RESUMO
BACKGROUND: The annual incidence of metabolic-associated fatty liver disease (MAFLD) in China has been increasing and is often overlooked owing to its insidious characteristics. Approximately 50% of the patients have a normal weight or are not obese. They are said to have lean-type MAFLD, and few studies of such patients are available. Because MAFLD is associated with abnormal lipid metabolism, lipid-targeted metabolomics was used in this study to provide experimental evidence for early diagnosis and pathogenesis. AIM: To investigate the serum fatty-acid metabolic characteristics in lean-type MAFLD patients using targeted serum metabolomic technology. METHODS: Between January and June 2022, serum samples were collected from MAFLD patients and healthy individuals who were treated at Shanghai Putuo District Central Hospital for serum metabolomics analysis. Principal component analysis and orthogonal partial least squares-discriminant analysis models were developed, and univariate analysis was used to screen for biomarkers of lean-type MAFLD and analyze metabolic pathways. UPLC-Q-Orbitrap/MS content determination was used to determine serum palmitic acid (PA), oleic acid (OA), linoleic acid (LA), and arachidonic acid (AA) levels in lean-type MAFLD patients. RESULTS: Urea nitrogen and uric acid levels were higher in lean-type MAFLD patients than in healthy individuals (P < 0.05). Alanine transaminase and cholinesterase levels were higher in lean-type MAFLD patients than in healthy individuals (P < 0.01). The expression of high-density lipoprotein and apolipoprotein A-1 were lower in lean-type MAFLD patients than in healthy individuals (P < 0.05) and the expression of triglycerides and fasting blood glucose were increased (P < 0.01). A total of 65 biomarkers that affected the synthesis and metabolism of fatty acids were found with P < 0.05 and variable importance in projection > 1". The levels of PA, OA, LA, and AA were significantly increased compared with healthy individuals. CONCLUSION: The metabolic profiles of lean-type MAFLD patients and healthy participants differed significantly, yielding 65 identified biomarkers. PA, OA, LA, and AA exhibited the most significant changes, offering valuable clinical guidance for prevention and treatment of lean-type MAFLD.
Assuntos
Biomarcadores , Ácidos Graxos , Metabolômica , Hepatopatia Gordurosa não Alcoólica , Humanos , Metabolômica/métodos , Masculino , Feminino , Pessoa de Meia-Idade , Ácidos Graxos/sangue , Ácidos Graxos/metabolismo , Biomarcadores/sangue , Adulto , Hepatopatia Gordurosa não Alcoólica/sangue , Hepatopatia Gordurosa não Alcoólica/diagnóstico , China/epidemiologia , Metabolismo dos Lipídeos , Estudos de Casos e Controles , Magreza/sangue , Magreza/diagnósticoRESUMO
OBJECTIVE: The standardization of warfarin anticoagulant therapy is the key to lifelong treatment for patients after heart valve replacement. The present study explored the possible risk factors for anxiety and depression during the coronavirus disease 2019 (COVID-19) pandemic and analyzed the influence of psychological state on medication safety. METHODS: Eligible patients received a web-based questionnaire survey via the Wenjuanxing platform during outpatient visits. Depression was evaluated by the Self-Rating Depression Scale (SDS). Anxiety was evaluated by the Self-Rating Anxiety Scale (SAS). Medication adherence was evaluated by the Morisky scale. RESULTS: A total of 309 patients (aged 52.2±11.4 years) were included in the present study. The SDS score of all included patients was 36.9±9.4 points, of which 11 (3.6%) patients were diagnosed as having depression. The SAS score of all included patients was 43.1±9.3 points, of which 71 (23%) patients were diagnosed as having anxiety. Seven patients (2.3%) had both anxiety and depression. Logistic regression analysis revealed that only monthly income was an independent influencing factor for depression. Regarding anxiety, patients who underwent repeated operations had a 2.264-fold greater risk, and patients who received combination medication had a 2.140-fold greater risk. More bleeding events and coagulation disorders could be observed in patients with anxiety, depression or both. When anxiety occurred, patients showed worse medication adherence. However, depression had no significant effect on medication adherence. CONCLUSION: During the COVID-19 pandemic, the detection rate of mental illnesses such as anxiety and depression was high, which seriously affected the medication safety of warfarin. Analysis of its influencing factors will provide a reference for further standardized regulation of warfarin anticoagulant therapy after valve replacement.
