Areca catechu—From farm to food and biomedical applications

The family Arecaceae includes 181 genera and 2,600 species with a high diversity in physical characteristics. Areca plants, commonly palms, which are able to grow in nearly every type of habitat, prefer tropical and subtropical climates. The most studied species Areca catechu L. contains phytochemicals as phenolics and alkaloids with biological properties. The phenolics are mainly distributed in roots followed by fresh unripe fruits, leaves, spikes, and veins, while the contents of alkaloids are in the order of roots, fresh unripe fruits, spikes, leaves, and veins. This species has been reputed to provide health effects on the cardiovascular, respiratory, nervous, metabolic, gastrointestinal, and reproductive systems. However, in many developing countries, quid from this species has been associated with side effects, which include the destruction of the teeth, impairment of oral hygiene, bronchial asthma, or oral cancer. Despite these side effects, which are also mentioned in this work, the present review collects the main results of biological properties of the phytochemicals in A. catechu. This study emphasizes the in vitro and in vivo antioxidant, antimicrobial, anticancer, and clinical effectiveness in humans. In this sense, A. catechu have demonstrated effectiveness in several reports through in vitro and in vivo experiments on disorders such as antimicrobial, antioxidant, or anticancer. Moreover, our findings demonstrate that this species presents clinical effectiveness on neurological disorders. Hence, A. catechu extracts could be used as a bioactive ingredient for functional food, nutraceuticals, or cosmeceuticals. However, further studies, especially extensive and comprehensive clinical trials, are recommended for the use of Areca in the treatment of diseases.     

Novel Approaches to Optimization of Levodopa Therapy for Parkinson’s Disease

Levodopa (LD) is the most effective medication to treat Parkinson’s disease (PD). However, motor fluctuations and drug-induced dyskinesia compromise the long-term success of levodopa therapy in PD. These response complications are due, at least in part, to fluctuating LD plasma levels (as a result of erratic gastric emptying, variable jejunal absorption, and most importantly, the short half-life of LD) with standard levodopa formulations. Keeping levodopa concentrations as constant as possible is the target for improving the pharmacokinetics and developing new ways of LD administration. In this article, we review novel oral and non-oral LD formulations including the ones that have successfully completed phase 3 clinical trials and have come to market and ones that are still in earlier phases of clinical development.     

Characterization of Leachates from 6 Root Canal Sealers

Introduction

The aim of this study was to evaluate 6 different endodontic sealers by characterizing their leachates and comparing their solubility in water over a 4-week period.

Presence and antibiotic resistance of Porphyromonas gingivalis,Prevotella intermedia,and Prevotella nigrescens in children

BACKGROUND/AIMS: Only limited information exists about the prevalence in children of pathogens associated with periodontitis. The aim of the present study was to determine by culture whether 8-11-year-old children carry Porphyromonas gingivalis, Prevotella intermedia, and/or P. nigrescens in samples from the gingiva and/or the buccal mucosa taken before, and after caries treatment and oral hygiene instruction. A second aim was to assess the proportion of subjects who had gram-negative anaerobes carrying the tet(Q) and erm(F) genes, suggesting antibiotic resistance to tetracycline or erythromycin. METHOD: A total of 150 children provided gingival and buccal swab bacterial samples that were cultured for P. gingivalis, P. intermedia, and P. nigrescens. The species was verified using DNA-DNA hybridization with species-specific probes made from the variable region of the 16S rRNA sequences. Antibiotic-resistant genes, tet(Q) and erm(F), were identified using specific DNA-DNA hybridization with specific DNA probes. RESULTS: A total of 116 isolates of black-pigmented bacteria were cultured from 47 (31%) of 150 children. Five isolates were identified as P. gingivalis, 29 as P. intermedia, 33 as P. nigrescens, and 49 as other species. In general, the bacteria were not culturable at more than one time period. We found that 55% of these 47 children harbored black pigmented bacteria that carried either one or both of the two antibiotic-resistant genes studied (tet(Q), and erm(F)). CONCLUSION: The present study demonstrated that children not exposed to regular dental treatment carry bacteria outside the gingival sulcus that have been associated with periodontitis, and that standard treatment procedures may not clear the presence of the putative pathogens. In addition, antibiotic-resistant genes are common in identifiable gram-negative anaerobes, including putative pathogens.     

