| 1. |
- Ling, Jiaxin, et al.
(författare)
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Is heparan sulfate a target for inhibition of RNA virus infection?
- 2022
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Ingår i: American Journal of Physiology - Cell Physiology. - : American Physical Society. - 0363-6143 .- 1522-1563. ; 322:4, s. C605-C613
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Forskningsöversikt (refereegranskat)abstract
- Heparan sulfate (HS) is a linear polysaccharide attached to a core protein, forming heparan sulfate proteoglycans (HSPGs) that are ubiquitously expressed on the surface of almost all mammalian cells and the extracellular matrix. HS orchestrates the binding of various signal molecules to their receptors, thus regulating many biological processes, including homeostasis, metabolism, and various pathological processes. Due to its wide distribution and negatively charged properties, HS is exploited by many viruses as a cofactor to attach to host cells. Therefore, inhibition of the interaction between virus and HS is proposed as a promising approach to mitigate viral infection, including SARS-CoV-2. In this review, we summarize the interaction manners of HS with viruses with focus on significant pathogenic RNA viruses, including alphaviruses, flaviviruses, and coronaviruses. We also provide an overview of the challenges we may face when using HS mimetics as antivirals for clinical treatment. More studies are needed to provide a further understanding of the interplay between HS and viruses both in vitro and in vivo, which will favor the development of specific antiviral inhibitors.
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| 2. |
- Nahain, Abdullah Al, et al.
(författare)
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Antiviral Activities of Heparan Sulfate Mimetic RAFT Polymers Against Mosquito-borne Viruses
- 2024
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Ingår i: ACS Applied Bio Materials. - : American Chemical Society (ACS). - 2576-6422. ; 7:5, s. 2862-2871
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Tidskriftsartikel (refereegranskat)abstract
- Mosquito-borne viruses are a major worldwide health problem associated with high morbidity and mortality rates and significant impacts on national healthcare budgets. The development of antiviral drugs for both the treatment and prophylaxis of these diseases is thus of considerable importance. To address the need for therapeutics with antiviral activity, a library of heparan sulfate mimetic polymers was screened against dengue virus (DENV), Yellow fever virus (YFV), Zika virus (ZIKV), and Ross River virus (RRV). The polymers were prepared by RAFT polymerization of various acidic monomers with a target MW of 20 kDa (average Mn ∼ 27 kDa by GPC). Among the polymers, poly(SS), a homopolymer of sodium styrenesulfonate, was identified as a broad spectrum antiviral with activity against all the tested viruses and particularly potent inhibition of YFV (IC50 = 310 pM). Our results further uncovered that poly(SS) exhibited a robust inhibition of ZIKV infection in both mosquito and human cell lines, which points out the potential functions of poly(SS) in preventing mosquito-borne viruses associated diseases by blocking viral transmission in their mosquito vectors and mitigating viral infection in patients.
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| 3. |
- Rich, Rebecca L., et al.
(författare)
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A global benchmark study using affinity-based biosensors
- 2009
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Ingår i: Analytical Biochemistry. - : Elsevier BV. - 0003-2697 .- 1096-0309. ; 386:2, s. 194-216
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Tidskriftsartikel (refereegranskat)abstract
- To explore the variability in biosensor studies, 150 participants from 20 countries were given the same protein samples and asked to determine kinetic rate constants for the interaction. We chose a protein system that was amenable to analysis using different biosensor platforms as well as by users of different expertise levels. The two proteins (a 50-kDa Fab and a 60-kDa glutathione S-transferase [GST] antigen) form a relatively high-affinity complex, so participants needed to optimize several experimental parameters, including ligand immobilization and regeneration conditions as well as analyte concentrations and injection/dissociation times. Although most participants collected binding responses that could be fit to yield kinetic parameters, the quality of a few data sets could have been improved by optimizing the assay design. Once these outliers were removed, the average reported affinity across the remaining panel of participants was 620 pM with a standard deviation of 980 pM. These results demonstrate that when this biosensor assay was designed and executed appropriately, the reported rate constants were consistent, and independent of which protein was immobilized and which biosensor was used.
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| 4. |
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| 5. |
- Chen, Xiaoping, et al.
