Thursday, November 26, 2020

Effects of Dietary Protein Levels on Bamei Pig Intestinal Colony Compositional Traits

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Diets containing different crude protein levels (16%, 14%, and 12%) were created to feed Bamei pigs in order to study the effect of these compositions on intestinal colonies. Therefore, 27 healthy Bamei pigs of similar weight () were selected and randomly divided into three groups for microbial diversity analysis. The results of this study show that microbial diversities and abundances in Bamei pig jejunum and caecum samples after feeding with different dietary protein levels were significantly different. Dietary crude protein level exerted no significant effect on the Shannon index for cecum microbes in these pigs, while Simpson, ACE, and Chao1 indices for group I were all significantly higher than those of either the control group or group II (). Indeed, data show that microbial diversities and abundance s in the 14% protein level group were higher than those in either the 16% or 12% groups. Dominant bacteria present in jejunum and cecum samples given low-protein diets were members of the phyla Firmicutes and Bacteroidetes. Data show that as dietary crude protein level decreases, representatives of the microbial flora genus Lactobacillus in jejunum and cecum samples gradually increases. Values for the KEGG functional prediction of microbial flora at different dietary protein levels also show that genes of jejunum and cecum microorganisms were mainly enriched in the "metabolism" pathway and indicate that low protein diets increase intestinal metabolic activity. Therefore, we recommend that Bamei pig dietary protein levels are reduced 2% from their existing level of 16% crude protein. We also suggest that essential synthetic amino acids (AA) are added to optimize this ideal protein model as this will increase intestinal flora diversity in these pigs and enhance health. These chang es will have a positive effect in promoting the healthy growth of Bamei pigs.
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Hydroethanolic Extract from Bridelia atroviridis Müll. Arg. Bark Improves Haematological and Biochemical Parameters in Nicotinamide-/Streptozotocin-Induced Diabetic Rats

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Bridelia atroviridis Müll. Arg. (B. atroviridis) is a plant used in Cameroonian traditional medicine to manage diabetes. The effects of hydroethanolic barks extract from B. atroviridis were evaluated on diabetes disorders including hematology, inflammatory, and oxidative stress parameters. The in vitro antioxidant capacity of the hydroethanolic bark extract (70 : 30) was evaluated. Nicotinamide-/streptozotocin-induced diabetic rats were daily treated with the B. atroviridis extract for fifteen days. Glycemia were evaluated every 5 days, insulin sensibility test was performed, and haematological, inflammatory, and oxidative stress parameters were analysed. Histomorphometry of the pancreas was realized. The extract was able to scavenge free radicals in vitro and decrease significantly the blood glucose levels. The treatment resulted in a significant alleviation of insulin resistance, anemia, leukocytopenia, and thrombocytopenia observed in untreated diabetic rats. The extract significantly decreased proinflammatory cytokines TNF-α, IL-1β, and IL-10. The rate of reduced glutathione was increased in the pancreas, whereas the catalase activity and nitrite concentration were decreased. Diabetic control showed a reduced size of Langerhans islet, whereas the size of islets was large in treated groups. The hydroethanolic extract of B. atroviridis was able to improve glycemia and alleviate haematological and inflammatory parameters disorders observed in diabetic conditions, probably due to its antidiabetic, anti-inflammatory, and antioxidant capacities.
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Effect of Sheng-Jiang Powder on Gut Microbiota in High-Fat Diet-Induced NAFLD

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Background and Aims. Nonalcoholic fatty liver disease (NAFLD) is an alarming global health problem that is predicted to be the major cause of cirrhosis, hepatocellular carcinoma, and liver transplantation by next decade. Gut microbiota have been revealed playing an important role in the pathogenesis of NAFLD. Sheng-Jiang Powder (SJP), an empirical Chinese medicine formula to treat NAFLD, showed great hepatoprotective properties, but the impact on gut microbiota has never been identified. Therefore, we performed this study to investigate the effect of SJP on gut microbiota in NAFLD mice. Methods. NAFLD was induced by 12 weeks' high-fat diet (HFD) feeding. Mice were treated with SJP/normal saline daily for 6 weeks. Blood samples were obtained for serum biochemical indices and inflammatory cytokines measure ment. Liver tissues were obtained for pathological evaluation and oil red O staining. The expression of lipid metabolism-related genes was quantified by RT-PCR and Western blotting. Changes in gut microbiota composition were analyzed by the 16s rDNA sequencing technique. Results. HFD feeding induced significant increase in bodyweight and serum levels of TG, TC, ALT, and AST. The pathological examination revealed obvious hepatic steatosis in HFD feeding mice. Coadministration of SJP effectively protected against bodyweight increase and lipid accumulation in blood and liver. Increased expression of PPARγ mRNA was observed in HFD feeding mice, but a steady elevation of PPARγ protein level was only found in SJP-treated mice. Meanwhile, the expression of FASN was much higher in HFD feeding mice. Microbiome analysis revealed obvious changes in gut microbiota composition among diverse groups. SJP treatment modulated the relative abundance of short-chain fatty acids (SCFAs) producing bact eria, including norank-f-Erysipelotrichaceae and Roseburia. Conclusions. SJP is efficient in attenuating HFD-induced NAFLD, and it might be partly attributed to the regulation of gut microbiota.
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The Therapeutic Effect of Active Vitamin D Supplementation in Preventing the Progression of Diabetic Nephropathy in a Diabetic Mouse Model

