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Serine protease 50 (PRSS50/TSP50) is highly expressed in spermatocytes. Our study investigated its role in testicular development and spermatogenesis. Initially, PRSS50 knockdown was observed to impair DNA synthesis in spermatocytes. To further explore this, we generated PRSS50 knockout ( Prss50 -/- ) mice ( Mus musculus), which exhibited abnormal spermatid nuclear compression and reduced male fertility. Furthermore, dysplastic seminiferous tubules and decreased sex hormones were observed in 4-week-old Prss50 -/- mice, accompanied by meiotic progression defects and increased apoptosis of spermatogenic cells. Mechanistic analysis indicated that PRSS50 deletion resulted in increased phosphorylation of extracellular signal-regulated protein kinases 1 and 2 (ERK1/2) and elevated levels of MAP kinase phosphatase 3 (MKP3), a specific ERK antagonist, potentially accounting for testicular dysplasia in adolescent Prss50 -/- mice. Taken together, these findings suggest that PRSS50 plays an important role in testicular development and spermatogenesis, with the MKP3/ERK signaling pathway playing a significant role in this process.
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Sistema de Señalización de MAP Quinasas , Meiosis , Ratones Noqueados , Espermatozoides , Animales , Masculino , Ratones , Meiosis/fisiología , Espermatozoides/fisiología , Espermatogénesis/fisiología , Fosfatasa 6 de Especificidad Dual/genética , Fosfatasa 6 de Especificidad Dual/metabolismo , Testículo/metabolismo , Serina Endopeptidasas/genética , Serina Endopeptidasas/metabolismoRESUMEN
BACKGROUND: Previous research and safety advocacy groups have proposed various behaviors for older adults to actively engage in medication safety. However, little is known about how older adults perceive the importance and reasonableness of these behaviors in ambulatory settings. OBJECTIVE: This study aimed to assess older adults' perceptions of the importance and reasonableness of 8 medication safety behaviors in ambulatory settings and compare their responses with those of younger adults. METHODS: We conducted a survey of 1222 adults in the United States using crowdsourcing to evaluate patient behaviors that may enhance medication safety in community settings. A total of 8 safety behaviors were identified based on the literature, such as bringing medications to office visits, confirming medications at home, managing medication refills, using patient portals, organizing medications, checking medications, getting help, and knowing medications. Respondents were asked about their perception of the importance and reasonableness of these behaviors on a 5-point Likert rating scale in the context of collaboration with primary care providers. We assessed the relative ranking of behaviors in terms of importance and reasonableness and examined the association between these dimensions across age groups using statistical tests. RESULTS: Of 1222 adult participants, 125 (10.2%) were aged 65 years or older. Most participants were White, college-educated, and had chronic conditions. Older adults rated all 8 behaviors significantly higher in both importance and reasonableness than did younger adults (P<.001 for combined behaviors). Confirming medications ranked highest in importance (mean score=3.78) for both age groups while knowing medications ranked highest in reasonableness (mean score=3.68). Using patient portals was ranked lowest in importance (mean score=3.53) and reasonableness (mean score=3.49). There was a significant correlation between the perceived importance and reasonableness of the identified behaviors, with coefficients ranging from 0.436 to 0.543 (all P<.001). CONCLUSIONS: Older adults perceived the identified safety behaviors as more important and reasonable than younger adults. However, both age groups considered a behavior highly recommended by professionals as the least important and reasonable. Patient engagement strategies, common and specific to age groups, should be considered to improve medication safety in ambulatory settings.
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The integrity of the intestinal mucosal barrier is crucial for protecting the intestinal epithelium against invasion by commensal bacteria and pathogens, thereby combating colitis. The investigation revealed that the absence of TSP50 compromised the integrity of the intestinal mucosal barrier in murine subjects. This disruption facilitated direct contact between intestinal bacteria and the intestinal epithelium, thereby increasing susceptibility to colitis. Mechanistic analysis indicated that TSP50 deficiency in intestinal stem cells (ISCs) triggered aberrant activation of the TGF-ß signaling pathway and impeded the differentiation of goblet cells in mice, leading to impairment of mucosal permeability. By inhibiting the TGF-ß pathway, the functionality of the intestinal mucosal barrier is successfully restored and mitigated colitis in TSP50-deficient mice. In conclusion, TSP50 played a crucial role in maintaining the intestinal mucosal barrier function and exhibited the preventive effect against the development of colitis by regulating the TGF-ß signaling pathway.
