Flavonostilbenes natural hybrids from Rhamnoneuron balansae as potential antitumors targeting ALDH1A1: molecular docking, ADMET, MM-GBSA calculations and molecular dynamics studies.

Several studies have linked Cancer stem cells (CSCs) to cancer resistance development to chemotherapy and radiotherapy. ALDH1A1 is a key enzyme that regulates the gene expression of CSCs and creates an immunosuppressive tumor microenvironment. It was reported that quercetin and resveratrol were among the inhibitors of ALDH1A1. In early 2022, it was reported that new 11 flavonostilbenes (rhamnoneuronal D-N) were isolated from Rhamnoneuron balansae as potential antiaging natural products. Rhamnoneuronal H (5) could be envisioned as a natural hybrid of quercetin and resveratrol. It was therefore hypothesized that 5 and its analogous isolates rhamnoneuronal D-G (1-4) and rhamnoneuronal I-N (6-11) would have potential ALDH1A1 inhibitory activity. To this end, all isolates were subjected to molecular docking, MM-GBSA, ADMET, and molecular dynamics simulations studies to assess their potential as new leads for cancer treatment targeting ALDH1A1. In silico findings revealed that natural hybrid 5 has a similar binding affinity, judged by MM-GBSA, to the ALDH1A1 active site when compared to the co-crystalized ligand (-64.71 kcal/mole and -64.12 kcal/mole, respectively). Despite having lesser affinity than that of the co-crystalized ligand, the rest of the flavonostilbenes, except 2-4, displayed better binding affinities (-37.55 kcal/mole to -58.6 kcal/mole) in comparison to either resveratrol (-34.44 kcal/mole) or quercetin (-36.48 kcal/mole). Molecular dynamic simulations showed that the natural hybrids 1, 5-11 are of satisfactory stability up to 100 ns. ADMET outcomes indicate that these hybrids displayed acceptable properties and hence could represent an ideal starting point for the development of potent ALDH1A1 inhibitors for cancer treatment.Communicated by Ramaswamy H. Sarma.

Prevalence of vulvovaginal candidiasis among pregnant women in Africa: A systematic review and meta-analysis.

INTRODUCTION: Vulvovaginal candidiasis (VVC) is a yeast infection of the vulva, which is caused by Candida species and affects women worldwide. Pregnant women are more vulnerable to VVC due to certain risks. Moreover, their offspring are also exposed to the risk of preterm birth. In this context, ascertaining the burden of VVC is of paramount importance and this meta-analysis was conducted to estimate the occurrence of VVC among pregnant women in Africa. METHODOLOGY: Database search was carried out through PubMed, Scopus, Science-Direct, and Google Scholar from the date of inception until December 2020. All the studies on the prevalence of VVC among African pregnant women were included in the analysis. The pooled prevalence was estimated based on the Random-effect model DerSimonian-Laird approach with Freeman- Tukey double arcsine transformed proportion. Heterogeneity was assessed using I2 test and subsequently explored using subgroup and meta-regression analysis. RESULTS: A total of Sixteen records having a sample size 4,185 were included in this study. The overall prevalence of VVC was pooled at 29.2% (CI 95%: 23.4 - 33.0). Subgroup analysis revealed a higher prevalence in Eastern Africa, followed by Western Africa and North Africa (35%, 28%, and 15% respectively). Moderator analysis indicated that the studies that used advanced methods of detection had a higher prevalence (p = 0.048). In addition, the large sample size was associated with higher prevalence (p ≤ 0.001). No other moderators were found to be statistically significant. CONCLUSIONS: The overall prevalence of VVC among African pregnant women is comparable to other studies worldwide. However, appropriate identification techniques and larger sample size could likely be associated with an increased prevalence. Our findings necessitate the need for further investigations to determine the geographical distribution of VVC across African regions.

Detection of antifungal drug-resistant and ERG11 gene mutations among clinical isolates of Candida species isolated from Khartoum, Sudan.

