Many questions on the SARS-CoV-2 pathogenesis remain to answer. The SARS-CoV-2 genome encodes some accessory proteins that are essential for infection. Notably, accessory proteins of SARS-CoV-2 play ...significant roles in affecting immune escape and viral pathogenesis. Therefore SARS-CoV-2 accessory proteins could be considered putative drug targets. IFN-I and IFN-III responses are the primary mechanisms of innate antiviral immunity in infection clearance. Previous research has shown that SARS-CoV-2 suppresses IFN-β by infecting host cells via ORF3a, ORF3b, ORF6, ORF7a, ORF7b, ORF8, and ORF9b. Furthermore, ORF3a, ORF7a, and ORF7b have a role in blocking IFNα signaling, and ORF8 represses IFNβ signaling. The ORF3a, ORF7a, and ORF7b disrupt the STAT1/2 phosphorylation. ORF3a, ORF6, ORF7a, and ORF7b could prevent the ISRE promoter activity. The main SARS-CoV-2 accessory proteins involved in immune evasion are discussed here for comprehensive learning on viral entry, replication, and transmission in vaccines and antiviral development.
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GEOZS, IJS, IMTLJ, KILJ, KISLJ, NLZOH, NUK, OILJ, PNG, SAZU, SBCE, SBJE, UILJ, UL, UM, UPCLJ, UPUK, ZAGLJ, ZRSKP
Abstract
Antibiotics have received great attention because of their abuse and potential hazards to the human health and environment. In the current work, peroxymonosulfate (PMS) was added to a cerium ...oxide (CeO2)/ultrasonic (US) system for tetracycline (TC) degradation. CeO2 nanoparticles (NPs) were synthesized by a simple and cost-effective method using Stevia rebaudiana leaf extract and cerium nitrate as precursors. The as-synthesized CeO2 NPs were characterized by X-ray diffraction, field emission scanning electron microscopy, and Fourier-transform infrared spectroscopy analysis. The effects of catalyst dosage, PMS concentration, US power, initial antibiotic concentration, and pH on TC removal were investigated. The results confirmed the formation of CeO2 NPs with a fluorite structure, spherical shape, and average particle size of 29 nm. The removal efficiency of TC was 92.6% in the optimum oxidation conditions (TC = 15 mg/L, PMS = 50 mM, CeO2 = 0.6 g/L, pH = 6, and US = 70 W) and followed the zero-order kinetics. Experiment scavenger demonstrated both sulfate and hydroxyl radicals (SO4•−, •OH) were responsible for degrading antibiotics. Biogenic CeO2 NPs and ultrasound waves-activated PMS is a promising technology for water pollution caused by contaminants such as pharmaceuticals.
Healthcare workers may pave the way for increased infections in hospitalized patients by coagulase-negative staphylococci (CoNS). Biofilm formation and antibiotic resistance are the major problems ...posed by CoNS in nosocomial infections. In this study, we determined biofilm production level and the distribution of biofilm-associated and virulence genes, including icaADBC, aap, bhp, atlE, embp, and fbe, as well as IS256, IS257, mecA, and ACME clusters (arc-A, opp-3AB) among 114 clinical (n = 57) and healthcare workers (n = 57) CoNS isolates in Kerman, Iran. In this study, more than 80% (n = 96) of isolates were methicillin-resistant CoNS (MR-CoNS). Out of 114 isolates, 33% (n = 38) were strong biofilm producers. Strong biofilm formation was found to be significantly different between clinical and healthcare workers' isolates (P < 0.050). In addition, 28% (n = 32) of isolates were positive for icaADBC simultaneously, and all were strong biofilm producers. The prevalence of icaADBC, mecA, bhp, fbe, and IS256 in clinical isolates was higher than that in healthcare workers' isolates (P < 0.050). A significant relationship was observed between clinical isolates and the presence of icaADBC, mecA, bhp, and IS256. Although these elements were detected in healthcare workers' isolates, they were more frequent in clinical isolates compared to those of healthcare workers. The high prevalence of ACME clusters in healthcare workers' isolates and biofilm formation of these isolates partially confirms the bacterial colonization in the skin of healthcare workers. Isolating MR-CoNS from healthcare workers' skin through similar genetic elements to clinical isolates, such as icaADBC, mecA, and IS256, calls for appropriate strategies to control and prevent hospital infections.
