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1.
Front Pharmacol ; 13: 807651, 2022.
Artigo em Inglês | MEDLINE | ID: mdl-35370667

RESUMO

Overview: The treatment of chronic renal failure (CRF) with traditional Chinese medicine has attracted much attention, but its mechanism is not clear. Network pharmacology is an effective strategy for exploring the interaction mechanisms between Chinese herbs and diseases, however, it still needs to be validated in cell and/or animal experiments due to its virtual screening characteristics. Herein, the anti-CRF mechanism of the Fushengong decoction (FSGD) was investigated using a dual-dimension network pharmacological strategy combined with in vivo experiment. Methods: The traditional Chinese medicine systems pharmacology (TCMSP) database (https://tcmspw.com) and UHPLC-MS/MS technology were used to identify the effective compounds of FSGD in theory and practice, such as quercetin, formononetin, and pachymic acid. The putative targets of FSGD and CRF were obtained from the Swisstarget prediction platform and the Genecards database, respectively. The common target pathways between FSGD and CRF were got from the dual-dimension network pharmacology analysis, which integrated the cross-common targets from the TCMSP components-Swisstarget-Genecards-Venn platform analysis in theory, and the UHPLC-MS/MS identified effective ingredients-Swisstarget screening, such as TNF and PI3K/AKT. Furthermore, system molecular determinations were used to prove the dual-dimension network pharmacology study through CRF rat models, which were constructed using adenine and treated with FSGD for 4 weeks. Results: A total of 121 and 9 effective compounds were obtained from the TCMSP database and UHPLC-MS/MS, respectively. After dual-dimension network pharmacology analysis, the possible mechanism of PTEN/PI3K/AKT/NF-κB pathway was found for FSGD in CRF. In vivo experiments indicated that FSGD can play a role in protecting renal function and reducing fibrosis by regulating the PTEN/PI3K/AKT/NF-κB pathway. These findings provide a reference for FSGD in CRF. Conclusion: Based on the theoretical and practical dual-dimension network pharmacology analysis for FSGD in CRF, the possible molecular mechanism of PTEN/PI3K/AKT/NF-κB was successfully predicted, and these results were verified by in vivo experiments. In this study, the dual-dimension network pharmacology was used to interpret the key signal pathway for FSGD in CRF, which also proved to be a smart strategy for the study of effective substances and pharmacology in FSGD.

2.
FASEB J ; 36 Suppl 12022 May.
Artigo em Inglês | MEDLINE | ID: mdl-35556877

RESUMO

The neural crest (NC) is a unique migratory stem cell population only existed during vertebrate embryogenesis. It has remarkable multipotency to give rise to various cell types including osteoblasts and chondrocytes, which contribute to majority of the cranial skeleton development. Defects in NC development led to many congenital diseases, including cleft palate and craniofacial abnormities. Recently, the Hippo-Yap pathway, a conserved fundamental pathway has been indicated to play a key role in NCCs. Yet, the roles of Yap and Taz, function as Hippo signaling effectors, in NCC cells are still poorly understood. To understand the roles of Yap and Taz, we performed both in vitro, ex vivo and in vivo studies using O9-1 NC cells and Yap/Taz conditionally knockout (CKO) mice driven by Wnt1creSOR. We found that Yap/Taz are required for the osteogenic versus chondrogenic cell fate decision of NC cells. Yap/Taz prevent O9-1 NC cells from differentiating into chondrocytes to favor osteogenesis, and Yap/Taz deficiency in NC cells resulted in chondrogenesis instead of osteogenesis. Notably, in vivo, we observed NC-derived cranial bone defects accompanied by ectopic cartilage formation. From RNA-seq and CUT/RUN datasets we found that Yap/Taz directly regulate key genes that govern osteogenesis (Dlx5, Runx2,…) and chondrogenesis (Sox9/5/6,…). Interestingly, many of those genes are known Wnt target genes. Moreover, our data from ATAC-seq, PLA and Co-IP demonstrated that Yap/Taz directly interact with ß-catenin to coordinately regulate related genes expression in NCCs to orchestrate the osteogenic or chondrogenic cell fate, such as the key chondrogenesis gene Sox9. In summary, our data indicated that Yap/Taz play pivotal roles in determining osteogenesis or chondrogenesis of NC, partly through interactions with the Wnt-ß-catenin pathway, which reveal potential novel diagnostic and therapeutic targets for the NC-derived diseases.

3.
Front Neurosci ; 16: 858717, 2022.
Artigo em Inglês | MEDLINE | ID: mdl-35573287

RESUMO

The management of eating behavior in bulimia nervosa (BN) patients is a complex process, and BN involves activity in multiple brain regions that integrate internal and external functional information. This functional information integration occurs in brain regions involved in reward, cognition, attention, memory, emotion, smell, taste, vision and so on. Although it has been reported that resting-state brain activity in BN patients is different from that of healthy controls, the neural mechanisms remain unclear and need to be further explored. The fractional amplitude of low-frequency fluctuation (fALFF) analyses are an important data-driven method that can measure the relative contribution of low-frequency fluctuations within a specific frequency band to the whole detectable frequency range. The fALFF is well suited to reveal the strength of interregional cooperation at the single-voxel level to investigate local neuronal activity power. FC is a brain network analysis method based on the level of correlated dynamics between time series, which establishes the connection between two spatial regions of interest (ROIs) with the assistance of linear temporal correlation. Based on the psychological characteristics of patients with BN and the abnormal brain functional activities revealed by previous neuroimaging studies, in this study, we investigated alterations in regional neural activity by applying fALFF analysis and whole-brain functional connectivity (FC) in patients with BN in the resting state and to explore correlations between brain activities and eating behavior. We found that the left insula and bilateral inferior parietal lobule (IPL), as key nodes in the reorganized resting-state neural network, had altered FC with other brain regions associated with reward, emotion, cognition, memory, smell/taste, and vision-related functional processing, which may have influenced restrained eating behavior. These results could provide a further theoretical basis and potential effective targets for neuropsychological treatment in patients with BN.

