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1.
Ther Adv Chronic Dis ; 13: 20406223221091177, 2022.
Artigo em Inglês | MEDLINE | ID: mdl-35924009

RESUMO

Observational findings achieved that gut microbes mediate human metabolic health and disease risk. The types of intestinal microorganisms depend on the intake of food and drugs and are also related to their metabolic level and genetic factors. Recent studies have shown that chronic inflammatory pain is closely related to intestinal microbial homeostasis. Compared with the normal intestinal flora, the composition of intestinal flora in patients with chronic inflammatory pain had significant changes in Actinomycetes, Firmicutes, Bacteroidetes, etc. At the same time, short-chain fatty acids and amino acids, the metabolites of intestinal microorganisms, can regulate neural signal molecules and signaling pathways, thus affecting the development trend of chronic inflammatory pain. Glucocorticoids and non-steroidal anti-inflammatory drugs in the treatment of chronic inflammatory pain, the main mechanism is to affect the secretion of inflammatory factors and the abundance of intestinal bacteria. This article reviews the relationship between intestinal microorganisms and their metabolites on chronic inflammatory pain and the possible mechanism.

2.
J Am Heart Assoc ; 11(15): e025063, 2022 Aug 02.
Artigo em Inglês | MEDLINE | ID: mdl-35894088

RESUMO

Background In people with peripheral artery disease, post hoc analyses of the LITE (Low Intensity Exercise Intervention in Peripheral Artery Disease) randomized trial were conducted to evaluate the effects of walking exercise at a pace inducing ischemic leg symptoms on walking velocity and the Short Physical Performance Battery, compared with walking exercise without ischemic leg symptoms and compared with a nonexercising control group. Methods and Results Participants with peripheral artery disease were randomized to: home-based walking exercise that induced ischemic leg symptoms; home-based walking exercise conducted without ischemic leg symptoms; or a nonexercising control group for 12 months. Outcomes were change of walking velocity over 4 m and change of the Short Physical Performance Battery (0-12, with 12=best) at 6- and 12-month follow-up. A total of 264 participants (48% women, 61% Black race) were included. Compared with walking exercise without ischemic symptoms, walking exercise that induced ischemic symptoms improved change in usual-paced walking velocity over 4 m at 6-month (0.056 m/s [95% CI, 0.019-0.094 m/s]; P<0.01) and 12-month follow-up (0.084 m/s [95% CI, 0.049-0.120 m/s]; P<0.01), change in fast-paced of walking velocity over 4 m at 6-month follow-up (P=0.03), and change in the Short Physical Performance Battery at 12-month follow-up (0.821 [95% CI, 0.309-1.334]; P<0.01). Compared with control, walking exercise at a pace inducing ischemic symptoms improved change in usual-paced walking velocity over 4 m at 6-month follow-up (0.066 m/s [95% CI, 0.021-0.111 m/s]; P<0.01). Conclusions In people with peripheral artery disease, those who walked for exercise at a comfortable pace without ischemic leg symptoms slowed their walking speed during daily life and worsened the Short Physical Performance Battery score, a potentially harmful effect, compared with people who walked for exercise at a pace inducing ischemic leg symptoms. Compared with a control group who did not exercise, home-based walking exercise at a pace inducing ischemic leg symptoms significantly improved change of walking velocity over 4 m at 6-month follow-up, but this benefit did not persist at 12-month follow-up. Registration URL: https://www.clinicaltrials.gov; Unique identifier: NCT02538900.


Assuntos
Perna (Membro) , Doença Arterial Periférica , Terapia por Exercício/métodos , Feminino , Humanos , Extremidade Inferior , Masculino , Doença Arterial Periférica/diagnóstico , Doença Arterial Periférica/terapia , Desempenho Físico Funcional , Caminhada
3.
Prog Transplant ; 32(3): 252-260, 2022 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-35702045

RESUMO

Introduction: Utilizing allografts from donors after cardiac death (DCD) has improved organ availability, and DCD livers comprise a growing proportion of transplantations. However, it has been suggested that DCD transplantations have worse outcomes. Research Questions: We aimed to characterize outcomes in a large cohort of DCD transplantations, identify trends in outcomes over time, and identify factors associated with the development of biliary complications. Design: We conducted an observational retrospective cohort study of patients receiving DCD liver allografts within a large academic teaching hospital with a high transplantation volume. Consecutive patients who underwent Type III DCD liver transplantation from 2006-2016 were included in our cohort. Re-transplantations and multi-organ transplant recipients were excluded. Results: Ninety-six type III DCD transplantations occurred between 2006-2016. We report a 1one-year patient survival of 90.6% (87) and a 5five-year patient survival of 69.8% (67). Twenty-nine (30.2%) patients experienced any biliary complication in the first year following discharge, with 17 (17.7%) experiencing ischemic cholangiopathy. Five-year patient (P = 0.04) and graft (P = 0.005) survival improved over time. Post-operative biliary complications experienced during index admission and prior to discharge were found to be associated with the development of biliary complications (P = 0.005) and ischemic cholangiopathy (P = 0.01) following discharge. Conclusion: Our data suggested that outcomes using DCD allografts have improved, however biliary complications remain a significant issue in DCD transplantation. Patients who experienced post-operative biliary complications during index admission may require more frequent screening to allow the initiation of earlier treatment for biliary complications.


