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1.
Proc Natl Acad Sci U S A ; 120(32): e2309967120, 2023 08 08.
Artigo em Inglês | MEDLINE | ID: mdl-37523551

RESUMO

Body fat distribution is a heritable risk factor for cardiovascular and metabolic disease. In humans, rare Inhibin beta E (INHBE, activin E) loss-of-function variants are associated with a lower waist-to-hip ratio and protection from type 2 diabetes. Hepatic fatty acid sensing promotes INHBE expression during fasting and in obese individuals, yet it is unclear how the hepatokine activin E governs body shape and energy metabolism. Here, we uncover activin E as a regulator of adipose energy storage. By suppressing ß-agonist-induced lipolysis, activin E promotes fat accumulation and adipocyte hypertrophy and contributes to adipose dysfunction in mice. Mechanistically, we demonstrate that activin E elicits its effect on adipose tissue through ACVR1C, activating SMAD2/3 signaling and suppressing PPARG target genes. Conversely, loss of activin E or ACVR1C in mice increases fat utilization, lowers adiposity, and drives PPARG-regulated gene signatures indicative of healthy adipose function. Our studies identify activin E-ACVR1C as a metabolic rheostat promoting liver-adipose cross talk to restrain excessive fat breakdown and preserve fat mass during prolonged fasting, a mechanism that is maladaptive in obese individuals.


Assuntos
Diabetes Mellitus Tipo 2 , Lipólise , Humanos , Camundongos , Animais , Ativinas/metabolismo , Adiposidade/genética , Diabetes Mellitus Tipo 2/metabolismo , PPAR gama/metabolismo , Obesidade/metabolismo , Tecido Adiposo/metabolismo , Receptores de Ativinas Tipo I/genética , Receptores de Ativinas Tipo I/metabolismo
2.
Arch Microbiol ; 205(7): 267, 2023 Jun 23.
Artigo em Inglês | MEDLINE | ID: mdl-37351731

RESUMO

Pests like the phytophagous bug Empoasca onukii Matsuda frequently harm tea plants. The harm this insect does to agricultural and environmentally sensitive places is extremely harmful since physical and chemical prevention and control are still the primary methods of handling it. Therefore, it is important to develop pest management strategies. Recent research has demonstrated that pathogenic fungus and the gut microbiota interact to induce host and death, and that the gut microbiota, which has a dramatic effect on the host, can engage in pest control. The advancement of genome editing technologies is also new to the field of pest management. The diversity, function, and research methodologies of insect gut microbiota are summarized in this work, and discusses E. onukii Matsuda control options as well as the importance of insect gut microbiome in pest management. In comparison to traditional pesticides and physical prevention and control, the interaction between pathogenic fungi represented by Beauveria bassiana and intestinal microorganisms, as well as their participation in pest management, causes physiological stress on the host, which meets the new requirements of modern agricultural green development and has a protective effect on habitat fragmentation areas (Karst region). Exploring additional harmful fungus for pest management and fully using the specific traits of insect gut microbiota to achieve "killing insects with bacteria" would be a promising technique from this standpoint.


Assuntos
Camellia sinensis , Hemípteros , Praguicidas , Animais , Insetos , Chá
3.
Cancer Cell Int ; 22(1): 89, 2022 Feb 21.
Artigo em Inglês | MEDLINE | ID: mdl-35189891

RESUMO

OBJECTIVE: To evaluate the efficacy and safety of P-ALG (porcine anti-lymphocyte globulin) and R-ATG (rabbit anti-thymocyte globulin) in the conditioning regime for patients with acquired aplastic anemia who underwent HLA-haploidentical hematopoietic stem cell transplantation (halpo-HSCT). METHODS: A total of 91 patients with acquired aplastic anemia who received haplo-HSCT at our center between January 2014 and December 2020 were retrospectively reviewed. Twenty-eight patients were in the P-ALG group while sixty-three patients were in the R-ATG group. RESULTS: The median time was 11 versus 13 days (P = 0.294) for myeloid engraftment and 12.5 versus 15 days (P = 0.465) for platelet engraftment in the P-ALG and R-ATG groups, respectively. There were no significant difference in 5-year overall survival (74.83% ± 8.24% vs 72.29% ± 6.26%, P = 0.830), GVHD-free, failure-free survival (71.05% ± 8.65% vs 62.71% ± 6.22%, P = 0.662), failure-free survival (74.83% ± 8.24% vs 66.09% ± 5.84%, P = 0.647) and transplantation-related mortality (25.17% ± 8.24% vs 26.29% ± 6.22%, P = 0.708) between the two groups. The incidence of aGVHD (acute graft versus host disease) (65.39% ± 9.33% vs 62.71% ± 6.30%, P = 0.653), II-IV aGVHD (38.46% ± 9.54% vs 35.64% ± 6.24%, P = 0.695), III-IV aGVHD (19.23% ± 7.73% vs 10.53% ± 4.07%, P = 0.291), cGVHD (chronic graft versus host disease) (22.22% ± 12.25% vs 22.31% ± 6.30%, P = 0.915), and moderate to severe cGVHD (5.56% ± 5.40% vs 9.28% ± 4.46%, P = 0.993) were not significantly different. Similar outcomes were observed between the P-ALG and R-ATG groups for severe bacterial infection (17.9% vs 25.4%, P = 0.431), invasive fungal diseases (3.6% vs 9.5%, P = 0.577) and graft rejection (0% vs 9.5%, P = 0.218). However, the incidence of cytomegalovirus infection and Epstein-Barr virus infection was significantly lower in the P-ALG group (46.4% vs 71.4%, P = 0.022; 3.6% vs 25.4%, P = 0.014). CONCLUSION: The efficacy and safety of P-ALG were similar with R-ATG in the setting of haplo-HSCT for patients with acquired aplastic anemia patients. P-ALG could be an alternative for R-ATG.

