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PURPOSE: The aim of this study was to investigate the relationship between obesity and lower extremity arterial disease (LEAD) in patients with type 2 diabetes mellitus (T2DM). METHODS: This retrospective study included 1821 patients with type 2 diabetes: 364 patients with LEAD and 1457 patients without LEAD. The patients were divided into training and internal test cohorts in a 7:3 ratio. LASSO regression analysis was used in the training cohort to filter relevant variables. Univariate and multivariate regression analyses were conducted to assess independent risk factors. A diagnostic nomogram was constructed and its discrimination was evaluated using the area under the ROC curve (AUC). The consistency was assessed using a calibration plot. The clinical application of the nomogram was evaluated by performing a decision curve analysis (DCA) and validated by an internal test cohort of the training cohorts. RESULTS: The LEAD group exhibited significantly higher values in obesity-related indices compared to the non-LEAD group, including waist circumference (WC), waist-to-hip ratio (WHR), waist-to-height ratio (WHtR), conicity index (CI), body adiposity index (BAI), and abdominal volume index (AVI). Multivariate analysis identified BMI, CI, BAI, and other parameters as independent risk factors for LEAD. A nomogram was constructed, and the AUC value of the nomogram was 0.746 in the training cohort and 0.663 in the internal test cohort. CONCLUSION: Obesity-related indices are associated with LEAD in patients with T2DM. Therefore, it is important to manage waist circumference and weight to reduce the risk of LEAD in patients with T2DM.
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Previous findings have indicated a marked upregulation of SNORA71A in gallbladder cancer (GBC) tissues compared to normal samples. However, the precise role and molecular mechanisms of SNORA71A in GBC remain largely unknown. Moreover, gemcitabine (GEM) drug resistance has been found to lead to unfavorable outcomes and recurrence in GBC patients. Therefore, this study aims to investigate the impact of SNORA71A on GBC and explore its potential effects on the sensitivity of GBC cells to GEM. RT-qPCR was conducted to assess SNORA71A level in matched normal and GBC tissues. Cell proliferation was examined through CCK-8 and 5-ethynyl-2'-deoxyuridine (EdU) assays. Additionally, the expression of proteins in GBC cells was analyzed using western blot assay. The level of SNORA71A was notably higher in GBC tissues relative to normal tissues. SNORA71A overexpression led to increased GBC cell proliferation and invasion. Conversely, SNORA71A deficiency strongly suppressed GBC cell proliferation and invasion and triggered cell apoptosis and ferroptosis. Additionally, downregulation of SNORA71A obviously enhanced the antiproliferative and anti-invasive effects of GEM on GBC cells, whereas these changes were reversed by inhibiting ferroptosis. Furthermore, deficiency of SNORA71A further augmented the GEM-induced downregulation of p-Akt, Nrf2, and GPX4 in NOZ cells; however, these effects were reversed by ferroptosis inhibition. Collectively, these findings suggested that downregulation of SNORA71A may increase the sensitivity of GBC cells to GEM by triggering ferroptosis through inhibiting the AKT/NRF2/GPX4 signaling pathway.
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Hyperuricemic nephropathy (HN) is characterized by increased serum uric acid levels that incite renal inflammation. While omega-3 polyunsaturated fatty acids (PUFAs) are known for their anti-inflammatory properties, their impact on HN remains unclear. This study explored the effects of omega-3 PUFAs, specifically docosahexaenoic acid (DHA) and eicosapentaenoic acid (EPA), on HN. Using a mouse model induced by adenine and potassium oxonate, we treated HN mice with DHA, EPA, or both for four weeks. The results showed that omega-3 PUFAs significantly reduced serum uric acid levels and improved kidney function, with DHA, EPA, and their combination showing similar efficacy. Transcriptome sequencing and further analysis revealed that these fatty acids alleviate renal pyroptosis by reducing key markers such as NOD-like receptor pyrin containing 3 (NLRP3), cleaved gasdermin-D, caspase-1, and interleukin-1ß. To further investigate the underlying mechanism, we focused on G-protein coupled receptor 120 (GPR120), a receptor activated by DHA. The use of a GPR120 antagonist (AH7614) partially blocked DHA's effects, while the agonist (TUG891) mimicked its anti-pyroptotic actions. Co-immunoprecipitation assays showed that DHA activates GPR120, leading to its internalization and interaction with ß-arrestin2, ultimately inhibiting NLRP3 inflammasome formation and reducing inflammation. Overall, omega-3 PUFAs, particularly through GPR120 activation, appear to protect against renal inflammation in HN by modulating the NLRP3/caspase-1/GSDMD pathway.
