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Failed skin wound healing, through delayed wound healing or wound dehiscence, is a global public health issue that imposes significant burdens on individuals and society. Although the application of growth factor is an effective method to improve the pace and quality of wound healing, the clinically approved factors are limited. Parathyroid hormone (PTH) demonstrates promising results in wound healing by promoting collagen deposition and cell migration, but its application is limited by potentially inhibitory effects when administered continuously and locally. Through partially replacing and repeating the amino acid domains of PTH(1-34), we previously designed a novel PTH analog, PTH(3-34)(29-34) or MY-1, and found that it avoided the inhibitory effects of PTH while retaining its positive functions. To evaluate its role in wound healing, MY-1 was encapsulated in liposomes and incorporated into the methacryloyl gelatin (GelMA) hydrogel, through which an injectable nanocomposite hydrogel (GelMA-MY@Lipo, or GML) was developed. In vitro studies revealed that the GML had similar properties in terms of the appearance, microstructure, functional groups, swelling, and degradation capacities as the GelMA hydrogel. In vitro drug release testing showed a relatively more sustainable release of MY-1, which was still detectable in vivo 9 days post-application. When the GML was topically applied to the wound areas of rat models, wound closure as well as tensile strength were improved. Further studies showed that the effects of GML on wound repair and tensile strength were closely related to the promotion of fibroblast migration to the wound area through the controlled release of MY-1. Mechanically, MY-1 enhanced fibroblast migration by activating PI3K/AKT signaling and its downstream molecule, Rac1, by which it increased fibroblast aggregation in the early stage and resulting in denser collagen deposition at a later time. Overall, these findings demonstrated that the nanocomposite hydrogel system promoted skin wound healing and increased tensile strength, thus offering new potential in the treatment of wound healing.
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Movimento Celular , Fibroblastos , Hidrogéis , Lipossomos , Fosfatidilinositol 3-Quinases , Proteínas Proto-Oncogênicas c-akt , Transdução de Sinais , Resistência à Tração , Cicatrização , Cicatrização/efeitos dos fármacos , Animais , Lipossomos/química , Fibroblastos/efeitos dos fármacos , Fibroblastos/metabolismo , Movimento Celular/efeitos dos fármacos , Hidrogéis/química , Proteínas Proto-Oncogênicas c-akt/metabolismo , Transdução de Sinais/efeitos dos fármacos , Ratos , Fosfatidilinositol 3-Quinases/metabolismo , Proteínas rac1 de Ligação ao GTP/metabolismo , Ratos Sprague-Dawley , Masculino , Camundongos , Gelatina/química , Pele/efeitos dos fármacos , Pele/metabolismoRESUMO
Ginsenoside Rb1, known as gypenoside III, exerts antidepressant-like effects in previous studies. It has also been indicated that ginsenoside Rb1 regulated neuroinflammation via inhibiting NF-κB signaling. According to the evidence that astrocytes can regulate microglia and neuroinflammation by secreting complement C3, the present study aimed to demonstrate the molecular mechanisms underlying ginsenoside Rb1-induced antidepressant-like effects from the astrocytic and microglial complement C3 pathway. The complement C3 mediated mechanism of ginsenoside Rb1 was investigated in mice exposed to chronic restraint stress (CRS). The results showed that ginsenoside Rb1 reversed the depressive-like behaviors in CRS. Treatment with ginsenoside Rb1 reduced both the number of astrocytes and microglia. In addition, ginsenoside Rb1 suppressed TLR4/NF-κB/C3 signaling in the astrocytes of the hippocampus. Furthermore, ginsenoside Rb1 attenuated the contents of synaptic protein including synaptophysin and PSD95 in microglia, suggesting the inhibition of microglia-mediated synaptic elimination caused by CRS. Importantly, ginsenoside Rb1 also maintained the dendritic spines in mice. In conclusion, our results demonstrate that ginsenoside Rb1 produces the antidepressant-like effects by inhibiting astrocyte TLR4/NF-κB/C3 signaling to covert microglia from a pro-inflammatory phenotype (amoeboid) towards an anti-inflammatory phenotype (ramified), which inhibit the synaptic pruning in the hippocampus.
