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Lunde May opublikował 5 miesięcy, 1 tydzień temu
Nowadays, apart from having to know first-line Helicobacter pylori eradication regimens well, we must also be prepared to face treatment failures. The aim of this review is to summarize the role of rifabutin in the management of H. pylori infection. Bibliographical searches were performed in PubMed. Data on resistance and efficacy of rifabutin-containing regimens on H. pylori eradication were meta-analyzed. Mean H. pylori rifabutin resistance rate (39 studies, including 9721 patients) was 0.13%; when studies only including patients naïve to H. pylori eradication treatment were considered, this figure was even lower (0.07%). Mean H. pylori eradication rate (by intention-to-treat) with rifabutin-containing regimens (3052 patients) was 73%. Respective cure rates for second-, third-, fourth- and fifth-line therapies, were 79%, 69%, 69% and 72%. Most studies administered rifabutin 300 mg/day, which seemed to be more effective than 150 mg/day. The ideal length of treatment remains unclear, but 10-12-day regimens are generally recommended. Adverse events to rifabutin treatment in H. pylori studies were relatively infrequent (15%), and severe adverse events were exceptional (myelotoxicity was the most significant, although always reversible). In summary, rifabutin-containing therapy represents an encouraging strategy generally restricted, at present, to patients where previous (usually multiple) eradication regimens have failed.γ-Aminobutyric acid (GABA) is a widely distributed non-protein amino acid mediated the regulation of nitrate uptake and Al3+ tolerance in plants. However, there are few reports about the involvement of GABA in the regulation of iron (Fe) acquisition and translocation. Here, we show that GABA regulates Fe homeostasis in rice seedlings. Exogenous GABA decreased the chlorophyll concentration in leaves, with or without Fe supply. Over-expression of glutamate decarboxylase (GAD) gene, coding a crucial enzyme of GABA production, elevated endogenous GABA content and caused more leaf chlorosis than wild type (Nipponbare). GABA inhibited Fe transportation from roots to shoots and GABA application elevated the expression levels of Fe deficiency (FD)-related genes under conditions of Fe-sufficiency (FS), suggesting that GABA is a regulator of Fe translocation. Using Perls’ blue staining, we found that more ferric iron (Fe3+) was deposited in the epidermal cells of roots treated with GABA compared with control roots. Anatomic section analysis showed that GABA treatment induced more aerenchyma formation compared with the control. Aerenchyma facilitated the oxidization of soluble ferrous iron (Fe2+) into insoluble Fe3+, resulted in Fe precipitation in the epidermis, and inhibited the transportation of Fe from roots to shoots.The development, progression, or stabilization of the atherosclerotic plaque depends on the pro-inflammatory and anti-inflammatory macrophages. The influx of the macrophages and the regulation of macrophage phenotype, inflammatory or anti-inflammatory, are controlled by the small GTPase RhoA and its downstream effectors. Therefore, macrophages and the components of the RhoA pathway are attractive targets for anti-atherosclerotic therapies, which would inhibit macrophage influx and inflammatory phenotype, maintain an anti-inflammatory environment, and promote tissue remodeling and repair. Here, we discuss the recent findings on the role of macrophages and RhoA pathway in the atherosclerotic plaque formation and resolution and the novel therapeutic approaches.Background Existing standardized biofilm assays focus on simple mono-species or bacterial-only models. Incorporating Candida albicans into complex biofilm models can offer a more appropriate and relevant polymicrobial biofilm for the development of oral health products. Aims This study aimed to assess the importance of interkingdom interactions in polymicrobial oral biofilm systems with or without C. albicans, and test how these models respond to oral therapeutic challenges in vitro. Materials and Methods Polymicrobial biofilms (two models containing 5 and 10 bacterial species, respectively) were created in parallel in the presence and absence of C. albicans and challenged using clinically relevant antimicrobials. The metabolic profiles and biomasses of these complex biofilms were estimated using resazurin dye and crystal violet stain, respectively. Quantitative PCR was utilized to assess compositional changes in microbial load. Additional assays, for measurements of pH and lactate, were included to monitor fluctuations in virulence „biomarkers.” Results An increased level of metabolic activity and biomass in the presence of C. albicans was observed. Bacterial load was increased by more than a factor of 10 in the presence of C. albicans. Assays showed inclusion of C. albicans impacted the biofilm virulence profiles. C. albicans did not affect the biofilms’ responses to the short-term incubations with different treatments. Conclusions The interkingdom biofilms described herein are structurally robust and exhibit all the hallmarks of a reproducible model. To our knowledge, these data are the first to test the hypothesis that yeasts may act as potential „keystone” components of oral biofilms.In this study, kaempferol (KFL) shows hepatoprotective activity against zearalenone (ZEA)-induced oxidative stress and its underlying mechanisms in in vitro and in vivo models were investigated. Oxidative stress plays a critical role in the pathophysiology of various hepatic ailments and is normally regulated by reactive oxygen species (ROS). ZEA is a mycotoxin known to exert toxicity via inflammation and ROS accumulation. This study aims to explore the protective role of KFL against ZEA-triggered hepatic injury via the