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1.
Plant J ; 2024 Apr 12.
Artigo em Inglês | MEDLINE | ID: mdl-38606539

RESUMO

The Phyllanthaceae family comprises a diverse range of plants with medicinal, edible, and ornamental value, extensively cultivated worldwide. Polyploid species commonly occur in Phyllanthaceae. Due to the rather complex genomes and evolutionary histories, their speciation process has been still lacking in research. In this study, we generated chromosome-scale haplotype-resolved genomes of two octoploid species (Phyllanthus emblica and Sauropus spatulifolius) in Phyllanthaceae family. Combined with our previously reported one tetraploid (Sauropus androgynus) and one diploid species (Phyllanthus cochinchinensis) from the same family, we explored their speciation history. The three polyploid species were all identified as allopolyploids with subgenome A/B. Each of their two distinct subgenome groups from various species was uncovered to independently share a common diploid ancestor (Ancestor-AA and Ancestor-BB). Via different evolutionary routes, comprising various scenarios of bifurcating divergence, allopolyploidization (hybrid polyploidization), and autopolyploidization, they finally evolved to the current tetraploid S. androgynus, and octoploid S. spatulifolius and P. emblica, respectively. We further discuss the variations in copy number of alleles and the potential impacts within the two octoploids. In addition, we also investigated the fluctuation of metabolites with medical values and identified the key factor in its biosynthesis process in octoploids species. Our study reconstructed the evolutionary history of these Phyllanthaceae species, highlighting the critical roles of polyploidization and hybridization in their speciation processes. The high-quality genomes of the two octoploid species provide valuable genomic resources for further research of evolution and functional genomics.

2.
Support Care Cancer ; 32(4): 256, 2024 Mar 28.
Artigo em Inglês | MEDLINE | ID: mdl-38546900

RESUMO

BACKGROUND: For patients with nasopharyngeal carcinoma (NPC), the incidence of malnutrition is quite high, and malnutrition has severe effects on NPC patients. However, there is currently no recognized gold standard or specific nutritional assessment tool available to assess malnutrition in NPC patients. Our objective was to develop and verify a new nomogram model for NPC patients. METHODS: Data were collected from NPC patients. To evaluate risk factors for malnutrition, univariate and multivariate logistic regression analyses were used. Based on the risk factors, a new nomogram model was developed. The efficacy of the model was evaluated and validated. RESULTS: Logistic regression analysis showed that age ≥ 65 years, the number of chemotherapy cycles completed ≥ 1, a high total radiation dose received, low body mass index (BMI), low albumin, and low chloride were the risk factors. The assessment effect of the new model was good by evaluation and validation; it can be used as an assessment tool for malnutrition in NPC patients. CONCLUSIONS: Age ≥ 65 years, completing ≥ 1 chemotherapy cycles, a high total radiation dose received, low BMI, low albumin, and low chloride levels are risk factors for malnutrition in NPC patients. The assessment effect of the new model, developed based on these risk factors, is good, and it can be used as an assessment tool for malnutrition in NPC patients.


Assuntos
Desnutrição , Neoplasias Nasofaríngeas , Humanos , Idoso , Carcinoma Nasofaríngeo/patologia , Nomogramas , Neoplasias Nasofaríngeas/radioterapia , Cloretos/uso terapêutico , Fatores de Risco , Desnutrição/epidemiologia , Desnutrição/etiologia , Albuminas
3.
Diabetol Metab Syndr ; 16(1): 21, 2024 Jan 19.
Artigo em Inglês | MEDLINE | ID: mdl-38238828

