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1.
Arterioscler Thromb Vasc Biol ; 44(7): 1628-1645, 2024 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-38813696

RESUMO

BACKGROUND: Pericoronary epicardial adipose tissue (EAT) is a unique visceral fat depot that surrounds the adventitia of the coronary arteries without any anatomic barrier. Clinical studies have demonstrated the association between EAT volume and increased risks for coronary artery disease (CAD). However, the cellular and molecular mechanisms underlying the association remain elusive. METHODS: We performed single-nucleus RNA sequencing on pericoronary EAT samples collected from 3 groups of subjects: patients undergoing coronary bypass surgery for severe CAD (n=8), patients with CAD with concomitant type 2 diabetes (n=8), and patients with valvular diseases but without concomitant CAD and type 2 diabetes as the control group (n=8). Comparative analyses were performed among groups, including cellular compositional analysis, cell type-resolved transcriptomic changes, gene coexpression network analysis, and intercellular communication analysis. Immunofluorescence staining was performed to confirm the presence of CAD-associated subclusters. RESULTS: Unsupervised clustering of 73 386 nuclei identified 15 clusters, encompassing all known cell types in the adipose tissue. Distinct subpopulations were identified within primary cell types, including adipocytes, adipose stem and progenitor cells, and macrophages. CD83high macrophages and FOSBhigh adipocytes were significantly expanded in CAD. In comparison to normal controls, both disease groups exhibited dysregulated pathways and altered secretome in the primary cell types. Nevertheless, minimal differences were noted between the disease groups in terms of cellular composition and transcriptome. In addition, our data highlight a potential interplay between dysregulated circadian clock and altered physiological functions in adipocytes of pericoronary EAT. ANXA1 (annexin A1) and SEMA3B (semaphorin 3B) were identified as important adipokines potentially involved in functional changes of pericoronary EAT and CAD pathogenesis. CONCLUSIONS: We built a complete single-nucleus transcriptomic atlas of human pericoronary EAT in normal and diseased conditions of CAD. Our study lays the foundation for developing novel therapeutic strategies for treating CAD by targeting and modifying pericoronary EAT functions.


Assuntos
Tecido Adiposo , Doença da Artéria Coronariana , Pericárdio , Transcriptoma , Humanos , Pericárdio/metabolismo , Pericárdio/patologia , Feminino , Masculino , Pessoa de Meia-Idade , Doença da Artéria Coronariana/genética , Doença da Artéria Coronariana/patologia , Doença da Artéria Coronariana/metabolismo , Idoso , Tecido Adiposo/metabolismo , Tecido Adiposo/patologia , Diabetes Mellitus Tipo 2/genética , Diabetes Mellitus Tipo 2/metabolismo , Diabetes Mellitus Tipo 2/complicações , Adipócitos/metabolismo , Adipócitos/patologia , Doenças das Valvas Cardíacas/genética , Doenças das Valvas Cardíacas/patologia , Doenças das Valvas Cardíacas/metabolismo , Doenças das Valvas Cardíacas/cirurgia , Perfilação da Expressão Gênica/métodos , Estudos de Casos e Controles , Ponte de Artéria Coronária , Análise de Célula Única , Macrófagos/metabolismo , Macrófagos/patologia , Redes Reguladoras de Genes , Tecido Adiposo Epicárdico
2.
BMC Cancer ; 23(1): 463, 2023 May 19.
Artigo em Inglês | MEDLINE | ID: mdl-37208633