PI3K/Akt-regulated Nrf2 pathway. KFL augmented the phosphorylation of PI3K and Akt, which may stimulate antioxidative and antiapoptotic signaling in hepatic cells. KFL upregulated Nrf2 phosphorylation and the expression of antioxidant genes HO-1 and NQO-1 in a dose-dependent manner under ZEA-induced oxidative stress. Nrf2 knockdown via small-interfering RNA (siRNA) inhibited the KFL-mediated defence against ZEA-induced hepatotoxicity. In vivo studies showed that KFL decreased inflammation and lipid peroxidation and increased H2O2 scavenging and biochemical marker enzyme expression. KFL was able to normalize the expression of liver antioxidant enzymes SOD, CAT and GSH and showed a protective effect against ZEA-induced pathophysiology in the livers of mice. These outcomes demonstrate that KFL possesses notable hepatoprotective roles against ZEA-induced damage in vivo and in vitro. These protective properties of KFL may occur through the stimulation of Nrf2/HO-1 cascades and PI3K/Akt signaling.Chronic hepatitis B virus (HBV) infection is a major global health problem. It can cause progressive liver fibrosis leading to cirrhosis with end-stage liver disease, and a markedly increased risk of hepatocellular carcinoma. In the last two decades, substantial progress has been made in the treatment of chronic hepatitis, B. However, HBV is often reactivated after stopping nucloes(t)ide analogues because antivirals alone do not directly target covalently closed circular DNA, which is the template for all viral RNAs. Therefore, although currently available antiviral therapies achieve suppression of HBV replication in the majority of patients, hepatitis B surface antigen (HBsAg) loss and seroconversion is rarely achieved despite long-term antiviral treatment (HBsAg loss of less than 10% in 5 years). Various clinical trials of agents that interrupt the HBV life cycle in hepatocytes have been conducted. Potential treatment strategies and new agents are emerging as HBV cure. A combination of current and new anti-HBV agents may increase the rate of HBsAg seroclearance; thus, optimized regimens must be validated. Here, we review the newly investigated therapeutic compounds and the results of preclinical and/or clinical trials.Due to the non-uniform tension and compression strength of concrete, carbon fiber can be added to concrete to improve its static tensile behavior and increase the tension-compression ratio. In view of the destructive consequences of impacts and explosions, it is necessary to study the dynamic responses of carbon fiber reinforced concrete (CFRC) structures. Therefore, the effects of the stress rates and carbon fiber contents on the dynamic tension behavior of CFRC were investigated in this paper. The dynamic splitting tests of concrete with the fiber contents of 0, 0.1, 0.2, and 0.3% were carried out by using a split Hopkinson pressure bar (SHPB) device with a diameter of 74 mm. We found that with the increase of fiber content, the static tensile strength of CFRC increases obviously, but the increased amplitude tends to decrease. The dynamic tensile strength and dynamic increase factor (DIF) both increase with the increase of stress rate, but the growth rate slows down, showing an obvious rate effect. The rate sensitivity of ordinary concrete is higher than CFRC. There are significant differences in the influence of carbon fiber on the dynamic and static strength of concrete. In the design of concrete mixing proportion, the content of carbon fiber should be appropriately selected to meet the requirements of dynamic and static mechanical properties.Lin28A and Lin28B are two homologues of the same family of RNA binding proteins (RBPs). The function and molecular mechanism of Lin28A in the formation of primordial germ cells (PGCs) are very clear, but the related research on Lin28B is rarely reported. Here, we found that the overexpression of Lin28B can promote the formation of PGC in vivo. Furthermore, the overexpression of Lin28B also resulted in the inhibition of totipotency gene expression and upregulated the PGCs marker genes, and a significant increase in the number of PGCs in genital ridge, as detected by Periodic Acid-Schiff(PAS) staining. However, the inhibited Lin28B expression showed completely opposite results, which were confirmed on the PGC induction model in vitro. Mechanistically, we found that the overexpression of Lin28B can inhibit the maturation of let-7a-3p, and the results of high-throughput sequencing indicated that let-7a-3p was a negative regulator of the formation process of PGCs. Therefore, we conclude that our results determine that Lin28B participates in the formation of PGCs through let-7a-3p, which set a theoretical foundation for improving the function and mechanism of Lin28 family in the formation of PGCs.Even though the characteristics of polymer materials are sensitive to temperature, the mechanical properties of polymer nanocomposites have rarely been studied before, especially for the fatigue behavior of hybrid polymer nanocomposites. Hence, the tensile quasi-static and fatigue tests for the epoxy nanocomposites reinforced with multi-walled carbon nanotubes (CNTs) and graphene nanoplatelets (GNPs) were performed at different temperatures in the study to investigate the temperature-dependent synergistic effect of hybrid nano-fillers on the studied properties. The temperature and the filler ratio were the main variables considered in the experimental program. A synergistic index was employed to quantify and evaluate the synergistic effect of hybrid fillers on the studied properties. Experimental results show that both the monotonic and fatigue strength decrease with increasing temperature significantly. The nanocomposites with a MWCNT (multi-walled CNT) GNP ratio of 91 display higher monotonic modulus/strength and fatigue strength than those with other filler ratios.