Hypoxia-Inducible Factor Stabilizers: a New Avenue for Reducing BP While Helping Hemoglobin?

Anemia of chronic kidney disease (CKD) is common and is associated with diminished quality of life, cognitive impairment, cardiovascular morbidity, hospitalizations, and mortality. As the prevalence of end-stage renal disease continues to rise, the management of anemia represents a growing economic burden. Erythropoiesis-stimulating agents (ESA) are the mainstay of anemia management but their use is limited due to the associated cardiovascular adverse events. Prolyl hydroxylase domain enzyme (PHD) inhibitors are a new class of drugs that stabilize the hypoxia-inducible factors and are under clinical investigation for the treatment of renal anemia. The advantages of PHD inhibitors include the oral route of administration, improved iron profile, restoration of diurnal rhythm of erythropoietin secretion, and endogenous erythropoietin production near physiological range. Emerging but limited data indicates a small blood pressure lowering effect of PHD inhibitors. The effect of PHD inhibitors on cardiovascular endpoints and the potential risks of CKD progression and pulmonary hypertension remains to be addressed in the ongoing clinical trials.     

PARP1: A potential biomarker for gastric cancer

Gastric cancer (GC) is the third leading cause of cancer mortality worldwide, with an overall 5-y survival rate of 25%. The majority of GCs are caused by infectious agents, including the bacterium Helicobacter pylori (H. pylori) and Epstein–Barr virus (EBV). Furthermore, inappropriate repair of DNA damage can also result in genomic instability, which has shown to be a key factor in carcinogenesis of different regions including gastric region. Present study was designed to explore the association between base excision repair pathway genes, PARP1 and APEX1 and gastric pathology and H. pylori infection. Two hundred gastric cancer tissue samples (114 H. pylori positive and 86 H. pylori negative) and adjacent uninvolved area taken as controls was used for expression analysis of BER pathway genes at mRNA level and protein levels using quantitative PCR (qPCR) and immunohistochemistry (IHC) respectively. Oxidative stress and DNA damage was also determined by measuring the level of antioxidant enzymes and comet assay respectively. Significant upregulation in PARP1 (p < 0.001) and APEX1 (p < 0.02) was observed in GC tissue samples compared to controls and this upregulation was more pronounced in H. pylori positive cases (HPGC) (PARP1, p < 0.02: APEX1, p < 0.04) than H. pylori negative cases (HNGC). Upregulation of BER pathway genes in HPGC was found correlated with smoking status (p < 0.0001), T stage (p < 0.01) and lymph node metastasis (p < 0.03). Moreover, immunohistochemical staining of BER pathway genes was found correlated with a number of clinicopathological characteristics such as tumor type (p < 0.03), tumor size (p < 0.01) and lymph node metastasis (p < 0.01). Expression levels of APEX1 and PARP1 gene also correlated with increased oxidative burden (p < 0.0001) and DNA damage (p < 0.001) in GC patients. Survival analysis showed that upregulation of PARP1 gene was associated with poor overall survival outcome of gastric cancer patients (HR = 2.04 (95% CI = 1.10–3.76; p < 0.02). Univariate and multivariate cox regression analysis showed the upregulated PARP1 gene (HR = 5.03; 95%CI (2.22–11.35); p = 0.0001), positive smoking status (HR = 3.58; 95%CI (1.67–7.65); p = 0.001), positive status for H pylori infection (HR = 4.38; 95%CI (1.82–10.56); p = 0.001) and advance N-stage (HR = 5.29; 95%CI (2.28–12.24); p = 0.0001) were independent prognostic factors for gastric cancer and may serve as a valuable biomarker for the diagnosis and progression of GC and can be helpful in developing individualized treatment strategies for treating GC.     