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BACKGROUND: Re-epithelialization is important in the process of wound healing. Various methods have been identified to expedite the process, but their clinical application remains limited. While parathyroid hormone (PTH) has shown promising results in wound healing due to its role in promoting collagen deposition and cell migration, application is limited by its potentially inhibitive effects when being continuously and locally administrated. Herein, we developed a novel PTH analog, Human parathyroid hormone (hPTH) (3-34/29-34) (henceforth MY-1), by partially replacing and repeating the amino acid sequences of hPTH (1-34), and evaluated its effect on skin wound re-epithelialization. METHODS: CCK-8, colony formation unit assay, and Ki67 immunofluorescent staining were performed to evaluate the effect of MY-1 on HaCaT cell proliferation. Then, wound scratch assay, Transwell assay and lamellipodia staining were carried out to evaluate the effect of MY-1 on cell migration. Moreover, the epithelial-mesenchymal transition (EMT) markers were measured using qPCR and western blot analysis. For in-vivo drug delivery, gelatin methacryloyl (GelMA) hydrogel was employed to load the MY-1, with the physicochemical characteristics evaluated prior to its application in wound models. Then, MY-1's role in wound healing was determined via acute skin wound models. Finally, the mechanism that MY-1 activated was also detected on HaCaT cells and in-vivo wound models. RESULTS: In-vitro, MY-1 accelerated the migration and EMT of HaCaT cells, while having little effect on cell proliferation. GelMA and MY-1-incorporated GelMA hydrogels showed similar physicochemical characteristics and were used in the in-vivo studies, where the results revealed that MY-1 led to a stronger re-epithelialization by inducing basal keratinocyte migration and EMT. Further studies on in-vivo wound models and in-vitro HaCaT cells revealed that MY-1 regulated cell migration and EMT through activating PI3K/AKT signaling. The parathyroid hormone type 1 receptor (PTHR1), the main receptor of PTH, was found to be the upstream of PI3K/AKT signaling, through interfering PTHR1 expression with a small interference RNA following detection of the PI3K/AKT activation. CONCLUSION: Collectively, our study demonstrated that MY-1 accelerates skin wound re-epithelialization by inducing keratinocyte migration and EMT via PTHR1-PI3K/AKT axis activation. Video Abstract.
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Fosfatidilinositol 3-Quinases , Reepitelização , Humanos , Proteínas Proto-Oncogênicas c-akt , Transição Epitelial-Mesenquimal , Movimento Celular , Células HaCaTRESUMO
OBJECTIVE: To investigate the correlation of frailty with ED in Chinese elderly men. METHODS: This community-based study was conducted with a sample of 258 Chinese men aged 60 to 83 years old in Fuyang City, Anhui Province. All the participants completed a standard questionnaire on demographics, lifestyle, underlying diseases and medical and sexual histories. They also scored on the Chinese version of Tilburg Frailty Indicator (TFI) and International Index of Erectile Function-5 (IIEF-5). RESULTS: The incidence rates of ED and frailty in the elderly men were 85.27% and 75.58%, respectively. The ED patients, compared with the non-ED males, had a significantly older age (ï¼»71.25 ± 5.83ï¼½ vs ï¼»66.92 ± 5.44ï¼½ yr, P < 0.01) and higher body mass index (ï¼»24.37 ± 3.31ï¼½ vs ï¼»23.35 ± 2.97ï¼½ kg/m 2, P < 0.05), incidence of diabetes mellitus (38.0% vs 19.2%, P < 0.05) and TFI scores (8.61 ± 4.29 vs 5.95 ± 4.36, P < 0.05), but lower education and frequency of irregular intercourse (less than once a week) (all P<0.05). Multivariate analysis indicated that diabetes (ORï¼3.292ï¼95% CIï¼1.236ï¼8.768), irregular intercourse (ORï¼2.425ï¼95% CIï¼1.114ï¼5.279), and scores of frailty (ORï¼4.502ï¼95% CIï¼1.905ï¼10.640) were regarded as independent risk factors for ED (all P < 0.05). CONCLUSION: There is a strong correlation between ED and frailty in elderly men. Sexual health care for elderly ED patients should be more focused on the multidimensional assessment and treatment of senile frailty.