Assuntos
Transplante de Fígado , Obtenção de Tecidos e Órgãos , Morte , Sobrevivência de Enxerto , Humanos , Incidência , Transplante de Fígado/efeitos adversos , Complicações Pós-Operatórias/epidemiologia , Complicações Pós-Operatórias/etiologia , Estudos Retrospectivos , Doadores de Tecidos
4.
Cancer Imaging ; 22(1): 21, 2022 May 03.
Artigo em Inglês | MEDLINE | ID: mdl-35505388

RESUMO

PURPOSES: To evaluate the value of Color Doppler Flow Imaging (CDFI), Superb Microvascular Imaging (SMI) and Contrast-enhanced Ultrasound Microflow Imaging (MFI) in display the microvascular blood flow signals in renal solid lesions. METHODS: 142 patients with 144 renal masses were examined by CDFI, SMI and MFI simultaneously. We compared the difference of blood flow grading and vascular architecture based on CDFI, SMI and MFI. RESULTS: The blood flow signals detection rates of CDFI, SMI and MFI were 78.5% (113/144), 88.9% (128/144) and 93.8% (135/144), respectively. Concentrated on blood flow grading, The coincidence rates of CDFI and SMI were 64.58% (93/144) and 81.25% (117/144) referring to MFI, respectively. Blood flow grade 2-3 in CDFI is significantly lower than SMI(x2 = 5.557, P = 0.018) and MFI (x2 = 10.165, P = 0.001). Whereas there was no significant difference between SMI and MFI (x2 = 2.372, P = 0.499). Concentrated on vascular architecture, the coincidence rates of CDFI and SMI were 56.25% (81/144) and 75.69% (109/144) referring to MFI, respectively. Vascular architecture type IV and V in CDFI was significantly lower than SMI (x2 = 18.217, P < 0.001) and MFI (x2 = 29.518, P < 0.001). Whereas there was no significant difference between SMI and MFI (x2 = 3.048, P = 0.550). The sensitivity and specificity of CDFI, SMI and MFI in the diagnosis of renal mass were 61.29% and 90.20%, 79.57% and 88.24%, 88.17% and 84.31% respectively. The areas under the ROC curve of the three were 0.757, 0.839 and 0.862, respectively. There was a statistically significant difference between CDFI and MFI (Z = 3.687, P = 0.0002), while there was no statistically significant difference between SMI and MFI (Z = 1.167, P = 0.2431). CONCLUSION: SMI and MFI are superior to CDFI in showing blood flow signals in renal solid masses, and it can perform blood flow and vascular architecture more accurately. ADVANCES IN KNOWLEDGE: SMI is similar to MFI in its ability to display fine vessels and diagnostic efficiency, and has application value in the diagnosis and differential diagnosis of renal solid masses.


Assuntos
Microvasos , Ultrassonografia Doppler em Cores , Humanos , Microvasos/diagnóstico por imagem , Curva ROC , Sensibilidade e Especificidade , Ultrassonografia/métodos , Ultrassonografia Doppler em Cores/métodos
5.
J Affect Disord ; 308: 155-159, 2022 07 01.
Artigo em Inglês | MEDLINE | ID: mdl-35429523

RESUMO

BACKGROUND: Physical disability is a cause of depression among acute stroke patients. Although previous studies have shown that physical disability, perceived social support, mental resilience, and post-stroke depression are significantly related, the interaction mechanism remains unclear. METHODS: Convenience sampling was used to recruit participants from a tertiary hospital in Daqing City, Heilongjiang Province, China from October 2020 to May 2021. Participants completed the Barthel Index Rating Scale, Multidimensional Scale of Perceived Social Support, Connor-Davidson Resilience Scale and Zung Self-Rating Depression Scale. We used the PROCESS macro for SPSS to determine the mediating effect of perceived social support and resilience between disability and depression. RESULT: A total of 259 acute stroke patients participated in this study and completed the questionnaire survey. Stroke patients' BI scores was positively correlated with perceived social support (r = 0.26, P < 0.01) and resilience (r = 0.25, P < 0.01), and negatively correlated with depression (r = -0.47, P < 0.01). Perceived social support was positively correlated with resilience (r = 0.55, P < 0.01) and negatively correlated with depression (r = -0.41, P < 0.01). Resilience was negatively correlated with depression (r = -0.43, P < 0.01). Perceived social support and resilience played a mediating role of 10.27% and 5.74% of the total effects of disability and post-stroke depression, respectively. Meanwhile, the chain mediating effect of perceived social support and resilience (7%) was also significant. LIMITATIONS: The cross-sectional study design limited the inference of causal relationships between variables. This study used convenience sampling to select research participants from a single hospital, they were all acute stroke patients from the same region of China. Participants in our study were in high BI status, and thirty of them had a low level of education, which may contribute to the possibility of selection bias. Meanwhile, the low level of education and the poor eye-sight of old people prevents them from completing the questionnaire by themselves. So we collected data in the form of "researcher reading questionnaire items and recording participant responses" for the majority of participants (257 subjects), and only 2 participants completed it independently. Furthermore, the findings of this study may not apply to stroke survivors from other backgrounds. CONCLUSION: This study found that disability can directly predict post-stroke depression, and indirectly predict post-stroke depression through the mediating effect of perceived social support and resilience, and the chain mediating effect of perceived social support-resilience. Therefore, reducing the degree of disability of acute stroke patients and improving their perceived social support and resilience may help prevent post-stroke depression.


