Cestrum diurnum L. (Solanaceae) is a fragrant ornamental tree cultivated in different parts around the world. In this study, the essential oil (EO) of the aerial parts was extracted by ...hydrodistillation (HD), steam distillation (SD) and microwave‐assisted hydro‐distillation (MAHD). GC/MS analysis of the three EOs revealed that phytol represents the major component in SD‐EO and MAHD‐EO (40.84 and 40.04 %, respectively); while in HD‐EO it only represented 15.36 %. The SD‐EO showed a strong antiviral activity against HCoV‐229E with IC50 of 10.93 μg/mL, whereas, MAHD‐EO and HD‐EO showed a moderate activity with IC50 values of 119.9 and 148.2 μg/mL, respectively. The molecular docking of EO major components: phytol, octadecyl acetate and tricosane showed a strong binding to coronavirus 3‐CL (pro). Moreover, the three EOs (50 μg/mL) decreased the levels of NO, IL‐6 and TNF‐α and suppressed IL‐6 and TNF‐α gene expression in LPS‐induced inflammation model in RAW264.7 macrophage cell lines.
Hepatocellular carcinoma (HCC) is a leading cause of cancer-related death in Egypt. A deep understanding of the molecular events occurring in HCC can facilitate the development of novel diagnostic ...and/or therapeutic approaches. In the present study, we describe a novel axis of
-miR-661-PTPN11 mRNA proposed by in silico and in vitro analysis and its role in HCC pathogenesis. We observe a reduction in the expression levels of
and PTPN11 mRNA in HCC patients' sera tested compared with control subjects. The reduction occurs with a concomitant increase in the expression of miR-661. Furthermore, the introduction of exogenous
into Hep-G2 or SNU449 cell lines results in detectable decrease in cellular viability and an increase in apoptotic manifestations that is associated with G1 accumulation and CCDN1 overexpression. Altogether, these findings indicate the tumor-suppressive role of
in HCC, which acts through miR-661 inhibition, along with a subsequent PTPN11 mRNA increase, where PTPN11 is known to inhibit cell proliferation in many forms of cancer. Our study encourages further investigation of the role of circRNAs in cancer and their potential use as molecular biomarkers.
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Chitosan (CS) is a biopolymer and has reactive amine/hydroxyl groups facilitated its modifications. The purpose of this study is improvement of (CS) physicochemical properties and its ...capabilities as antiviral and antitumor through modification with 1-(2-oxoindolin-3-ylidene)thiosemicarbazide (3A) or 1-(5-fluoro-2-oxoindolin-3-ylidene)thiosemicarbazide (3B) via crosslinking of poly(ethylene glycol)diglycidylether (PEGDGE) using microwave-assisted as green technique gives (CS-I) and (CS-II) derivatives. However, (CS) derivatives nanoparticles (CS-I NPs) and (CS-II NPs) are synthesized via ionic gelation technique using sodium tripolyphosphate (TPP). Structures of new (CS) derivatives are characterized using different tools. The anticancer, antiviral efficiencies and molecular docking of (CS) and its derivatives are assayed. (CS) derivatives and its nanoparticles show enhancement in cell inhibition toward (HepG-2 and MCF-7) cancer cells in comparison with (CS). (CS-II NPs) reveals the lowest IC50 values are 92.70 ± 2.64 μg/mL and 12.64 µ g/mL against (HepG-2) cell and SARS-CoV-2 (COVID-19) respectively and the best binding affinity toward corona virus protease receptor (PDB ID 6LU7) −5.71 kcal / mol. Furthermore, (CS-I NPs) shows the lowest cell viability% 14.31 ± 1.48 % and the best binding affinity −9.98 kcal/moL against (MCF-7) cell and receptor (PDB ID 1Z11) respectively. Results of this study demonstrated that (CS) derivatives and its nanoparticles could be potentially employed for biomedical applications.
Background
Recent studies and reports have documented the ability of the co-circulating seasonal influenza A/H1N1 (ancestor: 2009 pandemic H1N1) and A/H3N2 to exchange their genetic segments, ...generating a novel H1N2 strain in different geographical localities around the world with an ability to infect human. This raises concerns and triggers alarms to develop a multivalent vaccine that can protect against the documented H1- and H3-type human influenza A viruses (IAVs).
Results
Here, we generated a PR8-based vaccine strain that carries the HA gene segment from the contemporary H1N1 virus while the NA gene segment was derived from a currently circulating influenza A/H3N2 strain. A recombinant PR8-based H1N2 vaccine strain (rgH1N2), engineered by reassortment between influenza A/H1N1 and A/H3N2 to mimic the documented human influenza A/H1N2, was used for immunization to provoke immunogenicity and cross-antigenicity against the H1- and H3-type human IAVs and was evaluated for its immunogenicity and effectiveness in mice. Following challenge infection of rgH1N2-vaccinated mice with contemporary influenza A/H1N1 and A/H3N2, results revealed that rgH1N2-vaccinated mice showed less viral shedding, more survival, and less body weight loss compared to control unvaccinated groups and vaccinated mice with rgH1N1 and rgH3N2.