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Diabetes Mellitus , Disfunção Erétil , Fragilidade , Idoso , Masculino , Humanos , Pessoa de Meia-Idade , Idoso de 80 Anos ou mais , Disfunção Erétil/epidemiologia , Disfunção Erétil/etiologia , Fragilidade/epidemiologia , Fragilidade/complicações , Envelhecimento , Comportamento Sexual , Inquéritos e QuestionáriosRESUMO
Cisplatin, a commonly used chemotherapy drug, can increase the survival rate of cancer patients. However, it often causes various side effects, including neuronal deficit-induced cognitive impairment. Considering that curcumin is effective in neuronal protection, the action of curcumin on cognitive improvement was evaluated in cisplatin-treated C57BL/6 mice in the present study. Our results first showed that curcumin restored impaired cognitive behaviors. Consistent with this, neurogenesis and synaptogenesis were improved by curcumin. In addition, cisplatin-induced dysfunction of apoptosis-related proteins was partly reversed by curcumin. Moreover, cisplatin-induced autophagy was enhanced by curcumin. Our results also indicated that cisplatin induced autophagy through the endoplasmic reticulum (ER) stress-mediated ATF4-Akt-mTOR signaling pathway. Curcumin activated AMPK-JNK signaling, which mediated both mTOR inhibition and Bcl-2 upregulation and in turn enhanced autophagy and suppressed apoptosis, respectively. In contrast, pretreatment with the autophagy inhibitor 3-methyladenine (3-MA) completely abolished the effects of curcumin on cognitive improvement and improved neurogenesis, synaptogenesis and autophagy. Our results show that cognitive improvement induced by curcumin during chemotherapy is mediated by the enhancement of hippocampal autophagy.
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Anti-Inflamatórios não Esteroides/uso terapêutico , Antineoplásicos/toxicidade , Autofagia/efeitos dos fármacos , Disfunção Cognitiva/induzido quimicamente , Disfunção Cognitiva/tratamento farmacológico , Curcumina/uso terapêutico , Animais , Anti-Inflamatórios não Esteroides/farmacologia , Autofagia/fisiologia , Cisplatino/toxicidade , Disfunção Cognitiva/patologia , Curcumina/farmacologia , Hipocampo/efeitos dos fármacos , Hipocampo/patologia , Masculino , Aprendizagem em Labirinto/efeitos dos fármacos , Aprendizagem em Labirinto/fisiologia , Camundongos , Camundongos Endogâmicos C57BL , Distribuição AleatóriaRESUMO
OBJECTIVE: To compare two ELISA methods for the detection of the prostatic exosomal protein (PSEP) in the urine. METHODS: Using the double-antibody sandwich (DAS) method and the indirect method of ELISA, we detected PSEP in the urine samples from 100 IIIA chronic prostatitis (CP) patients and another 100 normal healthy males. Meanwhile, we examined 30 clinical urine samples using the diluent (0.1 mol/L PBS buffer) and the urine matrix standard curves to verify the consistency of the standard diluent with the sample collected. Result: The sensitivities of DAS and indirect ELISA were 89% versus 87% and their specificities 91% versus 90%, with total consistency rates of 90% versus 88.5%, with no statistically significant difference in between. The scatter plot for the results of the PBS diluent and the urine matrix standard curves showed a good linearity (R2 = 0.999). No significant difference was found in the results of detection of the clinical urine samples in different matrices. CONCLUSIONS: Considering the characteristics of PSEP, the indirect ELISA method is more practical and feasible for the clinical detection of PSEP in the urine samples of prostatitis patients.