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Background: Diabetes is associated with the incidence and prognosis of various malignancies, most notably endometrial cancer (EC). This study investigated the connection between diabetes and EC, with a specific focus on elucidating the biological implications of the diabetes mellitus (DM)-related gene WFS1. Methods: Using the CTD, GeneCards, and GSEA databases, we identified WFS1 as a diabetes-related gene and then conducted an extensive investigation focusing on WFS1 in the context of EC. First, we identified WFS1 as the target gene and obtained EC data from the TCGA database. Then, comprehensive analyses and verification experiments, including differential expression analysis, prognostic modeling, functional enrichment analysis, gene mutation profiling, assessment of immune cell infiltration, immunophenoscore (IPS), tumor stemness index scoring, drug sensitivity analysis, single-cell transcriptomic analysis, glycolytic pathway analysis, and clinical verification, were performed to comprehensively evaluate the clinical value of WFS1 in EC. Results: The EC group had significantly lower WFS1 expression, with an AUC of 0.857 for the ROC diagnostic curve. Overall survival analysis revealed that WFS1 was an independent risk factor for EC; low WFS1 expression was correlated with a poor prognosis. Stemness index analysis revealed that decreased WFS1 expression was associated with increased tumor grade and enhanced tumor stemness, suggesting increased malignancy of EC. In addition, WFS1 expression was correlated with tumor microenvironment features such as immune cell infiltration. WFS1 was also associated with tumor drug resistance. Conclusion: EC patients with low WFS1 expression have a worse prognosis. WFS1 can be used as diagnostic and prognostic marker for EC.
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Biomarcadores Tumorais , Neoplasias do Endométrio , Proteínas de Membrana , Humanos , Feminino , Neoplasias do Endométrio/genética , Neoplasias do Endométrio/imunologia , Neoplasias do Endométrio/mortalidade , Proteínas de Membrana/genética , Prognóstico , Biomarcadores Tumorais/genética , Regulação Neoplásica da Expressão Gênica , Microambiente Tumoral/imunologia , Microambiente Tumoral/genética , Pessoa de Meia-Idade , Diabetes Mellitus/genética , Diabetes Mellitus/imunologia , Perfilação da Expressão GênicaRESUMO
Polygonatum sibiricum polysaccharides (PSP) has been shown to possess multiple pharmacological functions. Our previous study found that PSP could protect against acute liver injury during sepsis via inhibiting inflammatory response. However, the underlying molecular mechanism by which PSP alleviates septic acute liver injury (SALI) remains unknown. Herein, TMT-based quantitative proteomics was utilized to explore the essential pathways and proteins involved in the protective effects of PSP on SALI. The results revealed that 632 and 176 differentially expressed proteins (DEPs) were identified in Model_vs_Control and PSP_vs_Model, respectively. GO annotation showed similar trends, suggesting that these DEPs were primarily involved in the cellular anatomical entity in Cellular Component, the cellular processe and the biological regulation in Biological Process, the binding and the catalytic activity in Molecular Function. Meanwhile, KEGG enrichment analysis implied that four common pathways, including the NF-κB signaling pathway, the IL-17 signaling pathway, the TNF signaling pathway and the Toll-like receptor signaling pathway, were closely associated with the pathogenesis of sepsis among the top 20 remarkably enriched pathways in Model_vs_Control_up and PSP_vs_Model_down. Moreover, the levels of several common DEPs, including TLR2, IKKi, JunB and CXCL9, were validated by WB, which was in line with the results of