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Colitis , Animales , Humanos , Ratones , Colitis/inducido químicamente , Colitis/prevención & control , Mucosa Intestinal , Intestinos , Factor de Crecimiento Transformador beta/metabolismoRESUMEN
Nasopharyngeal carcinoma (NPC) originates in the epithelial cells of the nasopharynx and is a common malignant tumor in southern China and Southeast Asia. Metastasis of NPC remains the main cause of death for NPC patients even though the tumor is sensitive to radiotherapy and chemotherapy. Here, we found that the transmembrane protein tetraspanin1 (TSPAN1) potently inhibited the in vitro migration and invasion, as well as, the in vivo metastasis of NPC cells via interacting with the IKBB protein. In addition, TSPAN1 was essential in preventing the overactivation of the NF-kB pathway in TSPAN1 overexpressing NPC cells. Furthermore, reduced TSPAN1 expression was associated with NPC metastasis and the poor prognosis of NPC patients. These results uncovered the suppressive role of TSPAN1 against NF-kB signaling in NPC cells for preventing NPC metastasis. Its therapeutic value warrants further investigation.
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Carcinoma , Neoplasias Nasofaríngeas , Humanos , Carcinoma Nasofaríngeo/patología , FN-kappa B/genética , FN-kappa B/metabolismo , Neoplasias Nasofaríngeas/metabolismo , Línea Celular Tumoral , Transducción de Señal , Movimiento Celular/genética , Regulación Neoplásica de la Expresión Génica , Tetraspaninas/genética , Tetraspaninas/metabolismoRESUMEN
BACKGROUND: Studies have revealed that intrinsic neural activity varies over time. However, the temporal variability of brain local connectivity in internet gaming disorder (IGD) remains unknown. The purpose of this study was to explore the alterations of static and dynamic intrinsic brain local connectivity in IGD and whether the changes were associated with clinical characteristics of IGD. METHODS: Resting-state functional magnetic resonance imaging (rs-fMRI) scans were performed on 36 individuals with IGD (IGDs) and 44 healthy controls (HCs) matched for age, gender and years of education. The static regional homogeneity (sReHo) and dynamic ReHo (dReHo) were calculated and compared between two groups to detect the alterations of intrinsic brain local connectivity in IGD. The Internet Addiction Test (IAT) and the Pittsburgh Sleep Quality Index (PSQI) were used to evaluate the severity of online gaming addiction and sleep quality, respectively. Pearson correlation analysis was used to evaluate the relationship between brain regions with altered sReHo and dReHo and IAT and PSQI scores. Receiver operating characteristic (ROC) curve analysis was used to reveal the potential capacity of the sReHo and dReHo metrics to distinguish IGDs from HCs. RESULTS: Compared with HCs, IGDs showed both increased static and dynamic intrinsic local connectivity in bilateral medial superior frontal gyrus (mSFG), superior frontal gyrus (SFG), and supplementary motor area (SMA). Increased dReHo in the left putamen, pallidum, caudate nucleus and bilateral thalamus were also observed. ROC curve analysis showed that the brain regions with altered sReHo and dReHo could distinguish individuals with IGD from HCs. Moreover, the sReHo values in the left mSFG and SMA as well as dReHo values in the left SMA were positively correlated with IAT scores. The dReHo values in the left caudate nucleus were negatively correlated with PSQI scores. CONCLUSIONS: These results showed impaired intrinsic local connectivity in frontostriatothalamic circuitry in individuals with IGD, which may provide new insights into the underlying neuropathological mechanisms of IGD. Besides, dynamic changes of intrinsic local connectivity in caudate nucleus may be a potential neurobiological marker linking IGD and sleep quality.
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Conducta Adictiva , Juegos de Video , Humanos , Trastorno de Adicción a Internet/diagnóstico por imagen , Imagen por Resonancia Magnética , Encéfalo/diagnóstico por imagen , Corteza Prefrontal , Mapeo Encefálico/métodos , Conducta Adictiva/diagnóstico por imagen , InternetRESUMEN
Distant metastasis is the primary reason for treatment failure in patients with nasopharyngeal carcinoma (NPC). In this study, we investigated the effect of ulinastatin (UTI) on NPC metastasis and its underlying mechanism. Highly-metastatic NPC cell lines S18 and 58F were treated with UTI and the effect on cell proliferation, migration, and invasion were determined by MTS and Transwell assays. S18 cells with luciferase-expressing (S18-1C3) were injected into the left hind footpad of nude mice to establish a model of spontaneous metastasis from the footpad to popliteal lymph node (LN). The luciferase messenger RNA (mRNA) was measured by quantitative polymerase chain reaction (qPCR), and the metastasis inhibition rate was calculated. Key molecular members of the UTI-related uPA, uPAR, and JAT/STAT3 signaling pathways were detected by qPCR and immunoblotting. UTI suppressed the migration and infiltration of S18 and 5-8F cells and suppressed the metastasis of S18 cells in vivo without affecting cell proliferation. uPAR expression decreased from 24 to 48 h after UTI treatment. The antimetastatic effect of UTI is partly due to the suppression of uPA and uPAR. UTI partially suppresses NPC metastasis by downregulating the expression of uPA and uPAR.