RESUMO

BACKGROUND: Treatment options for pretreated triple-negative breast cancer (TNBC) are limited. This study aimed to evaluate the efficacy and safety of apatinib, an antiangiogenic agent, in combination of etoposide for pretreated patients with advanced TNBC. METHODS: In this single-arm phase II trial, patients with advanced TNBC who failed to at least one line of chemotherapy were enrolled. Eligible patients received oral apatinib 500 mg on day 1 to 21, plus oral etoposide 50 mg on day 1 to 14 of a 3-week cycle until disease progression or intolerable toxicities. Etoposide was administered up to six cycles. The primary endpoint was progression-free survival (PFS). RESULTS: From September 2018 to September 2021, 40 patients with advanced TNBC were enrolled. All patients received previous chemotherapy in the advanced setting, with the median previous lines of 2 (1-5). At the cut-off date on January 10, 2022, the median follow-up was 26.8 (1.6-52.0) months. The median PFS was 6.0 (95% confidence interval [CI]: 3.8-8.2) months, and the median overall survival was 24.5 (95%CI: 10.2-38.8) months. The objective response rate and disease control rate was 10.0% and 62.5%, respectively. The most common adverse events (AEs) were hypertension (65.0%), nausea (47.5%) and vomiting (42.5%). Four patients developed grade 3 AE, including two with hypertension and two with proteinuria. CONCLUSIONS: Apatinib combined with oral etoposide was feasible in pretreated advanced TNBC, and was easy to administer. CLINICAL TRIAL REGISTRATION: Chictr.org.cn, (registration number: ChiCTR1800018497, registration date: 20/09/2018).


Assuntos
Antineoplásicos , Hipertensão , Neoplasias de Mama Triplo Negativas , Humanos , Etoposídeo/efeitos adversos , Antineoplásicos/uso terapêutico , Neoplasias de Mama Triplo Negativas/tratamento farmacológico , Hipertensão/induzido quimicamente
3.
BMC Geriatr ; 23(1): 198, 2023 03 30.
Artigo em Inglês | MEDLINE | ID: mdl-36997928

RESUMO

BACKGROUND: Postoperative delirium (POD) is a common postoperative complication associated with multiple adverse consequences on patient outcomes and higher medical expenses. Preoperative anxiety has been suggested as a possible precipitating factor for the development of POD. As such, we aimed to explore the association between preoperative anxiety and POD in older surgical patients. METHODS: Electronic databases including MEDLINE (via PubMed), EMBASE (via Embase.com), Web of Science Core Collection, Cumulative Index to Nursing and Allied Health Literature (CINAHL Complete; via EBSCOhost) and clinical trial registries were systematically searched to identify prospective studies examining preoperative anxiety as a risk factor for POD in older surgical patients. We used Joanna Briggs Institute Critical Appraisal Checklist for Cohort Studies to assess the quality of included studies. The association between preoperative anxiety and POD was summarized with odds ratios (ORs) and 95% confidence intervals (CIs) using DerSimonian-Laird random-effects meta-analysis. RESULTS: Eleven studies were included (1691 participants; mean age ranging between 63.1-82.3 years). Five studies used a theoretical definition for preoperative anxiety, with the Anxiety subscale of Hospital Anxiety and Depression Scale (HADS-A) as the instrument being most often used. When using dichotomized measures and within the HADS-A subgroup analysis, preoperative anxiety was significantly associated with POD (OR = 2.17, 95%CI: 1.01-4.68, I2 = 54%, Tau2 = 0.4, n = 5; OR = 3.23, 95%CI: 1.70-6.13, I2 = 0, Tau2 = 0, n = 4; respectively). No association was observed when using continuous measurements (OR = 0.99, 95%CI: 0.93-1.05, I2 = 0, Tau2 = 0, n = 4), nor in the subgroup analysis of STAI-6 (six-item version of state scale of Spielberger State-Trait Anxiety Inventory, OR = 1.07, 95%CI: 0.93-1.24, I2 = 0, Tau2 = 0, n = 2). We found the overall quality of included studies to be moderate to good. CONCLUSIONS: An unclear association between preoperative anxiety and POD in older surgical patients was found in our study. Given the ambiguity in conceptualization and measurement instruments used for preoperative anxiety, more research is warranted in which a greater emphasis should be placed on how preoperative anxiety is operationalized and measured.


Assuntos
Delírio , Delírio do Despertar , Humanos , Idoso , Idoso de 80 Anos ou mais , Delírio/diagnóstico , Delírio/epidemiologia , Delírio/etiologia , Estudos Prospectivos , Ansiedade/diagnóstico , Complicações Pós-Operatórias/diagnóstico , Complicações Pós-Operatórias/epidemiologia , Complicações Pós-Operatórias/etiologia , Fatores de Risco
4.
BMC Med Res Methodol ; 21(1): 132, 2021 06 26.
Artigo em Inglês | MEDLINE | ID: mdl-34174838

