Search

Acanthospermum hispidum DC (Asteraceae), a traditional medicinal plant, plays a role as an alternative remedy for various diseases, such as bacterial and viral infections, jaundice, malaria, fever, gastrointestinal disorders, headache, convulsions, and snake bites. Flavonoids, alkaloids, saponins, tannins, terpenes, steroids, and cardioactive glycosides are the distinct classes of metabolites in the plant. Although A. hispidum was suggested as a promising antitumor phytomedicine, no studies identified its potential cytotoxic components. In this study, the cytotoxic compounds of A. hispidum were isolated using chromatographic techniques guided by in vitro MTT cytotoxicity assay against selected cancer cell lines; breast cancer (MCF7), colorectal adenocarcinoma (HT29), and hepatoblastoma (HepG2). The selective index (SI) was assessed on MRC5 (Normal human fetal lung fibroblast) cell line. The dichloromethane fraction (DCM) showed remarkable cytotoxic activity against MCF7 and HT29 (%Cell viability; 46.15 and 60.5, respectively). Hence, the main bioactive fraction from DCM was purified to afford two phytosterols; stigmasterol (1) and β-sitosterol (2), which were identified by 1-D and 2-D NMR spectroscopy. Cytotoxic evaluation of 1 and 2 revealed that β-sitosterol showed better selective cytotoxicity against MCF7 and HT29 (IC50 4.07 μg/mL, SI 2.63; IC50 4.52 μg/mL, SI 2.37) compared to stigmasterol (IC50 5.43 μg/mL, SI 1.38; IC50 4.21 μg/mL, SI 1.78), respectively. Bioinformatic assessments of drug-likeness and ADMET properties demonstrated that most criteria were obeyed by the investigated compounds except for their poor solubility, which recommended the preparation of special dosage forms, such as nanoformulation to enhance their oral bioavailability. Swiss Target prediction indicated that nuclear receptors represent the main target class (40%). Whereas caspase-3 stimulant activity (a key enzyme in apoptosis) was predicted by the PASS prediction tool as a potential anticancer mechanism. Our study suggests A. hispidum as a potential source of bioactive phytosterols and as a chemopreventive medicinal plant.

Background: Type 2 diabetes mellitus (T2DM) is defined by a wide variety of metabolic abnormalities, persistent hyperglycemia, and a slew of other complications. Catharanthus roseus L. (apocyanaceae), remarkably notable as Vinca Rosea, appears to be the source of the active component hirsutidin, which is reported in various diseases. Objective: The study intended to appraise the antidiabetic capability of hirsutidin in a high-fat diet (HFD) and streptozotocin (STZ) induced diabetes in experimental rats. Materials and methods: An experimental rodent T2DM model was elicited by consuming an HFD regimen with STZ 50 mg/kg, i.p. dose formulated in a 0.1 M cold citrate buffer (pH 4.5). The test drug hirsutidin (10 and 20 mg/kg) and the standard drug glimeclamide (5 mg/kg) were administered daily for six weeks. The efficacy of hirsutidin was observed on several diabetes parameters. The average body weight and an array of biochemical markers were determined, including blood glucose, insulin, dyslipidemia (lipid profile), total protein (TP), liver injury [aspartate aminotransferase (AST), alanine aminotransferase (ALT)], inflammation [IL-6, IL-1β, tumor necrosis factor-α (TNF-α)], oxidative stress [malondialdehyde (MDA)] and antioxidant status [catalase (CAT), glutathione (GSH), and superoxide dismutase (SOD)]. In addition, the concentrations of leptin, adiponectin, and resistin were also assessed. Also, molecular docking studies were undertaken to investigate critical targets associated with diabetes, including TNF-α, insulin, adiponectin, and leptin. Results: Diabetes induction with HFD/STZ resulted in hyperglycemia (significantly reduced blood glucose and increased insulin level), dyslipidemia (significantly reduced TC, TG and increased HDL), total protein (significantly reduced), oxidative stress and antioxidant status (significantly reduced MDA and increased CAT, SOD and GSH levels), inflammation (significantly decreased IL-6, IL-1β, TNF-α), liver damage (significantly reduced AST, ALT), and specific hormones such as adiponectin, leptin significantly improved and resistin significantly reduced as evidenced by biochemical data in this study. Intermolecular interactions of ligands and docking score, hirsutidin proteins TNF-α (2AZ5), Insulin (4IBM), Adiponectin (6KS1), Leptin (7Z3Q) with binding energy of -6.708, -7.674, -7.2 and -7.547 Kcal/mol. Conclusion: Hirsutidin may have an evidential hypoglycemic outcome and may exhibit potent antidiabetic activity in HFD/STZ-induced T2DM in rats. Treatment with hirsutidin significantly improved glycemic control, lipid metabolism, oxidative stress, inflammation, and liver function. Additionally, it normalized dysregulated levels of adiponectin, leptin, and resistin. Molecular docking confirmed its strong binding affinity to key diabetic targets.

