Barrett’s esophagus: Review of natural history and comparative efficacy of endoscopic and surgical therapies

Barrett's esophagus (BE) is the precursor to esophageal adenocarcinoma (EAC). Progression to cancer typically occurs in a stepwise fashion through worsening dysplasia and ultimately, invasive neoplasia. Established EAC with deep involvement of the esophageal wall and/or metastatic disease is invariably associated with poor long-term survival rates. This guides the rationale of surveillance of Barrett’s in an attempt to treat lesions at an earlier, and potentially curative stage. The last two decades have seen a paradigm shift in management of Barrett’s with rapid expansion in the role of endoscopic eradication therapy (EET) for management of dysplastic and early neoplastic BE, and there have been substantial changes to international consensus guidelines for management of early BE based on evolving evidence. This review aims to assist the physician in the therapeutic decision-making process with patients by comprehensive review and summary of literature surrounding natural history of Barrett’s by histological stage, and the effectiveness of interventions in attenuating the risk posed by its natural history. Key findings were as follows. Non-dysplastic Barrett’s is associated with extremely low risk of progression, and interventions cannot be justified. The annual risk of cancer progression in low grade dysplasia is between 1%-3%; EET can be offered though evidence for its benefit remains confined to highly select settings. High-grade dysplasia progresses to cancer in 5%-10% per year; EET is similarly effective to and less morbid than surgery and should be routinely performed for this indication. Risk of nodal metastases in intramucosal cancer is 2%-4%, which is comparable to operative mortality rate, so EET is usually preferred. Submucosal cancer is associated with nodal metastases in 14%-41% hence surgery remains standard of care, except for select situations.     

Diet and nutrition against inflammatory bowel disease: Trick or treat(ment)?

Even if the relationships between nutrition and inflammatory bowel disease (IBD) remain underexplored, the current literature is providing, day by day, much more evidence on the effects of various diets in both prevention and treatment of such illnesses. Wrong dietary habits, together with other environmental factors such as pollution, breastfeeding, smoke, and/or antibiotics, are among the theoretical pathogenetic causes of IBD, whose multifactorial aetiology has been already confirmed. While some of these risk factors are potentially reversible, some others cannot be avoided, and efficient treatments become necessary to prevent IBD spread or recurrence. Furthermore, the drugs currently available for treatment of such disease provide low-to-no effect against the symptoms, making the illnesses still strongly disabling. Whether nutrition and specific diets will prove to effectively interrupt the course of IBD has still to be clarified and, in this sense, further research concerning the applications of such dietary interventions is still needed.     

Matrine,oxymatrine, and compound Kushen injection from the roots of Sophora flavescens: an overview of their anticancer activities

In the present review, we updated current information on the chemistry, contents, and anticancer properties of matrine (MT), oxymatrine (OMT), and compound Kushen injection (CKI). The anticancer properties were focused on lung, breast, and liver cancer cells because they are most susceptible. Sources of information were from Google, Google Scholar, PubMed, PubMed Central, Science Direct, PubChem, J-Stage, Directory of Open Access Journals (DOAJ), and China National Knowledge Infrastructure (CNKI). Reference was also made on botanical websites, such as Flora of China and World Flora Online. MT and OMT are dominant quinolizidine alkaloids from the roots of Sophora flavescens (Kushen) of the family Fabaceae. Against lung, breast, and liver cancer cells, MT and OMT inhibit cell proliferation; induce cell cycle arrest, apoptosis, and autophagy; restrict angiogenesis; and inhibit cell metastasis, invasion, and migration. The processes involve various molecular targets and signaling pathways. CKI is a traditional Chinese medicine (TCM) composed of root extracts of S. flavescens and Smilax glabra (Baituling) of the family Smilacaceae. With MT and OMT as major components, CKI has been approved for the treatment of cancer in China more than 20 years ago. In recent years, systematic reviews and meta-analysis have been undertaken to evaluate the anticancer effects of CKI. When CKI is used alone and in combination with chemotherapy of western medicine, there is much to be learned concerning their interactions besides their individual and integrated efficacy. Some perspectives of MT, OMT, and CKI are discussed, and their suggestions for future research are provided.     