RESUMO

BACKGROUND: Despite experimental evidence suggesting that pain sensitivity is not impaired by cognitive impairment, observational studies in nursing home residents have observed an inverse association between cognitive impairment and resident-reported or staff-assessed pain. Under the hypothesis that the inverse association may be partially attributable to differential misclassification due to recall and communication limitations, this study implemented a missing data approach to quantify the absolute magnitude of misclassification of pain, pain frequency, and pain intensity by level of cognitive impairment. METHODS: Using the 2016 Minimum Data Set 3.0, we conducted a cross-sectional study among newly admitted US nursing home residents. Pain presence, severity, and frequency is assessed via resident-reported measures. For residents unable to communicate their pain, nursing home staff document pain based on direct resident observation and record review. We estimate a counterfactual expected level of pain in the absence of cognitive impairment by multiply imputing modified pain indicators for which the values were retained for residents with no/mild cognitive impairment and set to missing for residents with moderate/severe cognitive impairment. Absolute differences (∆) in the presence and magnitude of pain were calculated as the difference between documented pain and the expected level of pain. RESULTS: The difference between observed and expected resident reported pain was greater in residents with severe cognitive impairment (∆ = -10.2%, 95% Confidence Interval (CI): -10.9% to -9.4%) than those with moderate cognitive impairment (∆ = -4.5%, 95% CI: -5.4% to -3.6%). For staff-assessed pain, the magnitude of apparent underreporting was similar between residents with moderate impairment (∆ = -7.2%, 95% CI: -8.3% to -6.0%) and residents with severe impairment (∆ = -7.2%, 95% CI: -8.0% to -6.3%). Pain characterized as "mild" had the highest magnitude of apparent underreporting. CONCLUSIONS: In residents with moderate to severe cognitive impairment, documentation of any pain was lower than expected in the absence of cognitive impairment. This finding supports the hypothesis that an inverse association between pain and cognitive impairment may be explained by differential misclassification. This study highlights the need to develop analytic and/or procedural solutions to correct for recall/reporter bias resulting from cognitive impairment.


Assuntos
Disfunção Cognitiva , Casas de Saúde , Estudos Transversais , Humanos , Dor , Medição da Dor
5.
Mol Phylogenet Evol ; 144: 106713, 2020 03.
Artigo em Inglês | MEDLINE | ID: mdl-31863901

RESUMO

The amount of plastome sequence data available has soared in the last decade, but the nature of plastome evolution during rapid radiations is largely unknown. Moreover, although there is increasing evidence showing that plastomes may have undergone adaptive evolution in order to allow adaptation to various environments, few studies have systematically investigated the role of the plastome in alpine adaptation. To address these questions, we sequenced and analyzed 12 representative species of Rhodiola, a genus which includes ca. 70 perennial herbs mainly growing in alpine habitats in the Qinghai-Tibet Plateau and the Hengduan Mountains. Rapid radiation in this genus was triggered by the uplift of the Qinghai-Tibet Plateau. We also included nine species of Crassulaceae as the outgroups. All plastomes were conserved with respect to size, structure, and gene content and order, with few variations: each contained 134 genes, including 85 protein-coding genes, 37 tRNAs, 8 rRNAs, and 4 potential pseudogenes. Four types of repeat sequence were detected. Slight contraction and expansion of the inverted repeats were also revealed. Both the genome-wide alignment and sequence polymorphism analyses showed that the inverted repeats and coding regions were more conserved than the single-copy regions and the non-coding regions. Positive selection analyses identified three genes containing sites of positive selection (rpl16, ndhA, ndhH), and one gene with a faster than average rate of evolution (psaA). The products of these genes may be involved in the adaptation of Rhodiola to alpine environments such as low CO2 concentration and high-intensity light.