RESUMO

BACKGROUND: Time in range (TIR), as an important glycemic variability (GV) index, is clearly associated with disease complications in type 1 diabetes (T1D). Metabolic dysregulation is also involved in the risks of T1D complications. However, the relationship between metabolites and TIR remains poorly understood. We used metabolomics to investigate metabolic profile changes in T1D patients with different TIR. METHODS: This study included 85 T1D patients and 81 healthy controls. GV indices, including TIR, were collected from continuous glucose monitoring system. The patients were compared within two subgroups: TIR-L (TIR < 50%, n = 21) and TIR-H (TIR > 70%, n = 14). To screen for differentially abundant metabolites and metabolic pathways, serum and urine samples were obtained for untargeted metabolomics by ultra-performance liquid chromatography‒mass spectrometry. Correlation analysis was conducted with GV metrics and screened biomarkers. RESULTS: Metabolites were significantly altered in T1D and subgroups. Compared with healthy controls, T1D patients had higher serum levels of 5-hydroxy-L-tryptophan, 5-methoxyindoleacetate, 4-(2-aminophenyl)-2,4-dioxobutanoate, and 4-pyridoxic acid and higher urine levels of thromboxane B3 but lower urine levels of hypoxanthine. Compared with TIR-H group, The TIR-L subgroup had lower serum levels of 5-hydroxy-L-tryptophan and mevalonolactone and lower urine levels of thromboxane B3 and phenylbutyrylglutamine. Dysregulation of pathways, such as tryptophan, vitamin B6 and purine metabolism, may be involved in the mechanism of diabetic complications related to glycemic homeostasis. Mevalonolactone, hypoxanthine and phenylbutyrylglutamine showed close correlation with TIR. CONCLUSIONS: We identified altered metabolic profiles in T1D individuals with different TIR. These findings provide new insights and merit further exploration of the underlying molecular pathways relating to diabetic complications.

4.
J Diabetes Complications ; 38(2): 108652, 2024 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-38190779

RESUMO

BACKGROUND: Diabetic kidney disease (DKD) is a secondary complication of diabetes mellitus and a leading cause of chronic kidney disease. AIM: To investigate the impact of long-term canagliflozin treatment on DKD and elucidate its underlying mechanism. METHODS: DKD model was established using high-fat diet and streptozotocin in male C57BL/6J mice (n = 30). Mice were divided into five groups and treated for 12 weeks. 1) normal control mice, 2) DKD model, 3) mice treated low-dose of canagliflozin, 4) high-dose of canagliflozin and 5) ß-hydroxybutyrate. Mice kidney morphology and function were evaluated, and a metabolomics analysis was performed. RESULTS: Canagliflozin treatment reduced blood creatinine and urine nitrogen levels and improved systemic insulin sensitivity and glucose tolerance in diabetic mice. Additionally, a decrease in histological lesions including collagen and lipid deposition in the kidneys was observed. ß-hydroxybutyrate treatment did not yield a comparable outcome. The metabolomics analysis revealed that canagliflozin induced alterations in amino acid metabolism profiles in the renal tissue of diabetic mice. CONCLUSION: Canagliflozin protects the kidneys of diabetic mice by increasing the levels of essential amino acids, promoting mitochondrial homeostasis, mitigating oxidative stress, and stimulating the amino acid-dependent tricarboxylic acid cycle.


Assuntos
Diabetes Mellitus Experimental , Nefropatias Diabéticas , Inibidores do Transportador 2 de Sódio-Glicose , Animais , Masculino , Camundongos , Ácido 3-Hidroxibutírico/uso terapêutico , Aminoácidos , Canagliflozina/farmacologia , Canagliflozina/uso terapêutico , Diabetes Mellitus Experimental/complicações , Diabetes Mellitus Experimental/tratamento farmacológico , Diabetes Mellitus Experimental/metabolismo , Nefropatias Diabéticas/tratamento farmacológico , Nefropatias Diabéticas/prevenção & controle , Nefropatias Diabéticas/etiologia , Rim/patologia , Camundongos Endogâmicos C57BL , Inibidores do Transportador 2 de Sódio-Glicose/farmacologia , Inibidores do Transportador 2 de Sódio-Glicose/uso terapêutico
5.
Cell Signal ; 114: 111009, 2024 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-38092300