AbstractEmergent records propose that Aspergillus niger endophytic fungus is a vital source for various bioactive molecules possessing many biological properties. The current study was designed to inspect the antibacterial and anti-Toxoplasma potentials of Ficus retusa-derived endophytic fungi. After isolation and identification (using 18S rRNA gene sequencing) of A. niger endophytic fungus, LC/MS was utilized for identification and authentication of the chemical profile of the A. niger endophyte extract. Then, the fungal extract was assessed for its antibacterial and antibiofilm activities against Klebsiella pneumoniae clinical isolates. Additionally, its efficacy against Toxoplasma gondii was elucidated in vivo. The fungal extract displayed antibacterial activity against K. pneumoniae isolates with minimum inhibitory concentration values of 64–512 µg/mL. It also possessed a membrane potential dissipating effect using flow cytometry. Moreover, it formed distorted cells with rough surfaces and deformed shapes using a scanning electron microscope (SEM). Regarding its antibiofilm activity, it resulted in a dysregulation of the genes encoding biofilm formation (fimH, mrkA and mrkD) using qRT-PCR in nine K. pneumoniae isolates. The in vivo anti-Toxoplasma potential was demonstrated by decreasing the mortality rate of mice and reducing the tachyzoites’ count in the peritoneal fluids and liver impression smears of mice. In addition, the deformities of the parasite decreased, as revealed by SEM and the inflammation in tissues diminished. Thus, A. niger endophytic fungi could be a valuable source of antibacterial and anti-Toxoplasma compounds.

The inflammatory reaction is induced by several factors like stimulation of different enzymes, oxidative stress, and production of various proinflammatory mediators. Here, we elucidated the phytochemical profile of Euphorbia milii ethanol extract (EMEE) then, we studied its anti-inflammatory potential using a carrageenan-induced paw edema model in rats. It was found that the average paw edoema weight substantially declined (p

The increasing rates of morbidity and mortality owing to bacterial infections, particularly Staphylococcus aureus have necessitated finding solutions to face this issue. Thus, we elucidated the phytochemical constituents and antibacterial potential of Cleome droserifolia extract (CDE). Using LC-ESI-MS/MS, the main phytoconstituents of CDE were explored, which were kaempferol-3,7-O-bis-alpha-L-rhamnoside, isorhamnetin, cyanidin-3-glucoside, kaempferide, kaempferol-3-O-alpha-L-rhamnoside, caffeic acid, isoquercitrin, quinic acid, isocitrate, mannitol, apigenin, acacetin, and naringenin. The CDE exerted an antibacterial action on S. aureus isolates with minimum inhibitory concentrations ranging from 128 to 512 µg/mL. Also, CDE exhibited antibiofilm action using a crystal violet assay. A scanning electron microscope was employed to illuminate the effect of CDE on biofilm formation, and it considerably diminished S. aureus cell number in the biofilm. Moreover, qRT-PCR was performed to study the effect of CDE on biofilm gene expression (cna, fnbA, and icaA). The CDE revealed a downregulating effect on the studied biofilm genes in 43.48% of S. aureus isolates. Regarding the in vivo model, CDE significantly decreased the S. aureus burden in the liver and spleen of CDE-treated mice. Also, it significantly improved the mice’s survival and substantially decreased the inflammatory markers (interleukin one beta and interleukin six) in the studied tissues. Furthermore, CDE has improved the histology and tumor necrosis factor alpha immunohistochemistry in the liver and spleen of the CDE-treated group. Thus, CDE could be considered a promising candidate for future antimicrobial drug discovery studies.