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Ensaio de Imunoadsorção Enzimática/métodos , Exossomos , Prostatite , Proteinúria/diagnóstico , Doença Crônica , Humanos , Masculino , Prostatite/diagnóstico , Proteínas/análiseRESUMO
OBJECTIVE: To investigate the clinical value of the prostate small extracorporeal protein (PSEP) level in the urine in evaluating the therapeutic effect on chronic prostatitis (CP). METHODS: Totally 188 CP patients were treated with minocycline and Ningmitai Capsules in our hospital and regularly returned for follow-up examination from November 2017 to November 2018. Based on the results of treatment after 4 and 8 weeks of medication, we divided the patients into a cured, an effective and an ineffective group and compared the contents of PSEP in the urine samples of the three groups of patients before and after treatment. RESULTS: Compared with the baseline, the PSEP content in the urine after 4 weeks of medication was decreased in the cured group (n = 20) (ï¼»3.63 ± 3.81ï¼½ vs ï¼»1.16 ± 0.41ï¼½ ng/ml, P < 0.05), effective group (n = 85) (ï¼»4.13 ± 4.05ï¼½ vs ï¼»2.97 ± 2.89ï¼½ ng/ml, P > 0.05) and ineffective group (n = 83) (ï¼»4.72 ± 2.98ï¼½ vs ï¼»3.74 ± 1.31ï¼½ ng/ml, P > 0.05), and so was that after 8 weeks of treatment in the cured group (n = 48) (ï¼»3.72 ± 3.51ï¼½ vs ï¼»0.89 ± 0.37ï¼½ ng/ml, P < 0.05), effective group (n = 106) (ï¼»4.37 ± 3.93ï¼½ vs ï¼»1.83 ± 0.71ï¼½ ng/ml, P < 0.05) and ineffective group (n = 34) (ï¼»4.61 ± 3.59ï¼½ vs ï¼»3.58 ± 1.15ï¼½ ng/ml, P > 0.05). CONCLUSIONS: The PSEP level in the urine can be used as an index for clinical evaluation of the therapeutic effect on chronic prostatitis.
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Prostatite , Proteínas/análise , Urinálise , Doença Crônica , Medicamentos de Ervas Chinesas/uso terapêutico , Humanos , Masculino , Minociclina/uso terapêutico , Prostatite/tratamento farmacológico , Prostatite/urinaRESUMO
Syzygium aromaticum has been widely used in traditional medicine. Our study investigated the safety and antidepressant-like effects of the essential oil of S. aromaticum after acute or long-term treatment. Using GC-MS, a total of eight volatile constituents were identified in the essential oil of S. aromaticum. The single LD50 was approximately 4500 mg/kg based on a 24-h acute oral toxicity study. In a long-term repeated toxicity study of this essential oil (100, 200, and 400 mg/kg, p.âo.), only 400 mg/kg induced a significant decrease in body weight. In addition, no significant changes in relative organ weights and histopathological analysis were observed in all doses of essential oil-treated mice compared with the control group. Furthermore, acute S. aromaticum essential oil administration by gavage exerted antidepressant-like effects in the forced swimming test (200 mg/kg, p < 0.05) and tail suspension test (100 and 200 mg/kg, p < 0.05). Long-term S. aromaticum essential oil treatment via gavage significantly increased sucrose preference (50 mg/kg, p < 0.05; 100 and 200 mg/kg, p < 0.01) as well as elevated the protein levels of hippocampal p-ERK, p-CREB, and brain-derived neurotrophic factor in mice exposed to chronic unpredictable mild stress. These results confirmed the safety of the essential oil of S. aromaticum and suggested that its potent antidepressant-like property might be attributed to the improvement in the hippocampal pERK1/2-pCREB-BDNF pathway in rats exposed to chronic unpredictable mild stress.
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Antidepressivos/uso terapêutico , Fator Neurotrófico Derivado do Encéfalo/metabolismo , Hipocampo/metabolismo , Óleos Voláteis/uso terapêutico , Fitoterapia , Estresse Psicológico/tratamento farmacológico , Syzygium/química , Animais , Antidepressivos/farmacologia , Proteína de Ligação a CREB , Proteína de Ligação ao Elemento de Resposta ao AMP Cíclico/metabolismo , MAP Quinases Reguladas por Sinal Extracelular/metabolismo , Preferências Alimentares , Elevação dos Membros Posteriores , Masculino , Camundongos Endogâmicos ICR , Óleos Voláteis/química , Óleos Voláteis/farmacologia , Extratos Vegetais/farmacologia , Extratos Vegetais/uso terapêutico , Ratos Sprague-Dawley , Sacarose/administração & dosagem , NataçãoRESUMO
OBJECTIVE: To systematically review the role of two common prostheses(metal on metal and metal on polythene)in total hip replacement. METHODS: Studies on two prostheses(metal on metal and metal on polythene)in total hip replacement were searched in databases including PubMed, EMBASE, the Cochrane library, CNKI database, WANFANG database, and VIP database using key words including"metal on metal", "metal on polythene", and "total hip replacement". Meta-analysis was performed using RevMan 5.2 software. RESULTS: Metal on metal group was superior to metal on polythene group in terms of Harris function evaluation(WMDï¼4.40, 95%CI: 3.50-5.31, P<0.01), operation time(WMDï¼6.82, 95%CI: 4.50-9.13, P<0.01), whereas other indicators showed no significant difference between these two groups. CONCLUSIONS: Compared with the prosthesis, metal on metal is better than metal on polythene in improving the Harris function when applied for total hip replacement. However, more high-quality large-scale randomized controlled trials are required to further verify it.