RESUMO

AIMS: Glucokinase (GCK) acts as the glucose sensor in maintaining glucose homeostasis. The inactivating mutation of the GCK gene leads to glucokinase-maturity onset diabetes of the young (GCK-MODY). This study aims to gain further insights into the molecular alterations triggered by GCK partial inactivation in hepatocytes, potentially underlying the favorable prognosis of GCK-MODY. MAIN METHODS: A GCK knockdown HepG2 cell model was established, and the integration of proteomics and metabolomics was used to gain a comprehensive understanding of the molecular pathway changes caused by GCK inactivation in the liver. KEY FINDINGS: Proteomic analysis identified 257 differential proteins. KEGG pathway enrichment analysis showed that protein expression changes in the GCK knockdown group were significantly enriched in central carbon metabolism, the TCA cycle, amino acid metabolism and the oxidative phosphorylation pathway. Among them, enzymes in the TCA cycle (PC, IDH2, SDH) were significantly downregulated in GCK-knockdown group. Targeted metabolomics revealed that in the GCK knockdown hepatocytes, TCA cycle intermediates were significantly decreased, including pyruvate, oxaloacetate, citrate and succinic acid, and three metabolites increased including glycine, betaine and homocysteine. These metabolic alterations in turn reduced the accumulation of reactive oxygen species in GCK knockdown hepatocytes. Correlation analysis indicated that TCA cycle metabolites were positively correlated with proteins involved in the TCA cycle, carbon metabolism, glycolysis, Ras signaling, fibrosis and inflammation. SIGNIFICANCE: In conclusion, GCK knockdown reduced TCA cycle flux and oxidative stress in hepatocytes by influencing the levels of key transcription factors and enzymes, providing a comprehensive understanding of the effects of GCK partial inactivation on liver metabolism and molecular mechanisms.


Assuntos
Diabetes Mellitus Tipo 2 , Glucoquinase , Humanos , Glucoquinase/genética , Glucoquinase/metabolismo , Proteômica , Hepatócitos/metabolismo , Fígado/metabolismo , Glucose , Mutação
6.
Cell Biosci ; 13(1): 230, 2023 Dec 20.
Artigo em Inglês | MEDLINE | ID: mdl-38124132

RESUMO

Type I interferon (IFN-I) plays crucial roles in the regulation of inflammation and it is associated with various inflammatory diseases including systemic lupus erythematosus (SLE), rheumatoid arthritis (RA), and periodontitis, impacting people's health and quality of life. It is well-established that IFN-Is affect immune responses and inflammatory factors by regulating some signaling. However, currently, there is no comprehensive overview of the crucial regulatory role of IFN-I in distinctive pathways as well as associated inflammatory diseases. This review aims to provide a narrative of the involvement of IFN-I in different signaling pathways, mainly mediating the related key factors with specific targets in the pathways and signaling cascades to influence the progression of inflammatory diseases. As such, we suggested that IFN-Is induce inflammatory regulation through the stimulation of certain factors in signaling pathways, which displays possible efficient treatment methods and provides a reference for the precise control of inflammatory diseases.

7.
Diabetol Metab Syndr ; 15(1): 206, 2023 Oct 24.
Artigo em Inglês | MEDLINE | ID: mdl-37875989

RESUMO

BACKGROUND: Maturity-onset diabetes of the young type 2 (MODY2) is a rare genetic disorder characterized as mild fasting hyperglycemia with low risk of vascular complications caused by glucokinase gene mutation. This study aims to investigate metabolites alteration associated with MODY2, exploring possible mechanism underlying characteristic clinical manifestations and low cardiovascular risks of MODY2 and providing serum metabolite biomarkers to facilitating MODY2 diagnosis. METHODS: Fasting serum samples from MODY2, type 1 diabetes (T1DM) and healthy individuals were collected. By using targeted metabolomics via liquid chromatography-tandem mass spectrometry platform, we quantified the metabolites involved in tricarboxylic acid (TCA) cycle and one-carbon metabolism. RESULTS: Metabolomic profiling revealed significant difference of intermediates from central metabolism cycle, methionine cycle and several amino acids between MODY2 and T1DM groups. Among these, serum citrate, α-ketoglutaric acid, serine, glycine, glutamine and homocysteine were significantly elevated in MODY2 patients compared with T1DM patients; and compared with healthy subjects, malate and methionine levels were significantly increased in the two groups of diabetic patients. The correlation analysis with clinical indexes showed that α- ketoglutarate, serine, glycine, and glutamine were negatively correlated with blood glucose indicators including fasting blood glucose, HbA1c, and GA, while citrate was positively correlated with C-peptide. And homocysteine displayed positive correlation with HDL and negative with C-reactive protein, which shed light on the mechanism of mild symptoms and low risk of cardiovascular complications in MODY2 patients. A panel of 4 metabolites differentiated MODY2 from T1DM with AUC of 0.924, and a combination of clinical indices and metabolite also gained good diagnostic value with AUC 0.948. CONCLUSION: In this research, we characterized the metabolite profiles of TCA cycle and one-carbon metabolism in MODY2 and T1DM and identified promising diagnostic biomarkers for MODY2. This study may provide novel insights into the pathogenesis and clinical manifestations of MODY2.