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DOBA, IZUM, KILJ, NUK, PILJ, PNG, SAZU, SIK, UILJ, UKNU, UL, UM, UPUK
Essential tremor (ET) is a neurological disease that impairs motor and cognitive functioning. A variant of the Lingo-1 genetic locus is associated with a heightened ET risk, and increased expression ...of cerebellar Lingo-1. Lingo-1 has been associated with neurodegenerative processes; however, neuroprotection from ET-associated degeneration can be conferred by the protein Sirt1. Sirt1 activity can be promoted by Resveratrol (Res) and 1,25-dihydroxyvitamin D3 (VitD3), and thus these factors may exert neuroprotective properties through a Sirt1 mechanism. As Res and VitD3 are linked to Sirt1, enhancing Sirt1 could counteract the negative effects of increased Lingo-1. Therefore, we hypothesized that a combination of Res-VitD3 in a harmaline injection model of ET would modulate Sirt1 and Lingo-1 levels. As expected, harmaline exposure (10 mg/kg/every other day; i.p.) impaired motor coordination, enhanced tremors, rearing, and cognitive dysfunction. When Res (5 mg/kg/day; i.p.) and VitD3 (0.1 mg/kg/day; i.p.) were given to adult rats (n = 8 per group) an hour before harmaline, tremor severity, rearing, and memory impairment were reduced. Individual treatment with Res and VitD3 decreased Lingo-1 gene expression levels in qPCR assays. Co-treatment with Res and VitD3 increased and decreased Sirt1 and Lingo-1 gene expression levels, respectively, and in some cases, beneficial effects on behavior were noted, which were not seen when Res or VitD3 were individually applied. Taken together, our study found that Res and VitD3 improved locomotor and cognitive deficits, modulated Sirt1 and Lingo-1. Therefore, we would recommend co-treatment of VitD3 and Res to leverage complementary effects for the management of ET symptoms.
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IZUM, KILJ, NUK, PILJ, PNG, SAZU, UL, UM, UPUK
Multidrug-resistant (MDR) Escherichia coli, a species that is a leading cause of urinary tract infections (UTIs) and is a major global public health concern. This study was designed to detect the ...differences in antibiotic resistance patterns, the production and type of extended spectrum β-lactamases (ESBLs), and the clonal relationships among E. coli isolates from UTIs and fecal samples.
Antibacterial resistance was determined by the disk diffusion method. ESBL, carbapenemase, and AmpC-producing isolates were detected phenotypically. Then, the ESBL genes were sequenced to detect the type. Enterobacterial repetitive intergenic consensus-polymerase chain reaction (ERIC-PCR) was performed on the ESBL-positive isolates.
The most common effective antibacterial agents were colistin, imipenem, and amikacin. Among the isolates, 204 (56.6%) were MDR. Of the 163 ESBL-positive isolates, 11 (6.7%) produced AmpC, and the frequencies of beta-lactamase-positive genes were as follows: bla CTX-Mgroup1, 76%; bla TEM1, 74.8%; bla SHV12, 1.2%; and bla OXA1, 12.88%. ERIC PCR showed a diverse pattern, suggesting that clonal spread of E. coli in this area is uncommon, and that most of the infecting strains are endogenous.
The high rates of antibacterial-resistant and MDR isolates are quite important since these strains can act as source of resistant bacteria that can be spread in the community. Controlling antibiotic use, against inappropriate use and abuse, in the community and continuous surveillance of emerging resistance traits are critical to controlling the spread of resistance.
Molecular typing such as spa typing is used to control and prevent Staphylococcus aureus widespread in hospitals and communities. Hence, the aim of this study was to find the most common types of S. ...aureus strain circulating in Shiraz via spa and SCCmec typing methods.
Total of 159 S. aureus isolates were collected from two tertiary hospitals in Shiraz. Isolates were identified by biochemical tests. Antimicrobial susceptibility tests were performed by standard disk diffusion method and then genetic analysis of bacteria was performed using SCCmec and spa typing. In this study 31.4% of the isolates were methicillin-resistant S. aureus. The majority of isolates were SSCmec type III. Spa type t030 was the most prominent type among MRSA strains. For the first time in Iran, spa003, t386, t1877, t314, t186, t1816, t304, t325, t345 were reported in this study. It was shown that there is a possibility that these spa types are native to this region. Our findings showed that SCCmec II, III and IV disseminate from hospital to community and vice versa. Thus, effective monitoring of MRSA in hospital and community is necessary.
