Abnormal Protein Metabolism Research Articles

Key extracellular proteins and TF-miRNA co-regulatory network in diabetic foot ulcer: Bioinformatics and experimental insights.

Diabetic foot ulcers (DFUs), a serious complication of diabetes, are associated with abnormal extracellular protein (EP) metabolism. The identification of key EPs and their regulatory networks is crucial for the understanding of DFU formation and development of effective treatments. In this study, a large-scale bioinformatics analysis was conducted to identify potential therapeutic targets and experimental validation was performed to ensure the reliability and biological relevance of the findings. Due to the comprehensive profiling of DFU samples provided by the GSE80178 dataset, we initially selected it to derive differentially expressed genes (DEGs) associated with DFU. Subsequently, utilizing the UniProt database and annotated EP list from the Human Protein Atlas annotation database, we screened for extracellular protein-related differentially expressed genes (EP-DEGs) due to their crucial role in the pathogenesis and healing of DFU. We examined EP-DEG pathway enrichment and protein-protein interaction networks, analyzed paired full-thickness skin tissue samples from 24 patients with DFUs and healthy controls, and performed polymerase chain reaction (PCR) experiments to validate candidate genes. Ultimately, we constructed a transcription factor (TF)-microRNA (miRNA)-hub gene co-regulatory network to explore upstream and downstream regulatory connections based on validated DEGs. Four crucial candidate genes (FMOD, LUM, VCAN, and S100A12) were identified and verified via PCR analysis. The TF-miRNA-hub EP-DEG regulatory network contained the pivotal TFs TRIM28 and STAT3 and the miRNAs hsa-mir-20a-5p, hsa-miR-21, and hsa-miR-203. The findings of this study advance our understanding of the pathology of DFU by defining key roles of specific EPs and elucidating a comprehensive regulatory network. These insights pave the way for novel approaches to improve DFU treatment outcomes.

Exploration of mitochondrial autophagy related genes in the diagnosis model construction and molecular marker mining of Alzheimer's disease based on multi-omics integration.

Key features of Alzheimer's disease include neuronal loss, accumulation of beta-amyloid plaques, and formation of neurofibrillary tangles. These changes are due in part to abnormal protein metabolism, particularly the accumulation of amyloid beta. Mitochondria are the energy production centers within cells and are also the main source of oxidative stress. In AD, mitochondrial function is impaired, leading to increased oxidative stress and the production of more reactive oxidative substances, further damaging cells. Mitophagy is an important mechanism for maintaining mitochondrial health, helping to clear damaged mitochondria, prevent the spread of oxidative stress, and reduce abnormal protein aggregation. To this end, this article conducts an integrated analysis based on DNA methylation and transcriptome data of AD. After taking the intersection of the genes where the differential methylation sites are located and the differential genes, machine learning methods were used to build an AD diagnostic model. This article screened five diagnostic genes ATG12, CSNK2A2, CSNK2B, MFN1 and PGAM5 and conducted experimental verification. The diagnostic genes discovered and the diagnostic model constructed in this article can provide reference for the development of clinical diagnostic models for AD.

A Comprehensive Review on Alzheimer’s Disease its Pathogenesis, Epidermiology, Diagnostics and Treatment