Assuntos
Resiliência Psicológica , Acidente Vascular Cerebral , China , Estudos Transversais , Depressão/epidemiologia , Depressão/etiologia , Humanos , Apoio Social , Acidente Vascular Cerebral/complicações , Inquéritos e Questionários
6.
JAMA Netw Open ; 5(3): e222318, 2022 03 01.
Artigo em Inglês | MEDLINE | ID: mdl-35289856

RESUMO

Importance: Abundant evidence links obesity with adverse health consequences. However, controversies persist regarding whether overweight status compared with normal body mass index (BMI; calculated as weight in kilograms divided by height in meters squared) is associated with longer survival and whether this occurs at the expense of greater long-term morbidity and health care expenditures. Objective: To examine the association of BMI in midlife with morbidity burden, longevity, and health care expenditures in adults 65 years and older. Design, Setting, and Participants: Prospective cohort study at the Chicago Heart Association Detection Project in Industry, with baseline in-person examination between November 1967 and January 1973 linked with Medicare follow-up between January 1985 and December 2015. Participants included 29 621 adults who were at least age 65 years in follow-up and enrolled in Medicare. Data were analyzed from January 2020 to December 2021. Exposures: Standard BMI categories. Main Outcomes and Measures: (1) Morbidity burden at 65 years and older assessed with the Gagne combined comorbidity score (ranging from -2 to 26, with higher score associated with higher mortality), which is a well-validated index based on International Classification of Diseases, Ninth Revision codes for use in administrative data sets; (2) longevity (age at death); and (3) health care costs based on Medicare linkage in older adulthood (aged ≥65 years). Results: Among 29 621 participants, mean (SD) age was 40 (12) years, 57.1% were men, and 9.1% were Black; 46.0% had normal BMI, 39.6% were overweight, and 11.9% had classes I and II obesity at baseline. Higher cumulative morbidity burden in older adulthood was observed among those who were overweight (7.22 morbidity-years) and those with classes I and II obesity (9.80) compared with those with a normal BMI (6.10) in midlife (P < .001). Mean age at death was similar between those who were overweight (82.1 years [95% CI, 81.9-82.2 years]) and those who had normal BMI (82.3 years [95% CI, 82.1-82.5 years]) but shorter in those who with classes I and II obesity (80.8 years [95% CI, 80.5-81.1 years]). The proportion (SE) of life-years lived in older adulthood with Gagne score of at least 1 was 0.38% (0.00%) in those with a normal BMI, 0.41% (0.00%) in those with overweight, and 0.43% (0.01%) in those with classes I and II obesity. Cumulative median per-person health care costs in older adulthood were significantly higher among overweight participants ($12 390 [95% CI, $10 427 to $14 354]) and those with classes I and II obesity ($23 396 [95% CI, $18 474 to $28 319]) participants compared with those with a normal BMI (P < .001). Conclusions and Relevance: In this cohort study, overweight in midlife, compared with normal BMI, was associated with higher cumulative burden of morbidity and greater proportion of life lived with morbidity in the context of similar longevity. These findings translated to higher total health care expenditures in older adulthood for those who were overweight in midlife.


Assuntos
Longevidade , Medicare , Adulto , Idoso , Idoso de 80 Anos ou mais , Índice de Massa Corporal , Estudos de Coortes , Humanos , Masculino , Morbidade , Estudos Prospectivos , Estados Unidos/epidemiologia
7.
PeerJ ; 10: e12866, 2022.
Artigo em Inglês | MEDLINE | ID: mdl-35178301

RESUMO

BACKGROUND: Paraquat (PQ) is an effective and widely used herbicide and causes numerous fatalities by accidental or voluntary ingestion. However, neither the final cytotoxic mechanism nor effective treatments for PQ poisoning have been discovered. Phenotypic drug discovery (PDD), which does not rely on the molecular mechanism of the diseases, is having a renaissance in recent years owing to its potential to address the incompletely understood complexity of diseases. Herein, the C. elegans PDD model was established to pave the way for the future phenotypic discovery of potential agents for treating PQ poisoning. METHODS: C. elegans were treated with PQ-containing solid medium followed by statistical analysis of worm survival, pharyngeal pumping, and movement ability. Furthermore, coenzyme Q10 (CoQ10) was used to test the C. elegans model of PQ poisoning by measuring the levels of reactive oxygen species (ROS) and malondialdehyde (MDA), mitochondrial morphology, and worm survival rate. Additionally, we used the classic mice model of PQ intoxication to evaluate the validity of the C. elegans model of PQ poisoning by measuring the effect of CoQ10 as a potential antidote for PQ poisoning. RESULTS: In the C. elegans model of PQ poisoning, 5 mg/mL PQ increased the levels of ROS, MDA content, mitochondrial fragments, which significantly shortened the lifespan, while CoQ10 alleviated these phenotypes. In the mice model of PQ poisoning, CoQ10 increased the chance of survival in PQ poisoned mice while reducing ROS, MDA content in lung tissue and inhibiting PQ-induced lung edema. Moreover, CoQ10 alleviated the lung morphopathological changes induced by PQ. CONCLUSION: Here we established a C. elegans model of PQ poisoning, whose validity was confirmed by the classic mice model of PQ intoxication.

