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1.
Acta Pharmacol Sin ; 2024 May 15.
Artigo em Inglês | MEDLINE | ID: mdl-38750074

RESUMO

Hypoxia-ischemia (HI) is one of the main causes of neonatal brain injury. Mitophagy has been implicated in the degradation of damaged mitochondria and cell survival following neonatal brain HI injury. Pleckstrin homology-like domain family A member 1 (PHLDA1) plays vital roles in the progression of various disorders including the regulation of oxidative stress, the immune responses and apoptosis. In the present study we investigated the role of PHLDA1 in HI-induced neuronal injury and further explored the mechanisms underlying PHLDA1-regulated mitophagy in vivo and in vitro. HI model was established in newborn rats by ligation of the left common carotid artery plus exposure to an oxygen-deficient chamber with 8% O2 and 92% N2. In vitro studies were conducted in primary hippocampal neurons subjected to oxygen and glucose deprivation/-reoxygenation (OGD/R). We showed that the expression of PHLDA1 was significantly upregulated in the hippocampus of HI newborn rats and in OGD/R-treated primary neurons. Knockdown of PHLDA1 in neonatal rats via lentiviral vector not only significantly ameliorated HI-induced hippocampal neuronal injury but also markedly improved long-term cognitive function outcomes, whereas overexpression of PHLDA1 in neonatal rats via lentiviral vector aggravated these outcomes. PHLDA1 knockdown in primary neurons significantly reversed the reduction of cell viability and increase in intracellular reactive oxygen species (ROS) levels, and attenuated OGD-induced mitochondrial dysfunction, whereas overexpression of PHLDA1 decreased these parameters. In OGD/R-treated primary hippocampal neurons, we revealed that PHLDA1 knockdown enhanced mitophagy by activating FUNDC1, which was abolished by FUNDC1 knockdown or pretreatment with mitophagy inhibitor Mdivi-1 (25 µM). Notably, pretreatment with Mdivi-1 or the knockdown of FUNDC1 not only increased brain infarct volume, but also abolished the neuroprotective effect of PHLDA1 knockdown in HI newborn rats. Together, these results demonstrate that PHLDA1 contributes to neonatal HI-induced brain injury via inhibition of FUNDC1-mediated neuronal mitophagy.

2.
J Pineal Res ; 75(1): e12885, 2023 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-37183291

RESUMO

Hypoxia-ischemia (HI) of the brain not only impairs neurodevelopment but also causes pineal gland dysfunction, which leads to circadian rhythm disruption. However, the underlying mechanism of circadian rhythm disruption associated with HI-induced pineal dysfunction remains unknown. The zinc finger protein repressor protein with a predicted molecular mass of 58 kDa (RP58) is involved in the development and differentiation of nerve cells. In this study, we established an HI model in neonatal rats to investigate the expression of RP58 and its role in pineal dysfunction and circadian rhythm disruption induced by HI. We demonstrated that RP58 was highly expressed in the pineal gland under normal conditions and significantly downregulated in the pineal gland and primary pinealocytes following HI. Knockdown of RP58 decreased the expression of enzymes in the melatonin (Mel) synthesis pathway (tryptophan hydroxylase 1 [TPH1], acetylserotonin O-methyltransferase [ASMT], and arylalkylamine N-acetyltransferase [AANAT]) and clock genes (circadian locomotor output cycles kaput [CLOCK] and brain and muscle ARNT-like 1 [BMAL1]), and it also reduced the production of Mel, caused pineal cell injury, and disrupted circadian rhythms in vivo and in vitro. Similarly, HI reduced the expression of Mel synthesis enzymes (TPH1, ASMT, and AANAT) and clock genes (CLOCK and BMAL1), and caused pineal injury and circadian rhythm disruption, which were exacerbated by RP58 knockdown. The detrimental effect of RP58 knockdown on pineal dysfunction and circadian rhythm disruption was reversed by the addition of exogenous Mel. Furthermore, exogenous Mel reversed HI-induced pineal dysfunction and circadian rhythm disruption, as reflected by improvements in Mel production, voluntary activity periods, and activity frequency, as well as a diminished decrease in the expression of Mel synthesis enzymes and clock genes. The present study suggests that RP58 is an endogenous source of protection against pineal dysfunction and circadian rhythm disruption after neonatal HI.


