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Background and Aim: The study aims to investigate the feasibility of further radiation dose reduction via the application of a high iodine delivery rate combined with automatic current modulation technology (high noise index) in head and neck computed tomography angiography. Methods: Sixty-four patients who underwent routine head and neck computed tomographic angiography were randomly divided into two groups: a low-dose group of 32 cases and an ultra-low-dose group of 32 cases. The same image reconstruction technique was applied in both groups using the 50% adaptive statistical iterative reconstruction method. Quantitative and qualitative image quality assessment of the carotid artery, computed tomographic dose index volume, dose length product, and effective dose of the two groups were analyzed. Results: The two groups were not significantly (P>0.05) different in age, gender, and body mass index. Significant (P Conclusions: Application of a higher iodine delivery rate combined with automatic current modulation technology (high noise index) in an existing low tube voltage protocol can further decrease the radiation dose and the total volume of contrast agent while maintaining similar image quality for patients undergoing computed tomography angiography of the head and neck, which can be recommended as the conventional scanning method.

Hepatocellular carcinoma (HCC) is a major cause of cancer-related death throughout the world, with constant increasing morbidity and mortality. Existing studies suggest that immunotherapy is beneficial to the treatment of advanced HCC. At present, it is imperative to identify biomarkers suitable for HCC immunotherapy. In this paper, the mRNA expression data of HCC were downloaded from The Cancer Genome Atlas, and Stromal Score, Immune Score and ESTIMATE Score of each sample were calculated. Weighted gene co-expression network analysis clustered the pretreated genes into eight modules. The brown module that was remarkably associated with Immune Score was identified by module eigengene-immune trait analysis, in which genes were mainly enriched in immune-related pathways. Four hub genes (CCR5, CD53, ITGB2, and TYROBP) related to tumor immunity, were screened out by intramodular gene connectivity combined with protein-protein interaction network topology analysis. Kaplan-Meier survival analysis presented a correlation between high expression of CCR5 and CD53, and better prognoses of HCC patients. TIMER analysis revealed a positive correlation between expression of each hub gene and immune cell infiltration level, and a positive correlation between the expression of each hub gene and the expression of immunosuppressive factors CTLA4 and PDCD1. Gene set enrichment analysis displayed that there was an evident difference in the activation of cytokines and the activation of immune signal transduction-related pathways between high- and low-expression groups of each hub gene. In conclusion, this study identified four potential genetic markers associated with HCC immunity and assessed their association with HCC patient's prognosis and immune microenvironment. The study results are expected to provide theoretical guidance for immunotherapy of HCC patients.

Background The high risks for childhood respiratory diseases are associated with exposure to ambient air pollution. However, there are few studies that have explored the association between air pollution exposure and respiratory diseases among young children (particularly aged 0–2 years) based on the entire population in a megalopolis. Methods Daily hospital admission records were obtained from 54 municipal hospitals in Wuhan city, China. We included all children (aged 0–2 years) hospitalized with respiratory diseases between January 2017 and December 2018. Individual air pollution exposure assessment was used in Land Use Regression model and inverse distance weighted. Case-crossover design and conditional logistic regression models were adopted to estimate the hospitalization risk associated with air pollutants. Results We identified 62,425 hospitalizations due to respiratory diseases, of which 36,295 were pneumonia. Particulate matter with an aerodynamic diameter less than 2.5 μm (PM2.5) and nitrogen dioxide (NO2) were significantly associated with respiratory diseases and pneumonia. ORs of pneumonia were 1.0179 (95% CI 1.0097–1.0260) for PM2.5 and 1.0131 (95% CI 1.0042–1.0220) for NO2 at lag 0–7 days. Subgroup analysis suggested that NO2, Ozone (O3) and sulfur dioxide (SO2) only showed effects on pneumonia hospitalizations on male patients, but PM2.5 had effects on patients of both genders. Except O3, all pollutants were strongly associated with pneumonia in cold season. In addition, children who aged elder months and who were in central urban areas had a higher hospitalization risk. Conclusions Air pollution is associated with higher hospitalization risk for respiratory diseases, especially pneumonia, among young children, and the risk is related to gender, month age, season and residential location.

Background Atopic dermatitis (AD) is a chronic relapsing skin disease that has long-term physical and mental health impacts on children with this condition. Current treatments mainly include anti-inflammatory, antibacterial, and anti-allergic interventions, systemic therapy, and recently emerging target-focused agents. However, these treatments have limited effectiveness and unwanted side effects. The use of traditional Chinese medicine (TCM) in the treatment of AD has a long history, with promising efficacies, low toxicity, and improvements in the quality of life of patients with AD. Longmu Tang granule, a TCM, has been used to effectively treat AD since 2008 through doctors’ prescriptions. To scientifically evaluate the clinical efficacy and safety of Longmu Tang granule, we proposed to launch a single-centred, double-blinded, randomised, placebo-controlled trial. Methods In this single-centred, double-blinded, randomised, placebo-controlled clinical trial conducted at Xiyuan Hospital of China Academy of Chinese Medical Sciences, a total of 60 participants will be randomly assigned (1:1) to receive the Longmu Tang granule or placebo granule for 8 weeks. The primary outcome will be evaluated using the index of Scoring Atopic Dermatitis. The secondary outcomes will be evaluated using the Children’s Dermatology Life Quality Index and the number cancellation test. The mechanistic evidence will be the serum levels of inflammatory cytokines, including immunoglobulin E, tumour necrosis factor-α, interleukin-1, and interleukin-6. Discussion The results of this trial will provide evidence of the efficacy and safety of the Longmu Tang granule and prove its anti-inflammatory action in patients with AD. Trial registration Chinese Clinical Trial Registry Chictr.org ID: ChiCTR2100041591. Registered on 1 January 2021

Serotonin (5-hydroxytryptamine, 5-HT) has been recognized as a potent pro-inflammatory mediator. Increasing the bioavailability and preventing the formation of 5-HT can reduce the inflammatory response in the body. Moreover, 5-HT is considered as an important central physiologic mediator of intestinal function by regulating intestinal motility, permeability, and other functions. The dysfunction of intestinal serotonergic system causes intestinal barrier damage and further leads to the increase of bacterial endotoxin (LPS) translocation into the liver, which contributes to the development of non-alcoholic fatty liver disease (NAFLD). In addition, increasing the expression of serotonin reuptake transporter (SERT) and decreasing the expression of tryptophan hydroxylase1 (TPH1) can relieve the symptoms of NAFLD. Tryptophan (TRP), as a precursor of 5-HT synthesis, plays an important role in gut homeostasis and energy metabolism. Previous studies have found that TRP supplementation aggravates fatty liver degeneration by producing 5-HT, which activates mTOR signaling pathway in mice fed a high fat and high fructose diet. However, recent researches reveal that TRP supplementation stabilizes the intestinal barrier damage by increasing the expression of occludin and reduces the accumulation of fatty acids in liver. Although the effects of TRP supplementation on NAFLD are not clear and the specific mechanism needs to be further explored. A better understanding of the mechanisms of 5-HT on the liver and gut may open new therapeutic strategies in NAFLD.