The global impact of Alzheimer's disease (AD) is significant. The current prevalence of Major Neurocognitive Disorder is estimated to affect approximately 44 million individuals. Presently, the United States harbors a population of approximately 6.2 million individuals who are afflicted by Alzheimer's disease (AD) dementia. It is of significance to highlight that mortality associated with Alzheimer's disease (AD) exceeds the combined mortality rates of both breast cancer and prostate cancer. Based on the findings of the National Institute on Aging, the frequency of Alzheimer's disease (AD) exhibits a twofold rise every five years subsequent to attaining the age of 65. Furthermore, with the ongoing process of population aging, an increasingly substantial portion of the population is affected by this particular condition. Based on forecasts, it is anticipated that the United States will experience a financial impact of $355 billion in 2021 as a result of Alzheimer's disease (AD).
 Furthermore, same projections indicate that this amount is expected to increase significantly to over $1.5 trillion by the year 2050. As a result, this would place a significant financial strain on the country. Alzheimer's disease (AD) is a neurodegenerative condition that is distinguished by the existence of extracellular amyloid β (Aβ) plaques and intracellular neurofibrillary tangles consisting of hyperphosphorylated τ-protein. The aforementioned abnormal characteristics primarily present themselves inside the cortical and limbic regions of the human brain. The aforementioned ailment is characterized by the presence of memory impairment and a progressive deterioration of neurocognitive abilities. The atypical division of amyloid precursor protein (APP) by β-secretases and γ-secretases leads to the production of Aβ40 and Aβ42 individual molecules, which then undergo the process of oligomerization and aggregation, finally culminating in the formation of senile plaques. The aforementioned disease is additionally aggravated by pathogenic microorganisms, including the human immunodeficiency virus (HIV).
 Moreover, within the framework of disease pathophysiology, the presence of heightened amounts of Aβ peptides within the central nervous system induces the infiltration of microglial cells. Presently, there exists a notable focus within the realm of scientific inquiry on gaining a comprehensive understanding of the pathological nature of Alzheimer's disease (AD) by means of exploring diverse pathways.
 These mechanisms include the abnormal metabolism of tau proteins, the presence of β-amyloid, the inflammatory response, as well as the damage caused by cholinergic dysfunction and free radicals. The ultimate objective of this research is to develop efficacious treatments that can effectively halt or alter the progression of AD. The present study provides an analysis of the pathophysiological mechanisms underlying Alzheimer's disease, as well as an examination of the diagnostic methods employed in its identification. Furthermore, the review explores the many therapy modalities now utilized in managing this neurodegenerative disorder.

A Triterpenoid Lupeol as an Antioxidant and Anti-Neuroinflammatory Agent: Impacts on Oxidative Stress in Alzheimer’s Disease

Alzheimer’s disease (AD) is the most common neurodegenerative disease illustrated by neuronal dysfunctions, leading to memory weaknesses and personality changes mostly in the aged population worldwide. The exact cause of AD is unclear, but numerous studies have addressed the involvement of oxidative stress (OS), induced by reactive oxygen species (ROS), to be one of the leading causes in developing AD. OS dysregulates the cellular homeostasis, causing abnormal protein and lipid metabolism. Nutrition plays a pivotal role in modulating the antioxidant system and decreases the neuronal ROS level, thus playing an important therapeutic role in neurodegenerative diseases, especially in AD. Hence, medicinal herbs and their extracts have received global attention as a commercial source of antioxidants Lupeol. Lupeol is a pentacyclic triterpenoid and has many biological functions. It is available in fruits, vegetables, and medicinal plants. It has shown effective antioxidant and anti-inflammatory properties, and higher blood–brain barrier permeability. Also, the binding and inhibitory potentials of Lupeol have been investigated and proved to be effective against certain receptor proteins and enzymes in AD studies by computational molecular docking approaches. Therefore, AD-related research has gained interest in investigating the therapeutic effects of Lupeol. However, despite its beneficial effects in AD, there is still a lack of research in Lupeol. Hence, we compiled in this analysis all preclinical research that looked at Lupeol as an antioxidant and anti-inflammatory agent for AD.

Efektivitas Antidiabetik Oral Baik Kombinasi Maupun Tunggal Pada Pasien Diabetes Mellitus Tipe Ii Di Rsud Caruban

Diabetes Mellitus is a group of chronic metabolic disorders due to abnormal metabolism of carbohydrates, fats, and proteins, characterized by hyperglycemia which is results in long-term microvascular, macrovascular and neuropathic complications. Oral antidiabetic therapy is the main pharmacological therapy to treat type II diabetes mellitus. This therapy can be oral antidiabetic therapy. Thus, to find out the effectiveness of either combination or single of antidiabetics on diabetes mellitus patients, researchers conducted a studies of inpatients at RSUD Madiun. This study included as non-experimental observational study with a cross-sectional study design at RSUD Caruban. Data were collected from Medical Records in October 2018. The sampling method that used in this study was non probability with purposive sampling technique, so there are 58 patients as a total sample. The results showed that the effectiveness of controlling blood sugar levels when using an effective single ADO was Metformin, because Metfomin was able to reduce blood sugar levels with an average length of stay of 6.17 and the effectiveness of controlling blood sugar levels when using an effective combination of ADO was Metformin and acarbosa, because Metfomin and acarbosa are able to reduce blood sugar average length of stay 7 days inpatient.