4.
PLoS Comput Biol ; 17(3): e1008777, 2021 03.
Artigo em Inglês | MEDLINE | ID: mdl-33711014

RESUMO

Cancer occurs via an accumulation of somatic genomic alterations in a process of clonal evolution. There has been intensive study of potential causal mutations driving cancer development and progression. However, much recent evidence suggests that tumor evolution is normally driven by a variety of mechanisms of somatic hypermutability, which act in different combinations or degrees in different cancers. These variations in mutability phenotypes are predictive of progression outcomes independent of the specific mutations they have produced to date. Here we explore the question of how and to what degree these differences in mutational phenotypes act in a cancer to predict its future progression. We develop a computational paradigm using evolutionary tree inference (tumor phylogeny) algorithms to derive features quantifying single-tumor mutational phenotypes, followed by a machine learning framework to identify key features predictive of progression. Analyses of breast invasive carcinoma and lung carcinoma demonstrate that a large fraction of the risk of future clinical outcomes of cancer progression-overall survival and disease-free survival-can be explained solely from mutational phenotype features derived from the phylogenetic analysis. We further show that mutational phenotypes have additional predictive power even after accounting for traditional clinical and driver gene-centric genomic predictors of progression. These results confirm the importance of mutational phenotypes in contributing to cancer progression risk and suggest strategies for enhancing the predictive power of conventional clinical data or driver-centric biomarkers.


Assuntos
Biomarcadores Tumorais , Mutação/genética , Neoplasias , Algoritmos , Biomarcadores Tumorais/genética , Biomarcadores Tumorais/metabolismo , Biologia Computacional , Diagnóstico por Computador , Progressão da Doença , Humanos , Aprendizado de Máquina , Neoplasias/diagnóstico , Neoplasias/epidemiologia , Neoplasias/genética , Neoplasias/patologia , Fenótipo , Filogenia
5.
BMC Neurol ; 22(1): 304, 2022 Aug 19.
Artigo em Inglês | MEDLINE | ID: mdl-35986246

RESUMO

BACKGROUND: Neuropathic pain is a common complication in neuromyelitis optica spectrum disorder (NMOSD), which seriously affects the quality of life of NMOSD patients, with no satisfactory treatment. And risk factors of neuropathic pain are still uncertain. OBJECTIVE: To investigate the risk factors of neuropathic pain in a NMOSD cohort. MATERIALS AND METHODS: Our study was a retrospective case-cohort study, the patients diagnosed with NMOSD in the Department of Neurology from the Second Affiliated Hospital of Guangzhou University of Chinese Medicine from January 2011 to October 2021 were screened. Inclusion criteria were: (1) patients diagnosed as NMOSD according to the International Panel for NMO Diagnosis (IPND) criteria, (2) the aquaporin-4 immunoglobulin G antibodies (AQP4-IgG) test was performed. Patients without AQP4-IgG antibody were excluded. Clinical data, including sex, age of the first onset, symptoms of the first episode including neuropathic pain and attack types, localization of lesions of the first episode on Magnetic Resonance Imaging (MRI), Extended disability status Scale (EDSS) of the first onset, treatment of immunosuppression in the first acute phase, disease modifying therapy (DMT), treatment of neuropathic pain and APQ4-IgG status were collected from the hospital system database. Neuropathic pain was defined according to the International Association for the Study of Pain criteria and was described as "pain arising as a direct consequence of a lesion or disease affecting the somatosensory system". RESULTS: One hundred nineteen patients were screened and finally 86 patients fulfilling the inclusion and exclusion criteria were enrolled in our study. The prevalence of neuropathic pain in patients with NMOSD was 43.0%. Univariate analysis showed that the factors associated with neuropathic pain were the age at the onset, the attack type of optic neuritis, the attack type of myelitis, length of spinal cord involvement, localization of thoracic lesion, optic lesion, upper thoracic lesions, lower thoracic lesions, extended spinal cord lesions (≥ 3 spinal lesions), extended thoracic lesions (≥ 4 thoracic lesions), intravenous immunoglobulin and mycophenolate mofetil. Multivariate regression analysis showed that extended thoracic lesions (OR 20.21 [1.18-346.05], P = 0.038) and age (OR 1.35 (1-1.81) P = 0.050) were independently associated with neuropathic pain among NMOSD patients and that gender (OR 12.11 (0.97-151.64) P = 0.053) might be associated with neuropathic pain among NMOSD patients. CONCLUSION: Extended thoracic lesions (≥ 4 thoracic lesions), age and gender might be independent risk factors of neuropathic pain among patients with NMOSD. However, with a small sample size and predominantly female, caution must be applied and these results need validating in further cohorts.


