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1.
Pharm Biol ; 61(1): 249-258, 2023 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-36655341

RESUMO

CONTEXT: Chaihu Shugan San (CHSGS) was effective in the treatment of functional dyspepsia (FD). OBJECTIVE: To investigate the mechanism of CHSGS in FD through dynamin-related protein 1 (Drp-1)-mediated interstitial cells of cajal (ICC) mitophagy. MATERIALS AND METHODS: Forty Sprague-Dawley (SD) rats were randomly divided into control, model, mdivi-1, mdivi-1 + CHSGS and CHSGS groups. Tail-clamping stimulation was used to establish the FD model. Mdivi-1 + CHSGS and CHSGS groups were given CHSGS aqueous solution (4.8 g/kg) by gavage twice a day. Mdivi-1 (25 mg/kg) was injected intraperitoneally once every other week for 4 w. Mitochondrial damage was observed by corresponding kits and related protein expressions were assessed by Immunofluorescence and (or) Western Blot. RESULTS: Compared with the mean value of the control group, superoxide dismutase (SOD) and citrate synthase (CS) in the model group were decreased by 11% and 35%; malondialdehyde (MDA) and reactive oxygen species (ROS) were increased by 1.2- and 2.8-times; ckit fluorescence and protein expressions were decreased by 85% and 51%, co-localization expression of LC3 and voltage dependent anion channel 1 (VDAC1), Drp-1 and translocase of the outer mitochondrial membrane 20 (Tom20) were increased by 10.1- and 5.4-times; protein expressions of Drp-1, Beclin-1, and LC3 were increased by 0.5-, 1.4-, and 2.5-times whereas p62 was decreased by 43%. After mdivi-1 and (or) CHSGS intervention, the above situation has been improved. DISCUSSION AND CONCLUSION: CHSGS could improve mitochondrial damage and promote gastric motility in FD rats by regulating Drp-1-mediated ICC mitophagy.


Assuntos
Dispepsia , Células Intersticiais de Cajal , Animais , Ratos , Dispepsia/tratamento farmacológico , Dispepsia/metabolismo , Células Intersticiais de Cajal/metabolismo , Mitofagia , Ratos Sprague-Dawley
2.
J Ethnopharmacol ; 305: 116114, 2023 Apr 06.
Artigo em Inglês | MEDLINE | ID: mdl-36587455

RESUMO

ETHNOPHARMACOLOGICAL RELEVANCE: As a traditional Chinese medicine formula, Jingxin Zhidong Formula (JXZDF) based on ancient amber powder has been prescribed to alleviate tic disorders (TD) according to our clinical practice for many years. However, the underlying molecular mechanisms remain largely unknown. AIM OF STUDY: To explore the potential mechanism of JXZDF in the treatment of TD by using network pharmacology and experimental validation. MATERIALS AND METHODS: The chemical components of JXZDF were detected and the potential pathway enrichment analyses were conducted based on network pharmacology. Finally, we performed cell viability assays and Western blotting on LPS-induced BV-2 cells, and subsequently performed behavioral tests and Western blotting in SD rats model for TD to explore the mechanism of JXZDF on TD. RESULTS: By LC-ESI-MS/MS system and searching the databases, we identified 5 key compounds and 29 hub targets of JXZDF on TD. KEGG enrichment analysis showed that PI3K/AKT signaling pathway may be the key pathway for JXZDF on TD. The vitro experimental results proved that JXZDF can inhibit the phosphorylation of PI3K and AKT proteins on LPS-induced BV-2 cells. The animal experimental results indicated that JXZDF can effectively alleviate the stereotypic behavior and hyperactivity of the TD rats, and downregulated PI3K/AKT pathway to inhibit microglia activation in the hippocampus tissue. CONCLUSION: This study indicated that JXZDF can change microglial activation and expression of proinflammatory mediators through the inactivation of PI3K/AKT signaling pathway, which may be one of the mechanisms of JXZDF in treating TD.


Assuntos
Medicamentos de Ervas Chinesas , Transtornos de Tique , Animais , Ratos , Ratos Sprague-Dawley , Lipopolissacarídeos/toxicidade , Farmacologia em Rede , Fosfatidilinositol 3-Quinases , Proteínas Proto-Oncogênicas c-akt , Espectrometria de Massas em Tandem , Medicamentos de Ervas Chinesas/farmacologia , Medicamentos de Ervas Chinesas/uso terapêutico , Simulação de Acoplamento Molecular
3.
J Ethnopharmacol ; 305: 116125, 2023 Apr 06.
Artigo em Inglês | MEDLINE | ID: mdl-36603786