Rapid discrimination of Brucellosis in sheep using serum Fourier transform infrared spectroscopy combined with PCA-LDA algorithm

Brucellosis in sheep is an infectious disease caused by Brucella melitensis in sheep. The current conventional serological methods for screening Brucella-infected sheep have the disadvantage of time consuming and low accuracy, so a simple, rapid and highly accurate screening method is needed. The aim of this study was to evaluate the feasibility of diagnosing Brucella-infected sheep by serum samples based on the Fourier transform infrared (FTIR) spectroscopy. In this study, FTIR spectroscopy of serum from Brucella-infected sheep (n = 102) and healthy sheep (n = 125) revealed abnormal protein and lipid metabolism in serum from Brucella-infected sheep compared to healthy sheep. Principal component analysis-Linear discriminant analysis (PCA-LDA) method was used to differentiate the FTIR spectra of serum from Brucella-infected sheep and healthy sheep in the protein band (3700–3090 cm−1) and lipid band (3000–2800 cm−1), and its overall diagnostic accuracy was 100% (sensitivity 100%, specificity 100%). In conclusion, our results suggest that serum FTIR spectroscopy combined with PCA-LDA algorithm has great potential for brucellosis in sheep screening.

Diabetes mellitus type 1 and coronary artery disease with severe systolic heart failure in 25 year-old adult

Diabetes mellitus (DM) type 1 accounts for up to 90% of all cases of diabetes among children, adolescents and young adults (10 % are represented by T2DM, MODY, etc.). DM is characterized not only by glucose metabolism disorder, but also by abnormal protein and lipid metabolism, leading to severe macrovascular complications. A clinical case of diabetes type 1, hyperlipidemia, coronary artery disease (CAD) and chronic heart failure (HF) in a 25-year-old adult has been demonstrated. The medical examination revealed lipid metabolism disorders, multivessel coronary artery disease, which required myocardial revascularization, and severe heart failure with a reduced ejection fraction (HFrEF). The clinical case demonstrates that proper cardiovascular examination should be performed in all patients with diabetes and lipid disorders, regardless of age and type of diabetes. The authors also consider the use of sodium-glucose

Data-independent acquisition-based quantitative proteomic analysis of m.3243A>G MELAS reveals novel potential pathogenesis and therapeutic targets.

The pathogenesis of mitochondrial myopathy, encephalopathy, lactic acidosis and stroke like episodes (MELAS) syndrome has not been fully elucidated. The m.3243A > G mutation which is responsible for 80% MELAS patients affects proteins with undetermined functions. Therefore, we performed quantitative proteomic analysis on skeletal muscle specimens from MELAS patients. We recruited 10 patients with definitive MELAS and 10 age- and gender- matched controls. Proteomic analysis based on nanospray liquid chromatography-mass spectrometry (LC-MS) was performed using data-independent acquisition (DIA) method and differentially expressed proteins were revealed by bioinformatics analysis. We identified 128 differential proteins between MELAS and controls, including 68 down-regulated proteins and 60 up-regulated proteins. The differential proteins involved in oxidative stress were identified, including heat shock protein beta-1 (HSPB1), alpha-crystallin B chain (CRYAB), heme oxygenase 1 (HMOX1), glucose-6-phosphate dehydrogenase (G6PD) and selenoprotein P. Gene ontology and kyoto encyclopedia of genes and genomes pathway analysis showed significant enrichment in phagosome, ribosome and peroxisome proliferator-activated receptors (PPAR) signaling pathway. The imbalance between oxidative stress and antioxidant defense, the activation of autophagosomes, and the abnormal metabolism of mitochondrial ribosome proteins (MRPs) might play an important role in m.3243A > G MELAS. The combination of proteomic and bioinformatics analysis could contribute potential molecular networks to the pathogenesis of MELAS in a comprehensive manner.

