RESUMO
Vibrio anguillarum is one of the major pathogens responsible for bacterial infections in marine environments, causing significant impacts on the aquaculture industry. The misuse of antibiotics leads to bacteria developing multiple drug resistances, which is detrimental to the development of the fisheries industry. In contrast, live attenuated vaccines are gradually gaining acceptance and widespread recognition. In this study, we constructed a double-knockout attenuated strain, V. anguillarum ΔspeA-aroC, to assess its potential for preparing a live attenuated vaccine. The research results indicate a significant downregulation of virulence-related genes, including Type VI secretion system, Type II secretion system, biofilm synthesis, iron uptake system, and other related genes, in the mutant strain. Furthermore, the strain lacking the genes exhibited a 67.47% reduction in biofilm formation ability and increased sensitivity to antibiotics. The mutant strain exhibited significantly reduced capability in evading host immune system defenses and causing in vivo infections in spotted sea bass (Lateolabrax maculatus), with an LD50 that was 13.93 times higher than that of the wild-type V. anguillarum. Additionally, RT-qPCR analysis of immune-related gene expression in spotted sea bass head kidney and spleen showed a weakened immune response triggered by the knockout strain. Compared to the wild-type V. anguillarum, the mutant strain caused reduced levels of tissue damage. The results demonstrate that the deletion of speA and aroC significantly reduces the biosynthesis of biofilms in V. anguillarum, leading to a decrease in its pathogenicity. This suggests a crucial role of biofilms in the survival and invasive capabilities of V. anguillarum.
Assuntos
Bass , Doenças dos Peixes , Vibrioses , Vibrio , Animais , Vibrioses/microbiologia , Bass/microbiologia , Virulência/genética , Vibrio/genética , Antibacterianos , Doenças dos Peixes/microbiologiaRESUMO
INTRODUCTION: Peritoneal dialysis-related peritonitis (PDRP) should be treated as soon as possible by an empirical regimen without waiting for effluent bacterial culture results. We retrospectively investigated patients treated with vancomycin plus levofloxacin as a treatment regimen if there was no response to cefazolin plus ceftazidime. MATERIALS AND METHODS: We collected records of adult patients with PDRP from January 1, 2013, to November 30, 2020. The characteristics of episodes of PDRP with no response to cefazolin plus ceftazidime treated by intraperitoneal (IP) injection of vancomycin plus levofloxacin were analyzed. RESULTS: 118 episodes of PDRP were recorded, among which 115 episodes were treated with IP antibiotics. 93 episodes were treated with cefazolin plus ceftazidime. In 38 episodes, treatment was switched to IP injection of vancomycin plus levofloxacin if there was no response to cefazolin plus ceftazidime. 26/38 (68.4%) episodes were cured by vancomycin plus levofloxacin. Fever, diabetes, fasting glucose, a decrease in effluent leukocytes on day 3 and day 5, and Charlson Comorbidity Index (CCI) scores were significantly different between uncured and cured episodes. No variable was associated with treatment failure after multiple logistic regression. Fever, diabetes, a decrease in effluent leukocytes on day 3, and CCI score were associated with treatment failure after univariable logistic regression. CONCLUSION: Vancomycin plus levofloxacin may be effective if patients are not responsive to cefazolin plus ceftazidime.
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Diabetes Mellitus , Diálise Peritoneal Ambulatorial Contínua , Diálise Peritoneal , Peritonite , Adulto , Humanos , Ceftazidima/uso terapêutico , Cefazolina/uso terapêutico , Vancomicina/uso terapêutico , Levofloxacino/uso terapêutico , Estudos Retrospectivos , Diálise Peritoneal Ambulatorial Contínua/efeitos adversos , Quimioterapia Combinada , Antibacterianos/uso terapêutico , Diálise Peritoneal/efeitos adversos , Peritonite/etiologia , Peritonite/microbiologiaRESUMO
OBJECTIVES: A high peritoneal transport status is a risk factor for mortality and causes technical failure in patients on peritoneal dialysis (PD). High peritoneal transport status is associated with malnutrition and inflammation in patients with PD. The prognostic nutritional index (PNI) is a marker determined by the serum albumin level and lymphocyte count in the peripheral blood. The aim of this study is to investigate the association between PNI and high peritoneal transport status in patients with PD. METHODS: We retrospectively investigated patients with PD from January 1, 2013 to May 31, 2020, in 4 PD centers. Patients with PD were divided into 2 groups according to PNI quartiles: the low PNI group (PNI ≤ 36.6) and the high PNI group (PNI > 36.6). The demographics and clinical and laboratory baseline data of the 2 groups were collected and compared. The association between PNI and high peritoneal transport status was analyzed by multivariate logistic regression analysis. RESULTS: A total of 404 patients with PD were enrolled in our study. A total of 77 (19.06%) patients had high peritoneal transport status. After adjusting for age, sex, body mass index, hypertension, diabetes mellitus, residual urine volume, current smoking status, pre-existing cardiovascular disease, hemoglobin, white blood cell count, triglycerides, and intact parathyroid hormone, low PNI levels were significantly associated with high peritoneal transport status (odds ratio 3.42, 95% confidence interval 1.82-5.18, P = .0056). Subgroup analysis showed that there was no interaction among PNI and age, sex, diabetes, body mass index, pre-existing cardiovascular disease, or current smoking. CONCLUSION: As a marker for malnutrition and inflammation, a low level of PNI is an independent risk factor for high peritoneal transport status in patients with PD.