Conclusions
This study highlights the applicability of the PR8-based H1N2 vaccine strain to protect against seasonal IAVs and emphasizes the role of both surface proteins, HA and NA, to stimulate protective and neutralizing antibodies against circulating influenza A/H1N1 and A/H3N2 strains.
Acute Coronary Syndrome (ACS) stands as a significant contributor to cardiovascular mortality, necessitating improved diagnostic tools for early detection and tailored therapeutic interventions. ...Current diagnostic modalities, exhibit limitations in sensitivity and specificity, urging the quest for novel biomarkers to enhance discrimination of the different stages of ACS including unstable angina, Non-ST-segment Elevation Myocardial Infarction (NSTEMI), and ST-segment Elevation Myocardial Infarction (STEMI).
This study investigated the potential of a plasma-circulating multi-noncoding RNA (ncRNA) panel, comprising four miRNAs (miR-182–5p, miR-23a-3p, miR-146a-5p, and miR-183–5p) and three lncRNAs (SNHG15, SNHG5, and RMRP), selected based on their intricate involvement in ACS pathogenesis and signaling pathways regulating post-myocardial infarction (MI) processes. The differential expression of these ncRNAs was validated in sera of ACS patients and healthy controls via real-time polymerase chain reaction (RT-PCR).
Analysis revealed a marked upregulation of the multi-ncRNAs panel in ACS patients. Notably, miRNA-182–5p and lncRNA-RMRP exhibited exceptional discriminatory power, indicated by the high area under the curve (AUC) values (0.990 and 0.980, respectively). Importantly, this panel displayed superior efficacy in discriminating between STEMI and NSTEMI, outperforming conventional biomarkers like creatine kinase-MB and cardiac troponins. Additionally, the four miRNAs and lncRNA RMRP showcased remarkable proficiency in distinguishing between STEMI and unstable angina.
The findings underscore the promising potential of the multi-ncRNA panel as a robust tool for early ACS detection, and precise differentiation among ACS subtypes, and as a potential therapeutic target.
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The date palm (
Phoenix dactylifera
) is an important cultivated crop in arid areas. Here, we studied the effect of plant genotype and type of fertilizers on the eukaryotic community structures of ...the date palm rhizosphere. Samples were collected from one wild population, five cultivars from two farms, and a factorial fertilizer experiment (organic, chemical, and biofertilizer) in Qatar. The eukaryotic communities were sequenced using a next-generation sequencing method. A total of 2422 Operational Taxonomic Units (OTUs) were identified as belonging to 15 phyla,
Chlorophyta
,
Streptophyta
,
Imbricatea
,
Chytridiomycota
,
Ascomycota
,
Olpidiomycota
, being dominant. The wild-type date palms showed a low number of OTUs compared to cultivated date palms, potentially due to the strong influence of soil salinity and low moisture level. However, the wild-type date palm hosted the highest number of unique OTUs. PCA revealed that the eukaryotic microbiome of the wild date palms was separated from the cultivated date palms and that the eukaryotic microbial diversity varied between date palm cultivars in similar environments. Using the highest amounts of biofertilizer and chemical fertilizer decreased the species diversity within the samples. However, a high concentration of biofertilizer combined with a low concentration of chemical fertilizers enhanced the eukaryotic diversity within the samples. We conclude that cultivar type (biotic factor), type of fertilizer, and dosage (abiotic factor) play significant roles in determining the microbiome diversity of the rhizosphere. The wild date palm population could potentially host salt and drought-tolerating eukaryotes that should be further investigated for future development of biofertilizers suitable for drylands.
Aiming to achieve efficient activity against severe acute respiratory syndrome coronavirus (SARS-CoV-2), the expansion of the structure- and ligand-based drug design approaches was adopted, which has ...been recently reported by our research group. Purine ring is a corner stone in the development of SARS-CoV-2 main protease (M
) inhibitors. The privileged purine scaffold was elaborated to achieve additional affinity based on hybridization and fragment-based approaches. Thus, the characteristic pharmacophoric features that are required for the inhibition of M
and RNA-dependent RNA polymerase (RdRp) of SARS-CoV-2 were utilized along with the crystal structure information of both targets. The designed pathways involved rationalized hybridization with large sulfonamide moieties and a carboxamide fragment for the synthesis of ten new dimethylxanthine derivatives. The synthesis was performed under diverse conditions to afford
-alkylated xanthine derivatives, and cyclization afforded tricyclic compounds. Molecular modeling simulations were used to confirm and gain insights into the binding interactions at both targets' active sites. The merit of designed compounds and the
studies resulted in the selection of three compounds that were evaluated
to estimate their antiviral activity against SARS-CoV-2 (compounds 5, 9a and 19 with IC
values of 38.39, 8.86 and 16.01 μM, respectively). Furthermore, oral toxicity of the selected antiviral candidates was predicted, in addition to cytotoxicity investigations. Compound 9a showed IC
values of 8.06 and 3.22 μM against M
and RdRp of SARS-CoV-2, respectively, in addition to promising molecular dynamics stability in both target active sites. The current findings encourage further specificity evaluations of the promising compounds for confirming their specific protein targeting.