Assuntos
Melatonina , Glândula Pineal , Ratos , Animais , Melatonina/metabolismo , Animais Recém-Nascidos , Fatores de Transcrição ARNTL/metabolismo , RNA Mensageiro/metabolismo , Ritmo Circadiano/fisiologia , Glândula Pineal/metabolismo , Hipóxia/metabolismo , Isquemia/metabolismo , Arilalquilamina N-Acetiltransferase/genética , Arilalquilamina N-Acetiltransferase/metabolismo
3.
Nature ; 552(7685): 368-373, 2017 12 21.
Artigo em Inglês | MEDLINE | ID: mdl-29236692

RESUMO

The mechanistic target of rapamycin complex 1 (mTORC1) controls cell growth and metabolism in response to nutrients, energy levels, and growth factors. It contains the atypical kinase mTOR and the RAPTOR subunit that binds to the Tor signalling sequence (TOS) motif of substrates and regulators. mTORC1 is activated by the small GTPase RHEB (Ras homologue enriched in brain) and inhibited by PRAS40. Here we present the 3.0 ångström cryo-electron microscopy structure of mTORC1 and the 3.4 ångström structure of activated RHEB-mTORC1. RHEB binds to mTOR distally from the kinase active site, yet causes a global conformational change that allosterically realigns active-site residues, accelerating catalysis. Cancer-associated hyperactivating mutations map to structural elements that maintain the inactive state, and we provide biochemical evidence that they mimic RHEB relieving auto-inhibition. We also present crystal structures of RAPTOR-TOS motif complexes that define the determinants of TOS recognition, of an mTOR FKBP12-rapamycin-binding (FRB) domain-substrate complex that establishes a second substrate-recruitment mechanism, and of a truncated mTOR-PRAS40 complex that reveals PRAS40 inhibits both substrate-recruitment sites. These findings help explain how mTORC1 selects its substrates, how its kinase activity is controlled, and how it is activated by cancer-associated mutations.


Assuntos
Proteínas Adaptadoras de Transdução de Sinal/metabolismo , Microscopia Crioeletrônica , Alvo Mecanístico do Complexo 1 de Rapamicina/química , Alvo Mecanístico do Complexo 1 de Rapamicina/ultraestrutura , Proteína Enriquecida em Homólogo de Ras do Encéfalo/metabolismo , Proteínas Adaptadoras de Transdução de Sinal/química , Motivos de Aminoácidos , Sítios de Ligação , Biocatálise , Domínio Catalítico , Cristalografia por Raios X , Ativação Enzimática , Humanos , Alvo Mecanístico do Complexo 1 de Rapamicina/agonistas , Alvo Mecanístico do Complexo 1 de Rapamicina/antagonistas & inibidores , Modelos Moleculares , Mutação , Neoplasias/genética , Ligação Proteica , Domínios Proteicos , Proteína Enriquecida em Homólogo de Ras do Encéfalo/química , Proteína Enriquecida em Homólogo de Ras do Encéfalo/ultraestrutura , Proteína Regulatória Associada a mTOR/química , Proteína Regulatória Associada a mTOR/metabolismo , Proteínas Quinases S6 Ribossômicas 70-kDa/metabolismo , Transdução de Sinais , Sirolimo/metabolismo , Especificidade por Substrato , Proteína 1A de Ligação a Tacrolimo/metabolismo
4.
BMC Urol ; 23(1): 201, 2023 Dec 05.
Artigo em Inglês | MEDLINE | ID: mdl-38053112

RESUMO

OBJECTIVES: To describe a technique to improve exposure of prostate during extraperitoneal robot-assisted radical prostatectomy (EP-RARP). MATERIAL AND METHODS: From March 2020 to June 2022, a total of 41 patients with prior intra-abdominal surgery underwent EP-RARP. Twenty-three patients improved exposure by traction of prostate through urinary catheter. The catheter traction prostatectomy (CTP) group was compared with the standard prostatectomy (SP) group using three robotic arms (18 patients) in terms of estimated blood loss (EBL), operative time, positive surgical margin rate, the recovery rate of urinary continence, Gleason score and postoperative hospital stays. Differences were considered significant when P < 0.05. RESULTS: The operative time was lower in the CTP group (109.63 min vs. 143.20 min; P < 0.001). EBL in the CTP group was 178.26 ± 30.70 mL, and in the standard prostatectomy group, it was 347.78 ± 53.53 mL (P < 0.001). No significant differences with regard to postoperative hospital stay, recovery rate of urinary continence, catheterization time and positive surgical margin were observed between both groups. No intraoperative complications occurred in all the patients. After 6 months of follow-up, the Post-op Detectable prostate specific antigen was similar between the two groups. CONCLUSION: CTP is a feasible, safe, and valid procedure in EP-RARP. Application of CTP improved the exposure of prostate, reduced operative time and blood loss in comparison with the conventional procedure.