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Neoplasias Nasofaríngeas , Animales , Ratones , Humanos , Carcinoma Nasofaríngeo/tratamiento farmacológico , Carcinoma Nasofaríngeo/metabolismo , Carcinoma Nasofaríngeo/patología , Ratones Desnudos , Línea Celular Tumoral , Neoplasias Nasofaríngeas/tratamiento farmacológico , Neoplasias Nasofaríngeas/patología , Luciferasas , Movimiento Celular , Invasividad Neoplásica , Metástasis de la NeoplasiaRESUMEN
In this paper, a molybdenum disulfide fluorescent probe with an Fe3+ fluorescent system was first synthesized by the hydrothermal method for the detection of iron ion concentration in oral solution of protein succinate. It was characterized by infrared, fluorescence, X-ray photoelectron spectroscopy, scanning electron microscopy, and transmission electron microscopy. The probes were found to have good stability, photobleaching, and storage stability. The effects of dilution, pH, reaction time, and iron ion concentration on the fluorescent system were also investigated. The relative fluorescence intensity [(I0 - I)/I0] showed a good linear relationship with the iron ion concentration in the range of 0-50 µM, with the linear equation [(I0 - I)/I0] = 0.0148[Fe3+] + 0.0833 (r2 = 0.9943, n = 11) and the detection limit of 2.43 µM. The reaction mechanism was also explored, as well as its ion selectivity, reversibility, accuracy, precision, and concentration of Fe ions in the actual sample. It was found that the probe can selectively detect Fe ions with a certain degree of reversibility, accuracy, precision, and ideal recovery, and it can be used for the determination of Fe3+ in proteosuccinic acid oral solution.
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BACKGROUND: Engaging patients in health behaviors is critical for better outcomes, yet many patient partnership behaviors are not widely adopted. Behavioral economics-based interventions offer potential solutions, but it is challenging to assess the time and cost needed for different options. Crowdsourcing platforms can efficiently and rapidly assess the efficacy of such interventions, but it is unclear if web-based participants respond to simulated incentives in the same way as they would to actual incentives. OBJECTIVE: The goals of this study were (1) to assess the feasibility of using crowdsourced surveys to evaluate behavioral economics interventions for patient partnerships by examining whether web-based participants responded to simulated incentives in the same way they would have responded to actual incentives, and (2) to assess the impact of 2 behavioral economics-based intervention designs, psychological rewards and loss of framing, on simulated medication reconciliation behaviors in a simulated primary care setting. METHODS: We conducted a randomized controlled trial using a between-subject design on a crowdsourcing platform (Amazon Mechanical Turk) to evaluate the effectiveness of behavioral interventions designed to improve medication adherence in primary care visits. The study included a control group that represented the participants' baseline behavior and 3 simulated interventions, namely monetary compensation, a status effect as a psychological reward, and a loss frame as a modification of the status effect. Participants' willingness to bring medicines to a primary care visit was measured on a 5-point Likert scale. A reverse-coding question was included to ensure response intentionality. RESULTS: A total of 569 study participants were recruited. There were 132 in the baseline group, 187 in the monetary compensation group, 149 in the psychological reward group, and 101 in the loss frame group. All 3 nudge interventions increased participants' willingness to bring medicines significantly when compared to the baseline scenario. The monetary compensation intervention caused an increase of 17.51% (P<.001), psychological rewards on status increased willingness by 11.85% (P<.001), and a loss frame on psychological rewards increased willingness by 24.35% (P<.001). Responses to the reverse-coding question were consistent with the willingness questions. CONCLUSIONS: In primary care, bringing medications to office visits is a frequently advocated patient partnership behavior that is nonetheless not widely adopted. Crowdsourcing platforms such as Amazon Mechanical Turk support efforts to efficiently and rapidly reach large groups of individuals to assess the efficacy of behavioral interventions. We found that crowdsourced survey-based experiments with simulated incentives can produce valid simulated behavioral responses. The use of psychological status design, particularly with a loss framing approach, can effectively enhance patient engagement in primary care. These results support the use of crowdsourcing platforms to augment and complement traditional approaches to learning about behavioral economics for patient engagement.
