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1.
Front Bioeng Biotechnol ; 9: 757906, 2021.
Artigo em Inglês | MEDLINE | ID: mdl-34746110

RESUMO

Peripheral nerve injuries have become a common clinical disease with poor prognosis and complicated treatments. The development of tissue engineering pointed a promising direction to produce nerve conduits for nerve regeneration. Electrical and mechanical stimulations have been incorporated with tissue engineering, since such external stimulations could promote nerve cell proliferation, migration and differentiation. However, the combination of electrical and mechanical stimulations (electromechanical stimulation) and its effects on neuron proliferation and axon outgrowth have been rarely investigated. Herein, silver nanowires (AgNWs) embedded polydimethylsiloxane (PDMS) electrodes were developed to study the effects of electromechanical stimulation on rat pheochromocytoma cells (PC12 cells) behaviors. AgNWs/PDMS electrodes demonstrated good biocompatibility and established a stable electric field during mechanical stretching. PC12 cells showed enhanced proliferation rate and axon outgrowth under electrical stimulation alone, and the cell number significantly increased with higher electrical stimulation intensity. The involvement of mechanical stretching in electrical stimulation reduced the cell proliferation rate and axon outgrowth, compared with the case of electrical stimulation alone. Interestingly, the cellular axons outgrowth was found to depend on the stretching direction, where the axons prefer to align perpendicularly to the stretch direction. These results suggested that AgNWs/PDMS electrodes provide an in vitro platform to investigate the effects of electromechanical stimulation on nerve cell behaviors and can be potentially used for nerve regeneration in the future.

2.
J Neurol ; 2021 Nov 28.
Artigo em Inglês | MEDLINE | ID: mdl-34839456

RESUMO

BACKGROUND: The prevalence of dementia in China, particularly in rural areas, is consistently increasing; however, research on population-attributable fractions (PAFs) of risk factors for dementia is scarce. METHODS: We conducted a cross-sectional survey, namely, the China Multicentre Dementia Survey (CMDS) in selected rural and urban areas from 2018 to 2020. We performed face-to-face interviews and neuropsychological and clinical assessments to reach a consensus on dementia diagnosis. Prevalence and weighted PAFs of eight modifiable risk factors (six classical: less childhood education, hearing impairment, depression, physical inactivity, diabetes, and social isolation, and two novels: olfactory decline and being unmarried) for all-cause dementia were estimated. RESULTS: Overall, CMDS included 17,589 respondents aged ≥ 65 years, 55.6% of whom were rural residents. The age- and sex-adjusted prevalence for all-cause dementia was 9.11% (95% CI 8.96-9.26), 5.19% (5.07-5.31), and 11.98% (11.8-12.15) in the whole, urban, and rural areas of China, respectively. Further, the overall weighted PAFs of the eight potentially modifiable risk factors were 53.72% (95% CI 52.73-54.71), 50.64% (49.4-51.89), and 56.54% (55.62-57.46) in the whole, urban, and rural areas of China, respectively. The eight risk factors' prevalence differed between rural and urban areas. Lower childhood education (PAF: 13.92%) and physical inactivity (16.99%) were primary risk factors in rural and urban areas, respectively. CONCLUSIONS: The substantial urban-rural disparities in the prevalence of dementia and its risk factors exist, suggesting the requirement of resident-specific dementia-prevention strategies.

