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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.
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
3.
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
4.
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.

5.
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
6.
Zhongguo Yi Liao Qi Xie Za Zhi ; 47(1): 99-105, 2023 Jan 30.
Artigo em Chinês | 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
7.
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
8.
Sci Rep ; 12(1): 5470, 2022 03 31.
Artigo em Inglês | MEDLINE | ID: mdl-35361837

RESUMO

This study explored the differences in emotional memory between adolescents with and without suicidal ideation. Fifty adolescents with depression and suicidal ideation, 36 with depression but no suicidal ideation, and 41 healthy controls rated the emotional valence of positive, neutral, and negative pictures. Then, the recognition of the images was evaluated 72 h later. Adolescents with suicidal ideation reported more negative emotional valence scores for positive and neutral pictures and were significantly less likely to recognize negative pictures than were those without suicidal ideation. The performance of adolescents with suicidal ideation on the negative picture recognition test was closely related to anxiety, depression severity, and intensity of suicidal ideation. The negative bias toward neutral stimuli and cognitive impairment may be important risk factors for adolescents with suicidal ideation. Improving emotional memory via targeted management approaches may help young people with suicidal ideation.


Assuntos
Transtorno Depressivo , Ideação Suicida , Adolescente , Ansiedade , Transtornos de Ansiedade , Humanos , Fatores de Risco
9.
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.

10.
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.

11.
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.

12.
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
13.
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
14.
Exp Neurol ; 344: 113814, 2021 10.
Artigo em Inglês | MEDLINE | ID: mdl-34280452

RESUMO

The functional roles of microRNAs (miRNAs) have been studied in various diseases, including hypoxic-ischemic brain damage (HIBD). However, changes in the expression of miRNAs and the underlying mechanisms in the pineal gland during HIBD remain unknown. Based on the previous study by microRNA array, hundreds of miRNAs showed altered expression patterns in the pineal gland in a rat model of HIBD. MiR-375-3p was found to be significantly upregulated and abundant in the pineal gland. Further investigation in an in vitro HI model of pinealocytes showed that miRNA-375 exacerbated the damage to pineal function. After oxygen-glucose deprivation / reoxygenation (OGD/R), miR-375-3p expression increased, while aralkylamine N-acetyltransferase (AANAT) expression and melatonin (MT) secretion decreased. Overexpression of miRNA-375 in pinealocytes aggravated the influence of OGD/R on AANAT expression and MT secretion. Because miRNA-375 overexpression in pinealocytes induced decreased rasd1 mRNA and protein expression, rasd1 may mediate the effect of miR-375-3p on pineal function. Furthermore, miR-375-3p aggravated the cognitive impairment caused by HIBD in rats, as observed by Morris water maze test, and also affected emotion and circadian rhythm in HIBD-treated rats. Thus, miR-375-3p may be a key regulatory molecule in the pineal gland following HIBD, and targeting of miR-375-3p may represent a new strategy for the treatment of HIBD.


Assuntos
Hipóxia-Isquemia Encefálica/fisiopatologia , MicroRNAs/metabolismo , Glândula Pineal/fisiopatologia , Animais , Ritmo Circadiano/fisiologia , Disfunção Cognitiva/etiologia , Disfunção Cognitiva/metabolismo , Disfunção Cognitiva/fisiopatologia , Emoções/fisiologia , Feminino , Hipóxia-Isquemia Encefálica/complicações , Hipóxia-Isquemia Encefálica/metabolismo , Masculino , Glândula Pineal/metabolismo , Ratos , Ratos Sprague-Dawley
15.
Neural Regen Res ; 16(10): 2071-2077, 2021 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-33642396