Assuntos
Neuralgia , Neuromielite Óptica , Aquaporina 4 , Autoanticorpos , Estudos de Coortes , Feminino , Humanos , Imunoglobulina G , Masculino , Neuralgia/epidemiologia , Neuromielite Óptica/complicações , Neuromielite Óptica/diagnóstico , Neuromielite Óptica/epidemiologia , Qualidade de Vida , Estudos Retrospectivos , Fatores de Risco
6.
BMC Infect Dis ; 22(1): 303, 2022 Mar 29.
Artigo em Inglês | MEDLINE | ID: mdl-35351036

RESUMO

BACKGROUND: To analyze the clinical features, risk factors and outcomes of Aeromonas bloodstream infections (BSIs) in patients with hematological diseases to establish an effective optimal therapy against it. METHODS: A retrospective study was performed by reviewing medical records of patients admitted to a tertiary blood disease hospital in China. Patients with hematological diseases who suffered from Aeromonas bacteremia during January 2002 to December 2020 were enrolled in this study. RESULTS: A total of 63 patients who developed Aeromonas bacteremia were enrolled in the study, and 91.9% of patients were neutropenic at the onset of BSIs. The major complications were skin and soft tissue infection (SSTI) (22.2%), followed by gastroenteritis (19.0%) and pneumonia (14.3%). High carbapenem resistance rates (70.8% for imipenem, 71.4% for meropenem) were note among the cases. Furthermore, Aeromonas strains isolated from five individuals developed resistance to quinolone, ß-lactams and tigecycline during the therapy. The 30-day mortality rate was 15.9%, while bacteremia with SSTI showed a much worse prognosis, with 50.0% (7/14) of the patients dying within 30 days of initiating the therapy. In the multivariate analysis, SSTI (OR = 28.72; 95% CI, 1.50-551.30; P = 0.026) and shock (OR = 47.58; 95% CI,1.06-2126.80; P = 0.046) were independent risk factors for mortality. CONCLUSIONS: Aeromonas bacteremia usually occurred in patients with neutropenic status, and patients with SSTIs were more likely to show a worse prognosis. Carbapenems should be avoided in patients with Aeromonas BSIs and SSTIs given high resistance rate.


Assuntos
Aeromonas , Bacteriemia , Doenças Hematológicas , Bacteriemia/tratamento farmacológico , Bacteriemia/epidemiologia , Doenças Hematológicas/complicações , Humanos , Estudos Retrospectivos , Fatores de Risco
7.
J Stroke Cerebrovasc Dis ; 31(6): 106448, 2022 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-35366621

RESUMO

BACKGROUND: Previous studies have shown high triglyceride (TG) is associated with platelet hyperactivation in metabolic syndrome patients. However, limited information is available regarding this relationship on dual anti-platelet therapy (DAPT) in ischemic stroke (IS). In this study, we attempted to evaluate the association between TG and high on-treatment platelet reactivity (HTPR) in IS patients. METHODS: Ischemic stroke patients who received maintenance doses of clopidogrel and aspirin were categorized and analyzed retrospectively in this research. The platelet reactivity was assessed by Thromboelastography (TEG). If ADP-induced platelet inhibition rate (ADPi)<30%, it was defined as HTPR, else, it would be defined as normal on-treatment platelet reactivity (NTPR). Patients were divided into high-TG-level and lower-TG-level based on a TG level of 1.7mmol/L, the cutoff point of hypertriglyceridemia. A logistic regression model was applied to calculate the odds ratio (OR) and 95% confidence interval (CI). RESULTS: A total of 123 patients were included in this study and 24 (19.51%) patients were identified as HTPR. HTPR was observed in 36.2% of the patients in high-TG-level (TG≥1.7mmol/L) group while only 9.2% of the patients in the low-TG-level group (TG<1.7mmol/L) were HTPR (P<0.001 ). According to multivariate analysis, TG≥1.7mmol/L was independently associated with HTPR (OR=14.715, 2.445-88.549,P=0.003). CONCLUSIONS: High TG is an independent predictor of HTPR in IS patients. For IS patients with high TG level undergoing DAPT, platelet reactivity should be monitored to identify HTPR, which may proactively help to optimize the anti-platelet therapy.


Assuntos
AVC Isquêmico , Acidente Vascular Cerebral , Plaquetas/metabolismo , Humanos , AVC Isquêmico/diagnóstico , AVC Isquêmico/tratamento farmacológico , Inibidores da Agregação Plaquetária/efeitos adversos , Testes de Função Plaquetária , Estudos Retrospectivos , Acidente Vascular Cerebral/induzido quimicamente , Acidente Vascular Cerebral/diagnóstico , Acidente Vascular Cerebral/tratamento farmacológico , Resultado do Tratamento , Triglicerídeos
8.
Zhongguo Zhong Yao Za Zhi ; 47(12): 3361-3371, 2022 Jun.
Artigo em Zh | MEDLINE | ID: mdl-35851130