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Artroplastia de Quadril , Próteses e Implantes , HumanosRESUMO
What is already known about this topic?: Injury is a significant public health issue, particularly among the elderly population. However, the extent of this problem varies significantly based on age, gender, and geographic location. What is added by this report?: This study aims to examine the changing patterns of injury mortality rates in China over a 35-year period and assess the age-period-cohort effects on mortality trends. What are the implications for public health practice?: This study examines the evolving patterns of injury mortality in the elderly population and identifies potential high-risk groups. The findings offer valuable insights for informing injury prevention policies.
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BACKGROUND: Diosgenin is a well-known steroid saponin possessing neuroprotective activities. However, it is unknown whether diosgenin could alleviate depression-like symptoms. METHODS: The antidepressant-like effect of diosgenin was investigated in mice induced by chronic restraint stress. The effects of diosgenin on behaviors, inflammation, neuroendocrine, neurotrophic function, and gut microbiota were evaluated. RESULTS: The results showed that diosgenin alleviated the depressive-like behaviors in mice. In addition, diosgenin was found to reduce serum concentrations of proinflammatory cytokines and the activity of the hypothalamic-pituitary-adrenal (HPA) axis. Besides, diosgenin could activate hippocampal brain-derived neurotrophic factor (BDNF)/TrkB/ERK/CREB signaling pathway and improve the expression of postsynaptic protein PSD95. Meanwhile, the neurogenesis which was inhibited by chronic restraint stress, was totally reversed by diosgenin. Moreover, diosgenin increased the abundance of phylum Firmicutes and the genus Lactobacillus in stressed mice. The results further showed that diosgenin caused a strong correlation between gut microbiota composition and inflammation, the HPA axis activity, or hippocampus neurotrophic function. LIMITATIONS: Only male mice were used for evaluation in the present study, which limits the understanding of effects of diosgenin on the both sexes. In addition, the results only indicate microbiota at the phylum or genus mediate the regulation of neuroinflammation, neuroendocrine, and neurotrophic function, but does not elucidate how microbiota modulate the systems via their primary or secondary metabolites. CONCLUSIONS: The present study shows that diosgenin exerts the antidepressant activity, which is associated with the enhancement of neurotrophic function and the inhibition of inflammatory and neuroendocrine activities via the regulation of gut microbiota.
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Diosgenina , Microbioma Gastrointestinal , Masculino , Feminino , Camundongos , Animais , Diosgenina/farmacologia , Diosgenina/uso terapêutico , Sistema Hipotálamo-Hipofisário , Sistema Hipófise-Suprarrenal , Inflamação/tratamento farmacológico , Antidepressivos/farmacologia , Antidepressivos/uso terapêuticoRESUMO
Depression is a multifaceted psychiatric disorder that affects a significant number of individuals worldwide, and its pathophysiology encompasses a variety of mechanisms, including the induction of endoplasmic reticulum (ER) stress, which has been correlated with depressive-like behaviors in animal models. Yamogenin, a bioactive compound derived from traditional Chinese medicine Dioscorea species, possesses diverse pharmacological properties. This investigation aimed to explore the antidepressant-like effects of yamogenin and the underlying mechanisms involved. By utilizing a murine model of lipopolysaccharide (LPS)-induced depressive-like behavior, we demonstrated that yamogenin enhanced sucrose preference and reduced immobility time in the forced swimming test. These effects were observed alongside the attenuation of ER stress through modulation of the PERK/eIF2α/ATF4/CHOP signaling pathway in the prefrontal cortex. Moreover, yamogenin augmented the expression of the antiapoptotic protein Bcl-2 while diminishing the expression of the proapoptotic protein caspase-3. Additionally, yamogenin exhibited inhibitory effects on microglial activation but did not elicit the promotion of brain-derived neurotrophic factor (BDNF) signaling. Collectively, our findings propose that yamogenin exerts antidepressant-like effects in LPS-induced mice by inhibiting ER stress and microglial activation. This study contributes novel insights into the potential utilization of yamogenin as a natural antidepressant agent.
