THE IMMUNOTHERAPEUTIC EFFECT OF IL-22 VERSUS PRAZIQUANTEL TREATMENT AGAINST S.MANSONI –INDUCED LIVER FIBROSIS IN MICE

Background/Aim:Praziquantel (PZQ), the primary medication for schistosomiasis treatment, exhibits a potential resistance by the parasite. Therefore, the development of a new effective treatment is obligated. Interleukin-22 (IL-22) has been reported to have a hepatoprotective effect. The current study aimed to compare the effectiveness of IL-22 treatment versus PZQ against S. mansoni - induced liver fibrosis in mice. Materials and Methods: Forty male albino mice were divided into control, infected, IL-22 (0.36 µg/kg),  and PZQ (a single dose of 600 mg/kg) groups. PZQ was administered alone or in combination with IL-22. Inflammatory indicators [tumor necrosis factor-α (TNF-α), interleukin-17 (IL-17), IL-22, and immunoglobulin E (IgE)], hepatic expressions of signal transducer and activator of transcription 3 (STAT3), β-catenin, and miR let-7a gene expressions, and liver granuloma index (GI) were estimated. Results:The present result revealed a significant (P <0.05) reduction in liver GI and the pro-inflammatory cytokine, TNF-α, after the treatment with IL-22. Moreover, the treatment enhanced significantly (P <0.05) let-7a miRNA and STAT3 gene expressions as well as downregulated (P <0.05) β-catenin mRNA, which in turn could reduce fibrosis resulting from S. mansoni infection. On the other hand, PZQ treatment alone or in combination with IL-22 reduced significantly (P <0.05) proinflammatory cytokines and IgE but failed to decrease GI or β-catenin gene expression, which might cause a negative impact on liver fibrosis.  Conclusion:IL-22 could be a potential immunotherapeutic agent for S.mansoni-induced liver fibrosis, compared to PZQ, through activating STAT3 and let-7a downstream signalling pathways and inhibiting β-catenin pathway

Chromatin establishes an immature version of neuronal protocadherin selection during the naive-to-primed conversion of pluripotent stem cells.

In the mammalian genome, the clustered protocadherin (cPCDH) locus provides a paradigm for stochastic gene expression with the potential to generate a unique cPCDH combination in every neuron. Here we report a chromatin-based mechanism that emerges during the transition from the naive to the primed states of cell pluripotency and reduces, by orders of magnitude, the combinatorial potential in the human cPCDH locus. This mechanism selectively increases the frequency of stochastic selection of a small subset of cPCDH genes after neuronal differentiation in monolayers, 10-month-old cortical organoids and engrafted cells in the spinal cords of rats. Signs of these frequent selections can be observed in the brain throughout fetal development and disappear after birth, except in conditions of delayed maturation such as Down's syndrome. We therefore propose that a pattern of limited cPCDH-gene expression diversity is maintained while human neurons still retain fetal-like levels of maturation

Immunological characterization of chromogranins A and B and secretogranin II in the bovine pancreatic islet

Antisera against chromogranin A and B and secretogranin II were used for analysing the bovine pancreas by immunoblotting and immunohistochemistry. All three antigens were found in extracts of fetal pancreas by one dimensional immunoblotting. A comparison with the soluble proteins of chromaffin granules revealed that in adrenal medulla and in pancreas antigens which migrated identically in electrophoresis were present. In immunohistochemistry, chromogranin A was found in all pancreatic endocrine cell types with the exception of most pancreatic polypeptide-(PP-) producing cells. For chromogranin B, only a faint immunostaining was obtained. For secretorgranin II, A-and B-cells were faintly positive, whereas the majority of PP-cells exhibited a strong immunostaining for this antigen. These results establish that chromogranins A and B and secretogranin II are present in the endocrine pancreas, but that they exhibit a distinct cellular localization

DNMT3L Modulates Significant and Distinct Flanking Sequence Preference for DNA Methylation by DNMT3A and DNMT3B In Vivo

The DNTM3A and DNMT3B de novo DNA methyltransferases (DNMTs) are responsible for setting genomic DNA methylation patterns, a key layer of epigenetic information. Here, using an in vivo episomal methylation assay and extensive bisulfite methylation sequencing, we show that human DNMT3A and DNMT3B possess significant and distinct flanking sequence preferences for target CpG sites. Selection for high or low efficiency sites is mediated by the base composition at the −2 and +2 positions flanking the CpG site for DNMT3A, and at the −1 and +1 positions for DNMT3B. This intrinsic preference reproducibly leads to the formation of specific de novo methylation patterns characterized by up to 34-fold variations in the efficiency of DNA methylation at individual sites. Furthermore, analysis of the distribution of signature methylation hotspot and coldspot motifs suggests that DNMT flanking sequence preference has contributed to shaping the composition of CpG islands in the human genome. Our results also show that the DNMT3L stimulatory factor modulates the formation of de novo methylation patterns in two ways. First, DNMT3L selectively focuses the DNA methylation machinery on properly chromatinized DNA templates. Second, DNMT3L attenuates the impact of the intrinsic DNMT flanking sequence preference by providing a much greater boost to the methylation of poorly methylated sites, thus promoting the formation of broader and more uniform methylation patterns. This study offers insights into the manner by which DNA methylation patterns are deposited and reveals a new level of interplay between members of the de novo DNMT family