RESUMO

A high performance liquid chromatography(HPLC) method was established to analyze the components in Shengjiang Powder(SJP) such as emodin and curcumin and explore its therapeutic effect on experimental autoimmune encephalomyelitis(EAE) mice. To be specific, HPLC was performed to determine the content of compounds in SJP such as emodin and curcumin. A total of 72 female SPF C57 BL/6 mice were randomized into control group(equivalent volume of ultrapure water, ig), model group(equivalent volume of ultrapure water, ig), low-, medium-, and high-dose SJP groups(SJP, ig), and positive control group(prednisone acetate, ig), 12 each group. EAE was induced in mice except the control group. Administration began from the first day after immunization. The general conditions, symptom score, and body weight of the mice were recorded. On the 21 st day, mouse brain tissues were separrated. Then hematoxylin-eosin(HE) staining and Luxol Fast Blue(LFB) staining were used to detect the pathological changes of brain tissues. Immunohistochemistry(IHC) was employed to determine the myelin basic protein(MBP) level, and Western blot the expression of occludin and claudin-5, as well as the levels of interleukin-6(IL-6) and proteins in the Janus kinase 2(JAK2)/signal transducer and activator of transcription 3(STAT3) pathway and their phosphorylation levels. The mRNA expression of IL-6, JAK2, and STAT3 was detected by real-time quantitative polymerase chain reaction(qPCR). Finally, molecular docking of six main active components in SJP, including emodin and curcumin, with IL-6, JAK2 and STAT3 was performed, and the binding affinity was evaluated. The results showed that the established HPLC method demonstrated high precision, reproducibility, stability, and high recovery of samples. Compared with the model group, SJP reduced the clinical symptom score and alleviate the inflammatory infiltration of brain white matter and demyelination of EAE mice. At the same time, SJP increased the expression of occludin and claudin-5, down-regulated the mRNA expression of IL-6, JAK2, and STAT3, as well as the levels of IL-6/JAK/STAT3 proteins and the phosphorylation levels, with significant difference. Molecular docking suggested that the six active components in SJP had high binding energy with IL-6, JAK2, and STAT3 proteins. The established HPLC method is simple, accurate, and highly sensitive, which can simultaneously determine the content of emodin and curcumin in SJP. SJP may alleviate the clinical symptoms of EAE by inhibiting IL-6/JAK2/STAT3 signaling pathway, protecting the blood-brain barrier, and relieving the inflammatory response and demyelinization of brain tissue.


Assuntos
Curcumina , Emodina , Encefalomielite Autoimune Experimental , Animais , Cromatografia Líquida de Alta Pressão , Claudina-5/metabolismo , Encefalomielite Autoimune Experimental/tratamento farmacológico , Encefalomielite Autoimune Experimental/genética , Feminino , Interleucina-6/genética , Interleucina-6/metabolismo , Janus Quinase 2/genética , Janus Quinase 2/metabolismo , Camundongos , Camundongos Endogâmicos C57BL , Simulação de Acoplamento Molecular , Ocludina/metabolismo , Pós , RNA Mensageiro , Reprodutibilidade dos Testes , Fator de Transcrição STAT3/genética , Fator de Transcrição STAT3/metabolismo , Transdução de Sinais , Água/metabolismo
9.
Anal Chem ; 93(32): 11167-11175, 2021 08 17.
Artigo em Inglês | MEDLINE | ID: mdl-34347445

RESUMO

Dissecting site-specific functions of O-glycosylation requires simultaneous identification and quantification of differentially expressed O-glycopeptides by mass spectrometry. However, different dissociation methods have not been systematically compared in their performance in terms of identification, glycosite localization, and quantification with isobaric labeling. Here, we conducted this comparison on highly enriched unlabeled O-glycopeptides with higher-energy collision dissociation (HCD), electron-transfer/collision-induced dissociation (ETciD), and electron transfer/higher-energy collisional dissociation (EThcD), concluding that ETciD and EThcD with optimal supplemental activation resulted in superior identification of glycopeptides and unambiguous site localizations than HCD in a database search by Sequest HT. We later described a pseudo-EThcD strategy that in silico concatenates the electron transfer dissociation spectrum with the paired HCD spectrum acquired sequentially for the same precursor ions, which combines the identification advantage of ETciD/EThcD with the superior reporter ion quality of HCD. We demonstrated its improvements in identification and quantification of isobaric mass tag-labeled O-glycopeptides and showcased the discovery of the specific glycosites of GalNAc transferase 11 (GALNT11) in HepG2 cells.


Assuntos
Glicopeptídeos , Espectrometria de Massas em Tandem , Transporte de Elétrons , Glicopeptídeos/metabolismo , Glicosilação , Íons
10.
Clin Infect Dis ; 71(Suppl 4): S386-S393, 2020 12 23.
Artigo em Inglês | MEDLINE | ID: mdl-33367574

RESUMO

BACKGROUND: Pseudomonas aeruginosa (PA) bloodstream infection (BSI) is a common complication in patients with acute leukemia (AL), and the prevalence of antibiotic-resistant strains poses a serious problem. However, there is limited information regarding antibiotic resistance, clinical characteristics, and outcomes of PA BSI in AL patients. This study explored characteristics associated with the clinical outcomes of AL patients with PA BSI and analyzed factors associated with BSI caused by multidrug-resistant (MDR) or carbapenem-resistant strains. METHODS: This single-center retrospective study enrolled hospitalized AL patients who developed PA BSI during January 2014-December 2019. The Kaplan-Meier method was used to plot survival curves. Multivariate logistic regression analyses were also performed. RESULTS: Of 293 eligible patients with PA BSI, 55 (18.8%) received inappropriate empirical antibiotic therapy within 48 hours of BSI onset, whereas up to 65.8% MDR-PA BSI patients received inappropriate empirical treatment. The 30-day mortality rate was 8.5% for all patients. However, the 30-day mortality rates were 28.9% and 5.5% in MDR-PA BSI and non-MDR-PA BSI patients, respectively (P < .001). On multivariate analysis, previous use of quinolones (odds ratio [OR], 5.851 [95% confidence interval {CI}, 2.638-12.975]) and piperacillin/tazobactam (OR, 2.837 [95% CI, 1.151-6.994]) were independently associated with MDR-PA BSI; and MDR-PA BSI (OR, 7.196 [95% CI, 2.773-18.668]), perianal infection (OR, 4.079 [95% CI, 1.401-11.879]), pulmonary infection (OR, 3.028 [95% CI, 1.231-7.446]), and age ≥55 years (OR, 2.871 [95% CI, 1.057-7.799]) were independent risk factors for 30-day mortality. CONCLUSIONS: MDR increases mortality risk in PA BSI patients, and previous antibiotic exposure is important in MDR-PA BSI development. Rational antibiotic use based on local antimicrobial susceptibility and clinical characteristics can help reduce antibiotic resistance and mortality.


