RESUMO
Protein phosphatases are post-translational regulators of Toxoplasma gondii proliferation, tachyzoite-bradyzoite differentiation and pathogenesis. Here, we identify the putative protein phosphatase 6 (TgPP6) subunits of T. gondii and elucidate their role in the parasite lytic cycle. The putative catalytic subunit TgPP6C and regulatory subunit TgPP6R likely form a complex whereas the predicted structural subunit TgPP6S, with low homology to the human PP6 structural subunit, does not coassemble with TgPP6C and TgPP6R. Functional studies showed that TgPP6C and TgPP6R are essential for parasite growth and replication. The ablation of TgPP6C significantly reduced the synchronous division of the parasite's daughter cells during endodyogeny, resulting in disordered rosettes. Moreover, the six conserved motifs of TgPP6C were required for efficient endodyogeny. Phosphoproteomic analysis revealed that ablation of TgPP6C predominately altered the phosphorylation status of proteins involved in the regulation of the parasite cell cycle. Deletion of TgPP6C significantly attenuated the parasite virulence in mice. Immunization of mice with TgPP6C-deficient type I RH strain induced protective immunity against challenge with a lethal dose of RH or PYS tachyzoites and Pru cysts. Taken together, the results show that TgPP6C contributes to the cell division, replication and pathogenicity in T. gondii.
Assuntos
Parasitos , Fosfoproteínas Fosfatases , Toxoplasma , Animais , Humanos , Camundongos , Domínio Catalítico , Ciclo Celular/genética , Divisão Celular , Parasitos/metabolismo , Proteínas de Protozoários/genética , Proteínas de Protozoários/metabolismo , Toxoplasma/metabolismo , Virulência/genética , Fosfoproteínas Fosfatases/genética , Fosfoproteínas Fosfatases/metabolismoRESUMO
OBJECTIVE: Our previous study found that overexpression of uncoupling protein-2 (UCP2) had a protective effect on lipopolysaccharide (LPS)-induced sepsis cardiomyocytes. The aim of this study was to explore the effect and mechanism of uncoupling protein-2 (UCP2) on myocardial ischemia-reperfusion injury. METHODS: In this study, we established hypoxia-reoxygenation (HR) injury model in rats and isolated cardiomyocytes of newborn rats. We also carried out following methods which include virus transfection technology, cell counting Kit-8 (CCK8), flow cytometry, enzyme linked immunosorbent assay (ELISA), Western blot (WB), quantitative reverse transcription PCR (RT qPCR), transmission electron microscopy, fluorescence colocalization and immunoprecipitation. MAIN RESULTS: The results of this study showed that hypoxia-reoxygenation treatment in cardiomyocytes increased UCP2, myocardial enzyme and myocardial apoptosis and weakened cardiomyocyte viability. We observed increased cardiomyocyte viability and mitochondrial membrane potential, decreased myocardial enzyme and myocardial apoptosis, Inhibition of oxidative stress when UCP2 was overexpressed in cardiomyocytes. It also can Increase ATP and stabilize mitochondrial dynamics. Further studies founded that Sirtuin-3(SIRT3) changed with the expression of UCP2, which was confirmed by fluorescence co-localization and immunoprecipitation. CONCLUSIONS: Our findings revealed that UCP2 and SIRT3 were important targets of anti-myocardial injury by inhibiting cellular oxidative stress and stabilizing mitochondrial dynamics.
Assuntos
Sirtuína 3 , Animais , Ratos , Hipóxia , Dinâmica Mitocondrial , Estresse Oxidativo , Sirtuína 3/genética , Sirtuína 3/metabolismo , Proteína Desacopladora 2/genética , Proteína Desacopladora 2/metabolismoRESUMO
Toxoplasma gondii is a widely spread opportunistic pathogen that can infect nearly all warm-blooded vertebrates and cause serious toxoplasmosis in immunosuppressed animals and patients. However, the relationship between the host's innate immune system and effector proteins is poorly understood, particularly with regard to how effectors antagonize cGAS-STING signaling during T. gondii infection. In this study, the ROP5 from the PRU strain of T. gondii was found to promote cGAS-STING-mediated immune responses. Mechanistically, ROP5 interacted with STING through predicted domain 2 and modulated cGAS-STING signaling in a predicted domain 3-dependent manner. Additionally, ROP5 strengthened cGAS-STING signaling by enhancing the K63-linked ubiquitination of STING. Consistently, ROP5 deficient PRU (PRUΔROP5) induced fewer type I IFN-related immune responses and replicated faster than the parental strain in RAW264.7 cells. Taken together, this study provides new insights into the mechanism by which ROP5 regulates T. gondii infection and provides new clues for strategies to prevent and control toxoplasmosis.