Concomitant overexpression of mir‐182‐5p and mir‐182‐3p raises the possibility of IL‐17–producing Treg formation in breast cancer by targeting CD3d,ITK, FOXO1, and NFATs: A meta‐analysis and experimental study

T cells are polarized toward regulatory T cells (Tregs) in tumor microenvironment by the shuttling of microRNAs that target T cell–activating signaling pathways. We evaluated the expression of the miR‐182 cluster (miR‐96, 182, and 183) in peripheral blood mononuclear cells (PBMCs) of patients with breast cancer (BC), and T cell polarization by the expression of FOXO1, NFATs, ITK, TCR/CD3 complex, and IL‐2/IL‐2RA. Twenty‐six microRNAs overexpressed in tumor tissues and sera of these patients were extracted by a meta‐analysis. Then, the expression of the miR‐182 cluster was investigated in PBMCs and sera of these patients and correlated with their targets in PBMCs. Finally, miR‐182 was cloned into Jurkat cells to evaluate its effects on T cell polarization. FOXO1, CD3d, ITK, NFATc3, NFATc4, and IL‐2RA were targeted by miR‐182, due to which their expression decreased in PBMCs of patients. Although IL‐6, IL‐17, and TGF‐β increased after miR‐182 transduction, IL‐2 dramatically decreased. We revealed CD4⁺FOXP3⁺ T cell differentiation in the miR‐182–transduced group. Although miR‐182 has inhibitory effects on T cells by the inhibition of FOXO1, TCR/CD3 complex, NFATs, and IL‐2/IL‐2RA signaling pathways, it increases FOXP3, TGF‐β, and IL‐17 expression to possibly drive T cell deviation toward the transitional state of IL‐17–producing Tregs and Treg formation in the end.     

Cardiac resynchronization therapy response is associated with shorter duration of atrial fibrillation

BACKGROUND: Atrial fibrillation (AF) is commonly associated with heart failure. The benefit of cardiac resynchronization therapy (CRT) on atrial remodeling has been demonstrated. However, biventricular pacing did not reduce the global incidence of AF. We evaluated the relationship between CRT response and AF duration. METHODS: We retrospectively analyzed data from 96 patients (59 +/- 15 years; 78% male) who underwent CRT. All patients had class III-IV New York Heart Association (NYHA) symptoms despite maximal medical therapy, left ventricular ejection fraction (LVEF) < or = 35%, QRS >130 ms, and sinus rhythm before implantation. CRT response in patients who survived at six months of follow-up was defined as: (1) no hospitalization for heart failure and (2) improvement of one or more grades in the NYHA classification. RESULTS: CRT responders (n = 54) and non-responders (n = 42) had similar baseline characteristics, including the incidence of persistent AF within six months before implantation. Six months after implantation, when compared to baseline, CRT responders exhibited a significant decrease in left atrial size (47.5 +/- 7.1 mm vs 44.6 +/- 7.7 mm, P < 0.01) and in the incidence of persistent AF (17% vs 2%, P = 0.02). At six months, CRT responders demonstrated shorter mean AF duration (7.5 +/- 43.3 hours vs 48.8 +/- 129.0 hours, P = 0.03) and lower incidence of persistent AF (2% vs 19%, P = 0.004) compared to nonresponders. CONCLUSION: CRT response is associated with a reversal of atrial remodeling and a shorter AF duration.     

Future of combination therapy with dabrafenib and trametinib in metastatic melanoma

Introduction: Combination therapy with BRAF and MEK inhibitors is a recommended treatment strategy for metastatic melanoma patients with BRAF^V600 mutations. This treatment provides significant response rates and little added toxicity, with relatively improved survival outcomes compared to RAF/MEK inhibitor monotherapy and chemotherapy.

Areas covered: This review covers the pharmacology, efficacy, and toxicity data derived from clinical studies of dabrafenib, trametinib, and the combination thereof. The major downfall of combiDT is the limited durability of response, which is largely due to acquired resistance in the MAPK pathway.

Expert opinion: Future directions of combiDT concentrate on further combinations with immunotherapy or other targeted inhibitors, referred to triple-agent therapy, which may be essential to improving durability of responses and overcoming resistance.     

Depression and glioblastoma,complicated concomitant diseases: a systemic review of published literature

Glioblastoma multiforme (GBM) is the most common primary brain cancer. Depression is a common co-morbidity of this condition. Despite this common interaction, relatively little research has been performed on the development of GBM-associated depression. We performed a literary search of the PubMed database for articles published relating to GBM and depression. A total of 85 articles were identified with 46 meeting inclusion criteria. Depression significantly impacts care, decreasing medication compliance, and patient survival. Diagnostically, because depression and GBM share intricate neuro-connectivity in a way that effect functionality, these diseases can be mistaken for alternative psychological or pathological disorders, complicating care. Therapeutically, anti-depressants have anti-tumor properties; yet, some have been shown to interfere with GBM treatment. One reason for this is that the pathophysiological development of depression and GBM share several pathways including altered regulation of the 5-HT receptor, norepinephrine, and 3′:5′-cyclic monophosphate. Over time, depression can persist after GBM treatment, affecting patient quality of life. Together, depression and GBM are complicated concomitant diseases. Clinicians must be aware of their co-existence. Because of overlapping molecular pathways involved in both diseases, careful medication selection is imperative to avoid potential adverse interactions. Since GBMs are the most common primary brain cancer, physicians dealing with this disease should be prepared for the development of depression as a potential sequela of this condition, given the related pathophysiology and the known poor outcomes.