Assuntos
Sequência Conservada/fisiologia , Evolução Molecular , Genomas de Plastídeos/genética , Rhodiola/classificação , Rhodiola/genética , Sequência de Bases , Crassulaceae/classificação , Crassulaceae/genética , Ecossistema , Variação Genética/fisiologia , Genoma de Planta/fisiologia , Filogenia , Polimorfismo Genético , Sequências Repetitivas de Ácido Nucleico/genética , Tibet
6.
Med Sci Monit ; 21: 3929-34, 2015 Dec 16.
Artigo em Inglês | MEDLINE | ID: mdl-26675282

RESUMO

BACKGROUND MiRNAs play important roles in regulating many fundamental biological processes. Deregulation of miRNAs is involved in the initiation and progression of cancer. MiR-193b is regarded as tumor suppressor in many types of cancers. However, the role of miR-193b in ovarian cancer is poorly understood. MATERIAL AND METHODS The expression level of miR-193b in ovarian cancer cell lines and ovarian cancer samples was evaluated using quantitative real-time reverse transcription-PCR (qRT-PCR). The ovarian cancer patients were categorized into a high miR-193b expression group and a low miR-193b expression group according to the median miR-193b expression level. The correlation between tissue miR-193b expression and the patients' clinicopathological factors, as well as survival, was also analyzed. RESULTS The results showed that the miR-193b expression was significantly down-regulated in ovarian cancer cell lines and tumor tissues compared with normal controls. In addition, tissue miR-193b expression was positively correlated with FIGO stage (P=0.001), histological grade (P=0.032), ascites (P=0.019), lymph node metastasis (P=0.003), and tumor size (P=0.041). Among 116 patients with ovarian cancer examined, the 5-year overall survival (OS) rates were 62.5% and 22.01% in patients with high and low miR-193b expression, respectively (P=0.003). Multivariate analysis showed that tissue miR-193b is an independent prognostic factor in patients with ovarian cancer (HR=4.219; P=0.015). CONCLUSIONS Reduction of miR-193b was found in ovarian cancer and its lower expression was associated with poorer prognosis. Tissue miR-193b showed potential as novel biomarker for ovarian cancer.


Assuntos
Biomarcadores Tumorais/metabolismo , MicroRNAs/metabolismo , Neoplasias Ovarianas/diagnóstico , Linhagem Celular Tumoral , Regulação para Baixo , Diagnóstico Precoce , Feminino , Humanos , Neoplasias Ovarianas/metabolismo , Neoplasias Ovarianas/patologia , Fatores de Risco , Análise de Sobrevida
7.
Drug Alcohol Depend ; 235: 109429, 2022 06 01.
Artigo em Inglês | MEDLINE | ID: mdl-35427982

RESUMO

BACKGROUND: Despite gabapentin's misuse and abuse potential and associated adverse events, few algorithms are available to detect gabapentin misuse and/or abuse in claims data. This study aims to develop an algorithm to identify gabapentin misuse and/or abuse in administrative claims data. METHODS: We developed an algorithm to identify gabapentin misuse and/or abuse over a 12-month period based on input from 21 clinical experts. We implemented the algorithm among 334,128 patients with at least one dispensed prescription of gabapentin between December 1, 2017 and December 1, 2018 in the IBM® MarketScan® Research Databases. We described the characteristics of patients who potentially misused and/or abused gabapentin and assessed factors associated with misuse and/or abuse using logistic regression. RESULTS: The algorithm identified 17.6% of patients with gabapentin use who potentially misused and/or abused gabapentin. Factors associated with potential gabapentin misuse and/or abuse included men (adjusted odds ratio (aOR): 1.08; 95% confidence interval (CI): 1.06-1.10), comorbid conditions (e.g., drug and alcohol dependence (aOR: 1.31; 95% CI: 1.24-1.39); bipolar disorder (aOR: 1.34; 95% CI: 1.27-1.41)), and medication use (e.g., opioids (aOR: 1.23; 95% CI: 1.20-1.26), muscle relaxants (aOR: 1.24; 95% CI: 1.21-1.27), or serotonin-norepinephrine reuptake inhibitors (aOR: 1.33; 95% CI: 1.29-1.36)). CONCLUSIONS: Approximately one in six patients with gabapentin use potentially misused and/or abused gabapentin in a large commercial claims database. Multiple comorbidities and drug use were associated with gabapentin misuse and/or abuse. Monitoring requirements and individualized safety measures should be put in place for patients at elevated risks of gabapentin misuse and/or abuse.