8.
Front Pharmacol ; 14: 1232539, 2023.
Artigo em Inglês | MEDLINE | ID: mdl-37876725

RESUMO

Periodontitis, a condition that results in periodontal attachment loss and alveolar bone resorption, contributes to the global burden of oral disease. The underlying mechanism of periodontitis involves the dysbiosis and dyshomeostasis between host and oral microbes, among which the macrophage is one of the major innate immune cell players, producing interferon ß (IFNß) in response to bacterial infection. The objective of this research was to examine the interaction of macrophages with periodontitis and the role and mechanism of IFNß on macrophages. IFNß has been shown to have the potential to induce the differentiation of M1 to M2 macrophages, which are stimulated by low levels of lipopolysaccharide (LPS). Additionally, IFNß has been demonstrated to promote the production of ISG15 by macrophages, which leads to the inhibition of the innate immune response. Moreover, our investigation revealed that IFNß has the potential to augment the secretion of ISG15 and its downstream cytokine, IL10, in LPS-stimulated macrophages. Single-cell analysis was conducted on the gingival tissues of patients with periodontitis, which revealed a higher proportion of macrophages in the periodontitis-diseased tissue and increased expression of IFNß, ISG15, and IL10. Gene Set Enrichment Analysis indicated that bacterial infection was associated with upregulation of IFNß, ISG15, and IL10. Notably, only IL10 has been linked to immunosuppression, indicating that the IFNß-ISG15-IL10 axis might promote an anti-inflammatory response in periodontitis through IL10 expression. It is also found that macrophage phenotype transitions in periodontitis involve the release of higher levels of IFNß, ISG15, and IL10 by the anti-inflammatory M2 macrophage phenotype compared to the pro-inflammatory M1 phenotype and myeloid-derived suppressor cells (MDSCs). This implies that the IFNß-induced production of IL10 might be linked to the M2 macrophage phenotype. Furthermore, cell communication analysis demonstrated that IL10 can promote fibroblast proliferation in periodontal tissues via STAT3 signaling.

9.
Nutrition ; 116: 112199, 2023 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-37722250

RESUMO

OBJECTIVES: It is necessary to construct an evaluation index for patients with nasopharyngeal carcinoma during peri-radiotherapy to provide a reference for the evaluation of the quality of nutritional management of patients with nasopharyngeal carcinoma during peri-radiotherapy. The aim of this study was to construct a set of scientific, comprehensive, and feasible indicators for evaluating the quality of nutrition management in patients with nasopharyngeal carcinoma during peri-radiotherapy to provide a unified reference basis for objective nutritional evaluation of these patients during the peri-radiotherapy period and to provide insights to the clinical treatment and care of these patients. METHODS: A multidisciplinary research team was set up from December 2021 to April 2022. We took the three-dimensional quality structure model as the theoretical framework; based on the literature review, the first draft of the nutrition management quality evaluation index for patients with nasopharyngeal carcinoma during peri-radiotherapy was formed by a semi-structured interview. The Delphi correspondence method was used to survey 18 experts from 12 cities in China. The multidimensional analytical hierarchy process was used to determine the evaluation index and weight of nutrition management quality of patients with nasopharyngeal carcinoma during peri-radiotherapy. RESULTS: The effective questionnaire recovery rates of the two rounds of letters were 90.005% and 100%, respectively, and the expert authority coefficients were 0.906 and 0.918, respectively. The Kendall harmony coefficients of the two rounds of letters were 0.271 to 0.313 and 0.309 to 0.349, respectively. The nutrition management quality evaluation index of patients with nasopharyngeal carcinoma during peri-radiotherapy was constructed and included 3 first-level indexes, 10 second-level indexes, and 71 third-level indexes. CONCLUSION: The evaluation index of the nutrition management quality of patients with nasopharyngeal carcinoma during peri-radiotherapy is scientific and reliable, and it may have a certain guiding significance for nurses to evaluate the quality of nutrition management of these patients during this period.