Assuntos
Neoplasias da Próstata , Procedimentos Cirúrgicos Robóticos , Robótica , Masculino , Humanos , Próstata , Procedimentos Cirúrgicos Robóticos/métodos , Margens de Excisão , Tração , Neoplasias da Próstata/cirurgia , Neoplasias da Próstata/etiologia , Prostatectomia/métodos , Cateteres Urinários , Resultado do Tratamento
5.
Zhongguo Yi Liao Qi Xie Za Zhi ; 47(1): 99-105, 2023 Jan 30.
Artigo em Zh | MEDLINE | ID: mdl-36752016

RESUMO

Objective To rapidly screen patients with novel coronavirus pneumonia (COVID-19) infection including asymptomatic ones. Method Established a rapid detection test kit, and evaluated analytical and clinical performance of it. Result The minimum limit of detection of the reagent was 9.75×102 TCID50/mL; there was no cross-reaction and interference in the high-concentration samples of 29 common respiratory pathogens tested. The diagnostic sensitivity of clinical samples was 98.56%, specificity was 99.00%, and the total coincidence rate was 98.85%; the consistency test Kappa value is 0.974 5. The stratified analysis of positive samples with different Ct values showed that the coincidence rate within each stratum was greater than 95%. Conclusion This COVID-19 antigen test kit with excellent detection performance, fast detection speed, and portable operation. It can be used as a supplementary method for existing nucleic acid detection methods for early screening of new coronavirus.


Assuntos
COVID-19 , Humanos , Teste para COVID-19 , Sensibilidade e Especificidade , SARS-CoV-2
6.
World J Surg Oncol ; 20(1): 213, 2022 Jun 23.
Artigo em Inglês | MEDLINE | ID: mdl-35739505

RESUMO

BACKGROUND: For patients with prior intra-abdominal surgery or multiple arteries, the retroperitoneal robot-assisted partial nephrectomy (rRAPN) is a better choice. The renal ventral tumor poses an additional challenge due to poor tumor exposure. This study is determined to assess the feasibility of an internal traction technique (ITT) in rRAPN for the management of renal ventral tumors. METHODS: From November 2019 to March 2021, a total of 28 patients with renal ventral tumor underwent rRAPN. All patients had prior abdominal surgery or multiple arteries. The ITT group (20 patients), which improved the tumor exposure by traction of the kidney with suture, was compared with the traditional technique group (8 patients) in terms of warm ischemia time, estimated blood loss and postoperative hospital stay, retroperitoneal drainage, R.E.N.A.L. score, and serum creatinine. Differences were considered significant when P < 0.05. RESULTS: All rRAPN surgeries were successful without conversion to radical nephrectomy or open partial nephrectomy. The warm ischemia time was lower in the ITT group (17.10 min vs. 24.63 min; P < 0.05). Estimated blood loss in the traditional technique group was 324.88 ± 79.42 mL, and in the ITT group, it was 117.45±35.25 mL (P < 0.05). No significant differences with regard to postoperative hospital stay, retroperitoneal drainage, R.E.N.A.L. score, and serum creatinine were observed between both groups. Surgical margins were negative and no intraoperative complications occurred in all the patients. After 10 months of follow-up, no recurrence or metastasis occurred in all cases. CONCLUSION: ITT is a feasible, safe, and valid procedure in rRAPN for renal ventral tumors. Application of ITT improved the exposure and reduces warm ischemic time in comparison with the conventional procedure.


Assuntos
Neoplasias Renais , Laparoscopia , Procedimentos Cirúrgicos Robóticos , Robótica , Creatinina , Humanos , Neoplasias Renais/patologia , Laparoscopia/métodos , Nefrectomia/métodos , Estudos Retrospectivos , Procedimentos Cirúrgicos Robóticos/efeitos adversos , Procedimentos Cirúrgicos Robóticos/métodos , Tração , Resultado do Tratamento
7.
Cancer Cell Int ; 21(1): 683, 2021 Dec 19.
Artigo em Inglês | MEDLINE | ID: mdl-34923957

RESUMO

BACKGROUND: Multiple myeloma (MM) is the most common malignant hematological disease in the people worldwide. Glaucocalyxin A (GLA) is a bioactive ent-kauranoid diterpenoid, that is derived from Rabdosia japonica var. GLA has been demonstrated that it had various pharmacological activities, such as anti-coagulation, anti-bacterial, anti-tumor, anti-inflammation, antioxidant activities. Although GLA has effective anti-tumor properties, its effects on multiple myeloma remain unclear. The aim of this study was to examine the possible anti-cancer effects of GLA and their molecular mechanisms on MM cells in vitro and in vivo. METHODS: To evaluate the role of GLA on the proliferation of MM cells in vitro and in vivo, we used MTT method to detect the role of GLA on the proliferation of MM cells. Cell apoptosis and cell cycle assay were evaluated by flow cytometry. Protein expressions in GLA-treated and untreated MM cells were evaluated by western blot analyses. MM xenograft nude mice model was used to investigate the role of GLA on the proliferation of MM cells in vivo. IHC assay was used to examine the role of GLA on the MM xenograft model in vivo. RESULTS: In the present study, we firstly reported the potent anti-myeloma activity of GLA on MM cells. We found that GLA could induce apoptosis in vitro and in vivo. GLA could inhibit the phosphorylation of the signal transducer and activator of transcription 3 (STAT3) and downregulate interleukin IL-6 induced STAT3 phosphorylation in MM. Overexpression of STAT3 could significantly prevent apoptosis induced by GLA; while knockdown of STAT3 enhanced it. Moreover, GLA could inhibit cell proliferation by inducing the cell cycle arrest. GLA reduced the expression of cell cycle-related proteins CCNB1, CCND1, CCND2, and CCND3 and increased the expression of p21 in MM cell lines. In addition, in the MM xenograft nude mice model, GLA exhibited very good anti-myeloma activity. Administration of GLA almost completely inhibited tumor growth within 19 days without physical toxicity. And the IHC results showed GLA significantly inhibited cell proliferation and interfered STAT3 pathway on MM xenograft model tumor tissues. CONCLUSIONS: Taken together, our present research indicated that GLA inhibits the MM cell proliferation, induces MM cell apoptosis and cell cycle arrest through blocking the activation of STAT3 pathway. Thus, GLA may be a potential therapeutic candidate for MM patients in the future.