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Diosgenina , Lipopolissacarídeos , Camundongos , Animais , Lipopolissacarídeos/farmacologia , Microglia , Antidepressivos/farmacologia , Diosgenina/farmacologia , Estresse do Retículo Endoplasmático , Depressão/metabolismoRESUMO
BACKGROUND: Inflammatory bowel disease (IBD) is a chronic, life-threatening inflammatory disease of gastrointestinal tissue characterized by inflammation of the gut. Recent studies have shown that gut microbiota is involved in the pathophysiology of IBD. However, it is unknown whether direct inhibition of NLR family pyrin domain containing 3 (NLRP3) inflammasome regulates IBD and alters gut microbiota. METHODS: Here, the NLRP3 expression was evaluated in the colon of IBD subjects. Then, we investigated the effects of NLRP3 inhibition by MCC950 on the gut microbiota and IBD-like symptoms induced by dextran sulfate sodium (DSS). RESULTS: Firstly, NLRP3 and IL-1ß levels were increased in patients with IBD as compared with healthy individuals. Then, the animal experiment showed that NLRP3 inhibition by MCC950 significantly attenuated IBD-like symptoms such as diarrhea and colonic inflammation in DSS-induced mice. In addition, NLRP3 inhibition inhibited NLRP3/ASC/caspase-1/IL-1ß signaling pathway in the colon, which was over-activated by DSS. Furthermore, MCC950 increased the abundance of phylum Firmicutes, decreased the abundance of phylum Bacteroidetes, and increased the Firmicutes/Bacteroidetes ratio, indicating that the inhibition of NLRP3 inflammasome could regulate the abundance of intestinal flora. According to correlation analysis, NLRP3 might produce its functional role in the regulation of oxidation indicators by changing the gut microbiota composition, especially the phylum Bacteroidota, genus Lactobacillus and species Lactobacillus reuteri. CONCLUSIONS: This study suggests that NLRP3 inflammasome inhibition attenuates IBD-like symptoms by regulating gut microbiota, and provides a basis for the clinical application of NLRP3 as a target for the treatment of IBD.
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Colite , Microbioma Gastrointestinal , Doenças Inflamatórias Intestinais , Humanos , Animais , Camundongos , Colite/induzido quimicamente , Colite/tratamento farmacológico , Proteína 3 que Contém Domínio de Pirina da Família NLR , Sulfato de Dextrana/efeitos adversos , Inflamassomos , Doenças Inflamatórias Intestinais/induzido quimicamente , Doenças Inflamatórias Intestinais/tratamento farmacológico , Doenças Inflamatórias Intestinais/metabolismo , Inflamação , Modelos Animais de DoençasRESUMO
Families of children affected by birth defects suffer from a significant psychological burden across the lifespan, but there have been few studies on this topic in China. Our goal was to assess depression among mothers of children with birth defects (MCBD) and to explore factors influencing depression among MCBD in China. A total of 154 mothers of affected children aged 0-3 years old (MCBD) and 321 mothers of healthy children (MHC) in the same age range took part in the study. The Center for Epidemiologic Studies Depression Scale was used to assess maternal depression, and logistic regression models were used to explore the factors influencing depression among MCBD. MCBD were more depressed than MHC and birth defects were associated with maternal depression after demographic variables were controlled. Poverty was the most important predictor of depression among MCBD. Appropriate interventions for depressed mothers are essential and should focus on poor families.