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Colaboración de las Masas , Motivación , Participación del Paciente , Humanos , Terapia Conductista , Colaboración de las Masas/métodos , Atención Primaria de Salud , Encuestas y CuestionariosRESUMEN
BACKGROUND: Heilongjiang Province is a frontier province with distinctive characteristics, fertile land and rich products. OBJECTIVE: This study provides a new method for qualitatively studying flavonoids in traditional Chinese medicine and a new auxiliary means for identifying flavonoid isomers. METHODS: The flavonoids in Polygala fallax Hemsl were identified by ultra-performance liquid chromatography-photo-diode array (PDA)-quadrupole-electro- static field orbitrap mass spectrometry tandem by UV Spectrum, primary and secondary high-resolution mass spectrometry (MS1/MS2) cleavage of fragments combined with databases, mass spectrometry cleavage patterns and literature. RESULTS: The established QSRR model was used to verify the flavonoids identified from the Polygala fallax Hemsl. CONCLUSION: The structure of multiple Polygala fallax Hemsl has been identified using various spectral methods. The tumor cytotoxic activity of the isolated compounds was evaluated. This paper is of great significance for further elucidating the pharmacodynamic substance basis and further developing and utilizing Polygala fallax Hemsl.
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Antineoplásicos , Neoplasias , Polygala , Humanos , Polygala/química , Flavonoides , Medicina Tradicional China , Extractos VegetalesRESUMEN
Objective: This study aimed to observe the diagnostic value of cranial magnetic resonance imaging (MRI) in patients with vascular dementia induced by ischemic stroke. Methods: The experiment was designed according to the randomized control principle. Two hundred and eighty patients with ischemic stroke who were admitted to Gucheng County Hospital between June 2019 and June 2021 were selected as research subjects. Patients without vascular dementia after stroke were included in the control group, and patients with vascular dementia after stroke were included in the observation group. The cranial MRI was performed in both groups. Result: Proportions of patients with large and moderate infarct lesions in brain tissues were significantly higher in the observation group than the control group. The data variation of relevant MRI detection indicators of the observation group was more obvious than that of the control group (P<0.05). The mini-mental state examination (MMSE) and Montreal cognitive assessment (MoCA) scores of the observation group were lower than those of the control group (P<0.05), but the HIS score was higher (P>0.05). Patients with changes in brain morphology were more in the observation group than the control group (P<0.05). Conclusion: Patients with vascular dementia induced by ischemic stroke are characterized by cortical atrophy, widening of the cerebral sulcus, large infarct lesion area and sparse cerebral white matter. Cranial MRI can effectively identify these features. The application of cranial MRI has some clinical values for early treatment and prognostic assessment.
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BACKGROUND: Metastasis is one of the main obstacles impeding the survival of nasopharyngeal carcinoma (NPC) patients, with the molecular mechanism underlying NPC metastasis still unclear. RESULTS: In this study, Cystatin A (CSTA) was found downregulated in NPC tissues with metastasis compared with those without metastasis. Shorter overall survival and distant metastasis-free survival were found in NPC patients with lower CSTA expression. Using functional assays, we found that CSTA prevented both the in vitro motility of NPC cells and their ability to metastasize in vivo. Transcriptome sequencing and western blot analysis revealed that CSTA inhibited the phosphorylation of AKT. Moreover, activating AKT using AKT agonist SG79 rescued the motility of CSTA-overexpressing NPC cells, whereas, treatment with AKT inhibitor MK2206 inhibited the motility of CSTA-knockdown NPC cells. Mechanically, immunoprecipitation coupled mass spectrometry found that CSTA interacted with the N6-adenosine-methyltransferase subunit METTL3 and promoted its ubiquitin-proteasome-mediated degradation following the upregulation of NKX3-1 and LHPP, which are negative regulators of AKT. Furthermore, knock-down of NKX3-1 and LHPP enhanced the motility of CSTA-overexpressing NPC cells. CONCLUSIONS: The inhibitory effect of CSTA upon NPC metastasis mainly depended on suppressing AKT signaling by the upregulation of NKX3-1 and LHPP expression resulting from the binding between CSTA and METLL3. Our study suggests that the CSTA-METLL3-NKX3-1/LHPP-AKT axis could be of therapeutic value for inhibiting NPC metastasis.