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Background. Diabetic nephropathy (DN) is one of the most common microvascular complications of diabetes and is the leading cause of end-stage renal disease (ESRD) and replacement therapy worldwide. Vitamin D levels in DN patients are very low due to the decrease in the synthesis and activity of 1-α hydroxylase in the proximal tubule cells and decrease in the vitamin D receptor abundance. To date, few studies have shown the antioxidant effects of 1α,25-dihydroxyvitamin D3 [1,25(OH)2D3] on hyperglycemia-induced renal injury. The selective activator of the vitamin D receptor, paricalcitol, reduces proteinuria and slows the progression of kidney injury. The precise mechanism through which vitamin D affects diabetic status and provides kidney protection remains to be determined. Methods. Diabetes mellitus (DM) w as induced in 94 8-week-old DBA/2J mice by intraperitoneal injection of streptozotocin (STZ). DM mice were randomly divided into receiving vehicle or treatment with paricalcitol, the active vitamin D analog, 1 week after DM induction or paricalcitol treatment 3 weeks after DM induction. An additional control group of healthy wild-type mice was not treated. Urine albumin, blood urea nitrogen, and creatinine levels were measured before and at the end of the paricalcitol treatment. Periodic acid-Schiff, immunohistochemistry staining, and western blot of the renal tissues of vitamin D receptor, villin, nephrin, and podocin expressions, were analyzed. Results. Paricalcitol treatment restored villin, nephrin, and podocin protein levels that were downregulated upon DM induction, and reduced fibronectin protein level. Vitamin D receptor activation by paricalcitol may reduce proteinuria of DN in mice and alleviate high-glucose-induced injury of kidney podocytes by regulating the key molecule s such nephrin-podocin. Conclusions. Paricalcitol treatment was associated with improved structural changes in type 1 diabetic mice including upregulation of vitamin D receptor expression, and decreased fibrosis markers such as fibronectin. These effects may contribute to the consistent benefit of vitamin D analog to slow the deterioration in glomerular function and reduce the risk of ESRD in patients with type 1 and 2 diabetes mellitus. Our results suggest that additional use of paricalcitol may be beneficial in treating patients with diabetes under standard therapeutic strategies.
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The Role of Oxymatrine in Amelioration of Acute Lung Injury Subjected to Myocardial I/R by Inhibiting Endoplasmic Reticulum Stress in Diabetic Rats

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Background. Oxymatrine (OMT) is the primary pharmacological component of Sophora flavescens Aiton., which has been shown to possess potent antifibrotic, antioxidant, and anti-inflammatory activities. The aim of the present study was to clarify the protective mechanism of OMT on acute lung injury (ALI) subjected to myocardial ischemia/reperfusion (I/R). Methods. A myocardial I/R-induced ALI model was achieved in diabetic rats by occluding the left anterior descending coronary artery for 1 h, followed by reperfusion for 1 h. The levels of inflammatory factors (tumor necrosis factor-α, interleukin- (IL-) 6, and IL-17) in bronchoalveolar lavage fluid were assessed using commercially available kits. The index of myocardial injury, including the detection of cardiac troponin I (cTnI), cardiac troponin T (cT nT), lactate dehydrogenase (LDH), and creatine kinase-MB (CK-MB), was also determined using commercially available kits. Hematoxylin and eosin staining and terminal deoxynucleotidyl transferase-mediated dUTP nick end labeling were used to identify histological changes. The expression levels of endoplasmic reticulum chaperone BiP (GRP78), DNA damage-inducible transcript 3 protein (CHOP), eukaryotic translation initiation factor 2-alpha kinase 3 (PERK), inositol dependent enzyme 1α (IRE1α), ATF6, caspase-3, -9, and-12, Bcl-2, and Bax were determined by Western blotting. The mRNA expression levels of GRP78 and CHOP were detected by reverse transcription-quantitative PCR. Results. Myocardial I/R increased the levels of cTnI, cTnT, LDH, and CK-MB in diabetic rats. Damaged and irregularly arranged myocardial cells were also observed, as well as more serious ALI with higher lung injury scores and WET/DRY ratios and lower PaO2. Moreover, the expression of key proteins of endoplasmic retic ulum stress (ERS) was increased by I/R injury, including phosphorylated- (p-) PERK, p-IRE1ɑ, and ATF6, as well as decreased levels of apoptosis. These effects were all significantly reversed by OMT treatment. Conclusions. OMT protects against ALI subjected to myocardial I/R by inhibiting ERS in diabetic rats.
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The Development of Three-DNA Methylation Signature as a Novel Prognostic Biomarker in Patients with Colorectal Cancer