RESUMO

Circadian rhythm disorder is a common, but often neglected, consequence of neonatal hypoxic-ischemic brain damage (HIBD). However, the underlying molecular mechanisms remain largely unknown. We previously showed that, in a rat model of HIBD, up-regulation of microRNA-325 (miR-325) in the pineal gland is responsible for the suppression of Aanat, a key enzyme involved in melatonin synthesis and circadian rhythm regulation. To better understand the mechanism by which miR-325 affects circadian rhythms in neonates with HIBD, we compared clinical samples from neonates with HIBD and samples from healthy neonates recruited from the First Affiliated Hospital of Soochow University (Dushuhu Branch) in 2019. We found that circulating miR-325 levels correlated positively with the severity of sleep and circadian rhythm disorders in neonates with HIBD. Furthermore, a luciferase reporter gene assay revealed that LIM homeobox 3 (LHX3) is a novel downstream target of miR-325. In addition, in miR-325 knock-down mice, the transcription factor LHX3 exhibited an miR-325-dependent circadian pattern of expression in the pineal gland. We established a neonatal mouse model of HIBD by performing double-layer ligation of the left common carotid artery and exposing the pups to a low-oxygen environment for 2 hours. Lhx3 mRNA expression was significantly down-regulated in these mice and partially rescued in miR-325 knockout mice subjected to the same conditions. Finally, we showed that improvement in circadian rhythm-related behaviors in animals with HIBD was dependent on both miR-325 and LHX3. Taken together, our findings suggest that the miR-325-LHX3 axis is responsible for regulating circadian rhythms and provide novel insights into the identification of potential therapeutic targets for circadian rhythm disorders in patients with neonatal HIBD. The clinical trial was approved by Institutional Review Board of Children's Hospital of Soochow University (approval No. 2015028) on July 20, 2015. Animal experiments were approved by Animal Care and Use Committee, School of Medicine, Soochow University, China (approval No. XD-2016-1) on January 15, 2016.

16.
Neural Regen Res ; 16(6): 1037-1043, 2021 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-33269748

RESUMO

Our previous studies have demonstrated that TP53-induced glycolysis and apoptosis regulator (TIGAR) can protect neurons after cerebral ischemia/reperfusion. However, the role of TIGAR in neonatal hypoxic-ischemic brain damage (HIBD) remains unknown. In the present study, 7-day-old Sprague-Dawley rat models of HIBD were established by permanent occlusion of the left common carotid artery followed by 2-hour hypoxia. At 6 days before induction of HIBD, a lentiviral vector containing short hairpin RNA of either TIGAR or gasdermin D (LV-sh_TIGAR or LV-sh_GSDMD) was injected into the left lateral ventricle and striatum. Highly aggressively proliferating immortalized (HAPI) microglial cell models of in vitro HIBD were established by 2-hour oxygen/glucose deprivation followed by 24-hour reoxygenation. Three days before in vitro HIBD induction, HAPI microglial cells were transfected with LV-sh_TIGAR or LV-sh_GSDMD. Our results showed that TIGAR expression was increased in the neonatal rat cortex after HIBD and in HAPI microglial cells after oxygen/glucose deprivation/reoxygenation. Lentivirus-mediated TIGAR knockdown in rats markedly worsened pyroptosis and brain damage after hypoxia/ischemia in vivo and in vitro. Application of exogenous nicotinamide adenine dinucleotide phosphate (NADPH) increased the NADPH level and the glutathione/oxidized glutathione ratio and decreased reactive oxygen species levels in HAPI microglial cells after oxygen/glucose deprivation/reoxygenation. Additionally, exogenous NADPH blocked the effects of TIGAR knockdown in neonatal HIBD in vivo and in vitro. These findings show that TIGAR can inhibit microglial pyroptosis and play a protective role in neonatal HIBD. The study was approved by the Animal Ethics Committee of Soochow University of China (approval No. 2017LW003) in 2017.

17.
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
18.
Comput Math Methods Med ; 2020: 1793517, 2020.
Artigo em Inglês | MEDLINE | ID: mdl-32952597

RESUMO

An artificial stent implantation is one of the most effective ways to treat coronary artery diseases. It is vital in vascular medical imaging, such as intravascular optical coherence tomography (IVOCT), to be able to track the position of stents in blood vessels effectively. We trained two models, the "You Only Look Once" version 3 (YOLOv3) and the Region-based Fully Convolutional Network (R-FCN), to detect metal support struts in IVOCT, respectively. After rotating the original images in the training set for data augmentation, and modifying the scale of the conventional anchor box in both two algorithms to fit the size of the target strut, YOLOv3 and R-FCN achieved precision, recall, and AP all above 95% in 0.4 IoU threshold. And R-FCN performs better than YOLOv3 in all relevant indicators.