Owing to the spread of resistance between pathogenic bacteria, searching for novel compounds with antibacterial activity is essential. Here, we investigated the potential antibacterial activity of Greek clover or Trigonella foenum-graecum herb extract on Salmonella typhimurium clinical isolates. The chemical profile of the herb was initially determined using LC-ESI-MS/MS, which explored 36 different compounds. Interestingly, the fenugreek extract possessed antibacterial action in vitro with minimum inhibitory concentrations of 64 to 512 µg/mL. The potential mechanism of action was studied by elucidating the effect of the fenugreek extract on the membrane properties of S. typhimurium bacteria, including the inner and outer membrane permeability and membrane integrity. Remarkably, the fenugreek extract had detrimental effects on the membrane properties in 40–60% of the isolates. Moreover, the in vivo antibacterial action was studied using a gastrointestinal infection model with S. typhimurium bacteria. Interestingly, the fenugreek extract (200 mg/kg) improved the infection outcomes in the tested mice. This was represented by the noteworthy decrease (p < 0.05) in the bacterial count in the small intestine and caecum tissues. The survival rate of the fenugreek-extract-treated mice significantly increased compared to the S. typhimurium-infected group. Additionally, there was an improvement in the histological and immunohistochemical features of tumor necrosis factor-alpha. In addition, using an ELISA and qRT-PCR, there was an improvement in the proinflammatory and oxidative stress markers in the fenugreek-extract-treated group. Consequently, fenugreek extract should be investigated further on other food pathogens.

IntroductionThe emergence of bacterial pathogens in environmental hosts represents a major risk to public health. This study aimed at characterizing seven novel environmental strains of K. quasipneumoniae using a genomic approach which was misidentified by phenotypic methods in a previous batch of 27 species thought to be K. pneumoniae.MethodsWhole-genome sequencing was performed using the Illumina platform, and the generated raw reads were de novo assembled. Comparative genomic, resistome, virulome, mobilome, and phylogeny were then investigated using dierent bioinformatics tools.ResultsSix strains were identified as K. quasipneumoniae subsp similipneumoniae and one as K. quasipneumoniae subsp. quasipneumoniae. All isolates were resistant to ampicillin, cephalexin, and amoxicillin-clavulanic acid and harbored the fosA, blaOKP types, oqxB, and oqxA genes. One isolate additionally harbored a gene cassettes consisting of blaSHV−1, blaOXA−1, aac(6′)-Ib-cr, catB genes. The aminoglycoside-modifying enzyme gene aph(3”)-Ia was bracketed by two insertion elements. Plasmid analyses showed that IncFIBK was the most prevalent plasmid, circulating in six isolates, while one isolate exhibited seven different plasmids. The isolates have virulence genes responsible for capsule formation, lipopolysaccharide, iron uptake aerobactin (iutA), salmochelins (iroE, iroN), enterobactin siderophore, adherence, and biofilm formation (mrkA, mrkB, mrkC, mrkD, mrkF, and mrkH).ConclusionOur study highlights the ecology and transmission of K. quasipneumoniae (which have the ability to disseminate to other environmental sources including animals) outside the clinical setting and the contribution of water, vegetables, and table surfaces as potential reservoirs of farm-to-fork transmission of disease via local markets in Khartoum, Sudan.

