Virus diseases that have emerged in the past two decades limit the production of important vegetable crops in tropical, subtropical, and temperate regions worldwide, and many of the causal viruses ...are transmitted by whiteflies (order Hemiptera, family Aleyrodidae). Most of these whitefly-transmitted viruses are begomoviruses (family Geminiviridae), although whiteflies are also vectors of criniviruses, ipomoviruses, torradoviruses, and some carlaviruses. Factors driving the emergence and establishment of whitefly-transmitted diseases include genetic changes in the virus through mutation and recombination, changes in the vector populations coupled with polyphagy of the main vector, Bemisia tabaci, and long distance traffic of plant material or vector insects due to trade of vegetables and ornamental plants. The role of humans in increasing the emergence of virus diseases is obvious, and the effect that climate change may have in the future is unclear.
Gut microbiota is involved in obesity, metabolic syndrome and the progression of nonalcoholic fatty liver disease (NAFLD). It has been recently suggested that the flavonoid quercetin may have the ...ability to modulate the intestinal microbiota composition, suggesting a prebiotic capacity which highlights a great therapeutic potential in NAFLD. The present study aims to investigate benefits of experimental treatment with quercetin on gut microbial balance and related gut-liver axis activation in a nutritional animal model of NAFLD associated to obesity. C57BL/6J mice were challenged with high fat diet (HFD) supplemented or not with quercetin for 16 weeks. HFD induced obesity, metabolic syndrome and the development of hepatic steatosis as main hepatic histological finding. Increased accumulation of intrahepatic lipids was associated with altered gene expression related to lipid metabolism, as a result of deregulation of their major modulators. Quercetin supplementation decreased insulin resistance and NAFLD activity score, by reducing the intrahepatic lipid accumulation through its ability to modulate lipid metabolism gene expression, cytochrome P450 2E1 (CYP2E1)-dependent lipoperoxidation and related lipotoxicity. Microbiota composition was determined via 16S ribosomal RNA Illumina next-generation sequencing. Metagenomic studies revealed HFD-dependent differences at phylum, class and genus levels leading to dysbiosis, characterized by an increase in Firmicutes/Bacteroidetes ratio and in Gram-negative bacteria, and a dramatically increased detection of Helicobacter genus. Dysbiosis was accompanied by endotoxemia, intestinal barrier dysfunction and gut-liver axis alteration and subsequent inflammatory gene overexpression. Dysbiosis-mediated toll-like receptor 4 (TLR-4)-NF-κB signaling pathway activation was associated with inflammasome initiation response and reticulum stress pathway induction. Quercetin reverted gut microbiota imbalance and related endotoxemia-mediated TLR-4 pathway induction, with subsequent inhibition of inflammasome response and reticulum stress pathway activation, leading to the blockage of lipid metabolism gene expression deregulation. Our results support the suitability of quercetin as a therapeutic approach for obesity-associated NAFLD via its anti-inflammatory, antioxidant and prebiotic integrative response.
•Dysbiosis is accompanied by gut-liver axis alteration in HFD-induced NAFLD.•Quercetin prevents dysbiosis-induced TLR4-mediated inflammation and lipotoxicity.•Quercetin counteracts inflammasome and reticulum stress pathway activation.•Modulatory effects displayed by quercetin counteract lipid metabolism deregulation.•Quercetin improves NAFLD via an integrative response including its prebiotic effect.
Summary
Background
In the past few years, growing interest was given to the relationship between the dental occlusion and the body balance. While most research focused on this relationship at static ...conditions, it is evident that the contribution of the sensory information for balance control is different depending on the environmental constraints.
Research question
The aim of the present paper was to elucidate whether the stomatognathic system (SS) contributes differently on body balance regulation according to the presence of external disturbances.
Methods
Literature regarding the different sources involved in the proprioceptive information to the SS was reviewed. The influence of dental occlusion on balance control at different external environments was then explored.
Results
The main findings are: (a) a plausible evidence between the masticatory and cervical muscles can be described; (b) a reciprocal connection between the trigeminal and vestibular nuclei supports the influence of the SS on body balance; (c) traditionally, research involving the relationship between the SS and balance control has focused on strictly controlled situations, thus, ignoring the sensory reweighting which occurs depending on the external disturbances; and (d) the afferences of dental occlusion for balance control seem strengthened when more difficult conditions are present.
Conclusion
Results of the present review suggest that afferent signals from dental occlusion effectively contribute to balance control when more external perturbations are present, that is unstable support surface, fatigue and tasks being performed. However, more studies are needed to elucidate the mechanisms by which dental occlusion may influence balance control focusing on different external environments.
