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Ligands as Stabilizers of G-Quadruplexes within Non-Coding RNAs.
An invasive form of intestinal Entamoeba (E.) histolytica infection, which causes amoebic liver abscess, is more common in men than in women. Immunopathological mechanisms are responsible for the more severe outcome in males. Here, we used a mouse model of hepatic amoebiasis to investigate the contribution of hepatic hypoxia-inducible factor (HIF)-1α to Th17/Treg responses in the context of the sex-specific outcome of liver damage.

C57BL/6J mice were infected intrahepatically with E. histolytica trophozoites. HIF-1α expression was determined by qPCR, flow cytometry and immunohistochemistry. Treg and Th17 cells were analysed by immunohistochemistry and flow cytometry. Finally, male and female hepatocyte-specific HIF-1α knockout mice were generated, and the effect of HIF-1α on abscess development, the cytokine milieu, and Th17/Treg differentiation was examined.

E. histolytica infection increased hepatic HIF-1α levels, along with the elevated frequencies of hepatic Tregs and Th17 cells. Whereas the Th17 cehe protein HIF-1α in hepatocytes, abscess formation is reduced; moreover, the sex difference in abscess size is abolished. These results suggest that HIF-1α modulates the immune response involved in the induction of immunopathology, resulting in differential disease susceptibility in males and females.
Infection with the parasite Entamoeba histolytica activates immunopathological mechanisms in male mice, which lead to liver abscesses that are larger than those in female mice. In the absence of the protein HIF-1α in hepatocytes, abscess formation is reduced; moreover, the sex difference in abscess size is abolished. These results suggest that HIF-1α modulates the immune response involved in the induction of immunopathology, resulting in differential disease susceptibility in males and females.The present work aimed to evaluate the efficacy of topical tacrolimus (0.01%) loaded propylene glycol (PG) modified nano-vesicles (Proglycosomes Nano-vesicles, PNVs) for the treatment of experimental dry eye syndrome (DES) in rabbits. DES was induced by topical application of atropine (1.0%) and benzalkonium chloride (0.1%) aqueous solution. PNVs treatment (PNV group) was compared with tacrolimus solution 0.01% (TAC group) and untreated group and healthy group were used as controls. PNV treated animals showed improved clinical performance with marked increase in tear production and tear break-up time (TBUT). Further, PNVs also subside ocular inflammation as evident from absence of matrix metalloprotenaise-9 and normal ocular surface temperature (32.3 ± 0.34 °C). Additionally, PNVs have positive effect on ocular and epithelial damage observed through low ocular surface staining score and improved globlet cell density. The PNV treatment was found to more effectively compared to TAC solution and most of the parameters were close to those of healthy animals. In conclusion, tacrolimus PNV formulation (0.01%) could be a potential therapy for treatment of dry eye syndrome.In vitro dissolution testing as a form of quality control has become a necessity in the pharmaceutical industry. As such, the need to establish a method that investigates the in vitro dissolution profile of inhaled products should be taken into account. The prime focus in this study was to examine the in-vitro in-vivo correlation utilising a modified version of the Twin Stage Impinger and to promote an in vitro dissolution model by enhancing the Fine Particle Dose (FPD) collection method for dry powder inhalers. The Twin Impinger was modified by inserting a stainless steel membrane holder disk in the base of the lower chamber. The design, with optimum drug deposition, was adopted for the dissolution study of budesonide and salbutamol. Afterwards, the membrane holder system was placed in the bottom of the dissolution vessel. Phosphate buffer saline (PBS), simulated lung fluid (SLF, Gamble solution) and Phosphate buffer (PB) were used in the study. The paddle dissolution apparatus, containing 300 mL of the medium, was operated at 75 rpm paddle speed. Samples were collected at defined time intervals and analysed using a validated HPLC method. The largest proportion of the budesonide dose was dissolved in PBS compared to PB and SLF. This was due to the presence of surfactant (0.2% w/v polysorbate), which enhances the wettability and the solubility of the poorly soluble drug (budesonide). The similarity factors for PBS and PB were 47.6 and 69.7, respectively, using SLF as a reference, whereas the similarity factor for salbutamol dissolution between PB and SLF was 81.3, suggesting PB is a suitable substitute. Comparison using both the predicted and actual in vivo pharmacokinetics (PK) values of the two drugs, as well as the pattern of their Concentration-Time (c-t) profiles, showed good similarity, which gave an indication of the validity of this in vitro dissolution method.The significant morbidity and mortality associated with severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection has underscored the need for novel antiviral strategies. Lipids play essential roles in the viral life cycle. The lipid composition of cell membranes can influence viral entry by mediating fusion or affecting receptor conformation. Upon infection, viruses can reprogram cellular metabolism to remodel lipid membranes and fuel the production of new virions. Further, several classes of lipid mediators, including eicosanoids and sphingolipids, can regulate the host immune response to viral infection. Here we summarize the existing literature on the mechanisms through which these lipid mediators may regulate viral burden in COVID-19. Further, we define the gaps in knowledge and identify the core areas in which lipids offer therapeutic promise for SARS-CoV-2.Phthalates are a class of endocrine disruptors found in a variety of consumer goods, and offspring can be exposed to these compounds during gestation and lactation. Our laboratory has found that perinatal exposure to an environmentally relevant mixture of