8.
BMC Pediatr ; 21(1): 410, 2021 09 18.
Artigo em Inglês | MEDLINE | ID: mdl-34537048

RESUMO

BACKGROUND: While great attention has been paid to motor and cognitive impairments in children with neonatal Hypoxic-Ischemic Encephalopathy (HIE), sleep related circadian rhythm problems, although commonly present, are often neglected. Subsequently, no early clinical indicators have been reported to correlate with sleep-related circadian dysfunction during development. METHODS: In this study, we first analyzed patterns of the amplitude integrated electroencephalogram (aEEG) in a cohort of newborns with various degrees of HIE. Next, during follow-ups, we collected information of sleep and circadian related problems in these patients and performed correlation analysis between aEEG parameters and different sleep/circadian disorders. RESULTS: A total of 101 neonates were included. Our results demonstrated that abnormal aEEG background pattern is significantly correlated with circadian rhythmic (r = 0.289, P = 0.01) and breathing issues during sleep (r = 0.237, P = 0.037). In contrast, the establishment of sleep-wake cycle (SWC) showed no correlation with sleep/circadian problems. Detailed analysis showed that summation of aEEG score, along with low base voltage (r = 0.272, P = 0.017 and r = -0.228, P = 0.048, respectively), correlates with sleep circadian problems. In contrast, background pattern (BP) score highly correlates with sleep breathing problem (r = 0.319, P = 0.004). CONCLUSION: Abnormal neonatal aEEG pattern is correlated with circadian related sleep problems. Our study thus provides novel insights into predictive values of aEEG in sleep-related circadian problems in children with HIE.


Assuntos
Hipóxia-Isquemia Encefálica , Transtornos do Sono-Vigília , Criança , Eletroencefalografia , Humanos , Hipóxia-Isquemia Encefálica/complicações , Hipóxia-Isquemia Encefálica/diagnóstico , Recém-Nascido , Isquemia , Sono , Transtornos do Sono-Vigília/diagnóstico , Transtornos do Sono-Vigília/etiologia
9.
Mar Drugs ; 19(10)2021 Sep 25.
Artigo em Inglês | MEDLINE | ID: mdl-34677438

RESUMO

Reactive oxygen species (ROS) are the key factors that cause many diseases in the human body. Polysaccharides from seaweed have been shown to have significant antioxidant activity both in vivo and in vitro. The ameliorative effect of Ulva lactuca polysaccharide extract (UPE) on renal injury induced by oxidative stress was analyzed. As shown by hematoxylin-eosin staining results, UPE can significantly improve the kidney injury induced by D-galactose (D-gal). Additionally, the protective mechanism of UPE on the kidney was explored. The results showed that UPE could decrease the levels of serum creatinine (Scr), blood urea nitrogen (BUN), serum cystatin C (Cys-C), lipid peroxidation, protein carbonylation, and DNA oxidative damage (8-OHdG) and improve kidney glutathione content. Moreover, UPE significantly increased the activities of superoxide dismutase and glutathione peroxidase and total antioxidant activity in mice. UPE also decreased the levels of inflammatory cytokines TNF-α and IL-6. Further investigation into the expression of apoptotic protein caspase-3 showed that UPE decreased the expression of apoptotic protein caspase-3. These results indicate that UPE has a potential therapeutic effect on renal injury caused by oxidative stress, providing a new theoretical basis for the treatment of oxidative damage diseases in the future.


Assuntos
Rim/efeitos dos fármacos , Estresse Oxidativo/efeitos dos fármacos , Extratos Vegetais/farmacologia , Polissacarídeos/farmacologia , Substâncias Protetoras/farmacologia , Ulva , Animais , Animais não Endogâmicos , Organismos Aquáticos , Modelos Animais de Doenças , Galactose , Masculino , Camundongos , Extratos Vegetais/química , Polissacarídeos/química , Substâncias Protetoras/química
10.
Br J Nutr ; 123(9): 975-986, 2020 05 14.
Artigo em Inglês | MEDLINE | ID: mdl-31787131