RESUMO

ETHNOPHARMACOLOGICAL RELEVANCE: Ulcerative colitis (UC) is a major cause of morbidity and mortality due to repetitive remissions and relapses, and many severe complications, including colitis-associated cancer (CAC). The San-Qi-Xue-Shang-Ning (SQ) formula has been utilized in clinical practice to treat gut diseases, but its pharmacological evidence is limited and awaits elucidation. AIM OF THE STUDY: Here, we elucidated the molecular mechanisms of the SQ formula. MATERIALS AND METHODS: Its therapeutic value in combating UC and CAC was predicted from network pharmacology and weighted gene co-expression network analysis (WGCNA). Experimental colitis models were established by feeding dextran sodium sulfate (DSS) to C57BL/6N mice for 7 days, and they were subjected to the SQ formula for 14 days. High-throughput technologies and biochemical investigations were executed to corroborate the anti-colitis effect. RESULTS: Network pharmacology and WGCNA demonstrated that the targets of the SQ formula were associated with interleukin-17 (IL-17), tumor necrosis factor (TNF), IL-1b and peroxisome proliferators-activated receptor (PPAR) signaling pathways, and correlated with the survival in patients with colorectal cancer. In mice with colitis, the SQ treatment hindered colitis progression in a dose-dependent manner, as evidenced by the rescued colon length and weight loss, improved colonic epithelial integrity, and abolished crypt loss. In addition to the suppressed serum IL-17, TNFα, and IL-1b levels, the SQ-treated colitis mice exhibited decreased colonic protein abundance of hypoxia-inducible factor-1α (HIF-1 α), PPARα, and Caspase3 (Casp3) with an increased PPARγ expression. Concurrently, the high dose of SQ promoted the alternative activation of peritoneal macrophages by increasing Arg1 and inhibiting iNOS2, thereby facilitating the migration of NCM460 cells and controlling TNF-induced reactive oxygen species production and apoptosis in intestinal organoids. In colitis-accompanied dysbiosis, the SQ formula reversed the decreased microbiota diversity indexes and restored the microbiome profile in the murine colitis models. CONCLUSION: The SQ formula is a potent anti-colitis drug that facilitates inflammation resolution and restores gut microbiota homeostasis.


Assuntos
Colite Ulcerativa , Colite , Microbiota , Camundongos , Animais , Colite Ulcerativa/induzido quimicamente , Colite Ulcerativa/tratamento farmacológico , Colite Ulcerativa/metabolismo , Interleucina-17/metabolismo , Camundongos Endogâmicos C57BL , Colite/induzido quimicamente , Colo , Homeostase , Sulfato de Dextrana/toxicidade , Modelos Animais de Doenças
4.
J Allergy Clin Immunol ; 151(1): 37-41, 2023 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-36608981

RESUMO

Food allergy (FA) affects 8% of US children. Navigating and managing FA permeates across multiple facets of childhood. In this article, we review research on social disparities in feeding practices, managing meals, and selecting childcare and schools. Key highlights include the following: (1) although preference for breast-feeding or formula feeding does not reduce FA risk, there are disparities in access to formula that may affect children with FA; (2) disparities likely exist in the early introduction to allergenic foods, though additional research is needed to identify barriers to following the most recent consensus guidelines on early introduction; (3) families with limited income face challenges in providing safe meals for their children; (4) disparities exist in early childcare options for preschool-age children, though there is a lack of research on FA practices in these settings; and (5) there is evidence that schools with different student demographics implement different types of FA policies. Further research is needed to better understand and characterize social disparities in FA prevention and management in early childhood and to develop evidence-based strategies to reduce them.


Assuntos
Hipersensibilidade Alimentar , Criança , Feminino , Pré-Escolar , Humanos , Lactente , Hipersensibilidade Alimentar/prevenção & controle , Aleitamento Materno , Estudantes , Instituições Acadêmicas , Consenso
5.
Orphanet J Rare Dis ; 18(1): 16, 2023 Jan 25.
Artigo em Inglês | MEDLINE | ID: mdl-36698214

RESUMO

BACKGROUND: Phenylalanine-free infant formula is an essential source of safe protein in a phenylalanine restricted diet, but its efficacy is rarely studied. We report a multicentre, open, longitudinal, prospective intervention study on a phenylalanine-free infant formula (PKU Start: Vitaflo International Ltd.). RESULTS: This was a 2-part study: part I (28 days short term evaluation) and part II (12 months extension). Data was collected on infant blood phenylalanine concentrations, dietary intake, growth, and gastrointestinal tolerance. Ten infants (n = 8 males, 80%), with a median age of 14 weeks (range 4-36 weeks) were recruited from 3 treatment centres in the UK. Nine of ten infants completed the 28-day follow-up (one caregiver preferred the usual phenylalanine-free formula and discontinued the study formula after day 14) and 7/9 participated in study part II. The phenylalanine-free infant formula contributed a median of 57% (IQR 50-62%) energy and 53% (IQR 33-66%) of total protein intake from baseline to the end of the part II extension study. During the 12-month follow-up, infants maintained normal growth and satisfactory blood phenylalanine control. Any early gastrointestinal symptoms (constipation, colic, vomiting and poor feeding) improved with time. CONCLUSION: The study formula was well tolerated, helped maintain good metabolic control, and normal growth in infants with PKU. The long-term efficacy of phenylalanine-free infant formula should continue to be observed and monitored.