Assuntos
Interferon Tipo I , Proteínas de Membrana , Proteínas de Protozoários , Toxoplasma , Ubiquitinação , Toxoplasma/imunologia , Toxoplasma/patogenicidade , Animais , Camundongos , Proteínas de Membrana/metabolismo , Proteínas de Membrana/genética , Proteínas de Protozoários/metabolismo , Proteínas de Protozoários/genética , Interferon Tipo I/metabolismo , Células RAW 264.7 , Humanos , Transdução de Sinais , Toxoplasmose/imunologia , Toxoplasmose/parasitologia , Toxoplasmose/metabolismo , Imunidade Inata , Nucleotidiltransferases/metabolismo , Nucleotidiltransferases/genéticaRESUMO
BACKGROUND: Although hepatitis B virus (HBV) infection remains the main cause of hepatocellular carcinoma (HCC) worldwide, metabolic syndrome, with its increase in prevalence, has become an important and significant risk factor for HCC. This study was designed to investigate the association of concurrent metabolic syndrome with long-term prognosis following liver resection for patients with HBV-related HCC. METHODS: From a Chinese, multicenter database, HBV-infected patients who underwent curative resection for HCC between 2010 and 2020 were identified. Long-term oncological prognosis, including overall survival (OS), recurrence-free survival (RFS), and early (≤2 years of surgery) and late (>2 years) recurrences were compared between patients with versus those without concurrent metabolic syndrome. RESULTS: Of 1753 patients, 163 (9.3%) patients had concurrent metabolic syndrome. Compared with patients without metabolic syndrome, patients with metabolic syndrome had poorer 5-year OS (47.5% vs. 61.0%; P = 0.010) and RFS (28.3% vs. 44.2%; P = 0.003) rates and a higher 5-year overall recurrence rate (67.3% vs. 53.3%; P = 0.024). Multivariate analysis revealed that concurrent metabolic syndrome was independently associated with poorer OS (hazard ratio: 1.300; 95% confidence interval: 1.018-1.660; P = 0.036) and RFS (1.314; 1.062-1.627; P = 0.012) rates, and increased rates of late recurrence (hazard ratio: 1.470; 95% confidence interval: 1.004-2.151; P = 0.047). CONCLUSIONS: In HBV-infected patients with HCC, concurrent metabolic syndrome was associated with poorer postoperative long-term oncologic survival outcomes. These results suggested that patients with metabolic syndrome should undergo enhanced surveillance for tumor recurrence even after 2 years of surgery to early detect late HCC recurrence. Whether improving metabolic syndrome can reduce postoperative recurrence of HCC deserves further exploration.
Assuntos
Carcinoma Hepatocelular , Hepatite B Crônica , Neoplasias Hepáticas , Síndrome Metabólica , Humanos , Hepatite B Crônica/complicações , Carcinoma Hepatocelular/cirurgia , Síndrome Metabólica/complicações , Neoplasias Hepáticas/etiologia , Neoplasias Hepáticas/cirurgiaRESUMO
BACKGROUND: Cancer case during pregnancy is rare, but it is the second leading cause of maternal mortality. CASE PRESENTATION: A-32-year old pregnant woman with a gestational age of 37 weeks was admitted to the hospital due to repeated coughing for 5 months. She received Veno-Venous Extracorporeal Membrane Oxygenation (V-V ECMO) treatment for severe hypoxemia after delivery. She was diagnosed with non-small cell lung cancer (NSCLC) with bone metastasis and pneumocystis pneumonia (PCP). She subsequently received anti-tumor therapy and anti-infective therapy. After treatment, her condition improved and she was weaned from ECMO. Two weeks after weaning ECMO, her condition worsened again. Her family chose palliative treatment, and she ultimately died. CONCLUSIONS: NSCLC is rare during pregnancy. At present, there is still a lack of standardized methods to manage these cases. For theses cases, the clinician should be wary of opportunistic infections, such as pneumocystis jirovecii (P. jirovecii) and Elizabethkingia spp. Specialized medical teams with abundant experience and multidisciplinary discussions from the perspectives of the patient's clinical characteristics as well as preferences are crucial for developing individualized and the best approach.
