ORCID Profile
0000-0003-0935-5142
Current Organisations
University of South Australia
,
Iran University of Medical Sciences
,
University of Lubeck
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Publisher: Oxford University Press (OUP)
Date: 27-09-2017
Abstract: Human noroviruses (HuNoV), members of the family Caliciviridae, are the major cause of acute viral gastroenteritis worldwide. Successful infection is linked to the ability of the protruding (P) domain of the viral capsid to bind histo-blood group antigens (HBGA). Binding to gangliosides plays a major role for many nonhuman calici- and noroviruses. Increasing evidence points to a broader role of sialylated carbohydrates such as gangliosides in norovirus infection. Here, we compare HBGA and ganglioside binding of a GII.4 HuNoV variant (MI001), previously shown to be infectious in a HuNoV mouse model. Saturation transfer difference nuclear magnetic resonance spectroscopy, native mass spectrometry (MS) and surface plasmon resonance spectroscopy were used to characterize binding epitopes, affinities, stoichiometry and dynamics, focusing on 3'-sialyllactose, the GM3 ganglioside saccharide and B antigen. Binding was observed for 3'-sialyllactose and various HBGAs following a multistep binding process. Intrinsic affinities (Kd) of fucose, 3'-sialyllactose and B antigen were determined for the in idual binding steps. Stronger affinities were observed for B antigen over 3'-sialyllactose and fucose, which bound in the mM range. Binding stoichiometry was analyzed by native MS showing the presence of four B antigens or two 3'-sialyllactose in the complex. Epitope mapping of 3'-sialyllactose revealed direct interaction of α2,3-linked sialic acid with the P domain. The ability of HuNoV to engage multiple carbohydrates emphasizes the multivalent nature of norovirus glycan-specificity. Our findings reveal direct binding of a GII.4 HuNoV P dimer to α2,3-linked sialic acid and support a broader role of ganglioside binding in norovirus infection.
Publisher: Mary Ann Liebert Inc
Date: 07-2021
Publisher: Informa UK Limited
Date: 07-2020
DOI: 10.2147/OTT.S249268
Publisher: Wiley
Date: 19-08-2015
Abstract: Human noroviruses recognize histo blood group antigens (HBGAs) as cellular attachment factors. Recently, it has been discovered that norovirus infection can be significantly enhanced by HBGA binding. Yet the attachment process and how it promotes host-cell entry is only poorly understood. The binding of a norovirus protruding (P) domain of a predominant GII.4 Saga strain to HBGAs at atomic resolution was studied. So far, independent and equivalent multiple binding sites were held responsible for attachment. Using NMR experiments we show that norovirus-HBGA binding is a cooperative multi-step process, and native mass spectrometry reveals four instead of two HBGA binding sites per P-dimer. An accompanying crystallographic study has disclosed four instead of two L-fucose binding sites per P-dimer of a related GII.10 strain1 further supporting our findings. We have uncovered a novel paradigm for norovirus-HBGA recognition that will inspire further studies into norovirus-host interactions.
Publisher: MDPI AG
Date: 24-04-2022
DOI: 10.3390/IJMS23094707
Abstract: Aluminium (Al) compounds are used as adjuvants in human and veterinary prophylactic vaccines due to their improved tolerability compared to other adjuvants. These Al-based adjuvants form microparticles (MPs) of heterogeneous sizes ranging from ~0.5 to 10 µm and generally induce type 2 (Th2)-biased immune responses. However, recent literature indicates that moving from micron dimension particles toward the nanoscale can modify the adjuvanticity of Al towards type 1 (Th1) responses, which can potentially be exploited for the development of vaccines for which Th1 immunity is crucial. Specifically, in the context of cancer treatments, Al nanoparticles (Al-NPs) can induce a more balanced (Th1/Th2), robust, and durable immune response associated with an increased number of cytotoxic T cells compared to Al-MPs, which are more favourable for stimulating an oncolytic response. In this review, we compare the adjuvant properties of Al-NPs to those of Al-MPs in the context of infectious disease vaccines and cancer immunotherapy and provide perspectives for future research.