Scope
Modulation of intestinal microbiota has emerged as a new therapeutic approach for non‐alcoholic fatty liver disease (NAFLD). Herein, it is addressed whether gut microbiota modulation by ...quercetin and intestinal microbiota transplantation can influence NAFLD development.
Methods and results
Gut microbiota donor mice are selected according to their response to high‐fat diet (HFD) and quercetin in terms of obesity and NAFLD‐related biomarkers. Germ‐free recipients displayed metabolic phenotypic differences derived from interactions between microbiota transplanted, diets, and quercetin. Based on the evaluation of hallmark characteristics of NAFLD, it is found that gut microbiota transplantation from the HFD‐non‐responder donor and the HFD‐fed donor with the highest response to quercetin results in a protective phenotype against HFD‐induced NAFLD, in a mechanism that involves gut–liver axis alteration blockage in these receivers. Gut microbiota from the HFD‐responder donor predisposed transplanted germ‐free mice to NAFLD. Divergent protective and deleterious metabolic phenotypes exhibited are related to definite microbial profiles in recipients, highlighting the predominant role of Akkermansia genus in the protection from obesity‐associated NAFLD development.
Conclusions
The results provide scientific support for the prebiotic capacity of quercetin and the transfer of established metabolic profiles through gut microbiota transplantation as a protective strategy against the development of obesity‐related NAFLD.
A potential preventive strategy of quercetin intake and intestinal microbiota transplantation on obesity‐associated non‐alcoholic fatty liver disease (NAFLD) is reported. Hight‐fat diet and quercetin administration result in different metabolic phenotypes, which are transmissible through gut microbiota transplantation to germ‐free mice. The interplay between intestinal microbiota profiles transplanted, diet, and quercetin results in metabolic phenotype transfer associated with protection or predisposition to develop obesity and NAFLD.
Childhood obesity has reached epidemic levels and is a serious health concern associated with metabolic syndrome, nonalcoholic fatty liver disease, and gut microbiota alterations. Physical exercise ...is known to counteract obesity progression and modulate the gut microbiota composition. This study aims to determine the effect of a 12-week strength and endurance combined training program on gut microbiota and inflammation in obese pediatric patients. Thirty-nine obese children were assigned randomly to the control or training group. Anthropometric and biochemical parameters, muscular strength, and inflammatory signaling pathways in mononuclear cells were evaluated. Bacterial composition and functionality were determined by massive sequencing and metabolomic analysis. Exercise reduced plasma glucose levels and increased dynamic strength in the upper and lower extremities compared with the obese control group. Metagenomic analysis revealed a bacterial composition associated with obesity, showing changes at the phylum, class, and genus levels. Exercise counteracted this profile, significantly reducing the Proteobacteria phylum and Gammaproteobacteria class. Moreover, physical activity tended to increase some genera, such as Blautia, Dialister, and Roseburia, leading to a microbiota profile similar to that of healthy children. Metabolomic analysis revealed changes in short-chain fatty acids, branched-chain amino acids, and several sugars in response to exercise, in correlation with a specific microbiota profile. Finally, the training protocol significantly inhibited the activation of the obesity-associated NLRP3 signaling pathway. Our data suggest the existence of an obesity-related deleterious microbiota profile that is positively modified by physical activity intervention. Exercise training could be considered an efficient nonpharmacological therapy, reducing inflammatory signaling pathways induced by obesity in children via microbiota modulation.
•The epoch of the Anthropocene, a period during which human activity has been the dominant influence on climate and the environment, has witnessed a decline in oxygen concentrations and an expansion ...of oxygen-depleted environments in both coastal and open ocean systems since the middle of the 20th century.•This review paper provides a synthesis of system-specific drivers of low oxygen in a range of case studies representing marine systems in the open ocean, on continental shelves, in enclosed seas and in the coastal environment.•Identification of similar and contrasting responses within and across system types and corresponding oxygen regimes is shown to be informative both in understanding and isolating key controlling processes and provides a sound basis for predicting change under anticipated future conditions.•Case studies were selected to achieve a balance in system diversity and global coverage.•Each case study describes system attributes, including the present-day oxygen environment and known trends in oxygen concentrations over time.•Central to each case study is the identification of the physical and biogeochemical processes that determine oxygen concentrations through the tradeoff between ventilation and respiration.•Spatial distributions of oxygen and time series of oxygen data provide the opportunity to identify trends in oxygen availability and have allowed various drivers of low oxygen to be distinguished through correlative and causative relationships.•Deoxygenation results from a complex interplay of hydrographic and biogeochemical processes and the superposition of these processes, some additive and others subtractive, makes attribution to any particular driver challenging.•System-specific models are therefore required to achieve a quantitative understanding of these processes and of the feedbacks between processes at varying scales.