Assuntos
Carcinoma Pulmonar de Células não Pequenas , Neoplasias Pulmonares , Pneumocystis carinii , Pneumonia por Pneumocystis , Humanos , Gravidez , Feminino , Recém-Nascido , Pneumonia por Pneumocystis/diagnóstico , Pneumonia por Pneumocystis/tratamento farmacológico , Gestantes , Neoplasias Pulmonares/complicaçõesRESUMO
Fasciola hepatica is a trematode leading to heavy economic setbacks to the livestock sector globally. The population's genetic information and intimate kinship level are frequently assessed using analysis of mitochondrial DNA. In this analysis, we retrieved cox1 (n = 247) and nad1 (n = 357) sequences of F. hepatica from the NCBI GenBank database and aligned the sequences with the respective reference sequences using MEGA software. The median joining network was drawn using PopArt software while neutrality and diversity indices were estimated with the help of DnaSp software. Neighbor-joining phylogenetic tree was constructed using the MEGA software package. A total of 46 and 98 distinctive haplotypes were observed for cox1 and nad1 genes, respectively. Diversity indices indicated high haplotype and nucleotide diversities in both genes. Positive Tajima's D and Fu's Fs values were found for the entire population of both the genes under study. The cox1 and nad1 gene segments in this study showed high Tajima's D values, suggesting a low likelihood of future population growth. The Tajima's D value of the nad1 gene sequence is lower (2.14910) than that of the cox1 gene sequence (3.40314), which suggests that the former is growing at a slower rate. However, the region-wise analysis revealed that both the cox1 and nad1 genes showed deviation from neutrality suggesting a recent population expansion as a result of an excess of low-frequency polymorphism. Furthermore, the overall host-wise analysis showed positive and significant Tajima's D values for the cox1 and nad1 gene sequences. To the best of our knowledge, this is the first attempt to provide insights into genetic variations and population structure of F. hepatica at a global scale using cox1 and nad1 genes. Our findings suggest the existence of specific variants of F. hepatica in different parts of the world and provide information on the molecular ecology of F. hepatica. The results of this study also mark a critical development in upcoming epidemiological investigations on F. hepatica and will also contribute to understanding the global molecular epidemiology and population structure of F. hepatica.
Assuntos
Fasciola hepatica , Animais , Fasciola hepatica/genética , Filogenia , Variação Genética , DNA Mitocondrial/genética , HaplótiposRESUMO
The identification of additional Echinococcus granulosus sensu lato (s.l.) complex species/genotypes in recent years raises the possibility that there might be more variation among this species in China than is currently understood. The aim of this study was to explore intra- and inter-species variation and population structure of Echinococcus species isolated from sheep in three areas of Western China. Of the isolates, 317, 322, and 326 were successfully amplified and sequenced for cox1, nad1, and nad5 genes, respectively. BLAST analysis revealed that the majority of the isolates were E. granulosus s.s., and using the cox1, nad1, and nad5 genes, respectively, 17, 14, and 11 isolates corresponded to Elodea canadensis (genotype G6/G7). In the three study areas, G1 genotypes were the most prevalent. There were 233 mutation sites along with 129 parsimony informative sites. A transition/transversion ratio of 7.5, 8, and 3.25, respectively, for cox1, nad1, and nad5 genes was obtained. Every mitochondrial gene had intraspecific variations, which were represented in a star-like network with a major haplotype with observable mutations from other distant and minor haplotypes. The Tajima's D value was significantly negative in all populations, indicating a substantial divergence from neutrality and supporting the demographic expansion of E. granulosus s.s. in the study areas. The phylogeny inferred by the maximum likelihood (ML) method using nucleotide sequences of cox1-nad1-nad5 further confirmed their identity. The nodes assigned to the G1, G3, and G6 clades as well as the reference sequences utilized had maximal posterior probability values (1.00). In conclusion, our study confirms the existence of a significant major haplotype of E. granulosus s.s. where G1 is the predominant genotype causing of CE in both livestock and humans in China.
Assuntos
Equinococose , Echinococcus granulosus , Animais , Humanos , Ovinos , Echinococcus granulosus/genética , Tibet , Equinococose/epidemiologia , Equinococose/veterinária , China , Genótipo , Haplótipos , Mutação , Filogenia , Variação GenéticaRESUMO
PURPOSE: With increasing life expectancy, the number of elderly patients (≥ 65 years) with hepatocellular carcinoma (HCC) has steadily increased. Hepatectomy remains the first-line treatment for HCC patients. However, the prognosis of hepatectomy for elderly patients with HCC remains unclear. METHODS: Clinical and follow-up data from 1331 HCC patients who underwent surgery between 2008 and 2020 were retrospectively retrieved from a multicentre database. Patients were divided into elderly (≥ 65 years) and non-elderly (< 65 years) groups, and PSM was used to balance differences in the baseline characteristics. The postoperative major morbidity and cancer-specific survival (CSS) of the two groups were compared and the independent factors that were associated with the two study endpoints were identified by multivariable regression analysis. RESULTS: Of the 1331 HCC patients enrolled in this study, 363 (27.27%) were elderly, while 968 (72.73%) were not. After PSM, 334 matched samples were obtained. In the propensity score matching (PSM) cohort, a higher rate of major morbidity was found in elderly patients (P = 0.040) but the CSS was similar in the two groups (P = 0.087). Multivariate analysis revealed that elderly age was not an independent risk factor associated with high rates of major morbidity (P = 0.117) or poor CSS (P = 0.873). The 1-, 3- and 5-year CSS rates in the elderly and non-elderly groups were 91.0% versus 86.2%, 71.3% versus 68.8% and 55.9% versus 58.0%, respectively. Preoperative alpha fetoprotein (AFP) level, ChildâPugh grade, intraoperative blood transfusion, extended hemi hepatectomy, and tumour diameter could affect the postoperative major morbidity and preoperative AFP level, cirrhosis, ChildâPugh grade, macrovascular invasion, microvascular invasion (MVI), satellite nodules, and tumor diameter were independently and significantly associated with CSS. CONCLUSION: Age itself had no significant effect on the prognosis of elderly patients with HCC after hepatectomy. Hepatectomy can be safely performed in elderly patients after cautious perioperative management.