8.
Eur J Pharmacol ; 919: 174829, 2022 Mar 15.
Artigo em Inglês | MEDLINE | ID: mdl-35181336

RESUMO

Recent discoveries have implicated the potential of Cannabidiol (CBD) in the prevention of Alzheimer's disease (AD). However, how CBD affects such neurodegenerative disorders remains unclear. Herein, Caenorhabditis elegans (C. elegans) was used as the model organism to elucidate the mechanism by which CBD ameliorates AD in vivo. CBD was found to alleviate the progression of Aß-induced AD but not tau protein-induced AD or α-syn-induced Parkinson's disease. CBD inhibited the aggregation of Aß in C. elegans. However, CBD failed to prevent the formation of ß-sheet aggregation in vitro. Moreover, CBD was found to scavenge reactive oxygen species (ROS) in vivo without inducing the overexpression of antioxidative genes. In addition, CBD treatment enhanced the worm resistance to oxidative stress, which was independent of the classical transcription factors DAF-16 and SKN-1. These results supported that the in vivo antioxidative activity of CBD was most likely due to its intrinsic antioxidative property. Furthermore, the phenolic hydroxyl groups of CBD were found to be critical for scavenging ROS in vitro and in vivo, alleviating the aggregation of Aß in vivo, and ameliorating Aß-associated neurotoxicity. These studies show that CBD protects against AD in C. elegans via the ROS scavenging activity of its phenolic hydroxyl groups, which provides insight for further structure-activity relationship studies of CBD as an AD therapeutic.


Assuntos
Doença de Alzheimer/tratamento farmacológico , Canabidiol/farmacologia , Sequestradores de Radicais Livres/farmacologia , Animais , Caenorhabditis elegans/efeitos dos fármacos , Canabidiol/química , Canabidiol/uso terapêutico , Sequestradores de Radicais Livres/química , Sequestradores de Radicais Livres/uso terapêutico , Estresse Oxidativo/efeitos dos fármacos , Espécies Reativas de Oxigênio/metabolismo , Relação Estrutura-Atividade
9.
Reprod Sci ; 2022 Jan 01.
Artigo em Inglês | MEDLINE | ID: mdl-34973152

RESUMO

Ovarian cancer (OC) is a highly malignant disease that seriously threatens women's health and poses challenges for clinicians. MicroRNAs (miRNAs) have recently been intensively studied in the field of oncology due to their regulatory roles in gene expressions through RNA degradation and/or translation inhibition. This review summarizes the current studies on miRNAs in OC and introduces the latest updates of miRNAs in the early screening, treatment, and prognostic prediction of OC, thereby demonstrating the clinical significance of miRNAs in OC. Further exploration on potential targets of miRNAs in OC may provide new insights on optimizing the diagnosis and treatment of OC. MiRNAs are important driving factors for the progression of OC and the dysregulation of miRNAs can serve as biomarkers in the diagnosis, treatment and prognosis of OC. Therefore, miRNAs are potential biological targets for early screening, targeted therapy, drug resistance monitoring, and prognosis improvement in malignancies such as OC.

10.
Transplantation ; 106(5): 1004-1011, 2022 May 01.
Artigo em Inglês | MEDLINE | ID: mdl-34342962

RESUMO

BACKGROUND: Noninvasive biomarkers distinguishing early immune activation before acute rejection (AR) could more objectively inform immunosuppression management in liver transplant recipients (LTRs). We previously reported a genomic profile distinguishing LTR with AR versus stable graft function. This current study includes key phenotypes with other causes of graft dysfunction and uses a novel random forest approach to augment the specificity of predicting and diagnosing AR. METHODS: Gene expression results in LTRs with AR versus non-AR (combination of other causes of graft dysfunction and normal function) were analyzed from single and multicenter cohorts. A 70:30 approach (61 ARs; 162 non-ARs) was used for training and testing sets. Microarray data were normalized using a LT-specific vector. RESULTS: Random forest modeling on the training set generated a 59-probe classifier distinguishing AR versus non-AR (area under the curve 0.83; accuracy 0.78, sensitivity 0.70, specificity 0.81, positive predictive value 0.54, negative predictive value [NPV] 0.89; F-score 0.61). Using a locked threshold, the classifier performed well on the testing set (accuracy 0.72, sensitivity 0.67, specificity 0.73, positive predictive value 0.48, NPV 0.86; F-score 0.56). Probability scores increased in samples preceding AR versus non-AR, when liver function tests were normal, and decreased following AR treatment (P < 0.001). Ingenuity pathway analysis of the genes revealed a high percentage related to immune responses and liver injury. CONCLUSIONS: We have developed a blood-based biologically relevant biomarker that can be detected before AR-associated graft injury distinct from LTR never developing AR. Given its high NPV ("rule out AR"), the biomarker has the potential to inform precision-guided immunosuppression minimization in LTRs.


Assuntos
Transplante de Rim , Transplante de Fígado , Biomarcadores , Rejeição de Enxerto/diagnóstico , Rejeição de Enxerto/genética , Humanos , Transplante de Fígado/efeitos adversos , Complicações Pós-Operatórias , Transcriptoma
11.
Reprod Biomed Online ; 44(1): 185-192, 2022 01.
Artigo em Inglês | MEDLINE | ID: mdl-34801402

