Uncommon fatty acids and cardiometabolic health

Cardiovascular disease (CVD) is a major cause of mortality. The effects of several unsaturated fatty acids on cardiometabolic health, such as eicosapentaenoic acid (EPA) docosahexaenoic acid (DHA), α linolenic acid (ALA), linoleic acid (LA), and oleic acid (OA) have received much attention in past years. In addition, results from recent studies revealed that several other uncommon fatty acids (fatty acids present at a low content or else not contained in usual foods), such as furan fatty acids, n-3 docosapentaenoic acid (DPA), and conjugated fatty acids, also have favorable effects on cardiometabolic health. In the present report, we searched the literature in PubMed, Embase, and the Cochrane Library to review the research progress on anti-CVD effect of these uncommon fatty acids. DPA has a favorable effect on cardiometabolic health in a different way to other long-chain n-3 polyunsaturated fatty acids (LC n-3 PUFAs), such as EPA and DHA. Furan fatty acids and conjugated linolenic acid (CLNA) may be potential bioactive fatty acids beneficial for cardiometabolic health, but evidence from intervention studies in humans is still limited, and well-designed clinical trials are required. The favorable effects of conjugated linoleic acid (CLA) on cardiometabolic health observed in animal or in vitro cannot be replicated in humans. However, most intervention studies in humans concerning CLA have only evaluated its effect on cardiometabolic risk factors but not its direct effect on risk of CVD, and randomized controlled trials (RCTs) will be required to clarify this point. However, several difficulties and limitations exist for conducting RCTs to evaluate the effect of these fatty acids on cardiometabolic health, especially the high costs for purifying the fatty acids from natural sources. This review provides a basis for better nutritional prevention and therapy of CVD

Coexistence of Microbial Species in Structured Communities by Forming a Hawk-Dove Game Like Interactive Relationship

Microorganisms evolve kinds of elaborate interaction models that can form relatively stable communities in a wide range of ecosystems. It is recognized that the spatial genetic structure of microbes in surface-attached environments lays a good foundation for the persistence of polymicrobial communities in adverse conditions. However, the interacting dynamics of microbes in facilitating the formation and stabilization of community structure still remains elusive. In this study, we identify a hawk-dove game like interspecific relationship between the two Gram-negative opportunistic pathogens Pseudomonas aeruginosa and Klebsiella pneumoniae, which naturally coexist in insect gut and can cocolonize human tissues. Specifically, although P. aeruginosa had significant competitive advantage over cocultured K. pneumoniae on solid medium with rich nutrient factors, K. pneumoniae could resist the suppression of P. aeruginosa by enhancing the expression of membrane transporters induced by the extracellular metabolites of P. aeruginosa. By contrast, under the condition that K. pneumoniae had a growth advantage but P. aeruginosa met a metabolic burden in producing quorum-sensing-controlled extracellular products, the frequency of K. pneumoniae would be slightly higher than P. aeruginosa during the coexistence because K. pneumoniae was also capable of exploiting the extracellular metabolite from P. aeruginosa. In addition, P. aeruginosa quorum-sensing variant could reap benefits from K. pneumoniae in turn and reach a relatively stable two species equilibrium. These findings provide an explanation for the formation and maintenance of polymicrobial communities in different spatially structured environments, and thus may contribute to understanding the complex interspecific interactions of microbes in local communities and shed new light on the development of social microbiology

Pseudomonas aeruginosa Quorum-Sensing and Type VI Secretion System Can Direct Interspecific Coexistence During Evolution

It is reported that a wide range of bacterial infections are polymicrobial, and the members in a local microcommunity can influence the growth of neighbors through physical and chemical interactions. Pseudomonas aeruginosa is an important opportunistic pathogen that normally causes a variety of acute and chronic infections, and clinical evidences suggest that P. aeruginosa can be frequently coisolated with other pathogens from the patients with chronic infections. However, the interspecific interaction and the coexisting mechanism of P. aeruginosa with coinfecting bacterial species during evolution still remain largely unclear. In this study, the relationships of P. aeruginosa with other Gram-positive (Staphylococcus aureus) and Gram-negative (Klebsiella pneumoniae) are investigated by using a series of on-plate proximity assay, in vitro coevolution assay, and RNA-sequencing. We find that although the development of a quorum-sensing system contributes P. aeruginosa a significant growth advantage to compete with S. aureus and K. pneumoniae, the quorum-sensing regulation of P. aeruginosa will be decreased during evolution and thus provides a basis for the formation of interspecific coexistence. The results of comparative transcriptomic analyses suggest that the persistent survival of S. aureus in the microcommunity has no significant effect on the intracellular transcriptional pattern of P. aeruginosa, while a more detailed competition happens between P. aeruginosa and K. pneumoniae. Specifically, the population of P. aeruginosa with decreased quorum-sensing regulation can still restrict the proportion increase of K. pneumoniae by enhancing the type VI secretion system-elicited cell aggressivity during further coevolution. These findings provide a general explanation for the formation of a dynamic stable microcommunity consisting of more than two bacterial species, and may contribute to the development of population biology and clinical therapy

Genes as early responders regulate quorum-sensing and control bacterial cooperation in Pseudomonas aeruginosa.

