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BACKGROUND: Severe acute pancreatitis (SAP) has a mortality of 30% with no current targeted therapy. The potential protective effect of insulin on AP has been reported and needs to be confirmed. Thus, we aim to examine the effect of insulin treatment on the outcome of AP patients. METHODS: A retrospective study was performed using data from the Medical Information Mart for Intensive Care (MIMIC) database. Kruskal-Wallis test, t-tests, and Pearson's chi-squared test were used to compare differences between groups. Propensity score matching and further nearest neighbor matching were used to construct a matched cohort. Cox proportional hazards regression analyses, logistic regression analyses, and the doubly robust estimation method were used to assess the relationship between insulin use and mortality. RESULTS: Nine hundred patients were enrolled in the final analysis. Insulin was associated with better outcomes in AP patients admitted to ICU, and could act as an independent predictor for 30-day mortality (HR = 0.36, 95% CI = 0.24-0.55). Subgroup analysis showed that AP patients with heart failure or without kidney disease or respiratory failure may not benefit from insulin treatment. CONCLUSIONS: Insulin treatment is independently associated with lower 30-day mortality in AP patients, except for those with heart failure or without kidney disease or respiratory failure.
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Insuficiência Cardíaca , Insulinas , Nefropatias , Pancreatite , Insuficiência Respiratória , Humanos , Pancreatite/tratamento farmacológico , Estudos Retrospectivos , Estudos de Coortes , Prognóstico , Estado Terminal/terapia , Doença Aguda , Insuficiência Cardíaca/complicações , Nefropatias/complicações , Unidades de Terapia IntensivaRESUMO
BACKGROUND: The relationship between surgical sperm retrieval of different etiologies and clinical pregnancy is unclear. We aimed to develop a robust and interpretable machine learning (ML) model for predicting clinical pregnancy using the SHapley Additive exPlanation (SHAP) association of surgical sperm retrieval from testes of different etiologies. METHODS: A total of 345 infertile couples who underwent intracytoplasmic sperm injection (ICSI) treatment with surgical sperm retrieval due to different etiologies from February 2020 to March 2023 at the reproductive center were retrospectively analyzed. The six machine learning (ML) models were used to predict the clinical pregnancy of ICSI. After evaluating the performance characteristics of the six ML models, the Extreme Gradient Boosting model (XGBoost) was selected as the best model, and SHAP was utilized to interpret the XGBoost model for predicting clinical pregnancies and to reveal the decision-making process of the model. RESULTS: Combining the area under the receiver operating characteristic curve (AUROC), accuracy, precision, recall, F1 score, brier score, and the area under the precision-recall (P-R) curve (AP), the XGBoost model has the best performance (AUROC: 0.858, 95% confidence interval (CI): 0.778-0.936, accuracy: 79.71%, brier score: 0.151). The global summary plot of SHAP values shows that the female age is the most important feature influencing the model output. The SHAP plot showed that younger age in females, bigger testicular volume (TV), non-tobacco use, higher anti-müllerian hormone (AMH), lower follicle-stimulating hormone (FSH) in females, lower FSH in males, the temporary ejaculatory disorders (TED) group, and not the non-obstructive azoospermia (NOA) group all resulted in an increased probability of clinical pregnancy. CONCLUSIONS: The XGBoost model predicts clinical pregnancies associated with testicular sperm retrieval of different etiologies with high accuracy, reliability, and robustness. It can provide clinical counseling decisions for patients with surgical sperm retrieval of various etiologies.
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Aprendizado de Máquina , Recuperação Espermática , Humanos , Estudos Retrospectivos , Feminino , Masculino , Gravidez , Adulto , Testículo , Infertilidade Masculina/etiologia , Injeções de Esperma Intracitoplásmicas , Taxa de GravidezRESUMO
A series of novel indole derivatives were synthesized and evaluated for their antiproliferative activity against three selected cancer cell lines (MGC803, EC-109 and PC-3). Among these analogues, 2-(5-methoxy-1H-indol-1-yl)-N-(4-methoxybenzyl)-N-(3,4,5-trimethoxyphenyl)acetamide (V7) showed the best inhibitory activity against MGC803 cells with an IC50 value of 1.59 µM. Cellular mechanisms elucidated that V7 inhibited colony formation, induced apoptosis and arrested cell cycle at G2/M phase. Importantly, indole analogue V7 inhibited NEDDylation pathway and MAPK pathway against MGC803 cells.