Assuntos
Fórmulas Infantis , Fenilcetonúrias , Lactente , Masculino , Humanos , Estudos Prospectivos , Fenilalanina , Proteínas
6.
Biometals ; 2023 Jan 27.
Artigo em Inglês | MEDLINE | ID: mdl-36705875

RESUMO

While endotoxin (lipopolysaccharide) can be harmful and contribute to morbidity and mortality with Gram-negative sepsis or necrotizing enterocolitis in preterm infants, non-toxic amounts are produced as part of the neonatal microbiome and may be present in enteral nutrition and medications administered. The United States Food and Drug Administration has given guidance for endotoxin concentration limits for intravenous medications and fluids of 5 endotoxin units/kg/hour (120 endotoxin units/kg/day), but no guidance for amounts of endotoxin in enteral products. To determine baseline exposure to infants in the neonatal intensive care unit, we examined endotoxin content of enteral formulas and fortification used for preterm infants, as well as bovine lactoferrin products. We also examined endotoxin exposure and outcomes in very low birth weight infants. Endotoxin content was measured using kinetic chromogenic limulus amebocyte lysate analysis. Daily endotoxin exposure from enteral formulas ranged between < 75 to 7110 endotoxin units/kg and from lactoferrin products from 7 to 3720 endotoxin units/kg. In examining neonatal outcomes from a bovine lactoferrin product studied at three different escalating doses (100, 200, and 300 mg/kg/day), we measured endotoxin in the lactoferrin product and daily exposure was 1089 (N = 10), 2178 (N = 10) and 3287 (N = 11) endotoxin units/kg, respectively. There were no cases of necrotizing enterocolitis or mortality and no lactoferrin-related adverse effects in these patients. Enteral endotoxin daily exposures from lactoferrin products are similar to amounts in preterm enteral nutrition and appear safe and not associated with patient harm. Testing enteral products and establishing safety limits may improve care of high risk patients.

7.
Environ Toxicol Pharmacol ; 98: 104065, 2023 Jan 11.
Artigo em Inglês | MEDLINE | ID: mdl-36640921

RESUMO

This study was conducted to estimate the daily dietary intakes of melamine for human milk-fed (HMF) babies and mixed-fed (MF) babies. It was carried out in 70 mother-baby pairs (40 babies in the HMF group and 30 babies in the MF group). Human milk, formula milk, and baby urine samples were collected to assess the dietary exposure of babies. Melamine concentrations were analyzed by using a competitive enzyme-linked immunosorbent assay. Melamine was determined in 82.5 % of the human milk samples in the HMF group (median: 0.75 µg/L) while it was present in 96.7 % of human milk samples (median: 1.25 µg/L) and 96.7 % in formula milk samples (median: 0.95 µg/kg) in the MF group. The mean urinary melamine concentration of HMF babies (1.20 ± 0.21 µg/L) was not significantly different than MF babies (1.35 ± 0.49 µg/L). Melamine exposure was calculated as 0.12 µg/kg bw/day and 0.24 µg/kg bw/day in HMF and MF babies, respectively. Melamine exposure in both groups was below the tolerable daily intake. There were no significant associations between melamine exposure and various features of babies and mothers. As a result, it can be suggested that Turkish babies (aged 0-6 months) are not at risk for high melamine exposure through the diet.

8.
Nutrients ; 15(2)2023 Jan 12.
Artigo em Inglês | MEDLINE | ID: mdl-36678256

RESUMO

A controlled-neonatal piglet trial was conducted to evaluate the impact of a plant-based infant formula containing buckwheat and almonds as the main source of protein compared to a commercially available dairy-based formula on the gut health parameters. Two day old piglets were fed either a plant-based or a dairy-based formula until day 21. Gut microbiome, cytokines, growth and metabolism related outcomes, and intestinal morphology were evaluated to determine the safety of the plant-based infant formula. This study reported that the plant-based formula-fed piglets had a similar intestinal microbiota composition relative to the dairy-based formula-fed group. However, differential abundance of specific microbiota species was detected within each diet group in the small and large intestinal regions and fecal samples. Lactobacillus&nbsp;delbrueckii, Lactobacillus&nbsp;crispatus, and Fusobacterium sp. had higher abundance in the small intestine of plant-based formula-fed piglets compared to the dairy-based group. Bacteroides nordii, Enterococcus sp., Lactobacillus crispatus, Prevotella sp., Ruminococcus lactaris, Bacteroides nordii, Eisenbergiella sp., Lactobacillus crispatus, Prevotella sp., and Akkermansia muciniphila had greater abundance in the large intestine of the plant based diet fed piglets relative to the dairy-based diet group. In the feces, Clostridiales, Bacteroides uniformis, Butyricimonasvirosa, Cloacibacillus porcorum, Clostridium clostridioforme, and Fusobacterium sp. were abundant in dairy-based group relative to the plant-based group. Lachnospiraceae, Clostridium scindens, Lactobacillus coleohominis, and Prevetolla sp. had greater abundance in the feces of the plant-based group in comparison to the dairy-based group. Gut morphology was similar between the plant and the dairy-based formula-fed piglets. Circulatory cytokines, magnesium, triiodothyronine (T3), thyroxine (T4), thyroid stimulating hormone (TSH), vitamin D, vitamin K, and IgE levels were similar among all piglets independent of dietary group. Overall, the present study demonstrated that a plant-based formula with buckwheat and almonds as the primary source of protein can support similar gut microbiota growth and health outcomes compared to a dairy-based infant formula.