Assuntos
Neoplasias Nasofaríngeas , Avaliação Nutricional , Humanos , Carcinoma Nasofaríngeo/radioterapia , Neoplasias Nasofaríngeas/radioterapia , Neoplasias Nasofaríngeas/tratamento farmacológico , China
10.
Biomolecules ; 13(8)2023 07 31.
Artigo em Inglês | MEDLINE | ID: mdl-37627267

RESUMO

BACKGROUND: Despite the increasing prevalence rate of nonalcoholic fatty liver disease (NAFLD) worldwide, efficient pharmacotherapeutic regimens against NAFLD still need to be explored. Previous studies found that pioglitazone and metformin therapy could partly ameliorate NAFLD, but their combination therapy effects have not been researched. In the present study, we assessed the protective effects of metformin and pioglitazone combination therapy on liver lipid metabolism in high-fat diet (HFD)-fed mice and investigated the molecular mechanism. METHODS: Male C57BL/6 mice were divided into five groups: normal control; HFD control; metformin monotherapy; pioglitazone monotherapy and combined therapy. After 8 weeks of pharmacological intervention, glucose and lipid metabolism characteristics, hepatic histology, lipidomics profiling and RNA-seq analysis were performed. RESULTS: The combination of pioglitazone and metformin significantly ameliorated HFD-induced metabolic disturbance and the hepatic oil red O area. A lipidomics analysis showed that combined therapy could significantly reduce the high levels of free fatty acids (FFA), diacylglycerol and triglycerides, while a set of glycerophospholipids and sphingolipids were increased in the combined therapy group. Consistently, an RNA-seq analysis also showed a remarkable reduction in genes associated with FFA uptake and de novo lipogenesis, including Cd36, Fads1, Fads2, Fasn, Scd1, Elovl5 and Pklr in the combined therapy group. CONCLUSIONS: Pioglitazone and metformin might have a synergistic protective effect on NAFLD by improving hepatic lipid profiles in HFD-induced mice. Further studies are needed to verify the clinical effects.


Assuntos
Metabolismo dos Lipídeos , Hepatopatia Gordurosa não Alcoólica , Masculino , Animais , Camundongos , Camundongos Endogâmicos C57BL , Camundongos Obesos , Pioglitazona/farmacologia , Hepatopatia Gordurosa não Alcoólica/tratamento farmacológico
11.
Chemosphere ; 339: 139426, 2023 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-37467853

RESUMO

In this work, for the removal of azo dyes that cause environmental pollution, TiO2-ZnO has been modified with graphitic carbon nitride (g-C3N4) to form an advanced hetero-linked photocatalyst. With this catalyst, photocatalytic hydrogen production and photodegradation activity against methylene orange (MO) and rhodamineB (RhB) dye removal were studied. The synthesized nanostructure was extensively characterized by several techniques such as XRD, TEM, UV-Vis and fluorescence spectrophotometer (PL) techniques. According to the analysis, a significant increase in the photocatalytic efficiency of TiO2-ZnO was determined after it was modified with g-C3N4 nanostructures. The combination between TiO2-ZnO and g-C3N4 was shown to be responsible for the improvement in photocatalytic activity because it significantly decreased electron-hole recombination. After 90 min the 62.81% of MO dye was removed but at 120 min only 57% of RhB was degraded. In addition, the antibacterial activity of TiO2-ZnO/g-C3N4 catalyst was carried out against gram positive and gram negatif bacteria. The bacterial inhibition (%) of TiO2-ZnO/g-C3N4 catalyst.was found to be 44 % against E. coli and 33 % against at 100 µg/ml concentration. In line with the analyzes obtained with this study, important results have been revealed for the application of photocatalytic methods in more industrial dimensions in the production of hydrogen, which is a valuable energy type.