The International Natural Product Sciences Taskforce (INPST) and the power of Twitter networking exemplified through #INPST hashtag analysis

Background: The development of digital technologies and the evolution of open innovation approaches have enabled the creation of diverse virtual organizations and enterprises coordinating their activities primarily online. The open innovation platform titled "International Natural Product Sciences Taskforce" (INPST) was established in 2018, to bring together in collaborative environment individuals and organizations interested in natural product scientific research, and to empower their interactions by using digital communication tools. Methods: In this work, we present a general overview of INPST activities and showcase the specific use of Twitter as a powerful networking tool that was used to host a one-week "2021 INPST Twitter Networking Event" (spanning from 31st May 2021 to 6th June 2021) based on the application of the Twitter hashtag #INPST. Results and Conclusion: The use of this hashtag during the networking event period was analyzed with Symplur Signals (https://www.symplur.com/), revealing a total of 6,036 tweets, shared by 686 users, which generated a total of 65,004,773 impressions (views of the respective tweets). This networking event's achieved high visibility and participation rate showcases a convincing example of how this social media platform can be used as a highly effective tool to host virtual Twitter-based international biomedical research events

Heavy metals exchange among the aquatic environment in the Mediterranean coast of Egypt

225-233The deposition of some heavy metals (Fe, CU Zn, Co, Ni, Cd and Pb), as an inorganic contaminant is described for two sites in the southeastern Mediterranean waters namely El-Mex Bay and Baltim zone. The concentration of heavy metals were studied in water, suspended matter, surficial sediments and the shells and soft tissues of bivalve mollusc, Venerupis decussata decussata L. to compare the influence of anthropogenic effect on the aquatic systems. The metal contents of the different environmental compartments in El-Mex zone were found to increase by several times compared to that recorded in Baltim region which is subjected to pronounced coastal erosion. The essential heavy metals (Fe, Cu and in) were found to be more concentrated in the soft parts, and were inversely related to size, (P<0.05) without gender. Pb, Cd, Co and Ni were more concentrated in the shells by factors of 16 4.2, 6.06 and 1.56 respectively. So shells may act for the removal of these metals (particularly Pb) from the surrounding medium. The concentration of some metals in El-Mex Bay showed an obvious increase with time. The increased concentration of some metals was found to affect growth and condition index in Venerupis

Protective effects of red wine polyphenols and grape-seed proanthocyanidin extract on acetaminophen-induced liver injury

Abstract The present study was designed to examine the potential protective effects of red wine polyphenols (RWPs) and grape seed proanthocyanidin extract (GSPE) against acetaminophen-induced hepatotoxicity. Silymarin was used as a standard reference hepatoprotective agent. A single dose of acetaminophen (800 mg/kg), injected intraperitoneally to male rats, caused a significant increase in serum ALT, AST, alkaline phosphatase (ALP), bilirubin, total cholesterol (TC), triglycerides(TG), tumor necrosis factor alpha (TNF-α), and liver contents of thiobarbituric acid reactive substances (TBARS) measured as malondialdehyde (MDA) and nitric oxide (NO) with significant decrease in serum albumin, HDL cholesterol, reduced glutathione (GSH) and hepatic activities of catalase (CAT), superoxide dismutase (SOD) and caspase-3 in liver tissue as compared with the control group. On the other hand, administration of each of GSPE (100 mg/kg/day, p.o.), RWPs (40 mg/kg/day, p.o.) and silymarin (100 mg/kg/day, p.o.) for 15 consecutive days significantly ameliorated the liver injury which confirmed by the histopathological examination. It was concluded that RWPs and GSPE showed protective effects against acute acetaminophen hepatotoxicity where RWPs were more effective than GSPE; most probably through their antioxidant, anti-inflammatory and anti-apoptotic effects

Organic sources in the Egyptian seawater around Alexandria coastal area as integrated from polycyclic aromatic hydrocarbons (PAHs)

This paper represents the first comprehensive survey and provides important data on PAHs concentration and composition in Alexandria coastal seawater. The compositions of PAHs determined in all samples are to be used as chemical markers for identifying different sources of PAH pollution in the surface seawater of Alexandria coastal area. The quantitative analysis of PAHs showed a concentration ranging from 8970.939 to 1254756.00 ng/L, which exceeds the maximum admissible concentrations of PAHs (200 ng/L) for the water standard of European Union. The calculated diagnostic ratios suggested that the sources of PAHs at the majority of the studied area are derived primarily from pyrogenic sources from incomplete fuel combustion of the boats and vehicle engines with lesser amounts of PAHs contributed from petrogenic sources. Some stations displayed mixed sources in comparison to many other studied marine systems, the PAH concentrations detected at Alexandria area were considered to be higher and pose health risks to aquatic bodies