Assuntos
Anticoagulantes , Ansiedade , COVID-19 , Depressão , Implante de Prótese de Valva Cardíaca , Adesão à Medicação , Varfarina , Humanos , COVID-19/psicologia , COVID-19/epidemiologia , Varfarina/uso terapêutico , Varfarina/efeitos adversos , Varfarina/administração & dosagem , Pessoa de Meia-Idade , Masculino , Feminino , Estudos Transversais , Anticoagulantes/uso terapêutico , Depressão/epidemiologia , Depressão/tratamento farmacológico , Implante de Prótese de Valva Cardíaca/efeitos adversos , Adulto , Adesão à Medicação/psicologia , Idoso , SARS-CoV-2 , Fatores de Risco , Inquéritos e Questionários , PandemiasRESUMO
BACKGROUND: Synovial inflammation plays a crucial role in osteoarthritis (OA). Gastrodin (GAS), an active ingredient derived from the Gastrodia elata Blume rhizome, possesses antioxidant and anti-inflammatory pharmacological effects. This research aimed to evaluate the function and molecular mechanism of GAS on human fibroblast-like synoviocytes of osteoarthritis (HFLS-OA) induced by interleukin (IL)-1ß. METHODS: The impact of GAS on the viability of IL-1ß-treated HFLS-OA cells was assessed using the cell counting kit-8 (CCK-8). Quantitative real-time reverse transcription PCR (qRT-PCR) was employed to detect changes in IL-8, IL-6, monocyte chemotactic protein-1 (MCP-1), tumor necrosis factor (TNF)-α, and Gremlin-1 mRNA expression in each group. Corresponding kits were utilized to measure the catalase (CAT) and superoxide dismutase (SOD) activities, as well as the nitric oxide (NO) level. Western blot analysis was conducted to examine the expression of extracellular matrix degradation-associated proteins and nuclear factor kappa-B (NF-κB) pathway-correlated proteins in each group. RESULTS: GAS significantly promoted the proliferation of IL-1ß-induced HFLS-OA cells and concurrently down-regulated Gremlin-1 mRNA expression (p < 0.05). Through the down-regulation of Gremlin-1 expression, GAS exhibited the following effects: decreased IL-8, IL-6, and TNF-α mRNA expression, as well as NO levels (p < 0.05); increased SOD and CAT activities (p < 0.05); down-regulated matrix metallopeptidase 13 (MMP-13) and MMP-1 protein expression levels (p < 0.01); and up-regulated collagen II protein expression level (p < 0.01) in IL-1ß-treated HFLS-OA cells. Additionally, GAS decreased phospho-inhibitory kappa B (p-IκB)/IκB, phospho-inhibitory kappa B kinase (p-IKK)/IKK, and p-p65/p65 ratios in IL-1ß-induced HFLS-OA cells by inhibiting Gremlin-1 expression (p < 0.01). CONCLUSION: GAS demonstrates a positive impact on inflammation, oxidative stress, and extracellular matrix degradation in IL-1ß-mediated HFLS-OA cells. This effect is achieved by suppressing Gremlin-1 expression and reducing NF-κB pathway activity.
Assuntos
Álcoois Benzílicos , Matriz Extracelular , Glucosídeos , Inflamação , Interleucina-1beta , NF-kappa B , Estresse Oxidativo , Sinoviócitos , Humanos , Glucosídeos/farmacologia , Interleucina-1beta/metabolismo , Álcoois Benzílicos/farmacologia , NF-kappa B/metabolismo , Estresse Oxidativo/efeitos dos fármacos , Inflamação/metabolismo , Inflamação/patologia , Matriz Extracelular/metabolismo , Matriz Extracelular/efeitos dos fármacos , Sinoviócitos/efeitos dos fármacos , Sinoviócitos/metabolismo , Sinoviócitos/patologia , Fibroblastos/metabolismo , Fibroblastos/efeitos dos fármacos , Transdução de Sinais/efeitos dos fármacos , Osteoartrite/patologia , Osteoartrite/metabolismo , Osteoartrite/tratamento farmacológico , Peptídeos e Proteínas de Sinalização IntercelularRESUMO
BACKGROUND: Trimethylamine-N-oxide (TMAO) is linked with obesity, while limited evidence on its relationship with body fat distribution. Herein, we investigated the associations between serum TMAO and longitudinal change of fat distribution in this prospective cohort study. METHODS: Data of 1964 participants (40-75y old) from Guangzhou Nutrition and Health Study (GNHS) during 2008-2014 was analyzed. Serum TMAO concentration was quantified by HPLC-MS/MS at baseline. The body composition was assessed by dual-energy X-ray absorptiometry at each 3-y follow-up. Fat distribution parameters were fat-to-lean mass ratio (FLR) and trunk-to-leg fat ratio (TLR). Fat distribution changes were derived from the coefficient of linear regression between their parameters and follow-up duration. RESULTS: After an average of 6.2-y follow-up, analysis of covariance (ANCOVA) and linear regression displayed women with higher serum TMAO level had greater increments in trunk FLR (mean ± SD: 1.47 ± 4.39, P-trend = 0.006) and TLR (mean ± SD: 0.06 ± 0.24, P-trend = 0.011). Meanwhile, for women in the highest TMAO tertile, linear mixed-effects model (LMEM) analysis demonstrated the annual estimated increments (95% CI) were 0.03 (95% CI: 0.003 - 0.06, P = 0.032) in trunk FLR and 1.28 (95% CI: -0.17 - 2.73, P = 0.083) in TLR, respectively. In men, there were no similar significant observations. Sensitivity analysis yielded consistent results. CONCLUSION: Serum TMAO displayed a more profound correlation with increment of FLR and TLR in middle-aged and older community-dwelling women in current study. More and further studies are still warranted in the future. TRIAL REGISTRATION: NCT03179657.