Publisher: Elsevier BV
Date: 08-2021
Publisher: Springer Science and Business Media LLC
Date: 08-09-2016
DOI: 10.1208/S12249-015-0405-Y
Abstract: In the current study, antidiabetic activity and toxic effects of zinc oxide nanoparticles (ZnO) were investigated in diabetic rats compared to zinc sulfate (ZnSO4) with particular emphasis on oxidative stress parameters. One hundred and twenty male Wistar rats were ided into two healthy and diabetic groups, randomly. Each major group was further sub ided into five subgroups and then orally supplemented with various doses of ZnO (1, 3, and 10 mg/kg) and ZnSO4 (30 mg/kg) for 56 consecutive days. ZnO showed greater antidiabetic activity compared to ZnSO4 evidenced by improved glucose disposal, insulin levels, and zinc status. The altered activities of erythrocyte antioxidant enzymes as well as raised levels of lipid peroxidation and a marked reduction of total antioxidant capacity were observed in rats receiving ZnO. ZnO nanoparticles acted as a potent antidiabetic agent, however, severely elicited oxidative stress particularly at higher doses.
Publisher: Elsevier BV
Date: 02-2020
DOI: 10.1016/J.JEP.2019.112331
Abstract: Undesired effects of synthetic antidiabetic agents have made researchers to seek for safer and healthier resources. With this aspect, herbal materials have attracted substantial research interest and are being extensively investigated. Considering that herb-drug interactions can be a double-edged sword presenting both risks and benefits, investigation of such interactions is greatly in demand. to investigate possible beneficial effects of hydroalcoholic extract of SecurigeraSecuridaca seed (HESS) on antioxidant capacity, fibroblast growth factor 21 (FGF21) and insulin resistance in Streptozotocin (STZ)-induced diabetic rats, alone and in combination with glibenclamide. Forty male Wistar rats were randomly ided in to eight equal groups including healthy and diabetic controls and six treated groups with a various doses of HESS alone and in combination with glibenclamide, for 35 consecutive days. Serum s les were taken and analyzed for biochemical profile, HOMA indexes, FGF21, oxidative/nitrosative stress and inflammatory biomarkers as compared with the controls. Moreover, total phenolic and flavonoid contents of herbal extract were assessed. The herbal extract was found to be rich in flavonoid and phenolic components. Both of glibenclamide and the HESS decreased glucose and insulin resistance, as well as increased body weight and insulin sensitivity. Moreover, the extract could mitigate oxidative/nitrosative stress and inflammation dose-dependently, however, the standard drug was less effective than HESS. Induction of diabetes increased FGF21 levels and both of the treatments could reduce its contents, however, glibenclamide was more effective than HESS. The results clearly show that there is no contradiction between HESS and glibenclamide. Moreover, the herbal extract could augment antioxidant and anti-inflammatory properties of the standard drug.
Publisher: Elsevier BV
Date: 07-2017
DOI: 10.1016/J.JTEMB.2017.04.013
Abstract: The cardio-protective effects of zinc oxide nanoparticles (Zn NPs) against diabetes-induced cardiopathy were evaluated and compared with zinc sulfate (ZnSO
Publisher: Informa UK Limited
Date: 29-11-2017
DOI: 10.1080/09553002.2018.1400709
Abstract: The current study was undertaken to evaluate radioprotective effects of selenium (Se) nanoparticles in irradiation-induced nephropathy of mice model compared to sodium selenite. Forty-five mice were ided into three major groups including control, Se nanoparticle, and sodium selenite. Each major group was further sub ided into three more groups receiving various doses of 0, 2, and 8 Gy gamma irradiation. Both of the supplements were administered intraperitoneally with the dose of 0.1 mg/kg for 14 consecutive days. At the end of each week, the animals were exposed to gamma radiation and 48 h after the last exposure, the animals were humanely euthanized, then blood and renal tissue s les were taken. Serum creatinine, urea, cystatin C, and beta-2-microglobulin levels as well as activities of renal antioxidant enzymes, superoxide dismutase, glutathione peroxidase and catalase, also malondialdehyde level, total antioxidant capacity, renal tissue Se content, and histopathological features were assessed. The results showed that both of the supplements could normalize aforementioned indices. However, selenium nanoparticles (Se-NPs) were more effective than sodium selenite. Conclusively, Se-NPs as an emerging potent antioxidant agent can protect against irradiation-induced nephropathy.