The epoch of the Anthropocene, a period during which human activity has been the dominant influence on climate and the environment, has witnessed a decline in oxygen concentrations and an expansion of oxygen-depleted environments in both coastal and open ocean systems since the middle of the 20th century. This paper provides a review of system-specific drivers of low oxygen in a range of case studies representing marine systems in the open ocean, on continental shelves, in enclosed seas and in the coastal environment. Identification of similar and contrasting responses within and across system types and corresponding oxygen regimes is shown to be informative both in understanding and isolating key controlling processes and provides a sound basis for predicting change under anticipated future conditions. Case studies were selected to achieve a balance in system diversity and global coverage. Each case study describes system attributes, including the present-day oxygen environment and known trends in oxygen concentrations over time. Central to each case study is the identification of the physical and biogeochemical processes that determine oxygen concentrations through the tradeoff between ventilation and respiration. Spatial distributions of oxygen and time series of oxygen data provide the opportunity to identify trends in oxygen availability and have allowed various drivers of low oxygen to be distinguished through correlative and causative relationships. Deoxygenation results from a complex interplay of hydrographic and biogeochemical processes and the superposition of these processes, some additive and others subtractive, makes attribution to any particular driver challenging. System-specific models are therefore required to achieve a quantitative understanding of these processes and of the feedbacks between processes at varying scales.
Scope
Gut microbiota contributes to non‐alcoholic fatty liver disease (NAFLD) pathogenesis by multiple mechanisms not yet completely understood. Novel differential features between germ‐free mice ...(GFm) transplanted with protective or non‐protective cecal microbiota against NAFLD are investigated.
Methods and results
Gut microbiota composition, plasma, and fecal bile acids (BAs) and liver mRNAs are quantified in GFm recipients from four donor mice differing in NAFLD severity (control diet, high‐fat diet HFD‐responder, HFD‐non‐responder, and quercetin‐supplemented HFD). Transplanted GFm are on control or HFD for 16‐weeks. Multivariate analysis shows that GFm colonized with microbiota from HFD‐non‐responder and quercetin supplemented‐HFD donors (protected against NAFLD) clusters together, whereas GFm colonized with microbiota from control and HFD‐responder mice (non‐protected against NAFLD) establishes another cluster. Protected phenotype is associated with increased gut Desulfovibrio and Oscillospira, reduced gut Bacteroides and Oribacterium, lower primary and higher secondary BAs in plasma and feces, induction of hepatic BA transporters, and repression of hepatic lipogenic and BA synthesis genes.
Conclusion
Protective gut microbiota associates with increased specific secondary BAs, which likely inhibit lipogenic pathways and enhance bile flow in the liver. This novel cross‐talk between gut and liver, via plasma BAs, that promotes protection against NAFLD may have clinical and nutritional relevance.
A microbiota‐derived protected phenotype against non‐alcoholic fatty liver disease (NAFLD) in mice is reported. This phenotype associates with increased gut Desulfovibrio and Oscillospira, reduced gut Bacteroides and Oribacterium, lower primary and higher secondary bile acids (Bas) in plasma and feces, induction of hepatic BA transporters, and repression of hepatic lipogenic and BA synthesis genes.
Frailty is a common condition among critically ill patients. Usually evaluated in a mixed population of medical, cardiac and surgical patients, we aimed to assess the impact of frailty on short- and ...long-term mortality exclusively in critically ill older medical patients.
We included 285 patients aged≥70 years admitted to ICU (2009–2017). Comorbidities, severity scores, treatment intensity and complications were recorded. Pre-hospital frailty, measured by Clinical Frailty Scale (CFS), was defined as a score ≥ 5 according to this scale.
Prevalence of frailty (CFS ≥ 5) of 18.6%. Frail patients were more likely to be female (64.2% vs. 35.6%, p < .001) or suffer from heart failure (17% vs. 6%,p = .021). Apache II score was higher in frail than in non-frail patients (27.4 ± 7.1 vs. 24.8 ± 8.6,p = .041). Age, comorbidities, treatment intensity, complications, and ICU and hospital length of stay were similar between frail and non-frail patients. Life-sustaining treatment limitation was more frequent in frail patients (47.2% vs. 20.7%,p < .001). Except for ICU mortality, frailty was an independent predictor of short- and long-term mortality after adjustment for sociodemographic, comorbidities, severity scores, treatment intensity and complications.
Frailty (CFS ≥ 5) was independently associated with short- and long-term mortality in older patients admitted to ICU exclusively due to a medical reason.