Assuntos
Uso Indevido de Medicamentos sob Prescrição , Transtornos Relacionados ao Uso de Substâncias , Algoritmos , Analgésicos Opioides/uso terapêutico , Gabapentina/efeitos adversos , Humanos , Masculino , Razão de Chances , Transtornos Relacionados ao Uso de Substâncias/diagnóstico , Transtornos Relacionados ao Uso de Substâncias/tratamento farmacológico , Transtornos Relacionados ao Uso de Substâncias/epidemiologia
8.
J Pain Res ; 15: 443-454, 2022.
Artigo em Inglês | MEDLINE | ID: mdl-35177933

RESUMO

BACKGROUND: Gabapentinoids have been prescribed off-label for almost all types of pain. The geographic variation in the use of gabapentinoids as analgesics remains unknown. OBJECTIVE: To describe the geographic variation in gabapentinoids, opioids and concurrent use of both for pain by US state and metropolitan statistical area (MSA). METHODS: We conducted a cross-sectional study on December 1, 2018, among commercially insured adults aged 18-64 years without epilepsy or opioid use disorders using IBM® MarketScan® Research Databases. We described the geographic variation in the analgesic regimens (gabapentinoids, opioids and concurrent use of both) by state and MSA, and assessed factors associated with the geographic variation using multilevel logistic regression. RESULTS: We included 9,314,197 beneficiaries; 1.4% had gabapentinoids, 1.5% had opioids and 0.3% had concurrent use of both. The majority of gabapentinoid use lacked an FDA-approved indication. Use of the analgesic regimens varied across states (gabapentinoids (median (interquartile range)): 1.4% (1.2-1.7%); opioids: 1.5% (1.2-1.9%); both: 0.3% (0.2-0.4%)) and MSAs (gabapentinoids: 1.6% (1.3-2.0%); opioids: 1.8% (1.3-2.3%); both: 0.3% (0.2-0.5%)). Demographics explained the largest proportion of the between-state and between-MSA variation. The pattern of the geographic variation in gabapentinoids was similar to that of opioids across states and MSAs. CONCLUSION: Gabapentinoids were as commonly used as opioids for pain in a commercially insured population (mostly off-label). The geographic variation in gabapentinoids was similar to that of opioids, which suggests that gabapentinoids may be widely used as alternatives or adjuvants to opioids across the US.

9.
Pain ; 163(7): 1370-1377, 2022 07 01.
Artigo em Inglês | MEDLINE | ID: mdl-34711763

RESUMO

ABSTRACT: Neuropathic pain is a common condition experienced by older adults. Prevalence estimates of neuropathic pain and descriptive data of pharmacologic management among nursing home residents are unavailable. We estimated the prevalence of neuropathic pain diagnoses and described the use of pain medications among nursing home residents with possible neuropathic pain. Using the Minimum Data Set 3.0 linked to Medicare claims for residents living in a nursing home on November 30, 2016, we included 473,815 residents. ICD-10 codes were used to identify neuropathic pain diagnoses. Identification of prescription analgesics/adjuvants was based on claims for the supply of medications that overlapped with the index date over a 3-month look-back period. The prevalence of neuropathic pain was 14.6%. Among those with neuropathic pain, 19.7% had diabetic neuropathy, 27.3% had back and neck pain with neuropathic involvement, and 25.1% had hereditary or idiopathic neuropathy. Among residents with neuropathic pain, 49.9% received anticonvulsants, 28.6% received antidepressants, 19.0% received opioids, and 28.2% had no claims for analgesics or adjuvants. Resident characteristics associated with lack of medications included advanced age, dependency in activities of daily living, cognitive impairment, and diagnoses of comorbid conditions. A diagnosis of neuropathic pain is common among nursing home residents, yet many lack pharmacologic treatment for their pain. Future epidemiologic studies can help develop a more standard approach to identifying and managing neuropathic pain among nursing home residents.


Assuntos
Atividades Cotidianas , Neuralgia , Idoso , Analgésicos/uso terapêutico , Humanos , Medicare , Neuralgia/diagnóstico , Neuralgia/tratamento farmacológico , Neuralgia/epidemiologia , Casas de Saúde , Prevalência , Estados Unidos/epidemiologia
10.
PLoS One ; 17(7): e0271266, 2022.
Artigo em Inglês | MEDLINE | ID: mdl-35834541