Assuntos
Bacteriemia , Leucemia , Infecções por Pseudomonas , Adulto , Antibacterianos/farmacologia , Antibacterianos/uso terapêutico , Bacteriemia/tratamento farmacológico , Bacteriemia/epidemiologia , Farmacorresistência Bacteriana Múltipla , Humanos , Pessoa de Meia-Idade , Infecções por Pseudomonas/tratamento farmacológico , Infecções por Pseudomonas/epidemiologia , Pseudomonas aeruginosa , Estudos Retrospectivos , Fatores de Risco
11.
Biol Blood Marrow Transplant ; 25(9): e285-e292, 2019 09.
Artigo em Inglês | MEDLINE | ID: mdl-31054985

RESUMO

The clinical outcomes of autologous hematopoietic stem cell transplantation (ASCT) in acute myelogenous leukemia (AML) have improved over time. Indeed, numerous studies have demonstrated that ASCT is associated with a lower relapse rate and acceptable nonrelapse mortality compared with chemotherapy alone in patients with AML. In addition, ASCT is also associated with comparable overall survival outcomes to those of allogeneic hematopoietic stem cell transplantation in some patients with AML. To date, age, cytogenetic and molecular risk stratification, and minimal residual disease (MRD) status have been shown to be closely related to clinical outcomes following ASCT. ASCT is recommended for patients with favorable-risk and intermediate-risk AML in first complete remission and patients with acute promyelocytic leukemia in second complete remission for whom a matched sibling donor is not available. MRD status pre-ASCT is the most important factor to consider when determining whether a patient is eligible for ASCT and can effectively predict clinical outcomes after ASCT. Advanced age is not an absolute contradiction for ASCT. In this review, we describe the literature and clinical trials evaluating the outcomes of ASCT in patients with AML and discuss the indications for ASCT therapy. Because the greatest concern in ASCT recipients is early relapse, important factors that should be monitored before ASCT and future perspectives in this area are also presented.


Assuntos
Transplante de Células-Tronco Hematopoéticas , Leucemia Promielocítica Aguda/terapia , Autoenxertos , Humanos , Leucemia Promielocítica Aguda/sangue , Neoplasia Residual
12.
Acta Pharmacol Sin ; 37(11): 1442-1448, 2016 Nov.
Artigo em Inglês | MEDLINE | ID: mdl-27641736

RESUMO

AIM: Aspirin resistance has an incidence of 5%-65% in patients with ischemic stroke, who receive the standard dose of aspirin, but the platelet function is inadequately inhibited, thereby leading to thrombotic events. Numerous evidence shows that thromboxane A2 receptor (TXA2 receptor, encoded by TBXA2R), lipoprotein-associated phospholipase A2 (Lp-PLA2, encoded by PLA2G7) and platelet endothelial aggregation receptor-1 (PEAR1, encoded by PEAR1) are crucial in regulating platelet activation, and P-glycoprotein (P-gp, encoded by MDR1) influences the absorption of aspirin in the intestine. In this study we examined the correlation between MDR1, TBXA2R, PLA2G7, PEAR1 genetic polymorphisms and platelet activity in Chinese ischemic stroke patients receiving aspirin therapy. METHODS: A total of 283 ischemic stroke patients receiving 100 mg aspirin for 7 d were genotyped for polymorphisms in MDR1 C3435T, TBXA2R (rs1131882), PLA2G7 (rs1051931, rs7756935), and PEAR1 (rs12566888, rs12041331). The platelet aggregation response was measured using an automatic platelet aggregation analyzer and a commercially available TXB2 ELISA kit. RESULTS: Thirty-three patients (11.66%) were insensitive to aspirin treatment. MDR1 3435TT genotype carriers, whose arachidonic acid (AA) or adenosine diphosphate (ADP)-induced platelet aggregation was lower than that of CC+CT genotype carriers, were less likely to suffer from aspirin resistance (odds ratio=0.421, 95% CI: 0.233-0.759). The TBXA2R rs1131882 CC genotype, which was found more frequently in the aspirin-insensitive group (81.8% vs 62.4%) than in the sensitive group, was identified as a risk factor for aspirin resistance (odds ratio=2.712, 95% CI: 1.080-6.810) with a higher level of AA-induced platelet aggregation. Due to the combined effects of PLA2G7 rs1051931 and rs7756935, carriers of the AA-CC haplotype had a higher level of ADP-induced platelet aggregation, and were at considerably higher risk of aspirin resistance than noncarriers (odds ratio=8.233, 95% CI: 1.590-42.638). CONCLUSION: A considerable portion (11.66%) of Chinese ischemic stroke patients are insensitive to aspirin treatment, which may be correlated with the MDR1 C3435T, TBXA2R (rs1131882), and PLA2G7 (rs1051931-rs7756935) polymorphisms.


