Diabetic wound healing of aloe vera major phytoconstituents through TGF-ß1 suppression via in-silico docking, molecular dynamic simulation and pharmacokinetic studies.

To restore the integrity of the skin and subcutaneous tissue, the wound healing process involves a complex series of well-orchestrated biochemical and cellular events. Due to the existence of various active components, accessibility and few side effects, some plant extracts and their phytoconstituents are recognised as viable options for wound healing agents. To find possible inhibitors of diabetic wound healing, four main constituents of aloe vera were identified from the literature. TGF-ß1 and the compounds were studied using molecular docking to see how they interacted with the active site of target protein (PDB ID: 6B8Y). The pharmacokinetics investigation of the aloe emodin with the highest dock score complied with all the Lipinski's rule of five and pharmacokinetics criteria. Conformational change in the docked complex of Aloe emodin was investigated with the Amber simulation software, via a molecular dynamic (MD) simulation. The MD simulations of aloe emodin bound to TGF-ß1 showed the significant structural rotations and twists occurring from 0 to 200 ns. The estimate of the aloe emodin-TGF-ß1 complex's binding free energy has also been done using MM-PBSA/GBSA techniques. Additionally, aloe emodin has a wide range of enzymatic activities since their probability active (Pa) values is >0.700. 'Aloe emodin', an active extract of aloe vera, has been identified as the key chemical in the current investigation that can inhibit diabetic wound healing. Both in-vitro and in-vivo experiments will be used in a wet lab to confirm the current computational findings.Communicated by Ramaswamy H. Sarma.

High prevalence of multidrug resistant ESBL- and plasmid mediated AmpC-producing clinical isolates of Escherichia coli at Maputo Central Hospital, Mozambique.

BACKGROUND: Epidemiological data of cephalosporin-resistant Enterobacterales in Sub-Saharan Africa is still restricted, and in particular in Mozambique. The aim of this study was to detect and characterize extended-spectrum ß-lactamase (ESBL) - and plasmid-mediated AmpC (pAmpC)-producing clinical strains of Escherichia coli at Maputo Central Hospital (MCH), a 1000-bed reference hospital in Maputo, Mozambique. METHODS: A total of 230 clinical isolates of E. coli from urine (n = 199) and blood cultures (n = 31) were collected at MCH during August-November 2015. Antimicrobial susceptibility testing was performed by the disc diffusion method and interpreted according to EUCAST guidelines. Isolates with reduced susceptibility to 3rd generation cephalosporins were examined further; phenotypically for an ESBL-/AmpC-phenotype by combined disc methods and genetically for ESBL- and pAmpC-encoding genes by PCR and partial amplicon sequencing as well as genetic relatedness by ERIC-PCR. RESULTS: A total of 75 isolates with reduced susceptibility to cefotaxime and/or ceftazidime (n = 75) from urine (n = 58/199; 29%) and blood (n = 17/31; 55%) were detected. All 75 isolates were phenotypically ESBL-positive and 25/75 (33%) of those also expressed an AmpC-phenotype. ESBL-PCR and amplicon sequencing revealed a majority of blaCTX-M (n = 58/75; 77%) dominated by blaCTX-M-15. All AmpC-phenotype positive isolates (n = 25/75; 33%) scored positive for one or more pAmpC-genes dominated by blaMOX/FOX. Multidrug resistance (resistance ≥ three antibiotic classes) was observed in all the 75 ESBL-positive isolates dominated by resistance to trimethoprim-sulfamethoxazole, ciprofloxacin and gentamicin. ERIC-PCR revealed genetic diversity among strains with minor clusters indicating intra-hospital spread. CONCLUSION: We have observed a high prevalence of MDR pAmpC- and/or ESBL-producing clinical E. coli isolates with FOX/MOX and CTX-Ms as the major ß-lactamase types, respectively. ERIC-PCR analyses revealed genetic diversity and some clusters indicating within-hospital spread. The overall findings strongly support the urgent need for accurate and rapid diagnostic services to guide antibiotic treatment and improved infection control measures.

Fluoroquinolone, Macrolide, and Ketolide Resistance in Haemophilus parainfluenzae from South Africa.

Fluoroquinolones and ketolides are among the drugs of choice for the treatment of Haemophilus parainfluenzae infections. There has been a report of an emerging fluoroquinolone and telithromycin resistance in H. parainfluenzae isolates from the private sector of KwaZulu-Natal Province of South Africa that necessitates molecular investigation. The aim of this study is to characterize these resistance delineating mutations in genes commonly associated with reduced susceptibility. Ten H. parainfluenzae isolates retrieved from the sputum of 10 patients with H. parainfluenzae pneumonia were subjected to sensitivity testing by the disc diffusion and CLSI broth microdilution methods, polymerase chain reaction (PCR) and DNA sequencing of selected genes associated with resistance were carried out, while repetitive extragenic palindromic PCR (REP-PCR) was used to ascertain clonality. Fluoroquinolone resistance was attributed to the following amino acid substitutions: S84F, D88Y in GyrA, and S84Y/L, S138T, and M198 L change in ParC of the isolates. The plasmid-mediated quinolone resistance gene aac-(6')-Ib-cr was detected for the first time in four isolates of H. parainfluenzae and D420 N change was observed in ParE in one isolate. Macrolide and ketolide resistance were ascribed to the resistance genes mef (A), msr (D), and erm (B) detected in the isolates. REP-PCR analysis showed that the isolates were not clonal. All the observed resistance mechanisms are first reports in Africa. There is an emerging fluoroquinolone and macrolide resistance in H. parainfluenzae in South Africa that is attributable to known/novel resistance mechanisms, necessitating the monitoring of this pathogen as a potential opportunistic pathogen in a country with a high HIV and AIDS prevalence.

An investigation of the antimicrobial and anti-inflammatory activities of crocodile oil.

ETHNOPHARMACOLOGICAL RELEVANCE: Crocodile oil has been used by traditional practitioners world-wide to treat microbial infections and inflammatory conditions. However, the scientific rationale behind its use is not completely understood. This study provides an updated fatty acid profile and novel scientific evidence of the antimicrobial and anti-inflammatory properties of crocodile oil, obtained from the Nile crocodile (Crocodylus niloticus), justifying its use by traditional healers. MATERIALS AND METHODS: The fatty acid content of the oil was determined by gas chromatography and the major fatty acids were identified. A microplate method was used to assess activity of the oil against Staphylococcus aureus, Klebsiella pneumoniae and Candida albicans. The anti-inflammatory activity of the oil was assessed by oral administration and topical application, utilising a mouse model of acute croton oil-induced contact dermatitis. RESULTS: Sixteen fatty acids were identified with oleic, palmitic and linoleic acid being the major components of the oil. The optimal activity of the oil against the bacteria and fungus was obtained with 15% and 6% (w/v) oil respectively. No significant selectivity was observed against the bacterial species, but Candida albicans was more susceptible. The anti-inflammatory assays showed optimal activity at 3h after the oral administration of oil (60.8±5.5%) and at 12h after topical application (57.5±5.9%). This suggested a short duration of action when the oil was orally administered, and a longer duration of action when it was topically applied. CONCLUSIONS: Subsequent studies may be directed towards the investigation of the mechanisms of action of the antimicrobial and anti-inflammatory activities of crocodile oil and its fatty acids.