3.
Zhongguo Gu Shang ; 34(10): 895-900, 2021 Oct 25.
Artigo em Chinês | MEDLINE | ID: mdl-34726014

RESUMO

OBJECTIVE: To compare the clinical efficacy of femoral head replacement and internal fixation in the treatment of unstable intertrochanteric fractures in the elderly. METHODS: Retrospective analysis of 70 cases of unstable intertrochanteric fractures treated from January 2016 to January 2019 and meeting the inclusion and exclusion criteria, 39 cases were fixed with closed reduction and new proximal femoral intramedullary nail(InterTAN), and 31 cases were treated with open trochanter reconstruction and artificial femoral head replacement. The operation time, intraoperative bleeding, hospital stay, weight bearing time, postoperative complication rate and hip function recovery (Harris score) were compared between two groups. RESULTS: All cases were followed up for 12 to 24 months. There were no significant differences in intraoperative bleeding and hospital stay between the two groups (P>0.05). The operation time in replacement group was longer than that in internal fixation group (P< 0.05). The postoperative weight-bearing time in replacement group was significantly earlier than that in internal fixation group (P<0.05). In the replacement group, there were 1 case of pulmonary infection, 1 case of deep venous thrombosis and 1 case of periprosthetic fracture;in the internal fixation group, there were 4 cases of pulmonary infection, 3 cases of internal fixation failure, 3 cases of cerebral infarction and 2 cases of urinary infection;there was significant difference between two groups (P< 0.05). The Harris score in replacement group was higher than that in internal fixation group one month after operation (P< 0.05), but there was no significant difference between two groups at 12 months after operation(P>0.05). CONCLUSION: InterTAN and femoral head replacement can treat unstable intertrochanteric fractures in the elderly, but femoral head replacement can move down early, improve the quality of life at the end of life, reduce postoperative complications and facilitate the treatment of coexisting diseases in internal medicine.


Assuntos
Fraturas do Fêmur , Fixação Intramedular de Fraturas , Fraturas do Quadril , Idoso , Pinos Ortopédicos , Cabeça do Fêmur , Fixação Interna de Fraturas , Fraturas do Quadril/cirurgia , Humanos , Qualidade de Vida , Estudos Retrospectivos , Resultado do Tratamento
4.
Transcription ; 12(4): 219-231, 2021 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-34719335

RESUMO

During transcription, RNA polymerase (RNAP) translocates along the helical template DNA while maintaining high transcriptional fidelity. However, all genomes are dynamically twisted, writhed, and decorated by bound proteins and motor enzymes. In prokaryotes, proteins bound to DNA, specifically or not, frequently compact DNA into conformations that may silence genes by obstructing RNAP. Collision of RNAPs with these architectural proteins, may result in RNAP stalling and/or displacement of the protein roadblock. It is important to understand how rapidly transcribing RNAPs operate under different levels of supercoiling or in the presence of roadblocks. Given the broad range of asynchronous dynamics exhibited by transcriptional complexes, single-molecule assays, such as atomic force microscopy, fluorescence detection, optical and magnetic tweezers, etc. are well suited for detecting and quantifying activity with adequate spatial and temporal resolution. Here, we summarize current understanding of the effects of torsion and roadblocks on prokaryotic transcription, with a focus on single-molecule assays that provide real-time detection and readout.

5.
Nanomaterials (Basel) ; 11(11)2021 Nov 14.
Artigo em Inglês | MEDLINE | ID: mdl-34835829

RESUMO

Ferroelectric thin film capacitors have triggered great interest in pulsed power systems because of their high-power density and ultrafast charge-discharge speed, but less attention has been paid to the realization of flexible capacitors for wearable electronics and power systems. In this work, a flexible Ba0.5Sr0.5TiO3/0.4BiFeO3-0.6SrTiO3 thin film capacitor is synthesized on mica substrate. It possesses an energy storage density of Wrec ~ 62 J cm-3, combined with an efficiency of η ~ 74% due to the moderate breakdown strength (3000 kV cm-1) and the strong relaxor behavior. The energy storage performances for the film capacitor are also very stable over a broad temperature range (-50-200 °C) and frequency range (500 Hz-20 kHz). Moreover, the Wrec and η are stabilized after 108 fatigue cycles. Additionally, the superior energy storage capability can be well maintained under a small bending radius (r = 2 mm), or after 104 mechanical bending cycles. These results reveal that the Ba0.5Sr0.5TiO3/0.4BiFeO3-0.6SrTiO3 film capacitors in this work have great potential for use in flexible microenergy storage systems.