•Frailty condition was exclusively evaluated in critically ill older medical patients (≥ 70 years).•Frailty (CFS ≥ 5) was associated with short- and long- term mortality after controlling for several variables.•ICU mortality is not a suitable form of assessing the impact of frailty in older critically ill patients admitted to ICU.•Frailty assessment should be routinely included in thedecision-making process of older medical patients admitted to ICU.
Treatment of β-lactamase positive bacterial infections with a combination of amoxicillin (AMOX) and clavulanic acid (CLAV) causes idiosyncratic drug-induced liver injury (iDILI) in a relevant number ...of patients, often with features of intrahepatic cholestasis. This study aims to determine serum bile acid (BA) levels in amoxicillin/clavulanate (A+C)-iDILI patients and to investigate the mechanism of cholestasis by A+C in human in vitro hepatic models. In six A+C-iDILI patients, significant elevations of serum primary conjugated BA definitely demonstrated A+C-induced cholestasis. In cultured human Upcyte hepatocytes and HepG2 cells, CLAV was more cytotoxic than AMOX, and, at subcytotoxic concentrations, it altered the expression of more than 1,300 genes. CLAV, but not AMOX, downregulated the expression of key genes for BA transport (BSEP, NTCP, OSTα and MDR2) and synthesis (CYP7A1 and CYP8B1). CLAV also caused early oxidative stress, with reduced GSH/GSSG ratio, along with induction of antioxidant nuclear factor erythroid 2-related factor 2 (NRF2) target genes. Activation of NRF2 by sulforaphane also resulted in downregulation of NTCP, OSTα, ABCG5, CYP7A1 and CYP8B1. CLAV also inhibited the BA-sensor farnesoid X receptor (FXR), in agreement with the downregulation of FXR targets BSEP, OSTα and ABCG5. We conclude that CLAV, the culprit molecule in A+C, downregulates several key biliary transporters by modulating NRF2 and FXR signaling, thus likely promoting intrahepatic cholestasis. On top of that, increased ROS production and GSH depletion may aggravate the cholestatic injury by A+C.
Mechanisms involved in CLAV-induced cholestasis. Schematic representation of a human hepatocyte with basolateral and canalicular biliary transporters. Blue lines with arrows represent the genes of biliary transporters. Green-pointed and red-blocked arrows represent activating or repressing events. An “X” through a point arrow represents a loss of activation. Green and red ovals represent proteins that result activated/upregulated or inhibited/downregulated by CLAV. ROS. Reactive oxygen species. BA: bile acids, PL: phospholipids, Chol: cholesterol, GS-conj: glutathione conjugates, Bil: bilirubin, GSSG, oxidized glutathione. Display omitted
•Amoxicillin-clavulanate raises serum primary conjugated bile acids in DILI patients.•Clavulanate is the culprit of cholestasis by amoxicillin-clavulanate in hepatocytes.•Clavulanate downregulates expression of bile acid transporter and synthesis genes.•Clavulanate causes early oxidative stress, decreases GSH and induces NRF2 signalling.•Clavulanate inhibits FXR activation by agonists, in agreement with BSEP repression.
Childhood obesity has reached epidemic levels, representing one of the most serious public health concerns associated with metabolic syndrome and non-alcoholic fatty liver disease (NAFLD). There is ...limited clinical experience concerning pediatric NAFLD patients, and thus the therapeutic options are scarce. The aim of this study was to evaluate the benefits of exercise on gut microbiota composition and functionality balance, and consequent effects on early obesity and NAFLD onset in an
model. Juvenile (21-day-old) male Wistar rats fed a control diet or a high-fat diet (HFD) were subjected to a combined aerobic and resistance training protocol. Fecal microbiota was sequenced by an Illumina MiSeq system, and parameters related to metabolic syndrome, fecal metabolome, intestinal barrier integrity, bile acid metabolism and transport, and alteration of the gut-liver axis were measured. Exercise decreased HFD-induced body weight gain, metabolic syndrome and hepatic steatosis, as a result of its lipid metabolism modulatory capacity. Gut microbiota composition and functionality were substantially modified as a consequence of diet, age and exercise intervention. In addition, the training protocol increased
,
and
genera, correlating with a beneficial metabolomic profile, whereas
,
and
showed an opposite pattern. Exercise effectively counteracted HFD-induced microbial imbalance, leading to intestinal barrier preservation, which, in turn, prevented deregulation of the gut-liver axis and improved bile acid homeostasis, determining the clinical outcomes of NAFLD. In conclusion, we provide scientific evidence highlighting the benefits of gut microbiota composition and functionality modulation by physical exercise protocols in the management of early obesity and NAFLD development.
PDF
