Role of Obesity,Physical Exercise,Adipose Tissue-Skeletal Muscle Crosstalk and Molecular Advances in Barrett’s Esophagus and Esophageal Adenocarcinoma

Both obesity and esophageal adenocarcinoma (EAC) rates have increased sharply in the United States and Western Europe in recent years. EAC is a classic example of obesity-related cancer where the risk of EAC increases with increasing body mass index. Pathologically altered visceral fat in obesity appears to play a key role in this process. Visceral obesity may promote EAC by directly affecting gastroesophageal reflux disease and Barrett’s esophagus (BE), as well as a less reflux-dependent effect, including the release of pro-inflammatory adipokines and insulin resistance. Deregulation of adipokine production, such as the shift to an increased amount of leptin relative to “protective” adiponectin, has been implicated in the pathogenesis of BE and EAC. This review discusses not only the epidemiology and pathophysiology of obesity in BE and EAC, but also molecular alterations at the level of mRNA and proteins associated with these esophageal pathologies and the potential role of adipokines and myokines in these disorders. Particular attention is given to discussing the possible crosstalk of adipokines and myokines during exercise. It is concluded that lifestyle interventions to increase regular physical activity could be helpful as a promising strategy for preventing the development of BE and EAC.     

Molecular Basis of Essentiality of Early Critical Steps in the Lipopolysaccharide Biogenesis in Escherichia coli K-12: Requirement of MsbA,Cardiolipin, LpxL,LpxM and GcvB

To identify the physiological factors that limit the growth of Escherichia coli K-12 strains synthesizing minimal lipopolysaccharide (LPS), we describe the first construction of strains devoid of the entire waa locus and concomitantly lacking all three acyltransferases (LpxL/LpxM/LpxP), synthesizing minimal lipid IV_A derivatives with a restricted ability to grow at around 21 °C. Suppressors restoring growth up to 37 °C of Δ(gmhD-waaA) identified two independent single-amino-acid substitutions—P50S and R310S—in the LPS flippase MsbA. Interestingly, the cardiolipin synthase-encoding gene clsA was found to be essential for the growth of ΔlpxLMP, ΔlpxL, ΔwaaA, and Δ(gmhD-waaA) bacteria, with a conditional lethal phenotype of Δ(clsA lpxM), which could be overcome by suppressor mutations in MsbA. Suppressor mutations basS A20D or basR G53V, causing a constitutive incorporation of phosphoethanolamine (P-EtN) in the lipid A, could abolish the Ca⁺⁺ sensitivity of Δ(waaC eptB), thereby compensating for P-EtN absence on the second Kdo. A single-amino-acid OppA S273G substitution is shown to overcome the synthetic lethality of Δ(waaC surA) bacteria, consistent with the chaperone-like function of the OppA oligopeptide-binding protein. Furthermore, overexpression of GcvB sRNA was found to repress the accumulation of LpxC and suppress the lethality of LapAB absence. Thus, this study identifies new and limiting factors in regulating LPS biosynthesis.     

Exogenous Asymmetric Dimethylarginine (ADMA) in Pathogenesis of Ischemia-Reperfusion-Induced Gastric Lesions: Interaction with Protective Nitric Oxide (NO) and Calcitonin Gene-Related Peptide (CGRP)

Asymmetric dimethylarginine (ADMA) is an endogenous nitric oxide (NO) synthesis inhibitor and pro-inflammatory factor. We investigated the role of ADMA in rat gastric mucosa compromised through 30 min of gastric ischemia (I) and 3 h of reperfusion (R). These I/R animals were pretreated with ADMA with or without the combination of l-arginine, calcitonin gene-related peptide (CGRP) or a small dose of capsaicin, all of which are known to afford protection against gastric lesions, or with a farnesoid X receptor (FXR) agonist, GW 4064, to increase the metabolism of ADMA. In the second series, ADMA was administered to capsaicin-denervated rats. The area of gastric damage was measured with planimetry, gastric blood flow (GBF) was determined by H₂-gas clearance, and plasma ADMA and CGRP levels were determined using ELISA and RIA. ADMA significantly increased I/R-induced gastric injury while significantly decreasing GBF, the luminal NO content, and the plasma level of CGRP. This effect of ADMA was significantly attenuated by pretreatment with CGRP, l-arginine, capsaicin, or a PGE₂ analogue. In GW4064 pretreated animals, the I/R injury was significantly reduced and this effect was abolished by co-treatment with ADMA. I/R damage potentiated by ADMA was exacerbated in capsaicin-denervated animals with a further reduction of CGRP. Plasma levels of IL-10 were significantly decreased while malonylodialdehyde (MDA) and plasma TNF-α contents were significantly increased by ADMA. In conclusion, ADMA aggravates I/R-induced gastric lesions due to a decrease of GBF, which is mediated by a fall in NO and CGRP release, and the enhancement of lipid peroxidation and its pro-inflammatory properties.     

Macroalgal Defense against Competitors and Herbivores

Macroalgae are the source of many harmful allelopathic compounds, which are synthesized as a defense strategy against competitors and herbivores. Therefore, it can be predicted that certain species reduce aquaculture performance. Herein, the allelopathic ability of 123 different taxa of green, red, and brown algae have been summarized based on literature reports. Research on macroalgae and their allelopathic effects on other animal organisms was conducted primarily in Australia, Mexico, and the United States. Nevertheless, there are also several scientific reports in this field from South America and Asia; the study areas in the latter continents coincide with areas where aquaculture is highly developed and widely practiced. Therefore, the allelopathic activity of macroalgae on coexisting animals is an issue that is worth careful investigation. In this work, we characterize the distribution of allelopathic macroalgae and compare them with aquaculture locations, describe the methods for the study of macroalgal allelopathy, present the taxonomic position of allelopathic macroalgae and their impact on coexisting aquatic competitors (Cnidaria) and herbivores (Annelida, Echinodermata, Arthropoda, Mollusca, and Chordata), and compile information on allelopathic compounds produced by different macroalgae species. This work gathers the current knowledge on the phenomenon of macroalgal allelopathy and their allelochemicals affecting aquatic animal (competitors and predators) worldwide and it provides future research directions for this topic.