RESUMO

RESEARCH QUESTION: Does cholesterol metabolism differ in patients with diminished ovarian reserve (DOR) compared to patients with normal ovarian reserve (NOR)? DESIGN: The current research included 72 women with NOR and 86 women with DOR. Data on the cholesterol metabolism in granulosa cells of these women were analysed. RESULTS: On the day of human chorionic gonadotrophin injection, serum oestradiol and progesterone in the DOR group were significantly lower than in the control group (P < 0.001). There were no significant differences in serum concentrations of total cholesterol, triglyceride, high-density lipoprotein and low-density lipoprotein between the NOR and DOR groups. The cholesterol-regulated gene SCAP in granulosa cells from women with DOR was down-regulated (P = 0.024). Cholesterol synthesis and transport genes (e.g. IDI1, FDFT1, CYP51A1, SRB1 and STARD1) were also significantly decreased (P = 0.026, P = 0.044, P = 0.049, P = 0.004 and P < 0.001, respectively). In granulosa cells of patients with DOR, cholesterol-related substances such as coprostanone, 11A-acetoxyprogesterone and 17α-hydroxyprogesterone were significantly reduced (P = 0.0008, P = 0.0269, P = 0.0337, respectively). CYP19A1, a key steroidogenesis gene, was significantly reduced (P = 0.009). 17α-hydroxyprogesterone and oestradiol decreased (P = 0.004 and P = 0.039, respectively). CONCLUSION: Decreased cholesterol metabolism affecting steroid hormone synthesis in granulosa cells might be a possible mechanism for DOR.


Assuntos
Infertilidade Feminina , Doenças Ovarianas , Reserva Ovariana , Estradiol/metabolismo , Feminino , Células da Granulosa/metabolismo , Humanos , Infertilidade Feminina/metabolismo , Masculino , Doenças Ovarianas/metabolismo , Reserva Ovariana/genética
12.
Cancer Discov ; 12(1): 74-89, 2022 01.
Artigo em Inglês | MEDLINE | ID: mdl-34548309

RESUMO

Receptor tyrosine-protein kinase ERBB3 (HER3) is expressed in most EGFR-mutated lung cancers but is not a known mechanism of resistance to EGFR inhibitors. HER3-DXd is an antibody-drug conjugate consisting of a HER3 antibody attached to a topoisomerase I inhibitor payload via a tetrapeptide-based cleavable linker. This phase I, dose escalation/expansion study included patients with locally advanced or metastatic EGFR-mutated non-small cell lung cancer (NSCLC) with prior EGFR tyrosine kinase inhibitor (TKI) therapy. Among 57 patients receiving HER3-DXd 5.6 mg/kg intravenously once every 3 weeks, the confirmed objective response rate by blinded independent central review (Response Evaluation Criteria in Solid Tumors v1.1) was 39% [95% confidence interval (CI), 26.0-52.4], and median progression-free survival was 8.2 (95% CI, 4.4-8.3) months. Responses were observed in patients with known and unknown EGFR TKI resistance mechanisms. Clinical activity was observed across a broad range of HER3 membrane expression. The most common grade ≥3 treatment-emergent adverse events were hematologic toxicities. HER3-DXd has clinical activity in EGFR TKI-resistant cancers independent of resistance mechanisms, providing an approach to treat a broad range of drug-resistant cancers. SIGNIFICANCE: In metastatic EGFR-mutated NSCLC, after disease progression on EGFR TKI therapy, treatment approaches include genotype-directed therapy targeting a known resistance mechanism or chemotherapy. HER3-DXd demonstrated clinical activity spanning known and unknown EGFR TKI resistance mechanisms. HER3-DXd could present a future treatment option agnostic to the EGFR TKI resistance mechanism.See related commentary by Lim et al., p. 16.This article is highlighted in the In This Issue feature, p. 1.


Assuntos
Anticorpos Monoclonais Humanizados/uso terapêutico , Antineoplásicos Imunológicos/uso terapêutico , Camptotecina/análogos & derivados , Carcinoma Pulmonar de Células não Pequenas/tratamento farmacológico , Neoplasias Pulmonares/tratamento farmacológico , Idoso , Anticorpos Monoclonais Humanizados/administração & dosagem , Antineoplásicos Imunológicos/administração & dosagem , Camptotecina/administração & dosagem , Camptotecina/uso terapêutico , Carcinoma Pulmonar de Células não Pequenas/mortalidade , Carcinoma Pulmonar de Células não Pequenas/secundário , Intervalo Livre de Doença , Relação Dose-Resposta a Droga , Receptores ErbB/antagonistas & inibidores , Receptores ErbB/genética , Feminino , Humanos , Infusões Intravenosas , Neoplasias Pulmonares/mortalidade , Neoplasias Pulmonares/patologia , Masculino , Pessoa de Meia-Idade , Metástase Neoplásica , Resultado do Tratamento
13.
J Am Heart Assoc ; 10(24): e021917, 2021 12 21.
Artigo em Inglês | MEDLINE | ID: mdl-34913367

RESUMO

Background Associations of 1-year change in functional performance measures with subsequent mobility loss and mortality in people with lower extremity peripheral artery disease are unknown. Methods and Results Six-minute walk and 4-meter walking velocity (usual and fastest pace) were measured at baseline and 1 year later in 612 people with peripheral artery disease (mean age 71±9 years, 37% women). Participants were categorized into tertiles, based on 1-year changes in walking measures. Cox proportional hazards models were used to examine associations between 1-year change in each walking measure and subsequent mobility loss and mortality, respectively, adjusting for potential confounders. Compared with the best tertile, the worst tertile (ie, greatest decline) in 1-year change in each performance measure was associated with higher rates of mobility loss: 6-minute walk (Tertile 1 [T1] cumulative incidence rate [IR], 72/160; Tertile 3 [T3] IR, 47/160; hazard ratio [HR], 2.35; 95% CI, 1.47-3.74), usual-paced 4-meter walking velocity (T1 IR, 54/162; T3 IR, 57/162; HR, 2.21; 95% CI, 1.41-3.47), and fast-paced 4-meter walking velocity (T1 IR, 61/162; T3 IR, 58/162; HR, 1.81; 95% CI, 1.16-2.84). Compared with the best tertile, the worst tertiles in 1-year change in 6-minute walk (T1 IR, 66/163; T3 IR, 54/163; HR, 1.61; 95% CI, 1.07-2.43) and fast-paced 4-meter walking velocity (T1 IR, 63/166; T3 IR, 44/166; HR, 1.75; 95% CI, 1.16, 2.64) were associated with higher mortality. Conclusions In people with peripheral artery disease, greater 1-year decline in 6-minute walk or 4-meter walking velocity may help identify people with peripheral artery disease at highest risk for mobility loss and mortality.