Orchestration of the circadian clock and its association with Alzheimer's disease: Role of endocannabinoid signaling

Circadian rhythms are 24-hour natural rhythms regulated by the suprachiasmatic nucleus, also known as the "master clock". The retino-hypothalamic tract entrains suprachiasmatic nucleus with photic information to synchronise endogenous circadian rhythms with the Earth’s light-dark cycle. However, despite the robustness of circadian rhythms, an unhealthy lifestyle and chronic photic disturbances cause circadian rhythm disruption in the suprachiasmatic nucleus’s TTFL loops via affecting glutamate and γ-aminobutyric acid-mediated neurotransmission in the suprachiasmatic nucleus. Recently, considerable evidence has been shown correlating CRd with the incidence of Alzheimer's disease. The present review aims to identify the existence and signalling of endocannabinoids in CRd induced Alzheimer's disease through retino-hypothalamic tract- suprachiasmatic nucleus-cortex. Immunohistochemistry has confirmed the expression of cannabinoid receptor 1 in the suprachiasmatic nucleus to modulate the circadian phases of the master clock. Literature also suggests that cannabinoids may alter activity of suprachiasmatic nucleus by influencing the activity of their major neurotransmitter γ-aminobutyric acid or by interacting indirectly with the suprachiasmatic nucleus’s two other major inputs i.e., the geniculo-hypothalamic tract-mediated release of neuropeptide Y and serotonergic inputs from the dorsal raphe nuclei. Besides, the expression of cannabinoid receptor 2 ameliorates cognitive deficits via reduction of tauopathy and microglial activation. In conclusion, endocannabinoids may be identified as a putative target for correcting CRd and decelerating Alzheimer’s disease.     

Forensic pathological characteristics of explosion trauma in confined space terrorist mass fatalities classified with a 3-dimensional model

BackgroundExplosion fatalities are the severest type of violent crimes. These involve the use of explosive devices in terrorist like activities in confined spaces in civilian or military settings, with mass number of people present all around. A stark dearth of literature for the forensic interpretation of such catastrophes is astonishing.PurposeCharacterization of the pattern of the multitude of injuries in explosions in confined spaces as guide for investigations and growth of literature on this entity.MethodologyA review of the archives of the forensic examinations of mass fatalities due to an explosion in a metro car was undertaken. It was combined with the reconstruction of the events by developing a three-dimensional model of this incident that involved seventeen fatalities.ResultsAll the decedents showed differential pattern of fatal injuries under the influence of damaging explosion factors (DEFs). The causative forces were characterized as gas-detonation (in all the cases), damaging effect by shock waves (59% of the cases), and impact of fragmentation and collision of the body (thrown off) with nearby objects. Traumatic effect due to shrapnel as well as blunt force was noted in 82% of the cases. Gross destruction of head due to combined effect of gas-detonation and fragmentation was seen in 29% of the cases.ConclusionAn interpretation of the nature and pattern of injuries in confined space explosions can help to estimate the location of deceased/s with respect to the epicenter and the type of DEFs.     

Redox active or thiol reactive? Optimization of rapid screens to identify less evident nuisance compounds

Compounds that exhibit assay interference or undesirable mechanisms of bioactivity are routinely encountered in assays at various stages of drug discovery. We observed that assays for the investigation of thiol-reactive and redox-active compounds have not been collected in a comprehensive review. Here, we review these assays and subject them to experimental optimization to improve their reliability. We demonstrate the usefulness of our assay cascade by assaying a library of bioactive compounds, chemical probes, and a set of approved drugs. These high-throughput assays should complement the array of wet-lab and in silico assays during the initial stages of hit discovery campaigns to pursue only hit compounds with tractable mechanisms of action.