Micro‐computed tomographic analysis of the radial geometry of intrarenal artery‐vein pairs in rats and rabbits: Comparison with light microscopy

We assessed the utility of synchrotron‐radiation micro‐computed tomography (micro‐CT) for quantification of the radial geometry of the renal cortical vasculature. The kidneys of nine rats and six rabbits were perfusion fixed and the renal circulation filled with Microfil. In order to assess shrinkage of Microfil, rat kidneys were imaged at the Australian Synchrotron immediately upon tissue preparation and then post fixed in paraformaldehyde and reimaged 24 hours later. The Microfil shrank only 2‐5% over the 24 hour period. All subsequent micro‐CT imaging was completed within 24 hours of sample preparation. After micro‐CT imaging, the kidneys were processed for histological analysis. In both rat and rabbit kidneys, vascular structures identified in histological sections could be identified in two‐dimensional (2D) micro‐CT images from the original kidney. Vascular morphology was similar in the two sets of images. Radial geometry quantified by manual analysis of 2D images from micro‐CT was consistent with corresponding data generated by light microscopy. However, due to limited spatial resolution when imaging a whole organ using contrast‐enhanced micro‐CT, only arteries ≥100 and ≥60 μm in diameter, for the rat and rabbit respectively, could be assessed. We conclude that it is feasible and valid to use micro‐CT to quantify vascular geometry of the renal cortical circulation in both the rat and rabbit. However, a combination of light microscopic and micro‐CT approaches are required to evaluate the spatial relationships between intrarenal arteries and veins over an extensive range of vessel size.     

Hydroxyapatite in Oral Care Products—A Review

Calcium phosphate compounds form the inorganic phases of our mineralised tissues such as bone and teeth, playing an important role in hard tissue engineering and regenerative medicine. In dentistry and oral care products, hydroxyapatite (HA) is a stable and biocompatible calcium phosphate with low solubility being used for various applications such as tooth remineralisation, reduction of tooth sensitivity, oral biofilm control, and tooth whitening. Clinical data on these products is limited with varied results; additionally, the effectiveness of these apatite compounds versus fluoride, which has conventionally been used in toothpaste, has not been established. Therefore, this review critically evaluates current research on HA oral care, and discusses the role and mechanism of HA in remineralisation of both enamel and dentine and for suppressing dentine sensitivity. Furthermore, we position HA’s role in biofilm management and highlight the role of HA in dental applications by summarising the recent achievement and providing an overview of commercialised HA dental products. The review also indicates the existing limitations and provides direction for future research and commercialisation of apatite-based oral care products.     

Whole-genome sequencing for optimized patient management

Whole-genome sequencing of patient DNA can facilitate diagnosis of a disease, but its potential for guiding treatment has been under-realized. We interrogated the complete genome sequences of a 14-year-old fraternal twin pair diagnosed with dopa (3,4-dihydroxyphenylalanine)-responsive dystonia (DRD; Mendelian Inheritance in Man #128230). DRD is a genetically heterogeneous and clinically complex movement disorder that is usually treated with l-dopa, a precursor of the neurotransmitter dopamine. Whole-genome sequencing identified compound heterozygous mutations in the SPR gene encoding sepiapterin reductase. Disruption of SPR causes a decrease in tetrahydrobiopterin, a cofactor required for the hydroxylase enzymes that synthesize the neurotransmitters dopamine and serotonin. Supplementation of l-dopa therapy with 5-hydroxytryptophan, a serotonin precursor, resulted in clinical improvements in both twins.     

Echinacea plants as antioxidant and antibacterial agents: From traditional medicine to biotechnological applications

The genus Echinacea consists of 11 taxa of herbaceous and perennial flowering plants. In particular, Echinacea purpurea (L.) Moench is widely cultivated all over the United States, Canada, and in Europe, exclusively in Germany, for its beauty and reported medicinal properties. Echinacea extracts have been used traditionally as wound healing to improve the immune system and to treat respiratory symptoms caused by bacterial infections. Echinacea extracts have demonstrated antioxidant and antimicrobial activities, and to be safe. This survey aims at reviewing the medicinal properties of Echinacea species, their cultivation, chemical composition, and the potential uses of these plants as antioxidant and antibacterial agents in foods and in a clinical context. Moreover, the factors affecting the chemical composition of Echinacea spp. are also covered.