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Carcinoma , Neoplasias Nasofaríngeas , Humanos , Carcinoma/patología , Cistatina A , Transición Epitelial-Mesenquimal , Metiltransferasas , Carcinoma Nasofaríngeo/genética , Neoplasias Nasofaríngeas/genética , Neoplasias Nasofaríngeas/metabolismo , Neoplasias Nasofaríngeas/patología , Proteínas Proto-Oncogénicas c-akt/metabolismoRESUMEN
The primary symptom of diabetic encephalopathy (DE), a kind of central diabetic neuropathy caused by diabetes mellitus (DM), is cognitive impairment. In addition, the tetracyclic oxindole alkaloid isorhynchophylline (IRN) helps lessen cognitive impairment. However, it is still unclear how IRN affects DM and DE and what mechanisms are involved. The effectiveness of IRN on brain insulin resistance was carefully examined in this work, both in vitro and in vivo. We found that IRN accelerates spliced form of X-box binding protein 1 (sXBP1) translocation into the nucleus under high glucose conditions in vitro. IRN also facilitates the nuclear association of pCREB with sXBP1 and the binding of regulatory subunits of phosphatidylinositol 3-kinase (PI3K) p85α or p85ß with XBP1 to restore high glucose impairment. Also, IRN treatment improves high glucose-mediated impairment of insulin signaling, endoplasmic reticulum stress, and pyroptosis/apoptosis by depending on sXBP1 in vitro. In vivo studies suggested that IRN attenuates cognitive impairment, ameliorating peripheral insulin resistance, activating insulin signaling, inactivating activating transcription factor 6 (ATF6) and C/EBP homology protein (CHOP), and mitigating pyroptosis/apoptosis by stimulation of sXBP1 nuclear translocation in the brain. In summary, these data indicate that IRN contributes to maintaining insulin homeostasis by activating sXBP1 in the brain. Thus, IRN is a potent antidiabetic agent as well as an sXBP1 activator that has promising potential for the prevention or treatment of DE.
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Diabetes Mellitus , Resistencia a la Insulina , Humanos , Oxindoles/farmacología , Proteína 1 de Unión a la X-Box , Fosfatidilinositol 3-Quinasas , Estrés del Retículo Endoplásmico , Insulina , Glucosa , Diabetes Mellitus/tratamiento farmacológicoRESUMEN
Minimal hepatic encephalopathy (MHE) is strongly associated with neuroinflammation. Nevertheless, the underlying mechanism of the induction of inflammatory response in MHE astrocytes remains not fully understood. In the present study, we investigated the effect and mechanism of S100B, a predominant isoform expressed and released from mature astrocytes, on MHE-like neuropathology in the MHE rat model. We discovered that S100B expressions and autocrine were significantly increased in MHE rat brains and MHE rat brain-derived astrocytes. Furthermore, S100B stimulates VEGF expression via the interaction between TLR2 and RAGE in an autocrine manner. S100B-facilitated VEGF autocrine expression further led to a VEGFR2 and COX-2 interaction, which in turn induced the activation of NFÆB, eventually resulting in inflammation and oxidative stress in MHE astrocytes. MHE astrocytes supported impairment of neuronal survival and growth in a co-culture system. To sum up, a comprehensive understanding of the role of S100B-overexpressed MHE astrocyte in MHE pathogenesis may provide insights into the etiology of MHE.