Assuntos
Doenças Cardiovasculares , Desnutrição , Diálise Peritoneal , Humanos , Avaliação Nutricional , Estado Nutricional , Prognóstico , Doenças Cardiovasculares/complicações , Estudos Retrospectivos , Desnutrição/epidemiologia , Desnutrição/complicações , Fatores de Risco , Inflamação/epidemiologia , Inflamação/complicaçõesRESUMO
BACKGROUND: Pozzi protocol (methylprednisolone intravenous infusion in 1st-3rd-5th months and oral steroid for 6 months) has been thought to be the classic therapy for IgA nephropathy (IgAN) patients with proteinuria> 1.0 g/24 h. There is no consensus on the treatments for IgAN with active pathological changes, especially for IgAN patients with crescents proportion < 50%. This study aimed to evaluate the effectiveness and safety of the treatment protocol of methylprednisolone intravenous infusion at the 1st-2nd-3rd months for IgAN patients with crescents. METHODS: In this prospective, randomized, controlled, non-blind study, 68 IgAN patients with crescents proportion < 50% were divided into the 1-2-3 group receiving 0.25 g/d methylprednisolone intravenously for 3 consecutive days in the 1st-2nd-3rd months, and oral prednisone 0.5 mg/kg/d on consecutive days for 6 months and the 1-3-5 group with the same intravenous methylprednisolone treatment in the 1st-3rd-5th months, and the same oral prednisone. The primary outcome measure was remission of proteinuria (complete or partial); while the secondary outcome measures were deterioration of renal function (evidenced by a 50% rise from baseline serum creatinine levels, or a 25% decline from baseline eGFR levels). RESULTS: There was no significant difference in incidence of crescents (median 14.66% vs. 11.45%, p = 0.143) between the 1-2-3 and 1-3-5 groups. From month 1 to month 6, there was a decreasing trend in the levels of urine protein and serum creatinine and an increasing trend in eGFR in both groups. The mean period of remission in the 1-2-3 group seemed shorter. Overall, there were 55 (80.89%) patients meeting remission. The rates of remission in the 1-2-3 group and 1-3-5 group were 85.3 and 76.47%, respectively (P = 0.644). The 1-2-3 group had lower creatinine and higher eGFR than the 1-3-5 group, but the difference was not significant. The complication rate was 11.11 and 15.79% in the two groups, respectively. There was no significant difference in the complications between groups. CONCLUSIONS: Both the 1st-3rd-5th and 1st-2nd-3rd protocols can effectively alleviate proteinuria and protect renal function in IgAN patients with crescents but the 1st-2nd-3rd protocol seemed to have better effectiveness. TRIAL REGISTRATION: ClinicalTrials.gov, Identifier: NCT02160132 , Registered June 10, 2014.