Assuntos
Distribuição da Gordura Corporal , Metilaminas , Humanos , Metilaminas/sangue , Feminino , Pessoa de Meia-Idade , Masculino , Estudos Prospectivos , Idoso , Distribuição da Gordura Corporal/métodos , Adulto , Absorciometria de Fóton/métodos , Composição Corporal , Estudos de Coortes , ChinaRESUMO
PURPOSE: To measure the micro-foci distance away from gross tumor and to provide reference to create the clinical target volume (CTV) margin for boost radiotherapy in rectal adenocarcinoma. METHODS: Twenty-eight rectal cancer surgical specimens of only total mesorectal excision were collected. The pathological specimens were retrospectively measured, and the nearest distance between the tumor micro-foci and gross tumor was microscopically measured. The "in vivo-in vitro" retraction factor was calculated as the ratio of the deepest thickness laterally and the vertical height superior/inferiorly of the rectal tumor measured in MRI and those measured in immediate pathological specimens. The retraction factor during pathological specimen processing was calculated as the distance ratio before and after dehydration in the lateral, superior, and inferior sides by the "knot marking method." The distances of tumor micro-foci were individually corrected with these two retraction factors. RESULTS: The mean "in vivo-in vitro" tumor retraction factors were 0.913 peripherally and 0.920 superior/inferiorly. The mean tumor specimen processing retraction factors were 0.804 peripherally, 0.815 inferiorly, and 0.789 superiorly. Of 28 patients, 14 cases (50.0%) had 24 lateral micro-foci, 8 cases (28.6%) had 13 inferior micro-foci, and 7 cases (25.0%) had 19 superior micro-foci. The 95th percentiles of the micro-foci distance for 28 patients were 6.44 mm (peripheral), 5.54 mm (inferior), and 5.42 mm (superior) after retraction correction. CONCLUSION: The micro-foci distances of 95% of rectal adenocarcinoma patients examined were within 6.44 mm peripherally, 5.54 mm inferiorly, and 5.42 mm superiorly. These findings provide reference to set the boost radiotherapy CTV margin for rectal cancer.
RESUMO
BACKGROUND: The primary screening technique for precancerous lesions and cervical cancer is human papillomavirus (HPV) testing, and HPV self-sampling has been shown to be consistent with clinician sampling in terms of the accuracy of the results and may improve cervical cancer screening rates. The aim of this study was to understand the level of awareness, experience, acceptability, and preference for vaginal HPV self-sampling among women in Jiangsu, Zhejiang, and Shanghai, China, and to analyze the possible influencing factors to determine the feasibility of implementing self-sampling. METHODS: Overall, 1793 women were included in the data analysis. A self-administered questionnaire was utilized. In addition to descriptive analysis, univariate and multivariate analyses were used to explore the associations between sociodemographic features, history of cervical cancer screening, and the level of awareness, experience, acceptability, and preference for HPV self-samples. RESULTS: The participants' level of awareness of and experience with HPV self-sampling were moderate. A total of 88.8% of participants rated the acceptability as "high", and self-sampling was preferred by 64.2% of them for cervical cancer screening. People aged 45 to 54 years showed a preference for both clinician sampling(OR = 1.762 (1.116-2.163)) and self-sampling (OR = 1.823 (1.233-2.697)). Those who had graduated from high school or above (OR = 2.305 (1.517-3.503), OR = 2.432 (1.570-3.768), OR = 3.258 (2.024-5.244)) preferred clinician-sampling, and those with a bachelor's degree or above (OR = 1.664 (1.042-2.657)) preferred self-sampling. Middle- and high-income individuals showed no preference for either sampling method (OR < 1). CONCLUSIONS: HPV self-sampling is widely accepted, but awareness, experience and preferences need to be improved. These results may help to adjust public health strategies for the early inclusion of HPV self-sampling as a screening method in national initiatives to prevent cervical cancer.
Assuntos
Detecção Precoce de Câncer , Conhecimentos, Atitudes e Prática em Saúde , Infecções por Papillomavirus , Aceitação pelo Paciente de Cuidados de Saúde , Neoplasias do Colo do Útero , Adulto , Idoso , Feminino , Humanos , Pessoa de Meia-Idade , Adulto Jovem , China/epidemiologia , Estudos Transversais , Detecção Precoce de Câncer/métodos , Detecção Precoce de Câncer/psicologia , Papillomavirus Humano , Infecções por Papillomavirus/diagnóstico , Aceitação pelo Paciente de Cuidados de Saúde/estatística & dados numéricos , Aceitação pelo Paciente de Cuidados de Saúde/psicologia , Preferência do Paciente/estatística & dados numéricos , Autocuidado/métodos , Autocuidado/estatística & dados numéricos , Manejo de Espécimes/métodos , Inquéritos e Questionários , Neoplasias do Colo do Útero/diagnóstico , Neoplasias do Colo do Útero/virologia , Esfregaço Vaginal/métodos , Esfregaço Vaginal/estatística & dados numéricosRESUMO
AIMS: This two-wave, longitudinal study aimed to examine the potential moderating and mediating effects of resilience on the association between perceived school bullying and psychotic-like experiences among Chinese sexual minority adolescents. METHODS: A total of 4192 senior high students were included and 984 (23.5%) of them were identified as a sexual minority (mean age = 16.68 years, SD = 0.71). Participants completed two online surveys during April 21 to May 12, 2021 and December 17 to 26, 2021, respectively, as well as completed self-report measures of sample characteristics, perceived school bullying, resilience, and psychotic-like experiences (including two dimensions: delusional experiences and hallucinatory experiences). RESULTS: Perceived school bullying and resilience were associated with psychotic-like experiences in sexual minority adolescents. Resilience mediated the relationship between perceived school bullying and subsequent psychotic-like experiences (b = 0.03, 95% CI = 0.01 ~ 0.04)/ delusional experiences (b = 0.03, 95% CI = 0.01 ~ 0.04)/ hallucinatory experiences (b = 0.02, 95% CI = 0.01 ~ 0.03). Additionally, resilience only moderated the associations of perceived school bullying with hallucinatory experiences (b = -0.06, 95% CI = -0.12 ~ -0.01). CONCLUSIONS: These findings indicated that resilience plays a crucial role in mediating or moderating the relationship between perceived school bullying and psychotic-like experiences. Assessing and reducing school bullying, as well as promoting resilience, may have important clinical implications for reducing the risk of psychotic-like experiences in sexual minority adolescents.