Assuntos
Nanocompostos , Óxido de Zinco , Água , Corantes , Escherichia coli , Nanocompostos/química , Hidrogênio/química
13.
Heliyon ; 9(7): e17718, 2023 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-37456029

RESUMO

With the ability to produce components with complex and precise structures, additive manufacturing or 3D printing techniques are now widely applied in both industry and consumer markets. The emergence of tissue engineering has facilitated the application of 3D printing in the field of biomedical implants. 3D printed implants with proper structural design can not only eliminate the stress shielding effect but also improve in vivo biocompatibility and functionality. By combining medical images derived from technologies such as X-ray scanning, CT, MRI, or ultrasonic scanning, 3D printing can be used to create patient-specific implants with almost the same anatomical structures as the injured tissues. Numerous clinical trials have already been conducted with customized implants. However, the limited availability of raw materials for printing and a lack of guidance from related regulations or laws may impede the development of 3D printing in medical implants. This review provides information on the current state of 3D printing techniques in orthopedic implant applications. The current challenges and future perspectives are also included.

14.
Nutrients ; 15(12)2023 Jun 19.
Artigo em Inglês | MEDLINE | ID: mdl-37375697

RESUMO

Maternal exercise benefits offspring's metabolic health with long-term repercussions. Here, we systematically reviewed the effects of maternal exercise on offspring obesity outcomes in adulthood. The primary outcome is body weight. The secondary outcomes are glucose and lipid profiles. Two independent authors performed a search in the databases PubMed, EMBASE, and Web of Science. A total of nine studies with 17 different cohorts consisting of 369 animals (two species) were included. Study quality was assessed using the SYRCLE risk of bias. The PRISMA statement was used to report this systematic review. The results showed that maternal exercise contributes to improved glucose tolerance, reduced insulin concentration, and lower total cholesterol and low density lipoprotein levels in adult offspring in mice, which are independent of maternal body weight and offspring dietary condition. Additionally, in rats, maternal exercise leads to a higher body weight in adult offspring, which might be attributed to the high-fat diet of offspring after weaning. These findings further support the metabolic beneficial role of maternal exercise on offspring in adulthood, although the issue of translating the results to the human population is still yet to be addressed.


Assuntos
Obesidade , Efeitos Tardios da Exposição Pré-Natal , Humanos , Adulto , Ratos , Camundongos , Animais , Feminino , Obesidade/etiologia , Obesidade/metabolismo , Peso Corporal , Dieta Hiperlipídica/efeitos adversos , Sobrepeso , Glucose , Fenômenos Fisiológicos da Nutrição Materna , Efeitos Tardios da Exposição Pré-Natal/metabolismo
15.
Adv Biol (Weinh) ; 7(9): e2200301, 2023 09.
Artigo em Inglês | MEDLINE | ID: mdl-37303127

RESUMO

This study aimed to enhance understanding of LMNA mutation-related lipodystrophy by elucidating genotype-phenotype correlations and potential molecular mechanisms. Clinical data from six patients with LMNA mutation-related lipodystrophy are analyzed, and four distinct LMNA mutations are identified. Associations between mutations and lipodystrophy phenotypes are assessed. Three LMNA mutation plasmids are constructed and transfected into HEK293 cells. Protein stability, degradation pathways, and binding proteins of mutant Lamin A/C are examined using Western blotting, co-immunoprecipitation, and mass spectrometry. Confocal microscopy is employed to observe nuclear structure. Four different LMNA mutations are identified in the six patients, all exhibiting lipodystrophy and metabolic disorders. Cardiac dysfunction is observed in two out of six patients. Metformin and pioglitazone are the primary treatments for glucose control. Confocal microscopy revealed nuclear blebbing and irregular cell membranes. Mutant Lamin A/C stability is significantly decreased, and degradation occurred primarily via the ubiquitin-proteasome system (UPS). Potential binding ubiquitination-related proteins of mutant Lamin A/C are identified. This study investigated LMNA mutation-related lipodystrophy, identifying four unique mutations and their connections to specific phenotypes. It is found to decreased mutant Lamin A/C stability and degradation primarily through the UPS, offering new insights into molecular mechanisms and potential therapeutic targets.