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Antineoplásicos/farmacologia , Indóis/química , Transdução de Sinais/efeitos dos fármacos , Antineoplásicos/química , Apoptose/efeitos dos fármacos , Linhagem Celular Tumoral , Proliferação de Células/efeitos dos fármacos , Dano ao DNA/efeitos dos fármacos , Desenho de Fármacos , Avaliação Pré-Clínica de Medicamentos , Pontos de Checagem da Fase G2 do Ciclo Celular/efeitos dos fármacos , Humanos , Indóis/farmacologia , Proteínas Quinases Ativadas por Mitógeno/metabolismo , Neoplasias Gástricas/metabolismo , Neoplasias Gástricas/patologia , Relação Estrutura-Atividade , Enzimas de Conjugação de Ubiquitina/metabolismoRESUMO
Chalcone is a common scaffold found in many biologically active compounds. The chalcone scaffold was also frequently utilized to design novel anticancer agents with potent biological efficacy. Aiming to continue the research of effective chalcone derivatives to treat cancers with potent anticancer activity, fourteen amino chalcone derivatives were designed and synthesized. The antiproliferative activity of amino chalcone derivatives was studied in vitro and 5-Fu as a control group. Some of the compounds showed moderate to good activity against three human cancer cells (MGC-803, HCT-116 and MCF-7 cells) and compound 13e displayed the best antiproliferative activity against MGC-803 cells, HCT-116 cells and MCF-7 cells with IC50 values of 1.52 µM (MGC-803), 1.83 µM (HCT-116) and 2.54 µM (MCF-7), respectively which was more potent than the positive control (5-Fu). Further mechanism studies were explored. The results of cell colony formatting assay suggested compound 10e inhibited the colony formation of MGC-803 cells. DAPI fluorescent staining and flow cytometry assay showed compound 13e induced MGC-803 cells apoptosis. Western blotting experiment indicated compound 13e induced cell apoptosis via the extrinsic/intrinsic apoptosis pathway in MGC-803 cells. Therefore, compound 13e might be a valuable lead compound as antiproliferative agents and amino chalcone derivatives worth further effort to improve amino chalcone derivatives' potency.
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Antineoplásicos/síntese química , Antineoplásicos/farmacologia , Chalcona/síntese química , Chalcona/farmacologia , Técnicas de Química Sintética , Apoptose/efeitos dos fármacos , Linhagem Celular Tumoral , Proliferação de Células/efeitos dos fármacos , Sobrevivência Celular/efeitos dos fármacos , Chalcona/análogos & derivados , Ensaios de Seleção de Medicamentos Antitumorais , Humanos , Concentração Inibidora 50 , Estrutura Molecular , Relação Estrutura-AtividadeRESUMO
Alzheimer's disease, one of the most common neurodegenerative diseases, is pathologically characterized by Amyloid beta containing plaques and neurofibrillary tangles. Amyloid beta (Aß) induces neuronal apoptosis through the intracellular Ca2+ increase, subsequent hyperactivation of cyclin-dependent kinase 5 (Cdk5) and mitochondrial abnormality. Recently, Cdk5 was identified as an upstream regulator of mitochondrial fission during neuronal apoptosis, but the underlying mechanism remains unclear. Here, in vitro phosphorylation assays showed that Cdk5 could phosphorylate the recombinant Drp1 at Serine 579. Aß1-42 stimulation increased the phosphorylation level of Drp1 at Serine 579 in mouse cortical neurons. Cdk5 inhibitor roscovitine and knockdown of Cdk5 by a lentiviral vector expressing shRNA targeting Cdk5 (Lenti-Cdk5-shRNA) efficiently prevented Aß1-42 induced Drp1 phosphorylation in neurons. In addition, Aß1-42 stimulation induced markedly mitochondrial fission in neurons. Roscovitine, Lenti-Cdk5-shRNA and expression of phospho-defect mutatant GFP-Drp1-S579A in neurons attenuated Aß1-42 induced mitochondrial fission, whereas expression of phospho-mimetic mutant GFP-Drp1-S579D alone resulted in mitochondiral fission similar to Aß1-42 stimulation. Moreover, Roscovitine and Lenti-Cdk5-shRNA suppressed the cleavage of caspase-3 and protected neurons against Aß1-42 induced neuronal apoptosis.Thus, our data indicate that Drp1 is a direct target of Cdk5, and Cdk5-mediated phosphorylation of Drp1 at Serine 579 regulates Aß1-42 induced mitochondrial fission and neuronal toxicity.