proteomics. Therefore, the protective effects of PSP on SALI might exert via blocking the above-mentioned inflammation pathways. Significance: PSP, recognized as a key component of Polygonatum sibiricum, exhibits a range of pharmacological functions. Our previous study found that PSP could protect against SALI, yet failing to clarify the mechanism of action. To reveal the underlying molecular mechanism involved in the protective effects of PSP on SALI, a TMT-based quantitative proteomic analysis was performed to detect and analyse the DEPs in liver tissue among the control group, the model group and the PSP group in this study. The results provide theoretical references for exploring the action mechanism of drugs and facilitate the comprehensive utilization of PSP. SIGNIFICANCE: PSP have been identified as the most crucial components of Polygonatum sibiricum with various pharmacological functions. Our previous study found that PSP could protect against SALI, but the mechanism of action remains unknown. To reveal the underlying molecular mechanism involved in the protective effects of PSP on SALI, a TMT-based quantitative proteomic analysis was performed to detect and analyse the DEPs in liver tissue among the control group, the model group and the PSP group in this study. The results provide theoretical references for exploring the action mechanism of drugs and facilitate the comprehensive utilization of PSP.
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Background: Chronic obstructive pulmonary disease (COPD) currently ranks among the top three causes of mortality worldwide, presenting as a prevalent and complex respiratory ailment. Ongoing research has underscored the pivotal role of immune function in the onset and progression of COPD. The immune response in COPD patients exhibits abnormalities, characterized by diminished anti-infection capacity due to immune senescence, heightened activation of neutrophils and macrophages, T cell infiltration, and aberrant B cell activity, collectively contributing to airway inflammation and lung injury in COPD. Objective: This review aimed to explore the pivotal role of the immune system in COPD and its therapeutic potential. Methods: We conducted a review of immunity and COPD published within the past decade in the Web of Science and PubMed databases, sorting through and summarizing relevant literature. Results: This article examines the pivotal roles of the immune system in COPD. Understanding the specific functions and interactions of these immune cells could facilitate the development of novel therapeutic strategies and interventions aimed at controlling inflammation, enhancing immune function, and mitigating the impact of respiratory infections in COPD patients.
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Human intestinal bacteria are the primary producers of azo reductase, and the content of azo reductase is closely associated with various intestinal diseases, including ulcerative colitis (UC). The rapid detection of changes in azo reductase levels is crucial for diagnosing and promptly intervening in UC. In this study, a therapeutic agent, FAI, specifically targeting UC, was designed and synthesized. This agent was developed by linking the anti-inflammatory drug indomethacin to flavonols with antioxidant activity via an azo bond (off-on). Breakage of the azo bond breaks results in the release of both fluorophores and drugs, achieving targeted tracing and integrated treatment effects. In vivo and in vitro fluorescence imaging experiments were used to demonstrate the potential of FAI in the diagnosis of UC, together with synergistic therapeutic effects through the release of both fluorophores and anti-inflammatory agents. Therefore, this diagnostic agent shows promise as a potential tool for diagnosing and treating UC.