Assuntos
Limitação da Mobilidade , Doença Arterial Periférica , Caminhada , Idoso , Idoso de 80 Anos ou mais , Feminino , Humanos , Estudos Longitudinais , Masculino , Pessoa de Meia-Idade , Doença Arterial Periférica/mortalidade , Doença Arterial Periférica/fisiopatologia , Caminhada/fisiologia
14.
Reprod Sci ; 2021 Nov 30.
Artigo em Inglês | MEDLINE | ID: mdl-34846706

RESUMO

More than 40% of infertile men are diagnosed with oligoasthenozoospermia and the incidence is still rising, but the effective treatments are not been found until now. Astragalin, one of the main active ingredients in traditional Chinese medicine, may be effective in the treatment of oligoasthenozoospermia. This study investigated the pharmacological effects of astragalin for treatment of oligoasthenozoospermia in male mice, induced by cyclophosphamide (CTX). Male mice were intraperitoneally injected by CTX (50 mg/kg), and astragalin (30 mg/kg) was given via oral gavage once daily. RNA-seq analysis highlighted astragalin upregulated gene expression of anti-apoptosis (AKT1and BCL2-XL), cell proliferation (ETV1, MAPKAPK2, and RPS6KA5) and synthesis of testosterone (STAR, CYP11A1, and PRKACB), but downregulated gene expression of cell apoptosis (BAD, BCL-2, CASPASE9, and CASPASE3) in mouse testis. Astragalin also significantly reversed the reduction in body weight, reproductive organs index, and sperm parameters (sperm concentration, viability, and motility) induced by CTX, and restored testicular abnormal histopathologic morphology induced by CTX. Furthermore, astragalin dramatically rescued the gene expression related to spermatogenesis (AKT1, BCL-2, CASPASE9, CASPASE3, MAPKAPK2, RPS6KA5, STAR, and PRKACB), and increased the level of testosterone by improving related proteins (STAR, CYP11A1, PRKACB) for oligoasthenozoospermia induced by CTX. In conclusion, astragalin may be a potential beneficial agent for oligoasthenozoospermia by increasing the testosterone levels in testis.

15.
Clin J Am Soc Nephrol ; 16(10): 1539-1551, 2021 10.
Artigo em Inglês | MEDLINE | ID: mdl-34620649

RESUMO

BACKGROUND AND OBJECTIVES: Subclinical acute rejection is associated with poor outcomes in kidney transplant recipients. As an alternative to surveillance biopsies, noninvasive screening has been established with a blood gene expression profile. Donor-derived cellfree DNA (cfDNA) has been used to detect rejection in patients with allograft dysfunction but not tested extensively in stable patients. We hypothesized that we could complement noninvasive diagnostic performance for subclinical rejection by combining a donor-derived cfDNA and a gene expression profile assay. DESIGN, SETTING, PARTICIPANTS, & MEASUREMENTS: We performed a post hoc analysis of simultaneous blood gene expression profile and donor-derived cfDNA assays in 428 samples paired with surveillance biopsies from 208 subjects enrolled in an observational clinical trial (Clinical Trials in Organ Transplantation-08). Assay results were analyzed as binary variables, and then, their continuous scores were combined using logistic regression. The performance of each assay alone and in combination was compared. RESULTS: For diagnosing subclinical rejection, the gene expression profile demonstrated a negative predictive value of 82%, a positive predictive value of 47%, a balanced accuracy of 64%, and an area under the receiver operating curve of 0.75. The donor-derived cfDNA assay showed similar negative predictive value (84%), positive predictive value (56%), balanced accuracy (68%), and area under the receiver operating curve (0.72). When both assays were negative, negative predictive value increased to 88%. When both assays were positive, positive predictive value increased to 81%. Combining assays using multivariable logistic regression, area under the receiver operating curve was 0.81, significantly higher than the gene expression profile (P<0.001) or donor-derived cfDNA alone (P=0.006). Notably, when cases were separated on the basis of rejection type, the gene expression profile was significantly better at detecting cellular rejection (area under the receiver operating curve, 0.80 versus 0.62; P=0.001), whereas the donor-derived cfDNA was significantly better at detecting antibody-mediated rejection (area under the receiver operating curve, 0.84 versus 0.71; P=0.003). CONCLUSIONS: A combination of blood-based biomarkers can improve detection and provide less invasive monitoring for subclinical rejection. In this study, the gene expression profile detected more cellular rejection, whereas donor-derived cfDNA detected more antibody-mediated rejection.


