Type-2 Diabetes Mellitus Individuals Carry Different Periodontal Bacteria

ABSTRACT Objective: To identify etiologic microbiota associated periodontal diseases among diabetes patients and the factors related to the most commonly identified bacteria species. Material and Methods: Periodontal plaque samples from 11 diabetic participants and 13 non-diabetic controls were collected to assess their aerobic and anaerobic bacterial growth. Different distinct colonies were identified by microscopic and 16srDNA sequencing. Pearson's chi-square tests were conducted to examine any association between categorical variables. Results: The diabetic subjects revealed a more intense plaque formation with a mean plaque index of 2.4 compared to 1.8 in non-diabetics. A total of 86 bacteria were isolated from 24 plaque samples, 44 were aerobic, and 42 were anaerobic. Only aerobic isolates, 22 from diabetic patients and 22 from non-diabetic patients, were evaluated in these analyses. Bacillus spp. (B. cereus mainly) and Klebsiella spp. (K. pneumoniae, K. aerogenes, K. oxytoca) were detected markedly higher in non-diabetic individuals than in diabetic subjects (p=0.026 and p=0.021, respectively). Some bacteria were only identified in the dental plaque of diabetic individuals, namely, Bacillus mojavensis, Enterobacter cloacae, Proteus mirabilis, Staphylococcus epidermidis, Staphylococcus hominis, Staphylococcus pasteuri, Streptococcus mutans, and Streptococcus pasteurianus. The presence of acid reflux and jaundice were significantly associated with the most common bacterial isolate, namely Bacillus spp., with the p-values of 0.007 and 0.001, respectively. Conclusion: Type-2 diabetes mellitus is associated with a higher amount of dental plaques. Periodontal plaque samples from diabetic and non-diabetic subjects possess differential microbial communities. Diabetic plaques contain more versatile microbes predominated by gram-positive streptococci and staphylococci.

The epidemiology and estimated etiology of pathogens detected from the upper respiratory tract of adults with severe acute respiratory infections in multiple countries, 2014-2015.

INTRODUCTION: Etiology studies of severe acute respiratory infections (SARI) in adults are limited. We studied potential etiologies of SARI among adults in six countries using multi-pathogen diagnostics. METHODS: We enrolled both adults with SARI (acute respiratory illness onset with fever and cough requiring hospitalization) and asymptomatic adults (adults hospitalized with non-infectious illnesses, non-household members accompanying SARI patients, adults enrolled from outpatient departments, and community members) in each country. Demographics, clinical data, and nasopharyngeal and oropharyngeal specimens were collected from both SARI patients and asymptomatic adults. Specimens were tested for presence of 29 pathogens utilizing the Taqman® Array Card platform. We applied a non-parametric Bayesian regression extension of a partially latent class model approach to estimate proportions of SARI caused by specific pathogens. RESULTS: We enrolled 2,388 SARI patients and 1,135 asymptomatic adults from October 2013 through October 2015. We detected ≥1 pathogen in 76% of SARI patients and 67% of asymptomatic adults. Haemophilus influenzae and Streptococcus pneumoniae were most commonly detected (≥23% of SARI patients and asymptomatic adults). Through modeling, etiology was attributed to a pathogen in most SARI patients (range among countries: 57.3-93.2%); pathogens commonly attributed to SARI etiology included influenza A (14.4-54.4%), influenza B (1.9-19.1%), rhino/enterovirus (1.8-42.6%), and RSV (3.6-14.6%). CONCLUSIONS: Use of multi-pathogen diagnostics and modeling enabled attribution of etiology in most adult SARI patients, despite frequent detection of multiple pathogens in the upper respiratory tract. Seasonal flu vaccination and development of RSV vaccine would likely reduce the burden of SARI in these populations.

Identification of novel non-coding RNA-based negative feedback regulating the expression of the oncogenic transcription factor GLI1.