RESUMO

Loess has the characteristics of large porosity, loose structure, uniform composition and strong collapsibility. When encountering heavy rainfall and irrigation prone to saturation, resulting in loess landslides, roadbed subsidence and dam instability. In order to study the effect of dry density and shear rate on the shear strength of saturated remolded loess, the consolidated undrained (CU) test was carried out in Yan'an City by using SLB-6A stress-strain controlled triaxial shear permeability test instrument. The shear rate, confining pressure and dry density were controlled during the test. The dry densities of the samples were 1.5 g / cm3, 1.6 g / cm3 and 1.7 g / cm3, respectively. CU tests of saturated remolded loess were carried out at different shear rates under the confining pressures of 100 kPa, 150 kPa and 200 kPa, respectively. It is found that the stress-strain curve of saturated remolded loess gradually moves upward with the increase of dry density. With the increase of dry density, the cohesion and internal friction angle of remolded saturated loess samples increase. At the same shear rate, with the increase of dry density, the deviatoric stress of the specimen increases significantly.


Assuntos
Eliminação de Resíduos , Cidades , Fenômenos Físicos , Eliminação de Resíduos/métodos , Resistência ao Cisalhamento
11.
Materials (Basel) ; 15(21)2022 Oct 28.
Artigo em Inglês | MEDLINE | ID: mdl-36363168

RESUMO

The Nb4AlC3 MAX phase can be regarded as a TMC structure with stacking faults, which has great potential as a novel solid hydrogen storage material. Herein, we used ab initio calculations for understanding the hydrogen incorporation into Nb4AlC3 MAX phases, including equilibrium structural characteristics, energy changes, electronic structures, bonding characteristics, and diffusion paths. According to the calculated results, H has thermal stability in the interstice of the Nb-Al layer, and the most probable insertion site is an octahedron (3-site) composed of three Nb atoms and three Al atoms. When C vacancies are introduced, the Nb-C layer has a specific storage capacity for H. In addition, Al vacancies can also be used as possible sites for H incorporation. Moreover, the introduction of vacancies significantly increase the hydrogen storage capacity of the MAX phase. According to the electronic structure and bonding characteristics, the excellent hydrogen storage ability of the Nb4AlC3 structure may be due to the formation of ionic bonds between H and Nb/Al. It is worth noting that the H-Al bond in the 1-site is a covalent bond and an ionic bond key mixture. The linear synchronous transit optimization study shows that only H diffusion in Al vacancies is not feasible. In conclusion, the Nb-Al layer in Nb4AlC3 can provide favorable conditions for the continuous insertion and subsequent extraction of H, while the vacancy structure is more suitable for H storage. Our work provides solid theoretical results for understanding the hydrogen incorporation into Nb4AlC3 MAX phases that can be helpful for the design of advanced hydrogen storage materials.

12.
J Womens Health (Larchmt) ; 30(11): 1637-1644, 2021 11.
Artigo em Inglês | MEDLINE | ID: mdl-33450162

RESUMO

Objective: We described the burden of illness and health-related quality of life (HRQoL) in adults with spondyloarthritis (SpA) using a nationally representative sample. Materials and Methods: We identified participants with SpA using the Amor classification criteria (probable: score 5 or definite: ≥6) and complete data on HRQoL from the 2009 to 2010 National Health and Nutrition Examination Survey (n = 231). HRQoL was measured using the Healthy Days Measures including self-rated health status (excellent/very good, good, fair/poor), number of activity-restricted days, and number of unhealthy mental and physical health days in the past month (range: 0-30). Other domains including clinical assessments, comorbidities, physical functioning, and medication use were also explored. Results: Only 39% of the sample met the Amor criteria for definite SpA. Although 58% of those with definite SpA had seen a doctor >3 times in the past year, 2.5% women and 4.1% men had ever been told by a physician that they have ankylosing spondylitis. Among those with definite SpA, racial/ethnic diversity was observed in women (13.6% non-Hispanic Black, 23.2% Hispanic) and men (11.6% non-Hispanic Black, 11.2% Hispanic). Overall, 41.6% women and 49.7% men rated their health as fair/poor. For other HRQoL measures, 25.4% women and 20.4% men reported ≥15 activity-restricted days and 39.7% women and 41.4% men reported ≥15 physically unhealthy days. Conclusion: Both men and women rank health as poor with indications that it affects QoL. Although our small sample size limits definitive statements, we observed trends that warrant further confirmation in larger population-based samples.