6.
Zhongguo Shi Yan Xue Ye Xue Za Zhi ; 29(5): 1528-1532, 2021 Oct.
Artigo em Chinês | MEDLINE | ID: mdl-34627435

RESUMO

OBJECTIVE: To investigate the clinical characteristics of myelodysplastic syndrome (MDS) patients with chromosome 21 karyotype abnormality. METHODS: The clinical data of 155 patients with MDS were retrospectively analyzed, the clinical characteristics, survival and factors affecting prognosis of chromosome 21 karyotype abnormality patients were analyzed. RESULTS: Among 155 MDS patients, 4 were 5q- syndrome, 41 were MDS-EB-I, 35 were MDS-EB-II, 27 were MDS-SLD, 46 were MDS-MLD, 1 was MDS-RS-SLD, and 1 was MDS-U. The median follow-up time was 11.0(0.1-120.9) months. Among 155 MDS patients, 13 (9.0%) showed chromosome 21 abnormalities. Among the 13 patients with chromosome 21 karyotype abnormalities, there were 5 cases with simple +21 karyotype, 1 case with del (21q12), 1 case with +8, +21, 1 case with i(21q), 1 case with 20q-, +21, and 4 cases with complex karyotype involving chromosome 21; including 2 cases of MDS-SLD, 4 cases of MDS-MLD, 5 cases of MDS-EB-I and 2 cases of MDS-EB-II. The median survival time of the patients was 3.1 (0.1-6.7) months. CONCLUSION: Chromosome 21 karyotype abnormality is rare in MDS, and the prognosis is worse than the patients without chromosome 21 abnormalities.


Assuntos
Cromossomos Humanos Par 21 , Síndromes Mielodisplásicas , Humanos , Cariótipo , Cariotipagem , Síndromes Mielodisplásicas/genética , Estudos Retrospectivos
7.
Front Aging Neurosci ; 13: 736026, 2021.
Artigo em Inglês | MEDLINE | ID: mdl-34658839

RESUMO

Objective: To evaluate the altered expression of peripheral clock genes, circulating melatonin levels, and their correlations with sleep-wake phenotypes including probable rapid eye movement sleep behavior disorder (pRBD) symptoms in a relatively large population of Parkinson's disease (PD) patients. Methods: We determined the expression profiles of five principal clock genes, BMAL1, CLOCK, CRY1, PER1, and PER2, in the peripheral blood mononuclear cells (PBMCs) of PD patients (n = 326), and healthy controls (HC, n = 314) using quantitative real-time PCR. Melatonin concentration in the plasma of two groups was evaluated by enzyme-linked immunosorbent assay. Then we performed comprehensive association analyses on the PBMCs clock gene expression, plasma melatonin levels and sleep characteristics. Results: Our data showed that the expression levels of BMAL1, CLOCK, CRY1, PER1, and PER2 were significantly decreased in the PBMCs of PD as compared with that of HC (P < 0.05). PD patients had reduced plasma melatonin levels compared with HC (P < 0.0001). pRBD and excessive daytime sleepiness are common in these PD patients and are associated with the expression levels of all five clock genes (r = -0.344∼-0.789, P < 0.01) and melatonin concentration (r = -0.509∼-0.753, P < 0.01). Statistical analyses also revealed that a combination of five clock genes and melatonin could reach a high diagnostic performance (areas under the curves, 97%) for PD comorbid pRBD. Conclusion: This case-control study demonstrates that peripheral BMAL1, CLOCK, CRY1, PER1, PER2, and melatonin levels are altered in PD patients and may serve as endogenous markers for sleep and wakefulness disturbances of PD.