Background:  Candida species are one of the most important opportunistic fungal pathogens that cause both superficial and systemic infections, especially in immunocompromised individuals. Considering the sharp increase in the rate of  Candida infections, and resistance to commonly used antifungal agents in the last decades; this study was conducted to determine the rate of resistance among clinical isolates of  Candida species, and to characterize some of the resistant genes among resistant isolates collected in Khartoum.  Methods: This is a cross-sectional laboratory-based study included 100 pre-screened  Candida species isolates from Khartoum state hospitals. Chromogenic media was used for  Candida isolation and/or identification. The standard disc diffusion method was performed to investigate the susceptibility to fluconazole, itraconazole, and amphotericin. Following genomic DNA extraction, the entire  ERG11 gene was amplified from some C. albicans resistant isolates, sequenced, and further analyzed. Results: Out of 100 clinical isolates collected, 51% were  C. albicans, followed by  C. glabrata (31%),  C. krusie (8%),  C. tropicals (5%), and C. dupliniens (5%). Resistance rate was 23% for fluconazole, 4% for itraconazole, while there were no amphotericin resistant isolates detected. C. albicans  ERG11 gene sequence reveals 15 different mutations. Among these, three (D116E, E266D, and V488I) were missense mutations; however, these substitutions do not contribute to fluconazole resistance. Conclusion:  C. albicans was found to be the most common species. Resistance against fluconazole was observed most frequently; however, mutations in ERG11 are unlikely to be the reason behind fluconazole resistance among these isolates.

Characterization of Pathogenic Bacteria Isolated from Sudanese Banknotes and Determination of Their Resistance Profile.

BACKGROUND: Banknotes are one of the most exchangeable items in communities and always subject to contamination by pathogenic bacteria and hence could serve as vehicle for transmission of infectious diseases. This study was conducted to assess the prevalence of contamination by pathogenic bacteria in Sudanese banknotes, determine the susceptibility of the isolated organisms towards commonly used antibiotics, and detect some antibiotic resistance genes. METHODS: This study was carried out using 135 samples of Sudanese banknotes of five different denominations (2, 5, 10, 20, and 50 Sudanese pounds), which were collected randomly from hospitals, food sellers, and transporters in all three districts of Khartoum, Bahri, and Omdurman. Bacterial prevalence was determined using culture-based techniques, and their sensitivity patterns were determined using the Kirby-Bauer disk diffusion method. Genotypic identification was carried out using PCR and 16S rDNA sequencing. Antibiotic resistance genes of some isolates were detected using PCR technique. RESULTS: All Sudanese banknotes were found to be contaminated with pathogenic bacteria. Klebsiella pneumoniae was found to be the most frequent isolate (23%), whereas Bacillus mycoides (15%) was the most abundant Gram-positive isolate. There was a significant relationship between the number of isolates and the banknote denomination with p value <0.05 (the lower denomination showed higher contamination level). Our study has isolated bacteria that are resistant to penicillins and cephalosporins. Multidrug-resistant strains harboring resistant genes (mecA, blaCTX-M, and blaTEM) were also detected. CONCLUSION: All studied Sudanese banknotes were contaminated with pathogenic bacteria, including multidrug-resistant strains, and may play a significant role in the transmission of bacterial infections.

Activity of Aristolochia bracteolata against Moraxella catarrhalis.

A bioassay-guided fractionation of methanol extract of Aristolochia bracteolata whole plant was carried out in order to evaluate its antimicrobial activity and to identify the active compounds in this extract. Antibacterial and antifungal activities of methanol extract against gram-positive, gram-negative, and fungal strains were investigated by the agar disk diffusion method. Among the strains tested, Moraxella catarrhalis and sea urchin-derived Bacillus sp. showed the highest sensitivity towards the methanol extract and hence they are used as test organisms for the bioassay-guided fractionation. From this extract, aristolochic acid 1 (AA-1) has been isolated and has showed the greatest antibacterial activity against both standard strain and clinical isolates of Moraxella catarrhalis with equal minimum inhibitory concentration (MIC) and minimum bactericidal concentration (MBC) values of 25 and 50 µg/mL. Modification of the AA-1 to AA-1 methyl ester completely abolished the antibacterial activity of the compound and the piperonylic acid moiety of AA-1 which suggested that the coexistence of phenanthrene ring and free carboxylic acid is essential for AA-1 antibacterial activity.