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Astrocitos , Animales , Ratas , Astrocitos/metabolismo , Inflamación/metabolismo , Neuroprotección , Estrés Oxidativo , Subunidad beta de la Proteína de Unión al Calcio S100/metabolismo , Subunidad beta de la Proteína de Unión al Calcio S100/farmacología , Factores de Crecimiento Endotelial VascularRESUMEN
OBJECTIVES: This study sought to further verify the protective mechanism of Melatonin (MT) against ovarian damage through animal model experiments and to lay a theoretical and experimental foundation for exploring new approaches for ovarian damage treatment. METHOD: The wet weight and ovarian index of rat ovaries were weighted, and the morphology of ovarian tissues and the number of follicles in the pathological sections of collected ovarian tissues were recorded. And the serum sex hormone levels, the key proteins of the autophagy pathway (PI3K, AKT, mTOR, LC3II, LC3I, and Agt5) in rat ovarian tissues, as well as the viability and mortality of ovarian granulosa cells in each group were measured by ELISA, western blotting, CCK8 kit and LDH kit, respectively. RESULTS: The results showed that MT increased ovarian weight and improved the ovarian index in ovarian damage rats. Also, MT could improve autophagy-induced ovarian tissue injury, increase the number of primordial follicles, primary follicles, and sinus follicles, and decrease the number of atretic follicles. Furthermore, MT upregulated serum AMH, INH-B, and E2 levels downregulated serum FSH and LH levels in ovarian damage rats and activated the PI3K/AKT/mTOR signaling pathway. Besides, MT inhibited autophagic apoptosis of ovarian granulosa cells and repressed the expression of key proteins in the autophagic pathway and reduced the expression levels of Agt5 and LC3II/I. CONCLUSIONS: MT inhibits granulosa cell autophagy by activating the PI3K/Akt/mTOR signaling pathway, thereby exerting a protective effect against ovarian damage.
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Melatonina , Ovario , Animales , Apoptosis , Autofagia , Femenino , Hormona Folículo Estimulante , Células de la Granulosa/metabolismo , Células de la Granulosa/patología , Melatonina/metabolismo , Melatonina/farmacología , Melatonina/uso terapéutico , Fosfatidilinositol 3-Quinasas/metabolismo , Fosfatidilinositol 3-Quinasas/farmacología , Proteínas Proto-Oncogénicas c-akt/metabolismo , Proteínas Proto-Oncogénicas c-akt/farmacología , Ratas , Serina-Treonina Quinasas TOR/metabolismo , Serina-Treonina Quinasas TOR/farmacologíaRESUMEN
Puerarin, a bioactive flavone compound isolated from Pueraria (Wild.), provides hepatoprotection by anti-inflammatory, anti-alcoholism, and regulating mechanistic target of rapamycin (mTOR). Building evidence suggests that the activation of mTOR reduces liver injuries associated with alcohol consumption and metabolism. However, the poor water solubility, low bioavailability, and short half-life of puerarin hinder its clinical application. The utility of mesoporous silicon nanoparticles (MSNs) can improve traditional Chinese medicine limitations. Stober methods were used to fabricate MSNs@Pue, and the size, zeta potentials and drug encapsulation efficiency were characterized by a series of analytical methods. IVIS Imaging System demonstrated liver-targeted bio-distribution, and then high-throughput sequencing, immunoproteomics and ultrastructure methods indicated autophagy related protective mechanism, followed by curative effect evaluation for the treatment efficacy. An acute-on chronic ethanol-drinking according to Gao-binge model induced alcoholic hepatitis (AH) pathology and resulted in hepatic hyper-autophagy, which was improved with MSNs@Pue administration (puerarin: 30 mM, 42 mg/kg; intravenously [i.v.]). Ethanol-fed mice were found to have increased expression of autophagy-related proteins (Atg3, Atg7, LC3 and p62). In contrast, MSNs@Pue administration significantly decreased the expression of these proteins and alleviated fatty droplets infiltration in damaged liver. Furthermore, acute-on-chronic ethanol feeding also resulted in the activiation of ERK activation and mTOR expression, which were reversed with MSNs@Pue administration and better than the usage of puerarin alone. Results point to MSNs@Pue mediated ERK/mTOR signaling pathway activation as a possible protective strategy to improve AH, which provides a strategy and evidence for treating liver disease using an MSN delivery system.