Assuntos
Glomerulonefrite por IGA/tratamento farmacológico , Glucocorticoides/uso terapêutico , Metilprednisolona/uso terapêutico , Prednisona/uso terapêutico , Adulto , Feminino , Glomerulonefrite por IGA/patologia , Glucocorticoides/efeitos adversos , Humanos , Infusões Intravenosas , Masculino , Metilprednisolona/efeitos adversos , Prednisona/efeitos adversos , Estudos Prospectivos , Resultado do Tratamento , Adulto JovemRESUMO
Paralichthys olivaceus is the kind of cold-water benthic marine fish. In the early stages of development, the symmetrical juveniles transform into an asymmetrical body shape through metamorphosis for adapting benthic life. After that, one side of the fish body is attached to the ground, and the eyes turn to the opposite side which is called ocular side. The body color also appears asymmetry. The skin on the ocular side is dark brown, and the skin on the blind side is white without pigmentation. Pseudo-albinism and hypermelanosis have been considered distinct body color disorders in flatfish. Pseudo-albinism and hypermelanosis in Paralichthys olivaceus are due to abnormal or uneven pigment distribution, due to the interaction of hereditary and environmental factors, rather than a single-nucleotide mutation of a specific gene. Here, we report three single-nucleotide polymorphisms (SNPs) responsible for both pseudo-albinism and hypermelanosis, which are located on two body color-related genes involved in melanogenesis-related pathways. c.2440C>A (P. V605I) and c.2271-96T>C are located on the Inositol 1,4,5-trisphosphate receptor type 2-like (ITPR2) (Gene ID: 109624047), they are located in exon 16 and the non-coding region, respectively, and c.2406C>A (P.H798N) is located in exon 13 of the adenylate cyclase type 6-like (AC6) gene(Gene ID: 109630770). ITPR2 and AC6 expression, which both participate in the thyroid hormone synthesis pathway associated with pseudo-albinism and hypermelanosis in P. olivaceus, were also investigated using qRT-PCR. In hypermelanotic fish, there were relatively higher levels of expression in ITPR2 and AC6 mRNA of hyper-pigmented skin of blind side than that of non-pigmented skin on the blind side and pigmented skin on the ocular side, while in pseudo-albino fish, expression level of ITPR2 and AC6 mRNA in pigmented skin of ocular side was significantly higher than that in non-pigmented skin both ocular and blind side. The results indicated that the expression of the two genes in abnormal parts of body color is positively correlated with pigmentation, suggesting that the influence of abnormal expression of two genes on the pigmentation in abnormal parts of body color deserves further study.
Assuntos
Proteínas de Peixes/metabolismo , Linguado/genética , Linguado/fisiologia , Receptores de Inositol 1,4,5-Trifosfato/metabolismo , Polimorfismo de Nucleotídeo Único , Pigmentação da Pele/genética , Adenilil Ciclases/genética , Adenilil Ciclases/metabolismo , Animais , Proteínas de Peixes/genética , Genótipo , Receptores de Inositol 1,4,5-Trifosfato/genéticaRESUMO
Although metabolomics are desirable to understand the pathophysiology of gestational diabetes mellitus (GDM), comprehensive metabolomic studies of GDM are rare. We aimed to offer a holistic view of metabolites alteration in GDM patients and investigate the possible multimarker models for GDM diagnosis. Biochemical parameters and perinatal data of 131 GDM cases and 138 controls were collected. Fasting serum samples at 75 g oral glucose tolerance test were used for metabolites by ultra performance liquid chromatography-quadrupole-time of flight-mass spectrometry, ultra performance liquid chromatography-triple triple-quadrupole-mass spectrometry and gas chromatography- time-of- flight mass spectrometry platforms. Significant changes were observed in free fatty acids, bile acids, branched chain amino acids, organic acids, lipids and organooxygen compounds between two groups. In receiver operating characteristic (ROC) analysis, different combinations of candidate biomarkers and metabolites in multimarker models achieved satisfactory discriminative abilities for GDM, with the values of area under the curve (AUC) ranging from 0.721 to 0.751. Model consisting of body mass index (BMI), retinol binding protein 4 (RBP4), n-acetylaspartic acid and C16:1 (cis-7) manifested the best discrimination [AUC 0.751 (95% CI: 0.693-0.809), p < 0.001], followed by model consisting of BMI, Cystatin C, acetylaspartic acid and 6,7-diketoLCA [AUC 0.749 (95% CI: 0.691-0.808), p < 0.001]. Metabolites alteration reflected disorders of glucose metabolism, lipid metabolism, amino acid metabolism, bile acid metabolism as well as intestinal flora metabolism in GDM state. Multivariate models combining clinical markers and metabolites have the potential to differentiate GDM subjects from healthy controls.
