No abstract

Flavonoids are well-known for their many therapeutic and pharmaceutical effects. In this study, we tested the antibacterial activity of 11 flavonoids extracted from some medicinal plants by the agar diffusion method. Then, we measured their antioxidant activity using the DPPH (2,2'-diphenyl-1-picrylhydrazyl) radical assay and we also tested their acute toxicity effect on mice. The results showed that apigenin-7-O-glucoside was more active against the Gram-positive bacteria and quercetin was more active against the Gram-negative ones. Also, quercetin and diosmin showed the best antioxidant activity. Quercetin, apigenin-7-O-glucoside, luteolin-7-O-glucoside and luteolin-3'-O-glucuronide gave the best acute toxicity values. It can be concluded that quercetin was the most interesting compound for all the tested activities. Also, we observed that the presence or the absence of substitutions in flavonoids influenced significantly the results obtained, whereas the substitution type had a low impact.

Missense variants in the RNA-helicase DHX37 are associated with either 46,XY gonadal dysgenesis or 46,XY testicular regression syndrome (TRS). DHX37 is required for ribosome biogenesis, and this subgroup of XY DSD is a new human ribosomopathy. In a cohort of 140 individuals with 46,XY DSD, we identified 7 children with either 46,XY complete gonadal dysgenesis or 46,XY TRS carrying rare or novel DHX37 variants. A novel p.R390H variant within the RecA1 domain was identified in a girl with complete gonadal dysgenesis. A paternally inherited p.R487H variant, previously associated with a recessive congenital developmental syndrome, was carried by a boy with a syndromic form of 46,XY DSD. His phenotype may be explained in part by a novel homozygous loss-of-function variant in the <i>NGLY1</i> gene, which causes a congenital disorder of deglycosylation. Remarkably, a homozygous p.T477H variant was identified in a boy with TRS. His fertile father had unilateral testicular regression with typical male genital development. This expands the DSD phenotypes associated with DHX37. Structural analysis of all variants predicted deleterious effects on helicase function. Similar to all other known ribosomopathies, the mechanism of pathogenesis is unknown.

We evaluated the effects of polymorphic markers within the b globin gene cluster on HbF expression in two groups. These groups were randomly selected from a survey of HbF distribution in a large population study of unrelated healthy Algerian adults (n=827). The first group contained individuals with normal HbF levels (0.1 ± 0.5%) and the second group contained individuals with raised HbF levels (0.8 ± 2.3%). Of the various polymorphic markers analysed, only the 7309 Gg A?G, the 7158 Gg C?T, the Gg IVS2 TC (TG) 9 AG (TG) 2 (CG) 2 and the 7540 b (AT) 9 T 5 sequence configurations were significantly associated with increased HbF levels. More than 84% of the subjects with elevated HbF levels carried one or several of these four marker configurations, suggesting that the b globin gene cluster exerts a significant effect on HbF expression in healthy individuals.

The aim of the study was to assess the frequency and diversity of carbapenemases and extended-spectrum β-lactamases (ESBL) produced by Escherichia coli isolates from patients hospitalised in the Regional Military Hospital of Constantine (Algeria). E. coli isolates were collected over a 2-year period from patients presenting E. coli infections. Strains with reduced susceptibility to ertapenem and/or positive for ESBL were characterised with regard to antibiotic resistance, bla genes, phylogenetic groups, O25 serotyping, quinolone resistance, repetitive sequence-based polymerase chain reaction (rep-PCR) profiles and multi-locus sequence typing (MLST). Of the 448 isolated E. coli, 94 (20.9 %) were multidrug-resistant. One of them (1.1 %) produced a bla OXA-48 and was identified as a B1 ST5 strain. The transposon bearing this gene was Tn1999.2. This strain was isolated from a patient coming from a border province with Tunisia, where this carbapenemase is endemic. In addition, 84 (18.8 %) isolates among them produced an ESBL with predominance (97.6 %) of bla CTX-M-15, which was coupled with qnr genes in 10.9 %. ESBL-producing strains were mainly detected in phylogroups D and A. They displayed 20 rep-PCR profiles and all the clonally related isolates were of the same sequence type (ST). Ten strains (9.4 %) belonged to the pandemic clone ST131. This study describes for the first time the presence of OXA-48-producing E. coli and the emergence of the intercontinental ST131 bla CTX-15-producing E. coli strains in Algeria.