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Flavonóis , Indometacina , Indometacina/uso terapêutico , Animais , Flavonóis/farmacologia , Flavonóis/química , Humanos , Camundongos , Colite Ulcerativa/tratamento farmacológico , Colite Ulcerativa/diagnóstico , Nitrorredutases/metabolismo , Desenho de Fármacos , Anti-Inflamatórios/farmacologia , Anti-Inflamatórios/uso terapêutico , Anti-Inflamatórios/química , Anti-Inflamatórios/síntese química , NADH NADPH Oxirredutases/antagonistas & inibidores , NADH NADPH Oxirredutases/metabolismo , Modelos Animais de DoençasRESUMO
OBJECTIVE: This study aimed to establish a uniform standard for the interpretation of HER2 gene and protein statuses in intrahepatic cholangiocarcinoma (ICC). We also intended to explore the clinical pathological characteristics, molecular features, RNA expression and immune microenvironment of HER2-positive ICC. METHODS: We analyzed a cohort of 304 ICCs using immunohistochemistry (IHC) and fluorescence in situ hybridization (FISH) to identify HER2 status. Comprehensive analyses of the clinicopathological, molecular genetic, and RNA expression characterizations of ICCs with varying HER2 statuses were performed using next-generation sequencing. We further investigated the tumor microenvironment of ICCs with different HER2 statuses using IHC and multiplex immunofluorescence staining. RESULTS: HER2/CEP17 ratio of ≥ 2.0 and HER2 copy number ≥ 4.0; or HER2 copy number ≥ 6.0 were setup as FISH positive criteria. Based on this criterion, 13 (4.27%, 13/304) samples were classified as having HER2 amplification. The agreement between FISH and IHC results in ICC was poor. HER2-amplified cases demonstrated a higher tumor mutational burden compared to non-amplified cases. No significant differences were observed in immune markers between the two groups. However, an increased density of CD8 + CTLA4 + and CD8 + FOXP3 + cells was identified in HER2 gene-amplified cases. CONCLUSION: FISH proves to be more appropriate as the gold standard for HER2 evaluation in ICC. HER2 gene-amplified ICCs exhibit poorer prognosis, higher mutational burden, and T cell exhaustion and immune suppressed microenvironment.
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Neoplasias dos Ductos Biliares , Colangiocarcinoma , Amplificação de Genes , Mutação , Receptor ErbB-2 , Microambiente Tumoral , Humanos , Colangiocarcinoma/genética , Colangiocarcinoma/patologia , Colangiocarcinoma/imunologia , Microambiente Tumoral/imunologia , Microambiente Tumoral/genética , Neoplasias dos Ductos Biliares/genética , Neoplasias dos Ductos Biliares/patologia , Neoplasias dos Ductos Biliares/imunologia , Feminino , Receptor ErbB-2/genética , Pessoa de Meia-Idade , Masculino , Idoso , Hibridização in Situ Fluorescente , Adulto , Biomarcadores Tumorais/genética , Linfócitos T/imunologia , Linfócitos T/patologia , Prognóstico , Exaustão das Células TRESUMO
OBJECTIVES: This study aimed to evaluate the psychometric properties of four candidate cognition bolt-on items and their combinations to the EQ-5D-5L. METHODS: Four cognition items (concentration, memory, calculation, and learning) were developed as separate questionnaire items, and were administered with the standard EQ-5D-5L to 640 individuals in a general population survey in China. From the 4 items, 11 compound items were constructed, and the 'worse level counts' rule was used to calculate a compound item score. Psychometric performance of the cognition bolt-ons was assessed in terms of informativity, convergent validity, explanatory power, and discriminatory power. RESULTS: The tested four cognition bolt-on items improved the informativity, convergent validity, explanatory power, and discriminatory power of EQ-5D-5L, with calculation and learning yielding better psychometric performance. The compound bolt-on items that coverd a range of cognitive functions demonstrated superior psychometric performance compared to single-aspect bolt-on items, with those items covering calculation and learning resulting in better psychometric performance. CONCLUSION: This study confirmed the validity of the tested cognition bolt-ons in a general Chinese population. It supported the use of a compound bolt-on item covering a range of cognitive functions such as the ability to calculate and learn.
