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BACKGROUND: Given the sparse data on the renin-angiotensin system (RAS) and its biological effector molecules ACE1 and ACE2 in pediatric COVID-19 cases, we investigated whether the ACE1 insertion/deletion (I/D) polymorphism could be a genetic marker for susceptibility to COVID-19 in Egyptian children and adolescents. METHODS: This was a case-control study included four hundred sixty patients diagnosed with COVID-19, and 460 well-matched healthy control children and adolescents. The I/D polymorphism (rs1799752) in the ACE1 gene was genotyped by polymerase chain reaction (PCR), meanwhile the ACE serum concentrations were assessed by ELISA. RESULTS: The ACE1 D/D genotype and Deletion allele were significantly more represented in patients with COVID-19 compared to the control group (55% vs. 28%; OR = 2.4; [95% CI: 1.46-3.95]; for the DD genotype; P = 0.002) and (68% vs. 52.5%; OR: 1.93; [95% CI: 1.49-2.5] for the D allele; P = 0.032). The presence of ACE1 D/D genotype was an independent risk factor for severe COVID-19 among studied patients (adjusted OR: 2.6; [95% CI: 1.6-9.7]; P < 0.001. CONCLUSIONS: The ACE1 insertion/deletion polymorphism may confer susceptibility to SARS-CoV-2 infection in Egyptian children and adolescents. IMPACT: Recent studies suggested a crucial role of renin-angiotensin system and its biological effector molecules ACE1 and ACE2 in the pathogenesis and progression of COVID-19. To our knowledge, ours is the first study to investigate the association of ACE1 I/D polymorphism and susceptibility to COVID-19 in Caucasian children and adolescents. The presence of the ACE1 D/D genotype or ACE1 Deletion allele may confer susceptibility to SARS-CoV-2 infection and being associated with higher ACE serum levels; may constitute independent risk factors for severe COVID-19. The ACE1 I/D genotyping help design further clinical trials reconsidering RAS-pathway antagonists to achieve more efficient targeted therapies.
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To fully evaluate and define the new drug molecule for its pharmacological characteristics and toxicity profile, pre-clinical and clinical studies are conducted as part of the drug research and development process. The average time required for all drug development processes to finish various regulatory evaluations ranges from 11.4 to 13.5 years, and the expense of drug development is rising quickly. The development in the discovery of newer novel treatments is, however, largely due to the growing need for new medications. Methods to identify Hits and discovery of lead compounds along with pre-clinical studies have advanced, and one example is the introduction of computer-aided drug design (CADD), which has greatly shortened the time needed for the drug to go through the drug discovery phases. The pharmaceutical industry will hopefully be able to address the present and future issues and will continue to produce novel molecular entities (NMEs) to satisfy the expanding unmet medical requirements of the patients as the success rate of the drug development processes is increasing. Several heterocyclic moieties have been developed and tested against many targets and proved to be very effective. In-depth discussion of the drug design approaches of newly found drugs from 2020 to 2022, including their pharmacokinetic and pharmacodynamic profiles and in-vitro and in-vivo assessments, is the main goal of this review. Considering the many stages these drugs are going through in their clinical trials, this investigation is especially pertinent. It should be noted that synthetic strategies are not discussed in this review; instead, they will be in a future publication.
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BACKGROUND: Given the sparse data on vitamin D status in pediatric COVID-19, we investigated whether vitamin D deficiency could be a risk factor for susceptibility to COVID-19 in Egyptian children and adolescents. We also investigated whether vitamin D receptor (VDR) FokI polymorphism could be a genetic marker for COVID-19 susceptibility. METHODS: One hundred and eighty patients diagnosed to have COVID-19 and 200 matched control children and adolescents were recruited. Patients were laboratory confirmed as SARS-CoV-2 positive by real-time RT-PCR. All participants were genotyped for VDR Fok1 polymorphism by RT-PCR. Vitamin D status was defined as sufficient for serum 25(OH) D at least 30 ng/mL, insufficient at 21-29 ng/mL, deficient at <20 ng/mL. RESULTS: Ninety-four patients (52%) had low vitamin D levels with 74 (41%) being deficient and 20 (11%) had vitamin D insufficiency. Vitamin D deficiency was associated with 2.6-fold increased risk for COVID-19 (OR = 2.6; [95% CI 1.96-4.9]; P = 0.002. The FokI FF genotype was significantly more represented in patients compared to control group (OR = 4.05; [95% CI: 1.95-8.55]; P < 0.001). CONCLUSIONS: Vitamin D deficiency and VDR Fok I polymorphism may constitute independent risk factors for susceptibility to COVID-19 in Egyptian children and adolescents. IMPACT: Vitamin D deficiency could be a modifiable risk factor for COVID-19 in children and adolescents because of its immune-modulatory action. To our knowledge, ours is the first such study to investigate the VDR Fok I polymorphism in Caucasian children and adolescents with COVID-19. Vitamin D deficiency and the VDR Fok I polymorphism may constitute independent risk factors for susceptibility to COVID-19 in Egyptian children and adolescents. Clinical trials should be urgently conducted to test for causality and to evaluate the efficacy of vitamin D supplementation for prophylaxis and treatment of COVID-19 taking into account the VDR polymorphisms.
