iTRAQ-based proteomics reveals the mechanism of action of Yinlai decoction in treating pneumonia in mice consuming a high-calorie diet

Objective:To uncover the underlying mechanisms of action of the Yinlai decoction on high-calorie dietinduced pneumonia through proteomics analysis.Methods:Based on the Gene Expression Omnibus(GEO)database,lung tissue samples from normal and high-fat diet(HFD)fed mice in the GSE16377 dataset were selected as test cohorts to identify differentially expressed genes and conduct bioinformatics analyses.In the animal experiments,mice were randomly divided into the control(N),high-calorie diet pneumonia(M),and Yinlai decoction treatment(Y)groups.Mice in the M group received high-calorie feed and a 0.5 mg/mL lipopolysaccharide solution spray for 30 min for 3 d.The mice in the Y group were intragastrically administered 2 mL/10 g Yinlai decoction twice daily for 3 d.Pathological evaluation of the lung tissue was performed.Differentially expressed proteins(DEPs)in the lung tissue were identified using quantitative proteomics and bioinformatics analyses.The drug-target relationships between Yinlai decoction and core DEPs in the lung tissue were verified using AutoDock Vina and Molecular Graphics Laboratory(MGL)Tools.DEPs were verified by western blot.Results:GEO data mining showed that an HFD altered oxidative phosphorylation in mouse lung tissue.The Yinlai decoction alleviated pathological damage to lung tissue and pneumonia in mice that were fed a high-calorie diet.A total of 47 DEPs were identified between the Y and M groups.Enrichment analysis revealed their association with energy metabolism pathways such as the tricarboxylic acid cycle(TCA)and oxidative phosphorylation.The protein-protein interaction network revealed that Atp5a1,Pdha1,and Sdha were the target proteins mediating the therapeutic effects of Yinlai decoction.Molecular docking results suggested that the mechanism of the therapeutic effect of Yinlai decoction involves the binding of brassinolide,praeruptorin B,chrysoeriol,and other components in Yinlai decoction to Atp5a1.Conclusion:The Yinlai decoction alleviated lung tissue damage and pneumonia in mice that were fed a high-calorie diet by regulating the TCA and oxidative phosphorylation.Our study highlights the importance of a healthy diet for patients with pneumonia and provides a scientific basis for the prevention and treatment of pneumonia through dietary adjustments.

Effect of Yinlai Decoction on the metabolic pathways in the lung of high-calorie diet-induced pneumonia rats

Objective:To search for specific metabolites in the lungs of pneumonia rats fed with a high-calorie diet,as well as explore the changes in the lung metabolites of young rats treated with Yinlai Decoction(YD)and its effects on inflammation-related metabolic pathways.Methods:Lipopolysaccharides(LPS)and a special high-calorie diet were used to induce Sprague Dawley(SD)rats to simulate the intestinal state of infant pneumonia.Liquid chromatography-mass spectrometry technology(LC-MS/MS)was used to detect metabolites in each group.Supervised orthogonal partial least squares discriminant analysis(OPLS-DA)model values were used for the detection results to find the differential metabolites.The metabolic pathways that are involved with the differential metabolites were clarified through enrichment analysis and topological analysis.Finally,the T cell receptor signaling pathway(TCR)signal conversion was analyzed by the network pharmacology method.Results:In the high-calorie diet combined with pneumonia group(M3),a total of 55 metabolites were determined to be different from the normal group(N).A total of 36 metabolites were determined to be different from those in the lung metabolites of the YD treatment group(T1).YD had a regulatory effect on glutathione metabolism,arginine and proline metabolism,ascorbic acid and aldehyde metabolism and phenylalanine metabolism.And the small molecule metabolites could act on the FYN and lymphocytespecific protein tyrosine kinase(LCK)target proteins in the TCR signaling pathway,thereby affecting the immune function of the lungs.Conclusion:A high-calorie diet can cause abnormal sphingolipid metabolism in the lungs of young rats,thereby creating chronic lung inflammation in young rats.YD has a beneficial effect when used to treat young rats with LPS-induced pneumonia fed on high-calorie diets.Its mechanisms of action may affect the body’s immune pathways by regulating the oxidative stress pathway affected by glutathione metabolism.

Effects of different diets on intestinal microbiota and nonalcoholic fatty liver disease development