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Plant wearable detection has garnered significant interest in advancing agricultural intelligence and promoting sustainable food production amidst the challenges of climate change. Accurately monitoring plant health and agrochemical residue levels necessitates qualities such as precision, affordability, simplicity, and noninvasiveness. Here, a novel attachable plasmonic film is introduced and designed for on-site detection of agrochemical residues utilizing surface-enhanced Raman spectroscopy (SERS). By functionalizing a thin polydimethylsiloxane film with silver nanoparticles via controlled droplet reactions in micro-well arrays, a plasmonic film is achieved that not only maintains optical transparency for precise analyte localization but also conforms closely to the plant surface, facilitating highly sensitive SERS measurements. The reliability of this film enables accurate identification and quantification of individual compounds and their mixtures, boasting an ultra-low detection limit ranging from 10-16 to 10-13 m, with mini mal relative standard deviation. To showcase its potential, on-field detection of pesticide residues on fruit surfaces is conducted using a handheld Raman spectrometer. This advancement in fabricating plasmonic nanostructures on flexible films holds promise for expanding SERS applications beyond plant monitoring, including personalized health monitoring, point-of-care diagnosis, wearable devices for human-machine interface, and on-site monitoring of environmental pollutants.
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Nanopartículas Metálicas , Prata , Análise Espectral Raman , Dispositivos Eletrônicos Vestíveis , Análise Espectral Raman/métodos , Prata/química , Nanopartículas Metálicas/química , Limite de Detecção , Dimetilpolisiloxanos/química , Nanoestruturas/química , Resíduos de Praguicidas/análiseRESUMO
BACKGROUND: This study aims to investigate relative peripheral refractive (RPR) characteristics in children with non-amblyopic myopic anisometropia and explore potential associations between relative peripheral refractive errors (RPRE) and myopia. METHODS: Relative peripheral refractive errors were assessed in 64 children diagnosed with non-amblyopic myopic anisometropia utilizing multispectral refraction topography (MRT). Two eyes of each patient were divided into into the more myopia eyes group (ME) and the fellow eyes group (FE). Evaluated parameters encompassed total defocus values (TRDV), defocus values at eccentricities spanning 0 to 15 degrees (RDV-15), 0 to 30 degrees (RDV-30), 0 to 45 degrees (RDV-45), as well as superior (RDV-S), inferior (RDV-I), temporal (RDV-T), and nasal (RDV-N) positions. RESULTS: The study revealed a noteworthy contrast in TRDV values between Group ME (0.52 ± 0.36) and Group FE (0.17 ± 0.41), with a substantial significance (P < 0.0001). While no significant RDV-15 difference emerged between Group ME (0.01 ± 0.05) and Group FE (-0.01 ± 0.07) (P > 0.05), a meaningful RDV-30 difference existed between Group ME (0.11 ± 0.14) and Group FE (0.03 ± 0.19) (P = 0.0017). A significant discrepancy in RDV-45 was also observed between Group ME (0.39 ± 0.29) and Group FE (0.13 ± 0.34) (P < 0.001). Notably, RDV-I and RDV-T positions demonstrated marked differences between Group ME and Group FE (P < 0.0001), whereas no significant disparity was noted in RDV-S and RDV-N positions (P > 0.05). CONCLUSION: Eyes exhibiting greater myopia manifested more hyperopic peripheral defocus in the context of anisometropia. MRT as a novel ophthalmic evaluation technique, holds promising potential for broader clinical applications in the future.
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Anisometropia , Miopia , Refração Ocular , Acuidade Visual , Humanos , Anisometropia/fisiopatologia , Anisometropia/complicações , Masculino , Feminino , Miopia/fisiopatologia , Miopia/complicações , Criança , Refração Ocular/fisiologia , Acuidade Visual/fisiologia , Topografia da Córnea/métodos , Adolescente , Pré-EscolarRESUMO
To clarify the relationship between microorganisms and physicochemical indicators of Xuanwei ham. Six ham samples for the first, second and third year were selected, respectively. The changes of physicochemical properties, the free fatty acids and microbial communities of Xuanwei ham were investigated by GC-MS and high-throughput sequencing technology. Results showed that scores of colour, overall acceptability, texture, taste and aroma were the highest in the third year sample. With increasing ripening time, moisture content, water activity (Aw), lightness (L*), springiness, and resilience decreased continuously, and yellowness (b*) was the highest in the second year sample. 31 free fatty acids were detected, and unsaturated fatty acids such as palmitoleic acid, oleic acid, and linoleic acid were the major fatty acids. The content of palmitoleic acid, oleic acid and eicosenoic acid increased significantly during processing. At the phylum level, the dominant bacteria were Proteobacteria and Firmicutes, and fungi were Ascomycota. At the genus level, the dominant bacteria were Staphylococcus and Psychrobacter, and fungi were Aspergillus. Correlation analysis showed that water content and Aw were closely related to microorganisms, and most unsaturated fatty acids were significantly correlated with microorganisms. These findings showed that microorganisms played an important role in the quality of Xuanwei ham, and provided a scientific basis for the quality control of Xuanwei ham.