RESUMO
STUDY QUESTION: Can exposure to palmitic acid (PA), a common saturated fatty acid, modulate autophagy in both human and mouse trophoblast cells through the regulation of acyl-coenzyme A-binding protein (ACBP)? SUMMARY ANSWER: PA exposure before and during pregnancy impairs placental development through mechanisms involving placental autophagy and ACBP expression. WHAT IS KNOWN ALREADY: High-fat diets, including PA, have been implicated in adverse effects on human placental and fetal development. Despite this recognition, the precise molecular mechanisms underlying these effects are not fully understood. STUDY DESIGN, SIZE, DURATION: Extravillous trophoblast (EVT) cell line HTR-8/SVneo and human trophoblast stem cell (hTSC)-derived EVT (hTSCs-EVT) were exposed to PA or vehicle control for 24 h. Female wild-type C57BL/6 mice were divided into PA and control groups (n = 10 per group) and subjected to a 12-week dietary intervention. Afterward, they were mated with male wild-type C57BL/6 mice and euthanized on Day 14 of gestation. Female ACBPflox/flox mice were also randomly assigned to control and PA-exposed groups (each with 10 mice), undergoing the same dietary intervention and mating with ACBPflox/floxELF5-Cre male mice, followed by euthanasia on Day 14 of gestation. The study assessed the effects of PA on mouse embryonic development and placental autophagy. Additionally, the role of ACBP in the pathogenesis of PA-induced placental toxicity was investigated. PARTICIPANTS/MATERIALS, SETTING, METHODS: The findings were validated using real-time PCR, Western blot, immunofluorescence, transmission electron microscopy, and shRNA knockdown approaches. MAIN RESULTS AND THE ROLE OF CHANCE: Exposure to PA-upregulated ACBP expression in both human HTR-8/SVneo cells and hTSCs-EVT, as well as in mouse placenta. PA exposure also induced autophagic dysfunction in HTR-8/SVneo cells, hTSCs-EVT, and mouse placenta. Through studies on ACBP placental conditional knockout mice and ACBP knockdown human trophoblast cells, it was revealed that reduced ACBP expression led to trophoblast malfunction and affected the expression of autophagy-related proteins LC3B-II and P62, thereby impacting embryonic development. Conversely, ACBP knockdown partially mitigated PA-induced impairment of placental trophoblast autophagy, observed both in vitro in human trophoblast cells and in vivo in mice. LARGE SCALE DATA: N/A. LIMITATIONS, REASONS FOR CAUTION: Primary EVT cells from early pregnancy are fragile, limiting research use. Maintaining their viability is tough, affecting data reliability. The study lacks depth to explore PA diet cessation effects after 12 weeks. Without follow-up, understanding postdiet impacts on pregnancy stages is incomplete. Placental abnormalities linked to elevated PA diet in embryos lack confirmation due to absence of control groups. Clarifying if issues stem solely from PA exposure is difficult without proper controls. WIDER IMPLICATIONS OF THE FINDINGS: Consuming a high-fat diet before and during pregnancy may result in complications or challenges in successfully carrying the pregnancy to term. It suggests that such dietary habits can have detrimental effects on the health of both the mother and the developing fetus. STUDY FUNDING/COMPETING INTEREST(S): This work was supported in part by the National Natural Science Foundation of China (82171664, 82301909) and the Natural Science Foundation of Chongqing Municipality of China (CSTB2022NS·CQ-LZX0062, cstc2019jcyj-msxmX0749, and cstc2021jcyj-msxmX0236). The authors declare that they have no conflict of interest. TRIAL REGISTRATION NUMBER: N/A.