Assuntos
Ácidos Nucleicos Livres/sangue , DNA/sangue , Perfilação da Expressão Gênica , Rejeição de Enxerto/diagnóstico , Transplante de Rim/efeitos adversos , Doadores de Tecidos , Transcriptoma , Adulto , Doenças Assintomáticas , Biomarcadores/sangue , Biópsia , Ácidos Nucleicos Livres/genética , DNA/genética , Feminino , Rejeição de Enxerto/sangue , Rejeição de Enxerto/genética , Rejeição de Enxerto/imunologia , Humanos , Masculino , Pessoa de Meia-Idade , Valor Preditivo dos Testes , Reprodutibilidade dos Testes , Resultado do Tratamento , Estados Unidos , Adulto Jovem
16.
Photochem Photobiol Sci ; 20(11): 1487-1495, 2021 Nov.
Artigo em Inglês | MEDLINE | ID: mdl-34709594

RESUMO

By using the density functional theory (DFT) and time-dependent density functional theory (TDDFT), the electronic structure and photophysical properties of a series of cyclometalated iridium(III) complexes bearing the substituted phenylpyrazole have been theoretically investigated. All studied iridium(III) complexes have the distorted octahedral geometry with cis-C,C, cis-O,O, and trans-N,N chelate disposition. The lowest lying singlet → singlet absorptions of all studied iridium(III) complexes are respectively located at 405 nm, 387 nm, 382 nm, 370 nm, and 387 nm. The calculated emission wavelengths for all studied iridium(III) complexes are 654 nm, 513 nm, 506 nm, 505 nm and 499 nm, respectively. The calculated emission wavelength for complex 4 at the CAM-B3LYP level is in good agreement with the experimental value. From the theoretical results, it can be seen that the electron-donating substituent groups have the important effect on the electronic structure and photophysical properties of all studied iridium(III) complexes. We hope that this study can provide valuable guidance for the design of new phosphorescent organic light-emitting diodes (OLEDs) materials.

17.
Neurosci Lett ; 761: 136114, 2021 09 14.
Artigo em Inglês | MEDLINE | ID: mdl-34274434

RESUMO

OBJECTIVE: Nicotine, a main active compound in tobacco, has been shown to attenuate amyloid-ß (Aß) mediated neurotoxicity. However, the detailed underlying mechanisms remains to be elucidated. In this study, nematode Caenorhabditis elegans (C. elegans) had been chosen as the model animal for dissecting the role of nicotine in the prevention of Aß-induced toxicity in vivo. METHODS: CL2120 and CL4176 transgenic worms of Alzheimer's disease (AD) models were treated with different concentrations of nicotine, and worm paralysis was monitored. Next, the effects of nicotine on Aß deposits, Aß oligomers, reactive oxygen species (ROS) and the oxidative stress resistance in worms were measured. Moreover, the pathway responsible for nicotine alleviating Aß-induced toxicity in vivo was explored by observing the oxidative stress resistance of skn-1 or daf-16 mutants in the presence of nicotine. Furthermore, the worm paralysis and Aß deposits were further checked in CL4176 worms with skn-1 RNA interference under the condition of nicotine. RESULTS: Nicotine (5 µM) attenuated AD-like symptoms of worm paralysis in CL2120 and CL4176 transgenic C. elegans. Nicotine did not inhibit Aß aggregation in vitro, however it suppressed Aß deposits and reduced the Aß oligomers to alleviate the toxicity induced by Aß overexpression in C. elegans. Although nicotine did not possess apparent intrinsic anti-oxidative activity, it decreased in vivo reactive oxygen species (ROS). Nicotine enhanced the oxidative stress resistance of C. elegans, which was mediated by SKN-1 but not DAF-16 signaling. Furthermore, skn-1 RNAi abrogated the effect of nicotine reducing Aß deposits in vivo and completely blocked nicotine preventing Aß induced worm paralysis. CONCLUSIONS: Nicotine reduces Aß oligomer formation and alleviates Aß-induced paralysis of C. elegans, which is mediated by SKN-1 signaling.


Assuntos
Doença de Alzheimer/metabolismo , Peptídeos beta-Amiloides/toxicidade , Proteínas de Caenorhabditis elegans/metabolismo , Proteínas de Ligação a DNA/metabolismo , Nicotina/farmacologia , Agonistas Nicotínicos/farmacologia , Fatores de Transcrição/metabolismo , Doença de Alzheimer/tratamento farmacológico , Peptídeos beta-Amiloides/efeitos dos fármacos , Animais , Caenorhabditis elegans , Proteínas de Caenorhabditis elegans/genética , Proteínas de Ligação a DNA/genética , Nicotina/uso terapêutico , Agonistas Nicotínicos/uso terapêutico , Espécies Reativas de Oxigênio/metabolismo , Fatores de Transcrição/genética
18.
Hepatology ; 74(2): 926-936, 2021 08.
Artigo em Inglês | MEDLINE | ID: mdl-34128254

RESUMO

BACKGROUND AND AIMS: Estimates of racial disparity in cirrhosis have been limited by lack of large-scale, longitudinal data, which track patients from diagnosis to death and/or transplant. APPROACH AND RESULTS: We analyzed a large, metropolitan, population-based electronic health record data set from seven large health systems linked to the state death registry and the national transplant database. Multivariate competing risk analyses, adjusted for sex, age, insurance status, Elixhauser score, etiology of cirrhosis, HCC, portal hypertensive complication, and Model for End-Stage Liver Disease-Sodium (MELD-Na), examined the relationship between race, transplant, and cause of death as defined by blinded death certificate review. During the study period, 11,277 patients met inclusion criteria, of whom 2,498 (22.2%) identified as Black. Compared to White patients, Black patients had similar age, sex, MELD-Na, and proportion of alcohol-associated liver disease, but higher comorbidity burden, lower rates of private insurance, and lower rates of portal hypertensive complications. Compared to White patients, Black patients had the highest rate all-cause mortality and non-liver-related death and were less likely to be listed or transplanted (P < 0.001 for all). In multivariate competing risk analysis, Black patients had a 26% increased hazard of liver-related death (subdistribution HR, 1.26; 95% CI, [1.15-1.38]; P < 0.001). CONCLUSIONS: Black patients with cirrhosis have discordant outcomes. Further research is needed to determine how to address these real disparities in the field of hepatology.