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Produtos da Carne , Animais , Produtos da Carne/microbiologia , Produtos da Carne/análise , Microbiologia de Alimentos , Bactérias/classificação , Microbiota , Manipulação de Alimentos/métodos , Suínos , Paladar , Ácidos Graxos Insaturados/análise , Cor , Cromatografia Gasosa-Espectrometria de Massas , Carne de Porco/microbiologia , Carne de Porco/análise , Odorantes/análise , Ácidos Graxos não Esterificados/análise , Ácidos Graxos MonoinsaturadosRESUMO
OBJECTIVE: The study aimed to investigate the efficacy and safety of semaglutide in weight loss in non-diabetic people. METHODS: In this study, 84 non-diabetic people who used semaglutide to lose weight in the outpatient department of our hospital from January 1, 2022, to June 30, 2022, were enrolled and compared for changes in body weight, waist circumference, Body Mass Index (BMI), fasting blood glucose, blood pressure, pulse, and body composition (body fat ratio, visceral fat area, and skeletal muscle) before treatment and 12 weeks after the treatment to analyze the weight loss efficacy and safety. RESULTS: After administering semaglutide 0.25 mg, 0.5 mg, 0.75 mg, or 1 mg subcutaneously once a week for 12 weeks, 84 participants in this study obtained an average weight loss of 5.91 ± 3.37 kg, equivalent to 6.15 ± 4.28% of baseline body weight, and there was also a significant reduction in visceral fat area and a slight reduction in blood pressure. The most common adverse reactions included gastrointestinal reactions (nausea, vomiting, and diarrhea), which were mild and subsided within 1-2 days. No severe adverse reaction, such as hypoglycemia and hypotension, was observed. CONCLUSION: Low-dose semaglutide has been found to be effective and safe for short-term weight loss in non-diabetic people.
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Anaplastic thyroid cancer (ATC) is the most aggressive type of thyroid cancer. While ATC is rare, its mortality is high. Standard treatments, such as surgery, radiotherapy, and chemotherapy, have demonstrated limited efficacy in managing ATC. However, the advent of immunotherapy has significantly improved the prognosis for patients with ATC. Immunotherapy effectively targets and eliminates tumor cells by using the power of the body's immune cells. The neoantigen is an atypical protein generated by somatic mutation, is exclusively observed in neoplastic cells, and is devoid of central tolerance. Neoantigens exhibit enhanced specificity towards tumor cells and display robust immunogenic properties. Currently, neoantigen therapy is primarily applied in immune checkpoint inhibitors and cellular immunotherapy, encompassing adoptive immunotherapy and tumor vaccines. This study discusses the mechanism, tumor microenvironment, clinical trials, adverse events, limitations and future directions associated with ATC immunotherapy.