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Hepatitis Alcohólica , Nanopartículas , Ratones , Animales , Silicio , Hepatitis Alcohólica/tratamiento farmacológico , Nanopartículas/química , Autofagia , Serina-Treonina Quinasas TOR , Etanol , Dióxido de Silicio/químicaRESUMEN
Background: Back muscle injury is the most common illness involved in aged people. Muscular satellite cells, playing a key role in the muscle repairing process, are gradually losing their regenerative ability with aging, which attenuates the injured muscle repairing process. Electroacupuncture at Weizhong acupoint has been widely used in the treatment of young and aged patients with back muscle damage. Its efficacy has been proven by a randomized double-blind placebo clinical trial. However, the rehabilitation mechanisms are largely unknown. This study will explore the possible mechanisms associated with electroacupuncture at the Weizhong acupoint (BL 40) promoting muscle repairing ability. Method: A total of 58 male and female Sprague-Dawley rats were divided into a younger group (4-month-old) and an aged group (16-month-old), younger and aged rats were further divided as a sham, injured, injured rats treated with electroacupuncture at Weizhong point or treated with Non-Weizhong point groups. The back muscle injury model was produced in rats as a previously described method with modification. Furthermore, Weizhong acupoints underwent electroacupuncture treatment with 15 V magnitude, 2 Hz/10 Hz frequency density, 1.0 mA current intensity, and 10 min each day for 10 consecutive days using HANS's electroacupuncture apparatus. After the last treatment, the paravertebral muscles and serum of all animals were undergone histological, immunohistochemistry, and flow cytometry analysis. Serum levels of Creatine Kinase (CK) and proinflammatory cytokine, interleukin 6 (IL-6), were measured separately by using ELISA kit. Results: Electroacupuncture of Weizhong (BL 40) acupoints significantly attenuated back muscle damage in both young and aged rats, increasing PAX7 (a marker of muscle satellite cells) and MYOD (major marker of myoblasts) cells, simultaneously, reducing serum proinflammatory cytokines, IL-6, and downregulation of p38 MAPK signaling in aged muscular satellite cells. Conclusion: Our studies suggest that electroacupuncture of Weizhong (BL 40) acupoints can restore aged back muscular satellite cells and their regeneration capacity. These suggested electroacupuncture may be a potential means of promoting rehabilitation for muscular injury in aged patients.
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Decision-making is one of the most critical activities of human beings. To better understand the underlying neurocognitive mechanism while making decisions under an economic context, we designed a decision-making paradigm based on the newsvendor problem (NP) with two scenarios: low-profit margins as the more challenging scenario and high-profit margins as the less difficult one. The EEG signals were acquired from healthy humans while subjects were performing the task. We adopted the Correlated Component Analysis (CorrCA) method to identify linear combinations of EEG channels that maximize the correlation across subjects ([Formula: see text]) or trials ([Formula: see text]). The inter-subject or inter-trial correlation values (ISC or ITC) of the first three components were estimated to investigate the modulation of the task difficulty on subjects' EEG signals and respective correlations. We also calculated the alpha- and beta-band power of the projection components obtained by the CorrCA to assess the brain responses across multiple task periods. Finally, the CorrCA forward models, which represent the scalp projections of the brain activities by the maximally correlated components, were further translated into source distributions of underlying cortical activity using the exact Low Resolution Electromagnetic Tomography Algorithm (eLORETA). Our results revealed strong and significant correlations in EEG signals among multiple subjects and trials during the more difficult decision-making task than the easier one. We also observed that the NP decision-making and feedback tasks desynchronized the normalized alpha and beta powers of the CorrCA components, reflecting the engagement state of subjects. Source localization results furthermore suggested several sources of neural activities during the NP decision-making process, including the dorsolateral prefrontal cortex, anterior PFC, orbitofrontal cortex, posterior cingulate cortex, and somatosensory association cortex.
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Toma de Decisiones , Electroencefalografía , Mapeo Encefálico/métodos , Corteza Cerebral/fisiología , Toma de Decisiones/fisiología , Giro del Cíngulo/fisiología , HumanosRESUMEN
BACKGROUND: Many patients with neurological disorders experience chronic fatigue, but the neural mechanisms involved are unclear. OBJECTIVE: Here we investigated whether the brain structural and functional connectivity alterations were involved in fatigue related to neuromyelitis optica spectrum disorder (NMOSD). METHODS: This prospective pilot study used structural and resting-state functional brain magnetic resonance imaging to compare total cortical thickness, cortical surface area, deep gray matter volume and functional connectivity (FC) between 33 patients with NMOSD and 20 healthy controls (HCs). Patients were subgrouped as low fatigue (LF) and high fatigue (HF). RESULTS: HF patients scored higher on the Hamilton Anxiety Rating Scale and Hamilton Rating Scale for Depression than LF patients and HCs. The two patient subgroups and HC group did not differ significantly in cortical thickness, cortical surface area and volumes of the bilateral caudate nucleus, bilateral putamen, bilateral amygdala, bilateral hippocampus, bilateral thalamus proper or right nucleus accumbens (p > 0.05). However, after correcting for age, sex, years of education, anxiety and depression, HF patients showed larger left pallidum than HCs (0.1573 ± 0.0214 vs 0.1372 ± 0.0145, p = 0.009). Meanwhile, both LF patients (0.0377 ± 0.0052 vs 0.0417 ± 0.0052, p = 0.009) and HF patients (0.0361 ± 0.0071 vs 0.0417 ± 0.0052, p = 0.013) showed smaller left nucleus accumbens than HCs.. Compared with LF patients, HF patients showed significantly decreased FC between the left pallidum and bilateral cerebellar posterior lobes. CONCLUSIONS: This was the first evidence linking structural and functional alterations in the brain to fatigue in NMOSD, and in the future, long term follow-up was necessary.