Assuntos
Carcinoma Hepatocelular , Neoplasias Hepáticas , Humanos , Idoso , Pessoa de Meia-Idade , Carcinoma Hepatocelular/cirurgia , Carcinoma Hepatocelular/patologia , Neoplasias Hepáticas/cirurgia , Neoplasias Hepáticas/patologia , alfa-Fetoproteínas/análise , Hepatectomia , Pontuação de Propensão , Estudos Retrospectivos , Recidiva Local de Neoplasia/cirurgia , PrognósticoRESUMO
Reports of paedoptera dermatitis are commonly found in tropical and subtropical regions, while reports in China are rare. In September 2022, an outbreak of paedoptera dermatitis occurred in a minority autonomous county in southwestern China. Here, we report 134 patients with paedoptera dermatitis who were treated at the People's Hospital of Sandu Shui Autonomous County. The skin lesions of these patients were mostly located on the face, neck, trunk, or multiple sites. The skin lesions were mainly distributed in patches and were characterized by vesicular linear or "kissing" lesions. Most patients felt burning pain, and few patients felt pruritus. The treatments with oral antihistamines, calamine lotion, steroids, and antibiotics were effective. For patients with ocular involvement, treatments with oral prednisone and bufexamac cream were effective. All patients recovered within 2 wk. There is a possibility of another outbreak of paedoptera dermatitis in the region. Awareness of the condition and its clinical features will prevent misdiagnosis. Early diagnosis and timely treatment lead to a better prognosis for paederus dermatitis. Simple preventive measures can be undertaken based on the behavioral pattern of this nocturnal beetle.
Assuntos
Besouros , Dermatite , Animais , Humanos , Surtos de Doenças , Hospitais , China/epidemiologia , Dermatite/tratamento farmacológico , Dermatite/epidemiologia , Dermatite/etiologiaRESUMO
A 29-year-old male presented with recurrent mucous bloody stools for more than a year. Colonoscopy revealed ill-defined, mildly congested and edematous mucosa with scattered erosion spots in the lower rectum, highly suspicious for proctitis. Histopathology showed diffuse infiltration of small to medium-sized lymphoid cells in the lamina propria. Immunohistochemistry indicated these cells were positive for CD20, CD79a, CD19, kappa and lambda light chains (partial), and negative for CD3, CD5, CD10, cyclin D and BCL-6. These results were consistent with mucosa-associated lymphoid tissue (MALT) lymphoma. Further investigations consisting of upper endoscopy, bone marrow biopsy, and whole-body PET/CT scan did not detect any extrarectal lesions. Based on these findings, the diagnosis of stage I primary rectal MALT lymphoma was made. The patient underwent 15 fractions of radiotherapy with a total dose of 30 Gy. His symptoms were alleviated following the treatment. A follow-up colonoscopy performed 3 months later showed complete resolution of the lesion.