To investigate the clinical and imaging characteristics of computed tomography (CT) in novel coronavirus pneumonia (NCP) caused by SARS-CoV-2.A retrospective analysis was performed on the imaging findings of patients confirmed with COVID-19 pneumonia who had chest CT scanning and treatment after disease onset. The clinical and imaging data were analyzed.Fifty patients were enrolled, including mild type in nine, common in 28, severe in 10 and critically severe in the rest three. Mild patients (29 years) were significantly (P0.03) younger than either common (44.5 years) or severe (54.7) and critically severe (65.7 years) patients, and common patients were also significantly (P0.03) younger than severe and critically severe patients. Mild patients had low to moderate fever (39.1 °C), 49 (98%) patients had normal or slightly reduced leukocyte count, 14 (28%) had decreased counts of lymphocytes, and 26 (52%) patients had increased C-reactive protein. Nine mild patients were negative in CT imaging. For all the other types of NCP, the lesion was in the right upper lobe in 30 cases, right middle lobe in 22, right lower lobe in 39, left upper lobe in 33 and left lower lobe in 36. The lesion was primarily located in the peripheral area under the pleura with possible extension towards the pulmonary hilum. Symmetrical lesions were seen in 26 cases and asymmetrical in 15. The density of lesion was mostly uneven with ground glass opacity as the primary presentation accompanied by partial consolidation and fibrosis.CT imaging presentations of NCP are mostly patchy ground glass opacities in the peripheral areas under the pleura with partial consolidation which will be absorbed with formation of fibrotic stripes if improved. CT scanning provides important bases for early diagnosis and treatment of NCP.

Nowadays, melatonin, previously considered only as a pharmaceutical product for rhythm regulation and sleep aiding, has shown its potential as a co-adjuvant treatment in intestinal diseases, however, its mechanism is still not very clear. A firm connection between melatonin at a physiologically relevant concentration and the gut microbiota and inflammation has recently established. Herein, we summarize their crosstalk and focus on four novelties. First, how melatonin is synthesized and degraded in the gut and exerts potentially diverse phenotypic effects through its diverse metabolites. Second, how melatonin mediates the activation and proliferation of intestinal mucosal immune cells with paracrine and autocrine properties. By modulating T/B cells, mast cells, macrophages and dendritic cells, melatonin immunomodulatory involved in regulating T-cell differentiation, intervening T/B cell interaction and attenuating the production of pro-inflammatory factors, achieving its antioxidant action via specific receptors. Third, how melatonin exerts antimicrobial action and modulates microbial components, such as lipopolysaccharide, amyloid-β peptides via nuclear factor κ-light-chain-enhancer of activated B cells (NF-κB) or signal transducers and activators of transcription (STAT1) pathway to modulate intestinal immune function in immune-pineal axis. The last, how melatonin mediates the effect of intestinal bacterial activity signals on the body rhythm system through the NF-κB pathway and influences the mucosal epithelium oscillation via clock gene expression. These processes are achieved at mitochondrial and nuclear levels to control the host immune cell development. Considering unclear mechanisms and undiscovered actions of melatonin in gut-microbiome-immune axis, it's time to reveal them and provide new insight for the outlook of melatonin as a potential therapeutic target in the treatment and management of intestinal diseases.

Background Gene therapy remains a significant challenge due to lots of barriers limiting the genetic manipulation technologies. As for non-viral delivery vectors, they often suffer insufficient performance due to inadequate cellular uptake and gene degradation in endosome or lysosome. The importance of overcoming these conserved intracellular barriers is increasing as the delivery of genetic cargo. Results A surface-functionalized non-viral vector involving the biomimetic mannitol moiety is initiated, which can control the cellular uptake and promote the caveolae-mediated pathway and intracellular trafficking, thus avoiding acidic and enzymatic lysosomal degradation of loaded gene internalized by clathrin-mediated pathway. Different degrees of mannitol moiety are anchored onto the surface of the nanoparticles to form bio-inspired non-viral vectors and CaP-MA-40 exhibits remarkably high stability, negligible toxicity, and significantly enhanced transgene expression both in vitro and in vivo. Conclusions This strategy highlights a paradigmatic approach to construct vectors that need precise intracellular delivery for innovative applications.

The intestinal tract is the shared locus of intestinal epithelial cells, immune cells, nutrient digestion and absorption, and microbial survival. The gut in animals faces continuous challenges in communicating with the external environment. Threats from endogenous imbalance and exogenous feeds, especially pathogens, could trigger a disorder of homeostasis, leading to intestinal disease and even systematic disease risk. As a part of the intestinal protective barrier, endogenous host defense peptides (HDPs) play multiple beneficial physiological roles in the gut mucosa. Moreover, enhancing endogenous HDPs is being developed as a new strategy for resisting pathogens and commensal microbes, and to maintain intestinal health and reduce antibiotic use. In recent years, multiple nutrients such as branched-chain amino acids, SCFAs, lactose, zinc, and cholecalciferol (vitamin D(3)) have been reported to significantly increase HDP expression. Nutritional intervention has received more attention and is viewed as a promising means to defend against pathogenic infections and intestinal inflammation. The present review focuses on current discoveries surrounding HDP expression and nutritional regulation of mechanisms in the gut. Our aim is to provide a comprehensive overview, referable tactics, and novel opinions.

Enterotoxigenic

Functional amino acids provide great potential for treating autophagy-related diseases by regulating autophagy. The purpose of the autophagy process is to remove unwanted cellular contents and to recycle nutrients, which is controlled by many factors. Disordered autophagy has been reported to be associated with various diseases, such as cancer, neurodegeneration, aging, and obesity. Autophagy cannot be directly controlled and dynamic amino acid levels are sufficient to regulate autophagy. To date, arginine, leucine, glutamine, and methionine are widely reported functional amino acids that regulate autophagy. As a signal relay station, mammalian target of rapamycin complex 1 (mTORC1) turns various amino acid signals into autophagy signaling pathways for functional amino acids. Deficiency or supplementation of functional amino acids can immediately regulate autophagy and is associated with autophagy-related disease. This review summarizes the mechanisms currently involved in autophagy and amino acid sensing, diverse signal transduction among functional amino acids and autophagy, and the therapeutic appeal of amino acids to autophagy-related diseases. We aim to provide a comprehensive overview of the mechanisms of amino acid regulation of autophagy and the role of functional amino acids in clinical autophagy-related diseases and to further convert these mechanisms into feasible therapeutic applications.