Assuntos
1-Alquil-2-acetilglicerofosfocolina Esterase/genética , Aspirina/uso terapêutico , Plaquetas/efeitos dos fármacos , Isquemia Encefálica/tratamento farmacológico , Inibidores da Agregação Plaquetária/uso terapêutico , Receptores de Superfície Celular/genética , Receptores de Tromboxano A2 e Prostaglandina H2/genética , Acidente Vascular Cerebral/tratamento farmacológico , Subfamília B de Transportador de Cassetes de Ligação de ATP/genética , Idoso , Povo Asiático , Isquemia Encefálica/sangue , Isquemia Encefálica/genética , Feminino , Frequência do Gene , Estudos de Associação Genética , Humanos , Desequilíbrio de Ligação , Masculino , Pessoa de Meia-Idade , Polimorfismo de Nucleotídeo Único , Acidente Vascular Cerebral/sangue , Acidente Vascular Cerebral/genética , Tromboxano B2/biossíntese , Tromboxano B2/sangue , Falha de Tratamento
13.
Acta Pharmacol Sin ; 37(7): 882-8, 2016 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-27133299

RESUMO

AIM: There is a high incidence of the antiplatelet drug clopidogrel resistance (CR) in Asian populations. Because clopidogrel is a prodrug, polymorphisms of genes encoding the enzymes involved in its biotransformation may be the primary influential factors. The goal of this study was to investigate the associations of polymorphisms of CYP3A4, NR1I2, CYP2C19 and P2RY12 genes with CR in Chinese patients with ischemic stroke. METHODS: A total of 191 patients with ischemic stroke were enrolled. The patients were treated with clopidogrel for at least 5 days. Platelet function was measured by light transmission aggregometry. The SNPs NR1I2 (rs13059232), CYP3A4(*)1G (rs2242480), CYP2C19(*)2 (rs4244285) and P2RY12 (rs2046934) were genotyped. RESULTS: The CR rate in this population was 36%. The CYP2C19(*)2 variant was a risk factor for CR ((*)2/(*)2+wt/(*)2 vs wt/wt, OR: 2.366, 95% CI: 1.180-4.741, P=0.014), whereas the CYP3A4(*)1G variant had a protective effect on CR ((*)1/(*)1 vs (*)1G/(*)1G+(*)1/(*)1G, OR: 2.360, 95% CI: 1.247-4.468, P=0.008). The NR1I2 (rs13059232) polymorphism was moderately associated with CR (CC vs TT+TC, OR: 0.533, 95% CI: 0.286-0.991, P=0.046). The C allele in P2RY12 (rs2046934) was predicted to be a protective factor for CR (CC+TC vs TT, OR: 0.407, 95% CI: 0.191-0.867, P=0.018). In addition, an association was found between hypertension and CR (P=0.022). CONCLUSION: The individuals with both the CYP2C19(*)2 allele and hypertension are at high risk of CR during anti-thrombosis therapy. The CYP3A4(*)1G allele, P2RY12 (rs2046934) C allele and NR1I2 (rs13059232) CC genotype may be protective factors for CR. The associated SNPs studied may be useful to predict clopidogrel resistance in Chinese patients with ischemic stroke.


Assuntos
Citocromo P-450 CYP2C19/genética , Citocromo P-450 CYP3A/genética , Resistência a Medicamentos/genética , Receptores Purinérgicos P2Y12/genética , Receptores de Esteroides/genética , Ticlopidina/análogos & derivados , Idoso , Povo Asiático/genética , Estudos de Casos e Controles , Clopidogrel , Feminino , Estudos de Associação Genética , Genótipo , Humanos , Hipertensão/genética , Masculino , Agregação Plaquetária/efeitos dos fármacos , Inibidores da Agregação Plaquetária , Polimorfismo de Nucleotídeo Único , Receptor de Pregnano X , Fatores de Proteção , Fatores de Risco , Acidente Vascular Cerebral/tratamento farmacológico , Acidente Vascular Cerebral/genética , Ticlopidina/farmacologia , Ticlopidina/uso terapêutico
14.
Sci Rep ; 14(1): 18307, 2024 08 07.
Artigo em Inglês | MEDLINE | ID: mdl-39112542

RESUMO

Pitaya (Hylocereus undulatus) is a significant cash crop in the karst region of Southwest China. Ecological stoichiometry is an essential method to research biogeochemical cycles and limiting elements. The purpose of this study was to explore the stoichiometric characteristics of C, N, and P in Karst pitaya orchards and fruit quality and to elucidate the mechanism and process of nutrient cycling. The results showed that: (1) Fruit quality was highest under the combination of chemical and organic fertilizers. Compared to the control, the contents of per-fruit weight, vitamin C, and soluble sugar increased significantly by 55.5%, 60.7%, and 23.0%, respectively, while the content of titratable acidity decreased significantly by 22.0%. (2) The content of soil nutrients under fertilization stress showed a downward trend in general, as did microbial biomass and extracellular enzyme activities. (3) Different fertilization treatments significantly affected the soil-microbial stoichiometry C:N ratio, C:P ratio, with research areas being significantly limited by C and P. (4) Spearman and PLS-SEM (partial least squares-structural equation model) analysis results showed that under the influence of fertilization, there was a significant positive effect between microorganisms and soil nutrients, but a significant negative effect between soil nutrients and quality. The results of this study offer an innovative perspective on pitaya quality research in Karst areas.