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Diabetes Gestacional/diagnóstico , Diabetes Gestacional/metabolismo , Modelos Biológicos , Adulto , Aminoácidos/metabolismo , Ácidos e Sais Biliares/metabolismo , Biomarcadores/metabolismo , Cromatografia Líquida , Feminino , Cromatografia Gasosa-Espectrometria de Massas , Glucose/metabolismo , Humanos , Metabolismo dos Lipídeos , Metabolômica , GravidezRESUMO
PURPOSE: To determine the safe range of shortening the spinal column at middle thoracic spine and to observe the changes in blood-spinal cord barrier (BSCB), microglia/macrophage activation and inducible nitric oxide synthase (iNOS) activity after shortening-induced spinal cord injury. METHODS: Dogs were allocated to four groups. Group A (control) underwent laminectomy of T7 without shortening the spinal column. Groups B, C and D had 1/3, 1/2, and 2/3 of T7 resected, respectively, followed by spinal shortening. Somatosensory evoked potential (SSEP) and hind-limb function were recorded periodically for 14 days after operation. Spinal cord blood flow (SCBF) and BSCB were detected at the acute phase of shortening. Microglia/macrophage reactions and iNOS activity were observed by immunohistochemistry. RESULTS: Shortening of 1/3 of a vertebral height caused no significant changes in SSEP and hind-limb function after operation, whereas shortening of 1/2 of the height caused SSEP abnormality and paraparesis, and severe neurologic deficit of hind-limb was observed when the shortening reached 2/3 of the height. SCBF increased temporarily and showed a trend of recovery when the shortening was within 1/2 of a vertebral segment height. When it reached 1/2 or 2/3 of the height, SCBF at 6 h post-operation was 86.33% or 74.95% of the baseline, and an increasing BSCB permeability was observed. In the subsequent 7 days, obvious activation of macrophage and increased number of iNOS-positive cells were observed. CONCLUSION: It is safe to shorten the spinal cord within 1/3 of a vertebral height in middle thoracic spine under two-segment laminectomy in canine. The BSCB disruption, macrophage activation, and increased iNOS activity were observed in the acute phase of the injury. These slides can be retrieved under Electronic Supplementary Material.
Assuntos
Traumatismos da Medula Espinal , Coluna Vertebral , Animais , Cães , Potenciais Somatossensoriais Evocados , Laminectomia , Medula Espinal/cirurgia , Traumatismos da Medula Espinal/cirurgia , Coluna Vertebral/cirurgiaRESUMO
Myomaker is a membrane protein that plays a crucial role in the fusion of myoblasts during muscle growth. DNA methylation, a significant factor, regulates gene expression. The aim of this study was to examine the methylation and mRNA expression patterns of the myomaker gene during 8 different postnatal developmental stages in the Japanese flounder (L: 7â¯days post hatch (dph); M1: 21â¯dph; M2: 28â¯dph; M3: 35â¯dph; J1: 90â¯dph; J2: 180â¯dph; A1: 24â¯months; A2: 36â¯months). Muscle tissue samples were taken from Japanese flounder at different postnatal development stages to measure the extent of DNA methylation and gene expression. Methylation level in the promoter and exon 1 of myomaker was measured using bisulfite sequencing, and the relative expression of myomaker during each developmental stage was measured by quantitative PCR. The relative expression levels of myomaker were up-regulated from stages L to M2, M3 to J2, and methylation of myomaker was negatively correlated with mRNA expression. Furthermore, the CpG site located at -26â¯bp in the promoter was the lowest methylated region in all developmental stages. These results offer a basis for understanding the mechanism by which myomaker regulates muscle formation during postnatal development.
Assuntos
Metilação de DNA/genética , Linguado/crescimento & desenvolvimento , Linguado/genética , Regulação da Expressão Gênica no Desenvolvimento , Proteínas Musculares/genética , Sequência de Aminoácidos , Animais , Sequência de Bases , Ilhas de CpG/genética , Éxons/genética , Japão , Proteínas Musculares/química , Proteínas Musculares/metabolismo , Músculos/efeitos dos fármacos , Músculos/metabolismo , Filogenia , Regiões Promotoras Genéticas , RNA Mensageiro/genética , RNA Mensageiro/metabolismoRESUMO
BACKGROUND: Insulin resistance and beta cell dysfunction were reported to be responsible for gestational diabetes mellitus (GDM). However, little is known about the heterogeneity of these factors and its influences on perinatal outcomes. We investigated whether subtypes of insulin resistance and beta cell dysfunction in gestational diabetes mellitus have different impacts on perinatal outcomes. METHODS: In this prospective cohort study, we followed 554 pregnant women and glucose challenge test was performed at 24-28th weeks of their gestation. Women with plasma glucose ≥ 7.8 mmol/L would be included and advised to undergo the diagnostic 75-g, 3-h oral glucose tolerance test. According to indices of measuring insulin resistance or beta cell function were below the 25th percentile of women with normal glucose tolerance (NGT), women with GDM were defined as three subtypes: GDM with the beta cell dysfunction, GDM with the insulin resistance defect or GDM with both traits mentioned above (GDM-mixed). Perinatal outcomes were documented. RESULTS: The levels of prepregnancy and maternal BMI in the GDM-mix group were higher compared to women in the NGT group (23.2 ± 4.0 vs 20.8 ± 3.7 kg/m2, P < 0.001; 24.5 ± 4.3 vs 21.8 ± 3.4 kg/m2, P < 0.001, respectively). Furthermore, women in GDM-mix group more likely to be subjected to LGA (P = 0.008) adverse perinatal outcomes (P = 0.005), although these differences were normalized after adjusting age, prepregnancy and maternal BMI (GDM-mix vs. NGT: P = 0.141 for LGA and P = 0.186 for adverse outcomes). On the other hand, all perinatal outcomes were similar between other two GDM subgroups and NGT group. CONCLUSIONS: Women with GDM display respective characteristics on metabolism disorders and confer discriminating risks of adverse perinatal outcomes because of this heterogeneity.