RESUMO
AIM: To investigate the metabolism and disposition characteristics of HSK7653 in healthy male Chinese participants. METHODS: A single oral dose of 80 µCi (25 mg) [14C]HSK7653 capsules was administered to six healthy participants, and blood, plasma, urine and faeces were collected. Quantitative and qualitative analysis was conducted to investigate the pharmacokinetics, blood-to-plasma ratio, mass balance and metabolism of HSK7653. RESULTS: The drug was well absorbed and reached a maximum concentration at 1.25 h. The drug-related components (HSK7653 and its metabolites) were eliminated slowly, with a half-life (t1/2) of 111 h. Unchanged HSK7653 contributed to more than 97% of the total radioactivity in all plasma samples. The blood-to-plasma ratio (0.573-0.845) indicated that HSK7653 did not tend to distribute into blood cells. At 504 h postdose, up to 95.9% of the dose was excreted, including 79.8% in urine and 16.1% in faeces. Most of the radioactivity (75.5% dose) in excreta was unchanged HSK7653. In addition, nine metabolites were detected in urine and faeces. The most abundant metabolite was M6-2, a dioxidation product of HSK7653, which accounted for 4.73% and 2.63% of the dose in urine and faeces, respectively. The main metabolic pathways of HSK7653 in vivo included oxidation, pyrrole ring opening and sulphonamide hydrolysation. CONCLUSION: HSK7653 was well absorbed, slightly metabolized and slowly excreted in humans. The high plasma exposure and long t1/2 of HSK7653 may contribute to its long-lasting efficacy as a long-acting dipeptidyl peptidase-4 inhibitor.
Assuntos
Diabetes Mellitus Tipo 2 , Inibidores da Dipeptidil Peptidase IV , Humanos , Masculino , Inibidores da Dipeptidil Peptidase IV/farmacocinética , Diabetes Mellitus Tipo 2/tratamento farmacológico , Diabetes Mellitus Tipo 2/metabolismo , Adulto , Biotransformação , Meia-Vida , Fezes/química , Adulto Jovem , Voluntários Saudáveis , Hipoglicemiantes/farmacocinética , Hipoglicemiantes/uso terapêutico , Administração OralRESUMO
Human milk represents the gold standard for infant nutrition, with approximately 50% of the energy in human milk derived from lipids. Odd-chain fatty acids (OCFAs) have been recognized as a category of bioactive milk fatty acids in recent research; however, limited data exist on OCFAs in human milk. This study collected human milk samples spanning the postpartum period from 0 to 400 days. Phospholipids containing OCFAs (PL-OCFAs) were determined in 486 human milk samples using hydrophilic liquid chromatography-electrospray ionization-triquadrupole-mass spectrometry. Triacylglycerols containing OCFAs (TAG-OCFAs) were analyzed in 296 human milk samples using ultra-performance liquid chromatography coupled with quadrupole time-of-flight mass spectrometry. The average total concentration of PL-OCFA ranged from 30.89 ± 14.27 mg L-1 to 93.48 ± 36.55 mg L-1 during lactation, and the average total TAG-OCFA content ranged from 103.1 ± 147.15 mg L-1 to 965.41 ± 651.67 mg L-1. Despite the lower absolute concentration of PL-OCFA, its relative concentration (8.75%-11.75%) was significantly higher than that of TAG-OCFA (0.37%-1.85%) throughout lactation. PC-OCFA, SM-OCFA and PE-OCFA are major sub-classes of PL-OCFA. Furthermore, C17:0 was the major chain length in both PL-OCFA and TAG-OCFA, followed by C15:0. C17:1 was characteristic of TAG-OCFA, while long-chain fatty acids C19:0, C21:0 and C23:0 were characteristic of PL-OCFA. Our findings highlighted the importance of bioactive lipids in human milk, suggesting that OCFAs could be targeted in future studies in relation to the health and development of infants.
Assuntos
Ácidos Graxos , Lactação , Leite Humano , Fosfolipídeos , Triglicerídeos , Humanos , Leite Humano/química , Feminino , Fosfolipídeos/análise , Fosfolipídeos/química , Triglicerídeos/química , Ácidos Graxos/análise , Ácidos Graxos/química , China , Adulto , População do Leste AsiáticoRESUMO
Background: Tolerogenic dendritic cells (DCs) are associated with poor prognosis of sepsis. Matrix metalloproteinases (MMPs) have been shown to have immunomodulatory effects. However, whether MMPs are involved in the functional reprogramming of DCs is unknown. The study aims to investigate the role of MMPs in sepsis-induced DCs tolerance and the potential mechanisms. Methods: A murine model of late sepsis was induced by cecal ligation and puncture (CLP). The expression levels of members of the MMP family were detected in sepsis-induced tolerogenic DCs by using microarray assessment. The potential roles and mechanisms underlying MMP8 in the differentiation, maturation and functional reprogramming of DCs during late sepsis were assessed both in vitro and in vivo. Results: DCs from late septic mice expressed higher levels of MMP8, MMP9, MMP14, MMP19, MMP25 and MMP27, and MMP8 levels were the highest. MMP8 deficiency significantly alleviated sepsis-induced immune tolerance of DCs both in vivo and in vitro. Adoptive transfer of MMP8 knockdown post-septic bone marrow-derived DCs protected mice against sepsis-associated lethality and organ dysfunction, inhibited regulatory T-cell expansion and enhanced Th1 response. Furthermore, the effect of MMP8 on DC tolerance was found to be associated with the nuclear factor kappa-B p65/ß-catenin pathway. Conclusions: Increased MMP8 levels in septic DCs might serve as a negative feedback loop, thereby suppressing the proinflammatory response and inducing DC tolerance.