Assuntos
Linfoma de Zona Marginal Tipo Células B , Proctite , Masculino , Humanos , Adulto , Linfoma de Zona Marginal Tipo Células B/diagnóstico por imagem , Reto/patologia , Tomografia por Emissão de Pósitrons combinada à Tomografia Computadorizada , Proctite/diagnóstico , BiópsiaRESUMO
The G allele of rs4702 polymorphism has been reported to reduce the production of mature BDNF and FURIN, both of which were closely associated with cognitive functions. Real-time PCR, ELISA and luciferase assay were performed to explore the interactions between miR-338-3p, FURIN and BDNF. T-RFLP was used to assess the intestinal flora in the stool samples of glioma patients after radiotherapy. We grouped the 106 glioma patients recruited according to the rs4702 polymorphism. The results showed no obvious correlation between rs4702 polymorphism and the expression of miR-338-3p. However, rs4702-A was associated with increased expression of FURIN and BDNF in the serum and PBMC of glioma patients after radiotherapy. Besides, the study found that rs4702-A was remarkably associated with increased enterotype I and decreased enterotype III in the stool of glioma patients after radiotherapy. Rs4702-A was also proved to be closely associated with increased MMSE, role functioning and social functioning at three months after radiotherapy. Furthermore, miR-338-3p repressed the expression of FURIN-G. Compared with G allele, the presence of A allele of rs4702 polymorphism in FURIN could obstruct the suppressive effect of miR-338-3p upon the expression of FURIN and BDNF in intestinal flora. Therefore, the carriers of A allele will be challenged with less risk of radiotherapy-induced cognitive impairment.
Assuntos
Disfunção Cognitiva , Glioma , MicroRNAs , Regiões 3' não Traduzidas/genética , Disfunção Cognitiva/genética , Furina/genética , Glioma/genética , Glioma/metabolismo , Glioma/radioterapia , Humanos , Leucócitos Mononucleares/metabolismo , MicroRNAs/genética , MicroRNAs/metabolismoRESUMO
OBJECTIVE: This study was designed to assess the impact of thoracic epidural analgesia (TEA) in patients with severe acute pancreatitis (SAP). METHODS: This is a single-centre retrospective study. In this study, the outcomes of SAP patients were compared between patients received TEA (TEA group) and without TEA (NTEA group). Early TEA was defined as TEA performed within 48 hours after onset. The main outcome was the mortality at 30 days after ICU admission, and secondary outcomes included the incidence of acute respiratory distress syndrome (ARDS), the acute renal injury (AKI) and sepsis, the hospital stay and hospitalization expenses. RESULTS: The mortality of SAP patients in TEA versus NTEA was 8.0% and 13.3% (p = .1520). Multivariate regression analysis showed significant difference in mortality between the TEA and NTEA groups (OR, 0.387; 95% CI, 0.168-0.892; p = .026). The incidence of ARDS in TEA versus NTEA was 46.0% and 62.4% (p = .0044); the proportion of patients requiring invasive ventilator assisted ventilation in TEA, and NTEA was 22.6% and 39.2% (p = .0016). The incidence of AKI in TEA versus NTEA was 27.7% and 45.3% (p = .0044); the proportion of patients needing for continuous renal replacement therapy (CRRT) in TEA and NTEA was 48.2% and 74.0% (p < .0001). The mortality of SAP patients in early TEA versus NTEA was 4.8% and 15.3% (p = .0263). CONCLUSIONS: TEA was associated with low incidence of ARDS and AKI in patients with SAP. Early TEA may benefit mortality in SAP patients and is a possible protective factor for the mortality of SAP patients.
Assuntos
Injúria Renal Aguda , Analgesia Epidural , Pancreatite , Síndrome do Desconforto Respiratório , Doença Aguda , Injúria Renal Aguda/epidemiologia , Humanos , Síndrome do Desconforto Respiratório/terapia , Estudos RetrospectivosRESUMO
BACKGROUND: Amoebiasis is caused by the protozoan Entamoeba histolytica, which is a rare infectious disease in developed countries. If the trophozoites enter the blood, it can spread through the body, such as brain, and lungs. Cases of simultaneous infection of multiple organs are extremely rare. CASE PRESENTATION: Here we report a case of simultaneous infection of amoeba in pulmonary pleura, urinary system and central nervous system. Although the patient received anti amoeba treatment, the prognosis of the patient was poor. CONCLUSIONS: In this patient, multiple extraintestinal amebic infections in the absence of clinically confirmed intestinal amebiasis or amebic liver abscess are rare and pose diagnostic challenges. The disseminated amebiasis has significantly increased the mortality. Early diagnosis and appropriate treatment may reduce the mortality of disseminated amebiasis.