Nutrients can regulate metabolic activities of living organisms through epigenetic mechanisms, including DNA methylation, histone modification, and RNA regulation. Since the nutrients required for early embryos and postpartum lactation are derived in whole or in part from maternal and lactating nutrition, the maternal nutritional level affects the growth and development of fetus and creates a profound relationship between disease development and early environmental exposure in the offspring’s later life. Protein is one of the most important biological macromolecules, involved in almost every process of life, such as information transmission, energy processing and material metabolism. Maternal protein intake levels may affect the integrity of the fetal genome and alter DNA methylation and gene expression. Most amino acids are supplied to the fetus from the maternal circulation through active transport of placenta. Some amino acids, such as methionine, as dietary methyl donor, play an important role in DNA methylation and body’s one-carbon metabolism. The purpose of this review is to describe effects of maternal dietary protein and amino acid intake on fetal and neonatal growth and development through epigenetic mechanisms, with examples in humans and animals.

Obesity is one of the main challenges of public health in the 21st century. Obesity can induce a series of chronic metabolic diseases, such as diabetes, dyslipidemia, hypertension and nonalcoholic fatty liver, which seriously affect human health. Gut-brain axis, the two-direction pathway formed between enteric nervous system and central nervous system, plays a vital role in the occurrence and development of obesity. Gastrointestinal signals are projected through the gut-brain axis to nervous system, and respond to various gastrointestinal stimulation. The central nervous system regulates visceral activity through the gut-brain axis. Brain-gut peptides have important regulatory roles in the gut-brain axis. The brain-gut peptides of the gastrointestinal system and the nervous system regulate the gastrointestinal movement, feeling, secretion, absorption and other complex functions through endocrine, neurosecretion and paracrine to secrete peptides. Both neuropeptide Y and peptide YY belong to the pancreatic polypeptide family and are important brain-gut peptides. Neuropeptide Y and peptide YY have functions that are closely related to appetite regulation and obesity formation. This review describes the role of the gutbrain axis in regulating appetite and maintaining energy balance, and the functions of brain-gut peptides neuropeptide Y and peptide YY in obesity. The relationship between NPY and PYY and the interaction between the NPY-PYY signaling with the gut microbiota are also described in this review.

As a major component of biologically active compounds in the body, proteins contribute to the synthesis of body tissues for the renewal and growth of the body. The high level of dietary protein and the imbalance of amino acid (AA) composition in mammals result in metabolic disorders, inefficient utilization of protein resources and increased nitrogen excretion. Fortunately, nutritional interventions can be an effective way of attenuating the nitrogen excretion and increasing protein utilization, which include, but are not limited to, formulating the AA balance and protein-restricted diet supplementing with essential AAs, and adding probiotics in the diet. This review highlights recent advances in the turnover of dietary proteins and mammal’s metabolism for health, in order to improve protein bioavailability through nutritional approach.

The intestinal homeostasis is an orchestrated dynamic equilibrium state composed of the coexistence and interactions among the nutrients, microbial flora, and immune system. The intestinal balance disorder can trigger a series of diseases, such as inflammatory bowel disease (IBD). Many of tryptophan (Trp) metabolites, such as kynurenine and indole, generated under a series of endogenous enzymes or microbial metabolism, have been reported enable to bind and activate the aryl hydrocarbon receptor (AhR), this series of process is termed the Trp-AhR pathway. The activated Trp-AhR pathway can induce the expression of downstream cytokines such as interleukin-22 (IL-22) and interleukin-17 (IL-17), thereby regulating the intestinal homeostasis. This review highlights the advance of Trp-AhR pathway in the regulation of intestinal homeostasis and provides some insights for the clinical strategies that expect to effectively prevent and treat gut diseases via intervening the Trp-AhR pathway.

Objective: This study aims to investigate the correlation between cerebral blood flow (CBF) values and neonatal behavioral neurological assessment (NBNA) in hypoxic-ischemic encephalopathy (HIE), the relationship between early CBF value changes and the prognosis of neonatal HIE, and the consistency between the clinical grading and magnetic resonance (MR) grading of HIE. Methods: Forty neonates with HIE were scanned using the three-dimensional arterial spin labeling (ASL) sequencing of the cranial Magnetic Resonance Imaging (MRI). These newborns were classified as having mild, moderate and severe HIE, according to the clinical grading, and as being normal or having mild, moderate, or severe HIE, according to the MRI grading. Then, the consistency of these two grading systems was compared. Afterwards, the differences in the CBF values of neonates in groups with mild, moderate and severe HIE were compared. In addition, these neonates were grouped according to their NBNA scores. A score of ≥35 was considered a good prognosis, while a score of ≤35 was considered a poor prognosis. The differences in CBF values between these two groups were compared, and the correlation between the CBF values and NBNA scores was determined. Results: There was a strong consistency between the evaluation results for the clinical grading and MR grading (kappa value = 0.672, P Conclusion: Early CBF values in the BG area and thalamus can objectively and visually reflect the severity of the HIE, and be used to predict the outcome of functional brain damage, allowing early neuroprotective treatment to be initiated. The higher the perfusion in the BG region and thalamus, the lower the NBNA score, and the worse the prognosis would likely be. ASL combined with the NBNA score provides a more comprehensive classification for HIE and a more accurate assessment of the clinical prognosis, providing more medical imaging information for early clinical treatment.

Over the past several decades, increasing global prevalence of obesity-related nonalcoholic fatty liver disease (NAFLD) has been one of main challenges to human health. Recently, increasing evidence has validated connections among short chain fatty acids (SCFAs), a physiologically relevant concentration, the intestinal microbiota, and host metabolism. In this review, we summarized crosstalk between SCFAs and host metabolism in relation to NAFLD pathophysiology, focusing on recent advances. Firstly, how SCFAs are generated and absorbed under different nutritional conditions in the gut. Secondly, how SCFAs maintain gut barrier and alleviate hepatic inflammatory responses. Thirdly, how SCFAs maintain hepatic energy balance through controlling appetite and mediating the glucose homeostasis at the systemic level. Fourthly, G-protein-coupled receptors (GPRs) are widely involved in the above metabolic processes regulated by SCFAs. Overall, this review aimed to provide new insights into the prospects of SCFAs as a potential therapeutic target in management of liver diseases.