RESUMO
Parkinson's disease (PD) is a common, chronic, and progressive degenerative disease of the central nervous system for which there is no effective treatment. Gastrodia elata is a well-known food and medicine homologous resource with neuroprotective potential. Gastrodia elata polysaccharide (GEP), which is a highly active and safe component in Gastrodia elata, is an important ingredient in the development of functional products. In this study, GEP was administered to 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP)-induced mice over 3 weeks to investigate its neuroprotective effects. The results showed that GEP significantly alleviated the motor dysfunction of PD mice, inhibited the accumulation of α-synuclein, and reduced the loss of dopaminergic neurons in the brain. Moreover, GEP increased the Bcl-2/Bax ratio and decreased the cleaved-caspase-3 level, suggesting that GEP may ameliorate PD by preventing MPTP-induced mitochondrial apoptosis. GEP also significantly inhibited the increase of GFAP and decreased the levels of TNF-α, IL-1ß, and IL-6 in the brain of PD mice, which may be the result of the inhibition of neuroinflammation by the inactivation of the TLR4/NF-κB pathway. Furthermore, the neuroprotective effects of GEP involve the gut-brain axis, as it has been shown that GEP regulated the dysbiosis of PD-related gut microbiota such as Akkermansia, Lactobacillus, Bacteroides, Prevotella, and Faecalibacterium, increased the content of microbial metabolites SCFAs in the colon and increased the level of occludin that repairs the intestinal barrier of PD mice. In conclusion, this study is expected to provide a theoretical basis for the development and application of functional products with GEP from the perspective of neuroprotective effects.
Assuntos
Gastrodia , Microbioma Gastrointestinal , Fármacos Neuroprotetores , Doença de Parkinson , Camundongos , Animais , Doença de Parkinson/metabolismo , Fármacos Neuroprotetores/farmacologia , Transdução de Sinais , Polissacarídeos/farmacologiaRESUMO
BACKGROUND: Gangliosides are crucial for early-life cognition and immunity development. However, limited data exist on gangliosides within the Chinese population, and maternal-to-fetal/infant ganglioside transport remains unclear. OBJECTIVES: This study aimed to investigate gangliosides concentrations and trajectories in Chinese human milk during the first 400 d of lactation, and seek to understand gangliosides transmission between mother and offspring. METHODS: This study involved 921 cross-sectional participants providing human milk samples across 0-400 d of lactation and 136 longitudinal participants offering maternal plasma, cord plasma, and human milk samples within the first 45 d postpartum. Ultrahigh-performance liquid chromatography-tandem mass spectrometry was used for the quantification of gangliosides. RESULTS: Human milk GM3 (Neu5Acα2-3Galß1-4GlcßCer) concentration increased from 2.29 ± 1.87 to 13.93 ± 4.82 µg/mL, whereas GD3 (Neu5Acα2-8Neu5Acα2-3Galß1-4GlcßCer) decreased from 17.94 ± 6.41 to 0.30 ± 0.50 µg/mL during the first 400 d postpartum (all P < 0.05). Consistent results were observed in cross-sectional and longitudinal participants. GD3 concentration gradually increased from maternal plasma (1.58 µg/mL) through cord plasma (2.05 µg/mL) to colostrum (21.35 µg/mL). Significant positive correlations were observed between maternal and cord plasma for both GM3 (r = 0.30, P < 0.001) and GD3 (r = 0.35, P < 0.001), and maternal plasma GD3 also correlated positively with colostrum concentrations (r = 0.21, P = 0.015). Additionally, in maternal and cord plasma, gangliosides were mainly linked with 16- and 18-carbon fatty acids. However, human milk GM3 showed a broad spectrum of fatty acid chain lengths, whereas GD3 was primarily tied to very long-chain fatty acids (≥20 carbon). CONCLUSIONS: We identified an increase in GM3 and a decrease in GD3 concentration in human milk, with GD3 notably more concentrated in cord plasma and colostrum. Importantly, ganglioside concentrations in maternal plasma positively correlated with those in cord plasma and colostrum. Our findings contribute to the existing Chinese data on gangliosides and enhance understanding of their transmission patterns from mother to offspring. This trial was registered at chictr.org.cn as ChiCTR1800015387.
Assuntos
Gangliosídeos , Leite Humano , Gravidez , Feminino , Humanos , Leite Humano/química , Gangliosídeos/análise , Estudos de Coortes , Estudos Transversais , Ácidos Graxos , Carbono , ChinaRESUMO
Intimate partner violence (IPV) against pregnant women negatively impacts women's and infants' health. Yet inconsistent results have been found regarding whether pregnancy increases or decreases the risk of IPV. To answer this question, we systematically searched for studies that provided data on IPV against women before pregnancy, during pregnancy, and after childbirth. Nineteen studies met our selection criteria. We meta-analyzed the nineteen studies for the pooled prevalence of IPV across the three periods and examined study characteristics that moderate the prevalence. Results showed the pooled prevalence estimates of IPV were 21.2% before pregnancy, 12.8% during pregnancy and 14.7% after childbirth. Although these findings suggest a reduction in IPV during pregnancy, our closer evaluation of the prevalence of IPV after childbirth revealed that the reduction does not appear to persist. The prevalence of IPV increased from 12.8% within the first year after childbirth to 24.0% beyond the first year. Taken together, we should not assume pregnancy protects women from IPV, as IPV tends to persist across a longer-term period. Future studies are needed to investigate if IPV transits into other less obvious types of violence during pregnancy. Moderator analyses showed the prevalence estimates significantly varied across countries by income levels and regions.