phthalates resulted in a decrease in cognitive flexibility and in neuron number in the adult rat medial prefrontal cortex (mPFC). Here, we examine effects of phthalate treatment on prenatal cellular proliferation and perinatal apoptosis in the mPFC. To examine the phthalate effects on cellular proliferation, dams consumed 0, 1, or 5 mg/kg of the phthalate mixture daily from embryonic day 2 (E2) through the day of birth (P0), and on E16 and E17, they were injected with BrdU. The mPFC of offspring was analyzed on P5 and showed a decrease in labelled cells in the phthalate exposed groups. To examine whether changes in BrdU density observed on P5 were due to altered cell survival, cell death was measured on E18, P0, and P5 using a TUNEL assay in a separate cohort of prenatally exposed offspring. There was an increase in TUNEL labelled cells at E18 in the phthalate exposed groups. In the final experiment, dams consumed the phthalate mixture from E2 through P10, at which time mPFC tissue was stained with TUNEL. Phthalate treated subjects showed a higher density of apoptotic cells at P10. These results indicate both pre- and postnatal phthalate exposure increases apoptosis in the male and female rat mPFC. While the impact of phthalates on proliferation cannot be ruled out, these data do not allow for definitive conclusions.Bio-desilication of fly ash containing a large amount of crystalline and amorphous silicate compound by silicate bacteria had the advantages of energy-saving, environment-friendly, and controllable cost. In this study, a bacteria strain with desilication ability on fly ash was isolated from the soil and identified as Bacillus amyloliquefaciens by 16sRNA and named ZGW-12. Through the bio-leaching treatment of fly ash by ZGW-12, it was found that the concentration of Si was 306.26 mg/L and the concentration of Al3+ was 0.5 mg/L in the pulp. The mechanism of bio-leaching using ZGW-12 was investigated by XRD, HPLC, SEM, and FTIR. The organic acid and amino acid in the bacteria culture medium and the pulp were detected, and it was found that the content of the acidic metabolites in the pulp was much larger than that of the bacteria culture medium. The ore sample particles adsorbed a large number of bacteria cells and took place obvious corrosion. The surface of the ore sample undergone hydroxylation reaction, and the diffraction peak of the silicate crystal compound was unchanged. ZGW-12 exhibits good performance in retaining aluminum and extracting silicon aspect. AVAILABILITY OF DATA AND MATERIAL (DATA TRANSPARENCY) All data were true and valid.Haematococcus pluvialis is the prime source of natural astaxanthin for commercial exploitation. The large-scale cultivation of H. pluvialis is one of the key technologies for the development of natural astaxanthin industry. So far, horizontal tubular photobioreactor (HTPBR) circulated by a centrifugal pump has been the main PBR for the large-scale cultivation of H. pluvialis. Shear stress is a negative factor in microalgal cultivation at different scales, particularly for large-scale cultivation. To reduce the adverse impact of shear stress, the tolerance of H. pluvialis to the shear stress during the induction stage was first investigated in this study. H. pluvialis aplanospore was not sensitive to stresses between 19.18 and 27.32 Pa, but was resulted in about 30% cell death under shear stress between 27.32 and 63.84 Pa. Accordingly, two centrifugal pumps with different impellers was selected in 400 L HTPBRs to study the outdoor photoinduction for astaxanthin accumulation. The highest astaxanthin productivity and astaxanthin concentration were obtained in HTPBRs using a centrifugal pump equipped with three unshrouded backward-bladed impellers. The HTPBR was then successfully scaled up to 800 L with a similar performance, showing good scalability.Nitrogen (N) affects common buckwheat quality by affecting starch and amino acids (AAs) content, but its molecular mechanism is still unclear. We selected two common buckwheat varieties with high and low starch content, and designed two treatments with 180 and 0 kg N/ha. Application of high-N led to significant increases in starch, amylose and amylopectin content. Selleckchem Sodium acrylate Of 1337 differentially expressed proteins (DEPs) induced by high-N conditions. 472DEPs were significantly upregulated and 176DEPs downregulated for Xinong9976. 239DEPs were significantly upregulated and 126DEPs downregulated for Beizaosheng. The six alpha-glucan phosphorylases, three alpha-amylases, one granule-bound starch synthase 1 and one sucrose synthase exhibited higher expression at the 180 kg N/ha than at the 0 kg N/ha. In addition, high-N application promoted arginine, leucine, isoleucine and valine biosynthesis. This study revealed the effect of N on the starch and AA content of common buckwheat and its mechanism. The crucial proteins identified may develop the quality of common buckwheat.There are several studies reporting that different plant-based metabolites are potential inhibitors of protein amyloid fibrillation. As chemical features of metabolites can regulate protein aggregation process, in the present in vitro investigation, tau protein was selected as a model of Alzheimer's disease to elaborate the inhibitory effect of syringic acid (SA) on its assembly and associated neurotoxicity in aggregation conditions. Extrinsic fluorescence, Congo red adsorption, and CD spectroscopic studies, TEM, size-exclusion chromatography, and MALDI-TOF mass spectrometry analysis along with MTT and qRT-PCR assays were performed to assess the inhibitory effects of SA against tau aggregation and neurotoxicity. It was shown that SA has the tendency to control the aggregation of the tau proteins through modulating the amyloid kinetic parameters, exposure of hydrophobic residues, and structural changes. Moreover, the structures formed in the presence of SA recovered the viability of neuron-like cells (SH-SY5Y) through regulation of endoplasmic reticulum stress signaling pathway by downregulation of ATF-6, caspase-8 and caspase-3 mRNA.
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