Assuntos
Amebíase , Disenteria Amebiana , Entamoeba histolytica , Entamebíase , Abscesso Hepático Amebiano , Amebíase/diagnóstico , Amebíase/tratamento farmacológico , Disenteria Amebiana/diagnóstico , Disenteria Amebiana/tratamento farmacológico , Entamebíase/diagnóstico , Entamebíase/tratamento farmacológico , Humanos , Abscesso Hepático Amebiano/diagnóstico , Abscesso Hepático Amebiano/tratamento farmacológicoRESUMO
OBJECTIVES: Previous studies have demonstrated that the paraventricular nucleus of the thalamus (PVT) is a key wakefulness-controlling nucleus in the thalamus. Therefore, PVT may also be involved in the process of general anesthesia. This study intends to explore the role of PVT in isoflurane anesthesia. METHODS: In the present study, we used the expression of c-Fos to observe the neuronal activity of PVT neurons under isoflurane anesthesia. We further recorded the effect of isoflurane anesthesia on the calcium signal of PVT glutamatergic neurons in real time with the help of calcium fiber photometry. We finally used chemogenetic technology to specifically regulate PVT glutamatergic neurons, and observed its effect on isoflurane anesthesia and cortical electroencephalography (EEG) in mice. RESULTS: We found that glutamatergic neurons of PVT exhibited high activity during wakefulness and low activity during isoflurane anesthesia. Activation of PVT glutamatergic neuronal caused an acceleration in emergence from isoflurane anesthesia accompanied with a decrease in EEG delta power (1-4 Hz). Whereas suppression of PVT glutamatergic neurons induced a delay recovery of isoflurane anesthesia, without affecting anesthesia induction. CONCLUSIONS: Assuming a pharmacokinetic explanation for results can be excluded, these results demonstrate that the PVT is involved in regulating anesthesia emergence.
Assuntos
Isoflurano , Anestesia Geral , Animais , Cálcio/metabolismo , Isoflurano/farmacologia , Camundongos , Neurônios , Núcleo Hipotalâmico Paraventricular , TálamoRESUMO
LncRNA-PTENP1 was reported to promote multiple myeloma cancer stem cell proliferation, and the G allele of rs7853346 polymorphism in lncRNA-PTENP1 was demonstrated to enhance the effect of lncRNA-PTENP1. In this study, we aimed to study the potential effect of lncRNA-PTENP1 and CCR2 mRNA polymorphisms on cognitive impairment in glioma patients. In this study, 279 glioma patients were recruited and grouped according to their genotypes of rs7853346 in PTENP1 and rs1799864 in CCR1. Pathogenic parameters were collected from patients before radiotherapy (month 0) or at month 1 and month 3 after radiotherapy to study the effect of rs7853346 and rs1799864 on cognitive impairment. Sequence analysis, luciferase assay, real-time PCR, and Western blot were performed to study the regulatory relationships between lncRNA-PTENP1, miR-18b, and CCR2. The glioma patient groups exhibited no significant differences concerning basic characteristics. However, the CG&GG/GG genotype alleviated radiotherapy-induced cognitive impairment by exhibiting the highest MMSE among the four groups. On the contrary, parameters including the severity of depression, bladder control, global health status, itchy skin, and weakness of legs all showed no difference among different patient groups at month 0, month 1, and month 3. Also, a long-term positive effect of CG&GG/GG genotype on role functioning and social functioning was also observed after radiotherapy. Compared with patients carrying the CC genotype of rs7853346, the expression of lncRNA-PTENP1 was reduced while the miR-19b level was elevated in patients carrying the CG&GG genotypes of rs7853346. Moreover, the expression of CCR2 mRNA was the highest in the CC/GA&AA group and the lowest in the CG&GG/GG group. Subsequent sequence analysis and luciferase assay indicated that miR-19b could bind to lncRNA-PTENP1 and 3'UTR of CCR2 mRNA, and the knockdown of lncRNA-PTENP1 led to evident up-regulation of miR-19b and down-regulation of CCR2 mRNA/protein in a cellular model, thus verifying the presence of the lncRNA-PTENP1/miR-19b/CCR2 mRNA signaling pathway. In conclusion, by studying the changes in the key parameters of glioma patients who were subjected to radiotherapy, we concluded that the rs7853346 polymorphism in lncRNA-PTENP1 and the rs1799864 polymorphism in CCR2 could independently affect cognitive impairment, while a more significant combined effect on cognitive impairment was exerted in glioma patients via the signaling pathway of PTENP1/miR-19b/CCR2.