RESUMO
PURPOSE: This study examined the longitudinal trajectories of adolescent survivors' nightmares after the Wenchuan earthquake and tested whether specific trajectory memberships of nightmares could predict depression and post-traumatic stress disorder (PTSD) in the 10 years after earthquake. METHODS: 610 adolescents exposed to the Wenchuan earthquake were surveyed on nightmares at 18 months (T18m), 24 months (T24m), and 30 months (T30m) after the earthquake. Depression and PTSD were assessed at baseline (T18m) and 10 years (T10y) after the catastrophe. Data were analyzed using linear regression analysis. RESULTS: The prevalence rates of frequent nightmares at three time points were 9.8%, 11.5%, and 9.3%, respectively. Five different trajectories of nightmares were identified: resistance (77.0%), recover (8.4%), delayed-dysfunction (7.9%), chronic-dysfunction (1.1%), and relapsing/remitting (5.6%). Additionally, we found that participants in relapsing/remitting, chronic or delayed dysfunction trajectories compared with those in the resistant group were more likely to experience depression and PTSD in young adulthood after adjusting for a wide range of covariates. CONCLUSIONS: Nightmares had heterogeneity after a catastrophic earthquake. Timely assessment and targeted interventions on specific nightmares are necessary for reducing the incidence of psychiatric disorders.
RESUMO
GnRH analogues were widely used for controlld ovary stimulation, but their effects on oocyte quality remain contradictory. This study aimed to explore the influence of GnRH analogues on oocyte quality in mice. A total of 120 mice were randomly assigned to four groups:(i)GnRH-a+PMSG group; (ii) GnRH-ant+PMSG group; (iii) PMSG group; (iv) Control group. Ovaries were collected for quantitative real-time polymerase chain reaction (qRT-PCR) to assess GDF9 and BMP15 mRNA expression, and protein expression were evaluated by western blotting. Moreover, embryo developmental progress in vitro and implantation rate in vivo were recorded. Compared with control group, both GDF9 mRNA and protein expressions were strengthened in PMSG group, but reduced in the presence of GnRH-a or GnRH-ant. The GnRH-a group exhibited decreased BMP15 mRNA expression compared to PMSG group, while the GnRH-ant group did not show the same pattern. BMP15 protein expression were not statisticlly different among the four groups. Notably, there was no statistically difference in the expression of these two factors between GnRH-a and GnRH-ant groups. The percentage of zygotes progressing to the 2-cell stage and percentage of 2-cell advancing to the blastocyst stage were similar in the PMSG group and control group. However, both the GnRH-a and GnRH-ant groups showed decreased embryos development rates compared to other two groups. The embryonic implantation rate in control group (53.3%) was higher than that in the GnRH-a and GnRH-ant groups (33.3% and 30.8%, P<0.05). The difference between the PMSG (45.0%) and GnRHa group was statistically significant (P value of 0.023), but not between the PMSG and GnRH-ant group (P value of 0.486). No statistical difference was confirmed between GnRH-a and GnRH-ant groups. Our findings shed light on the safety of GnRH analogues in ovary stimulation, and highlight the need for further research to establish optimal and effective controlled ovary stimulation protocol.
RESUMO
Continuously hyperglycation-induced lesion and poor blood flow contributed to the wound incurable and susceptible to infection. About fifteen percent of people with diabetes would develop ulcers during their lifetime, especially on the feet, which could lead to severe tissue destruction and eventual amputation. Various strategies were limited to accelerate wound healing in diabetic patients for high cost and unsatisfied effects. Geniposide is well-known for its anti-inflammation and anti-apoptosis in several pathological tissues. This study is to explore the protective effect of geniposide on wound healing rate, inflammatory response, nutritional function and cellular apoptosis in diabetic rats. Diabetic rats was induced by streptozotocin and defined as plasma glucose >300 mg/dl. Western blot and immunostaining technologies were performed to mark and quantify the target proteins. The oral administration of geniposide (200 mg/kg and 500 mg/kg) could significantly promote wound healing by the increment of lesion retraction in diabetic rats compared to model group. In the apoptotic study of skin wound in diabetic rats, the TUNEL-positive cells were greatly decreased in geniposide subgroups (P < 0.05). The levels of TNF-α, IL-1ß and IL-6 were significantly inhibited by geniposide with the IC50 value of 470 mg/kg, 464 mg/kg and 370 mg/kg body weight respectively, which might be related to the enhancement of the phosphorylation of PI3K and Akt proteins. Geniposide enhanced the repairment of skin wound in diabetic rats by inhibiting inflammatory response and apoptosis.