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Aims. The prognosis of colorectal cancer (CRC) remains poor. This study aimed to develop and validate DNA methylation-based signature model to predict overall survival of CRC patients. Methods. The methylation array data of CRC patients were retrieved from The Cancer Genome Atlas (TCGA) database. These patients were divided into training and validation datasets. A risk score model was established based on Kaplan-Meier and multivariate Cox regression analysis of training cohort and tested in validation cohort. Results. Among total 14,626 DNA methylation candidate markers, we found that a three-DNA methylation signature (NR1H2, SCRIB, and UACA) was significantly associated with overall survival of CRC patients. Subgroup analysis indicated that this signature could predict overall survival of CRC patients reg ardless of age and gender. Conclusions. We established a prognostic model consisted of 3-DNA methylation sites, which could be used as potential biomarker to evaluate the prognosis of CRC patients.
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The Nrf2/PGC1α Pathway Regulates Antioxidant and Proteasomal Activity to Alter Cisplatin Sensitivity in Ovarian Cancer

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Drug resistance remains a barrier in the clinical treatment of ovarian cancer. Proteasomal and antioxidant activities play important roles in tumor drug resistance, and increasing evidence suggests the existence of an interaction between antioxidant and proteasomal activities. However, the mechanism of the synergistic effects of proteasomal activity and antioxidation on tumor drug resistance is not completely clear. In this study, we compared two ovarian cancer cells, A2780 and SKOV3 cells. Among them, SKOV3 cell is a human clear cell carcinoma cell line that is resistant to platinum. We found that compared with the findings in A2780 cells, SKOV3 cells were less sensitive to both proteasomal inhibitor and cisplatin. Proteasomal inhibition enhanced the sensitivity of A2780 cells, but not SKOV3 cells, to cis platin. Notably, the Nrf2-mediated antioxidant pathway was identified as a resistance mechanism in proteasome inhibitor-resistant cells, but this was not the only factor identified in our research. In SKOV3 cells, PGC1α regulated the antioxidant activity of Nrf2 by increasing the phosphorylation of GSK3β, and in turn, Nrf2 regulated the transcriptional activity of PGC1α. Thus, Nrf2 and PGC1α synergistically participate in the regulation of proteasomal activity. Furthermore, the Nrf2/PGC1α pathway participated in the regulation of mitochondrial function and homeostasis, further regulating proteasomal activity in SKOV3 cells. Therefore, exploring the roles of PGC1α and Nrf2 in the regulation of proteasomal activity by antioxidant and mitochondrial functions may provide new avenues for reversing drug resistance in ovarian cancer.
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Neural Model Stealing Attack to Smart Mobile Device on Intelligent Medical Platform

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To date, the Medical Internet of Things (MIoT) technology has been recognized and widely applied due to its convenience and practicality. The MIoT enables the application of machine learning to predict diseases of various kinds automatically and accurately, assisting and facilitating effective and efficient medical treatment. However, the MIoT are vulnerable to cyberattacks which have been constantly advancing. In this paper, we establish a MIoT platform and demonstrate a scenario where a trained Convolutional Neural Network (CNN) model for predicting lung cancer complicated with pulmonary embolism can be attacked. First, we use CNN to build a model to predict lung cancer complicated with pulmonary embolism and obtain high detection accuracy. Then, we build a copycat model using only a small amount of data labeled by the target network, aiming to steal the established prediction model. Experimental results prove that the stolen model can also achieve a relatively high prediction outcome, revealing that the copycat network could successfully copy the prediction performance from the target network to a large extent. This also shows that such a prediction model deployed on MIoT devices can be stolen by attackers, and effective prevention strategies are open questions for researchers.
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Current and Potential Applications of Artificial Intelligence in Gastrointestinal Stromal Tumor Imaging