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Peptídeos beta-Amiloides/metabolismo , Apoptose , Quinase 5 Dependente de Ciclina/metabolismo , Dinaminas/metabolismo , Dinâmica Mitocondrial , Neurônios/metabolismo , Fragmentos de Peptídeos/metabolismo , Doença de Alzheimer/genética , Doença de Alzheimer/metabolismo , Doença de Alzheimer/patologia , Peptídeos beta-Amiloides/genética , Animais , Quinase 5 Dependente de Ciclina/genética , Dinaminas/genética , Humanos , Camundongos , Neurônios/patologia , Fragmentos de Peptídeos/genética , Fosforilação/genéticaRESUMO
OBJECTIVE: To investigate the levels of serum anti-Müllerian hormone (AMH) and inhibin B (INHB) in patients with unilateral cryptorchidism before and after orchidopexy. METHODS: This study included 58 cases of unilateral cryptorchidism treated by orchidopexy and 32 healthy controls. Before and at 6 months after surgery, we measured the length and circumference of the penis, the volume of the undescended testis, and levels of serum AMH and INHB. RESULTS: There were statistically significant differences between the unilateral cryptorchidism and healthy control groups in the levels of serum AMH (ï¼»102.80 ± 17.35 vs 108.76 ± 13.64ï¼½ ng/ml, P<0.05) and INHB (ï¼»70.24 ± 5.73ï¼½ vs ï¼» 77.72 ± 5.94ï¼½ pg/ml, P<0.05) at the baseline, but not at 6 months after orchidopexy (AMH: ï¼»109.76 ± 17.25ï¼½ vs ï¼»108.03 ± 14.13ï¼½ ng/ml, P>0.05; INHB: ï¼»75.76 ± 5.94ï¼½ vs ï¼»77.63 ± 5.99ï¼½ pg/ml, P>0.05). No remarkable differences were observed between the unilateral cryptorchidism and healthy control groups in the preoperative penile length (ï¼»2.05 ± 0.23ï¼½ vs ï¼»2.11 ± 0.22ï¼½ cm, P>0.05), penile circumference (ï¼»3.91 ± 0.23ï¼½ vs ï¼»3.99 ± 0.20ï¼½ cm, P>0.05) and volume of the undescended testis (ï¼»0.45 ± 0.02ï¼½ vs ï¼»0.46 ± 0.02ï¼½ ml, P>0.05), or in the postoperative penile length (ï¼»2.09 ± 0.23ï¼½ vs ï¼»2.16 ± 0.22ï¼½ cm, P>0.05), penile circumference (ï¼»4.00 ± 0.25ï¼½ vs ï¼»3.98 ± 0.19ï¼½ cm, P>0.05) and volume of the undescended testis (ï¼»0.45 ± 0.02ï¼½ vs ï¼»0.45 ± 0.02ï¼½ ml, P>0.05). Compared with the baseline, the cryptorchidism patients showed markedly increased levels of serum AMH (ï¼»102.80 ± 17.35ï¼½ vs ï¼»109.76 ± 17.25ï¼½ ng/ml, P<0.05) and INHB (ï¼»70.24 ± 5.73ï¼½ vs ï¼»75.76 ± 5.94ï¼½ pg/ml, P<0.05) after orchidopexy. CONCLUSIONS: Orchidopexy can elevate the levels of serum AMH and INHB and protect the testicular function of cryptorchidism patients.