Extra- versus intracranial atherosclerosis: two facets of the same problem

Atherosclerosis is a chronic disease of elastic and muscle-elastic type arteries, which occurs due to abnormal lipid and protein metabolism and is accompanied by the deposition of cholesterol and certain lipoprotein fractions in the lumen of blood vessels. The article discusses the history of atherosclerosis discovery, various theories of the development of atherosclerosis, main risk factors for the development of the disease. The main groups of biomarkers, their functions and specificity for the diagnosis of atherosclerosis are described, the diagnostic value of such methods as MR angiography, CT angiography and ultrasound is discussed. Different aspects of extra- and intracranial atherosclerosis are outlined. The main possibilities for developing therapeutic strategies to slow the progression and develop targeted therapy are considered, and the portrait of a patient with intracranial atherosclerosis, requiring screening, is described.

An Overview on the Aetiology and Treatment of Alzheimer's Disease

Alzheimer’s disease is a disease that mainly leads to the degeneration of cells in the brain and it causes dementia. This reduces thinking capacity and doesn't allow the person to be independently do their own work. Two main causes of AD are cholinergic and amyloid hypothesis. Other risk factors include age, genetics, infections in the brain etc. currently only two types of drugs can treat AD, cholinesterase enzyme inhibitors and NMDA antagonists, but these are only able to treat the symptoms not the whole disease. At this moment the researchers are trying to target several mechanisms such as abnormal tau protein metabolism, inflammation and damage in the cholinergic system.

Effect of Diabetes Mellitus on the Excretory Function of the Liver

Diabetes mellitus is an internationally recognized health problem and a leading cause of death worldwide. However, the most significant increase in prevalence is expected to occur in Asia and Africa, where most patients will be found by 2030. Diabetic Mellitus is a clinical and metabolic syndrome characterized by abnormal carbohydrate, protein, and fat metabolism resulting in hyperglycemia, increased protein breakdown, Ketosis or acidosis due to absolute or relative deficiency, and insulin resistance, thereby leading to vascular complications such as retinopathy, neuropathy, and nephropathy. This study evaluated the levels of plasma bilirubin, ALP, and GGT among diabetic patients. A total of eighty (80) individuals were recruited for the study comprising of forty (40) diabetes patients with age range 25-80 years and forty (40) control subjects with the age range of 20-30 years in Irrua/Ekpoma, Edo State, Nigeria. The study was carried out within six months (December 2018 - May 2019). All patients were diabetes. The serum Alkaline Phosphatase (ALP), gamma-glutamyl transferase (GGT), total and conjugated bilirubin were assayed by spectrophotometric method, and the data obtained were statistically analyzed using SPSS version 23.0 software. Serum levels of ALP, GGT, Total and unconjugated bilirubin were significantly elevated (P<0.05) among diabetes patients than control subjects except for conjugated bilirubin which was lower (P>0.05) when compared with that of the control subjects. The mean serum levels of ALP, GGT, total, unconjugated and conjugated bilirubin of male diabetes patients were non statistically significant (P>0.05) when compared with female diabetes subjects except the age (P<0.05). These findings indicate that hepatic injury was more likely among diabetes, and liver enzymes (ALP, GGT) are critical for monitoring glucose control concomitant with hepatic injury. Bilirubin is a potentially important biomarker for the assessment of the hepatic excretory system in diabetes mellitus.

Differential gene expression analysis for the identification of potential biomarkers for Niemann-Pick type C disease.

