-
Gene Jun 2024The adeno-associated virus (AAV) is a defective single-stranded DNA virus with the simplest structure reported to date. It constitutes a capsid protein and... (Review)
Review
The adeno-associated virus (AAV) is a defective single-stranded DNA virus with the simplest structure reported to date. It constitutes a capsid protein and single-stranded DNA. With its high transduction efficiency, low immunogenicity, and tissue specificity, it is the most widely used and promising gene therapy vector. The clustered regularly interspaced short palindromic sequence (CRISPR)/CRISPR-associated protein 9 (Cas9) gene editing system is an emerging technology that utilizes cas9 nuclease to specifically recognize and cleave target genes under the guidance of small guide RNA and realizes gene editing through homologous directional repair and non-homologous recombination repair. In recent years, an increasing number of animal experiments and clinical studies have revealed the great potential of AAV as a vector to deliver the CRISPR/cas9 system for treating genetic diseases and viral infections. However, the immunogenicity, toxicity, low transmission efficiency in brain and ear tissues, packaging size limitations of AAV, and immunogenicity and off-target effects of Cas9 protein pose several clinical challenges. This research reviews the role, challenges, and countermeasures of the AAV-CRISPR/cas9 system in gene therapy.
PubMed: 38945310
DOI: 10.1016/j.gene.2024.148733 -
Indian Journal of Medical Microbiology Jun 2024Genomic surveillance of positive SARS-CoV-2 samples is important to monitor the genetic changes occurring in virus, this was enhanced after the WHO designation of...
PURPOSE
Genomic surveillance of positive SARS-CoV-2 samples is important to monitor the genetic changes occurring in virus, this was enhanced after the WHO designation of XBB.1.16 as a variant under monitoring in March 2023. From 5 February till 6 May 2023 all positive SARS-CoV-2 samples were monitored for genetic changes.
METHODS
A total of 1757 samples having Ct value <25 (for E and ORF gene) from different districts of Rajasthan were processed for Next Generation Sequencing (NGS). The FASTA files obtained on sequencing were used for lineage determination using Nextclade and phylogenetic tree construction.
RESULTS AND CONCLUSIONS
Sequencing and lineage identification was done in 1624 samples. XBB.1.16 was the predominant lineage in 1413(87.0%) cases while rest was other XBB (207, 12.74%) and other lineages (4, 0.2%). Of the 1413 XBB.1.16 cases, 57.47% were males and 42.53% were females. Majority (66.53%) belonged to 19-59 year age. 84.15% of XBB.1.16 cases were infected for the first time. Hospitalization was required in only 2.2% cases and death was reported in 5 (0.35%) patients. Most of the cases were symptomatic and the commonest symptoms were fever, cough and rhinorrhoea. Co-morbidities were present in 414 (29.3%) cases. Enhanced genomic surveillance helped to rapidly identify the spread of XBB variant in Rajasthan. This in turn helped to take control measures to prevent spread of virus and estimate public health risks of the new variant relative to the previously circulating lineages. XBB variant was found to spread rapidly but produced milder disease.
PubMed: 38945273
DOI: 10.1016/j.ijmmb.2024.100659 -
Virologica Sinica Jun 2024Hand, foot and mouth disease (HFMD), mainly caused by enterovirus 71 (EV71), have frequently occurred in the Asia-Pacific region, posing a significant threat to the...
Hand, foot and mouth disease (HFMD), mainly caused by enterovirus 71 (EV71), have frequently occurred in the Asia-Pacific region, posing a significant threat to the health of infants and young children. Therefore, research on the infection mechanism and pathogenicity of enteroviruses is increasingly becoming important. The 3D polymerase, as the most critical RNA-dependent RNA polymerase (RdRp) for EV71 replication, is widely targeted to inhibit EV71 infection. In this study, we identified a novel host protein, AIMP2, capable of binding to 3D polymerase and inhibiting EV71 infection. Subsequent investigations revealed that AIMP2 recruits the E3 ligase SMURF2, which mediates the polyubiquitination and degradation of 3D polymerase. Furthermore, the antiviral effect of AIMP2 extended to the CVA16 and CVB1 serotypes. Our research uncovered the dynamic regulatory function of AIMP2 during EV71 infection, revealing a novel antiviral mechanism and providing new insights for the development of antienteroviral therapeutic strategies.