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Hormônio Antimülleriano/sangue , Criptorquidismo/sangue , Criptorquidismo/cirurgia , Inibinas/sangue , Orquidopexia , Estudos de Casos e Controles , Criptorquidismo/patologia , Humanos , Masculino , Tamanho do Órgão , Pênis/anatomia & histologia , Período Pós-Operatório , Período Pré-OperatórioRESUMO
OBJECTIVE: To investigate the influence of different procedures of testicular sperm retrieval on the levels of serum inhibin B (INHB), antisperm antibodies (AsAb), follicle-stimulating hormone (FSH), and testosterone (T) in patients with azoospermia. METHODS: We randomly assigned 210 azoospermia patients to receive testicular sperm extraction (TESE, n = 50), testicular sperm aspiration (TESA, n = 56), testicular fine needle aspiration (TEFNA, n = 64), or microscopic TESE (micro-TESE, n = 40). We measured the levels of serum INHB, FSH, and T and the positive rate of AsAb before and at 1 and 3 months after surgery. RESULTS: Compared with the baseline, the levels of serum FSH at 1 and 3 months after surgery showed no statistically significant differences in the TESE (ï¼»8.51 ± 4.34ï¼½ vs ï¼»8.76 ± 3.07ï¼½ and ï¼»7.24 ± 3.32ï¼½ IU/L, P >0.05), TESA (ï¼»7.70 ± 2.72ï¼½ vs ï¼»7.90 ± 4.57ï¼½ and ï¼»8.04 ± 3.65ï¼½ IU/L, P >0.05), TEFNA (ï¼»6.04 ± 3.17ï¼½ vs ï¼»6.08 ± 2.70ï¼½ and ï¼»6.10 ± 3.32ï¼½ IU/L, P >0.05), or micro-TESE group (ï¼»6.59 ± 2.74ï¼½ vs ï¼»6.89 ± 1.78ï¼½ and ï¼»6.75 ± 2.57ï¼½ IU/L, P >0.05); the positive rate of AsAb (IgM) was significantly increased at 1 month in the TESE (0.00 vs 14.00%, P <0.05) and micro-TESE groups (2.50% vs 15.00%, P <0.05), while the serum T level markedly decreased in the two groups (ï¼»16.52 ± 6.25ï¼½ vs ï¼»9.25 ± 5.76ï¼½ nmol/L and ï¼»14.16 ± 5.45ï¼½ vs ï¼»8.23 ± 4.12ï¼½ nmol/L, P <0.05); the levels of serum INHB were remarkably reduced at 1 and 3 months in the TESE (ï¼»70.56 ± 23.17ï¼½ vs ï¼»42.63 ± 15.34ï¼½ and ï¼»44.05 ± 18.47ï¼½ pg/ml, P <0.05), TESA (ï¼»68.71 ± 14.74ï¼½ vs ï¼»40.55 ± 20.51ï¼½ and ï¼»42.11 ± 19.34ï¼½ pg/ml, P <0.05), TEFNA (ï¼»76.81 ± 27.04ï¼½ vs ï¼»46.31 ± 19.28ï¼½ and ï¼»48.32 ± 20.54ï¼½ pg/ml, P <0.05), and micro-TESE groups (ï¼»74.74 ± 28.35ï¼½ vs ï¼»45.27 ± 18.83ï¼½ and ï¼»47.64 ± 28.34ï¼½ pg/ml, P <0.05), but with no statistically significant differences among the four groups (P >0.05). CONCLUSIONS: Different procedures of testicular sperm retrieval have different impacts on the testicular function and AsAb in patients with azoospermia.
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Azoospermia/sangue , Azoospermia/fisiopatologia , Recuperação Espermática , Espermatozoides/imunologia , Testículo/fisiopatologia , Anticorpos/sangue , Hormônio Foliculoestimulante/sangue , Humanos , Inibinas/sangue , Masculino , Testículo/metabolismo , Testosterona/sangueRESUMO
OBJECTIVE: To investigate the influence of unilateral cryptorchidism on the levels of serum anti-müllerian hormone (AMH) and inhibin B in children. METHODS: We enrolled 65 patients with unilateral cryptorchidism and 45 healthy children in this study. We measured the length and circumference of the penis, the testis volume in the cryptorchidism side, and the levels of serum AMH and inhibin B at the age of 6 and 12 months, respectively. RESULTS: Compared with the healthy controls, the patients with unilateral cryptorchidism showed significant decreases at 12 months in serum AMH (ï¼»108.06±12.40ï¼½ vs ï¼»103.26±17.57ï¼½ ng/ml, P<0.05) and inhibin B (ï¼»77.43±5.66ï¼½ vs ï¼»70.21±5.69ï¼½ pg/ml, P<0.05). No statistically significant differences were found in the length and circumference of the penis and the testis volume in the cryptorchidism side at 6 and 12 months (P>0.05), or in the levels of serum AMH and inhibin B at 6 months (P>0.05). CONCLUSIONS: Unilateral cryptorchidism affects the gonadal function of the patient, and orchiopexy should be timely performed in order to reduce its impact.
