conclusion Urinary NGAL reference interval will play an important role in promoting the clinical value of urinary NGAL.Agrobacterium tumefaciens species complex contains a set of diverse bacterial strains most of which are well known for their pathogenicity on agricultural plants causing crown gall diseases. Members of A. tumefaciens species complex are classified into several taxonomically distinct lineages called "genomospecies" (13 genomospecies until early 2021). Recently, two genomospecies, i.e., G19 (strains RnrT, Rew and Rnw) and G20 (strains OT33T and R13) infecting Rose sp. plants in Iran were described based on biochemical and molecular-phylogenetic data. Whole genome sequence-based core-genome phylogeny followed by average nucleotide identity (ANI) and digital DNA-DNA hybridization (dDDH) calculations performed in this study suggested that genomospecies G19 and G20 could be described as two novel and standalone species. In the phylogenetic tree, these two new genomospecies were clustered separately from other genomospecies/species of A. tumefaciens species complex. Moreover, both ANI and dDDH indices between the G19/G20 strains and other Rhizobiaceae members are clearly below the accepted thresholds for prokaryotic species description. Hence, Agrobacterium burrii sp. nov. is proposed to encompass the G19 strains, with RnrT = CFBP 8705T = DSM 112541T as type strain. Agrobacterium shirazense sp. nov. is also proposed to include G20 strains, with OT33T = CFBP 8901T = DSM 112540T as type strain.Leptomeningeal anastomoses are small distal anastomotic vessels also known as pial collaterals in the brain. These vessels redirect blood flow during an occlusion and are important for stroke treatment and outcome. Pial collaterals have unique hemodynamic forces and experience significantly increased luminal flow and shear stress after the onset of ischemic stroke. However, there is limited knowledge of how pial collaterals respond to flow and shear stress, and whether this response is altered in chronic hypertension. Using an in vitro system, pial collaterals from normotensive and hypertensive rats (n=6-8/group) were isolated and luminal flow was induced with intravascular pressure maintained at 40 mm Hg. Collateral lumen diameter was measured following each flow rate in the absence or presence of pharmacological inhibitors and activators. Collaterals from male and female Wistar rats dilated similarly to increased flow (2 µL/minute 58.4±18.7% versus 67.9±7.4%; P=0.275), and this response was prevented by inhibition of the transient receptor potential vanilloid type 4 channel, as well as inhibitors of nitric oxide and intermediate-conductance calcium-activated potassium channels, suggesting shear stress-induced activation of this pathway was involved. However, the vasodilation was significantly impaired in hypertensive rats (2 µL/minute 17.7±7.7%), which was restored by inhibitors of reactive oxygen species and mimicked by angiotensin II. Thus, flow- and shear stress-induced vasodilation of pial collaterals appears to be an important stimulus for increasing collateral flow during large vessel occlusion. Impairment of this response during chronic hypertension may be related to poorly engaged pial collaterals during ischemic stroke in hypertensive subjects.