Background: The continuous rise in the number of patients suffering from Helicobacter pylori is probably due to the changes in modern life. Nowadays, patients suffering from gastrointestinal problems are diagnosed through invasive and non-invasive techniques. The choice of a diagnostic test is influenced by factors such as the tests' sensitivity and specificity, the clinical conditions, and the cost-effectiveness of the testing strategy. This study aimed to compare molecular detection methods of H. pylori by polymerase chain reaction (PCR) targeting the 16S rRNA, ureA and glmM genes with an invasive histopathological technique. Methods: 290 gastric biopsies were collected using gastrointestinal endoscopy from patients with gastritis symptoms in different hospitals in Khartoum state. Two gastric biopsies were collected from each patient for PCR and histopathology. Results: A total of 103 (35.5%) samples were positive by histopathological examination, 88 (30.3%) by 16S rRNA, 39 (13.4%) by glmM gene, and 56 (19.3%) by ureA gene. The highest sensitivity was observed in 16S rRNA (46.6%), followed by glmM (24.3%) and ureA (23.3%). While the best specificity was observed in glmM gene (92.5%), followed by ureA (82.3%) and 16S rRNA (78.6%). Conclusion: PCR test targeting the 16S rRNA gene exhibited the best results for molecular detection of H. pylori compared to other genes.

Neuroinflammation is a serious immunomodulatory complex disorder that causes neurological and somatic ailments. The treatment of brain inflammation with new drugs derived from natural sources is a significant therapeutic goal. Utilizing LC-ESI-MS/MS analysis, the active constituents of Salvadora persica extract (SPE) were identified tentatively as exerting antioxidant and anti-inflammatory effects in natural medicine. Herein, we determined the antiviral potential of SPE against herpes simplex virus type 2 (HSV-2) using the plaque assay. HSV-2 is a neurotropic virus that can cause neurological diseases. SPE exhibited promising antiviral potential with a half-maximal cytotoxic concentration (CC50) of 185.960 ± 0.1 µg/mL and a half-maximal inhibitory concentration (IC50) of 8.946 ± 0.02 µg/mL. The in vivo study of the SPE impact against lipopolysaccharide (LPS)-induced neuroinflammation was performed using 42 mice divided into seven groups. All groups were administered LPS (0.25 mg/kg) intraperitoneally, except for the normal and SPE groups 1 and 2. Groups 5, 6, and 7 received 100, 200, and 300 mg/kg SPE. It was revealed that SPE inhibited acetylcholinesterase in the brain. It increased superoxide dismutase and catalase while decreasing malondialdehyde, which explains its antioxidative stress activity. SPE downregulated the gene expression of the inducible nitric oxide synthase, as well as the apoptotic markers (caspase-3 and c-Jun). In addition, it decreased the expression of the proinflammatory cytokines (interleukin-6 and tumor necrosis factor-alpha). Mice administered SPE (300 mg/kg) with LPS exhibited normal neurons in the cerebral cortices, hippocampus pyramidal layer, and cerebellum, as determined by the histopathological analysis. Therefore, using S. persica to prevent and treat neurodegeneration could be a promising new therapeutic strategy to be explored.