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Hormônio Antimülleriano/sangue , Criptorquidismo/sangue , Criptorquidismo/patologia , Inibinas/sangue , Estudos de Casos e Controles , Humanos , Lactente , Masculino , Orquidopexia , Tamanho do Órgão , Pênis/patologia , Testículo/patologia , Testículo/fisiopatologia , Fator de Crescimento Transformador betaRESUMO
From the same piece of graphene sheet, (3, 3) and (6, 0) carbon nanotube clips were obtained on the basis of the different manners of rolling. The nature of the electronic state varies differently with different manners of rolling and is significantly affected by zigzag edges. The intermediate structures formed during the rolling process were functionalized with fluorine and oxygen atoms to investigate the electronic states and nonlinear optical (NLO) responses. Passivation of the intermediate structures with fluorine neither changes the nature of electronic states and nor improves the NLO responses. In constrast, passivation with oxygen enhances the NLO properties and changes the electronic states of the structures upon passivating at the open zigzag edges.
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BACKGROUND/OBJECTIVES: Lysosomal/autophagic pathway plays important role in the early onset of acute pancreatitis (AP). However, its role in the later recovery phase of AP is unknown. This study aims to investigate the role of lysosomal/autophagic pathway in the self-limited program of AP and elucidate the underlying mechanisms. METHODS: AP was induced in the rat by 3% sodium taurocholate injection in the pancreaticobiliary duct. Serum amylase activity assay, histological examination, and cell death detection were used to assess the time course of AP severity. Meanwhile, the expression of LC3-II, p62 and Lamp-2 was measured to evaluate the status of autophagic flux. S6RP phosphorylation was detected to determine the time course of mTOR activation. Rapamycin was administered to block mTOR activity. RESULTS: AP developed in the rats to the most severe at 24 h but tended to self-restore at 36 and 48 h. The impairment of autophagic flux characterized by the accumulation of LC3-II and p62 and the depletion of Lamp-2 occurred at 24 h after AP induction followed by the restoration over the following 24 h. Furthermore, the phosphorylation of S6RP was increased at 36 and 48 h after AP induction despite the initial inhibition. Rapamycin treatment reduced the level of phospho-S6RP and inhibited the restoration of autophagic homeostasis and pancreatic tissue injury. CONCLUSIONS: Activation of mTOR is correlated with the improvement of autophagic flux and pancreatic injury, suggesting that mTOR activation plays a potential protective role in the later recovery of AP.
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Autofagia , Pancreatite/fisiopatologia , Serina-Treonina Quinases TOR/metabolismo , Doença Aguda , Animais , Biomarcadores/metabolismo , Western Blotting , Progressão da Doença , Marcação In Situ das Extremidades Cortadas , Lisossomos/fisiologia , Masculino , Pancreatite/metabolismo , Ratos , Ratos Sprague-DawleyRESUMO
A series of spiral donor-π-acceptor frameworks (i.e. 2-2, 3-3, 4-4, and 5-5) based on 4-nitrophenyldiphenylamine with π-conjugated linear acenes (naphthalenes, anthracenes, tetracenes, and pentacenes) serving as the electron donor and nitro (NO2 ) groups serving as the electron acceptor were designed to investigate the relationships between the nonlinear optical (NLO) responses and the spirality in the frameworks. A parameter denoted as D was defined to describe the extent of the spiral framework. The D value reached its maximum if the number of NO2 groups was equal to the number of fused benzene rings contained in the linear acene. A longer 4-nitrophenyldiphenylamine chain led to a larger D value and, further, to a larger first hyperpolarizability. Different from traditional NLO materials with charge transfer occurring in the one-dimensional direction, charge transfer in 2-2, 3-3, 4-4, and 5-5 occur in three-dimensional directions due to the attractive spiral frameworks, and this is of great importance in the design of NLO materials. The origin of such an enhancement in the NLO properties of these spiral frameworks was explained with the aid of molecular orbital analysis.
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Difenilamina/química , Antracenos/química , Elétrons , Naftalenos/química , Teoria Quântica , Relação Estrutura-AtividadeRESUMO
OBJECTIVE: To investigate the impact of chronic prostatitis/chronic pelvic pain syndrome (CP/CPPS) on sperm DNA fragmentation and nucleoprotein transition. METHODS: Based on the recommended methods in the WHO Laboratory Manual for the Examination and Processing of Human Semen (5th ed), we conducted routine semen analysis for 65 CP/CPPS patients and 30 healthy men. We also analyzed the results of papanicolaou staining, sperm DNA fragmentation and sperm nucleoprotein transition. RESULTS: Compared with the healthy control males, the CP/CPPS patients showed significant decreases in sperm concentration ([134.05 +/- 99.80] vs [94.75 +/- 92.07]) x 10(6)/ml, P <0.05), the percentage of morphologically normal sperm ([7.26 +/- 2.28] vs [5.61 +/- 3.40]%, P <0.05) and sperm progressive motility ([59.18 +/- 16.06] vs [47.68 +/- 17.62]%, P<0.05), but dramatic increases in sperm DNA fragmentation ([22.92 +/- 11.51] vs [43.58 +/- 17.07%, P<0.01) and sperm nucleoprotein transition ([23.26 +/- 5.97] vs [32.14 +/- 8.79]%, P<0.01). CONCLUSION: CP/CPPS significantly reduces sperm quality and male fertility.