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BACKGROUND: Contemporary data on the quantity and quality of medication use among older adults are lacking. This study examined recent trends in the number and appropriateness of prescription medication use among older adults in the United States. METHODS: Data from the National Health and Nutrition Examination Survey (NHANES) between 2011 and March 2020 were used, and 6 336 adult participants aged 65 and older were included. We examined the number of prescription medication, prevalence of polypharmacy (≥5 prescription drugs), use of potentially inappropriate medication (PIM), and use of recommended medications (angiotensin-converting enzyme inhibitor [ACEI]/angiotensin receptor blockers [ARBs] plus beta-blockers among patients with heart failure and ACEI/ARBs among patients with albuminuria). RESULTS: There has been a slight increase in the prevalence of polypharmacy (39.3% in 2011-2012 to 43.8% in 2017-2020, p for trendâ =â .32). Antihypertensive, antihyperlipidemic, antidiabetic medications, and antidepressants are the most commonly used medications. There was no substantial change in the use of PIM (17.0% to 14.7%). Less than 50% of older adults with heart failure received ACEI/ARBs plus beta-blockers (44.3% in 2017-2020) and approximately 50% of patients with albuminuria received ACEI/ARBs (54.0% in 2017-2020), with no improvement over the study period. Polypharmacy, older age, female, and lower socioeconomic status were generally associated with greater use of PIM but lower use of recommended medications. CONCLUSIONS: The medication burden remained high among older adults in the United States and the appropriate utilization of medications did not improve in the recent decade. Our results underscore the need for greater attentions and interventions to the quality of medication use among older adults.
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Prescrição Inadequada , Inquéritos Nutricionais , Polimedicação , Humanos , Idoso , Masculino , Feminino , Estados Unidos , Prescrição Inadequada/tendências , Prescrição Inadequada/estatística & dados numéricos , Vida Independente , Lista de Medicamentos Potencialmente Inapropriados/estatística & dados numéricos , Lista de Medicamentos Potencialmente Inapropriados/tendências , Idoso de 80 Anos ou mais , Uso de Medicamentos/tendências , Uso de Medicamentos/estatística & dados numéricos , Medicamentos sob Prescrição/uso terapêutico , Antagonistas Adrenérgicos beta/uso terapêutico , Inibidores da Enzima Conversora de Angiotensina/uso terapêutico , Antagonistas de Receptores de Angiotensina/uso terapêuticoRESUMO
RATIONALE: The mechanisms underlying major depressive disorder (MDD) in children and adolescents are unclear. Metabolomics has been utilized to capture metabolic signatures of various psychiatric disorders; however, urinary metabolic profile of MDD in children and adolescents has not been studied. OBJECTIVES: We analyzed urinary metabolites in children and adolescents with MDD to identify potential biomarkers and metabolic signatures. METHODS: Here, liquid chromatography-mass spectrometry was used to profile metabolites in urine samples from 192 subjects, comprising 80 individuals with antidepressant-naïve MDD (AN-MDD), 37 with antidepressant-treated MDD (AT-MDD) and 75 healthy controls (HC). We performed orthogonal partial least squares discriminant analysis to identify differential metabolites and employed logistic regression and receiver operating characteristic analysis to establish a diagnostic panel. RESULTS: In total, 143 and 71 differential metabolites were identified in AN-MDD and AT-MDD, respectively. These were primarily linked to lipid metabolism, molecular transport, and small molecule biochemistry. AN-MDD additionally exhibited dysregulated amino acid metabolism. Compared to HC, a diagnostic panel of seven metabolites displayed area under the receiver operating characteristic curves of 0.792 for AN-MDD, 0.828 for AT-MDD, and 0.799 for all MDD. Furthermore, the urinary metabolic profiles of children and adolescents with MDD significantly differed from those of adult MDD. CONCLUSIONS: Our research suggests dysregulated amino acid metabolism and lipid metabolism in the urine of children and adolescents with MDD, similar to results in plasma metabolomics studies. This contributes to the comprehension of mechanisms underlying children and adolescents with MDD.