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Anormalidades Congênitas , Depressão/psicologia , Saúde Mental , Mães/psicologia , Estudos de Casos e Controles , Pré-Escolar , China , Depressão/diagnóstico , Feminino , Nível de Saúde , Humanos , Lactente , Recém-Nascido , Modelos Logísticos , Masculino , Escalas de Graduação Psiquiátrica , Fatores de Risco , Fatores SocioeconômicosRESUMO
CONTEXT: The fruit of the Prunus mume Sieb. et Zucc (Rosaceae) is used as a health food or medicinal material in traditional herb medicine for a long time in Eastern Asian countries. OBJECTIVE: Our present study investigated the hypouricemic effect of the methanol extract from P. mume fruit (MPMF) in mice with potassium oxonate-induced hyperuremia. MATERIALS AND METHODS: Effect of MPMF (35, 70 and 140 mg/kg, p.o.) administrated for 7 days on the serum, liver, urinary uric acid levels and liver xanthine oxidase (XO) activity were assessed in mice. RESULTS: Hyperuricemic mice induced by potassium oxonate demonstrated an elevation in serum and liver uric acid levels (11.0 mg/dL and 0.52 mg/g tissue) and a reduction in urinary uric acid levels (49.9 mg/dL). Oral administration of 140 mg/kg MPMF for 7 days reversed the abnormalities in serum, liver and urinary uric acid levels (7.1 mg/dL, 0.37 mg/g tissue and 69.7 mg/dL, respectively). In addition, 70 and 140 mg/kg MPMF (3.1 and 2.9 nmol/min per mg protein) inhibited liver XO activity compared with hyperuricemic mice (3.9 nmol/min per mg protein). DISCUSSION AND CONCLUSION: The results indicated that the beneficial hypouricaemic effect of MPMF may be mediated, at least in part, by inhibiting XO activity in the liver. Our study suggests that P. mume and its extracts may have a considerable potential for development as an anti-gout agent for clinical application.
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Hiperuricemia/tratamento farmacológico , Extratos Vegetais/farmacologia , Prunus/química , Xantina Oxidase/antagonistas & inibidores , Administração Oral , Animais , Modelos Animais de Doenças , Relação Dose-Resposta a Droga , Frutas , Fígado/efeitos dos fármacos , Fígado/enzimologia , Masculino , Medicina Tradicional do Leste Asiático , Metanol/química , Camundongos , Ácido Oxônico/toxicidade , Extratos Vegetais/administração & dosagem , Ácido Úrico/sangue , Ácido Úrico/metabolismo , Ácido Úrico/urinaRESUMO
Although the personality traits (PT), patient-reported outcome (PRO), and chronic prostatitis (CP) symptoms in premature ejaculation (PE) have been evaluated, there was no study to assess their correlations in men with different PE syndromes. The purpose of this study was to assess the correlations between the PT, PRO, and CP symptoms in men with different PE syndromes. Between January 2019 and January 2021, a cross-sectional field study was conducted in our andrology clinic. Men with the complaints of PE were divided into lifelong PE (LPE), acquired PE (APE), variable PE (VPE), and subjective PE (SPE). All subjects were required to complete a verbal questionnaire with the PRO, National Institutes of Health Chronic Prostatitis Symptom Index (NIH-CPSI), and Temperament and Character Inventory (TCI-R). Finally, 479 men with the complaints of PE and 365 without the complaints of PE were enrolled. The incidence of PE syndromes in PE complaint group was as follows: LPE 16.70%, APE 48.85%, VPE 11.27%, and SPE 23.17%. Mean ages in PE complaint group were 42.53 ± 12.25 years. In the PE complaint group, the novelty seeking (NS) scores were strongest correlated with the personal distress and quality of life (QOL). The harm avoidance (HA) scores were strongest correlated with the severity of PE and pain syndromes. The self-transcendence (ST) scores were strongest correlated with the satisfaction with sexual intercourse and QOL. In addition, strongest association between the total scores of NIH-CPSI and the NS or ST scores was also found in the APE group. The HA scores were also strongest correlated with the total scores of NIH-CPSI in SPE. Strongest association between the total scores of NIH-CPSI and the NS/TI or ST/CI scores was also found in the APE group. The HA/TI scores were also strongest correlated with the total scores of NIH-CPSI in SPE.