RESUMO
OBJECTIVES: Survivors may suffer mental health problems following disasters, particularly posttraumatic stress disorder (PTSD) and depressive symptoms. However, few studies have explored longitudinal processes of co-occurring PTSD and depressive symptoms among adolescent survivors and their associated predictors and consequences. The present study examines the codevelopment of both symptoms postearthquake using a 10-year cohort. METHOD: A total of 1,357 senior high school students reported PTSD and depressive symptoms at 6, 12, 18, and 24 months after the 2008 Wenchuan earthquake. Self-report measures were also used to evaluate earthquake exposure, negative life events, social support, and trait resilience. At the 10-year follow-up (T10y), 799 participants reported their quality of life (QoL) online and 744 of them provided available data. A parallel-process latent class growth analysis was used to identify trajectories. Multinominal logistic and linear regressions were used, respectively, to analyze the predictors and consequences of these trajectories. RESULTS: Three comorbid trajectories were found: a resilient group (56.7%), a vulnerable group (33.3%), and a chronic high-risk group (9.9%). Gender, injury/missing/killed of family members, witnessing of traumatic sciences, negative life events, social support, and trait resilience were significant predictors of vulnerable and chronic high-risk groups. Finally, adolescents in these two groups were more likely to experience poorer QoL in adulthood. CONCLUSION: The results highlight the heterogeneity of depression-PTSD comorbidities among adolescent survivors. They also emphasize PTSD-depression symptoms predictors and their adverse impacts on life outcomes in adulthood. Individualized interventions should be provided for adolescents affected by natural disasters, especially those in the vulnerable and higher risk groups. (PsycInfo Database Record (c) 2023 APA, all rights reserved).
RESUMO
INTRODUCTION: Previous studies on associations between social support and quality of life (QoL) have usually employed a variable-centered approach, without considering individual variances in time-varying changes in social support. This study explores trajectories of social support and whether depressive symptoms mediate associations between social support trajectories and QoL 10 years after an earthquake. METHODS: Seven hundred and forty-four Chinese adolescents exposed to the Wenchuan earthquake were surveyed on social support at 6-, 18-, and 24-months and depressive symptoms at 30-months postearthquake (T30m ). They provided valid data on QoL after 10 years of the earthquake (T10y ). The latent class growth analysis was used to estimate social support trajectories. Mediation analysis was then conducted to test whether depressive symptoms at T30m mediated associations between social support trajectories and QoL at T10y . RESULTS: Three trajectories of social support were identified: low decreasing (31.6%), moderate decreasing (55.4%), and persistent high (13.0%) groups. Depressive symptoms significantly mediated the effects of social support trajectories (relative to the low support trajectory) on future QoL (95% CIs: 0.70-1.78 and 1.41-3.37 for moderate decreasing and persistent high groups, respectively). CONCLUSIONS: Social support shows individual differences over time. Moderate and high social support trajectories improve 10-year QoL partly by reducing depressive symptoms. Therefore, interventions aimed at enhancing social support and reducing depressive symptoms may be more effective in enhancing QoL in the aftermath of disasters.
Assuntos
Terremotos , Adolescente , Humanos , Estudos de Coortes , Qualidade de Vida , Depressão/epidemiologia , Apoio SocialRESUMO
BACKGROUND: Human breast milk is the primary source of choline and choline-containing compounds for infants at early stages of life. Choline data across lactation in Chinese human milk were limited. OBJECTIVE: This study aimed to quantify the five choline compounds in Chinese human breast milk and explore associated factors. METHODS: A total of 540 lactating mothers from the MUAI (Maternal Nutrition and Infant Investigation) study were included. The content of water-soluble choline (free choline, phosphocholine, glycerophosphocholine) and lipid-soluble choline (phosphatidylcholine, sphingomyelin) in 892 human milk samples collected from 0 to 400 days postpartum were examined, and associated factors were explored. RESULTS: Choline concentrations in human milk varied from postpartum day 0-400 (92.06 ± 65.22 to 171.01 ± 47.84 mg/L). Water-soluble choline was the major component (88.6%-93.8%) in human milk and ranged from 793.03 (659.22) to 1544.43 (443.32) µmol/L. Its trajectory followed that of total choline, increasing from colostrum to transitional milk and then declining in mature milk. In contrast, lipid-soluble choline accounted for 6.2%-11.4% over lactation and had an opposite trajectory. Choline composition varied by delivery mode and parity history. CONCLUSION: The concentrations of individual choline and choline-containing compounds during lactation in Chinese human breast milk were described for the first time. Our results address gaps in extant Chinese human milk choline data and support tailored dietary reference intakes for Chinese lactating women and infants. Our data describes the level and profile of choline from 0 to 400 days postpartum in Chinese human breast milk. This is the most updated data on choline and also the first report of water-soluble choline as the predominant type in Chinese human milk. Our results compensate for the deficiencies in data on choline in Chinese human milk. CLINICAL TRIAL REGISTRATION: Clinical Trial Registry number: ChiCTR1800015387. Web link to study on registry: https://www.chictr.org.cn/index.aspx.