Assuntos
Qualidade de Vida , Espondilartrite , Adulto , Efeitos Psicossociais da Doença , Feminino , Nível de Saúde , Humanos , Masculino , Inquéritos Nutricionais , Espondilartrite/epidemiologia
13.
Front Pharmacol ; 12: 774674, 2021.
Artigo em Inglês | MEDLINE | ID: mdl-34987398

RESUMO

Polydipsia and xerostomia are the most common complications that seriously affect oral health in patients with diabetes. However, to date, there is no effective treatment for diabetic xerostomia. Recent studies have reported that artesunate (ART) and metformin (Met) improve salivary gland (SG) hypofunction in murine Sjögren's syndrome. Therefore, aim of this study was to investigate the effect and underlying mechanism of artesunate (ART) alone and in combination with metformin (Met) on hyposalivation in type 2 diabetes mellitus (T2DM) rats. T2DM rats were induced using a high-fat diet and streptozotocin. SPF male Sprague-Dawley rats were divided into the following five groups: normal control group, untreated diabetic group, ART-treated diabetic group (50 mg/kg), Met-treated diabetic group (150 mg/kg), and ART/Met co-treated diabetic group (50 mg/kg ART and 150 mg/kg Met). ART and Met were intragastrically administered daily for 4 weeks. The general conditions, diabetes parameters and serum lipids were evaluated after drug treatment. Furthermore, we observed changes in the central superior salivatory nucleus (SSN) and SG, and changes in the AQP5 expression, parasympathetic innervation (AChE and BDNF expression), and PI3K/AKT pathway- (p-AKT, and p-PI3K), apoptosis- (Bax, Bcl-2, and Caspase3), and autophagy- (LC3 and P62) related markers expression in T2DM rats after treatment. Our results showed that ART or Met alone and ART/Met combination attenuated a range of diabetic symptoms, including weight loss, urine volume increase, water consumption increase, hyperglycemia, insulin resistance, glucose intolerance and dyslipidemia. More importantly, we found that these three treatments, especially ART/Met combination, mitigated hyposalivation in the T2DM rats via improving the central SSN and SGs damage in hyperglycemia. Our data also indicated that ART/Met attenuated SG damage though regulating the PI3K/Akt pathway to inhibit apoptosis and autophagy of SGs in the T2DM rats. Moreover, ART/Met preserved parasympathetic innervation (AChE and BDNF expression) in SGs to alleviate diabetes-induced hyposalivation likely through rescuing central SSN damage. Taken together, these findings might provide a novel rationale and treatment strategy for future treatment of diabetes-induced xerostomia in the clinic.

14.
Exp Ther Med ; 20(4): 3310-3315, 2020 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-32855702

RESUMO

Ovarian cancer is the eighth most common malignancy among women worldwide. Ovarian cancer exhibits no obvious symptoms in the early stage of tumorigenesis and currently, no effective methods for the early detection and treatment of ovarian cancer have been established. Therefore, the identification of novel targets is critical to the early diagnosis and clinical treatment of ovarian cancer. microRNAs (miRs) are small non-coding RNAs, which serve an important biological role in a number of physiological processes and in oncogenesis. Previous studies have reported that miRNA-193b is dysregulated in a variety of types of human cancer. However, the roles of miRNA-193b in human ovarian cancer has not been determined. The present study investigated the roles of miRNA-193b in human ovarian cancer cells. Reverse transcription-quantitative PCR results indicated that the expression of miRNA-193b in ovarian cancer cells was significantly down-regulated compared with non-malignant cells. Cell counting kit-8 results indicated that the up-regulation of miRNA-193b inhibited ovarian cancer cell proliferation and induced ovarian cancer cell apoptosis. The present study also indicated that stathmin 1 (STMN1) was a direct target of miRNA-193b, and the up-regulation of miRNA-193b significantly decreased the expression of STMN1 in ovarian cancer cells. In conclusion, the results demonstrated that miRNA-193b serves as a tumor suppressor in human ovarian cancer by inhibiting cell proliferation and inducing cell apoptosis. Therefore, the assessment of miRNA-193b may provide insight into a novel diagnostic biomarker and potential therapeutic target for patients with ovarian cancer.