Diseases and infections of the respiratory tract are common global causes of morbidity and mortality. Our study attempts to elucidate a novel remedy for respiratory ailments, in addition to identifying and quantifying the metabolites of Saussurea costus root extract (SCRE) using HPLC. Then, in vitro antiviral and in vivo lung protective effects were elucidated. The in vitro antiviral potential of SCRE was analyzed via plaque assay against the low pathogenic human coronavirus (HCoV-229E) and human influenza virus (H1N1). The value of the half maximal inhibitory concentrations (IC50) of SCRE against HCoV-229E and H1N1 influenza virus were 23.21 ± 1.1 and 47.6 ± 2.3 µg/mL, respectively. SCRE showed a histological improvement, namely a decrease in inducible nitric oxide synthase (iNOS) and caspase-3 immunoexpression in in vivo cyclophosphamide (CP)-induced acute lung injury (ALI). Moreover, there was a considerable decline in microRNA-let-7a gene expression and a significant rise in heme oxygenase-1 (HO-1) gene expression, with a marked decrease in the malondialdehyde (MDA) level. Molecular docking studies revealed that the major constituents of SCRE have a good affinity for caspase-3, HO-1, and iNOS proteins. In conclusion, a traditional plant SCRE could be a promising source of novel therapeutic agents for treating and protecting respiratory tract diseases. More future investigations should be carried out to reveal its efficacy clinically.

HPLC-UV was used to compare the major constituents of two Pelargonium × hortorum cultivars and Pelargonium sidoides root extract. It revealed the presence of catechin and gallic acid in high concentrations and the absence of umckalin in P. × hortorum root extracts. The antibacterial activity of these extracts was screened against 19 Pseudomonas aeruginosa clinical isolates. P. × hortorum root extracts showed the lowest MIC values (512–1024 µg/mL). This activity was concluded to be attributable to the high concentrations of catechin and gallic acid. The anti-biofilm activity of catechin, gallic acid, and their combination was examined by a crystal violet assay. The combination reduced the percentage of strong and moderate biofilm-forming isolates from 52.63% to 5.26%. The impact on lasI and lasR genes expression using qRT-PCR and simultaneous docking against LasR protein was explored. The combination downregulated lasI and lasR gene expression in eight and six P. aeruginosa isolates, respectively, and showed the greatest docking score. Additionally, the in vivo protection capability of this combination in infected mice showed enhancement in the survival rate. Our study revealed the potential biofilm and quorum-sensing-inhibitory activity of the catechin and gallic acid combination as a novel alternative to inhibit bacterial pathogenicity.

Klebsiella pneumoniae is an emergent pathogen causing respiratory tract, bloodstream, and urinary tract infections in humans. This study defines the genomic sequence data, genotypic and phenotypic characterization of K. pneumoniae clinically isolated from Al-Kharj, KSA. Whole-genome analysis of four K. pneumoniae strains was performed, including de novo assembly, functional annotation, whole-genome-phylogenetic analysis, antibiotic-resistant gene identification, prophage regions, virulent factor, and pan-genome analysis. The results showed that K6 and K7 strains were MDR and ESBL producers, K16 was an ESBL producer, and K8 was sensitive to all tested drugs except ampicillin. K6 and K7 were identified with sequence type (ST) 23, while K16 and K8 were identified with STs 353 and 592, respectively. K6 and K7 were identified with the K1 (wzi1 genotype) capsule and O1 serotype, while K8 was identified with the K57 (wzi206 genotype) capsule and O3b. K6 isolates harbored 10 antimicrobial resistance genes (ARGs) associated with four different plasmids; the chloramphenicol acetyltransferase (catB3), blaOXA-1 and aac(6′)-Ib-cr genes were detected in plasmid pB-8922_OXA-48. K6 and K7 also carried a similar gene cassette in plasmid pC1K6P0122-2; the gene cassettes were the trimethoprim-resistant gene (dfrA14), integron integrase (IntI1), insertion sequence (IS1), transposase protein, and replication initiation protein (RepE). Two hypervirulent plasmids were reported in isolates K6 and K7 that carried synthesis genes (iucA, iucB, iucC, iucD, and iutA) and iron siderophore genes (iroB, iroC, iroD, and iroN). The presence of these plasmids in high-risk clones suggests their dissemination in our region, which represents a serious health problem.