Assuntos
Fagopyrum , Microbioma Gastrointestinal , Prunus dulcis , Animais , Animais Recém-Nascidos , Biomarcadores , Citocinas/metabolismo , Fórmulas Infantis , Intestino Delgado/metabolismo , Suínos
9.
Food Microbiol ; 111: 104191, 2023 May.
Artigo em Inglês | MEDLINE | ID: mdl-36681390

RESUMO

Species identification and growth rates for a collection of Cronobacter strains from clinical and non-clinical sources have been previously reported. However, advancements in DNA sequencing-based identification methods now allow for more accurate identification. Here we report the sequence types (STs) for 24 strains of Cronobacter sakazakii and examine any possible correlation between sequence type and growth rate, which could influence risk through greater pathogen multiplication and reach of infectious doses during time between formula preparation and feeding. The most common clonal complexes (CCs) identified were C. sakazakii CC1 and CC4. CC1 strains belonged to ST1 (n = 8) and ST391 (n = 1), while CC4 included ST4 (n = 4), ST255 (n = 1) and ST295 (n = 1). Three strains were found to belong to CC100 and two were found to belong to ST64. The remaining STs identified were represented by single strains. CC4 strains have a slightly not significant tendency for faster growth rates at 25 °C; however, the small sample size suggests that more strains need to be analysed to determine if this is a true result. In conclusion, the growth rates of C. sakazakii strains do not appear to be strongly correlated to ST.


Assuntos
Cronobacter sakazakii , Cronobacter sakazakii/genética , Cronobacter sakazakii/crescimento & desenvolvimento , Fórmulas Infantis/microbiologia , Análise de Sequência de DNA
10.
Curr Eye Res ; : 1-7, 2023 Jan 02.
Artigo em Inglês | MEDLINE | ID: mdl-36593748

RESUMO

PURPOSE: Bootstrapping is a modern technique widely used in statistics to evaluate the performance of model parameters. The purpose of this study was to develop a strategy to identify and eliminate outliers in a dataset used for optimizing formula constants for lens power calculation. METHODS: In a dataset with N = 888 clinical cases treated with a monofocal aspherical intraocular lens (XC1/XY1, Hoya) constants for the SRKT, Haigis and Castrop formula were optimized and the prediction error PE calculated. The PE was bootstrapped NB = 1000 times, and the mean and trimmed mean of the bootstrapped PE were derived to generate the Bootlier plot showing the probability density function of the mean minus trimmed mean. With outliers this Bootlier plot shows some multimodality, and a Bootlier Index was extracted as a measure for multimodality. Outliers were removed from the tails of the PE distribution in a stepwise fashion until the Bootlier Index fell below a threshold of 0.001. RESULTS: With the entire dataset the mean/SD/median/mean absolute/root mean squared PE using the optimized formula constants were -0.0045/0.44415/0.0134/0.3406/0.4412 dpt with SRKT, 0.0065/0.3711/-0.0056/0.2830/0.3710 dpt with Haigis, and 0.0034/0.3452/0.0023/0.2683/0.3451 dpt with the Castrop formula. After identifying and removing outliers the respective metrics for the PE were -0.0036/0.4028/0.0134/0.3205/0.4026 dpt for the SRKT (13 cases removed), 0.0050/0.3375/-0.0056/0.2656/0.3373 dpt with Haigis (11 cases removed), and 0.0035/0.3168/0.0023/0.2531/0.3166 dpt with Castrop (11 cases removed). The multimodality in the Bootlier plots was reduced from 0/0.1567/0.0587/0.0258/0.0007/0 with SRKT, 0/0.0981/0.0261/0.0202/0.0003/0 with Haigis, and 0.0006/0.0006/0.0161/0.0191/0.0005/0 with Castrop for the entire dataset to values below 1e-3 for trimming both tails of the PE distribution by ⅛, », ½, 1, 2.5, and 5% respectively. CONCLUSION: We were able to prove that bootstrapping with outlier identification based on Bootlier plots and the Bootlier Index is a powerful tool to clean a dataset of outliers for formula constant optimization.

