Sodium butyrate inhibits angiogenesis of human intestinal microvascular endothelial cells through COX-2 inhibition

We examined the effect of sodium butyrate on in vitro angiogenesis and cyclooxygenase (COX) expression using primary cultures of human intestinal microvascular endothelial cells (HIMEC). Butyrate inhibited VEGF-induced cellular proliferation, transmigration and tube formation of HIMEC. Butyrate also inhibited COX-2 expression as well as prostaglandin (PG)E2 and PGI2 production, and administration of PGI2 analog partially reversed the effect of butyrate on HIMEC angiogenesis. These results indicate that sodium butyrate inhibits HIMEC angiogenesis through down-regulation of COX-2 expression and PG production, and suggest that anti-angiogenic mechanisms may also be involved in the inhibitory effect of sodium butyrate on tumor growth.     

Isolation and characterization of human esophageal microvascular endothelial cells: mechanisms of inflammatory activation

Gastroesophageal reflux disease is the most common malady of the esophagus, affecting 7% of the United States population. Histological assessment demonstrates classic inflammatory mechanisms including selective leukocyte recruitment and hemorrhage, suggesting a prominent role for the microvasculature. We isolated and characterized human esophageal microvascular endothelial cells (EC) (HEMEC), examined inflammatory activation in response to cytokines, LPS, and acidic pH exposure, and identified signaling pathways that underlie activation. HEMEC displayed characteristic morphological and phenotypic features including acetylated LDL uptake. TNF-alpha/LPS activation of HEMEC resulted in upregulation of the cell adhesion molecules (CAM) ICAM-1, VCAM-1, E-selectin, and mucosal addressin CAM-1 (MAdCAM-1), increased IL-8 production, and enhanced leukocyte binding. Both acid and TNF-alpha/LPS activation lead to activation of SAPK/JNK in HEMEC that was linked to VCAM-1 expression and U-937 leukocyte adhesion. Expression of constitutive inducible nitric oxide synthase in HEMEC was in marked contrast to intestinal microvascular endothelial cells. In this study, we demonstrate that HEMECs are phenotypically and functionally distinct from lower gut-derived endothelial cells and will facilitate understanding of inflammatory mechanisms in esophageal inflammation.     

Interactive relationship between Trp metabolites and gut microbiota: The impact on human pathology of disease

Tryptophan (Trp), an α-amino acid, is the precursor of serotonin (5-hydroxytryptamine, 5-HT), which is involved in a variety of features of metabolic function and human nutrition. Evidence highlights the role of Trp metabolites (exclusively 5-HT) in the gastrointestinal (GI) tract; however, the mechanisms of action involved in the release of 5-HT in the GI tract are still unknown. Considering the fact that variations of 5-HT may facilitate the growth of certain GI disorders, gaining a better understanding of the function and release of 5-HT in the GI tract would be beneficial. Additionally, investigating Trp metabolism may clarify the relationship between Trp and gut microbiota. It is believed that other metabolites of Trp (mostly that of the kynurenine pathway) may play a significant role in controlling gut microbiota function. In this review, we have attempted to summarize the current research investigating the relationship of gut microbiota, Trp and 5-HT metabolism (with particular attention paid to their metabolite type, as well as a discussion of the research methods used in each study). Taking together, regarding the role that Trp/5-HT plays in a range of physical and mental diseases, the gut bacterial types, as well as the related disorders, have been exclusively considered.     

Nickel oxide nanoparticles exert selective toxicity on skin mitochondria and lysosomes isolated from the mouse model of melanoma

Nickel oxide nanoparticles (NiO‐NPs) are progressively used for an immense number of new applications in modern industries sectors. Nevertheless, the toxic impact of NiO‐NPs has not been clearly elucidated on human melanoma cell lines at the cellular and molecular level. Hence, this study was designed to examine the in vitro cytotoxicity potentials of NiO‐NPs on malignant cutaneous melanoma (MCM) mitochondria. Results revealed that NiO‐NPs significantly increased reactive oxygen species level, lipid peroxidation, and mitochondrial membrane potential and decreased succinate dehydrogenase activity, glutathione level, and ATP content on skin mitochondria isolated from the mouse model of melanoma compared with the non‐cancerous mouse skin mitochondria. Our results revealed that NiO‐NPs induced lysosomal membrane labialization on mentioned mitochondria. The current study showed that NiO‐NPs could significantly induce selective cytotoxicity on MCM mitochondria. Therefore, this compound may be considered as a promising candidate for further in vivo and clinical studies to reach a new anti‐MCM drug.     

Will "Combined Prevention" Eliminate Racial/Ethnic Disparities in HIV Infection among Persons Who Inject Drugs in New York City?

It has not been determined whether implementation of combined prevention programming for persons who inject drugs reduce racial/ethnic disparities in HIV infection. We examine racial/ethnic disparities in New York City among persons who inject drugs after implementation of the New York City Condom Social Marketing Program in 2007. Quantitative interviews and HIV testing were conducted among persons who inject drugs entering Mount Sinai Beth Israel drug treatment (2007–2014). 703 persons who inject drugs who began injecting after implementation of large-scale syringe exchange were included in the analyses. Factors independently associated with being HIV seropositive were identified and a published model was used to estimate HIV infections due to sexual transmission. Overall HIV prevalence was 4%; Whites 1%, African-Americans 17%, and Hispanics 4%. Adjusted odds ratios were 21.0 (95% CI 5.7, 77.5) for African-Americans to Whites and 4.5 (95% CI 1.3, 16.3) for Hispanics to Whites. There was an overall significant trend towards reduced HIV prevalence over time (adjusted odd ratio = 0.7 per year, 95% confidence interval (0.6–0.8). An estimated 75% or more of the HIV infections were due to sexual transmission. Racial/ethnic disparities among persons who inject drugs were not significantly different from previous disparities. Reducing these persistent disparities may require new interventions (treatment as prevention, pre-exposure prophylaxis) for all racial/ethnic groups.     