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COVID-19 , Receptores de Calcitriol , Deficiencia de Vitamina D , Adolescente , Niño , Humanos , COVID-19/genética , Predisposición Genética a la Enfermedad , Genotipo , Receptores de Calcitriol/genética , Factores de Riesgo , SARS-CoV-2 , Vitamina D , Deficiencia de Vitamina D/complicaciones , Deficiencia de Vitamina D/genéticaRESUMEN
Biosurfactants are surface-active molecules with unique qualities and various uses. Many microorganisms produce secondary metabolites with surface-active characteristics that serve various antiviral functions. The HIV and Zika viruses were chosen for this study because they can spread from mother to child and result in potentially fatal infections in infants. Halophilic bacteria from the Red Sea solar saltern in Egypt were screened using drop collapse, emulsification activity, and oil displacement assays to produce biosurfactants and emulsifiers. Halobacterium jilantaiense strain JBS1 was the most effective strain of the Halobacteriaceae family. It had the best oil displacement test and emulsification activity against kerosene and crude oil, respectively. Among the ten isolates, it produced the most promising biosurfactant, also recognized by the GC-MASS library. This study evaluated biosurfactants from halophilic bacteria as potential antiviral drugs. Some of the computer methods we use are molecular docking, ADMET, and molecular dynamics. We use model organisms like the HIV reverse transcriptase (PDB: 5VZ6) and the Zika virus RNA-dependent RNA polymerase (ZV-RdRP). Molecular docking and molecular dynamics make the best complexes with 5VZ6 HIV-RT and flavone (C25) and 5wz3 ZV-RdRP and ethyl cholate (C8). Testing for ADMET toxicity on the complex revealed that it is the safest medicine conceivable. The 5VZ6-C25 and 5wz3-C8 complexes also followed the Lipinski rule. They made five hydrogen bond donors and ten hydrogen bond acceptors with 500 Da MW and a 5:1 octanol/water partition coefficient. Finally, extreme settings require particular adaptations for stability, and extremophile biosurfactants may be more stable.
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Active components in medicinal plants provide unlimited useful and traditional medicines. Antimicrobial activities are found in secondary metabolites in plant extracts such as argan oil. This experimental investigation aims to determine argan oil's volatile compounds and examine their in vitro antimicrobial properties. In silico simulations, molecular docking, pharmacokinetics, and drug-likeness prediction revealed the processes underlying the in vitro biological possessions. Gas chromatography-mass spectrometry (GC/MS) was used to screen argan oil's primary components. In silico molecular docking studies were used to investigate the ability of the selected bioactive constituents of argan oil to act effectively against Pseudomonas aeruginosa and Staphylococcus aureus (S. aureus) isolated from infections. The goal was to study their ability to interact with both bacteria's essential therapeutic target protein. The 21 chemicals in argan oil were identified by GC/MS. Docking results for all compounds with S. aureus and P. aeruginosa protease proteins ranged from -5 to -9.4 kcal/mol and -5.7 to -9.7 kcal/mol, respectively, compared to reference ligands. Our docking result indicates that the 10-octadecenoic acid, methyl ester was the most significant compound with affinity scores of -9.4 and -9.7 kcal/mol for S. aureus and P. aeruginosa proteins, respectively. The minimal bactericidal concentration (MBC) and minimal inhibitory concentration (MIC) of argan oil were 0.7 ± 0.03 and 0.5 ± 0.01 for S. aureus and 0.4 ± 0.01 and 0.3 ± 0.02 for P. aeruginosa, respectively. We confirmed the antimicrobial properties of argan oil that showed significant growth inhibition for S. aureus and P. aeruginosa.