RESUMO

The present study investigated the effects of Porphyra yezoensis enzyme degradation extract (PYEDE) on the brain injuries and neurodegenerative diseases due to oxidative stress. We used in vitro antioxidant systems to verify the antioxidant potential of PYEDE. The results indicated that the PYEDE alleviated weight loss and organ atrophy, reduced the levels of lipid peroxidation and protein carbonylation and elevated reduced glutathione (GSH) content in the serum and brains of the d-galactose-induced ageing model mice. The PYEDE also renewed the glutathione peroxidase (GSH-Px), superoxide dismutase and total antioxidant capability activities, down-regulated the inducible nitric oxide synthase activity and nitric oxide levels, normalised the hippocampal neurons and modulated multiple neurotransmitter systems by inhibiting the activities of acetylcholinesterase and monoamine oxidase in the up-regulation of acetylcholine, dopamine and noradrenaline levels. Overall, the PYEDE is a promising supplement for the alleviation of oxidative stress and age-associated brain diseases.


Assuntos
Envelhecimento/efeitos dos fármacos , Lesões Encefálicas/induzido quimicamente , Galactose/toxicidade , Estresse Oxidativo/efeitos dos fármacos , Extratos Vegetais/farmacologia , Porphyra/química , Animais , Antioxidantes/química , Antioxidantes/farmacologia , Lesões Encefálicas/tratamento farmacológico , Feminino , Glutationa/sangue , Radical Hidroxila , Malondialdeído , Camundongos , Camundongos Endogâmicos ICR , Extratos Vegetais/química , Carbonilação Proteica
11.
Mar Drugs ; 18(11)2020 Oct 28.
Artigo em Inglês | MEDLINE | ID: mdl-33126712

RESUMO

The aim of the study was to extract Porphyra haitanensis polysaccharides (PHPs) using the water extraction and alcohol precipitation methods and explore their antioxidant activity and physicochemical properties. The single-factor and Box-Behnken response surface methodologies were used to optimize the extraction of polysaccharides from Porphyra haitanensis. Our results showed that the polysaccharide yield was as high as 20.48% with a raw material to water ratio of 0.04, and extraction time of 3 h at 80 °C. The extraction rate observed was similar to the actual extraction rate, thus proving the reliability of the optimization model. The extracted polysaccharides primarily consisted of galactose, glucose, and fucose in the molar ratio 76.2:2.1:1, respectively. The high performance gel permeation chromatography (HPGPC) results showed that the molecular weight of the PHPs obtained was 6.3 × 105 Da, and the sulfate content was 2.7 mg/mL. Fourier infrared spectroscopy was used to analyze the functional groups and structures of the polysaccharides. The effect of concentration, temperature, and pH on the apparent viscosity of the PHPs solution were studied using rheology experiments, which revealed that PHPs were a "non-Newtonian fluid" with shear-thinning behavior. The viscosity of the PHPs gradually increased with increasing sugar concentration, and decreased with increasing temperature, acidity, and alkalinity. Detection of the antioxidant activity of OH*, DPPH*, and ABTS* revealed that the scavenging activity of ABTS* was higher than that of OH* and DPPH* in the concentration range of 1-5 mg/mL. In the experiments of simulating gastric juice and alpha amylase in vitro, it was found that PHPs can better resist digestion of alpha amylase, and have better resistance than fructooligosaccharide (FOS), so PHPs have potential prebiotic activity. These findings demonstrate the potential of PHPs for use in the food and cosmetic industries.


Assuntos
Antioxidantes/farmacologia , Digestão , Polissacarídeos/metabolismo , Polissacarídeos/farmacologia , Porphyra/metabolismo , Prebióticos , Antioxidantes/isolamento & purificação , Suco Gástrico/metabolismo , Concentração de Íons de Hidrogênio , Polissacarídeos/isolamento & purificação , Temperatura , Viscosidade , alfa-Amilases/metabolismo
12.
J Immunol ; 195(8): 3769-80, 2015 Oct 15.
Artigo em Inglês | MEDLINE | ID: mdl-26363056

RESUMO

Although dendritic cells (DCs) have been widely demonstrated to play essential roles in initiation of Th2 responses in helminth infections and allergic reactions, the mechanisms remain uncertain largely because DCs do not produce IL-4. In present investigation, we have uncovered a novel subset of DCs from mice infected with Th2-provoking pathogens Schistosoma japonica, which independently promoted Th2 cells via IL-4-dependent pathway. These DCs contained similar levels of IL-4 mRNA and higher levels of IL-12p40 mRNA comparing to basophils, correlating to their Th2-promoting and Th1-promoting dual polarization capacities. Characterized by expression of FcεRI(+), these DCs were induced independent of T cells. Further investigations revealed that Th2-promoting FcεRI(+) DCs were monocyte-derived inflammatory DCs, which were sufficient to induce Th2 cells in vivo. Egg Ags together with GM-CSF or IL-3 alone were able to stimulate the generation of Th2-promoting FcεRI(+) DCs from bone marrow cells in vitro. To our knowledge, our data for the first time demonstrate that IL-4-producing DCs are induced under some Th2-provoking situations, and they should play important roles in initiation of Th2 response.