PubMed: 38945214
DOI: 10.1016/j.virs.2024.06.009 -
Virologica Sinica Jun 2024Bats are the natural reservoir hosts for SARS-related coronavirus (SARSr-CoV) and other highly pathogenic microorganisms. Therefore, it is conceivable that an individual...
Bats are the natural reservoir hosts for SARS-related coronavirus (SARSr-CoV) and other highly pathogenic microorganisms. Therefore, it is conceivable that an individual bat may harbor multiple microbes. However, there is limited knowledge on the overall co-circulation of microorganisms in bats. Here, we conducted a 16-year monitoring of bat viruses in south and central China and identified 238 SARSr-CoV positive samples across nine bat species from ten provinces or administrative districts. Among these, 76 individual samples were selected for further metagenomics analysis. We found a complex microenvironment characterized by the general co-circulation of microbes from two different sources: mammal-associated viruses or environment-associated microbes. The later includes commensal bacteria, enterobacteria-related phages, and insect or fungal viruses of food origin. Results showed that 25% (19/76) of the samples contained at least one another mammal-associated virus, notably alphacoronaviruses (13/76) such as AlphaCoV/YN2012, HKU2-related CoV and AlphaCoV/Rf-HuB2013, along with viruses from other families. Notably, we observed three viruses co-circulating within a single bat, comprising two coronavirus species and one picornavirus. Our analysis also revealed the potential presence of pathogenic bacteria or fungi in bats. Furthermore, we obtained 25 viral genomes from the 76 bat SARSr-CoV positive samples, some of which formed new evolutionary lineages. Collectively, our study reveals the complex microenvironment of bat microbiome, facilitating deeper investigations into their pathogenic potential and the likelihood of cross-species transmission.
PubMed: 38945213
DOI: 10.1016/j.virs.2024.06.008 -
The Lancet. Infectious Diseases Jun 2024
PubMed: 38945150
DOI: 10.1016/S1473-3099(24)00415-8 -
Plant Physiology and Biochemistry : PPB Jun 2024The phytohormones cytokinins are essential mediators of developmental and environmental signaling, primarily during cell division and endophytic interactions, among...
The phytohormones cytokinins are essential mediators of developmental and environmental signaling, primarily during cell division and endophytic interactions, among other processes. Considering the limited understanding of the regulatory mechanisms that affect the growth and bioactivity of the medicinal plant Nepeta nuda (Lamiaceae), our study aimed to explore how cytokinins influence the plant's metabolic status. Exogenous administration of active cytokinin forms on in vitro N. nuda internodes stimulated intensive callus formation and de novo shoot regeneration, leading to a marked increase in biomass. This process involved an accumulation of oxidants, which were scavenged by peroxidases using phenolics as substrates. The callus tissue formed upon the addition of the cytokinin 6-benzylaminopurine (BAP) acted as a sink for sugars and phenolics during the allocation of nutrients between the culture medium and regenerated plants. In accordance, the cytokinin significantly enhanced the content of polar metabolites and their respective in vitro biological activities compared to untreated in vitro and wild-grown plants. The BAP-mediated accumulation of major phenolic metabolites, rosmarinic acid (RA) and caffeic acid (CA), corresponded with variations in the expression levels of genes involved in their biosynthesis. In contrast, the accumulation of iridoids and the expression of corresponding biosynthetic genes were not significantly affected. In conclusion, our study elucidated the mechanism of cytokinin action in N. nuda in vitro culture and demonstrated its potential in stimulating the production of bioactive compounds. This knowledge could serve as a basis for further investigations of the environmental impact on plant productivity.