Assuntos
Lipodistrofia , Doenças Metabólicas , Humanos , Lamina Tipo A/genética , Células HEK293 , Mutação , Lipodistrofia/genética
16.
Mol Nutr Food Res ; 67(16): e2200753, 2023 08.
Artigo em Inglês | MEDLINE | ID: mdl-37334884

RESUMO

SCOPE: Circadian rhythms profoundly impact metabolism and the gut microbiota. A maternal high-fat diet (HFD) exerts effects on the metabolic syndrome of adult offspring in a sex-specific manner, the underlying mechanisms, however, remain unclear. METHODS AND RESULTS: Female mice are fed an HFD and raise their offspring on a standard chow diet until 24 weeks. The glucose tolerance, insulin sensitivity, and diurnal rhythms of serum metabolic profiles are assessed in male and female adult offspring. Simultaneously, 16S rRNA is applied to characterize gut microbiota diurnal rhythms. The study finds that maternal HFD tends to deteriorate glucose tolerance and impairs insulin sensitivity in male offspring, but not female offspring, which can be associated with the circadian alterations of serum metabolic profiles in male offspring. As expected, maternal HFD sex-specifically alters diurnal rhythms of the gut microbiota, which exhibits putative associations with metabolic profiles in males. CONCLUSIONS: The present study identifies the critical role of gut microbiota diurnal rhythms in triggering sex-biased metabolic diurnal rhythms in response to maternal HFD, at least in part. As early life may be a critical window for preventing metabolic diseases, these findings provide the basis for developing chronobiology applications targeting the gut microbiota to combat early metabolic alterations, especially in males.


Assuntos
Microbioma Gastrointestinal , Resistência à Insulina , Feminino , Camundongos , Masculino , Animais , Dieta Hiperlipídica/efeitos adversos , Resistência à Insulina/fisiologia , Microbioma Gastrointestinal/fisiologia , RNA Ribossômico 16S , Glucose , Camundongos Endogâmicos C57BL
17.
Phytochemistry ; 213: 113771, 2023 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-37352949

RESUMO

Herein, 13 previously undescribed neo-clerodane diterpenoids (1-13) and 27 known analogs (14-40) were isolated from the aerial parts of Scutellaria barbata. Absolute configurations of undescribed compounds were assigned based on single-crystal X-ray diffraction analysis and comparison of experimental and circular dichroism. All isolates were evaluated for the inhibition of nitric oxide generation induced by lipopolysaccharide in RAW 264.7 macrophages. Compound 36 was found to be the most active with an IC50 value of 10.6 µM. Structure-activity relations of these neo-clerodane diterpenoids revealed that the α, ß-unsaturated-γ-lactone moiety with an exocyclic conjugated double bond was necessary for maintaining and increasing its activity. Further mechanistic studies show that compound 36 suppressed nitric oxide synthase enzymes (iNOS) expression without affecting iNOS activity. Additionally, compound 36 suppresses NF-κB signaling by inhibiting IκBα phosphorylation.


Assuntos
Diterpenos Clerodânicos , Scutellaria , Estrutura Molecular , Diterpenos Clerodânicos/farmacologia , Diterpenos Clerodânicos/química , Scutellaria/química , Lipopolissacarídeos/farmacologia , Macrófagos , Óxido Nítrico
18.
Support Care Cancer ; 31(5): 251, 2023 Apr 10.
Artigo em Inglês | MEDLINE | ID: mdl-37036536