Impact of Sense of Coherence on Oral Health Behaviors: A Systematic Review

Objectives

The aim of this review was to critically analyze the empirical evidence on the association between Sense of Coherence (SOC) and oral health behaviors through a systematic approach.

Methods

A systematic search up to April 2015 was carried out using the following electronic bibliographic databases: PubMed, Ovid MEDLINE; ISI Web of Science; and Ovid PsychInfo. Studies were included if they evaluated the relationship between SOC and oral health behaviors including tooth cleaning, fluoride usage, dietary habits, dental attendance, and smoking. We excluded studies that only assessed the relationship between oral health status and SOC without evaluating oral health behaviors. The New Castle Ottawa (NOS) quality assessment checklist was employed to evaluate the methodological quality of included studies.

Results

Thirty-nine potential papers met the preliminary selection criteria and following a full-text review, 9 papers were finally selected for this systematic review. Results provided by the included studies indicated different levels of association between SOC and oral health behaviors. The most frequent behaviors investigated were tooth brushing and dental attendance pattern. The impact of SOC on performing positive oral health behaviors, to some extent, was related to demographic and socio-economic factors. In addition, mothers’ SOC influenced children’s oral health practices.

Conclusions

A more favorable oral health behavior was observed among those with a stronger SOC suggesting that the SOC can be a determinant of oral health-related behaviors including tooth brushing frequency, daily smoking, and dental attendance.     

The effect of photobiomodulation therapy in common maxillofacial injuries: Current status

The use of photobiomodulation therapy (PBMT) may be used for treating trauma to the maxillofacial region. The effects of PBMT on maxillofacial injuries were discussed in this review article. The electronic databases Pubmed, Scopus, and Web of Science were thoroughly searched. This review included in vitro, in vivo, and clinical studies describing how PBMT can be used in maxillofacial tissue engineering and regenerative medicine. Some studies suggest that PBMT may offer a promising therapy for traumatic maxillofacial injuries because it can stimulate the differentiation and proliferation of various cells, including dental pulp cells and mesenchymal stem cells, enhancing bone regeneration and osseointegration. PBMT reduces pain and swelling after oral surgery and tooth extraction in human and animal models of maxillofacial injuries. Patients with temporomandibular disorders also benefit from PBMT in terms of reduced inflammation and symptoms. PBMT still has some limitations, such as the need for standardizing parameters. PBMT must also be evaluated further in randomized controlled trials in various maxillofacial injuries. As a result, PBMT offers a safe and noninvasive treatment option for patients suffering from traumatic maxillofacial injuries. PBMT still requires further research to establish its efficacy in clinical practice and determine the optimal parameters.     

Discovery and Computer Aided Potency Optimization of a Novel Class of Small Molecule CXCR4 Antagonists

Amongst the chemokine signalling axes involved in cancer, chemokine CXCL12 acting on chemokine receptor CXCR4 is particularly significant since it orchestrates migration of cancer cells in a tissue-specific metastatic process. High CXCR4 tumour expression is associated with poor prognosis of lung, brain, CNS, blood and breast cancers. We have identified a new class of small molecule CXCR4 antagonists based on the use of computational modelling studies in concert with experimental determination of in vitro activity against CXCL12-induced intracellular calcium mobilisation, proliferation and chemotaxis. Molecular modelling proved to be a useful tool in rationalising our observed potencies, as well as informing the direction of the synthetic efforts aimed at producing more potent compounds.     

Construction of a three-component regulatory network of transcribed ultraconserved regions for the identification of prognostic biomarkers in gastric cancer

Altered expression and functional roles of the transcribed ultraconserved regions (T-UCRs), as genomic sequences with 100% conservation between the genomes of human, mouse, and rat, in the pathophysiology of neoplasms has already been investigated. Nevertheless, the relevance of the functions for T-UCRs in gastric cancer (GC) is still the subject of inquiry. In the current study, we first used a genome-wide profiling approach to analyze the expression of T-UCRs in GC patients. Then, we constructed a three-component regulatory network and investigated potential diagnostic and prognostic values of the T-UCRs. The Cancer Genome Atlas Stomach Adenocarcinoma (TCGA-STAD) dataset was used as a resource for the RNA-sequencing data. FeatureCounts was utilized to quantify the number of reads mapped to each T-UCR. Differential expression analysis was then conducted using DESeq2. In the following, interactions between T-UCRs, microRNAs (miRNAs), and messenger RNAs (mRNAs) were combined into a three-component network. Enrichment analyses were performed and a protein–protein interaction (PPI) network was constructed. The R Survival package was utilized to identify survival-related significantly differentially expressed T-UCRs (DET-UCRs). Using an in-house cohort of GC tissues, expression of two DET-UCRs was furthermore experimentally verified. Our results showed that several T-UCRs were dysregulated in TCGA-STAD tumoral samples compared to nontumoral counterparts. The three-component network was constructed which composed of DET-UCRs, miRNAs, and mRNAs nodes. Functional enrichment and PPI network analyses revealed important enriched signaling pathways and gene ontologies such as “pathway in cancer” and regulation of cell proliferation and apoptosis. Five T-UCRs were significantly correlated with the overall survival of GC patients. While no expression of uc.232 was observed in our in-house cohort of GC tissues, uc.343 showed an increased expression, although not statistically significant, in gastric tumoral tissues. The constructed three-component regulatory network of T-UCRs in GC presents a comprehensive understanding of the underlying gene expression regulation processes involved in tumor development and can serve as a basis to investigate potential prognostic biomarkers and therapeutic targets.