11.
Clin Nutr ESPEN ; 53: 53-59, 2023 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-36657930

RESUMO

BACKGROUND: Various methods, including bioelectrical impedance analysis (BIA), are used for total body water (TBW) estimation. The objective of our study by BIA was to develop a new predication model based on corrected TBW for normal adult BMI, a concept similar to the standardization of glomerular filtration rate by relating it to the average adult body surface area. METHOD: We measured TBW by BIA in 335 children 3-21 years old with normal or excessive body weight. Based on our data, we derived a new prediction model for TBW (L) for females {[(72.784 + 0.4093 × weight)∗Corrected TBW]/100} and males {[(57.944 + 0.6551 × weight)∗Corrected TBW]/100}. For validation, we compared our prediction model with three other models on TBW by BIA and dilution methods. RESULTS: Our model's error size to predict TBW showed lower cross-validated root mean square error (CV-RMSE) as compared to three other models versus our dataset by BIA and two other datasets by dilution methods. Our model also showed a smaller error (2.059) in CV-RMSE as compared to other models by dilution methods (2.126, 2.873, and 4.384) for normal and excessive weight combined. This implies that our model is more robust when excessive weight individuals are included in the data.. CONCLUSION: Our prediction model for TBW estimation by BIA performs better as compared to some other models based on BIA and dilution method datasets. Furthermore, our prediction model is the only one that is devised to be applicable to children and young adults with both normal as well as excessive weight.


Assuntos
Composição Corporal , Água Corporal , Masculino , Feminino , Adulto Jovem , Humanos , Criança , Pré-Escolar , Adolescente , Adulto , Impedância Elétrica , Aumento de Peso , Técnicas de Diluição do Indicador
12.
J Cheminform ; 15(1): 9, 2023 Jan 19.
Artigo em Inglês | MEDLINE | ID: mdl-36658606

RESUMO

MF-LOGP, a new method for determining a single component octanol-water partition coefficients ([Formula: see text]) is presented which uses molecular formula as the only input. Octanol-water partition coefficients are useful in many applications, ranging from environmental fate and drug delivery. Currently, partition coefficients are either experimentally measured or predicted as a function of structural fragments, topological descriptors, or thermodynamic properties known or calculated from precise molecular structures. The MF-LOGP method presented here differs from classical methods as it does not require any structural information and uses molecular formula as the sole model input. MF-LOGP is therefore useful for situations in which the structure is unknown or where the use of a low dimensional, easily automatable, and computationally inexpensive calculations is required. MF-LOGP is a random forest algorithm that is trained and tested on 15,377 data points, using 10 features derived from the molecular formula to make [Formula: see text] predictions. Using an independent validation set of 2713 data points, MF-LOGP was found to have an average [Formula: see text] = 0.77 ± 0.007, [Formula: see text] = 0.52 ± 0.003, and [Formula: see text] = 0.83 ± 0.003. This performance fell within the spectrum of performances reported in the published literature for conventional higher dimensional models ([Formula: see text] = 0.42-1.54, [Formula: see text] = 0.09-1.07, and [Formula: see text] = 0.32-0.95). Compared with existing models, MF-LOGP requires a maximum of ten features and no structural information, thereby providing a practical and yet predictive tool. The development of MF-LOGP provides the groundwork for development of more physical prediction models leveraging big data analytical methods or complex multicomponent mixtures.

13.
Materials (Basel) ; 16(2)2023 Jan 07.
Artigo em Inglês | MEDLINE | ID: mdl-36676335

RESUMO

Corrugated cardboard boxes are generally used in modern supply chains for the handling, storage, and distribution of numerous goods. These packages require suitable strength to maintain adequate protection within the package; however, the presence and configuration of any cutouts on the sidewalls significantly influence the packaging costs and secondary paperboard waste. This study aims to evaluate the performance of CCBs by considering the influence of different cutout configurations of sidewalls. The compression strength of various B-flute CCB dimensions (200 mm, 300 mm, 400 mm, 500 m, and 600 mm in length, with the same width and height of 300 mm), each for five cutout areas (0%, 4%, 16%, 36%, and 64%) were experimentally observed, and the results were compared with the McKee formula for estimation. The boxes with cutout areas of 0%, 4%, 16%, 36%, and 64% showed a linear decreasing tendency in compression force. A linear relationship was found between compression strength and an increase in cutout sizes. Packages with 0% and 4% cutouts did not show significant differences in compression strength (p < 0.05). Furthermore, this study shows a possible way to modify the McKee estimation for such boxes after obtaining empirical test data since the McKee formula works with a relatively high error rate on corrugated cardboard boxes with sidewall cutouts. Utilizing the numerical and experimental results, a favorable estimation map can be drawn up for packaging engineers to better manage material use and waste. The results of the study showed that the McKee formula does not appropriately estimate the box compression strength for various cutout sizes in itself.