Quorum-sensing (QS) allows bacterial communication to coordinate the production of extracellular products essential for population fitness at higher cell densities. It has been generally accepted that a significant time duration is required to reach appropriate cell density to activate the relevant quiescent genes encoding these costly but beneficial public goods. Which regulatory genes are involved and how these genes control bacterial communication at the early phases are largely un-explored. By determining time-dependent expression of QS-related genes of the opportunistic pathogen Pseudomonas aerugionsa, we show that the induction of social cooperation could be critically influenced by environmental factors to optimize the density of population. In particular, small regulatory RNAs (RsmY and RsmZ) serving as early responders, can promote the expression of dependent genes (e.g. lasR) to boost the synthesis of intracellular enzymes and coordinate instant cooperative behavior in bacterial cells. These early responders, acting as a rheostat to finely modulate bacterial cooperation, which may be quickly activated under environment threats, but peter off when critical QS dependent genes are fully functional for cooperation. Our findings suggest that RsmY and RsmZ critically control the timing and levels of public goods production, which may have implications in sociomicrobiology and infection control

Supplemental Material - Construction and evaluation of an aging-associated genes-based model for pancreatic adenocarcinoma prognosis and therapies

Supplemental Material for Construction and evaluation of an aging-associated genes-based model for pancreatic adenocarcinoma prognosis and therapies by Junjie Zhao, Kelei Guan and Jiyuan Xing in International Journal of Immunopathology and Pharmacology</p

Effects of Multivitamin and Multimineral Supplementation on Blood Pressure: A Meta-Analysis of 12 Randomized Controlled Trials

Previous studies have not drawn a consistent conclusion about effect of multivitamin and multimineral supplementation (MVMS) on blood pressure. A comprehensive search of PubMed, Embase and Cochrane Library (up to May 2018) and references of relevant articles was undertaken. The present meta-analysis included 12 randomized controlled trials (RCTs), of which eight RCTs in 2011 subjects evaluated the effect of MVMS on blood pressure and four RCTs in 21,196 subjects evaluated the effect of MVMS on the risk of hypertension. MVMS had a lowering effect on systolic blood pressure (SBP) and diastolic blood pressure (DBP): the weighted mean difference (WMD) was &minus;1.31 mmHg (95% CI, &minus;2.48 to &minus;0.14 mmHg) and &minus;0.71 mmHg (95% CI, &minus;1.43 to 0.00 mmHg), respectively. Subgroup analysis indicated that the lowering effect of MVMS on blood pressure was only significant in 134 subjects with chronic disease but not in 1580 healthy subjects, and the WMD for systolic blood pressure (SBP) and DBP in subjects with chronic disease was &minus;6.29 mmHg (95% CI, &minus;11.09 to &minus;1.50 mmHg) and &minus;2.32 mmHg (95% CI, &minus;4.50 to &minus;0.13 mmHg), respectively. The effect size of MVMS on SBP in 58 hypertensive subjects (WMD, &minus;7.98 mmHg; 95% CI, &minus;14.95 to &minus;1.02 mmHg) was more than six times of that in 1656 normotensive subjects (WMD, &minus;1.25 mmHg; 95% CI, &minus;2.48 to &minus;0.02 mmHg). However, no significant effect on DBP was observed in both hypertensive and normotensive subgroups. There was no significant effect of MVMS on risk of hypertension in 22,852 subjects with a normal blood pressure at baseline. In conclusion, although MVMS had a significant lowering effect on blood pressure in normotensive subjects, the lowering effect was too small to effectively prevent future hypertension. MVMS may be an effective method for blood pressure control in subjects with chronic disease including hypertension, but the sample size of subjects with hypertension or other chronic disease was too small, and more well-designed RCTs are needed to confirm this result

Recent Advances in DNA Vaccines against Lung Cancer: A Mini Review

Lung cancer is regarded as the major causes of patient death around the world. Although the novel tumor immunotherapy has made great progress in the past decades, such as utilizing immune checkpoint inhibitors or oncolytic viruses, the overall 5-year survival of patients with lung cancers is still low. Thus, development of effective vaccines to treat lung cancer is urgently required. In this regard, DNA vaccines are now considered as a promising immunotherapy strategy to activate the host immune system against lung cancer. DNA vaccines are able to induce both effective humoral and cellular immune responses, and they possess several potential advantages such as greater stability, higher safety, and being easier to manufacture compared to conventional vaccination. In the present review, we provide a global overview of the mechanism of cancer DNA vaccines and summarize the innovative neoantigens, delivery platforms, and adjuvants in lung cancer that have been investigated or approved. Importantly, we highlight the recent advance of clinical studies in the field of lung cancer DNA vaccine, focusing on their safety and efficacy, which might accelerate the personalized design of DNA vaccine against lung cancer

RsmYZ regulated cooperation was induced by environmental nutrient factors.

<p>(A) Growth of WT PAO1 in M9<b> </b>minimal growth medium containing 1% adenosine (circle), 1% adenosine and 1% BSA as the dual carbon source (black square) and BSA was added after 40 hours cultivation (triangle). Expression of leadership and dependent genes of WT PAO1 were detected in M9<b> </b>minimal growth medium containing (B) 1% adenosine; (C) 0.5% adenosine+0.5% BSA; (D) 0.5% +0.5% BSA and the supernatants were removed every 4 hours; (E) 1% adenosine and then 1% BSA was added after 20 hours cultivation; (F) 1% adenosine and then 1% BSA was added after 40 hours cultivation. Data are means ± SEM, and representative of three experiments. *, <i>P</i><0.05; **, <i>P</i><0.01; ***, <i>P</i><0.001, one-way ANOVA (Tukey-Kramer post hoc).</p