The severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2) infection is the cause of coronavirus disease 2019 (COVID-19); a severe respiratory distress that has emerged from the city of Wuhan, ...Hubei province, China during December 2019. COVID-19 is currently the major global health problem and the disease has now spread to most countries in the world. COVID-19 has profoundly impacted human health and activities worldwide. Genetic mutation is one of the essential characteristics of viruses. They do so to adapt to their host or to move to another one. Viral genetic mutations have a high potentiality to impact human health as these mutations grant viruses unique unpredicted characteristics. The difficulty in predicting viral genetic mutations is a significant obstacle in the field. Evidence indicates that SARS-CoV-2 has a variety of genetic mutations and genomic diversity with obvious clinical consequences and implications. In this review, we comprehensively summarized and discussed the currently available knowledge regarding SARS-CoV-2 outbreaks with a fundamental focus on the role of the viral proteins and their mutations in viral infection and COVID-19 progression. We also summarized the clinical implications of SARS-CoV-2 variants and how they affect the disease severity and hinder vaccine development. Finally, we provided a massive phylogenetic analysis of the spike gene of 214 SARS-CoV-2 isolates from different geographical regions all over the world and their associated clinical implications.
Objectives
The aim of the current study was to minimize ocular irritation and prolong the pharmacological action of vancomycin via formulation into nanosized spherical niosomes loaded into ...pH‐sensitive in‐situ forming gel.
Methods
Stability and rheological behaviour of the various gelling systems were evaluated. The ability of the selected system to eradicate methicillin‐resistant Staphylococcus aureus (MRSA) infections was examined in vitro and in vivo. Draize technique was also used to assess ocular irritation in rabbits.
Key findings
Nanosized spherical niosomes loaded with vancomycin at high entrapment efficiency were prepared and integrated into polymeric solution that forms gel in situ upon instillation into the eye, to allow for a further increase in the ocular residence time. In MRSA‐infected rabbits, there were 180‐ and 2.5‐fold increases in the antibacterial efficacy after treatment with the vancomycin niosomal gels in comparison with the untreated animals and the animals treated with the vancomycin free drug solution, respectively.
Conclusions
The developed formulations demonstrated promising in‐vivo biocompatibility and antibacterial efficacy, signifying their potential application as ophthalmic preparation to overcome ocular infections induced by resistant bacterial strains while minimizing drug irritation and improving patient compliance.
Abstract
We aimed to isolate
Acinetobacter baumannii
(
A. baumannii
) from wound infections, determine their resistance and virulence profile, and assess the impact of Silver nanoparticles (AgNPs) on ...the bacterial growth, virulence and biofilm-related gene expression. AgNPs were synthesized and characterized using TEM, XRD and FTIR spectroscopy.
A. baumannii
(n = 200) were isolated and identified. Resistance pattern was determined and virulence genes (
afa/draBC, cnf1, cnf2, csgA, cvaC, fimH, fyuA, ibeA, iutA, kpsMT II, PAI, papC, PapG II, III, sfa/focDE
and
traT)
were screened using PCR. Biofilm formation was evaluated using Microtiter plate method. Then, the antimicrobial activity of AgNPs was evaluated by the well-diffusion method, growth kinetics and MIC determination. Inhibition of biofilm formation and the ability to disperse biofilms in exposure to AgNPs were evaluated. The effect of AgNPs on the expression of virulence and biofilm-related genes (
bap, OmpA, abaI, csuA/B, A1S_2091, A1S_1510, A1S_0690, A1S_0114
) were estimated using QRT-PCR. In vitro infection model for analyzing the antibacterial activity of AgNPs was done using a co-culture infection model of
A. baumannii
with human fibroblast skin cell line HFF-1 or Vero cell lines.
A. baumannii
had high level of resistance to antibiotics. Most of the isolates harbored the
fimH
,
afa/draBC
,
cnf1
,
csgA
and
cnf2,
and the majority of
A. baumannii
produced strong biofilms. AgNPs inhibited the growth of
A. baumannii
efficiently with MIC ranging from 4 to 25 µg/ml.
A. baumannii
showed a reduced growth rate in the presence of AgNPs. The inhibitory activity and the anti-biofilm activity of AgNPs were more pronounced against the weak biofilm producers. Moreover, AgNPs decreased the expression of
kpsMII
,
afa/draBC,bap, OmpA,
and
csuA/B
genes. The in vitro infection model revealed a significant antibacterial activity of AgNPs against extracellular and intracellular
A. baumannii
. AgNPs highly interrupted bacterial multiplication and biofilm formation. AgNPs downregulated the transcription level of important virulence and biofilm-related genes. Our findings provide an additional step towards understanding the mechanisms by which sliver nanoparticles interfere with the microbial spread and persistence.