Purpose: To investigate the Computed Tomography (CT) imaging characteristics and dynamic changes of COVID-19 pneumonia at different stages. Methods: Forty-six patients infected with COVID-19 who had chest CT scans were enrolled, and CT scans were performed 4-6 times with an interval of 2-5 days. Results: At the early stage (n=25), ground glass opacity was presented in 11 patients (11/25 or 44.0 %) and ground glass opacity mixed with consolidation in 13 (13/25 or 52.0 %) in the lung CT images. At the progressive stage (n=38), ground glass opacity was presented in only one patient (1/38 or 2.6 %) and ground glass opacity mixed with consolidation in 33 (33/38 or 86.8 %). In the early improvement stage (n=38), the imaging presentation was ground glass opacity alone in three patients (3/38 or 7.9 %) and ground glass opacity mixed with consolidation in 34 (34/38 or 89.5 %). In the late improvement (absorption) stage (n=33), the primary imaging presentation was ground glass presentation in eight patients (8/33 or 24.2 %) and ground glass opacity mixed with consolidation in 23 (23/33 or 69.7 %). The lesion reached the peak at 4-16 days after disease onset, and 26 (26/38 or 68.4 %) patients reached the disease peak within ten days. Starting from 6 to 20 days after onset, the disease began to be improved, with 30 (30/38 or 78.9 %) patients being improved within 15 days. Conclusion: COVID-19 pneumonia will progress to the peak stage at a mediate time of seven days and enter the improvement stage at twelve days. Computed tomography imaging of the pulmonary lesion has a common pattern from disease onset to improvement and recovery and provides important information for evaluation of the disease course and treatment effect.

In a complex, diverse intestinal environment, commensal microbiota metabolizes excessive dietary tryptophan to produce more bioactive metabolites connecting with kinds of diverse process, such as host physiological defense, homeostasis, excessive immune activation and the progression and outcome of different diseases, such as inflammatory bowel disease, irritable bowel syndrome and others. Although commensal microbiota includes bacteria, fungi, and protozoa and all that, they often have the similar metabolites in tryptophan metabolism process via same or different pathways. These metabolites can work as signal to activate the innate immunity of intestinal mucosa and induce the rapid inflammation response. They are critical in reconstruction of lumen homeostasis as well. This review aims to seek the potential function and mechanism of microbiota-derived tryptophan metabolites as targets to regulate and shape intestinal immune function, which mainly focused on two aspects. First, analyze the character of tryptophan metabolism in bacteria, fungi, and protozoa, and assess the functions of their metabolites (including indole and eight other derivatives, serotonin (5-HT) and d-tryptophan) on regulating the integrity of intestinal epithelium and the immunity of the intestinal mucosa. Second, focus on the mediator and pathway for their recognition, transfer and crosstalk between microbiota-derived tryptophan metabolites and intestinal mucosal immunity. Disruption of intestinal homeostasis has been described in different intestinal inflammatory diseases, available data suggest the remarkable potential of tryptophan-derived aryl hydrocarbon receptor agonists, indole derivatives on lumen equilibrium. These metabolites as preventive and therapeutic interventions have potential to promote proinflammatory or anti-inflammatory responses of the gut.

Long noncoding RNAs (lncRNAs) are emerging as critical mediators of various biological processes in the immune system. The current data showed that the lncRNA Malat1 is highly expressed in T cell subsets, but the function of Malat1 in T cell remains unclear. In this study, we detected the T cell development and both CD8(+) and CD4(+) T cell response to LCMV infection using Malat1(−/-) mice model. To our surprise, there were no significant defects in thymocytes at different developmental stages and the peripheral T cell pool with ablation of Malat1. During LCMV infection, Malat1(−/-) mice exhibited normal effector and memory CD8(+) T cells as well as T(FH) cells differentiation. Our results indicated that Malat1 is not essential for T cell development and T cell-mediated antiviral response though it expresses at very high level in different T cell populations.

Breast cancer is the most common female malignant tumors in the world. It seriously affects women's physical and mental health and the leading cause of cancer death among women. Our previous study demonstrated that diet-derived IFN-γ promoted the malignant transformation of primary bovine mammary epithelial cells by accelerating arginine depletion. The current study aimed to explore whether arginine addition could inhibit the degree of malignant transformation and its molecular mechanism. The results indicate that arginine addition could alleviate the malignant transformation of mammary epithelial cells induced by IFN-γ, including reducing cell proliferation, cell migration and colony formation, through the NF-κB-GCN2/eIF2α pathway. The in vivo experiments also consistently confirmed that arginine supplementation could significantly inhibit tumor growth in tumor-bearing mice. Furthermore, the investigation of the clinical data also revealed that the plasma or tissue from human breast cancer patients owned lower arginine level and higher IFN-γ level than that from patients with benign breast disease, showing IFN-γ may be a potential control target. Our findings demonstrate that arginine supplement could antagonize the malignant transformation of mammary epithelial cells induced by IFN-γ (nutritionally induced) both in vitro and in vivo, and IFN-γ was higher in breast cancer women. This might provide a novel strategy for the prevention and treatment of breast cancer regarding to nutrition.

Reactive oxygen species (ROS) are produced by living cells as normal cellular metabolic byproduct. Under excessive stress conditions, cells will produce numerous ROS, and the living organisms eventually evolve series of response mechanisms to adapt to the ROS exposure as well as utilize it as the signaling molecules. ROS molecules would trigger oxidative stress in a feedback mechanism involving many biological processes, such as apoptosis, necrosis and autophagy. Growing evidences have suggested that ROS play a critical role as the signaling molecules throughout the entire cell death pathway. Overwhelming production of ROS can destroy organelles structure and bio-molecules, which lead to inflammatory response that is a known underpinning mechanism for the development of diabetes and cancer. Cytochrome P450 enzymes (CYP) are regarded as the markers of oxidative stress, can transform toxic metabolites into ROS, such as superoxide anion, hydrogen peroxide and hydroxyl radical which might cause injury of cells. Accordingly, cells have evolved a balanced system to neutralize the extra ROS, namely antioxidant systems that consist of enzymatic antioxidants such as superoxide dismutase (SOD), catalase (CAT) and glutathione peroxidases (GPxs), thioredoxin (Trx) as well as the non-enzymatic antioxidants which collectively reduce oxidative state. Herein, we review the recent novel findings of cellular processes induced by ROS, and summarize the roles of cellular endogenous antioxidant systems as well as natural anti-oxidative compounds in several human diseases caused by ROS in order to illustrate the vital role of antioxidants in prevention against oxidative stress.

The harmful effects of mycotoxins on intestinal health have received worldwide attention. Mycotoxins are toxic secondary metabolites produced by filamentous fungi, and include aflatoxins, ochratoxins, patulin, fumonisins, zearalenone, trichothecenes, and ergot alkaloids. Insuring the absence or low levels of mycotoxins is critical for food and feed safety. Currently, the studies in this field have illuminated the adverse effects of mycotoxins on gut health including intestinal integrity and the gut-associated immune system. By affecting the proteins and peptides that serve vital functions in the immune system and host metabolism, mycotoxins are able to attack intestinal epithelium, which leads to poor intestinal health and integrity. This review focuses on the effects of exposure to mycotoxins on the intestinal barrier, especially the gut microbiome, intestinal local immune system, and tight junction proteins, which in return influence digestion, absorption, metabolism and transport of the nutrients in intestinal lumen. The crucial role of mycotoxins on microbial metabolism and antimicrobial properties is also assessed, which elucidates the relationship between exposure to mycotoxins and the intestinal microbiome. We hypothesize that the key small peptides and proteins regulate the causal relationship between mycotoxins and gut microbiome.