8.
BMC Cancer ; 21(1): 1135, 2021 Oct 23.
Artigo em Inglês | MEDLINE | ID: mdl-34688260

RESUMO

BACKGROUND: Clear cell renal cell carcinoma (ccRCC) is one of the most lethal urological malignancies, but the pathogenesis and prognosis of ccRCC remain obscure, which need to be better understand. METHODS: Differentially expressed genes were identified and function enrichment analyses were performed using three publicly available ccRCC gene expression profiles downloaded from the Gene Expression Omnibus database. The protein-protein interaction and the competing endogenous RNA (ceRNA) networks were visualized by Cytoscape. Multivariate Cox analysis was used to predict an optimal risk mode, and the survival analysis was performed with the Kaplan-Meier curve and log-rank test. Protein expression data were downloaded from Clinical Proteomic Tumor Analysis Consortium database and Human Protein Atlas database, and the clinical information as well as the corresponding lncRNA and miRNA expression data were obtained via The Cancer Genome Atlas database. The co-expressed genes and potential function of candidate genes were explored using data exacted from the Cancer Cell Line Encyclopedia database. RESULTS: Of the 1044 differentially expressed genes shared across the three datasets, 461 were upregulated, and 583 were downregulated, which significantly enriched in multiple immunoregulatory-related biological process and tumor-associated pathways, such as HIF-1, PI3K-AKT, P53 and Rap1 signaling pathways. In the most significant module, 36 hub genes were identified and were predominantly enriched in inflammatory response and immune and biotic stimulus pathways. Survival analysis and validation of the hub genes at the mRNA and protein expression levels suggested that these genes, particularly complement component 3 (C3) and fibronectin 1 (FN1), were primarily responsible for ccRCC tumorigenesis and progression. Increased expression of C3 or FN1 was also associated with advanced clinical stage, high pathological grade, and poor survival in patients with ccRCC. Univariate and multivariate Cox regression analysis qualified the expression levels of the two genes as candidate biomarkers for predicting poor survival. FN1 was potentially regulated by miR-429, miR-216b and miR-217, and constructed a bridge to C3 and C3AR1 in the ceRNA network, indicating a critical position of FN1. CONCLUSIONS: The biomarkers C3 and FN1 could provide theoretical support for the development of a novel prognostic tool to advance ccRCC diagnosis and targeted therapy.

9.
World J Clin Cases ; 9(26): 7750-7761, 2021 Sep 16.
Artigo em Inglês | MEDLINE | ID: mdl-34621825

RESUMO

BACKGROUND: Due to improvements in living standards, people are now paying more attention to their health. In China, more patients choose to go to large or well-known hospitals, which leads to constant crowding of outpatient clinics in these hospitals. AIM: To establish precision valuation reservation registration aimed at shortening waiting time, improving patient experience and promoting the satisfaction of outpatients and medical staff. METHODS: On the basis of the implementation of a conventional appointment system, more reasonable time intervals were set for different doctors by evaluating the actual capacity of each doctor to receive patients, and appointment times were made more accurate through intervention. The change in consultation waiting time of patients was then compared. Correlations between the consultation waiting time of patients and the satisfaction of patients or satisfaction of medical staff were analyzed. RESULTS: After precision valuation reservation registration, the average consultation waiting time of patients reduced from 18.47 min to 10.11 min (t = 8.90, P < 0.001). The satisfaction score of patients increased from 91.33 to 96.27 (t = -8.62, P < 0.001), and the satisfaction score of medical staff increased from 90.51 to 96.04 (t = -10.50, P < 0.001). The consultation waiting time of patients was negatively correlated with their satisfaction scores (γ = -0.89, P < 0.001). The consultation waiting time of patients was also negatively correlated with medical staff satisfaction scores (γ = -0.96, P < 0.001). CONCLUSION: Precision valuation reservation registration significantly shortened outpatient waiting times and improve the satisfaction of not only patients but also medical staff. This approach played an important role in improving outpatient services, provided a model that is supported by relevant evidence and could continuously improve the quality of management. Precision valuation reservation registration is worth promoting and applying in the clinic.