14.
Nutrients ; 15(2)2023 Jan 05.
Artigo em Inglês | MEDLINE | ID: mdl-36678154

RESUMO

Breastfeeding is the gold standard for early nutrition. Metabolites from the one-carbon metabolism pool are crucial for infant development. The aim of this study is to compare the breast-milk one-carbon metabolic profile to other biofluids where these metabolites are present, including cord and adult blood plasma as well as cerebrospinal fluid. Breast milk (n = 142), cord blood plasma (n = 23), maternal plasma (n = 28), aging adult plasma (n = 91), cerebrospinal fluid (n = 92), and infant milk formula (n = 11) samples were analyzed by LC-MS/MS to quantify choline, betaine, methionine, S-adenosylmethionine, S-adenosylhomocysteine, total homocysteine, and cystathionine. Differences between groups were visualized by principal component analysis and analyzed by Kruskal-Wallis test. Correlation analysis was performed between one-carbon metabolites in human breast milk. Principal component analysis based on these metabolites separated breast milk samples from other biofluids. The S-adenosylmethionine (SAM) concentration was significantly higher in breast milk compared to the other biofluids and was absent in infant milk formulas. Despite many significant correlations between metabolites in one-carbon metabolism, there were no significant correlations between SAM and methionine or total homocysteine. Together, our data indicate a high concentration of SAM in breast milk, which may suggest a strong demand for this metabolite during infant early growth while its absence in infant milk formulas may indicate the inadequacy of this vital metabolic nutrient.


Assuntos
Leite Humano , S-Adenosilmetionina , Adulto , Criança , Lactente , Feminino , Humanos , S-Adenosilmetionina/metabolismo , Cromatografia Líquida , Leite Humano/metabolismo , Carbono , Espectrometria de Massas em Tandem , Metionina/metabolismo , Racemetionina , S-Adenosil-Homocisteína/metabolismo , Homocisteína
15.
Phytomedicine ; 109: 154549, 2023 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-36610129

RESUMO

BACKGROUND: Acute lung injury (ALI) is a common complication of sepsis with poor effective interventions. Huashibaidu formula (HSBD) showed good therapeutic effects in treating coronavirus disease 2019 (COVID-19) patients. PURPOSE: This study was designed to investigate the therapeutic potential and precise mechanism of HSBD against sepsis-induced ALI based on network pharmacology and animal experiments. MATERIALS AND METHODS: Network pharmacology was used to predict the possible mechanism of HSBD against sepsis. Next, a sepsis-induced ALI rat model via intraperitoneal lipopolysaccharide (LPS) was constructed to evaluate the level of inflammatory cytokines and the degree of lung injury. The expression of inflammation-related signaling pathways, including TLR4/NF-κB and PI3K/Akt was determined by western blot. RESULTS: Network pharmacology analysis indicated that HSBD might have a therapeutic effect on sepsis mainly by affecting inflammatory and immune responses. Animal experiments demonstrated that HSBD protected the lung tissue from LPS-induced injury, and inhibited the levels of inflammatory cytokines such as interleukin (IL)-1ß, granulocyte-macrophage colony-stimulating factor (GM-CSF), interferon (IFN)-γ and tumor necrosis factor (TNF)-α in the serum and IL-1ß, IL-5, IL-6, IL-18, GM-CSF, IFN-γ and TNF-α in the lung tissue. Western blot results revealed that HSBD downregulated the expression of TLR4/NF-κB and upregulated the expression of PI3K/Akt. CONCLUSION: The therapeutic mechanism of HSBD against sepsis-induced ALI mainly involved suppressing cytokine storms and relieving inflammatory symptoms by regulating the expression of TLR4/NF-κB and PI3K/Akt. Our study provides a scientific basis for the mechanistic investigation and clinical application of HSBD in the treatment of sepsis and COVID-19.


Assuntos
Lesão Pulmonar Aguda , Síndrome da Liberação de Citocina , Sepse , Animais , Ratos , Lesão Pulmonar Aguda/tratamento farmacológico , Lesão Pulmonar Aguda/etiologia , COVID-19 , Síndrome da Liberação de Citocina/tratamento farmacológico , Síndrome da Liberação de Citocina/virologia , Citocinas/metabolismo , Fator Estimulador de Colônias de Granulócitos e Macrófagos/metabolismo , NF-kappa B/metabolismo , Fosfatidilinositol 3-Quinases , Proteínas Proto-Oncogênicas c-akt/metabolismo , Sepse/complicações , Sepse/tratamento farmacológico , Receptor 4 Toll-Like/metabolismo , Fator de Necrose Tumoral alfa/metabolismo
16.
Birth ; 2023 Jan 13.
Artigo em Inglês | MEDLINE | ID: mdl-36639828