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Neuromielitis Óptica , Encéfalo/diagnóstico por imagen , Encéfalo/patología , Humanos , Imagen por Resonancia Magnética/métodos , Neuromielitis Óptica/complicaciones , Neuromielitis Óptica/diagnóstico por imagen , Neuromielitis Óptica/patología , Proyectos Piloto , Estudios ProspectivosRESUMEN
Lyciumruthenicum Murray (L. ruthenicum) has been used both as traditional Chinese medicine and food. Recent studies indicated that anthocyanins are the most abundant bioactive compounds in the L. ruthenicum fruits. The purpose of this study was to investigate the preventive effects and the mechanism of the anthocycanins from the fruit of L. ruthenicum (ACN) in high-fat diet-induced obese mice. In total, 24 male C57BL/6J mice were divided into three groups: control group (fed a normal diet), high-fat diet group (fed a high-fat diet, HFD), and HFD +ACN group (fed a high-fat diet and drinking distilled water that contained 0.8% crude extract of ACN). The results showed that ACN could significantly reduce the body weight, inhibit lipid accumulation in liver and white adipose tissue, and lower the serum total cholesterol and low-density lipoprotein cholesterol levels compared to that of mice fed a high-fat diet. 16S rRNA gene sequencing of bacterial DNA demonstrated that ACN prevent obesity by enhancing the diversity of cecal bacterial communities, lowering the Firmicutes-to-Bacteroidota ratio, increasing the genera Akkermansia, and decreasing the genera Faecalibaculum. We also studied the inhibitory effect of ACN on pancreatic lipase. The results showed that ACN has a high affinity for pancreatic lipase and inhibits the activity of pancreatic lipase, with IC50 values of 1.80 (main compound anthocyanin) and 3.03 mg/mL (crude extract), in a competitive way. Furthermore, fluorescence spectroscopy studies showed that ACN can quench the intrinsic fluorescence of pancreatic lipase via a static mechanism. Taken together, these findings suggest that the anthocyanins from L. ruthenicum fruits could have preventive effects in high-fat-diet induced obese mice by regulating the intestinal microbiota and inhibiting the pancreatic lipase activity.
Asunto(s)
Dieta Alta en Grasa , Microbioma Gastrointestinal , Animales , Antocianinas/química , Antocianinas/farmacología , Colesterol/farmacología , Dieta Alta en Grasa/efectos adversos , Lipasa , Masculino , Ratones , Ratones Endogámicos C57BL , Ratones Obesos , Extractos Vegetales/farmacología , ARN Ribosómico 16SRESUMEN
Abstract Objectives: This study sought to further verify the protective mechanism of Melatonin (MT) against ovarian damage through animal model experiments and to lay a theoretical and experimental foundation for exploring new approaches for ovarian damage treatment. Method: The wet weight and ovarian index of rat ovaries were weighted, and the morphology of ovarian tissues and the number of follicles in the pathological sections of collected ovarian tissues were recorded. And the serum sex hormone levels, the key proteins of the autophagy pathway (PI3K, AKT, mTOR, LC3II, LC3I, and Agt5) in rat ovarian tissues, as well as the viability and mortality of ovarian granulosa cells in each group were measured by ELISA, western blotting, CCK8 kit and LDH kit, respectively. Results: The results showed that MT increased ovarian weight and improved the ovarian index in ovarian damage rats. Also, MT could improve autophagy-induced ovarian tissue injury, increase the number of primordial follicles, primary follicles, and sinus follicles, and decrease the number of atretic follicles. Furthermore, MT upregulated serum AMH, INH-B, and E2 levels downregulated serum FSH and LH levels in ovarian damage rats and activated the PI3K/AKT/mTOR signaling pathway. Besides, MT inhibited autophagic apoptosis of ovarian granulosa cells and repressed the expression of key proteins in the autophagic pathway and reduced the expression levels of Agt5 and LC3II/I. Conclusions: MT inhibits granulosa cell autophagy by activating the PI3K/Akt/mTOR signaling pathway, thereby exerting a protective effect against ovarian damage.