10.
Sci Rep ; 11(1): 20159, 2021 Oct 11.
Artigo em Inglês | MEDLINE | ID: mdl-34635711

RESUMO

Paraquat (PQ) is a widely used fast-acting pyridine herbicide. Accidental ingestion or self-administration via various routes can cause severe organ damage. Currently, no effective antidote is available commercially, and the mortality rate of poisoned patients is exceptionally high. Here, the efficacy of anthrahydroquinone-2-6-disulfonate (AH2QDS) was observed in treating PQ poisoning by constructing in vivo and ex vivo models. We then explored the detoxification mechanism of AH2QDS. We demonstrated that, in a rat model, the PQ concentration in the PQ + AH2QDS group significantly decreased compared to the PQ only group. Additionally, AH2QDS protected the mitochondria of rats and A549 cells and decreased oxidative stress damage, thus improving animal survival and cell viability. Finally, the differentially expressed genes were analysed in the PQ + AH2QDS group and the PQ group by NextGen sequencing, and we verified that Nrf2's expression in the PQ + AH2QDS group was significantly higher than that in the PQ group. Our work identified that AH2QDS can detoxify PQ by reducing PQ uptake and protecting mitochondria while enhancing the body's antioxidant activity.

11.
Soft Matter ; 17(46): 10421-10427, 2021 Dec 01.
Artigo em Inglês | MEDLINE | ID: mdl-34605528

RESUMO

Hydrogels are widely used in applications such as soft robots and flexible sensors due to their sensitivity to environmental stimuli. It is highly demanded to develop multiple-responsive hydrogel structures. In this work, we employ the 3D printing technique to fabricate a PNIPAM-PEGDA hydrogel bilayer that can change shape through controlling the temperature, solvent mixture and magnetic field. The PNIPAM gel is a typical thermo-responsive gel, showing a decrease in swelling ratio with increasing temperature. Meanwhile, the PNIPAM gels also exhibit the cononsolvency effect in ethanol-water mixtures with a smaller swelling ratio in the mixture compared with that in each pure solvent. In comparison, the swelling ratio of PEGDA gels is insensitive to changes in both the temperature and solvent composition. Thus, the bilayer structure of PNIPAM-PEGDA can bend in different directions and with different angles with changing the temperature and solvent composition. Finally, Fe3O4 nanoparticles are incorporated into the matrix of PEGDA gels, endowing the whole structure with deformation and motion in response to an external magnetic field.

12.
Stem Cell Res Ther ; 12(1): 556, 2021 Oct 30.
Artigo em Inglês | MEDLINE | ID: mdl-34717746

RESUMO

Intrauterine adhesion refers to endometrial repair disorders which are usually caused by uterine injury and may lead to a series of complications such as abnormal menstrual bleeding, recurrent abortion and secondary infertility. At present, therapeutic approaches to intrauterine adhesion are limited due to the lack of effective methods to promote regeneration following severe endometrial injury. Therefore, to develop new methods to prevent endometrial injury and intrauterine adhesion has become an urgent need. For severely damaged endometrium, the loss of stem cells in the endometrium may affect its regeneration. This article aimed to discuss the characteristics of various stem cells and their applications for uterine tissue regeneration.