The purpose of this study was to evaluate the clinical value of transvaginal elastography (TVES) combined with high-resolution transvaginal ultrasound (TVS) in the detection of parametrial invasion in cervical cancer and to compare the diagnostic performance with magnetic resonance imaging (MRI).52 women with histologically confirmed cervical cancer over a 2-year period were staged using International Federation of Gynecology and Obstetrics (FIGO) criteria and underwent MRI and TVES combined with TVS according to a standardized protocol before treatment. When assessing parametrial involvement with TVS, MRI, and combination of TVES and TVS, the findings were recorded and compared with histopathological results after surgery in early-stage disease (stage⩽IIa). Sensitivity, specificity accuracy, positive predictive value (PPV) and negative predictive value (NPV) were calculated for each method independently; subsequently, a matched-sample analysis was performed by using McNemar's test or chi-square test.Of 52 patients, 39 were early-stage disease (stage⩽IIa), and 13 were advanced-stage disease (stage⩾IIb) according to conventional FIGO staging. For the detection of parametrial infiltration, both the diagnostic sensitivity of MRI and the combination of TVS and TVES were statistically higher than alone TVS in early-stage of cervical cancer (P = 0.03 0.05). Both MRI and the combination of TVS and TVES had a sensitivity of 72.73%; specificity rates of 82.14% for MRI and 78.57% for the combination of TVES and TVS; and the diagnostic accuracy rates of 79.49% for MRI and 76.92% for the combination of TVES and TVS. A matched sample analysis revealed no statistically significant difference between the diagnostic performance of MRI and the combination of TVES and TVS in the assessment of parametrial invasion (all P values 0.05).TVES combined with TVS performed by a dedicated gynecologic radiologist should be considered a promising and economic method for pre-operative work-up for cervical cancer.

The covalently cross-linked chitosan-poly(ethylene glycol)1540 derivatives have been developed as a controlled release system with potential for the delivery of protein drug. The swelling characteristics of the hydrogels based on these derivatives as the function of different PEG content and the release profiles of a model protein (bovine serum albumin, BSA) from the hydrogels were evaluated in simulated gastric fluid with or without enzyme in order to simulate the gastrointestinal tract conditions. The derivatives cross-linked with difunctional PEG1540-dialdehyde via reductive amination can swell in alkaline pH and remain insoluble in acidic medium. The cumulative release amount of BSA was relatively low in the initial 2h and increased significantly at pH 7.4 with intestinal lysozyme for additional 12h. The results proved that the release-and-hold behavior of the cross-linked CS-PEG1540H-CS hydrogel provided a swell and intestinal enzyme controlled release carrier system, which is suitable for oral protein drug delivery.

Background Intravoxel incoherent motion (IVIM) diffusion-weighted imaging (DWI) is a functional magnetic resonance imaging (MRI) sequence. Purpose To evaluate the value of perfusion parameters derived from IVIM-DWI based on tumor edge region of interest (ROI) in differentiation in cervical cancer and investigate the relationship between IVIM and dynamic contrast-enhanced MRI (DCE-MRI). Material and Methods Thirty-three patients with pathologically diagnosed squamous cell carcinoma who underwent IVIM-DWI (nine b-values: 1–1000 s/mm2) and DCE-MRI were retrospectively assessed in this study. Parameters of IVIM (D, f, D*, fD*) and quantitative parameters of DCE-MRI (Ktrans, Kep, Ve) were derived using tumor edge ROI. Mann–Whitney U test was used to compare parameters between pathological grades and receiver operating characteristic (ROC) curves were used. Pearson’s correlation coefficient (r) evaluated the correlation between perfusion parameters derived from IVIM and DCE-MRI. Results The poorly differentiated group showed the significantly lower D value and the higher f, Ktrans and Kep values than the well-to-moderately differentiated group ( P Conclusion Perfusion parameters derived from IVIM based on tumor edge ROI may offer additional value in differentiation in cervical cancer, and the IVIM perfusion parameters showed moderate positive correlations with quantitative perfusion parameters from DCE-MRI, while f and fD* showed promising significance.

Background: It has been reported that compared with no local therapy (NLT), patients treated with local therapy (LT) using radiotherapy (RT) possess higher survival rate in metastatic prostate cancer (mPCa). The aim of this meta-analysis was to evaluate the impact of RT on prognosis in patients with mPCa. Methods: We retrieved the literature in PubMed, Embase, and Cochrane Library databases until June 2019 using structured search terms. Several studies were included, which evaluated patients with mPCa who received RT versus NLT. Results: A total of 14,542 patients were analyzed in 7 included papers (2 randomized controlled trials [RCTs] and 5 cohort retrospective studies [CRS]), and 2,232 mPCa patients were treated with RT and 12,310 with NLT. The data of RCTs and CRS were analyzed separately. In RCTs, RT was associated with no significant difference in overall survival (OS) (pooled hazard ratio [HR] = 0.96; 95% confidence interval [CI]: 0.85–1.09; p = 0.55; I2 = 42%) relative to NLT, while survival benefit was observed in the low-metastatic burden group (pooled HR = 0.68; 95% CI: 0.54–0.86; p = 0.001; I2 = 0%), and no survival benefit was observed in the high-metastatic burden group (pooled HR = 1.07; 95% CI: 0.92–1.24; p = 0.39; I2 = 0%). In CRS, RT results in lower cancer-specific mortality (CSM) (pooled HR = 0.49; 95% CI: 0.34–0.75; p < 0.00001; I2 = 0%) and higher OS (pooled HR = 0.61; 95% CI: 0.55–0.68; p < 0.00001; I2 = 0%) relative to NLT. Subsequent analysis demonstrated that high level of M-stage or N-stage was associated with increased CSM (pooled HR = 2.08; 95% CI: 1.69–2.55; p < 0.00001; I2 = 0% and pooled HR = 1.16; 95% CI: 1.03–1.30; p < 0.00001; I2 = 0%; respectively). Conclusions: Our observations in aggregate indicated that RT at least does not appear to be harmful and may be beneficial for low-metastatic burden patients and better condition patients. More prospective and randomized studies evaluating RT for mPCa are warranted.

Dietary protein is linked to the intestinal microorganisms. The decomposition of dietary protein can provide nutrients for microbial growth, which in turn can ferment protein to produce some metabolites. This review elaborates that the effects of different protein levels and types on intestinal microorganisms and their metabolites fermented by intestinal microorganisms, as well as the effects of these metabolites on organisms. It is well known that intestinal microbial imbalance can cause some diseases. Dietary protein supplementation can alter the composition of intestinal microorganisms and thus regulates the body health. However, protein can also produce some harmful metabolites. Therefore, how to rationally supplement protein is particularly important.