Non-coding RNAs are a complex class of nucleic acids, with growing evidence supporting regulatory roles in gene expression. Here we identify a non-coding RNA located head-to-head with the gene encoding the Glioma-associated oncogene 1 (GLI1), a transcriptional effector of multiple cancer-associated signaling pathways. The expression of this three-exon GLI1 antisense (GLI1AS) RNA in cancer cells was concordant with GLI1 levels. siRNAs knockdown of GLI1AS up-regulated GLI1 and increased cellular proliferation and tumor growth in a xenograft model system. Conversely, GLI1AS overexpression decreased the levels of GLI1, its target genes PTCH1 and PTCH2, and cellular proliferation. Additionally, we demonstrate that GLI1 knockdown reduced GLI1AS, while GLI1 overexpression increased GLI1AS, supporting the role of GLI1AS as a target gene of the GLI1 transcription factor. Activation of TGFß and Hedgehog signaling, two known regulators of GLI1 expression, conferred a concordant up-regulation of GLI1 and GLI1AS in cancer cells. Finally, analysis of the mechanism underlying the interplay between GLI1 and GLI1AS indicates that the non-coding RNA elicits a local alteration of chromatin structure by increasing the silencing mark H3K27me3 and decreasing the recruitment of RNA polymerase II to this locus. Taken together, the data demonstrate the existence of a novel non-coding RNA-based negative feedback loop controlling GLI1 levels, thus expanding the repertoire of mechanisms regulating the expression of this oncogenic transcription factor.

Nanoemulsions as vehicles for transdermal delivery of glycyrrhizin

The present investigation aims to evaluate an isotropic and thermodynamically stable nanoemulsion formulation for transdermal delivery of glycyrrhizin (GZ), with minimum surfactant and cosurfactant (Smix) concentrations that could improve its solubility, permeation enhancement, and stability. Pseudo-ternary phase diagrams were developed and various nanoemulsion formulations were prepared using soyabean oil as oil, Span 80, Brij 35 as a surfactant and isopropyl alcohol as a cosurfactant. Nanoemulsion formulations that passed the thermodynamic stability tests were characterized for pH, viscosity and droplet size using a transmission electron microscopy. The transdermal ability of glycyrrhizin through human cadaver skin was determined using Franz diffusion cells. The in vitro skin permeation profile of the optimized nanoemulsion formulation (NE2) was compared to that of conventional gel. A significant increase in permeability parameters such as steady-state flux (Jss) and permeability coefficient (Kp) was observed in the optimized nanoemulsion formulation (NE2), which consisted of 1 percent wt/wt of mono ammonium glycyrrhizinate (MAG), 32.4 percent Span 80, 3.7 percent Brij 35, 10 percent isopropyl alcohol, 46.5 percent soyabean oil and 6.4 percent distilled water. No obvious skin irritation was observed for the studied nanoemulsion formulation (NE2) or the gel. The results indicated that nanoemulsions are promising vehicles for transdermal delivery of glycyrrhizin through human cadaver skin, without the use of additional permeation enhancers, because excipients of nanoemulsions act as permeation enhancers themselves.

O objetivo da investigação é avaliar uma nanoemulsão isotrópica termodinamicamente estável para a administração transdérmica da glicirrizina (GZ), com concentrações mínimas de tensoativo e co-tensoativo (Smix), que poderiam melhorar a sua solubilidade, a permeação e a estabilidade. Os diagramas pseudo-ternários de fase foram desenvolvidos e diversas nanoemulsões foram preparadas com óleo de soja como óleo, Span 80, Brij 35 como tensoativos e álcool isopropílico como co-tensoativo. As nanoemulsões que passaram por testes de estabilidade termodinâmica foram caracterizadas por pH, viscosidade, tamanho de gota e microscopia eletrônica de transmissão. A capacidade transdérmica da glicirrizina em passar através da pele de cadáver humano foi determinada por células de difusão de Franz. O perfil in vitro de permeação cutânea da formulação otimizada (NE2) foi comparada com a de gel convencional. Observou-se aumento significativo nos parâmetros de permeabilidade, como fluxo de equilíbrio (JSS) e coeficiente de permeabilidade (Kp) na formulação otimizado (NE2), que consistiu de 1 por cento wt/wt de monoglicirrizinato de amônio (MAG), 32,4 por cento de Span 80, 3,7 por cento de Brij 35, 10 por cento de álcool isopropílico, 46,5 por cento de óleo de soja e 6,4 por cento de água destilada. Não se observou irritação óbvia da pele para as nanoemulsões estudadas (NE2) ou de gel. Os resultados indicaram que nanoemulsões são promissores veículos para a administração transdérmica de glicirrizina através da pele de cadáveres humanos, sem o uso adicional de promotor de permeação, porque excipientes de nanoemulsões atuam como promotores de permeação.