Niemann-Pick disease (NP) is a rare neurovisceral lysosomal lipid storage disorder. NPC (NP type C) is characterized by the accumulation of unesterified cholesterol and other lipids within the cell, the function of lysosomes usually is impaired as well as the autophagy flux. To better understand the molecular pathways affected in this disease, we perform a bioinformatic study. We used in silico methods to identify genes affected in this disease. The first approach was an analysis of microarray data from the public archive GEO2, accession number GSE124283. We studied gene expression of skin fibroblast from 55 individuals, 22 healthy controls (13 males and 9 females) and other 23 with NPC (12 males and 11 females), 16 patients suffering from infantile NPC, 5 juvenile NPC and 2 adults. The differential expression analysis was performed using limma package, genes with significative adjusted p value and fold change > 0.5 and < -0.5 were selected, we used topGO package to obtain the Gene Ontology. The analysis revealed that cellular components enriched were vesicle membrane, vacuolar lumen lysosome, cytoplasm vesicle, cytoskeletal fiber, nucleus and nucleoplasm. For molecular function were affected catalytic activity, cadherin binding and enzyme binding, and the biological process enriched were the phagosome maturation, lysosome organization, vesicular transport, apoptotic process, gene expression, proteosome-mediated ubiquitin, cell cycle, cellular macromolecule biosynthetic process and regulation of cellular response to stress. Our results were consistent with changes in cell homeostasis reported from NPC patients. Abnormal protein degradation and metabolism might contribute to the higher level of mortality in this disease. We propose that some of the DEGs that are more related to NPC disease according to our study, could have value as potential biomarkers of this disease helping to unravel the molecular mechanisms involve in this disease.

Prevalence of Periodontal Disease in a Group of Egyptian Children with Diabetes Mellitus Type 1

Abstract Background: Diabetes Mellitus (DM) is a serious meta-bolic syndrome with its two basic types resulting in abnormal fat, carbohydrate, and protein metabolism. Periodontal disease is considered as the sixth leading complication for individuals suffering from diabetes mellitus. Periodontal disease can be initiated, developed and progressed because of metabolic imbalances in the tissues which lower the diabetic patients resistance of diabetics to infection. Aim of Study: The aim of this study was tostudy periodontal disease experience in a group of diabetic children and the unmet treatment needs. 3 to 12 years old suffering from type 1 diabetes mellitus. Material and Methods: 91children with type 1 diabetes mellites, their ages range from 3 to 12 participated in the study with the mean time since the onset of diabetes was 5.41±3.13 years in boys and 4.88±2.29 years in girls. Results: There was a significant differencecorrelation between HbA1c and periodontitis and diabetic ketoacidosis attacks. Conclusion: Elevated blood glucose levels in patients with diabetes mellitus patients is prominently associated with periodontal disease in the form of periodontitis and xerostomia leading to high risk of ketoacidosis attacks.

Intragastric Administration of Casein Leads to Nigrostriatal Disease Progressed Accompanied with Persistent Nigrostriatal-Intestinal Inflammation Activited and Intestinal Microbiota-Metabolic Disorders Induced in MPTP Mouse Model of Parkinson's Disease.

Gut microbial dysbiosis and alteration of gut microbiota composition in Parkinson's disease (PD) have been increasingly reported, no recognized therapies are available to halt or slow progression of PD and more evidence is still needed to illustrate its causative impact on gut microbiota and PD and mechanisms for targeted mitigation. Epidemiological evidence supported an association between milk intake and a higher incidence of Parkinson's disease (PD), questions have been raised about prospective associations between dietary factors and the incidence of PD. Here, we investigated the significance of casein in the development of PD. The mice were given casein (6.75g/kg i.g.) for 21days after MPTP (25mg/kg i.p. × 5days) treatment, the motor function, dopaminergic neurons, inflammation, gut microbiota and fecal metabolites were observed. The experimental results revealed that the mice with casein gavage after MPTP treatment showed a persisted dyskinesia, the content of dopamine in striatum and the expression of TH in midbrain and ileum were decreased, the expression of Iba-1, CD4, IL-22 in midbrain and ileum increased continuously with persisted intestinal histopathology and intestinal barrier injury. Decreased intestinal bile secretion in addition with abnormal digestion and metabolism of carbohydrate, lipids and proteins were found, whereas these pathological status for the MPTP mice without casein intake had recovered after 24days, no significant differences were observed with regard to only treated with casein. Our study demonstrates that intestinal pathologic injury, intestinal dysbacteriosis and metabolism changes promoted by casein in MPTP mice ultimately exacerbated the lesions to dopaminergic neurons.