13.
J Am Chem Soc ; 143(41): 17226-17235, 2021 Oct 20.
Artigo em Inglês | MEDLINE | ID: mdl-34617746

RESUMO

We explore the selective electrocatalytic hydrogenation of lignin monomers to methoxylated chemicals, of particular interest, when powered by renewable electricity. Prior studies, while advancing the field rapidly, have so far lacked the needed selectivity: when hydrogenating lignin-derived methoxylated monomers to methoxylated cyclohexanes, the desired methoxy group (-OCH3) has also been reduced. The ternary PtRhAu electrocatalysts developed herein selectively hydrogenate lignin monomers to methoxylated cyclohexanes-molecules with uses in pharmaceutics. Using X-ray absorption spectroscopy and in situ Raman spectroscopy, we find that Rh and Au modulate the electronic structure of Pt and that this modulating steers intermediate energetics on the electrocatalyst surface to facilitate the hydrogenation of lignin monomers and suppress C-OCH3 bond cleavage. As a result, PtRhAu electrocatalysts achieve a record 58% faradaic efficiency (FE) toward 2-methoxycyclohexanol from the lignin monomer guaiacol at 200 mA cm-2, representing a 1.9× advance in FE and a 4× increase in partial current density compared to the highest productivity prior reports. We demonstrate an integrated lignin biorefinery where wood-derived lignin monomers are selectively hydrogenated and funneled to methoxylated 2-methoxy-4-propylcyclohexanol using PtRhAu electrocatalysts. This work offers an opportunity for the sustainable electrocatalytic synthesis of methoxylated pharmaceuticals from renewable biomass.

14.
Angew Chem Int Ed Engl ; 60(47): 24888-24893, 2021 11 15.
Artigo em Inglês | MEDLINE | ID: mdl-34553823

RESUMO

Described herein is an imidazole ring formation strategy for the synthesis of axially chiral N-arylbenzimidazoles by means of chiral phosphoric acid catalysis. Two sets of conditions were developed to transform two classes of 2-naphthylamine derivatives into structurally diverse N-arylbenzimidazole atropisomers with excellent chemo- and regioselectivity as well as high levels of enantiocontrol. It is worth reflecting on the unique roles played by the nitroso group in this domino reaction. It functions as a linchpin by first offering an electrophilic site (N) for the initial C-N bond formation while the resulting amine performs the nucleophilic addition to form the second C-N bond. Additionally, it could facilitate the final oxidative aromatization as an oxidant. The atropisomeric products could be conveniently elaborated to a series of axially chiral derivatives, enabling the exploitation of N-arylbenzimidazoles for their potential utilities in asymmetric catalysis.

15.
Eur J Med Chem ; 226: 113855, 2021 Dec 15.
Artigo em Inglês | MEDLINE | ID: mdl-34555614

RESUMO

Lysine-specific demethylase 5A (KDM5A, also named RBP2 or JARID1A) is a demethylase that can remove methyl groups from histones H3K4me1/2/3. It is aberrantly expressed in many cancers, where it impedes differentiation and contributes to cancer cell proliferation, cell metastasis and invasiveness, drug resistance, and is associated with poor prognosis. Pharmacological inhibition of KDM5A has been reported to significantly attenuate tumor progression in vitro and in vivo in a range of solid tumors and acute myeloid leukemia. This review will present the structural aspects of KDM5A, its role in carcinogenesis, a comparison of currently available approaches for screening KDM5A inhibitors, a classification of KDM5A inhibitors, and its potential as a drug target in cancer therapy.

16.
Nat Commun ; 12(1): 5067, 2021 Aug 20.
Artigo em Inglês | MEDLINE | ID: mdl-34417447

RESUMO

An overarching challenge of the electrochemical carbon dioxide reduction reaction (eCO2RR) is finding an earth-abundant, highly active catalyst that selectively produces hydrocarbons at relatively low overpotentials. Here, we report the eCO2RR performance of two-dimensional transition metal carbide class of materials. Our results indicate a maximum methane (CH4) current density of -421.63 mA/cm2 and a CH4 faradic efficiency of 82.7% ± 2% for di-tungsten carbide (W2C) nanoflakes in a hybrid electrolyte of 3 M potassium hydroxide and 2 M choline-chloride. Powered by a triple junction photovoltaic cell, we demonstrate a flow electrolyzer that uses humidified CO2 to produce CH4 in a 700-h process under one sun illumination with a CO2RR energy efficiency of about 62.3% and a solar-to-fuel efficiency of 20.7%. Density functional theory calculations reveal that dissociation of water, chemisorption of CO2 and cleavage of the C-O bond-the most energy consuming elementary steps in other catalysts such as copper-become nearly spontaneous at the W2C surface. This results in instantaneous formation of adsorbed CO-an important reaction intermediate-and an unlimited source of protons near the tungsten surface sites that are the main reasons for the observed superior activity, selectivity, and small potential.