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IZUM, KILJ, NUK, PILJ, PNG, SAZU, UL, UM, UPUK
is an important human pathogen that causes diseases such as urinary tract infections, pneumonia, bloodstream infections, bacteremia, and sepsis. The rise of multidrug-resistant strains has severely ...limited the available treatments for
infections. On the other hand,
activity (and related infections) urgently requires improved management strategies. A growing number of medical applications are using nanotechnology, which uses materials with atomic or molecular dimensions, to diagnose, eliminate, or reduce the activity of different infections. In this review, we start with the traditional treatment and detection method for
and then concentrate on selected studies (2015-2022) that investigated the application of nanoparticles separately and in combination with other techniques against
.
Extended spectrum β-lactamases (ESBLs) and AmpC β-lactamases enzyme are major sources of resistance to β-lactam antibiotics especially in Enterobacteriaceae such as Escherichia coli and Klebsiella ...pneumoniae. Increasing frequency of the co-existence of ESBLs with AmpC-β-lactamases in bacteria is a serious threat for treating bacterial infections.
The aim of this study was to determine the presence of AmpC and CTX-M types of β-lactamases in clinical isolates of E. coli and K. pneumoniae producing ESBLs.
Resistance to different antibiotics was determined using the standard disk diffusion method. ESBLs, MBLs and AmpC-β-lactamases were detected by the combination double disk test (CDDT) method and polymerase chain reaction (PCR) was used to determine bla CTX -M genes in the ESBLs and AmpC positive isolates.
The prevalence of ESBLs and AmpC-β-lactamase producer isolates was 181 (43.8%) and 133 (37.2%), respectively. The prevalence of bla CTX -M among isolates was 61 (14.7%).
Outbreak of isolates co-expressing AmpC-β-lactamases and ESBLs can cause serious problems in the future, regarding the treatment of infections caused by these common enteric pathogens.
With the spread of multi-drug-resistant (MDR) bacteria and the lack of effective antibiotics to treat them, developing new therapeutic methods and strategies is essential. In this study, we evaluated ...the antibacterial and antibiofilm activity of different formulations composed of ibuprofen (IBP), acetylsalicylic acid (ASA), and dexamethasone sodium phosphate (DXP) in combination with ciprofloxacin (CIP), gentamicin (GEN), cefepime (FEP), imipenem (IPM), and meropenem (MEM) on clinical isolates of
(
) and
(
) as well as the transcription levels of biofilm-associated genes in the presence of sub-MICs of IBP, ASA, and DXP. The minimal inhibitory concentrations (MICs), minimal biofilm inhibitory concentrations (MBICs), and minimum biofilm eradication concentrations (MBECs) of CIP, GEN, FEP, IPM, and MEM with/without sub-MICs of IBP (200 µg/mL), ASA (200 µg/mL), and DXP (500 µg/mL) for the clinical isolates were determined by the microbroth dilution method. Quantitative real-time-PCR (qPCR) was used to determine the expression levels of biofilm-related genes, including
in
and
in
at sub-MICs of IBP, ASA, and DXP. All
isolates were methicillin-resistant
(MRSA), and all
were resistant to carbapenems. IBP decreased the levels of MIC, MBIC, and MBEC for all antibiotic agents in both clinical isolates, except for FEP among
isolates. In MRSA isolates, ASA decreased the MICs of GEN, FEP, and IPM and the MBICs of IPM and MEM. In
, ASA decreased the MICs of FEP, IPM, and MEM, the MBICs of FEP and MEM, and the MBEC of FEP. DXP increased the MICs of CIP, GEN, and FEP, and the MBICs of CIP, GEN, and FEP among both clinical isolates. The MBECs of CIP and FEP for MRSA isolates and the MBECs of CIP, GEN, and MEM among
isolates increased in the presence of DXP. IBP and ASA at 200 µg/mL significantly decreased the transcription level of
in
, and IBP significantly decreased the transcription level of
in
. DXP at 500 µg/mL significantly increased the expression levels of
and
genes in
and
isolates, respectively. Our findings showed that the formulations containing ASA and IBP have significant effects on decreasing the MIC, MBIC, and MBEC levels of some antibiotics and can down-regulate the expression of biofilm-related genes such as
and
. Therefore, NSAIDs represent appropriate candidates for the design of new antibacterial and antibiofilm therapeutic formulations.
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IZUM, KILJ, NUK, PILJ, PNG, SAZU, UL, UM, UPUK