The objectives of this study were to determine rates, patterns, and mechanisms of antibiotic resistance, and to assess connections between chicken commensal, human commensal, and pathogenic ciprofloxacin-resistant Escherichia coli isolates. All E. coli isolates collected from chickens, their farmers, and patients in the Constantine region (North-east Algeria) were analyzed for bla and plasmid-mediated quinolone resistance (PMQR) gene contents, phylogroups, Rep-PCR profiles, and multilocus sequence types. A high prevalence of resistance to fluoroquinolones (51.4 % to ciprofloxacin) was recorded in avian isolates. Of these, 22.2 % carried the aac(6')-Ib-cr gene, whereas lower resistance levels to these antibiotics were recorded in chicken farmers' isolates. None of the commensal isolates harbored the qnr, qepA, or oqxAB genes. One human pathogenic isolate was ertapenem-resistant and harbored the bla OXA-48 gene, 84 showed an extended-spectrum β-lactamase phenotype, with bla CTX-M-15 gene prevalent in 87.2 % of them. Seventy isolates were resistant to fluoroquinolones, with aac(6')-Ib-cr present in 72.8 %, qnrB in 5.7 %, and qnrS in 10 %. Three Rep-PCR profiles were common to chicken commensal and human pathogenic isolates (phylogroups D and B1; ST21, ST48, and ST471 respectively); one was found in both chicken and chicken-farmer commensal strains (D; ST108), while another profile was identified in a chicken-farmer commensal strain and a human pathogenic one (B1; ST19). These findings suggest clonal and epidemiologic links between chicken and human ciprofloxacin-resistant E. coli isolates and the important role that poultry may play in the epidemiology of human E. coli infections in the Constantine region.

Introduction Just recently, it has been established that the angiotensin-converting enzyme (ACE) insertion/deletion (I/D) polymorphism is linked to the pathogenesis and to the evolution of human cancers. Therefore, the present study was concerned with the investigation of an eventual association between glioma and I/D polymorphism of the ACE gene. Methods The expression of ACE gene was detected by polymerase chain reaction restriction fragment length polymorphism (PCR-RFLP) analysis in 36 Algerian patients with glioma and 195 healthy controls. Results In glioma cases, allelic frequencies and genotypes distribution of the ACE I/D polymorphism were different from controls cases. ACE DD genotype were highly presented in glioma cases (63.9%) than controls (33.8%) and conferred 3.64-fold risk for predisposition in glioma cases (vs ID genotype, p<0.001). Recessive model (ACE II + ID genotypes vs DD) was associated with a 72% reduced risk of glioma (OR = 0.28, 95% CI: 0.13-0.60, p <0.001). Per copy D allele frequency was found higher in glioma cases (79.2%) than in controls (63.3 %), OR = 2.20, 95% CI: 1.20 - 4.03, p = 0.009. Conclusion The obtained data showed that the presence of the D allele might be a risk factor for the development of glioma. Further studies considering different ethnic groups with large samples are required to confirm this finding.

In a majority of individuals with disorders/differences of sex development (DSD) a genetic etiology is often elusive. However, new genes causing DSD are routinely reported and using the unbiased genomic approaches, such as whole exome sequencing (WES) should result in an increased diagnostic yield. Here, we performed WES on a large cohort of 125 individuals all of Algerian origin, who presented with a wide range of DSD phenotypes. The study excluded individuals with congenital adrenal hypoplasia (CAH) or chromosomal DSD. Parental consanguinity was reported in 36% of individuals. The genetic etiology was established in 49.6% (62/125) individuals of the total cohort, which includes 42.2% (35/83) of 46, XY non-syndromic DSD and 69.2% (27/39) of 46, XY syndromic DSD. No pathogenic variants were identified in the 46, XX DSD cases (0/3). Variants in the AR, HSD17B3, NR5A1 and SRD5A2 genes were the most common causes of DSD. Other variants were identified in genes associated with congenital hypogonadotropic hypogonadism (CHH), including the CHD7 and PROKR2. Previously unreported pathogenic/likely pathogenic variants (n = 30) involving 25 different genes were identified in 22.4% of the cohort. Remarkably 11.5% of the 46, XY DSD group carried variants classified as pathogenic/likely pathogenic variant in more than one gene known to cause DSD. The data indicates that variants in PLXNA3, a candidate CHH gene, is unlikely to be involved in CHH. The data also suggest that NR2F2 variants may cause 46, XY DSD.