17.
J Clin Invest ; 131(16)2021 08 16.
Artigo em Inglês | MEDLINE | ID: mdl-34396988

RESUMO

Ovarian cancer is the leading cause of gynecological malignancy-related deaths, due to its widespread intraperitoneal metastases and acquired chemoresistance. Mesothelial cells are an important cellular component of the ovarian cancer microenvironment that promote metastasis. However, their role in chemoresistance is unclear. Here, we investigated whether cancer-associated mesothelial cells promote ovarian cancer chemoresistance and stemness in vitro and in vivo. We found that osteopontin is a key secreted factor that drives mesothelial-mediated ovarian cancer chemoresistance and stemness. Osteopontin is a secreted glycoprotein that is clinically associated with poor prognosis and chemoresistance in ovarian cancer. Mechanistically, ovarian cancer cells induced osteopontin expression and secretion by mesothelial cells through TGF-ß signaling. Osteopontin facilitated ovarian cancer cell chemoresistance via the activation of the CD44 receptor, PI3K/AKT signaling, and ABC drug efflux transporter activity. Importantly, therapeutic inhibition of osteopontin markedly improved the efficacy of cisplatin in both human and mouse ovarian tumor xenografts. Collectively, our results highlight mesothelial cells as a key driver of ovarian cancer chemoresistance and suggest that therapeutic targeting of osteopontin may be an effective strategy for enhancing platinum sensitivity in ovarian cancer.


Assuntos
Osteopontina/metabolismo , Neoplasias Ovarianas/tratamento farmacológico , Neoplasias Ovarianas/metabolismo , Animais , Antineoplásicos/farmacologia , Linhagem Celular Tumoral , Cisplatino/farmacologia , Resistencia a Medicamentos Antineoplásicos , Epitélio/efeitos dos fármacos , Epitélio/metabolismo , Epitélio/patologia , Feminino , Humanos , Camundongos , Células-Tronco Neoplásicas/efeitos dos fármacos , Células-Tronco Neoplásicas/metabolismo , Células-Tronco Neoplásicas/patologia , Organoides/efeitos dos fármacos , Organoides/metabolismo , Organoides/patologia , Osteopontina/antagonistas & inibidores , Neoplasias Ovarianas/patologia , Comunicação Parácrina/efeitos dos fármacos , Transdução de Sinais/efeitos dos fármacos , Microambiente Tumoral/efeitos dos fármacos , Microambiente Tumoral/fisiologia , Ensaios Antitumorais Modelo de Xenoenxerto
18.
J Alzheimers Dis ; 83(4): 1741-1752, 2021.
Artigo em Inglês | MEDLINE | ID: mdl-34459393

RESUMO

BACKGROUND: Some studies have demonstrated an association between low and high body mass index (BMI) and an increased risk of dementia. However, only a few of these studies were performed in rural areas. OBJECTIVE: This cross-sectional study investigated the associations between BMI and cognitive impairment among community-dwelling older adults from rural and urban areas. METHODS: 8,221 older persons enrolled in the Hubei Memory & Ageing Cohort Study (HMACS) were recruited. Sociodemographic and lifestyle data, comorbidities, physical measurements, and clinical diagnoses of cognitive impairment were analyzed. Logistic regression was performed to assess the associations of BMI categories with cognitive impairment. A series of sensitivity analyses were conducted to test whether reverse causality could influence our results. RESULTS: Being underweight in the rural-dwelling participants increased the risk of cognitive impairment. Being overweight was a protective factor in rural-dwelling participants aged 65-69 years and 75-79 years, whereas being underweight was significantly associated with cognitive impairment (OR, 1.37; 95% CI: 1.03-1.83; p < 0.05). Sensitivity analyses support that underweight had an additive effect on the odds of cognitive impairment and was related to risk of dementia. Interaction test revealed that the differences between urban/rural in the relationship between BMI and cognitive impairment are statistically significant. CONCLUSION: Associations between BMI and cognitive impairment differ among urban/rural groups. Older people with low BMI living in rural China are at a higher risk for dementia than those living in urban areas.