AIM To study the effects of different diets on intestinal microbiota and nonalcoholic fatty liver disease(NAFLD) development at the same caloric intake.METHODS Thirty male Sprague-Dawley rats were randomized into five groups(six rats each). The control diet(CON) group and free high-fat diet(FFAT) group were allowed ad libitum access to a normal chow diet and a highfat diet, respectively. The restrictive high-fat diet(RFAT) group, restrictive high-sugar diet(RSUG) group, and high-protein diet(PRO) group were fed a highfat diet, a high-sugar diet, and a high-protein diet, respectively, in an isocaloric way. All rats were killed at 12 wk. Body weight, visceral fat index(visceral fat/body weight), liver index(liver/body weight), insulin resistance, portal lipopolysaccharide(LPS), serum alanine aminotransferase(ALT), serum aspartate aminotransferase(AST), and liver triglycerides were measured. The intestinal microbiota in the different groups of rats was sequenced using high-throughput sequencing technology.RESULTS The FFAT group had higher body weight, visceral fat index, liver index, peripheral insulin resistance, portal LPS, serum ALT, serum AST, and liver triglycerides compared with all other groups(P < 0.05). Taking the same calories, the RFAT and RSUG groups demonstrated increased body weight, visceral fat index, peripheral insulin resistance and liver triglycerides compared with the PRO group(P < 0.05). The RFAT group also showed increased portal LPS compared with the PRO group(P < 0.05). Unweighted Uni Frac principal coordinates analysis of the sequencing data revealed that the intestinal microbiota structures of the CON, FFAT, RSUG and PRO groups were roughly separated away from each other. Taxon-based analysis showed that, compared with the CON group, the FFAT group had an increased abundance of Firmicutes, Roseburia and Oscillospira bacteria, a higher ratio of Firmicutes to Bacteroidetes, and a decreased abundance of Bacteroidetes, Bacteroides and Parabacteroides bacteria(P < 0.05). The RFAT group showed an increased abundance of Firmicutes and decreased abundance of Parabacteroides bacteria(P < 0.05). The RSUG group showed an increased abundance of Bacteroidetes and Sutterella bacteria, higher ratio of Bacteroidetes to Firmicutes, and a decreased abundance of Firmicutes(P < 0.05). The PRO group showed an increased abundance of Bacteroidetes, Prevotella, Oscillospira and Sutterella bacteria, and a decreased abundance of Firmicutes(P < 0.05). Compared with the FFAT group, the RFAT group had an increased abundance of Bacteroidetes, higher ratio of Bacteroidetes to Firmicutes, and decreased abundance of Firmicutes and Oscillospira bacteria(P < 0.05).CONCLUSION Compared with the high-protein diet, the NAFLDinducing effects of high-fat and high-sugar diets are independent from calories, and may be associated with changed intestinal microbiota.

Apoptosis induced by a low-carbohydrate and high-protein diet in rat livers

AIM: To determine whether high-protein, high-fat, and low-carbohydrate diets can cause lesions in rat livers.METHODS: We randomly divided 20 female Wistar rats into a control diet group and an experimental diet group. Animals in the control group received an AIN-93 M diet, and animals in the experimental group received an Atkins-based diet(59.46% protein, 31.77% fat, and 8.77% carbohydrate). After 8 wk, the rats were anesthetized and exsanguinated for transaminases analysis, and their livers were removed for flow cytometry, immunohistochemistry, and light microscopy studies. We expressed the data as mean ± standard deviation(sd) assuming unpaired and parametric data; we analyzed differences using the student's t-test. statistical significance was set at P < 0.05.RESULTS: We found that plasma alanine aminotransferase and aspartate aminotransferase levels were significantly higher in the experimental group than in the control group. According to flow cytometry, the percentages of nonviable cells were 11.67% ± 1.12% for early apoptosis, 12.07% ± 1.11% for late apoptosis, and 7.11% ± 0.44% for non-apoptotic death in the experimental diet group and 3.73% ± 0.50% for early apoptosis, 5.67% ± 0.72% for late apoptosis, and 3.82% ± 0.28% for non-apoptotic death in the control diet group. The mean percentage of early apoptosis was higher in the experimental diet group than in the control diet group. Immunohistochemistry for autophagy was negative in both groups. sinusoidal dilation around the central vein and small hepatocytes was only observed in the experimental diet group, and fibrosis was not identified by hematoxylin-eosin or Trichrome Masson staining in either group.CONCLUSION: Eight weeks of an experimental diet resulted in cellular and histopathological lesions in rat livers. Apoptosis was our principal finding; elevated plasma transaminases demonstrate hepatic lesions.

Dietary manipulation and testosterone replacement therapy may explain changes in body composition after spinal cord injury: A retrospective case report

BACKGROUND Reduced level of physical activity,high-fat diet and skeletal muscle atrophy are key factors that are likely to contribute to deleterious changes in body composition and metabolic following spinal cord injury (SCI).Reduced caloric intake with lowering percentage macronutrients of fat and increasing protein intake may likely to improve body composition parameters and decrease ectopic adiposity after SCI.AIM To highlight the effects of dietary manipulation and testosterone replacement therapy (TRT) on body composition after SCI METHODS A 31-year-old male with T5 SCI was administered transdermal TRT daily for 16 wk.Caloric intake and percentage macronutrients were analyzed using dietary recalls.Magnetic resonance imaging and dual-energy x-ray absorptiometry were used to measure changes in body composition.RESULTS Caloric intake and fat percentage were reduced by 445 kcal/d and 6.5%,respectively.Total body weight decreased by 8%,body fat decreased by 29%,and lean mass increased by 7%.Thigh subcutaneous adipose tissue cross-sectional area was reduced by 31%.CONCLUSION Manipulation of caloric intake,fat percentage,and protein percentage may have influenced body composition after SCI.

An alternative model for fetal loss disorders associated with mare reproductive loss syndrome

Fertile chicken eggs were used as an alternative model for large animals to evaluate suspect toxic dietary ingredients for fetal loss disorders associated with mare reproductive loss syndrome(MRLS) and fetal losses in other livestock.Nitrate,ammonia,and sulfate may react with proteinaceous compounds to enable the formation of abiotic pathogenic nanoparticles which were constant findings in pathognomonic placental lesions associated with non-infectious fetal losses of previously unknown etiology in mares,chickens and other livestock.The pathogenic nanoparticles may be produced naturally by toxic elements associated with air pollution that affect pasture forages or crops,uninte ntionally by reactions of these elements in protein-mineral mixes in dietary rations,or endogenously within tissues of fetuses and adult animals.The nanoparticles may form niduses in small vessels and predispose animals to a host of secondary opportunistic diseases affecting the reproductive,respiratory and gastrointestinal tracts of animals.The newly recognized abiotic pathogenic micro and nanoparticles are associated with MRLS.The discovery of the pathogenic nanoparticles led to the identification of nitrate,ammonium,and sulfur,in the form of sulfate,that seemingly enable the formation of the pathogenic nanoparticles in embryonic and fetal tissues.