Assuntos
Cactaceae , Fertilizantes , Frutas , Fósforo , Solo , Solo/química , Fertilizantes/análise , Frutas/química , Frutas/crescimento & desenvolvimento , Fósforo/análise , Cactaceae/crescimento & desenvolvimento , Cactaceae/química , Nitrogênio/análise , China , Microbiologia do Solo , Carbono/análise , Biomassa
15.
Int Immunopharmacol ; 140: 112910, 2024 Oct 25.
Artigo em Inglês | MEDLINE | ID: mdl-39121604

RESUMO

This research investigated the intricate relationship between ferroptosis and sepsis by utilizing advanced genomic and pharmacological methodologies. Specifically, we obtained expression quantitative trait loci (eQTLs) for 435 genes associated with ferroptosis from the eQTLGen Consortium and detected notable cis-eQTLs for 281 of these genes. Next, we conducted a detailed analysis to assess the impact of these eQTLs on susceptibility to sepsis using Mendelian randomization (MR) with data from a cohort of 10,154 sepsis patients and 452,764 controls sourced from the UK Biobank. MR analysis revealed 16 ferroptosis-related genes that exhibited significant associations with sepsis outcomes. To bolster the robustness of these findings, sensitivity analyses were performed to assess pleiotropy and heterogeneity, thus confirming the reliability of the causal inferences. Furthermore, single-cell RNA sequencing data from sepsis patients offered a detailed examination of gene expression profiles, demonstrating varying levels of ferroptosis marker expression across different cell types. Pathway enrichment analysis utilizing gene set enrichment analysis (GSEA) further revealed the key biological pathways involved in the progression of sepsis. Additionally, the use of computational molecular docking facilitated the prediction of interactions between identified genes and potential therapeutic compounds, highlighting novel drug targets. In conclusion, our integrated approach combining genomics and pharmacology offers valuable insights into the involvement of ferroptosis in sepsis, laying the groundwork for potential therapeutic strategies targeting this cell death pathway to enhance sepsis management.


Assuntos
Ferroptose , Análise da Randomização Mendeliana , Locos de Características Quantitativas , Sepse , Análise de Célula Única , Ferroptose/genética , Humanos , Sepse/genética , Sepse/tratamento farmacológico , Genômica/métodos , Simulação de Acoplamento Molecular , Predisposição Genética para Doença
16.
Pest Manag Sci ; 80(2): 613-626, 2024 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-37740940

RESUMO

BACKGROUND: Tribe Zyginelline leafhoppers can transmit plant viruses and are important pests that affect agriculture, forestry, and animal husbandry, causing serious economic losses. The potential distribution patterns of Zyginellini will change under climate change. Therefore, the best-performing random forest and maximum entropy models among 12 commonly used ecological niche models, alongside an ensemble model, were selected to predict the changes in habitat suitability distribution of Zyginellini under current and future climate scenarios [represented by two shared socio-economic pathways (SSPs), namely SSP126 and SSP585, for three periods (2050s, 2070s, and 2090s)] in China and the Indo-China Peninsula for the first time. RESULTS: The results revealed that the distribution of Zyginellini was mainly dominated by minimum temperature of coldest month. Under current and future climate scenarios, Zyginellini was mostly distributed southeast of the 400 mm equivalent precipitation line in China, and Vietnam. Under the future SSP126 scenario, the alert areas will mainly be concentrated in Hunan, Jiangxi, Zhejiang, Anhui, and Hebei in China, alongside Myanmar and Thailand in the Indo-China Peninsula. Meanwhile, in the SSP585 scenario, the alert areas in China will increase, whereas there will be little change in the Indo-China Peninsula. Interestingly, from the current to the future, the cores of Zyginelline distribution occurred around rivers and mountains, and shifted from Guizhou along the Yuanjiang River system to higher latitudes in Hunan. CONCLUSION: Zyginellini prefers higher latitude river-mountain systems under climate change. Our results will contribute to effective pest control strategies and biogeographical research for Zyginellini alongside other Cicadellidae insects. © 2023 Society of Chemical Industry.


Assuntos
Mudança Climática , Hemípteros , Animais , Rios , Modelos Teóricos , Temperatura Baixa , China , Ecossistema
17.
Am J Mens Health ; 18(4): 15579883241264120, 2024.
Artigo em Inglês | MEDLINE | ID: mdl-39054777

RESUMO

Coronavirus disease 2019 (COVID-19) has been reported to decrease semen quality in reproductive-age men. Semen quality in vaccinated men after SARS-CoV-2 infection remains unclear. We recruited reproductive-age Chinese men scheduled for COVID-19 vaccination from December 2022 to March 2023. Among 1,639 vaccinated participants, an upward trend was found in sperm concentration (p < .001), progressive motility (p < .001), total motility (p < .001), total motile sperm count (TMSC) (p < .001), and normal morphology (p = .01) over time following COVID-19 recovery. Among men with an SARS-CoV-2 infection that lasted less than 30 days, men who received an inactivated vaccine booster had higher sperm progressive (p = .006) and total motility (p = .005) as well as TMSC (p = .008) than those without a booster vaccine, whereas no difference was found in semen parameters among men who received a recombinant protein vaccine. Similarly, an upward trend in semen quality was found among 122 men who provided semen samples before and after COVID-19. Higher risks of asthenozoospermia (odds ratio [OR] = 2.23, p < .001) and teratozoospermia (OR = 2.09, p = .03) were found among men who had an SARS-CoV-2 infection that lasted less than 30 days than among those without COVID-19. Collectively, after receiving SARS-CoV-2 vaccination, adverse but reversible semen parameters were observed in men recovering from COVID-19 over time. Recombinant protein vaccines and inactivated vaccine boosters should be recommended to all reproductive-age men.