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Diabetes Gestacional/patologia , Resistência à Insulina , Células Secretoras de Insulina/patologia , Resultado da Gravidez , Adulto , Glicemia/metabolismo , Diabetes Gestacional/sangue , Feminino , Teste de Tolerância a Glucose , Humanos , Insulina/sangue , Gravidez , Estudos ProspectivosRESUMO
OBJECTIVES: To measure the shear wave velocity (SWV) of the median nerve by Virtual Touch tissue imaging quantification (VTIQ; Siemens AG, Erlangen, Germany) through the beginning of the carpal tunnel and to determine whether VTIQ could be used to diagnose carpal tunnel syndrome. METHODS: This study recruited 49 consecutive patients (72 wrists) with a definitive diagnosis of carpal tunnel syndrome and 23 healthy volunteers (46 wrists). We measured the median nerve diameter and cross-sectional area by 2-dimensional sonography and the SWV by VTIQ. The interobserver variability was analyzed, and diagnostic values were evaluated by drawing a receiver operating characteristic curve. RESULTS: The median nerve SWV was significantly higher in the carpal tunnel syndrome group (3.857 m/s) than the control group (2.542 m/s; P < .05). A 3.0-m/s SWV cutoff value revealed sensitivity, specificity, positive predictive value, negative predictive value, and accuracy of 83.3%, 91.3%, 93.8%, 77.8%, and 86.4%, respectively. The interobserver agreement was excellent for the SWV measurements. CONCLUSIONS: The median nerve SWV at the carpal tunnel inlet is significantly higher in patients with carpal tunnel syndrome, for whom VTIQ appears to be a highly reproducible diagnostic technique.
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Síndrome do Túnel Carpal/diagnóstico por imagem , Síndrome do Túnel Carpal/fisiopatologia , Técnicas de Imagem por Elasticidade/métodos , Nervo Mediano/diagnóstico por imagem , Nervo Mediano/fisiopatologia , Adulto , Idoso , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Reprodutibilidade dos Testes , Sensibilidade e EspecificidadeRESUMO
Animal growth depends on feedback regulation of hormone levels and environmental conditions. Insulin-like growth factor-1 (Igf1) promotes cell growth and differentiation and represses apoptosis and is highly regulated by the environment. Moreover, animals modify physiological homeostasis under stressful conditions through epigenetics and genetic regulatory mechanisms. Therefore, a comprehensive understanding of the effects of salt on fish growth is needed. In this study, half smooth tongue sole (Cynoglossus semilaevis) were subjected to 15 salinity for 0, 7, and 60 days (D) to assess the effects of low salinity on liver cellularity and growth. The results show that low salinity changed liver morphology, suggesting an increase in energy expenditure to recover from the osmotic disruption. igf1 was upregulated in female fish under 15 salinity after 7D and may participate in molecular repair. igf1 was downregulated after 60D of salt stress, resulting in retarded growth. Methylation levels were opposite to those of gene expression, suggesting inhibited regulation. Furthermore, three exons in the igf1 gene had significantly different methylation levels in fish under salt stress. Notably, more putative transcription factor binding sites were located in CpG sites at higher methylation levels. igf1 is not a sex-related gene, as no difference in methylation level was detected between males and females in the control group. These results clarify liver damage and changes in DNA methylation and mRNA expression of igf1, providing insight into the adverse effects of low salt on growth of C. semilaevis and the epigenetics and regulatory mechanisms involved in stressful conditions.