Medium-chain fatty acids (MCFAs) are the main form of Medium Chain Triglycerides (MCTs) utilized by monogastric animals. MCFAs can be directly absorbed and supply rapid energy to promote the renewal and repair of intestinal epithelial cells, maintain the integrity of intestinal mucosal barrier function, and reduce inflammation and stress. In our review, we pay more attention to the role of MCFAs on intestinal microbiota and mucosa immunity to explore MCFA's positive effect. It was found that MCFAs and their esterified forms can decrease pathogens while increasing probiotics. In addition, being recognized via specific receptors, MCFAs are capable of alleviating inflammation to a certain extent by regulating inflammation and immune-related pathways. MCFAs may also have a certain value to relieve intestinal allergy and inflammatory bowel disease (IBD). Unknown mechanism of various MCFA characteristics still causes dilemmas in the application, thus MCFAs are used generally in limited dosages and combined with short-chain organic acids (SOAs) to attain ideal results. We hope that further studies will provide guidance for the practical use of MCFAs in animal feed.

Five new phloroglucinol derivatives, eucalyptins C-G (1-5), together with 13 known analogues (6-18) were isolated from the fruits of Eucalyptus globulus. The structures and absolute configurations of 1-5 were established by means of spectroscopic data analysis, computational calculation methods, and single-crystal X-ray diffraction. Compounds 1-18 were investigated for their immunosuppressive effects in vitro, and 1, 2, 6, and 7 displayed moderate inhibitory activities with IC50 values of 11.8, 10.2, 18.2, and 19.1 μM, respectively. The stimulation index (SI) of 1 was 64.2 and was compared to that of cyclosporine A (SI = 149.57). Further study demonstrated that 1 exhibited an immunosuppressive effect through inducing apoptosis and inhibiting cytokine secretion.

In this work two novel cationic lipids using natural tartaric acid as linking backbone were synthesized. These cationic lipids were simply constructed by tartaric acid backbone using head group 6-aminocaproic acid and saturated hydrocarbon chains dodecanol (T-C12-AH) or hexadecanol (T-C16-AH). The physicochemical properties, gel electrophoresis, transfection activities, and cytotoxicity of cationic liposomes were tested. The optimum formulation for T-C12-AH and T-C16-AH was at cationic lipid/dioleoylphosphatidylethanolamine (DOPE) molar ratio of 1 : 0.5 and 1 : 2, respectively, and N/P charge molar ratio of 1 : 1 and 1 : 1, respectively. Under optimized conditions, T-C12-AH and T-C16-AH showed effective gene transfection capabilities, superior or comparable to that of commercially available transfecting reagent 3β-[N-(N',N'-dimethylaminoethyl)carbamoyl]cholesterol (DC-Chol) and N-[2,3-dioleoyloxypropyl]-N,N,N-trimethylammonium chloride (DOTAP). The results demonstrated that the two novel tartaric acid-based cationic lipids exhibited low toxicity and efficient transfection performance, offering an excellent prospect as nonviral vectors for gene delivery.

Homeostasis of nutrient metabolism is critical for maintenance of the normal physiologic status of the cell and the integral health of humans and mammals. In vivo, there is a highly efficient and precise process involved in nutrient recycling and organelle cleaning. This process is named autophagy, and it can be induced in response to the dynamic change of nutrients. When cells face nutritional stress, such as stress caused by nutrient deficiency or nutrient excess, the autophagy pathway will be activated. Generally, when nutrients are withdrawn, cells will sense the signs of starvation and respond. AMP-activated protein kinase and the mammalian target of rapamycin, two of the major metabolic kinases, are responsible for monitoring cellular energy and the concentration of amino acids, respectively. Nutrient excess also induces autophagy, mainly via the reactive oxygen species and endoplasmic reticulum stress pathway. When nutritional stress activates the autophagy pathway, the nutrients or damaged organelles will be recycled for cell survival. However, if autophagy is overwhelmingly induced, autophagic cell death will possibly occur. The balance of the autophagy induction is the crucial factor for cell survival or death. Herein, we summarize the current knowledge on the induction of autophagy, the autophagy response under nutritional stresses, and autophagic cell death and related diseases, which will highlight the process of nutritional stress-induced autophagy and its important physiologic and/or pathologic roles in cell metabolism and diseases, and shed light on the research into the mechanism and clinical applications of autophagy induced by nutritional stresses.

Background Nuclear protein poly (ADP-ribose) polymerase-1 (PARP-1) is a key enzyme in the repair of DNA and is a promising target in the development of chemosensitizers. This study first investigated the inhibitory effects of amentoflavone (AMF) and its derivatives on PARP-1 and the potentiation of AMF on carboplatin (CBP) in non-small cell lung cancer (NSCLC). Purpose This study aims to evaluate the inhibitory effect of AMF against PARP-1 and its potentiation on CBP in lung cancer both in vitro and in vivo. Study design The inhibitory effect of AMF on PARP-1 was investigated using molecular docking and cell-free model of PARP-1 assay. Its potentiation on CBP in lung cancer was also evaluated. Methods Fluorescence resonance energy transfer assay was used to detect the inhibitory effects of AMF and its analogues on PARP-1. Molecular docking was employed to predict the binding mode of AMF and PARP-1. MTT assay, isobologram analysis, Hoechst staining, and Annexin V-PI double staining were used to confirm the potentiation of AMF on CBP in vitro. siRNA (PARP-1)-A549 cells were used to reveal the action target of AMF. Western blot analysis, immunohistochemistry, and Tunnel assay were employed to evaluate the potentiation of AMF on CBP in A549 xenograft mice. Results AMF and its analogues exerted excellent inhibitory effects on PARP-1 with IC50 values ranging from 0.198 μM to 0.409 μM. Docking experiment showed that AMF can stably bind to PARP-1 with a comparable binding energy to olaparib. AMF can decrease the expression of PAR induced by H2O2 in vitro. AMF synergistically increased the CBP anti-proliferative effect in A549. However, its potentiation nearly disappeared when the cells were transfected with siRNAs against PARP-1. Oral administration of AMF (100 mg/kg), combined with CBP, remarkably inhibited A549 tumor growth and ki67 expression, and increased apoptosis compared with CBP-alone group. Conclusion All results suggest that AMF can be a potential PARP-1 inhibitor and a candidate adjuvant agent to boost the anticancer effect of CBP in NSCLC.