Assuntos
Doença da Artéria Coronariana/diagnóstico por imagem , Doença da Artéria Coronariana/cirurgia , Stents , Tomografia de Coerência Óptica/métodos , Algoritmos , Biologia Computacional , Aprendizado Profundo , Humanos , Interpretação de Imagem Assistida por Computador/métodos , Interpretação de Imagem Assistida por Computador/estatística & dados numéricos , Conceitos Matemáticos , Metais , Desenho de Prótese , Tomografia de Coerência Óptica/estatística & dados numéricos
19.
Comput Math Methods Med ; 2020: 9689821, 2020.
Artigo em Inglês | MEDLINE | ID: mdl-32328157

RESUMO

The detection of recorded epileptic seizure activity in electroencephalogram (EEG) segments is crucial for the classification of seizures. Manual recognition is a time-consuming and laborious process that places a heavy burden on neurologists, and hence, the automatic identification of epilepsy has become an important issue. Traditional EEG recognition models largely depend on artificial experience and are of weak generalization ability. To break these limitations, we propose a novel one-dimensional deep neural network for robust detection of seizures, which composes of three convolutional blocks and three fully connected layers. Thereinto, each convolutional block consists of five types of layers: convolutional layer, batch normalization layer, nonlinear activation layer, dropout layer, and max-pooling layer. Model performance is evaluated on the University of Bonn dataset, which achieves the accuracy of 97.63%∼99.52% in the two-class classification problem, 96.73%∼98.06% in the three-class EEG classification problem, and 93.55% in classifying the complicated five-class problem.


Assuntos
Aprendizado Profundo , Diagnóstico por Computador/estatística & dados numéricos , Eletroencefalografia/estatística & dados numéricos , Redes Neurais de Computação , Convulsões/classificação , Convulsões/diagnóstico , Algoritmos , Biologia Computacional , Bases de Dados Factuais/estatística & dados numéricos , Humanos , Modelos Neurológicos , Modelos Estatísticos , Dinâmica não Linear , Processamento de Sinais Assistido por Computador
20.
Food Funct ; 11(3): 2173-2185, 2020 Mar 01.
Artigo em Inglês | MEDLINE | ID: mdl-32083631

RESUMO

The immunomodulatory effects of R-phycoerythrin (R-PE) from Porphyra haitanensis were investigated by a hydrocortisone (HC)-induced immunosuppressive model in the present research. The results showed that R-PE had immunomodulatory potential, such as increasing spleen and thymus indexes, ameliorating spleen morphology, enhancing the phagocytic capability of macrophages, promoting spleen T lymphocyte proliferation, and strengthening serum hemolysin formation. Furthermore, R-PE elevated the CD4+/CD8+ ratio and up-regulated the levels of cytokines for Th1, Th2, and Th17 and the mRNA expression of transcription factors T-bet, GATA3, and RORγt. Besides, the levels of cytokines for Treg and transcription factor Foxp3 were down-regulated. The levels of T-bet/GATA3 and RORγt/Foxp3 were increased. R-PE activated the phosphorylation of NF-κB through the TLR4-mediated differentiation pathway. These findings suggested that R-PE exerted immunomodulatory activities in the innate and adaptive immune systems through TLR4/NF-κB mediated CD4+ T cell activation and differentiation, which facilitated the further application of R-PE as an immunomodulator.


Assuntos
Fatores Imunológicos/farmacologia , NF-kappa B/metabolismo , Ficoeritrina/farmacologia , Porphyra/química , Linfócitos T/fisiologia , Animais , Diferenciação Celular , Hidrocortisona/farmacologia , Hospedeiro Imunocomprometido , Masculino , Camundongos , Camundongos Endogâmicos BALB C , NF-kappa B/genética , RNA Mensageiro , Baço/efeitos dos fármacos , Baço/metabolismo , Timo/efeitos dos fármacos , Timo/metabolismo , Receptor 4 Toll-Like
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