(författare)
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Risk factors for the delayed viral clearance in COVID‐19 patients
- 2021
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Ingår i: The Journal of Clinical Hypertension. - : John Wiley & Sons. - 1524-6175 .- 1751-7176. ; 23:8, s. 1483-1489
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Tidskriftsartikel (refereegranskat)abstract
- Comorbidities are important for the disease outcome of COVID-19, however, which underlying diseases that contribute the most to aggravate the conditions of COVID-19 patients are still unclear. Viral clearance is the most important laboratory test for defining the recovery of COVID-19 infections. To better understand which underlying diseases that are risk factors for delaying the viral clearance, we retrospectively analyzed 161 COVID-19 clinical cases in the Zhongnan Hospital of Wuhan University, Wuhan, China between January 5 and March 13, 2020. The demographic, clinical and laboratory data, as well as patient treatment records were collected. Univariable and multivariable analysis were performed to explore the association between delayed viral clearance and other factors by using logistic regression. Survival analyses by Kaplan-Meier and Cox regression modeling were employed to identify factors negatively influencing the viral clearance negatively. We found that hypertension and intravenous immunoglobulin adversely affected the time of viral RNA shedding. Hypertension was the most important risk factor to delay the SARS-CoV-2 virus clearance, however, the use of Angiotensin-Converting Enzyme Inhibitors(ACEI)/Angiotensin Receptor Blockers(ARB) did not shorten the time for virus clearance in these hypertensive patients’ virus clearance. We conclude that patients having hypertension and intravenous immunoglobulin may delay the viral clearance in COVID-19 patients.
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| 6. |
- Deng, Kaiqiang, et al.
(författare)
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The offshore wind speed changes in China: an insight into CMIP6 model simulation and future projections
- 2024
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Ingår i: CLIMATE DYNAMICS. - 0930-7575 .- 1432-0894. ; 62, s. 3305-3319
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Tidskriftsartikel (refereegranskat)abstract
- Offshore wind speed in China plays a key role in affecting air-sea interactions, coastal tides, and wind energy, but its changes in a warming climate and the associated causes remain unclear. Based on the ERA5 reanalysis and the Coupled Model Intercomparison Project Phase 6 (CMIP6) models, this study evaluates the past and future variations of wind speed at 10 m (WS10) over China's offshore seas in summer and winter. The results show that the CMIP6 multi-model mean performs well in simulating the climatological patterns (1981-2010) of WS10 for both seasons. The trends and leading variabilities in WS10 are also reasonably reproduced in the South China Sea (SCS). In the northern SCS, WS10 has strengthened during both seasons in the recent decades. In contrast, in the East China Sea (ECS), WS10 has increased (decreased) during summer (winter). Further attribution analysis suggests that the forcing of greenhouse gasses (aerosols) may make WS10 stronger (weaker) in the two seas and for both seasons, while natural variability tends to slow down (speed up) WS10 in the SCS and ECS during summer (winter). In addition, according to the CMIP6 model projections under various warming scenarios, WS10 is likely to increase over both the northern SCS and the ECS in summer, while WS10 will increase over the northern SCS but decrease over the ECS in winter. Differences in the projected WS10 changes in the ECS during summer and winter are attributed to the projected intensification (weakening) of the East Asian summer (winter) monsoon circulation.
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| 7. |
- Gao, Ruichang, et al.