Publisher: American Chemical Society (ACS)
Date: 02-08-2018
DOI: 10.1021/ACS.BIOMAC.8B00829
Abstract: Norovirus infection is the major cause of nonbacterial gastroenteritis in humans and has been the subject of numerous studies investigating the virus's biophysical properties and biochemical function with the aim of deriving novel and highly potent entry inhibitors to prevent infection. Recently, it has been shown that the protruding P domain dimer (P-dimer) of a GII.10 Norovirus strain exhibits two new binding sites for l-fucose in addition to the canonical binding sites. Thus, these sites provide a novel target for the design of multivalent fucose ligands as entry inhibitors of norovirus infections. In this current study, a first generation of multivalent fucose-functionalized glycomacromolecules was synthesized and applied as model structures to investigate the potential targeting of fucose binding sites in human norovirus P-dimer. Following previously established solid phase polymer synthesis, eight precision glycomacromolecules varying in number and position of fucose ligands along an oligo(amidoamine) backbone were obtained and then used in a series of binding studies applying native MS, NMR, and X-ray crystallography. We observed only one fucose per glycomacromolecule binding to one P-dimer resulting in similar binding affinities for all fucose-functionalized glycomacromolecules, which based on our current findings we attribute to the overall size of macromolecular ligands and possibly to steric hindrance.
Publisher: Elsevier BV
Date: 09-2021
Publisher: Springer Science and Business Media LLC
Date: 07-04-2017
Publisher: Elsevier BV
Date: 12-2020
Publisher: Maad Rayan Publishing Company
Date: 12-12-2019
DOI: 10.34172/BI.2020.20
Abstract: Introduction: Seeds of Securigera securidaca (L.) Degen & Dorfl are rich in flavonoids and phenolic acids which have potent biological effects. The current study was undertaken to evaluate the effects of hydroalcoholic extract of S. securidaca seeds (HESS) alone, and in combination with a standard drug, glibenclamide (GB) on paraoxonase1 (PON1) activity, lipid profile and peroxidation, and cardiovascular risk indices in streptozotocin (STZ) induced diabetic rats. Methods: Forty-eight male Wistar rats were randomly ided into eight equal groups and orally treated with various doses of HESS (100, 200, 400 mg/kg) alone and in combination with GB (5 mg/kg) for 35 consecutive days. After blood s ling, lipid profile including triglyceride (TG), cholesterol, high, low and very low-density lipoprotein-cholesterol (HDL-C, LDL-C, and VLDL-C), as well as serum PON1 activity, were assessed. Malondialdehyde (MDA), tumor necrosis factor-alpha (TNF-α), and high-sensitivity C-reactive protein (hs-CRP) levels were also measured. Several indices of cardiovascular risk and the correlation between PON1 activity and these indices were calculated based on the obtained results from the lipid profile. Results: Induction of diabetes could dramatically alter all of the parameters mentioned above, and the lower dose of HESS (100 mg/kg) was not effective in restoring the parameters. However, the higher doses (200 and 400 mg/kg) alone and in combination with GB could significantly improve lipid profile, restore PON1 activity, and decrease cardiovascular risk indices, MDA, as well. However, neither HESS nor GB could significantly reduce TNF-α and hs-CRP. A significant negative correlation also was detected between PON1 activity and cardiovascular risk indices. Conclusion: conclusively, HESS can be considered as a potent antihyperlipidemic agent with remarkable cardioprotective effects and can potentiate the antidiabetic effects of GB.
Publisher: Oxford University Press (OUP)
Date: 03-08-2016
Abstract: Recently, combined nuclear magnetic resonance (NMR), native mass spectrometry (MS) and X-ray crystallographic studies have demonstrated that binding of histo-blood group antigens (HBGAs) to norovirus capsid protein (P-dimers) is a cooperative process involving four binding pockets. Here, we show that binding to norovirus virus-like particles (VLPs) is even more complex. We performed saturation transfer difference (STD) NMR titration experiments with two representative genotypes of norovirus VLPs using l-fucose as a minimal HBGA. Compared to titrations with P-dimers, the corresponding binding isotherms reflect at least six distinct binding events.
Location: Iran (Islamic Republic of)
No related grants have been discovered for Ali Nazarizadeh Khangheshlaghi.