SARS-CoV-2 virus is transmitted in closed settings to people in contact with COVID-19 patients such as healthcare workers and household contacts. However, household person-to-person transmission ...studies are limited. Households participating in an ongoing cohort study of influenza incidence and prevalence in rural Egypt were followed. Baseline enrollment was done from August 2015 to March 2017. The study protocol was amended in April 2020 to allow COVID-19 incidence and seroprevalence studies. A total of 290 households including 1598 participants were enrolled and followed from April to October 2020 in four study sites. When a participant showed respiratory illness symptoms, a serum sample and a nasal and an oropharyngeal swab were obtained. Swabs were tested by RT-PCR for SARS-CoV-2 infection. If positive, the subject was followed and swabs collected on days three, six, nine, and 14 after the first swab day and a serum sample obtained on day 14. All subjects residing with the index case were swabbed following the same sampling schedule. Sera were collected from cohort participants in October 2020 to assess seroprevalence. Swabs were tested by RT-PCR. Sera were tested by Microneutralization Assay to measure the neutralizing antibody titer. Incidence of COVID-19, household secondary attack rate, and seroprevalence in the cohort were determined. The incidence of COVID-19 was 6.9% and the household secondary attack rate was 89.8%. Transmission within households occurred within two-days of confirming the index case. Infections were asymptomatic or mild with symptoms resolving within 10 days. The majority developed a neutralizing antibody titer by day 14 post onset. The overall seroprevalence among cohort participants was 34.8%. These results suggest that within-household transmission is high in Egypt. Asymptomatic or mild illness is common. Most infections seroconvert and have a durable neutralizing antibody titer.
Abstract
The present paper evaluates the photocatalytic degradation (
PCD
) performance of the biofabricated hematite nanoparticles (
α-HNPs
) for the degradation approach of the Cefotaxime (
Cfm
). ...The optimum pH of the solution to achieve the best
PCD
was found to be 10.5. The kinetics study for the
PCD
of the
Cfm
via
α-HNPs
has been investigated and the reaction was found to be fellow pseudo-first-order at R
2
= 0.992. The mass loading impact of
α-HNPs
was investigated and estimated for the maximum degradation of
Cfm
0.4 mg/mL. UV–Vis confirmed that
α-HNPs
had a direct transition bandgap at 3.78 eV at a maximum absorption wavelength of 362 nm with suspension stability for 7 days. The probable mechanism of the
Cfm PCD
via
α-HNPs
and the degradation pathway was conducted. The validation of the suspension stability of the
α-HNPs
(−68.6 ± 11.8 mV) was determined using the zeta potential investigation test. XRD investigation was conducted after
Cfm PCD
showing an average crystallite size of 27.0 nm. XRD, TEM, SEM, EDX, and FT-IR analyses have been conducted for the
α-HNPs
before and after
Cfm PCD
confirming the high efficiency for the reusability of the current biocatalyst
α-HNPs
for further use. TEM results of the particle sizes of
α-HNPs
were found at 19.2 ± 4.4 and 20.6 ± 7.4 nm respectively before and after
Cfm PCD
. The efficiency of the
Cfm PCD
was found to be 99.1% after 6 h. High potent as an antibacterial agent of
α-HNPs
was investigated either
α-HNPs
alone or after its
PCD
activity against
Cfm
. The antibacterial activity revealed high sensitivity, especially toward Gram-positive species indicating its promising ability against pathogenic issues. Interestingly,
Cfm@α-HNPs
showed superior anti-proliferative activity as tested by MTT assay and were able to induce apoptosis in MCF7 and HepG2 cell lines using the flow cytometry technique at 20.7% and 17% respectively. Also, The IC
50
of hydrogen peroxide scavenging was estimated and it was manifested that 635.8 and 665.6 μg/mL of
α-HNPs
before and after the
PCD
process of
Cfm
respectively.
Hepatitis E Virus is the most common cause of acute viral hepatitis globally. HEV infection is endemic in developing countries. Also, autochthonous and sporadic cases are reported in developed ...countries. HEV causes acute and chronic infections. Besides, extrahepatic manifestations including neurological, renal, haematological, acute pancreatitis and complications during pregnancy are associated with HEV infections. The pathogenesis of HEV in the extrahepatic tissues is either due to direct cytopathic effect mediated by the virus replication, or immunological mechanisms caused by an uncontrollable host response. Researchers have used different in vivo and in vitro models to study the pathogenesis of HEV in the extrahepatic tissues and analyse the host immune response against HEV infection. This review highlights the extrahepatic disorders associated with HEV infection. We focused on the in vivo and in vitro models as a tool for elucidating the HEV infection beyond the liver and studying the mechanisms of HEV induced tissue damages.