RESUMO

OBJECTIVE: This study is to explore the effect of the Plan-Do-Check-Act (PDCA) cycle on the nutritional management of patients with nasopharyngeal carcinoma (NPC). METHODS: A total of 100 NPC patients were randomly divided into a control group and a PDCA group, with 50 patients in each group. The control group adopted a routine nutritional management strategy, and the PDCA group adopted a PDCA cycle management strategy. The body weight, body mass index (BMI), hemoglobin, serum prealbumin, serum albumin, the Patient-Generated Subjective Global Assessment (PG-SGA) score, the Nutrition Risk Screening 2002 (NRS-2002) score, the incidence rate of nutritional risk, the grade of malnutrition, and the grade of oral mucositis were compared between the two groups. RESULTS: The body weight, BMI, and serum prealbumin in the PDCA group were higher than those in the control group, and the difference was statistically significant (p < 0.05). The NRS2002 score and PG-SGA score in the PDCA group were lower than those in the control group, and the differences were statistically significant (p < 0.05). The incidence of nutritional risk, the grade of malnutrition, and the grade of oral mucositis were less in the PDCA group than those in the control group (p < 0.05). There was no significant difference in hemoglobin and serum albumin between the two groups (p > 0.05). CONCLUSION: The PDCA cycle can improve body weight, BMI, and serum prealbumin in NPC patients. It can reduce the NRS2002 score, the PG-SGA score, the incidence of nutritional risk, the severity of malnutrition, and the severity of oral mucositis in NPC patients.


Assuntos
Desnutrição , Neoplasias Nasofaríngeas , Estomatite , Humanos , Pré-Albumina , Avaliação Nutricional , Carcinoma Nasofaríngeo/terapia , Estado Nutricional , Desnutrição/etiologia , Desnutrição/prevenção & controle , Peso Corporal , Albumina Sérica , Neoplasias Nasofaríngeas/terapia , Hemoglobinas , Estomatite/complicações
19.
Nano Lett ; 23(7): 2764-2770, 2023 Apr 12.
Artigo em Inglês | MEDLINE | ID: mdl-37010357

RESUMO

Two-dimensional (2D) semiconductors such as monolayer molybdenum disulfide (MoS2) are promising building blocks for ultrascaled field effect transistors (FETs), benefiting from their atomic thickness, dangling-bond-free flat surface, and excellent gate controllability. However, despite great prospects, the fabrication of 2D ultrashort channel FETs with high performance and uniformity remains a challenge. Here, we report a self-encapsulated heterostructure undercut technique for the fabrication of sub-10 nm channel length MoS2 FETs. The fabricated 9 nm channel MoS2 FETs exhibit superior performances compared with sub-15 nm channel length including the competitive on-state current density of 734/433 µA/µm at VDS = 2/1 V, record-low DIBL of ∼50 mV/V, and superior on/off ratio of 3 × 107 and low subthreshold swing of ∼100 mV/dec. Furthermore, the ultrashort channel MoS2 FETs fabricated by this new technique show excellent homogeneity. Thanks to this, we scale the monolayer inverter down to sub-10 nm channel length.

20.
Ann Transl Med ; 11(5): 211, 2023 Mar 15.
Artigo em Inglês | MEDLINE | ID: mdl-37007551

RESUMO

Background: Anxiety, depression, and dementia are important issues affecting the mental health of the older population. Given the relationship between mental health and physical disorders, it is particularly important to diagnose and identify these psychological problems in older people. Methods: Psychological data of 15,173 older people living in various districts and counties of Shanxi province, China, were extracted from data collected through the '13th Five-Year Plan for Healthy Aging-Psychological Care for the Elderly Project' of the National Health Commission of China in 2019. Three different ensemble learning classifiers [random forest (RF), Extreme Gradient Boosting (XGBoost) and Light Gradient Boosting Machine (LightGBM)] were evaluated, and the best classifier with the selected feature set was selected. The ratio of training to testing cases was 8:2. The predictive performance of the three classifiers was evaluated by calculating the area under the receiver operating characteristic curve (AUC), accuracy, recall, and F measurement based on 10-fold cross-validation and ranked by AUC. Results: All the three classifiers have achieved good prediction results. In the test set, the AUC value range for the three classifiers was 0.79 to 0.85. The LightGBM algorithm showed higher accuracy than both the baseline and XGBoost. A new machine learning (ML)-based model to predict mental health problems in older people was constructed. The model was interpretative and could hierarchically predict psychological problems including anxiety, depression, and dementia in older people. Experimental results showed that the method could accurately identify those suffering from anxiety, depression, and dementia in different age groups. Conclusions: A simple method model was designed based on only eight problems, which had good accuracy and was widely applicable to the older of all ages. Overall, this research approach avoided the need to identify older people with poor mental health through the traditional standardized questionnaire approach.

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