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The most common mesenchymal tumors are gastrointestinal stromal tumors (GISTs), which have malignant potential and can occur anywhere along the gastrointestinal system. Imaging methods are important and indispensable of GISTs in diagnosis, risk staging, therapy, and follow-up. The recommended imaging method for staging and follow-up is computed tomography (CT) according to current guidelines. Artificial intelligence (AI) applies and elaborates theses, procedures, modes, and utilization systems for simulating, enlarging, and stretching the intellectual capacity of humans. Recently, researchers have done a few studies to explore AI applications in GIST imaging. This article reviews the present AI studies in GISTs imaging, including preoperative diagnosis, risk stratification and prediction of prognosis, gene mutation, and targeted therapy response.
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Robot-assisted neurosurgery versus conventional treatment for intracerebral hemorrhage: A systematic review and meta-analysis

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Intracerebral hemorrhage (ICH) is bleeding within the brain caused by rupture of blood vessels. It is one of the subtypes of stoke which is second leading cause of death around the world [1]. According to AHA/ASA Guideline for the Management of Spontaneous Intracerebral Hemorrhage, commonly used treatments for ICH are medical treatment including hemostasis, coagulopathy, antiplatelets and deep vein thrombosis prophylaxis, blood-pressure-lowering treatment and surgery containing endoscopic treatment, craniotomy and minimally invasive surgical evacuation [2].
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The Effect of Laparoscopic Sleeve Gastrectomy on Gastroesophageal Reflux Disease

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Abstract

Background

The laparoscopic sleeve gastrectomy (LSG) has become one of the most popular surgical weight loss options. Since its inception as a procedure intended to promote durable weight loss, the association between LSG and gastroesophageal reflux disease (GERD) has been a point of debate. First and foremost, it is known that GERD occurs more frequently in the obese population. With the sleeve gastrectomy growing to be the predominant primary bariatric operation in the United States, it is imperative that we understand the impact of LSG on GERD.

Objective

To examine the effects of LSG on GERD symptoms.

Methods

One hundred and ninety-one bariatric surgery candidates completed a Gastroesophageal Reflux Disease-Health-Related Quality of Life (GERD-HRQL) questionnaire before and after undergoing elective LSG (mean follow-up time of 20.4 ± 2.7 months). Values were stratified by the presence or absence of preoperative GERD, GERD medications, age, gender, crural repair, patient satisfaction with present condition, and percent total weight loss (%TWL).

Results

For the entire group, mean weight loss, %TWL, and reduction in BMI were 79 pounds, 28.1%, and 12.7 kg/m2 respectively. Within the overall cohort, there was no significant change in GERD symptoms from before to after surgery (mean GERD-HRQL scores were 6.1 before and after surgery, p = 0.981). However, in a subgroup analysis, patients without GERD preoperatively demonstrated a worsening in mean GERD-HRQL scores after surgery (from 2.4 to 4.5, p = 0.0020). The percentage of change in the usage of medications to treat GERD was not statistically significant (from 37 to 32%, p = 0.233). The percent of patients satisfied with their condition postoperatively was significantly increased in those with preoperative GERD, older age, crural repair intraoperatively, and in those with the highest %TWL.

Conclusion

These results suggest that while overall LSG does not significantly affect GERD symptoms, patients without GERD preoperatively may be at risk for developing new or worsening GERD symptoms after surgery. It is important to remark that this is a review of the patient's clinical symptoms of GERD, not related to any endoscopic, pathological, or manometry studies. Such studies are necessary to fully establish the effect of LSG on esophageal health.

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[News] Carcinogenicity of acrolein, crotonaldehyde, and arecoline

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In October–November, 2020, a Working Group of 20 scientists from ten countries met remotely at the invitation of the International Agency for Research on Cancer (IARC) to finalise their evaluations of the carcinogenicity of acrolein, crotonaldehyde, and arecoline. Acrolein was classified as "probably carcinogenic to humans" (Group 2A) on the basis of "sufficient" evidence of carcinogenicity in experimental animals and "strong" mechanistic evidence. Crotonaldehyde and arecoline were classified as "possibly carcinogenic to humans" (Group 2B) on the basis of "strong" mechanistic evidence.
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