15.
Drugs Aging ; 37(2): 137-145, 2020 02.
Artigo em Inglês | MEDLINE | ID: mdl-31845208

RESUMO

BACKGROUND: Antiepileptic drugs (AEDs) are commonly used by nursing home residents, both on- and off-label. The landscape of AED use has changed over the past two decades; however, despite this, contemporaneous research on AED use in US nursing home residents is scant. OBJECTIVE: The aim of this study was to estimate the prevalence of AED use, describe prescribing patterns, identify factors associated with AED use, and assess whether these factors differ among AEDs with expanded indications in older adults (i.e. gabapentin, pregabalin, topiramate, and lamotrigine). METHODS: We conducted a cross-sectional study among 549,240 long-stay older residents who enrolled in fee-for-service Medicare and lived in 15,111 US nursing homes on 1 September 2016. Demographics and conditions associated with AED indications, epilepsy comorbidities, and safety data came from the Minimum Data Set Version 3.0 (MDS 3.0). Medicare Part D claims were used to identify AED use. Robust Poisson models and multinomial logistic models for clustered data estimated adjusted prevalence ratios (aPR), adjusted odds ratios (aOR), and 95% confidence intervals (CIs). RESULTS: Overall, 24.0% used AEDs (gabapentin [13.3%], levetiracetam [4.7%], phenytoin [1.9%], pregabalin [1.8%], and lamotrigine [1.2%]). AED use was associated with epilepsy (aPR 3.73, 95% CI 3.69-3.77), bipolar disorder (aPR 1.20, 95% CI 1.18-1.22), pain (aPRmoderate/severe vs. no pain 1.42, 95% CI 1.40-1.44), diabetes (aPR 1.27, 95% CI 1.26-1.28), anxiety (aPR 1.12, 95% CI 1.11-1.13), depression (aPR 1.17, 95% CI 1.15-1.18), or stroke (aPR 1.08, 95% CI 1.06-1.09). Residents with advancing age (aPR85+ vs. 65-74 years 0.73, 95% CI 0.73-0.74), Alzheimer's disease/dementia (aPR 0.87, 95% CI 0.86-0.88), or cognitive impairment (aPRsevere vs. no impairment 0.62, 95% CI 0.61-0.63) had decreased AED use. Gabapentinoid use was highly associated with pain (aORmoderate/severe vs. no pain 2.07, 95% CI 2.01-2.12) and diabetes (aOR 1.79, 95% CI 1.76-1.82), but not with an epilepsy indication. CONCLUSIONS: AED use was common in nursing homes, with gabapentin most commonly used (presumably for pain). That multiple comorbidities were associated with AED use underscores the need for future studies to investigate the safety and effectiveness of AED use in nursing home residents.


Assuntos
Anticonvulsivantes/uso terapêutico , Prescrições de Medicamentos/estatística & dados numéricos , Uso de Medicamentos/estatística & dados numéricos , Epilepsia/tratamento farmacológico , Casas de Saúde/estatística & dados numéricos , Padrões de Prática Médica/estatística & dados numéricos , Idoso , Idoso de 80 Anos ou mais , Anticonvulsivantes/administração & dosagem , Anticonvulsivantes/efeitos adversos , Comorbidade , Estudos Transversais , Epilepsia/epidemiologia , Feminino , Humanos , Masculino , Medicare Part D , Prevalência , Estados Unidos
16.
Mitochondrial DNA B Resour ; 3(2): 753-754, 2018 Jul 10.
Artigo em Inglês | MEDLINE | ID: mdl-33474311

RESUMO

Rhodiola rosea L. is used in herbal medicine in many countries for a long time. Here, its complete chloroplast genome was assembled and annotated. The genome is 151,348 bp long and comprises a pair of inverted repeat regions (IRs, 25,790 bp each), a large single-copy region (LSC, 82,716 bp), and a small single-copy region (SSC, 17,052 bp). It contained 113 gene species (79 protein coding, 29 tRNA, 4 rRNA, and 1 pseudogene), with 20 of them occurring in double copies. Introns were detected in 12 PCG and 5 tRNA species. The nucleotide composition is inhomogeneous (30.9% A, 19.2% C, 18.5% G, and 31.4% T) with an overall A + T content of 62.3%. Phylogenetic analysis indicated that Rhodiola rosea is sister to the remaining species of Rhodiola with maximum support in phylogeny.

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