To explore the clinical effects of bone filling bag vertebroplasty in treating osteoporotic vertebral compression fractures.The clinical data of 127 patients (145 vertebrae) with osteoporotic vertebral compression fractures who corresponded the criteria of inclusion and exclusion from December 2015 to June 2017 were retrospectively analyzed. Responsible vertebral bodies were identified by clinical situation, X-rays, CT scan, MRI. Among them, 95 cases (110 vertebrae) were treated by percutaneons kyphoplasty (PKP group), there were 34 males (42 vertebrae) and 61 females (68 vertebrae), with an average age of (73.92±7.14) years, 47 thoracic vertebra (T₈-T₁₂) and 63 lumbar vertebra (L₁-L₅). Other 32 patients (35 vertebrae) were treated by bone filling bag vertebroplasty(bone filling bag vertebroplasty group). There were 11 males (12 vertebrae) and 21 females (23 vertebrae), with an average age of (71.56±7.89) years, 16 thoracic vertebra (T₉-T₁₂) and 19 lumbar vertebra(L₁-L₅). Postoperative pain after 3 days, vertebral body height, improvement of lumbar function were recorded and bone cement diffusion and leakage were observed by X-rays.All operations were successful and no complications were found. In bone filling bag vertebroplasty group, operation time was (31.75±4.99) min, postoperative VAS score at 3 days was(2.38±0.94) points, anterior and middle height of the vertebral body were(19.54±2.36) mm and (18.16±2.65) mm, respectively; ODI score was(25.19±5.49) points, all above items after operation were better than preoperation(The clinical effect of bone filling bag vertebroplasty in the treatment of osteoporotic vertebral compression fractures is similar to percutaneous kyphoplasty, it can effectively relieve the pain, restore part vertebral body height and obviously reduce the leakage rate, with safer, it is a simple, rapid and effective therapeutic method.

Dietary protein is a vital nutrient for humans and animals, which is primarily digested into peptides and free amino acids (FAAs) in the upper gastrointestine with the help of proteases. The products are absorbed by the enterocytes and are metabolized in different organs of body. Dietary protein, peptides and FAAs that escape digestion and absorption of the small intestine will enter the large intestine for further fermentation by the vast gut microbiota. Particularly, amino acid (AAs) metabolism by bacteria occurs via either deamination or decarboxylation reactions and generates short chain fatty acids (SCFAs) or amines, respectively. These metabolites elicit a wide range of biological functions via different receptors and mechanisms. This review discusses the interaction between protein metabolites and gastrointestine, illustrates regulation of intestinal motility and immune response by SCFAs and their receptors, and focuses on modulation of intestinal inflammation and signal transduction by biogenic amines (BAs) involving polyamines and monoamine neurotransmitters.

Non-viral nanovectors have attracted much attention owing to their ability to condense genetic materials and their ease of modification. However, their poor stability, low biocompatibility and gene degradation in endosomes or lysosomes has significantly hampered their application in vivo and in the clinic. In an attempt to overcome these difficulties a series of bovine serum albumin (BSA)-calcium phosphate (CaP) nanoparticles were constructed. The CaP condenses with DNA to form nanocomplexes coated with a biomimetic corona of BSA. Such complexes may retain the inherent endocytosis profile of BSA, with improved biocompatibility. In particular the transgene performance may be enhanced by stimulating the cellular uptake pathway via caveolae-mediated endocytosis. Two methods were employed to construct and optimize the formulation of BSA-CaP nanomaterials. The optimized BSA-CaP-50-M2 nanoparticles prepared by our second method exhibited good stability, negligible cytotoxicity and enhanced transgene performance with long-term expression for 72 h in vivo even with a single dose. Determination of the cellular uptake pathway and Western blot revealed that cellular uptake of the designed BSA-CaP-50-M2 nanoparticles was mainly via caveolae-mediated endocytosis in a non-degradative pathway in which the biomimetic uptake profile of BSA was retained.

Butyrate, a four-carbon short-chain fatty acid, is produced through microbial fermentation of dietary fibers in the lower intestinal tract. Endogenous butyrate production, delivery, and absorption by colonocytes have been well documented. Butyrate exerts its functions by acting as a histone deacetylase (HDAC) inhibitor or signaling through several G protein-coupled receptors (GPCRs). Recently, butyrate has received particular attention for its beneficial effects on intestinal homeostasis and energy metabolism. With anti-inflammatory properties, butyrate enhances intestinal barrier function and mucosal immunity. However, the role of butyrate in obesity remains controversial. Growing evidence has highlighted the impact of butyrate on the gut-brain axis. In this review, we summarize the present knowledge on the properties of butyrate, especially its potential effects and mechanisms involved in intestinal health and obesity.

There is growing recognition that composition and metabolic activity of the gut microbiota can be modulated by the dietary proteins which in turn impact health. The amino acid composition and digestibility of proteins, which are influenced by its source and amount of intake, play a pivotal role in determining the microbiota. Reciprocally, it appears that the gut microbiota is also able to affect protein metabolism which gives rise to the view that function between the microbiota and protein can proceed in both directions. In response to the alterations in dietary protein components, there are significant changes in the microbial metabolites including short chain fatty acids (SCFAs), ammonia, amines, gases such as hydrogen, sulfide and methane which are cytotoxins, genotoxins and carcinogens associated with development of colon cancer and inflammatory bowel diseases. A suitable ratio between protein and carbohydrate or even a low protein diet is recommended based on the evidence that excessive protein intake adversely affects health. Supplying high and undigested proteins will encourage pathogens and protein-fermenting bacteria to increase the risk of diseases. These changes of microbiota can affect the gut barrier and the immune system by regulating gene expression in relevant signaling pathways and by regulating the secretion of metabolites. The objective of this review is to assess the impact of dietary proteins on microbiota composition and activity in the gastrointestinal tract. Attention should be given to the dietary strategies with judicious selection of source and supplementation of dietary protein to benefit gut health.

Matrix metalloproteinase (MMP)-2 and MMP-9 are important proteases involved in invasion and metastasis of various tumors. Extra-gastrointestinal stromal tumors (EGISTs) are rare neoplasms. This study was performed to assess MMP-2 and MMP-9 expression in EGIST tissue samples for association with clinicopathological data from the patients. Twenty-one surgical EGIST tissue specimens were collected for analysis of MMP-2 and MMP- 9 expression using immunohistochemistry. MMP-2 and MMP-9 proteins were expressed in all of the epithelial cell types of EGISTs, whereas they were only expressed in 75% of the spindle cell type, although there was no statistically significant difference (p0.05). Expression of MMP-2 and MMP-9 proteins was associated with tumor size, mitotic rate, tumor necrosis, and distant metastasis (p0.05). MMP-2 expression was linked with MMP-9 levels (p0.05). However, there was no correlation between MMP-9 expression and age, sex, primary site, or cell morphology in any of these 21 EGIST patients (p0.05). Moreover, expression of MMP-2 and MMP-9 proteins increased with the degree of EGIST risk. This study provided evidence of an association of MMP-2 and MMP-9 expression with advanced EGIST behavior.