Assuntos
Células Dendríticas/imunologia , Interleucina-4/imunologia , Schistosoma japonicum/imunologia , Esquistossomose Japônica/imunologia , Transdução de Sinais/imunologia , Células Th2/imunologia , Animais , Células Dendríticas/patologia , Subunidade p40 da Interleucina-12/genética , Subunidade p40 da Interleucina-12/imunologia , Interleucina-4/genética , Camundongos , Camundongos Endogâmicos BALB C , Camundongos Knockout , Receptores de IgE/genética , Receptores de IgE/imunologia , Esquistossomose Japônica/genética , Esquistossomose Japônica/patologia , Transdução de Sinais/genética , Células Th2/patologia
13.
Eur Radiol ; 26(6): 1732-41, 2016 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-26334507

RESUMO

OBJECTIVES: To noninvasively assess global cerebral blood flow (CBF), oxygen extraction fraction (OEF) and cerebral metabolic rate of oxygen (CMRO2) in young adults with end-stage renal disease (ESRD). METHODS: Thirty-six patients and 38 healthy volunteers were included and took part in MR examinations, blood and neuropsychological tests. CBF and OEF were measured by phase-contrast and T2-relaxation-under-spin-tagging MRI techniques, respectively. CMRO2 was computed from CBF, OEF and hematocrit according to Fick's principle. Correlations were performed between MR measurements, blood biochemistry measurements and neuropsychological test scores. RESULTS: Compared with controls, ESRD patients had elevated CBF (72.9 ± 12.5 vs. 63.8 ± 8.5 ml min(-1) 100 g(-1), P < 0.001), elevated OEF (47.2 ± 10.2 vs. 35.8 ± 5.4 %, P < 0.001), but unaffected CMRO2 (199.5 ± 36.4 vs. 193.8 ± 28.6 µmol O2 min(-1) 100 g(-1), P = 0.879). Hematocrit negatively correlated with CBF (r = -0.640, P < 0.001) and OEF (r = -0.701, P < 0.001), but not with CMRO2. Altered neuropsychological test scores of ESRD patients were associated with OEF and CBF, but not with CMRO2. There were weak relationships between eGFR and hematocrit (r = 0.308, P = 0.068) or CBF (r = 0.318, P = 0.059). CONCLUSION: Our findings suggested that anaemic young adults with ESRD may afford higher CBF and OEF to maintain a normal CMRO2. Despite this compensatory process, however, cognitive function was still impaired and its severity was correlated with their CBF and OEF abnormality. KEY POINTS: • Anaemic young adults with ESRD may afford higher CBF and OEF. • Anaemic young adults with ESRD maintain a normal CMRO 2 . • Cognitive function was still impaired in young ESRD adults. • The severity of cognitive dysfunction correlated with CBF and OEF changes.


Assuntos
Encéfalo/irrigação sanguínea , Falência Renal Crônica/fisiopatologia , Oxigênio/sangue , Adolescente , Adulto , Circulação Cerebrovascular/fisiologia , Feminino , Humanos , Falência Renal Crônica/metabolismo , Imageamento por Ressonância Magnética/métodos , Masculino , Consumo de Oxigênio/fisiologia , Adulto Jovem
14.
Foodborne Pathog Dis ; 12(4): 360-5, 2015 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-25692734

RESUMO

Inhibition of the binding of pathogenic adhesins to host glycans by suitable oligosaccharides forms the basis of antiadhesion therapies. Experiments were carried out to study the inhibition capability of oligosaccharides on the adhesion of four microorganisms (Escherichia coli, Vibrio cholerae, Campylobacter jejuni, and Salmonella Typhimurium) to HT-29 cells. Results showed that, in the absence of oligosaccharides, all of the four pathogens efficiently adhered to the cells. Cell adhesion with different bacteria was inhibited by distinct oligosaccharides (e.g., the adhesion number relative to control of V. cholerae could be significantly decreased by pectin oligosaccharide and chitooligosaccharide to about 16.1% and 18.9%, respectively). Saturation studies showed that the extent of antiadhesive effect for most of the suitable carbohydrates was dependent on their concentration. The observations from the study suggest that various carbohydrates may have antiadhesive activity and may be useful in future therapeutic study.