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Aminoácidos , Biomarcadores , Transtorno Depressivo Maior , Metabolismo dos Lipídeos , Metabolômica , Humanos , Transtorno Depressivo Maior/urina , Transtorno Depressivo Maior/metabolismo , Adolescente , Criança , Masculino , Feminino , Estudos de Casos e Controles , Aminoácidos/urina , Aminoácidos/metabolismo , Metabolismo dos Lipídeos/fisiologia , Biomarcadores/urina , Metabolômica/métodos , Antidepressivos/uso terapêutico , Cromatografia Líquida/métodos , Espectrometria de Massas/métodos , Curva ROCRESUMO
Arsenic (As) is a notorious environmental toxicant widely present in various natural environments. As exposure has been correlated with the decline in sperm motility. Yet, the mechanism has not been fully elucidated. Adult male C57 mice were given 0, 1, or 15 mg/L NaAsO2 for 10 weeks. The mature seminiferous tubules and sperm count were decreased in As-exposed mice. Sperm motility and several sperm motility parameters, including average path velocity (VAP), straight-line velocity (VSL), curvilinear velocity (VCL), beat-cross frequency (BCF), linearity (LIN), straightness (STR), and amplitude of lateral head displacement (ALH), were declined in As-exposed mice. RNA sequencing and transcriptomics analyses revealed that differentially expressed genes (DEGs) were mainly enriched in metabolic pathways. Untargeted metabolomics analyses indicated that energy metabolism was disrupted in As-exposed mouse testes. Gene set enrichment analysis showed that glycolysis and oxidative phosphorylation were disturbed in As-exposed mouse testes. As-induced disruption of testicular glucose metabolism and oxidative phosphorylation was further validated by RT-PCR and Western blotting. In conclusion, As exposure causes decline in sperm motility accompanied by energy metabolism disorders in mouse testes.
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Arsênio , Metabolismo Energético , Camundongos Endogâmicos C57BL , Motilidade dos Espermatozoides , Testículo , Animais , Masculino , Camundongos , Motilidade dos Espermatozoides/efeitos dos fármacos , Arsênio/toxicidade , Testículo/efeitos dos fármacos , Testículo/metabolismo , Metabolismo Energético/efeitos dos fármacos , Espermatozoides/efeitos dos fármacosRESUMO
This research addressed the drawbacks of the conventional hybrid structure and processing technique by presenting a novel distributed fiber optic sensor based on a hybrid Michelson and Mach-Zehnder interferometer. The sensor can achieve blind spot free positioning and has a wide response frequency, additionally its structure is not complex. It can obtain two phase signals from each of the two interferometers by using a demodulation method that uses a 3 × 3 optical coupler. To determine the position of the disturbance, we computed cross-correlations on the two signals following basic mathematical techniques. Markov Transition Field was used to transform the phase signals-which had been filtered by a band pass filter-into two-dimensional images. Tagged photos built a dataset, which is then fed into a neural network to identify patterns. Experiments have shown that the frequency response capacity of the structure was verified, and it was able to achieve location within 0-30â km with location errors of ±85 m. In a six-category pattern recognition, the testing set accuracy was 98.74%.
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Accumulating evidence reveals the metabolism and neurotransmitter systems are different in major depressive disorder (MDD) between adolescent and adult patients; however, much is still unknown from the gut microbiome perspective. To minimize confounding factors such as geographical location, ethnicity, diet, and drugs, we investigated the gut microbial differences between adolescent and adult male Sprague-Dawley rats. We exposed the adolescent rats to chronic unpredictable mild stress (CUMS) for 3 weeks and assessed their behavior using the sucrose preference test (SPT), open field test (OFT), and forced swimming test (FST). We collected and sequenced fecal samples after the behavioral tests and compared them with our previous data on adult rats. Both adolescent and adult CUMS rats exhibited reduced sucrose preference in SPT, reduced total distance in OFT, and increased immobility time in FST. Moreover, compared to their respective controls, the adolescent CUMS rats had distinct amplicon sequence variants (ASVs) mainly in the Muribaculaceae family, Bacteroidetes phylum, while the adult CUMS rats had those in the Lachnospiraceae family, Firmicutes phylum. In the adolescent group, the Muribaculaceae negatively correlated with FST and positively correlated with SPT and OFT. In the adult group, the different genera in the Lachnospiraceae showed opposite correlations with FST. Furthermore, the adolescent CUMS rats showed disrupted microbial functions, such as "Xenobiotics biodegradation and metabolism" and "Immune system", while the adult CUMS rats did not. These results confirmed the gut microbiota differences between adolescent and adult rats after CUMS modeling and provided new insight into the age-related influence on depression models.