57-Year-Old Woman With Weakness and Word-Finding Difficulties

57-Year-Old Woman With Weakness and Word-Finding Difficulties

Evaluation of Hypoglycaemic Effects of Dipeptidyl Peptidase–4 Inhibitors and Biguanide on Type-2 Diabetic subjects: A six months trial

Objective: This trial was conducted to evaluate the effectiveness of oral hypoglycemic agents on diabetic control and biochemical parameters of known diabetic subjects.&#x0D; Introduction: T2DM occurs due to abnormal metabolism of carbohydrate, proteins and lipids leading to increased blood glucose characterized by polyuria and polydypsia due to relative 5deficiency or lack of insulin. Beside dietary control and insulin therapy, various oral hypoglycemic such as sulfonylurea biguanide, thiazolidinedione, DPP–4 inhibitors, glucagon–like peptide inhibitors and SGL2.&#x0D; &#x0D; Material and Methods: This comparative trial was carried out on previously diagnosed type–2 diabetic subjects. This trial was conducted at health care centers of District Nowshehra viz. NMC Nowshehra, DHQ Hospital Nowshehra, and ICS, Peshawar in collaboration with KMC and PIMC Peshawar, Khyber Pakhtunkhwa, Pakistan. A total of 200 known diabetic subjects were randomly recruited on the basis of predetermined selection criteria and were splited into two groups. Group A having 100 diabetic subjects was given DPP–4 inhibitor; Sitagliptin 50 mg two times a day alone for six (06) months while Group B comprising of 100 patients were treated with combination of DPP–4 inhibitor (Sitagliptin 50 mg 1BD) and Metformin in a dose of 500 mg two times a day. Venous blood samples were taken from each patient in both fasting (10–12 hour night long fast) and random (2 hour post prandial) state. FBS, RBS, HbA1C, S. creatinine and fasting S. lipid profile were determined by using spectrophotometric colorimetric methods using kits (procured from Elitech, Spain) at 03 and 06 months follow up. Inclusion criteria was subjects with T2DM of age 18 years and above. T2DM patients on insulin, diabetic nephropathy and retinopathy were excluded. The data was analyzed by using SPSS software version 20.&#x0D; Results: Significant results (p &lt; 0.05) were seen for glycemic control (FBS, RBS, HbA1C) in Group B as compare to Group A patients.

Efektivitas Antidiabetik Oral Baik Tunggalmaupun Kombinasi Pada Pasien Diabetes Mellitus Tipe II Di RSUD Kota Madiun

Diabetes Mellitus is a group of chronic metabolic disorders due to abnormal metabolism of carbohydrates, fats, and proteins, characterized by hyperglycemia which is results in long-term microvascular, macrovascular and neuropathic complications. Oral antidiabetic therapy is the main pharmacological therapy to treat type II diabetes mellitus. This therapy can be oral antidiabetic therapy. Thus, to find out the effectiveness of either combination or single of antidiabetics on diabetes mellitus patients, researchers conducted a studies of inpatients at RSUD Madiun. This study included as non-experimental observational study with a cross-sectional study design at RSUD Madiun. Data were collected from Medical Records in October 2018. The sampling method that used in this study was non probability with purposive sampling technique, so there are 58 patients as a total sample. The results showed that the effectiveness of controlling blood sugar levels when using an effective single ADO was Metformin, because Metfomin was able to reduce blood sugar levels with an average length of stay of 6.17 and the effectiveness of controlling blood sugar levels when using an effective combination of ADO was Metformin and acarbosa, because Metfomin and acarbosa are able to reduce blood sugar average length of stay 7 days inpatient.

Comprehensive Review on Alzheimer's Disease: Causes and Treatment.