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Ejaculação Precoce , Prostatite , Adulto , Doença Crônica , Estudos Transversais , Ejaculação , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Medidas de Resultados Relatados pelo Paciente , Personalidade , Ejaculação Precoce/epidemiologia , Prostatite/complicações , Prostatite/epidemiologia , Qualidade de Vida , Inquéritos e Questionários , SíndromeRESUMO
INTRODUCTION: The study aimed to investigate the effects of ischemia on neuro-vascular units in transgenic mice, and to investigate the role of ischemia-hypoperfusion in the model of dual transgenic mice with dementia. MATERIAL AND METHODS: In this study, the ischemic model was generated by operating a bilateral common carotid artery micro-embolism. Mice were divided into four groups, including group 1: C57BL sham surgery group (control), group 2: C57BL ischemic group, group 3: amyloid precursor protein/presenilin-1 (APP/PS1) group, and group 4: APP/PS1 ischemic group. Each group comprised 20 mice. Spatial behavior and memory ability of mice were detected by Morris water maze and jumping platform test. Mouse hippocampus was observed by HE staining and Congo red staining. Ultrastructure of each group of neuro-cyclic units was observed by electron microscopy. Various biochemical indicators were detected by ELISA. Western blot detected the amount of protein expression. qRT-PCR identified mRNA expression. RESULTS: The results indicated that learning and memory functions of C57 ischemic mice were lower than those of control group. Positive expression area of APP in APP/PS1 ischemic group was higher than in APP/PS1 group. In APP/PS1 group and APP/PS1 ischemic group, the content of Ab was significantly higher than in C57 ischemic group. Electron microscopic observation revealed that there were more mitochondrial vacuoles in hippocampal neurons of APP/PS1 mice, and the structure was relatively intact. Mitochondrial vacuoles in hippocampus increased significantly, and vascular wall proliferated in APP/PS1 ischemic group. Compared with C57 control group, the content of vascular endothelial growth factor (VEGF) increased significantly in C57 ischemic group. CONCLUSIONS: Ischemia deteriorates the learning and memory function of transgenic mice, aggravates the damage of neuro-vascular units, and impairs the blood-brain barrier transport of Ab, leading to an increase in the concentration of Ab cerebrospinal fluid, and further deterioration of neuro-vascular units. At the same time, ischemia is an effective stimulating factor in the release of VEGF.
Assuntos
Doença de Alzheimer , Doença de Alzheimer/metabolismo , Peptídeos beta-Amiloides/metabolismo , Precursor de Proteína beta-Amiloide/genética , Precursor de Proteína beta-Amiloide/metabolismo , Animais , Modelos Animais de Doenças , Hipocampo/metabolismo , Isquemia/metabolismo , Aprendizagem em Labirinto , Camundongos , Camundongos Endogâmicos C57BL , Camundongos Transgênicos , Fator A de Crescimento do Endotélio Vascular/metabolismoRESUMO
Major depressive disorder is characterized by the deficiencies of monoamine neurotransmitters, neurotrophic factors and persistent neuroinflammation. Microglial activation has been associated with neuroinflammation-related mental diseases, accompanied by NLR family pyrin domain containing 3 (NLRP3) inflammasome. Here, we investigated the effect of NLRP3 inhibition by its small molecular inhibitor MCC950 on inflammatory activity and depressive-like mice induced by chronic unpredictable mild stress (CUMS), followed by the behavioral tests including sucrose preference test and forced swimming test. NLRP3/caspase-1/IL-1ß signaling and microglial morphology in the prefrontal cortex were measured. The results showed that CUMS caused a decrease in sucrose preference and an increase in immobility time, which were reversed by NLRP3 inhibitor MCC950. In addition, NLRP3 inhibition decreased the number of microglia and changed the activated state of microglia to a resting state by morphology 3D reconstruction. Moreover, NLRP3 inhibition inactivated NLRP3/caspase-1/IL-1ß signaling in the prefrontal cortex. The results from immunofluorescence demonstrated that NLRP3 and IL-1ß expression was decreased in microglia in response to MCC950 treatment. Accordingly, proinflammatory cytokines were also decreased by NLRP3 inhibition. In conclusion, this study demonstrates that microglial NLRP3 inhibition prevents stress-induced neuroinflammation in the prefrontal cortex and suggests that microglial NLRP3 could be one of the potential therapeutic targets for depression treatment.