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Linguados/metabolismo , Regulação da Expressão Gênica/efeitos dos fármacos , Fator de Crescimento Insulin-Like I/metabolismo , Fígado/metabolismo , RNA Mensageiro/metabolismo , Salinidade , Animais , Metilação de DNA , Feminino , Fator de Crescimento Insulin-Like I/genética , Masculino , RNA Mensageiro/genéticaRESUMO
High mobility group box 1 (HMGB1) plays an important role in the pathologic processes of endothelial permeability under oxidative stress. Trophoblast oxidative stress has been implicated in the pathophysiology of preeclampsia (PE). HMGB1 serum levels are increased in PE. However, the potential roles of HMGB1 in endothelial permeability in PE remain unclear. We assessed the effects of the hypoxic trophoblast on the permeability of the endothelial monolayer. Our results showed that the hypoxic trophoblast displayed higher HMGB1 mRNA, intracellular HMGB1 protein, and HMGB1 in conditioned medium than those of the normoxic trophoblast did. The hypoxic trophoblast conditioned medium increased the endothelial monolayer permeability and increased TLR 4 and caveolin-1 (CAV-1) protein expression in endothelial cells, which was inhibited by glycyrrhizic acid and HMGB1 small interfering RNA transfection to trophoblasts before hypoxia. The increased endothelial permeability induced by hypoxic trophoblast conditioned medium could be inhibited with TLR4 or CAV-1 gene silencing in endothelial cells. Immunoprecipitation showed that CAV-1 and TLR4 are colocalized in HUVECs and C57BL/6 mouse kidney. TLR4 small interfering RNA suppressed CAV-1 protein expression in endothelial cells upon stimulation of hypoxic trophoblast conditioned medium or HMGB1. We conclude that hypoxic trophoblasts play an important role in the mechanism of general edema (including protein urine) in PE via increasing endothelial monolayer permeability through the HMGB1/TLR4/CAV-1 pathway.
Assuntos
Caveolina 1/metabolismo , Proteína HMGB1/metabolismo , Hipóxia/metabolismo , Receptor 4 Toll-Like/metabolismo , Trofoblastos/metabolismo , Animais , Caveolina 1/antagonistas & inibidores , Caveolina 1/genética , Linhagem Celular , Permeabilidade da Membrana Celular/efeitos dos fármacos , Meios de Cultivo Condicionados/farmacologia , Feminino , Regulação da Expressão Gênica , Ácido Glicirrízico/farmacologia , Proteína HMGB1/genética , Proteína HMGB1/farmacologia , Células Endoteliais da Veia Umbilical Humana/citologia , Células Endoteliais da Veia Umbilical Humana/efeitos dos fármacos , Células Endoteliais da Veia Umbilical Humana/metabolismo , Humanos , Hipóxia/genética , Hipóxia/patologia , Camundongos , Camundongos Endogâmicos C57BL , Camundongos Transgênicos , Gravidez , RNA Interferente Pequeno/genética , RNA Interferente Pequeno/metabolismo , Transdução de Sinais , Receptor 4 Toll-Like/antagonistas & inibidores , Receptor 4 Toll-Like/genética , Trofoblastos/efeitos dos fármacos , Trofoblastos/patologiaRESUMO
Results from the published studies on the association between monocyte chemoattractant protein-1 (MCP-1) promoter -2518 A/G (rs1024611) gene polymorphism and systemic lupus erythematosus (SLE)/lupus nephritis (LN) are still conflicting. This meta-analysis was performed to evaluate the relationship between MCP-1 A/G gene polymorphism and SLE/LN and to explore whether MCP-1 A allele, AA genotype or GG genotype could become a predictive marker for SLE/LN risk. Association studies were identified from the databases of PubMed, Embase, Cochrane Library and CBM-disc (China Biological Medicine Database) as of 1 January 2014, and eligible investigations were synthesized using meta-analysis method. Results were expressed with odds ratios (OR) for dichotomous data, and 95% confidence intervals (CI) were also calculated. Sixteen investigations were identified for the analysis of association between MCP-1 A/G gene polymorphism and SLE, consisting of 2425 patients with SLE and 2567 controls. In the overall populations, Asians, Caucasian population, the association between MCP-1 A/G gene polymorphism and SLE susceptibility was not found. Interestingly, a trend toward an association between A allele/AA genotype and LN risk was observed in overall populations, although there was no statistical difference. However, this meta-analysis indicated that AA genotype was associated with LN risk in Caucasians (OR = 0.71; 95% CI: 0.54-0.93; p = 0.01). In conclusion, our results indicate that AA homozygous might be a significant genetic molecular marker to predict the SLE patients developing into LN in Caucasians. However, more investigations are required to further clarify this association.