Alzheimer’s disease (AD) is a disorder that causes degeneration of the cells in the brain and it is the main cause of dementia, which is characterized by a decline in thinking and independence in personal daily activities. AD is considered a multifactorial disease: two main hypotheses were proposed as a cause for AD, cholinergic and amyloid hypotheses. Additionally, several risk factors such as increasing age, genetic factors, head injuries, vascular diseases, infections, and environmental factors play a role in the disease. Currently, there are only two classes of approved drugs to treat AD, including inhibitors to cholinesterase enzyme and antagonists to N-methyl d-aspartate (NMDA), which are effective only in treating the symptoms of AD, but do not cure or prevent the disease. Nowadays, the research is focusing on understanding AD pathology by targeting several mechanisms, such as abnormal tau protein metabolism, β-amyloid, inflammatory response, and cholinergic and free radical damage, aiming to develop successful treatments that are capable of stopping or modifying the course of AD. This review discusses currently available drugs and future theories for the development of new therapies for AD, such as disease-modifying therapeutics (DMT), chaperones, and natural compounds.

SARS-CoV-2 induced intestinal responses with a biomimetic human gut-on-chip

Coronavirus disease 2019 (COVID-19), caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), has become a global pandemic. Clinical evidence suggests that the intestine is another high-risk organ for SARS-CoV-2 infection besides the lungs. However, a model that can accurately reflect the response of the human intestine to the virus is still lacking. Here, we created an intestinal infection model on a chip that allows the recapitulation of human relevant intestinal pathophysiology induced by SARS-CoV-2 at organ level. This microengineered gut-on-chip reconstitutes the key features of the intestinal epithelium-vascular endothelium barrier through the three-dimensional (3D) co-culture of human intestinal epithelial, mucin-secreting, and vascular endothelial cells under physiological fluid flow. The intestinal epithelium showed permissiveness for viral infection and obvious morphological changes with injury of intestinal villi, dispersed distribution of mucus-secreting cells, and reduced expression of tight junction (E-cadherin), indicating the destruction of the intestinal barrier integrity caused by virus. Moreover, the vascular endothelium exhibited abnormal cell morphology, with disrupted adherent junctions. Transcriptional analysis revealed abnormal RNA and protein metabolism, as well as activated immune responses in both epithelial and endothelial cells after viral infection (e.g., upregulated cytokine genes), which may contribute to the injury of the intestinal barrier associated with gastrointestinal symptoms. This human organ system can partially mirror intestinal barrier injury and the human response to viral infection, which is not possible in existing in vitro culture models. It provides a unique and rapid platform to accelerate COVID-19 research and develop novel therapies.

Different metabolomic responses of grass carp (Ctenopharyngodon idellus) to dietary tannin and rapeseed meal

In order to study the metabolomic responses of rapeseed meal on grass carp and the role that tannin plays in those responses, grass carp were fed four diets for an eight week trial. Two were practical diets: FM diet contained 10% fishmeal without rapeseed meal, RM diet contained 50% rapeseed meal without fishmeal; the other two were semi-purified diets without (T0) or with 1.25% (T1) of supplemental hydrolysable tannin. The tannin content in the RM diet was close to that of T1. The rate of weight gain for RM was significantly lower than FM, while the feed conversion ratio in the T1 was significantly higher than T0. The muscle lipid and protein content was significantly lower and glycogen higher in the RM and T1 compared to the other treatments. The percent of muscle-saturated fatty acid (SFA) in the RM and T1 groups was significantly lower than FM and T0 groups, respectively, while the mono-unsaturated fatty acid (MUFA) in the RM group was significantly higher than FM. The hepatic activities of alanine aminotransferase and aspartate aminotransferase were lower and the hepatic glycogen and malonaldehyde were higher in the T1 and RM than the other treatments. The total serum protein, globulin, and triglycerides were significantly higher in T1 and RM; the alanine aminotransferase in the T1 was significantly higher than T0; and the aspartate aminotransferase in the RM and T0 groups were significantly higher than the other treatments. In a metabolomic assay, 29 differential metabolites were identified between T0 and T1, 23 metabolites were downregulated, and 6 metabolites were upregulated in T1 compared to T0. Ninety-two differential metabolites were identified between FM and RM, 31 metabolites were downregulated, and 61 metabolites were upregulated in RM compared to FM. These indicated that lipid utilization and carbohydrate metabolism might be improved, while the protein metabolism was suppressed by rapeseed meal. The abnormal protein and lipid metabolism may be partly caused by tannin in the rapeseed meal, as the tannin contained within the rapeseed meal seemed to bring different effects that the tannin additive.