Background. Pulmonary aspergillosis is a lung infection caused by Aspergillus spp., which can cause severe illnesses in immunocompromised patients with underlying lung disease or who have asthma and inhale their spores. This study aimed to screen the antifungal susceptibility of Aspergillus spp. isolated from patients with underlying pulmonary infections and characterize the isolates using PCR and sequencing. Method. Three hundred and eighty-four sputum or bronchoalveolar lavage samples were collected and processed for the isolation and identification, and characterization of Aspergillus species and molecular amplification of the ITS1-5.8S-ITS2 region by the PCR and Sanger sequencing method. Antifungal susceptibility tests for itraconazole and voriconazole were performed using the E-test. Result. The overall results revealed that out of 384 patients, 32 (8.3%) were positive for fungal growth, including 28 (87.5%) Aspergillus spp. The highest resistance rate (100 and 44.4%) was obtained from itraconazole against A. niger and A. fumigatus. In contrast, voriconazole revealed the best activities against all tested fungi compared to itraconazole. All A. flavus were sensitive to voriconazole, while only 54.5% were sensitive to itraconazole. The MICs of E-test for Aspergillus spp were 1.6 ± 1.8 and 0.6 ± 0.93 for itraconazole and voriconazole, respectively. Conclusions. The prevalence of aspergillosis was high, with a significant association with underlying lung diseases. Voriconazole was the drug of choice for isolated fungi.

Background: The continuous rise in the number of patients suffering from Helicobacter pylori is probably due to the changes in modern life. Nowadays, patients suffering from gastrointestinal problems are diagnosed through invasive and non-invasive techniques. The choice of a diagnostic test is influenced by factors such as the tests' sensitivity and specificity, the clinical conditions, and the cost-effectiveness of the testing strategy. This study aimed to compare molecular detection methods of H. pylori by polymerase chain reaction (PCR) targeting the 16S rRNA, ureA and glmM genes with an invasive histopathological technique. Methods: 290 gastric biopsies were collected using gastrointestinal endoscopy from patients with gastritis symptoms in different hospitals in Khartoum state. Two gastric biopsies were collected from each patient for PCR and histopathology. Results: A total of 103 (35.5%) samples were positive by histopathological examination, 88 (30.3%) by 16S rRNA, 39 (13.4%) by glmM gene, and 56 (19.3%) by ureA gene. The highest sensitivity was observed in 16S rRNA (46.6%), followed by glmM (24.3%) and ureA (23.3%). While the best specificity was observed in glmM gene (92.5%), followed by ureA (82.3%) and 16S rRNA (78.6%). Conclusion: PCR test targeting the 16S rRNA gene exhibited the best results for molecular detection of H. pylori compared to other genes.

Background: The continuous rise in the number of patients suffering from Helicobacter pylori is probably due to the changes in modern life. Nowadays, patients suffering from gastrointestinal problems are diagnosed through invasive and non-invasive techniques. The choice of a diagnostic test is influenced by factors such as the tests' sensitivity and specificity, the clinical conditions, and the cost-effectiveness of the testing strategy. This study aimed to compare molecular detection methods of H. pylori by polymerase chain reaction (PCR) targeting the 16S rRNA, ureA and glmM genes with an invasive histopathological technique. Methods: 290 gastric biopsies were collected using gastrointestinal endoscopy from patients with gastritis symptoms in different hospitals in Khartoum state. Two gastric biopsies were collected from each patient for PCR and histopathology. Results: A total of 103 (35.5%) samples were positive by histopathological examination, 88 (30.3%) by 16S rRNA, 39 (13.4%) by glmM gene, and 56 (19.3%) by ureA gene. The highest sensitivity was observed in 16S rRNA (46.6%), followed by glmM (24.3%) and ureA (23.3%). While the best specificity was observed in glmM gene (92.5%), followed by ureA (82.3%) and 16S rRNA (78.6%). Conclusion: PCR test targeting the 16S rRNA gene exhibited the best results for molecular detection of H. pylori compared to other genes.