RESUMO

BACKGROUND: Better understanding of the factors associated with formula feeding during the hospital stay can help in identifying potential lactation problems and promote early intervention. Our aim was to ascertain factors associated with exclusive formula feeding in newborns of low-risk pregnancies. METHODS: A population-based, retrospective study using the United States vital statistics datasets (2014-2018) evaluating low-risk pregnancies with a nonanomalous singleton delivery from 37 to 41 weeks. People with hypertensive disorders, or diabetes, were excluded. Primary outcome was newborn feeding (breast vs exclusive formula feeding) during hospital stay. Adjusted relative risks (aRRs) with 95% confidence intervals (CI) were calculated. RESULTS: Of the 19 623 195 live births during the study period, 11 605 242 (59.1%) met inclusion criteria and among them, 1 929 526 (16.6%) were formula fed. Factors associated with formula feeding included: age < 20 years (aRR 1.31 [95% CI 1.31-1.32]), non-Hispanic Black (1.42, 1.41-1.42), high school education (1.69, 1.69-1.70) or less than high school education (1.94, 1.93, 1.95), Medicaid insurance (1.52, 1.51, 1.52), body mass index (BMI) < 18.5 (1.10, 1.09-1.10), BMI 25-29.9 (1.09, 1.09-1.09), BMI 30-34.9 (1.19, 1.19-1.20), BMI 35-39.9 (1.31, 1.30-1.31), BMI ≥ 40 (1.43, 1.42-1.44), multiparity (1.29, 1.29-1.30), lack of prenatal care (1.49, 1.48-1.50), smoking (1.75, 1.74-1.75), and gestational age (ranged from 37 weeks [1.44, 1.43-1.45] to 40 weeks [1.11, 1.11-1.12]). CONCLUSIONS: Using a large cohort of low-risk pregnancies, we identified several modifiable factors associated with newborn feeding (eg, prepregnancy BMI, access to prenatal care, and smoking cessation). Improving the breast feeding initiation rate should be a priority in our current practice to ensure equitable care for all neonates.

17.
J Asthma Allergy ; 16: 73-82, 2023.
Artigo em Inglês | MEDLINE | ID: mdl-36636707

RESUMO

Objective: This study estimates the budgetary impact of the introduction of amino-acid formula (AAF) as first-line management in the elimination diet of infants with suspected cow milk protein allergy (CMPA) in the Kingdom of Saudi Arabia (KSA), Kuwait, and the United Arab Emirates (UAE) from a health-care payer's perspective. Methods: A global decision tree model was adapted to compare estimated costs in current practice (extensively hydrolyzed formula [eHF] or soy formula [SF] with the proposed approach of early introduction of AAF as first-line treatment of CMPA in non-breast-fed infants). Model inputs were derived from explorative literature reviews and medical experts' opinions. All costs were reported in local currency, ie, Saudi Riyal (SAR) for KSA, Kuwaiti Dinar (KWD) for Kuwait, and United Arab Emirates Dirham (AED) for the UAE. Results: Cost savings with the early introduction of AAF were 10% (SAR 15102542) in KSA, 10% (KWD 306565) in Kuwait, 17% (AED 1842018) in the UAE government sector and 13% (AED 4232932) in the UAE private sector. The highest cost reduction was observed in the cost of soy formula (SF), with a 58% reduction both in KSA (SAR 4204540) and UAE public sector (AED 110331). A significant cost reduction in medication costs in Kuwait (37%; KWD 5630) and medical examination costs in the UAE private sector (50%; AED 1508918) was observed. Conclusion: Results indicated that the introduction of AAF as the first line in the management of CMPA is a cost-saving strategy for the Gulf Cooperation Council (GCC) countries-KSA, Kuwait, and UAE- from a health-care payer's perspective.

18.
Lett Appl Microbiol ; 76(1)2023 Jan 23.
Artigo em Inglês | MEDLINE | ID: mdl-36688780

RESUMO

Cronobacter sakazakii is an opportunistic foodborne pathogen in powdered infant formula (PIF) associated with several foodborne outbreaks. Biofilms of C. sakazakii in the PIF manufacturing plant may be a source of contamination, but information on the treatment of these biofilms is limited. This study investigated the inactivation of C. sakazakii biofilms on three food contact surfaces (stainless steel, silicone, and PVC) using high voltage atmospheric cold plasma (HVACP) applied as a dielectric barrier discharge in a 10:90 air: helium modified atmosphere. After the 90 s  of cold plasma exposure at 40 kV, C. sakazakii was reduced by ∼3 log CFU/coupon comparing to without cold plasma treatments. HVACP treatment caused cell shrinkage, fragmentation of the cell membrane, and leakage of cytoplasm. The inactivation of the cells on the surface was confirmed by live/dead staining. These above-mentioned results indicate the antibiofilm efficacy of HVACP on C. sakazakii isolates on various food contact surfaces.