Assuntos
Quimiocina CCL2/genética , Estudos de Associação Genética , Lúpus Eritematoso Sistêmico/genética , Nefrite Lúpica/genética , China , Predisposição Genética para Doença , Genótipo , Homozigoto , Humanos , Lúpus Eritematoso Sistêmico/patologia , Nefrite Lúpica/patologia , Polimorfismo de Nucleotídeo Único , População BrancaRESUMO
The gut microbiota constitutes a complex ecosystem that has an important impact on host health. In this study, genetically engineered zebrafish with inducible nitric oxide synthase (iNOS or NOS2) knockout were used as a model to investigate the effects of nos2a/nos2b gene single knockout and nos2 gene double knockout on intestinal microbiome composition and function. Extensive 16S rRNA sequencing revealed substantial changes in microbial diversity and specific taxonomic abundances, yet it did not affect the functional structure of the intestinal tissues. Notably, iNOS-deficient zebrafish demonstrated a decrease in Vibrio species and an increase in Aeromonas species, with more pronounced effects observed in double knockouts. Further transcriptomic analysis of the gut in double iNOS knockout zebrafish indicated significant alterations in immune-related and metabolic pathways, including the complement and PPAR signaling pathways. These findings underscore the crucial interplay between host genetics and gut microbiota, indicating that iNOS plays a key role in modulating the gut microbial ecology, host immune system, and metabolic responses.
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Adipose tissue is a crucial economically significant trait that significantly influences the meat quality and growth performance of domestic animals. To reveal the changes in adipose tissue metabolism during the growth of naturally grazing sheep, we evaluated the thickness, adipocyte morphology, fatty acid profile, and metabolite profile of subcutaneous adipose tissue (SAT) from naturally grazing Sunit sheep at 6, 18, and 30 months of age (referred to as Mth-6, Mth-18, and Mth-30, respectively). The fat thickness and adipocyte number were significantly increased with the growth of the sheep (p < 0.05), and the increase of which from Mth-18 to Mth-30 was less than that from Mth-6 to Mth-18. Additionally, the alpha-linolenic acid metabolism was enhanced and fatty acid (FA) elongation increased with growth. The metabolomic analysis revealed 76 differentially expressed metabolites (DEMs) in the SAT in different growth stages. Interestingly, we observed elongation of FAs in lipids correlated with sheep growth. Furthermore, the expression of acylcarnitines was downregulated, and fatty acid amides, aspartic acid, acetic acid and phosphocholine were upregulated in Mth-18 and Mth-30 compared to Mth-6. Altogether, the study found that the difference in SAT in Mth-6 was great compared to Mth-18 and Mth-30. An increase in fat deposition via adipocyte proliferation with the growth of the sheep in naturally grazing. The DEMs of acylcarnitines, fatty acid amides, aspartic acid, acetic acid, and phosphocholine emerged as potential key regulators of adipose tissue metabolism. These findings illustrate the variation in and metabolic mechanism of sheep adipose tissue development under natural grazing, thus providing valuable insights into improving the edible quality of sheep meat and developing the mutton sheep industry.
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OBJECTIVES: The Sarcopenia Index (SI) has the potential as a biomarker for sarcopenia, which is characterized by muscle loss. There is a clear association between sarcopenia and cognitive impairment. However, the relationship between SI and cognitive impairment is yet to be fully understood. METHODS: We employed data extracted from the U.S. National Health and Nutrition Examination Survey (NHANES) spanning the years 1999 to 2002. Our study encompassed individuals aged 65 to 80 who possessed accessible information regarding both SI and cognitive evaluations with a GFR ≥ 90. Cognitive function was assessed using the digit symbol substitution test (DSST). SI was calculated by serum creatinine (mg/dL)/cystatin C (mg/L)*100. Employing multivariate modeling, we estimated the connection between SI and cognitive performance. Furthermore, to enhance the reliability of our data analysis, we categorized SI using tertiles and subsequently calculated the P-value for trend. RESULTS: After adjustment for potential confounders, we found SI was significantly and positively correlated with cognitive function scores both in older female in the American population [ß = 0.160, 95 % confidence interval (CI) 0.050 to 0.271, P = 0.00461]. Similarly, when the total cognitive function score was treated as a categorical variable according to tertiles, higher SI was related to better total cognitive function scores in females [odds ratio (OR) = 3.968, 95 % CI 1.863 to 6.073, P = 0.00025] following adjustment for confounders. CONCLUSIONS: Higher SI was correlated with a lower prevalence of cognitive impairment among older adult women with normal kidney function.