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Introduction: Medicinal plants have been considered as potential source of therapeutics or as starting materials in drugs formulation. Methods: The current study aims to shed light on the therapeutic potential of the Amomum subulatom and Amomum xanthioides Fruits by analyzing the phytochemical composition of their seeds and fruits using gas chromatography-mass spectrometry (GC-MS) and high-performance liquid chromatography (HPLC) techniques to determine the presence of bioactive components such as flavonoids, phenols, vitamins, steroids, and essential oils. Results and Discussion: The protein content is usually higher than the total lipids in both species except the fruit of A. subulatum which contain more lipids than proteins. The total protein contents for A. subulatum were 235.03 ± 21.49 and 227.49 ± 25.82 mg/g dry weight while for A. xanthioides were 201.9 ± 37.79 and 294.99 ± 37.93 mg/g dry weight for seeds and fruit, respectively. The Carvacrol levels in A. subulatum is 20 times higher than that in A. xanthioides. Lower levels of α-Thujene, Phyllanderenes, Ascaridole, and Pinocarvone were also observed in both species. According to DPPH (2,2-diphenylpicrylhydrazyl) assay, seed the extract of A. subulatum exhibited the highest antioxidant activity (78.26±9.27 %) followed by the seed extract of A. xanthioides (68.21±2.56 %). Similarly, FRAP (Ferric Reducing Antioxidant Power) assay showed that the highest antioxidant activity was exhibited by the seed extract of the two species; 20.14±1.11 and 21.18±1.04 µmol trolox g-1 DW for A. subulatum and A. xanthioides, respectively. In terms of anti-lipid peroxidation, relatively higher values were obtained for the fruit extract of A. subulatum (6.08±0.35) and the seed extract of A. xanthioides (6.11±0.55). Ethanolic seed extracts of A. subulatum had the highest efficiency against four Gram-negative bacterial species which causes serious human diseases, namely Pseudomonas aeruginosa, Proteus vulgaris, Enterobacter aerogenes, and Salmonella typhimurium. In addition, P. aeruginosa was also inhibited by the fruit extract of both A. subulatum and A. xanthioides. For the seed extract of A. xanthioides, large inhibition zones were formed against P. vulgaris and the fungus Candida albicans. Finally, we have in silico explored the mode of action of these plants by performing detailed molecular modeling studies and showed that the antimicrobial activities of these plants could be attributed to the high binding affinity of their bioactive compounds to bind to the active sites of the sterol 14-alpha demethylase and the transcriptional regulator MvfR. Conclusion: These findings demonstrate the two species extracts possess high biological activities and therapeutical values, which increases their potential value in a number of therapeutic applications.
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The present study aims to evaluate the antimicrobial activity (in vitro study) of olive leaves powder (OLP) and its role in improving the broiler productivity, carcass criteria, blood indices, and antioxidant activity. A total of 270 one-day-old broiler chickens were distributed into 6 treatment groups as follows: the first group: basal diet without any supplementation, while the second, third, fourth, fifth, and sixth groups: basal diet supplemented with 50, 75, 100, 125, and 150 (µg/g), respectively. The in vitro study showed that the OLP has good antibacterial activity in the concentration-dependent matter; OLP 175 µg/mL inhibited the tested bacteria in the zones range of (0.8-4 cm), Klebsiella Pneumonaie (KP) was the most resistant bacteria to OLP concentration. The antioxidant activity of OLP increased with increasing the concentration of OLP compared to ascorbic acid, where OLP 175 µg/mL scavenged 91% of 2, 2-diphenyl-1-picrylhydrazyl (DPPH) free radicals compared to 93% scavenging activity of ascorbic acid. Broiler chickens fed diets with OLP had significantly (P < 0.05) higher body weight (BW) and body weight growth (BWG) than the control birds. The treatment with OLP significantly reduced the feed intake (FI) and feed conversion rate (FCR) when compared to control. Groups supplemented with OLP showed decreased abdominal fat deposition and a significant increase in the net carcass and breast muscle weight. OLP improved birds' blood parameters in comparison with control birds. All pathogenic bacterial numbers in caecal samples were decreased with elevating OLP levels, but the cecal Lactobacillus bacterial count was increased. In conclusion, OLP supplementation improved broiler chickens' performance, carcass traits, and blood parameters. Moreover, OLP improved birds' liver functions (reduced Alanine transaminase [ALT] and aspartate aminotransferase [AST] levels) in comparison with control. In addition, OLP promoted the antioxidant status, minimized the harmful microbial load, and increased beneficial bacterial count in the cecal contents of broilers.