Assuntos
Disfunção Cognitiva , Glioma , MicroRNAs , RNA Longo não Codificante , Regiões 3' não Traduzidas , Disfunção Cognitiva/genética , Glioma/genética , Humanos , MicroRNAs/genética , MicroRNAs/metabolismo , Polimorfismo de Nucleotídeo Único , RNA Longo não Codificante/genética , Receptores CCR2/genética , Transdução de Sinais/genéticaRESUMO
Parasitic infection is one of the many challenges facing livestock production globally. Cysticercosis tenuicollis is a common parasitic disease in domestic and wild ruminants (intermediate host) caused by the larval stage of Taenia hydatigena that primarily infects dogs (definitive host). Although genetic studies on this parasite exist, only a few describe the genetic variation of this parasite in Mongolia. Our aim was thus, to identify the mitochondrial differences in ovine isolates of Cysticercus tenuicollis entering China from Mongolia and comparison with existing Chinese isolates from sheep and goats based on the recently described PCR-RFLP method and mitochondrial genes of NADH dehydrogenase subunit 4 (nad4) and the NADH dehydrogenase subunit 5 (nad5). Sixty-nine isolates were collected during routine veterinary meat inspections from sheep that originated from Mongolia, at the modern slaughterhouses in Erenhot City, Inner Mongolia. Additional 114 cysticerci were also retrieved from sheep and goats from northern (Inner Mongolia Autonomous Region, Ningxia Hui Autonomous Region, and Gansu Province), western (Tibet Autonomous Region), and southern (Jiangxi Province and Guangxi Province) China. The PCR-RFLP approach of the nad5 showed nine mitochondrial subclusters A1, A2, A3, A5, A8, A9, A10, A11, and B of T. hydatigena isolates from sheep and goats from Mongolia and China. Meanwhile, haplogroup A1 RFLP profile was more widespread than other variants. These data supplements existing information on the molecular epidemiology of T. hydatigena in China and Mongolia and demonstrate the occurrence of similar genetic population structures in both countries.
Assuntos
Cisticercose , Doenças dos Ovinos , Taenia , Ovinos , Animais , Cães , Taenia/genética , Cysticercus/genética , Mongólia/epidemiologia , Variação Genética , Filogenia , China , Cisticercose/epidemiologia , Cisticercose/veterinária , Cisticercose/parasitologia , Doenças dos Ovinos/epidemiologia , Doenças dos Ovinos/parasitologia , CabrasRESUMO
PURPOSE: The aim of the current study was to explore the role of the basal forebrain (BF) in propofol anaesthesia. METHODS: In the present study, we observed the neural activities of the BF during propofol anaesthesia using calcium fibre photometry recording. Subsequently, ibotenic acid was injected into the BF to verify the role of the BF in propofol anaesthesia. Finally, to test whether GABAA receptors in the BF were involved in modulating propofol anaesthesia, muscimol (GABAA receptor agonist) and gabazine (GABAA receptor antagonist) were microinjected into the BF. Cortical electroencephalogram (EEG), time to loss of righting reflex (LORR), and recovery of righting reflex (RORR) under propofol anaesthesia were recorded and analysed. RESULTS: The activity of BF neurons was inhibited during induction of propofol anaesthesia and activated during emergence from propofol anaesthesia. In addition, non-specifical lesion of BF neurons significantly prolonged the time to RORR and increased delta power in the frontal cortex under propofol anaesthesia. Next, microinjection of muscimol into the BF delayed emergence from propofol anaesthesia, increased delta power of the frontal cortex, and decreased gamma power under propofol anaesthesia. Conversely, infusion of gabazine accelerated emergence times and decreased EEG delta power. CONCLUSIONS: The basal forebrain is involved in modulating frontal cortex delta activity and emergence from propofol anaesthesia. Additionally, the GABAA receptors in the basal forebrain are involved in regulating emergence propofol anaesthesia.
Assuntos
Anestesia , Prosencéfalo Basal , Propofol , Animais , Prosencéfalo Basal/metabolismo , Eletroencefalografia , Muscimol/farmacologia , Propofol/farmacologia , Ratos , Receptores de GABA-A/metabolismo , Ácido gama-Aminobutírico/farmacologiaRESUMO
Cysticercosis caused by the metacestode larval stage of Taenia hydatigena formerly referred to as Cysticercus tenuicollis is a disease of veterinary importance that constitutes a significant threat to livestock production worldwide, especially in endemic regions due to condemnation of visceral organs and mortality rate of infected young animals. While the genetic diversity among parasites is found to be potentially useful in many areas of research including molecular diagnostics, epidemiology and control, that of T. hydatigena across the globe remains poorly understood. In this study, analysis of the mitochondrial DNA (mtDNA) of adult worms and larval stages of T. hydatigena isolated from dogs, sheep and a wild boar in China showed that the population structure consists of two major haplogroups with very high nucleotide substitutions involving synonymous and non-synonymous changes. Compared with other cestodes such as Echinococcus spp., the genetic variation observed between the haplogroups is sufficient for the assignment of major haplotype or genotype division as both groups showed a total of 166 point-mutation differences between the 12 mitochondrial protein-coding gene sequences. Preliminary analysis of a nuclear protein-coding gene (pepck) did not reveal any peculiar changes between both groups which suggests that these variants may only differ in their mitochondrial makeup.