(författare)
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Sturgeon hydrolysates alleviate DSS-induced colon colitis in mice by modulating NF-kappa B, MAPK, and microbiota composition
- 2020
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Ingår i: Food & Function. - : ROYAL SOC CHEMISTRY. - 2042-6496 .- 2042-650X. ; 11:8, s. 6987-6999
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Tidskriftsartikel (refereegranskat)abstract
- Sturgeon muscle byproduct collected after caviar production is usually not fully utilized, and sometimes may be discarded, thus causing a lot of waste. Yet dietary protein hydrolysates, which may be derived from sturgeon muscle, have been reported to have versatile beneficial biological activities. Studying the biological activities of sturgeon muscle-derived hydrolysates holds much promise for adding value to sturgeon. The current study aimed to study the therapeutic anti-inflammatory effects of sturgeon muscle-derived hydrolysates and the underlying mechanisms. The administration of sturgeon hydrolysates (SH) significantly decreased the severity of DSS-induced damage, evidenced by increased body weight, colon length, and decreased disease activity index (DAI) and histological scores. SH also inhibited myeloperoxidase (MPO) activity and reduced the serum levels of IL-6, IL-1 beta, and TNF-alpha. Western blotting results revealed that SH suppressed DSS-induced activation of the NF-kappa B and MAPK pathways in the colon. Furthermore, SH partially restored the alteration of the gut microbiota in colitic mice. SH increased the Bacteroidetes/Firmicutes ratio and the relative abundance of Ruminococcaceae, Porphyromonadaceae, and Bacteroidetes S24-7, while decreased the abundance of potentially harmful bacteria Erysipelotrichaceae and Enterococcaceae. These results suggest that SH inhibited DSS-induced colitis by regulating the NF-kappa B and MAPK pathways and modulating microbiota composition.
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| 8. |
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| 9. |
- Li, Jinlin, et al.
(författare)
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The Epstein-Barr virus deubiquitinating enzyme BPLF1 regulates the activity of topoisomerase II during productive infection
- 2021
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Ingår i: PLoS Pathogens. - : Public Library of Science (PLoS). - 1553-7366 .- 1553-7374. ; 17:9
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Tidskriftsartikel (refereegranskat)abstract
- Topoisomerases are essential for the replication of herpesviruses but the mechanisms by which the viruses hijack the cellular enzymes are largely unknown. We found that topoisomerase-II (TOP2) is a substrate of the Epstein-Barr virus (EBV) ubiquitin deconjugase BPLF1. BPLF1 co-immunoprecipitated and deubiquitinated TOP2, and stabilized SUMOylated TOP2 trapped in cleavage complexes (TOP2cc), which halted the DNA damage response to TOP2-induced double strand DNA breaks and promoted cell survival. Induction of the productive virus cycle in epithelial and lymphoid cell line carrying recombinant EBV encoding the active enzyme was accompanied by TOP2 deubiquitination, accumulation of TOP2ccs and resistance to Etoposide toxicity. The protective effect of BPLF1 was dependent on the expression of tyrosyl-DNA phosphodiesterase 2 (TDP2) that releases DNA-trapped TOP2 and promotes error-free DNA repair. These findings highlight a previously unrecognized function of BPLF1 in supporting a non-proteolytic pathway for TOP2cc debulking that favors cell survival and virus production.
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| 10. |
- Ling, Jiaxin, et al.
(författare)
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Spatio-Temporal Mutational Profile Appearances of Swedish SARS-CoV-2 during the Early Pandemic
- 2020
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Ingår i: Viruses. - : MDPI. - 1999-4915. ; 12:9
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Tidskriftsartikel (refereegranskat)abstract
- Background: During the COVID-19 pandemic, the virus evolved, and we therefore aimed to provide an insight into which genetic variants were enriched, and how they spread in Sweden. Methods: We analyzed 348 Swedish SARS-CoV-2 sequences freely available from GISAID obtained from 7 February 2020 until 14 May 2020. Results: We identified 14 variant sites >= 5% frequency in the population. Among those sites, the D936Y substitution in the viral Spike protein was under positive selection. The variant sites can distinguish 11 mutational profiles in Sweden. Nine of the profiles appeared in Stockholm in March 2020. Mutational profiles 3 (B.1.1) and 6 (B.1), which contain the D936Y mutation, became the predominant profiles over time, spreading from Stockholm to other Swedish regions during April and the beginning of May. Furthermore, Bayesian phylogenetic analysis indicated that SARS-CoV-2 could have emerged in Sweden on 27 December 2019, and community transmission started on February 1st with an evolutionary rate of 1.5425 x 10(-3)substitutions per year. Conclusions: Our study provides novel knowledge on the spatio-temporal dynamics of Swedish SARS-CoV-2 variants during the early pandemic. Characterization of these viral variants can provide precious insights on viral pathogenesis and can be valuable for diagnostic and drug development approaches.
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