Assuntos
Aderência Bacteriana/efeitos dos fármacos , Campylobacter jejuni/efeitos dos fármacos , Escherichia coli/efeitos dos fármacos , Intestinos/microbiologia , Oligossacarídeos/farmacologia , Salmonella typhimurium/efeitos dos fármacos , Vibrio cholerae/efeitos dos fármacos , Campylobacter jejuni/fisiologia , Escherichia coli/fisiologia , Células HT29 , Humanos , Salmonella typhimurium/fisiologia , Vibrio cholerae/fisiologia
15.
Sci Rep ; 14(1): 14210, 2024 06 20.
Artigo em Inglês | MEDLINE | ID: mdl-38902285

RESUMO

Regular screening for cervical cancer is one of the best tools to reduce cancer incidence. Automated cell segmentation in screening is an essential task because it can present better understanding of the characteristics of cervical cells. The main challenge of cell cytoplasm segmentation is that many boundaries in cell clumps are extremely difficult to be identified. This paper proposes a new convolutional neural network based on Mask RCNN and PointRend module, to segment overlapping cervical cells. The PointRend head concatenates fine grained features and coarse features extracted from different feature maps to fine-tune the candidate boundary pixels of cell cytoplasm, which are crucial for precise cell segmentation. The proposed model achieves a 0.97 DSC (Dice Similarity Coefficient), 0.96 TPRp (Pixelwise True Positive Rate), 0.007 FPRp (Pixelwise False Positive Rate) and 0.006 FNRo (Object False Negative Rate) on dataset from ISBI2014. Specially, the proposed method outperforms state-of-the-art result by about 3 % on DSC, 1 % on TPRp and 1.4 % on FNRo respectively. The performance metrics of our model on dataset from ISBI2015 are slight better than the average value of other approaches. Those results indicate that the proposed method could be effective in cytological analysis and then help experts correctly discover cervical cell lesions.


Assuntos
Colo do Útero , Redes Neurais de Computação , Neoplasias do Colo do Útero , Humanos , Feminino , Neoplasias do Colo do Útero/patologia , Neoplasias do Colo do Útero/diagnóstico , Colo do Útero/patologia , Colo do Útero/diagnóstico por imagem , Colo do Útero/citologia , Processamento de Imagem Assistida por Computador/métodos , Algoritmos , Detecção Precoce de Câncer/métodos
16.
Appl Microbiol Biotechnol ; 97(7): 2841-50, 2013 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-23104645

RESUMO

A new kind of extracellular polysaccharide (EPS) from Pseudomonas fluorescens PGM37 was obtained and culture media was optimized using the statistical methods single factor experiments and response surface methodology (RSM) design. As a result, the optimum cultivation conditions initial pH value, medium volume, inoculum size, temperature, and rotation speed were 7.5, 100 mL/250 mL, 5%, 28 °C, and 180 rpm, respectively. The optimized media: sucrose 36.23 g L(-1), yeast extract 3.32 g L(-1), sodium chloride 1.13 g L(-1), and calcium chloride 0.20 g L(-1). The maximum predicted yield of EPS was 10.1163 g L(-1) under these conditions. The validation data was 10.012 g L(-1), which could strongly confirm the correlation between the experimental and theoretical values. Gas Chromatography analysis revealed that the polymer was made up of mannose and glucose in the ratio of 1:1. Infrared spectroscopy showed that the polysaccharide had ß-D-pyranoid configuration and contained no other substituent. Graded by different multiples of alcohol after specific degradation by enzyme and then detected by LC-ESI-MS, the EPS structure was ß-D-Glcp-(1, 4)-ß-D-Manp-(1, 4)-ß-D-Glcp-(1, 4)-ß-D-Manp. The moisture retention ability of the EPS was found to be superior to glycerol and only a little inferior to hyaluronic acid (HA), which presented potential application value in cosmetics and clinical medicine fields.


Assuntos
Meios de Cultura/química , Polissacarídeos Bacterianos/química , Polissacarídeos Bacterianos/metabolismo , Pseudomonas fluorescens/crescimento & desenvolvimento , Pseudomonas fluorescens/metabolismo , Cromatografia Gasosa-Espectrometria de Massas , Glucose/análise , Concentração de Íons de Hidrogênio , Manose/análise , Dados de Sequência Molecular , Espectrofotometria Infravermelho , Temperatura
17.
Front Psychiatry ; 14: 1036314, 2023.
Artigo em Inglês | MEDLINE | ID: mdl-37575578

RESUMO

Objective: To analyze the demographic and clinical characteristics and treatment among children and adolescents with depression in different age groups of onset. Methods: 635 children and adolescents with depression in a hospital from January 2014 to December 2021 were collected by e-case, and grouped according to age of onset, including 115 cases in childhood 8-12, 359 cases in early adolescence 13-1 and 161 cases in late adolescence 16-18, and the general conditions, clinical characteristics, and treatment were compared between the three groups. Results: Females had more onset and were more likely to have psychotic symptoms in childhood, short duration and hospitalization in early adolescence increased year by year, and males had more onset and less hospitalization in late adolescence. There were no statistical differences in medication regimen, suicide, length of hospitalization, or family history between the three groups. Conclusion: Children and adolescents with depression have their unique clinical characteristics at different age of onset and need to enhance prevention and individualized treatment.