Assuntos
DNA de Helmintos/genética , DNA Mitocondrial/genética , Taenia/genética , Teníase/veterinária , Sequência de Aminoácidos , Animais , China , DNA de Helmintos/química , DNA de Helmintos/metabolismo , DNA Mitocondrial/química , DNA Mitocondrial/metabolismo , Doenças do Cão/parasitologia , Cães , Haplótipos , Larva/genética , Larva/crescimento & desenvolvimento , Filogenia , Alinhamento de Sequência , Ovinos , Doenças dos Ovinos/parasitologia , Carneiro Doméstico , Sus scrofa , Suínos , Doenças dos Suínos/parasitologia , Taenia/crescimento & desenvolvimento , Taenia/metabolismo , Teníase/parasitologiaRESUMO
BACKGROUND AND AIMS: Although proprotein convertase subtilisin/kexin type 9 (PCSK9) inhibitors have been shown to improve cardiovascular outcomes, their effects on brain stroke risk are unclear. The present meta-analysis aimed to evaluate the effects of PCSK9 inhibitors on brain stroke prevention. METHODS AND RESULTS: We searched PubMed, Embase, Cochrane Library, Web of Science, and ClinicalTrials.gov for research published until December 30, 2020, to find randomized controlled trials (RCTs) of PCSK9 inhibitors for brain stroke prevention. Relative risk (RR) and 95% confidence intervals (CIs) were used to represent the outcomes. Seven RCTs with 57,440 participants, including 29,850 patients treated with PCSK9 inhibitors and 27,590 control participants, were included. PCSK9 inhibitors were associated with significant reductions in total brain stroke risk (RR, 0.77; 95% CI, 0.67-0.88; P < 0.001) and ischemic brain stroke risk (RR, 0.76; 95% CI, 0.66, 0.89; P < 0.001) in comparison with the control group. There was no significant difference in cardiovascular mortality (RR, 0.95; 95% CI, 0.84-1.07; P = 0.382) and the risk of hemorrhagic brain stroke (RR, 1.00; 95% CI, 0.66-1.51; P = 0.999) between patients treated with PCSK9 inhibitors and controls. PCSK9 inhibitors did not significantly increase the incidence of neurocognitive adverse events (RR, 1.02; 95% CI, 0.81-1.29; P = 0.85). Moreover, subgroup analysis showed no difference in cognitive function disorder risks among different PCSK9 inhibitors and treatment times. CONCLUSIONS: PCSK9 inhibitors significantly reduced the risk of total brain stroke and ischemic brain stroke without increasing the risk of brain hemorrhage and neurocognitive impairment.
Assuntos
Dislipidemias/tratamento farmacológico , AVC Isquêmico/prevenção & controle , Inibidores de PCSK9 , Inibidores de Serina Proteinase/uso terapêutico , Idoso , Dislipidemias/diagnóstico , Dislipidemias/epidemiologia , Feminino , Acidente Vascular Cerebral Hemorrágico/induzido quimicamente , Acidente Vascular Cerebral Hemorrágico/epidemiologia , Humanos , AVC Isquêmico/diagnóstico , AVC Isquêmico/epidemiologia , Masculino , Pessoa de Meia-Idade , Transtornos Neurocognitivos/induzido quimicamente , Transtornos Neurocognitivos/epidemiologia , Prevenção Primária , Fatores de Proteção , Medição de Risco , Fatores de Risco , Prevenção Secundária , Inibidores de Serina Proteinase/efeitos adversos , Resultado do TratamentoRESUMO
BACKGROUND: The surgical indications for liver hemangioma remain unclear. METHODS: Data from 152 patients with hepatic hemangioma who underwent hepatectomy between 2004 and 2019 were retrospectively reviewed. We analyzed characteristics including tumor size, surgical parameters, and variables associated with Kasabach-Merritt syndrome and compared the outcomes of laparoscopic and open hepatectomy. Here, we describe surgical techniques for giant hepatic hemangioma and report on two meaningful cases. RESULTS: Most (63.8%) patients with hepatic hemangioma were asymptomatic. Most (86.4%) tumors from patients with Kasabach-Merritt syndrome were larger than 15 cm. Enucleation (30.9%), sectionectomy (28.9%), hemihepatectomy (25.7%), and the removal of more than half of the liver (14.5%) were performed through open (87.5%) and laparoscopic (12.5%) approaches. Laparoscopic hepatectomy is associated with an operative time, estimated blood loss, and major morbidity and mortality rate similar to those of open hepatectomy, but a shorter length of stay. 3D image reconstruction is an alternative for diagnosis and surgical planning for partial hepatectomy. CONCLUSION: The main indication for surgery is giant (> 10 cm) liver hemangioma, with or without symptoms. Laparoscopic hepatectomy was an effective option for hepatic hemangioma treatment. For extremely giant hemangiomas, 3D image reconstruction was indispensable. Hepatectomy should be performed by experienced hepatic surgeons.