PubMed: 38945096
DOI: 10.1016/j.plaphy.2024.108884 -
Poultry Science Jun 2024This study aimed to investigate how various selenium sources affect the intestinal health of broiler chickens. A total of 384, one-day-old Arbor Acres broilers were...
This study aimed to investigate how various selenium sources affect the intestinal health of broiler chickens. A total of 384, one-day-old Arbor Acres broilers were weighed and randomly allocated to four treatment groups. The control diet was a basal diet added with: 0.2 mg/kg Sodium Selenite (SS-control), 0.2 mg/kg Selenium nano-particles (Nano-Se), 0.2 mg/kg Selenomethionine (SeMet), and 0.2 mg/kg Selenocysteine (Sec) as the treatments. The results indicated that Nano-Se and SeMet were effective in enhancing the villus height (VH) and the villus height/crypt depth ratio (VH/CD) in the jejunum compared to (SS) (P < 0.05). The inclusion of Nano-Se into the diets increased the mRNA levels of zonula occluden-1 (ZO-1), ZO-2, Occludin, Claudin-1, and Claudin-3 compared to the SS diet (P < 0.05). The SeMet increased the levels of ZO-1 and Claudin-3 compared to the SS (P < 0.05). Moreover, SeMet upregulated the marker genes of intestinal enteroendocrine cells, stem cells, and epithelial cells compared to the SS diet (P < 0.05). However, supplementation of Nano-Se reduced the mRNA levels of interleukin 1β (IL-1β), and IL-8 and the concentration of reactive oxygen species (ROS) in the jejunum compared to the SS (P < 0.05). The Nano-Se and SeMet also increased the protein levels of CAT and SOD compared to the SS and Sec diet (P < 0.05). The number of the goblet cells and Mucin-2 (Muc2) levels were the highest in the Nano-Se group (P < 0.05). The protein expression levels of goblet cell differentiation regulator (v-myc avian myelocytomatosis viral oncogene homolog, c-Myc) were highest in the Nano-Se compared to the SS diet (P < 0.05). The Nano-Se decreased the mRNA and protein levels of NLRP3 signaling pathway-related genes compared to the SS diet (P < 0.05). In conclusion, our study demonstrated that Nano-Se and SeMet are better at improving the intestinal health of 21-day-old broilers. Additionally, Nano-Se demonstrated superior antioxidant and anti-inflammatory effects, promoting the development of intestinal goblet cells by modifying the NLRP3 signaling pathway.
PubMed: 38945002
DOI: 10.1016/j.psj.2024.103958 -
Biomaterials Jun 2024We present a bioprinted three-layered airway model with a physiologically relevant microstructure for the study of severe acute respiratory syndrome coronavirus 2...
We present a bioprinted three-layered airway model with a physiologically relevant microstructure for the study of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection dynamics. This model exhibited clear cell-cell junctions and mucus secretion with an efficient expression of angiotensin-converting enzyme 2 (ACE2) and transmembrane serine protease 2 (TMPRSS2). Having infected air-exposed epithelial cells in the upper layer with a minimum multiplicity of infection of 0.01, the airway model showed a marked susceptibility to SARS-CoV-2 within one-day post-infection (dpi). Furthermore, the unique longevity allowed the observation of cytopathic effects and barrier degradation for 21 dpi. The in-depth transcriptomic analysis revealed dramatic changes in gene expression affecting the infection pathway, viral proliferation, and host immune response which are consistent with COVID-19 patient data. Finally, the treatment of antiviral agents, such as remdesivir and molnupiravir, through the culture medium underlying the endothelium resulted in a marked inhibition of viral replication within the epithelium. The bioprinted airway model can be used as a manufacturable physiological platform to study disease pathogeneses and drug efficacy.
PubMed: 38944967
DOI: 10.1016/j.biomaterials.2024.122689 -
Talanta Jun 2024The COVID-19 pandemic presents global challenges, notably with co-infections in respiratory tract involving SARS-CoV-2 variants and influenza strains. Detecting multiple...