Assuntos
/estatística & dados numéricos , Doença Hepática Terminal/mortalidade , Disparidades nos Níveis de Saúde , Disparidades em Assistência à Saúde/estatística & dados numéricos , Cirrose Hepática/mortalidade , Adulto , Idoso , Conjuntos de Dados como Assunto , Registros Eletrônicos de Saúde/estatística & dados numéricos , Doença Hepática Terminal/diagnóstico , Doença Hepática Terminal/patologia , Doença Hepática Terminal/cirurgia , Feminino , Seguimentos , Humanos , Cirrose Hepática/diagnóstico , Cirrose Hepática/patologia , Cirrose Hepática/cirurgia , Masculino , Pessoa de Meia-Idade , Índice de Gravidade de Doença , Análise de Sobrevida , Resultado do Tratamento
19.
J Am Heart Assoc ; 10(12): e017609, 2021 06 15.
Artigo em Inglês | MEDLINE | ID: mdl-34075780

RESUMO

Background In people with lower-extremity peripheral artery disease, the effects of exercise on patient-reported outcomes remain unclear. Methods and Results Four hundred four people with peripheral artery disease in 3 clinical trials were randomized to exercise (N=205) or a control group (N=199) and completed the 6-minute walk and the Walking Impairment Questionnaire distance score (score 0-100, 100=best) at baseline and 6-month follow-up. Compared with the control group, exercise improved 6-minute walk distance by +39.8 m (95% CI, 26.8-52.8, P<0.001) and the Walking Impairment Questionnaire distance score by +7.3 (95% CI, 2.4-12.1, P=0.003). In all, 2828 individual Walking Impairment Questionnaire distance score questions were completed at baseline and follow-up. Among participants who perceived no change in ability to walk 1 or more distances between baseline and follow-up, 6-minute walk improved in the exercise group and declined in the control group (+26.8 versus -6.5 m, P<0.001). Among participants who perceived that their walking ability worsened for 1 or more distances between baseline and follow-up, the 6-minute walk improved in the exercise group and declined in the control group (+18.4 versus -27.3 m, P<0.001). Among participants who reported worsening calf symptoms at follow-up, the exercise group improved and the control group declined (+28.9 versus -12.5 m, P<0.01). Conclusions In 3 randomized trials, exercise significantly improved the 6-minute walk distance in people with peripheral artery disease, but many participants randomized to exercise reported no change or decline in walking ability. These findings suggest a significant discrepancy in objectively measured walking improvement relative to perceived walking improvement in people with peripheral artery disease. Registration Information clinicaltrials.gov. Identifiers: NCT00106327, NCT01408901.


Assuntos
Terapia por Exercício , Tolerância ao Exercício , Claudicação Intermitente/terapia , Medidas de Resultados Relatados pelo Paciente , Doença Arterial Periférica/terapia , Teste de Caminhada , Caminhada , Idoso , Feminino , Humanos , Claudicação Intermitente/diagnóstico , Claudicação Intermitente/fisiopatologia , Masculino , Pessoa de Meia-Idade , Doença Arterial Periférica/diagnóstico , Doença Arterial Periférica/fisiopatologia , Valor Preditivo dos Testes , Ensaios Clínicos Controlados Aleatórios como Assunto , Recuperação de Função Fisiológica , Reprodutibilidade dos Testes , Fatores de Tempo , Resultado do Tratamento
20.
Indian J Microbiol ; : 1-13, 2021 Jun 01.
Artigo em Inglês | MEDLINE | ID: mdl-34092818

RESUMO

Lactobacillus has been reported to inhibit acute lung injury (ALI). However, the molecular mechanism of Lactobacillus casei (L. casei) in preventing ALI has not been identified, so we investigated whether L. casei pretreatment could inhibit the activation of TLR4/MyD88/NF-κB signaling pathway following ALI. ALI model was established by intraperitoneal injection of 2 mg/kg lipopolysaccharide (LPS) to female BALB/c mice. In L. casei LC2W group, mice were intragastrically administrated L. casei LC2W for a week, before the ALI modeling. The serum of normal BALB/c mice after intragastric administration of L. casei LC2W was used for in vitro cell assays. The serum was pre-incubated with mouse macrophage cell line (RAW264.7) and human lung cell line (HLF-A), then LPS was added to co-incubate. Compared with ALI model group, L. casei LC2W pretreatment significantly reduced lung pathological damage, the number of neutrophils and total cells in bronchoalveolar lavage fluid. Besides, L. casei LC2W pretreatment could significantly reverse the abnormal expression of ICAM-1, IL-6, TNF-α and IL-10 in lung tissue and serum, plus, L. casei LC2W significantly reduced the phosphorylation levels of IRAK-1 and NF-κB p65. In vitro, the serum decreased the up-regulation of IL-6 and TNF-α in cell lines induced by LPS. In conclusion, L. casei LC2W intragastric administration pretreatment could significantly improve LPS-induced ALI in mice, probably through circulation to reach the lungs so as to inhibit the inflammatory response induced by activation of TLR4/MyD88/NF-κB signaling pathway.

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