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Hypervirulent Klebsiella pneumoniae (hvKp) is a new emerging variant of K. pneumoniae that is increasingly reported worldwide. The variant hvKp is known to cause severe invasive community-acquired infections such as metastatic meningitis, pyogenic liver abscesses (PLA) and endophthalmitis, but its role in hospital-acquired infections (HAIs) is little known. The aim of this study was to evaluate the prevalence of hvKp among hospital-acquired (HA) K. pneumoniae infections in the intensive care unit (ICU) and to compare between hvKp and classical K. pneumoniae (cKP) regarding antimicrobial resistance pattern, virulence and molecular characteristics. The study was cross-sectional and included 120 ICU patients suffering from HA K. pneumoniae infections between January and September 2022. K. pneumoniae isolates were subjected to antimicrobial susceptibility testing and detection of extended-spectrum-ß-lactamase (ESBL) production by the Phoenix 100 automated microbiology system, string test, biofilm formation, serum resistance assay, and detection of virulence-associated genes (rmpA, rmpA2, magA, iucA) and capsular serotype-specific genes (K1, K2, K5, K20, K57) by polymerase chain reaction (PCR). Of 120 K. pneumoniae isolates, 19 (15.8%) were hvKp. The hypermucoviscous phenotype was more significantly detected in the hvKp group than in the cKP group (100% vs. 7.9%, p ≤ 0.001). The rate of resistance to different antimicrobial agents was significantly higher in the cKP group than that in the hvKp group. Fifty-three strains were identified as ESBL-producing strains, which was more frequent in the cKP group than in the hvKp group (48/101 [47.5%] vs. 5/19 [26.3%], respectively, p ≤ 0.001). The hvKP isolates were highly associated with moderate and strong biofilm formation than cKP isolates (p = 0.018 and p = 0.043 respectively). Moreover, the hvKP isolates were highly associated with intermediate sensitivity and re sistance to serum in the serum resistance assay (p = 0.043 and p = 0.016 respectively). K1, K2, rmpA, rmpA2, magA and iucA genes were significantly associated with hvKp (p ≤ 0.001, 0.004, <0.001, <0.001, 0.037 and <0.001, respectively). However, K5, K20 and K57 were not associated with hvKp. The hvKp strains have emerged as a new threat to ICU patients because of their ability to cause more severe and life-threatening infections than cKP. The string test alone as a laboratory test for screening of hvKp has become insufficient. Recently, hvKp was defined as hypermucoviscous- and aerobactin-positive. It is important to improve the awareness towards the diagnosis and management of hvKp infections.
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Background: Otitis externa and otitis media are two types of ear infections that affect people of all ages, although they are more common in newborns and young children. Antibiotic usage, healthcare, and advanced age all play a role in the development of this illness. Methods: Fifty-eight patients with various kinds of infections of the ears were voluntary patients attending the outpatient clinics of the Prince Mutaib Bin Abdulaziz Hospital in Sakaka, Al Jouf, Saudi Arabia, examined to evaluate the role of bacteria and the likely significance of plasmids in their antibiotic resistance as ear infectious agents. Results: Staphylococcus aureus and Pseudomonas aeruginosa are the most prevalent bacteria found in ear infections. The greatest number of major bacterial isolates were S. aureus (54%), followed by P. aeruginosa (13%), whereas a smaller number of isolates (3%) were from Streptococcus pyogenes, Bacillus subtilis, and Proteus vulgaris, respectively. Mixed growth was noted in 3.4% of instances. The isolation rate for Gram-positive organisms was 72%, while the rate for Gram-negative species was 28%. All the isolates had DNA greater than 14 kilobases. Hind III analysis of the plasmid DNA extracted from the resistant strains of ear infection demonstrated that antibiotic-resistance plasmids were extensively dispersed. Exotoxin A PCR amplification indicated 396 pb PCR-positive DNA for all identified samples, with the exception of three strains for which no band was observed. Patients in the epidemiological study ranged in number, but all were linked together for the purposes of the study because of their shared epidemiological characteristics. Conclusion: Vancomycin, linezolid, tigecycline, rifampin, and daptomycin are all antibiotics that have been shown to be effective against S. aureus and P. aeruginosa. Microbiological pattern evaluation and antibiotic sensitivity patterns of the microorganisms providing empirical antibiotics are becoming increasingly crucial to minimize issues and the development of antibiotic-resistant strains.