By whole exome sequencing, we identified a homozygous c.2086 C→T (p.R696C) TERT mutation in patients who present with a spectrum of variable bone marrow failure (BMF), raccoon eyes, dystrophic nails, ...rib anomalies, fragility fractures (FFs), high IgE level, extremely short telomere lengths (TLs), and skewed numbers of cytotoxic T cells with B and NK cytopenia. Haploinsufficiency in the other family members resulted in short TL and osteopenia. These patients also had the lowest bone mineral density Z-score compared to other BMF-patients. Danazol/zoledronic acid improved the outcomes of BMF and FFs. This causative TERT variant has been observed in one family afflicted with dyskeratosis congenita (DC), and thus, we also define a second report and new phenotype related to the variant which should be suspected in severe cases of DC with co-existent BMF, FFs, high IgE level and rib anomalies.
Pollination plays a significant role in the agriculture sector and serves as a basic pillar for crop production. Plants depend on vectors to move pollen, which can include water, wind, and animal ...pollinators like bats, moths, hoverflies, birds, bees, butterflies, wasps, thrips, and beetles. Cultivated plants are typically pollinated by animals. Animal-based pollination contributes to 30% of global food production, and bee-pollinated crops contribute to approximately one-third of the total human dietary supply. Bees are considered significant pollinators due to their effectiveness and wide availability. Bee pollination provides excellent value to crop quality and quantity, improving global economic and dietary outcomes. This review highlights the role played by bee pollination, which influences the economy, and enlists the different types of bees and other insects associated with pollination.
(1) Background: Drug repositioning is an unconventional drug discovery approach to explore new therapeutic benefits of existing drugs. Currently, it emerges as a rapid avenue to alleviate the ...COVID-19 pandemic disease. (2) Methods: Herein, we tested the antiviral activity of anti-microbial and anti-inflammatory Food and Drug Administration (FDA)-approved drugs, commonly prescribed to relieve respiratory symptoms, against Severe Acute Respiratory Syndrome Coronavirus 2 (SARS-CoV-2), the viral causative agent of the COVID-19 pandemic. (3) Results: Of these FDA-approved antimicrobial drugs, Azithromycin, Niclosamide, and Nitazoxanide showed a promising ability to hinder the replication of a SARS-CoV-2 isolate, with IC
of 0.32, 0.16, and 1.29 µM, respectively. We provided evidence that several antihistamine and anti-inflammatory drugs could partially reduce SARS-CoV-2 replication in vitro. Furthermore, this study showed that Azithromycin can selectively impair SARS-CoV-2 replication, but not the Middle East Respiratory Syndrome Coronavirus (MERS-CoV). A virtual screening study illustrated that Azithromycin, Niclosamide, and Nitazoxanide bind to the main protease of SARS-CoV-2 (Protein data bank (PDB) ID: 6lu7) in binding mode similar to the reported co-crystalized ligand. Also, Niclosamide displayed hydrogen bond (HB) interaction with the key peptide moiety GLN: 493A of the spike glycoprotein active site. (4) Conclusions: The results suggest that Piroxicam should be prescribed in combination with Azithromycin for COVID-19 patients.
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•Nanofibers might provide efficient topical nanodevice to overcome skin infections.•Vancomycin-loaded nanofibers (200 nm diameter) were prepared via electrospinning.•Nanofibers were ...tested in animal model of superficial MRSA skin infection.•Nanofibers demonstrated a superior in vitro and in vivo antibacterial efficiency.
Skin damage exposes the underlying layers to bacterial invasion, leading to skin and soft tissue infections. Several pathogens have developed resistance against conventional topical antimicrobial treatments and rendered them less effective. Recently, several nanomedical strategies have emerged as a potential approach to improve therapeutic outcomes of treating bacterial skin infections. In the current study, nanofibers were utilized for topical delivery of the antimicrobial drug vancomycin and evaluated as a promising tool for treatment of topical skin infections. Vancomycin-loaded nanofibers were prepared via electrospinning technique, and vancomycin-loaded nanofibers of the optimal composition exhibited nanosized uniform smooth fibers (ca. 200 nm diameter), high drug entrapment efficiency and sustained drug release patterns over 48 h. In vitro cytotoxicity assays, using several cell lines, revealed the biocompatibility of the drug-loaded nanofibers. In vitro antibacterial studies showed sustained antibacterial activity of the vancomycin-loaded nanofibers against methicillin-resistant Staphylococcus aureus (MRSA), in comparison to the free drug. The nanofibers were then tested in animal model of superficial MRSA skin infection and demonstrated a superior antibacterial efficiency, as compared to animals treated with the free vancomycin solution. Hence, nanofibers might provide an efficient nanodevice to overcome MRSA-induced skin infections and a promising topical delivery vehicle for antimicrobial drugs.
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