The COVID-19 pandemic presents global challenges, notably with co-infections in respiratory tract involving SARS-CoV-2 variants and influenza strains. Detecting multiple viruses simultaneously is crucial for accurate diagnosis, effective tracking infectious sources, and containment of the epidemic. This study uses a label-free surface-enhanced Raman spectroscopy (SERS) method using Au NPs/pZrO (250) and FIB-made Au NRs (100) to detect dual viruses, including SARS-CoV-2 Delta variant (D) and influenza A (A) or B (B) virus. Results demonstrate distinct peaks facilitating virus differentiation, especially between D and A or B, with clear disparities between substrates; specific peaks at 950 and 1337 cm are pivotal for discerning viruses using Au NPs/pZrO (250), while those at 1050, 1394, and 1450 cm and 1033, 1165, 1337, and 1378 cm are key for validation using Au NRs (100). Differences in substrate surface morphology and spatial disposition of accommodating viruses significantly influence hotspot formation and Raman signal amplification efficiency, thereby affecting the ability to distinguish various viruses. Furthermore, both substrates offer insights, even in the presence of oxymetazoline hydrochloride (an interfering substance), with practical implications in viral diagnosis. The customized design and reproducibility underscore efficient Raman signal amplification, even in challenging environments, highlighting potential for widespread virus detection.
PubMed: 38944940
DOI: 10.1016/j.talanta.2024.126466 -
Heart & Lung : the Journal of Critical... Jun 2024Factors associated with cardiovascular complications of COVID-19 remain understudied.
Cardiovascular complications in the course of COVID-19 - lessons learned and implications for the future care of patients with viral respiratory diseases: Data from a single center retrospective observational study.
BACKGROUND
Factors associated with cardiovascular complications of COVID-19 remain understudied.
OBJECTIVES
Here we investigate the occurrence and risk factors of arrythmias, myocardial infarction and/or stroke, and thromboembolism in the course of COVID-19.
METHODS
We have performed an observational study with prospectively designed data collection. Data of patients diagnosed with COVID-19 who were admitted from March 6th 2020 to November 30th 2021 in our Hospital were analyzed. Logistic regression was used to identify variables associated with the odds of early hospital death due to COVID-19.
RESULTS
Fourteen-point three percent of 1964 patients had cardiovascular complications, 6.36 % arrhythmias, 5.5 % thromboembolic events and 2.39 % myocardial infarction and/or stroke. Factors independently increasing the odds of arrhythmia were older age (OR=1.49 [95 % CI: 1.17-1.92], p = 0.02), longer time between admission and the first onset of symptoms (1.02 [0.99-1.05], p = 0.049), concomitant atrial fibrillation/flutter (2.84 [1.37-5.70], p = 0.004), nicotinism (2.49 [1.37-4.49], p = 0.002), and eGFR<60 ml/min/1.73m (2.44 [1.08-5.59], p = 0.033). Factors independently increasing the odds of myocardial infarction and/or stroke were dementia (4.55 [0.97-19.3], p = 0.044), hemiplegia (12.67 [3.12-46.1], p < 0.001), nicotinism (3.36 [1.30-10.4], p = 0.013) and higher C-reactive protein concentration (1.01 [1.00-1.01], p = 0.040). Factors independently increasing the odds of thromboembolic events were longer hospitalization (1.08 [1.05-1.10], p < 0.001) and higher d-dimers (1.04 [1.02-1.05], <0.001).
CONCLUSIONS
The risk of cardiovascular complications was especially pronounced in patients with older age, pre-existing cardiovascular disease and more sever pneumonia at presentation to care. This underlines the importance of close and careful clinical follow-up in the course of COVID-19 for specific patients' populations, including a pro-active approach in diagnosis.
PubMed: 38944910
DOI: 10.1016/j.hrtlng.2024.06.009