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A strain of Bacillus cereus was isolated from the Saudi Red Sea coast and identified based on culture features, biochemical characteristics, and phylogenetic analysis of 16S rRNA sequences. EPSR3 was a major fraction of exopolysaccharides (EPS) containing no sulfate and had uronic acid (28.7%). The monosaccharide composition of these fractions is composed of glucose, galacturonic acid, and arabinose with a molar ratio of 2.0: 0.8: 1.0, respectively. EPSR3 was subjected to antioxidant, antitumor, and anti-inflammatory activities. The results revealed that the whole antioxidant activity was 90.4 ± 1.6% at 1500 µg/mL after 120 min. So, the IC50 value against DPPH radical found about 500 µg/mL after 60 min. While using H2O2, the scavenging activity was 75.1 ± 1.9% at 1500 µg/mL after 60 min. The IC50 value against H2O2 radical found about 1500 µg/mL after 15 min. EPSR3 anticytotoxic effect on the proliferation of (Bladder carcinoma cell line) (T-24), (human breast carcinoma cell line) (MCF-7), and (human prostate carcinoma cell line) (PC-3) cells. The calculated IC50 for cell line T-24 was 121 ± 4.1 µg/mL, while the IC50 for cell line MCF-7 was 55.7 ± 2.3 µg/mL, and PC-3 was 61.4 ± 2.6 µg/mL. Anti-inflammatory activity was determined for EPSR3 using different methods as Lipoxygenase (LOX) inhibitory assay gave IC50 12.9 ± 1.3 µg/mL. While cyclooxygenase (COX-2) inhibitory test showed 29.6 ± 0.89 µg /mL. EPSR3 showed potent inhibitory activity against methicillin-resistant Staphylococcus aureus (MRSA) and coagulase-negative staphylococci. The exposure times of EPSR3 for the complete inhibition of cell viability of methicillin resistant S. aureus was found to be 5% at 60 min. Membrane stabilization inhibitory gave 35.4 ± 0.67 µg/mL. EPSR3 has antitumor activity with a reasonable margin of safety. The antitumor activity of EPSR3 may be attributed to its content from uronic acids with potential for cellular antioxidant and anticancer functional properties.
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Cancer and bacterial infection are the most serious problems threatening people's lives worldwide. However, the overuse of antibiotics as antibacterial and anticancer treatments can cause side effects and lead to drug-resistant bacteria. Therefore, developing natural materials with excellent antibacterial and anticancer activity is of great importance. In this study, different concentrations of chitosan (CS), graphene oxide (GO), and graphene oxide-chitosan composite (GO-CS) were tested to inhibit the bacterial growth of gram-positive (Bacillus cereus MG257494.1) and gram-negative (Pseudomonas aeruginosa PAO1). Moreover, we used the most efficient natural antibacterial material as an anticancer treatment. The zeta potential is a vital factor for antibacterial and anticancer mechanism, at pH 3-7, the zeta potential of chitosan was positive while at pH 7-12 were negative, however, the zeta potential for GO was negative at all pH values, which (p < 0.05) increased in the GO-CS composite. Chitosan concentrations (0.2 and 1.5%) exhibited antibacterial activity against BC with inhibition zone diameters of 4 and 12 mm, respectively, and against PAO1 with 2 and 10 mm, respectively. Treating BC and PAO1 with GO:CS (1:2) and GO:CS (1:1) gave a larger (p < 0.05) inhibition zone diameter. The viability and proliferation of HeLa cells treated with chitosan were significantly decreased (p < 0.05) from 95.3% at 0% to 12.93%, 10.33%, and 5.93% at 0.2%, 0.4%, and 0.60% concentrations of chitosan, respectively. Furthermore, CS treatment increased the activity of the P53 protein, which serves as a tumor suppressor. This study suggests that chitosan is effective as an antibacterial and may be useful for cancer treatment.