Assuntos
Cronobacter sakazakii , Cronobacter , Gases em Plasma , Humanos , Lactente , Microbiologia de Alimentos , Biofilmes , Fórmulas Infantis
19.
J Ethnopharmacol ; : 116198, 2023 Jan 20.
Artigo em Inglês | MEDLINE | ID: mdl-36690307

RESUMO

ETHNOPHARMACOLOGICAL RELEVANCE: Qingyihuaji Formula (QYHJ), a widely used traditional Chinese medicine (TCM), has been used to treat patients with cancer in China. However, the effect and mechanism of QYHJ on pancreatic ductal adenocarcinoma (PDAC) remains unclear. AIM OF THE STUDY: This study aimed to explore the roles and evaluate the possible underlying molecular mechanisms of QYHJ and its core component in PDAC using label-free quantitative proteomics in conjunction with network pharmacology-based analysis. MATERIALS AND METHODS: By screening differentially expressed proteins (DEPs) in proteomics and QYHJ-predicted gene sets, we identified QYHJ-related PDAC targets annotated with bioinformatic analysis. A subcutaneous tumor model was established to assess the role of QYHJ in vivo. The effects of quercetin (Que), a core component of QYHJ, on cell proliferation, migration, invasion, apoptosis, and autophagy in SW1990 and PANC-1 cells were investigated in vitro. Immunohistochemistry, western blotting, mRFP-GFP-LC3 adenovirus, and kinase analysis were used to determine the underlying mechanisms. RESULTS: Bioinformatics analysis revealed that 41 QYHJ-related PDAC targets were closely related to the cellular response to nitrogen compounds, positive regulation of cell death, regulation of epithelial cell apoptotic processes, and chemokine signaling pathways. CASP3, SRC, STAT1, PTPN11, PKM, and PAK1 with high expression were identified as hub DEPs in the PPI network, and these DEPs were associated with poor overall survival and STAT 1, MAPK/ERK, and PI3K/Akt/mTOR signaling pathways in PDAC patients. QYHJ significantly promoted tumor death in nude mice. Moreover, quercetin inhibited the proliferation, migration, and invasion of PDAC cells. Additionally, Que induced apoptosis and autophagy in PDAC cells. Mechanistically, QYHJ and Que significantly activated STAT 1 and remarkably inhibited the MAPK/ERK and PI3K/Akt/mTOR signaling pathways in vivo and in vitro, respectively. Importantly, ERK1/2 inactivation contributes to que-induced apoptosis in SW1990 and PANC-1 cells. CONCLUSIONS: These results suggest that QYHJ and Que are promising anti-PDAC avenues that benefit from their multiform mechanisms.

20.
Phytomedicine ; 109: 154565, 2023 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-36610125

RESUMO

BACKGROUND: Hepatocellular carcinoma (HCC) is a malignant tumor with high morbidity and mortality rates. E2F2 is an independent predictor of poor prognosis in HCC; however, The mechanism by which E2F2 promotes the progression of HCC remains unclear. The Shentao Ruangan (STR) formula exhibits antitumor efficacy against HCC; however, the underlying antitumor mechanisms remain unknown. PURPOSE: To explore the regulatory effect of E2F2 on the p53 signaling pathway and reveal the role and mechanism of STR in promoting cell apoptosis via the E2F2-p53 signaling pathway in HCC. METHODS: E2F2 overexpression or silencing by lentivirus in HepG2 cells were used to explore their influence on apoptosis and the p53 pathway. An H22 tumor-bearing mice model was used to determine the therapeutic efficacy of STR and its effects on the E2F2-p53 pathway. STR-mediated serum (STR-MS) was prepared, and its chemical constituents were identified using mass spectrometry. The effects of STR-MS on viability and apoptosis of HepG2 cells and the E2F2-p53 pathway were investigated and validated using rescue experiments. RESULTS: E2F2 overexpression significantly inhibited apoptosis and the p53 pathway in HepG2 cells, whereas E2F2-silenced HepG2 cells showed the reverse. This increased apoptosis was rescued by the addition of a p53 inhibitor (PFT-α) to E2F2-silenced HepG2 cells. In vivo, high doses of STR could remarkably inhibit the growth of xenografts, promote the apoptosis of hepatoma cells, downregulate E2F2, and activate the p53-dependent mitochondrial apoptotic pathway with good safety. In vitro, STR-MS exhibited similar effectiveness, and the best effect was achieved at 30% STR-MS concentration for 48 h. When 30% STR-MS was added to E2F2-overexpressing cells, the increased apoptosis and expression of key proteins in the p53-dependent mitochondrial apoptosis pathway were significantly rescued. CONCLUSION: Our findings demonstrate, for the first time, that E2F2 inhibits hepatoma cell apoptosis in a p53-dependent manner and that STR may promote apoptosis by regulating the E2F2-p53 pathway in HCC.


Assuntos
Carcinoma Hepatocelular , Neoplasias Hepáticas , Humanos , Animais , Camundongos , Carcinoma Hepatocelular/patologia , Neoplasias Hepáticas/patologia , Proteína Supressora de Tumor p53/metabolismo , Linhagem Celular Tumoral , Transdução de Sinais , Proliferação de Células , Apoptose , Células Hep G2 , Fator de Transcrição E2F2/metabolismo
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