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Fragmentação do DNA , Nucleoproteínas/genética , Prostatite/genética , Adulto , Estudos de Casos e Controles , Humanos , Masculino , Análise do Sêmen , Contagem de Espermatozoides , Motilidade dos Espermatozoides , Adulto JovemRESUMO
BACKGROUND: Acute skeletal muscle injuries are common physical or sports traumas. Cellular therapy has excellent potential for regeneration after skeletal muscle injury. Adipose-derived stem cells (ADSCs) are a more accessible type of stem cell. However, it has a low survival rate and differentiation efficiency in the oxidative stress-rich microenvironment after transplantation. Although molecular hydrogen (H2) possesses anti-inflammatory and antioxidant biological properties, its utility in mitochondrial and stem cell research has not been adequately explored. OBJECTIVE: This study aimed to reveal the role of H2 on adipose-derived stem cells' myogenic differentiation. METHODS: The protective effects of H2 in ADSCs were evaluated by MTT assay, live-dead cell staining, western blot analysis, immunofluorescence staining, confocal imaging, and transmission electron microscopy. RESULTS: An appropriate volume fraction of H2 significantly decreased mitochondrial reactive oxygen species (ROS) levels, increased the number of mitochondria, and promoted mitophagy, thus enhancing the survival and myogenic differentiation of ADSCs. CONCLUSION: This study reveals the application potential of H2 in skeletal muscle diseases or other pathologies related to mitochondrial dysfunction.
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Tecido Adiposo , Peróxido de Hidrogênio , Humanos , Peróxido de Hidrogênio/metabolismo , Peróxido de Hidrogênio/farmacologia , Células-Tronco , Diferenciação Celular/fisiologia , Hidrogênio/farmacologia , Hidrogênio/metabolismo , MitocôndriasRESUMO
Background: Volumetric Muscle Loss (VML) denotes the traumatic loss of skeletal muscle, a condition that can result in chronic functional impairment and even disability. While the body can naturally repair injured skeletal muscle within a limited scope, patients experiencing local and severe muscle loss due to VML surpass the compensatory capacity of the muscle itself. Currently, clinical treatments for VML are constrained and demonstrate minimal efficacy. Selenium, a recognized antioxidant, plays a crucial role in regulating cell differentiation, anti-inflammatory responses, and various other physiological functions. Methods: We engineered a porous Se@SiO2 nanocomposite (SeNPs) with the purpose of releasing selenium continuously and gradually. This nanocomposite was subsequently combined with a decellularized extracellular matrix (dECM) to explore their collaborative protective and stimulatory effects on the myogenic differentiation of adipose-derived mesenchymal stem cells (ADSCs). The influence of dECM and NPs on the myogenic level, reactive oxygen species (ROS) production, and mitochondrial respiratory chain (MRC) activity of ADSCs was evaluated using Western Blot, ELISA, and Immunofluorescence assay. Results: Our findings demonstrate that the concurrent application of SeNPs and dECM effectively mitigates the apoptosis and intracellular ROS levels in ADSCs. Furthermore, the combination of dECM with SeNPs significantly upregulated the expression of key myogenic markers, including MYOD, MYOG, Desmin, and myosin heavy chain in ADSCs. Notably, this combination also led to an increase in both the number of mitochondria and the respiratory chain activity in ADSCs. Conclusion: The concurrent application of SeNPs and dECM effectively diminishes ROS production, boosts mitochondrial function, and stimulates the myogenic differentiation of ADSCs. This study lays the groundwork for future treatments of VML utilizing the combination of SeNPs and dECM.