Assuntos
Vacinas contra COVID-19 , COVID-19 , Análise do Sêmen , Humanos , Masculino , COVID-19/prevenção & controle , Estudos Retrospectivos , Adulto , Vacinas contra COVID-19/administração & dosagem , SARS-CoV-2 , China , Contagem de Espermatozoides , Motilidade dos Espermatozoides , Pessoa de Meia-Idade
18.
Ecol Evol ; 14(7): e70003, 2024 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-39026963

RESUMO

Knowing the impacts of global climate change on the habitat suitability distribution of Limassolla leafhoppers contributes to understanding the feedback of organisms on climate change from a macroecological perspective, and provides important scientific basis for protecting the ecological environment and biodiversity. However, there is limited knowledge on this aspect. Thus, our study aimed to address this gap by analyzing Asian habitat suitability and centroid shifts of Limassolla based on 19 bioclimatic variables and occurrence records. Selecting five ecological niche models with the outstanding predictive performance (Maxlike, generalized linear model, generalized additive model, random forest, and maximum entropy) along with their ensemble model from 12 models, the current habitat suitability of Limassolla and its future habitat suitability under two Shared Socio-economic Pathways (SSP1-2.6 and SSP5-8.5) in the 2050s and 2090s were predicted. The results showed that the prediction results of the five models are generally consistent. Based on ensemble model, 11 potential biodiversity hotspots with high suitability were identified. With climate change, the suitable range of Limassolla will experience both expansion and contraction. In SSP5-8.52050s, the expansion area is 118.56 × 104 km2, while the contraction area is 25.40 × 104 km2; in SSP1-2.62090s, the expansion area is 91.71 × 104 km2, and the contraction area is 26.54 × 104 km2. Furthermore, the distribution core of Limassolla will shift toward higher latitudes in the northeast direction, and the precipitation of warmest quarter was found to have the greatest impact on the distribution of Limassolla. Our research results supported our four hypotheses. Finally, this research suggests establishing ecological reserves in identified contraction to prevent habitat loss, enhancing the protection of biodiversity hotspots, and pursuing a sustainable development path with reduced emissions.

19.
Ecol Evol ; 14(4): e11264, 2024 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-38606344

RESUMO

Erythroneurini is the largest tribe of the microleafhopper subfamily Typhlocybinae. Most prior research on this tribe has focused on traditional classification, phylogeny, and control of agricultural pests, and the phylogeography of the group remains poorly understood. In this study, the mitochondrial genomes of 10 erythroneurine species were sequenced, and sequences of four genes were obtained for 12 geographical populations of Seriana bacilla. The new sequence data were combined with previously available mitochondrial DNA sequence data and analyzed using Bayesian and Maximum-Likelihood-based phylogenetic methods to elucidate relationships among genera and species and estimate divergence times. Seriana was shown to be derived from within Empoascanara. Phylogeographic and population genetic analysis of the endemic Chinese species Seriana bacilla suggest that the species diverged about 54.85 Mya (95% HPD: 20.76-66.23 million years) in the Paleogene period and that population divergence occurred within the last 14 million years. Ancestral area reconstruction indicates that Seriana bacilla may have originated in the central region of Guizhou, and geographical barriers are the main factors affecting gene flow among populations. Ecological niche modeling using the MaxEnt model suggests that the distribution of the species was more restricted in the past but is likely to expand in the future years 2050 and 2070.

20.
Front Immunol ; 15: 1368487, 2024.
Artigo em Inglês | MEDLINE | ID: mdl-38846936

RESUMO

Background: Contactin-1 (CNTN1) antibody-positive nodopathy is rare and exhibits distinct clinical symptoms such as tremors and ataxia. However, the mechanisms of these symptoms and the characteristics of the cerebral spinal fluid (CSF) remain unknown. Case presentation: Here, we report a case of recurrent CNTN1 antibody-positive nodopathy. Initially, a 45-year-old woman experiencing numbness in the upper limbs and weakness in the lower limbs was diagnosed with chronic inflammatory demyelinating polyradiculoneuropathy (CIDP). Eleven years later, her symptoms worsened, and she began to experience tremors and ataxia. Tests for serum CNTN1, GT1a, and GQ1b antibodies returned positive. Subsequently, she was diagnosed with CNTN1 antibody-positive nodopathy and underwent plasmapheresis therapy, although the treatment's efficacy was limited. To gain a deeper understanding of the disease, we conducted a comprehensive literature review, identifying 52 cases of CNTN1 antibody-positive nodopathy to date, with a tremor prevalence of 26.9%. Additionally, we found that the average CSF protein level in CNTN1 antibody-positive nodopathy was 2.57 g/L, with 87% of patients exhibiting a CSF protein level above 1.5 g/L. Conclusion: We present a rare case of recurrent CNTN1 antibody-positive nodopathy. Our findings indicate a high prevalence of tremor (26.9%) and elevated CSF protein levels among patients with CNTN1 antibody-positive nodopathy.


Assuntos
Autoanticorpos , Contactina 1 , Humanos , Feminino , Pessoa de Meia-Idade , Autoanticorpos/sangue , Autoanticorpos/imunologia , Contactina 1/imunologia , Polirradiculoneuropatia Desmielinizante Inflamatória Crônica/imunologia , Polirradiculoneuropatia Desmielinizante Inflamatória Crônica/diagnóstico , Polirradiculoneuropatia Desmielinizante Inflamatória Crônica/terapia , Polirradiculoneuropatia Desmielinizante Inflamatória Crônica/sangue , Recidiva , Tremor/imunologia , Tremor/etiologia , Plasmaferese
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