Sexual dimorphism arises from genetic differences between male and female cells, and from systemic hormonal differences
. How sex hormones affect non-reproductive organs is poorly understood, yet ...highly relevant to health given the sex-biased incidence of many diseases
. Here we report that steroid signalling in Drosophila from the ovaries to the gut promotes growth of the intestine specifically in mated females, and enhances their reproductive output. The active ovaries of the fly produce the steroid hormone ecdysone, which stimulates the division and expansion of intestinal stem cells in two distinct proliferative phases via the steroid receptors EcR and Usp and their downstream targets Broad, Eip75B and Hr3. Although ecdysone-dependent growth of the female gut augments fecundity, the more active and more numerous intestinal stem cells also increase female susceptibility to age-dependent gut dysplasia and tumorigenesis, thus potentially reducing lifespan. This work highlights the trade-offs in fitness traits that occur when inter-organ signalling alters stem-cell behaviour to optimize organ size.
Despite the panzootic nature of emergent highly pathogenic avian influenza H5Nx viruses in wild migratory birds and domestic poultry, only a limited number of human infections with H5Nx viruses have ...been identified since its emergence in 1996. Few countries with endemic avian influenza viruses (AIVs) have implemented vaccination as a control strategy, while most of the countries have adopted a culling strategy for the infected flocks. To date, China and Egypt are the two major sites where vaccination has been adopted to control avian influenza H5Nx infections, especially with the widespread circulation of clade 2.3.4.4b H5N1 viruses. This virus is currently circulating among birds and poultry, with occasional spillovers to mammals, including humans. Herein, we will discuss the history of AIVs in Egypt as one of the hotspots for infections and the improper implementation of prophylactic and therapeutic control strategies, leading to continuous flock outbreaks with remarkable virus evolution scenarios. Along with current pre-pandemic preparedness efforts, comprehensive surveillance of H5Nx viruses in wild birds, domestic poultry, and mammals, including humans, in endemic areas is critical to explore the public health risk of the newly emerging immune-evasive or drug-resistant H5Nx variants.
Background
Severe acute respiratory syndrome
coronavirus 2
(
SARS
-
CoV
-
2
) is of a public health importance as it is continually evolving due to random mutations. New mutations can potentially ...affect the degree of infectiousness, virulence, and can increase the virus’ capability to evade adaptive immune responses of the body. Immunity is one of the key factors determining the extent of severity of
SARS-CoV-2
patients. Therefore, thinking about natural remedies is the way to boost immunity, keep the body protected, and able to fight the
SARS-CoV-2
virus. We aimed to make progress in the field of anti-
SARS-CoV-2
nutraceuticals, thus providing a safe and natural alternative to traditional chemically manufactured medications.
Methods
The cytotoxic activity (CC
50
) of the natural products was tested experimentally in vitro on the VERO-E6 cells using a crystal violet assay. The cells were then treated with different concentrations of the natural products of
Moringa oleifera
leaves extract, cinnamon bark oil extract, Manuka honey, and
Nigella sativa
oil. The inhibitory concentration 50 (IC
50
) value and the CC
50
value were calculated in order to measure the antiviral effect of on
SARS-CoV-2
virus compared to antiviral Remdesivir drug.
Results
The tested natural products of honey and extracts exhibited pronounced virucidal effect against one of the most challenging viruses worldwide which is the
SARS-CoV-2
virus. The results showed that the highest selectivity index was the Manuka honey + 20 UMF with SI of 10.23. The second sample following Manuka honey regarding its efficiency was the mixture of the three extracts with the honey (SI = 7.12), then followed by Remdesivir antiviral drug (SI = 3.3), then
Moringa oleifera
leaves extract (SI = 2.1). The last two products showing the least SI were
Nigella sativa
oil (SI = 1.6) and cinnamon bark oil (SI = 1.08), respectively.
Conclusions
Manuka honey + 20 UMF alone or combined with other three extracts of
Moringa oleifera
,
Nigella sativa
, and cinnamon bark oil have a much stronger in vitro antiviral effect on
SARS-CoV-2
virus than the traditional antiviral drug Remdesivir. Further research will be needed to test the effectiveness of these natural products in vivo as an antiviral remedy against
SARS-CoV-2
virus.
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