Umbelliferone (UMB) is a natural coumarin that has diverse biological activities. However, its potential to protect against liver fibrosis has not been reported yet. This study aimed to investigate ...the protective effect of UMB against carbon tetrachloride (CCl
)-induced liver fibrosis in rats. Rats received CCl
and UMB for 8 weeks and samples were collected for analyses. CCl
induced a significant increase in serum levels of liver function markers and pro-inflammatory cytokines. Treatment with UMB significantly ameliorated liver function markers and pro-inflammatory cytokines and prevented CCl
-induced histological alterations. CCl
promoted significant upregulation of α-smooth muscle actin (SMA), collagen I, collagen III, NF-κB p65, TGF-β1, and p-Smad3. Masson's trichrome staining revealed a significant fibrogenesis in CCl
-induced rats. Treatment with UMB suppressed TGF-β1/Smad3 signaling and downregulated α-SMA, collagen I, collagen III, and NF-κB p65. In addition, UMB diminished malondialdehyde and nitric oxide levels, boosted reduced glutathione and antioxidant enzymes, and upregulated the expression of PPARγ. In conclusion, our results demonstrated that UMB prevented CCl
-induced liver fibrosis by attenuating oxidative stress, inflammation, and TGF-β1/Smad3 signaling, and upregulating PPARγ. Therefore, UMB may be a promising candidate for preventing hepatic fibrogenesis, given that further research is needed to delineate the exact molecular mechanisms underlying its antifibrotic efficacy.
Abstract
Hepatitis C Virus (HCV) infection is a global health burden specially in Egypt, where HCV genotype 4a predominates. Control of HCV infection will remain a challenge until the development of ...an effective vaccine that protects against different genotypes. There are several HCV genotype 1 vaccines in the pipelines. Differences in antigenic structure among genotypes could make cross protection against other genotypes unlikely. To assess whether Egyptians can benefit from genotype 1-based vaccines, HCV-specific T cell responses were examined in 37 HCV genotype 4a-infected patients using an interferon gamma (IFNγ) ELISpot assay in response to 7 HCV overlapping 15mer peptide pools derived from both genotype 1b and 4a that cover most of the HCV genome. Twenty two (59%) and 16 (43%) subjects responded to at least one peptide pool derived from genotype 1b and 4a, respectively, with 39% exact match in responses. Importantly, responses in different genome segments showed ≥55% exact match in response to the pools tested except the NS5a region (25%). The average IFNγ total spot forming cells (SFC)/106 PBMC (+SE) in the responding subjects for genotype 1b and 4a was 484±89 and 544±77, respectively (p=0.6). There was no significant differences in the responses of those who resolved HCV infection or not (p=0.6). In conclusion, no significant differences were found in the T cell responses of Egyptians to genotype 1b and 4a antigens suggesting that they can benefit from a genotype 1b vaccine.
Abstract
In vitro. bioassay screening of 346 methanol extracts originated from 281 native and cultivated plant species growing in Egypt, and related to 81 families, was carried out for ...schistosomicidal activity. The extracts were bioassayed at 100 µg mL on viable Schistosoma mansoni. mature worms in culture medium. Viability of worms was examined after exposure for 24 h, and mortality determined. Negative (DMSO) and positive (praziquantel) controls were used. Of the tested plant extracts, 72 were found to possess reproducible in vitro. antischistosomal activity. These active extracts were further subjected to determination of their LC50 and LC90 values. Strong antischistosomal activity was found in the extracts of 15 species (possessing LC50 ≤ 15 µg mL), viz. Agave americana. L. var. marginata. Trel. (Agavaceae), A. lophantha. Schiede (Agavaceae), Furcraea selloa. C.Koch. (Agavaceae), Calotropis procera. (Aiton) W.T.Aiton (Asclepiadaceae), Pergularia tomentosa. L. (Asclepiadaceae), Asclepias sinaica. (Boiss.) Muschl. (Asclepiadaceae), Alkanna orientalis. (L.) Boiss. (Boraginaceae), Khaya grandifoliola. DC. (Meliaceae), Swietenia mahogani. (L.) Jacq. (Meliaceae), Pimenta racemosa. (Mill.) J.W.Moore (Myrtaceae), Pinus canariensis. C.Sm. (Pinaceae), Verbascum sinaiticum. L. (Scrophulariaceae), Solanum elaeagnifolium. Cav. (Solanaceae), S. nigrum. L. (Solanaceae), and Brachychiton rupestris. (Lindl.) K.Schum. (Sterculiaceae). These 15 species could represent promising bioactive sources that deserve further investigation, with the aim of finding novel antischistosomal agents. The current study represents the first report on a systematic screening of schistosomicidal activity utilizing a large number of plant species.
The idea of Integrated Sensing and Communication (ISAC) offers a promising solution to the problem of spectrum congestion in future wireless networks. This paper studies the integration of ...intelligent reflective surfaces (IRS) with ISAC systems to improve the performance of radar and communication services. Specifically, an IRS-assisted ISAC system is investigated where a multi-antenna base station (BS) performs multi-target detection and multi-user communication. A low complexity and efficient joint optimization of transmit beamforming at the BS and reflective beamforming at the IRS is proposed. This is done by jointly optimizing the BS beamformers and IRS reflection coefficients to minimize the Frobenius distance between the covariance matrices of the transmitted signal and the desired radar beam pattern. This optimization aims to satisfy the signal-to-interference-and-noise ratio (SINR) constraints of the communication users, the total transmit power limit at the BS, and the unit modulus constraints of the IRS reflection coefficients. To address the resulting complex non-convex optimization problem, an efficient alternating optimization (AO) algorithm combining fractional programming (FP), semi-definite programming (SDP), and second order cone programming (SOCP) methods is proposed. Furthermore, we propose robust beamforming optimization for IRS-ISAC systems by adapting the proposed optimization algorithm to the IRS channel uncertainties that may exist in practical systems. Using advanced tools from convex optimization theory, the constraints containing uncertainty are transformed to their equivalent linear matrix inequalities (LMIs) to account for the channels' uncertainty radius. The results presented quantify the benefits of IRS-ISAC systems under various conditions and demonstrate the effectiveness of the proposed algorithm.
Abstract
Hepatitis C Virus (HCV)-specific cell-mediated immunity (CMI) was reported in exposed individuals e.g. IV drug users without seroconversion or viremia. We investigated the HCV-specific CMI ...response in seronegative, aviremic healthcare workers (HCWs) at the National Liver Institute who are at high risk of becoming infected with HCV after occupational exposure as more than 70% of their patients are HCV-infected. We quantified the CMI responses in 15 Egyptian HCWs with a recent history of a needle stick injury and who remained seronegative and aviremic for at least four months. We used ex vivo enzyme-linked immunospot (ELISPOT) assay to quantify interferon gamma (IFNγ) production in response to 7 HCV genotype 4 overlapping 15mer peptide pools and phenotyped the responding cells by flow cytometry. A positive HCV-specific IFN-γ responses (>55 spot forming cells (SFCs)/million PBMC) was elicited for 2-6 HCV pools in 8 (53%) of the HCW while 7 (47%) subjects responded to one or none of the pools tested with a total mean of 1069 (SEM ±239) and 118 (±17) IFNγ SFC, respectively. In summary, the majority of HCW demonstrated HCV-specific T cell responses for multiple HCV peptides and remained uninfected despite their high-risk of exposure. These responses suggest that the percentage of subjects clearing the infection is much higher than reported and their potential role in protection from HCV infection is important for understanding HCV pathogenesis and vaccine development.
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