18.
Chemosphere ; 345: 140312, 2023 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-37863209

RESUMO

To investigate the degradation efficiency of conditioners and commercial microbial agents on estrogens (E1, 17α-E2, 17ß-E2, E3, EE2, and DES) in the composting process of dairy manure, seven different treatments (RHB-BF, OSP-BF, SD-BF, MR-BF, MR-FS, MR-EM, and MR-CK) under forced ventilation conditions were composted and monitored regularly for 30 days. The results indicated that the removal rates of estrogens in seven treatments ranged from 95.35% to 99.63%, meanwhile the degradation effect of the composting process on 17ß-Estradiol equivalent (EEQ) was evaluated, and the removal rate of ΣEEQ ranged from 96.42% to 99.72%. With the combined addition of rice husk biochar (RHB) or oyster shell powder (OSP) and bio-bacterial fertilizer starter cultures (BF), namely RHB-BF and OSP-BF obviously promoted the rapid degradation of estrogens. 17ß-E2 was completely degraded on the fifth day of composting in OSP-BF. Microbial agents have some promotional effect and enhances the microbial degradation of synthetic estrogen (EE2, DES). According to the results of RDA, pH and EC were the main environmental factors affecting on the composition and succession of estrogen-related degrading bacteria in composting system. As predominant estrogens-degrading genera, Acinetobacter, Bacillus, and Pseudomonas effected obviously on the change of estrogens contents. The research results provide a practical reference for effective composting of dairy manure to enhancing estrogens removal and decreasing ecological risk.


Assuntos
Compostagem , Congêneres do Estradiol , Estrogênios/metabolismo , Esterco , Estradiol/metabolismo , Solo/química
19.
Front Psychiatry ; 13: 1079456, 2022.
Artigo em Inglês | MEDLINE | ID: mdl-36699486

RESUMO

Objective: This study aimed to determine the hospitalization rates, length of stay, age at the time of admission, and sex distribution for major psychiatric disorders in children and adolescents and provide a reference for early intervention for these diseases and distribution of medical resources in hospitals. Methods: We screened 4,423 patients in the child and adolescent wards of the Anhui Provincial Mental Health Center from 2001 to 2020, and examined the top four (81.1%) mental health disorders that accounted for the overall proportion of patients admitted, namely schizophrenia (SCZ) (45.7%), depressive disorder (DD) (14.5%), bipolar disorder (BD) (9.3%), and childhood emotional disorder (CED) (11.6%), and for each disorder, the percentage of hospitalization, length of stay, age at admission, and sex distribution were analyzed. Results: From 2001 to 2020, there was a significantly decreasing trend in the proportion of hospitalizations for SCZ (p < 0.001) and an increasing trend for depression and CED (p < 0.001). In terms of length of stay, SCZ was significantly longer than the other three disorders (p < 0.001), whereas there was no significant difference between DD, BD, and CED, and there was no significant trend in length of stay for any of the four disorders. The age at admission for CED was significantly lower than that for the other three disorders (p < 0.001). There was a decreasing trend in the age at admission for DD (p = 0.011) and an increasing trend for BD (p = 0.001). A significant increase in the number of female patients admitted for SCZ, DD, and CED was observed, while there was no significant change in the sex ratio for BD. Conclusion: Although there is a significant downward trend in the percentage of hospitalizations for SCZ, it is still the most common psychiatric disorder in children and adolescents. We observed a significant increase in the percentage of hospitalizations for DD and CED. In addition, the proportion of female patients being hospitalized is on the rise, and this aspect requires continuous attention.

20.
Front Psychiatry ; 13: 798105, 2022.
Artigo em Inglês | MEDLINE | ID: mdl-35222115

RESUMO

BACKGROUND: Cognitive impairment is a core feature of schizophrenia that is more serious in patients with early-onset schizophrenia (EOS). However, the neuroimaging basis of cognitive functions, including neurocognition and social cognition, remains unclear in patients with EOS. METHODS: Forty-three patients with EOS underwent structural and resting state functional magnetic resonance imaging scans. Brain structure and function were evaluated through the analysis of brain gray matter volume (GMV) and amplitude of low-frequency fluctuations (ALFF). They underwent comprehensive assessments for neurocognition (verbal memory, verbal expression, attention, and executive function) and social cognition (theory of mind and attributional bias). Correlation analyses were conducted to detect the potential link between cognitive function indices and brain imaging parameters. RESULTS: First, neurocognition was linked to brain structure characterized by higher immediate recall scores associated with increased GMV in the left temporal pole, higher verbal fluency scores associated with increased GMV in the left temporal pole: middle temporal gyrus, and higher Stroop-word scores associated with increased GMV in the right middle frontal gyrus. Second, social cognition was related to brain function characterized by lower sense of reality scores associated with increased ALFF in the left precentral gyrus, higher scores of accidental hostility bias associated with increased ALFF in the right middle temporal gyrus, and higher scores of accidental aggression bias associated with increased ALFF in the left precentral gyrus. CONCLUSION: These findings may add to the existing knowledge about the cognitive function-brain relationship. They may have clinical significance for studying the mechanism of neurocognitive and social cognitive impairment in patients with EOS and providing potential neural targets for their treatment and intervention.

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