Assuntos
Sarcopenia , Humanos , Feminino , Estados Unidos/epidemiologia , Idoso , Sarcopenia/diagnóstico , Sarcopenia/epidemiologia , Estudos Transversais , Inquéritos Nutricionais , Reprodutibilidade dos Testes , Cognição/fisiologiaRESUMO
INTRODUCTION: Coagulation system dysfunction is associated with adverse outcomes of peritoneal dialysis (PD) and bacterial infection. We investigated the association between coagulation system and treatment failure of peritoneal dialysis-related peritonitis (PDRP). METHODS: We collected records of patients aged ≥18 years with PDRP. PDRP episodes were divided into: shortened activated partial thromboplastin time (APTT) group and prolonged APTT group, low D-dimer (DD) group and high DD group. The baseline characteristics of the groups were collected and compared. The association between APTT, DD and treatment failure of PDRP was analyzed using logistic regression analysis. RESULTS: Thirty episodes of treatment failure were observed in 110 episodes of PDRP in our study. After adjusting for variables, prolonged APTT (OR = 1.166 [1.049-1.296], p = 0.004) or high level of DD (OR = 1.374 [1.057-1.787], p = 0.017) was associated with treatment failure of PDRP. CONCLUSION: Prolonged baseline APTT or high level of DD increased the risk of treatment failure of PDRP.
Assuntos
Diálise Peritoneal , Peritonite , Humanos , Adolescente , Adulto , Prognóstico , Tempo de Tromboplastina Parcial , Diálise Peritoneal/efeitos adversos , Peritonite/microbiologia , Estudos RetrospectivosRESUMO
Given its high biological and pharmacological activities, curcumin (CUR) offers promising applications in functional foods. However, its low stability and bioavailability have greatly hindered its application in the food industry. The present study prepared cellulose nanofiber (CNF) from bamboo shoot processing byproducts and investigated its potential as a low-cost carrier. Our results showed that CUR was immobilized on CNF surfaces mainly through hydrogen bonding and eventually encapsulated in CNF matrices, forming a CNF-CUR complex with an encapsulation efficiency of 88.34% and a loading capacity of 67.95%. The CUR encapsulated in the complex showed improved stability after thermal and UV light treatments. Moreover, a slow and extended release pattern of CUR in a simulated gastrointestinal tract was observed, which could be appropriately described using the Korsmeyer-Peppas model. These results revealed that CNF is a promising protective carrier for the slow release of CUR, making it a better candidate for functional foods.
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Intramuscular connective tissue (IMCT) collagen is an important factor in meat quality. This study analyzed the characteristics of type I and III collagen in the IMCT of the semitendinosus (SD) and longissimus dorsi (LD) of Wuzhumuqin sheep at different growth stages (6, 9, 12, and 18 months). Utilizing sodium dodecyl sulfate-polyacrylamide gel electrophoresis (SDS-PAGE) and Fourier transform infrared spectroscopy (FTIR), collagen types I and III were successfully isolated and shown to contain an intact triple helix structure. Immunofluorescence revealed that these collagens were located in the endomysium and perimysium. Collagen-related genes were significantly expressed in sheep aged 9 and 12 months. The amino acid content increased with age in type I collagen whereas it decreased in type III collagen. Furthermore, type III collagen contained more hydroxyproline (Hyd) than type I collagen. Differential scanning calorimetry (DSC) revealed that the thermal stability of collagen increased with age, accompanied by a decrease in solubility. Semitendinosus muscle had more collagen cross-linkages than LD muscle due to the high pyridinoline (Pyr) content in the endomysium. Finally, a correlation analysis highlighted the multiple correlations between characteristics in different types of collagen during sheep growth. In summary, the collagen characteristics in the IMCT of sheep were impacted by collagen type, muscle type, and age. Furthermore, the various correlations between these characteristics may play an important role in the development of IMCT.
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Artificial intelligence (AI) has achieved significant progress in the field of drug discovery. AI-based tools have been used in all aspects of drug discovery, including chemical structure recognition. We propose a chemical structure recognition framework, Optical Chemical Molecular Recognition (OCMR), to improve the data extraction capability in practical scenarios compared with the rule-based and end-to-end deep learning models. The proposed OCMR framework enhances the recognition performances via the integration of local information in the topology of molecular graphs. OCMR handles complex tasks like non-canonical drawing and atomic group abbreviation and substantially improves the current state-of-the-art results on multiple public benchmark datasets and one internally curated dataset.