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Células-Tronco Mesenquimais , Nanocompostos , Selênio , Humanos , Dióxido de Silício , Espécies Reativas de Oxigênio/metabolismo , Selênio/farmacologia , Porosidade , Músculo Esquelético , Diferenciação CelularRESUMO
BACKGROUND: Esophageal cancer is a common malignant tumor of digestive tract with esophageal squamous cell carcinoma (ESCC) being the main histological subtype. This study aimed to identify potential hub gene associated with the pathophysiology of ESCC through bioinformatics analysis and experiment validation. METHODS: Three microarray datasets were obtained from the Gene Expression Omnibus (GEO) database. The overlapping differentially expressed genes (DEGs) were analyzed by GEO2R tool. Gene Ontology (GO) and Kyoto Encyclopedia of Genes (KEGG) pathway analyses were performed to predict the potential functions of DEGs. Nine hub genes were identified using protein-protein interaction (PPI) network and Cytoscape software. We selected RAD51-associated protein 1 (RAD51AP1) for further research because of its poor prognosis and it has not been sufficiently studied in ESCC. The effects of RAD51AP1 on proliferation, apoptosis, migration and invasion of ESCC cells were determined by in vitro functional assays. RESULTS: RAD51AP1 expression was significantly upregulated in ESCC tissues compared with normal tissues by using The Cancer Genome Atlas (TCGA) database. High expression of RAD51AP1 was associated with worse survival in ESCC patients. RAD51AP1 expression was positively associated with the enrichment of Th2 cells and T helper cells. Furthermore, CCK-8 and colony formation assays showed knockdown of RAD51AP1 inhibited the proliferation of ESCC cells. Flow cytometry analysis indicated knockdown of RAD51AP1 induced cell cycle arrest and apoptosis in ESCC cells. Transwell assay revealed knockdown of RAD51AP1 suppressed the migration and invasion of ESCC cells. CONCLUSIONS: Finally, our results demonstrated that RAD51AP1 silencing significantly inhibited cell proliferation and invasion in ESCC, thereby highlighting its potential as a novel target for ESCC treatment.
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Background: Acute skeletal muscle injuries are common among physical or sports traumas. The excessive oxidative stress at the site of injury impairs muscle regeneration. The authors have recently developed porous Se@SiO2 nanoparticles (NPs) with antioxidant properties. Methods: The protective effects were evaluated by cell proliferation, myogenic differentiation and mitochondrial activity. Then, the therapeutic effect was investigated in a cardiotoxin-induced muscle injury rat model. Results: Porous Se@SiO2 NPs significantly protected the morphological and functional stability of mitochondria, thus protecting satellite cells from H2O2-induced damage to cell proliferation and myogenic differentiation. In the rat model, intervention with porous Se@SiO2 NPs promoted muscle regeneration. Conclusion: This study reveals the application potential of porous Se@SiO2 NPs in skeletal muscle diseases related to mitochondrial dysfunction.
Muscle injuries are very common in daily life and in sports. When a muscle is injured, the local response inhibits the regeneration and differentiation of stem cells inside the muscle, thus hindering muscle regeneration. The authors have recently developed a nanoparticle with the ability to protect muscle stem cell function, promote stem cell proliferation and differentiation and facilitate muscle regeneration after skeletal muscle injury in rats. Thus, this study reveals the potential of porous Se@SiO2 nanoparticles in skeletal muscle diseases associated with mitochondrial dysfunction.
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Nanopartículas , Dióxido de Silício , Ratos , Animais , Dióxido de Silício/farmacologia , Porosidade , Peróxido de Hidrogênio/metabolismo , Estresse Oxidativo , Mitocôndrias/metabolismo , Regeneração/fisiologia , Músculos , Músculo Esquelético/lesões , Músculo Esquelético/fisiologiaRESUMO
On the basis of the famous staggered biphenalenyl diradical π dimer 1, the eclipsed biphenalenyl (1a), with no centrosymmetry, was obtained by rotating a layer of 1 by 60° around its central axis. Furthermore, the central carbon atoms of 1 and 1a were substituted by boron and nitrogen atoms to form 2 and 2a with a novel 2e-12c bond. We found that the novel 2e-12c bond is formed by the electron pair of the occupied orbital of the phenalenyl monomer substituted by the nitrogen atom and the unoccupied orbital of the phenalenyl monomer substituted by the boron atom. As a result of the novel 2e-12c bond, 2 and 2a exhibit a fascinating interlayer charge-transfer transition character, which results in a significant difference in the dipole moments (Δµ) between the ground state and the crucial excited state. The values of Δµ for 2 and 2a are 6.4315 and 6.9253 Debye, clearly larger than the values of 0 and 0.0015 Debye for 1 and 1a. Significantly, the boron/nitrogen substitution effect can greatly enhance the first hyperpolarizabilities (ß(0) ) of 2 and 2a with a novel 2e-12c bond compared with 1 and 1a with a traditional 2e-12c bond: 0 and 19 a.u. for 1 and 1a are much lower than 3516 and 12272 a.u. for 2 and 2a. Furthermore, the interaction energies (E(int) )of 2 and 2a are larger than those of 1 and 1a, which could be considered as a signature of reliability for the newly designed dimers. Our present work will be beneficial for further theoretical and experimental studies on the properties of molecules with the novel 2e-12c bond.