Polyphenols are the main active component of tea and are considered an antiatherosclerosis agent, protecting vascular endothelial cells (VECs) from injury and preventing cardiovascular diseases. Endothelin level, intracellular calcium concentration, and mitochondrial membrane potential in VECs directly reflect the function and injury status of cells. The objective of this study was to study the regulating effects of tea polyphenols on these factors in VECs injured by angiotensin II (Ang-II) and explore the protective effect of tea polyphenols on human VECs.In this study, human aortic vascular endothelial cells were divided into 4 groups: (1) a control group; (2) Ang-II group: Ang-II at a concentration of 10(-7) mol/L was added to the cells; (3) low-concentration tea polyphenols + Ang-II group: tea polyphenols at a concentration of 5 mg/L was added in addition to Ang-II; (4) high-concentration tea polyphenols + Ang-II group: tea polyphenols at a concentration of 25 mg/L was added in addition to Ang-II. One hundred microliters of supernatant was extracted before treatment and at 0.5, 6, and 24 hours after treatment in each group to establish the content of endothelin.The results showed the following: (1) tea polyphenols decreased the expression of endothelin-1 messenger RNA, which was increased by Ang-II (P0.01). (2) Tea polyphenols inhibited endothelin secretion induced by Ang-II (P0.01), and the inhibition of low-concentration tea polyphenols was superior to that of high concentration tea polyphenols (P0.01). (3) Tea polyphenols ameliorated the changes in intracellular calcium concentration and mitochondrial membrane potential induced by Ang-II (P0.01).This study suggests that tea polyphenols may effectively protect VECs against injury by regulating endothelin, intracellular calcium concentration, and mitochondrial membrane potential in VECs injured by Ang-II. Additionally, lower dose would be used clinically rather than the higher dose for obtaining better results.

Glucose and lipid are the major energy sources, and pivotal components of organic metabolism in mammals. Inappropriate diet directly influences the metabolic rate, and can alter the body's homeostasis. The underlying changes in energy storage and utilization would manifest as metabolic syndrome including obesity and high blood pressure, and high blood glucose, which are predisposing factors that significantly increase the risk for cardiovascular diseases and Type 2 Diabetes (T2D). Thus, it is essential to identify the genes that are involved in the process of glucose and lipid metabolism. Utilizing current advanced scientific methodology and technology, as well as computational resources has led to discovery of many novel genes with major roles in energy metabolism. In addition, many studies have focused on the functional analysis of the novel genes. Nowadays, uncovering the genes that are involved in glucose and lipid storage and utilization, as well as underlying pathways that regulate expression of those genes is an area of ongoing research. Here, we summarize the current research related to the novel genes regulating glucose and lipid metabolisms, which enable us to develop more efficient means of prevention and management of metabolic diseases such as T2D, obesity, high blood glucose, and hypertension.

Gastrointestinal homeostasis is a dynamic balance under the interaction between the host, GI tract, nutrition and energy metabolism. Glucose is the main energy source in living cells. Thus, glucose metabolic disorders can impair normal cellular function and endanger organisms' health. Diseases that are associated with glucose metabolic disorders such as obesity, diabetes, hypertension, and other metabolic syndromes are in fact life threatening. Digestive system is responsible for food digestion and nutrient absorption. It is also involved in neuronal, immune, and endocrine pathways. In addition, the gut microbiota plays an essential role in initiating signal transduction, and communication between the enteric and central nervous system. Gut-brain axis is composed of enteric neural system, central neural system, and all the efferent and afferent neurons that are involved in signal transduction between the brain and gut-brain. Gut-brain axis is influenced by the gut-microbiota as well as numerous neurotransmitters. Properly regulated gut-brain axis ensures normal digestion, absorption, energy production, and subsequently maintenance of glucose homeostasis. Understanding the underlying regulatory mechanisms of gut-brain axis involved in gluose homeostasis would enable us develop more efficient means of prevention and management of metabolic disease such as diabetic, obesity, and hypertension.

Type 2 diabetes has become a global public health problem affecting approximately 380 million people throughout the world. It can cause many complications and lead to greater mortality. At present, there is no available medicine for effectively preventing diabetes. L-arginine, a functional amino acid, the precursor of nitric oxide, plays a crucial role in maintenance, reproduction, growth, anti-aging and immunity for animals. Growing clinical evidence indicates that dietary L-arginine supplementation can reduce obesity, decrease arterial blood pressure, resist oxidation and normalize endothelial dysfunction to bring about remission of type 2 diabetes. The potential molecular mechanism may play a role in modulating glucose homeostasis, promoting lipolysis, maintaining hormone levels, ameliorating insulin resistance, and fetal programing in early stages. The possible signaling pathway of the beneficial effects of L-arginine likely involves L-arginine-nitric oxide pathway through which cell signal protein can be activated. Accumulating studies have indicated that L-arginine may have potential to prevent and/or relieve type 2 diabetes via restoring insulin sensitivity in vivo.

Accumulating evidence is dramatically increasing the access to the facts that the gut microbiota plays a pivotal role in host metabolism and health, which revealed the possibility of a plethora of associations between gut bacteria and human diseases. Several functional roles are carried out by a major class of the host's diet, such as fiber. Fiber is the main source of microbiota-accessible carbohydrate in the diet of humans. In the modern diet, it is difficult to intake sufficient dietary fiber as recommended. The low-fiber diet in the modern life, known as fiber gap, can trigger a substantial depletion of the human gut microbiota diversity and beneficial metabolites. The short-chain fatty acids are regarded as one of the major microbial metabolites of dietary fibers, which can improve intestinal mucosal immunity, as well as to be a source of energy for the liver. Thus, the loss of microbiota diversity has a potential negative function to various aspects of host health. Actually, the real "fiber gap" for ideal health and maintaining microbial diversity might be even more serious than currently appreciated. Herein, we briefly discuss the interactions between gut microbiota and the host diet, focusing specifically on the low-fiber diet. Gut bacteria in the context of the development of host low-fiber diets, which may lead to health and disorders, particularly include metabolic syndrome and obesity-related disease, IBD liver, disease, and colorectal cancer.

This study was conducted to evaluate the effects of grape-seed procyanidins in controlling weaning diarrhea using a rat model. Weaned rats were fed either the basal diet or basal diet supplemented with either 250 mg/kg grape-seed procyanidins or 2000 mg/kg ZnO. Treated rats had better performance with a reduced incidence of diarrhea (P < 0.05). Both ZnO and grape-seed procyanidins significantly reduced urinary lactulose to mannitol ratios (P < 0.05) and enhanced the mRNA and protein expression of the intestinal mucosal tight junction proteins Ocln/ZO-1 (P < 0.05). Grape-seed procyanidins increased the activities of SOD, GSH-Px, and GSH while decreasing the level of MDA in the intestinal mucosa (P < 0.05). Furthermore, an in vitro investigation revealed that supplementation with grape-seed procyanidins in IEC-6 intestinal epithelial cells significantly enhanced the expression of Ocln/ZO-1 under H(2)O(2)-induced oxidative stress. Collectively, these results indicate that grape-seed procyanidins have the potential to prevent weaning diarrhea by reducing intestinal permeability and improving antioxidant indices.