19.
Neurosci Lett ; 761: 136112, 2021 09 14.
Artigo em Inglês | MEDLINE | ID: mdl-34265417

RESUMO

Recent evidence has confirmed the association of glucocorticoid receptor (GR) gene variants with the "stress" endocrine axis in postpartum depression (PPD). Sirtuin 1(SIRT1) is an NAD+-dependent histone deacetylase and transcriptional enhancer of GR. However, to date, the function of the SIRT1 gene in the regulation of GR expression in PPD remains to be fully determined. A hormone-stimulated pregnancy (HSP) and subsequent "postpartum" withdrawal of estrogen was employed to mimic the fluctuations in estradiol associated with pregnancy and postpartum. We confirmed that estradiol benzoate withdrawal (EW)-rats displayed depression- and anxiety-like behaviors. These behavioral dysfunctions are associated with attenuated expression of SIRT1 and GR in the hippocampus. To assess the role of SIRT1, as well as its regulatory target directly, a selective SIRT1 activator (SRT2104) was infused into the hippocampus of EW-rats. We found that pharmacological activation of hippocampal SIRT1 blocks the development of depression-related, but not anxiety-related, phenotypes of PPD. In addition, the activation of SIRT1 leads to an increase in hippocampal GR expression in EW-rats. We further confirmed that SIRT1 physically interacts with GR in a glucocorticoid-dependent manner. Taken together, our results suggest that neuropathology in PPD is caused, at least in part, by the inhibition of the SIRT1-GR signaling pathway. Elevating SIRT1 levels, either pharmacologically or through other means, could represent a therapeutic strategy for PPD.

20.
Braz J Med Biol Res ; 54(8): e11184, 2021.
Artigo em Inglês | MEDLINE | ID: mdl-34320121

RESUMO

Hypertrophic scar (HS) formation is a common complication that develops after skin injury; however, there are few effective and specific therapeutic approaches for HS. Emodin has previously been reported to inhibit mechanical stress-induced HS inflammation. Here, we investigated the molecular mechanisms underlying the inhibitory effects of emodin on HS formation. First, we conducted in vitro assays that revealed that emodin inhibited M1 and M2 polarization in rat macrophages. We subsequently established a combined rat model of tail HS and dorsal subcutaneous polyvinyl alcohol (PVA) sponge-induced wounds. Rats were treated with emodin or vehicle (DMEM). Tail scar specimens were harvested at 14, 28, and 42 days post-incision and subjected to H&E staining and Masson's trichrome staining. Histopathological analyses confirmed that emodin attenuated HS formation and fibrosis. Macrophages were separated from wound cells collected from the PVA sponge at 3 and 7 days after implantation. Flow cytometry analysis demonstrated that emodin suppressed in vivo macrophage recruitment and polarization at the wound site. Finally, we explored the molecular mechanisms of emodin in modulating macrophage polarization by evaluating the expression levels of selected effectors of the Notch and TGF-ß pathways in macrophages isolated from PVA sponges. Western blot and qPCR assays showed that Notch1, Notch4, Hes1, TGF-ß, and Smad3 were downregulated in response to emodin treatment. Taken together, our findings suggested that emodin attenuated HS formation and fibrosis by suppressing macrophage polarization, which is associated with the inhibition of the Notch and TGF-ß pathways in macrophages.


Assuntos
Cicatriz Hipertrófica , Emodina , Animais , Cicatriz Hipertrófica/tratamento farmacológico , Cicatriz Hipertrófica/patologia , Emodina/farmacologia , Macrófagos , Ratos , Transdução de Sinais , Fator de Crescimento Transformador beta
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