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On the basis of the n-acenes (n = 1, 2, 3 and 4), the α-Li@n-acenes and ß-Li@n-acenes salts were selected to investigate how increasing the number n of conjugated benzenoid rings affects the linear and nonlinear optical responses. The α-Li@n-acenes and ß-Li@n-acenes salts are obtained by a lithium atom substituting the α-H and ß-H, respectively. In the present work, both ab initio (HF and MP2) and DFT (B3LYP, BhandHLYP, M05-2X, and CAM-B3LYP) methods are adopted to calculate the polarizability (α(0)) and first hyperpolarizability (ß(tot)) of the α-Li@n-acenes and ß-Li@n-acenes salts. MP2 results show that the α(0) values of both classes of lithium salts increase with increasing number n of conjugated benzenoid rings. Interestingly, we found that the ß(tot) values of α-Li@n-acenes and ß-Li@n-acenes salts take on opposite trends: the ß(tot) values of α-Li@n-acenes are decreasing slowly (2187 for α-Li@benzene > 1978 for α-Li@naphthalene > 1898 for α-Li@anthrecene > 1830 au for α-Li@tetracene) and inceasing remarkably (2738 for ß-Li@naphthalene < 3186 for ß-Li@anthrecene < 3314 au for ß-Li@tetracene) for ß-Li@n-acenes. Furthermore, we found that the ß(tot) values (2738-3314 au) of the ß-Li@n-acenes are larger than those of the α-Li@n-acenes (1830-2187 au). On the other hand, comparing the results of different methods, the ß(tot) values obtained by the M05-2X and CAM-B3LYP methods reproduce the polarizability and first hyperpolarizability of the α-Li@n-acenes and ß-Li@n-acenes salts well, which test and verify the results of the MP2 method. Our present work may be beneficial to development of high-performance organic NLO optical materials.
RESUMO
Phosphodiesterase type 5 (PDE5) inhibitors are used most commonly in the treatment of penile erectile dysfunction (ED). Recent studies show that PDE5 inhibitors are ideal drugs for treating ischemia-reperfusion injury. This review focuses on the results of basic and clinical researches on PDE5 inhibitors for the treatment of ischemia-reperfusion injury and provides some theoretical evidence for clinical options of the drugs.
Assuntos
Disfunção Erétil/tratamento farmacológico , Inibidores da Fosfodiesterase 5/uso terapêutico , Inibidores de Fosfodiesterase/uso terapêutico , Traumatismo por Reperfusão/tratamento farmacológico , Humanos , MasculinoRESUMO
OBJECTIVE: To investigate the effect of high ligation of the spermatic vein (HLSV) on DNA fragmentation in varicocele (VC) patients. METHODS: Thirty-four VC patients underwent HLSV. Sperm motion indexes and the results of papanicolaou staining and DNA fragmentation detection were analyzed before and 3 months after the operation according to the WHO guidelines. RESULTS: Compared with pre-operation, HLSV achieved a significant increase in the percentage of morphologically normal sperm (P < 0.01), and remarkable decreases in DNA fragmentation, sperm deformity index (SDI) and multiple anomalies index (MAI) (P < 0.01). The patients also showed significant increases in sperm concentration and the percentages of grade b sperm (P < 0.05) and grade a and a + b sperm (P < 0.01) after the operation. The post-operative percentages of sperm DNA fragmentation in those with grades I - III VC were markedly lower (P < 0.01), but showed no significant difference from that in those with subclinical VC (P > 0.05). The percentage of big-halo sperm was significantly increased (P < 0.01), while those of the medium-, small- and non-halo sperm remarkably decreased (P < 0.01) after HLSV. CONCLUSION: HLSV can effectively improve the sperm quality of VC patients.