4.
ACS Macro Lett ; 11(3): 347-353, 2022 Mar 15.
Artigo em Inglês | MEDLINE | ID: mdl-35575373

RESUMO

Development of soft actuators with complex practical functions is significant for imitating the behaviors of living organisms. However, it is still a challenge to fabricate artificial soft actuators with jellyfish-like synergistic deformation and fluorescence color change (SDFC) and autonomous dynamic behavior, but such a system could obviously endow the classic soft actuators with more functions. Herein, we proposed to utilize tetra(4-pyridylphenyl)ethylene (TPE-4N) luminogen with pH-responsive aggregation-induced emission (AIE) to fabricate the AIE active hydrogel, which could be further employed to obtain an anisotropic bilayer soft actuator based on strong interfacial adhesion with acrylic acid (AA) gels. Furthermore, artificial flower-shape actuators showing SDFC behaviors were demonstrated. On the basis of these findings, jellyfish-inspired autonomous gel actuators driven by a pH oscillator have been fabricated, in which periodical SDFC behaviors completely regulated by the system itself without repetitive on/off switches of external stimuli were well synchronized with the pH oscillator. The described combination of nonlinear chemistry and responsive hydrogels actuator opens pathways toward out-of-equilibrium SDFC devices with autonomous behavior useful for biomimetic fields.

5.
Biochem Biophys Res Commun ; 612: 70-76, 2022 Apr 21.
Artigo em Inglês | MEDLINE | ID: mdl-35504092

RESUMO

Acetaminophen (APAP) overdose induces acute liver injury (ALI), even acute liver failure (ALF). There is a significant unmet need to furtherly elucidate the mechanisms and find new therapeutic target. Recently, emerging evidence indicates that nicotinamide adenine dinucleotide (NAD+) plays a crucial role in APAP-induced ALI. Herein, we firstly investigated the protein expression of NAD kinase (NADK), as the rate-limiting enzyme converting NAD+ to nicotinamide adenine dinucleotide phosphate (NADP+), and found it was positively correlated with APAP-induced ALI in a dose- and time-dependent manner. Additionally, supplementation of N-acetylcysteine (NAC), known as an antidote of APAP, mitigated the ALI and downregulated the expression of NADK which was also in a dose-dependent manner. Moreover, pretreatment with methotrexate (MTX), the inhibitor of NADK, attenuated the levels of transaminases, alleviated morphological abnormalities, and improved oxidative stress triggered by APAP overdose, which was attributed to elevated hepatic NAD+ pool. Subsequently, the increased NAD+ upregulated the expression of Sirt1, SOD2 and attenuated DNA damage. Collectively, elevated expression of NADK is related to APAP-induced ALI, and inhibition of NADK alleviates the ALI through elevating liver NAD+ level and improving antioxidant capacity.

6.
Sheng Li Xue Bao ; 74(2): 225-236, 2022 Apr 25.
Artigo em Chinês | MEDLINE | ID: mdl-35503070

RESUMO

This study was to investigate the changes of autophagy in pancreatic tissue cells from hyperlipidemic acute pancreatitis (HLAP) rats and the molecular mechanism of autophagy to induce inflammatory injury in pancreatic tissue cells. Male Sprague Dawley (SD) rats were intraperitoneally injected with caerulein to establish acute pancreatitis (AP) model and then given a high fat diet to further prepare HLAP model. The HLAP rats were treated with autophagy inducer rapamycin or inhibitor 3-methyladenine. Pancreatic acinar (AR42J) cells were treated with caerulein to establish HLAP cell model. The HLAP cell model were treated with rapamycin or transfected with vascular endothelial growth factor (VEGF) siRNA. The inflammatory factors in serum and cell culture supernatant were detected by ELISA method. The histopathological changes of pancreatic tissue were observed by HE staining. The changes of ultrastructure and autophagy in pancreatic tissue were observed by electron microscopy. The expression levels of Beclin-1, microtubule- associated protein light chain 3-II (LC3-II), mammalian target of rapamycin complex 1 (mTORC1), and VEGF were measured by immunohistochemistry and Western blot. The results showed that, compared with control group, the autophagy levels and inflammatory injury of pancreatic tissue cells from HLAP model rats were obviously increased, and these changes were aggravated by rapamycin treatment, but alleviated by 3-methyladenine treatment. In HLAP cell model, rapamycin aggravated the autophagy levels and inflammatory injury, whereas VEGF siRNA transfection increased mTORC1 protein expression, thus alleviating the autophagy and inflammatory injury of HLAP cell model. These results suggest that VEGF-induced autophagy plays a key role in HLAP pancreatic tissue cell injury, and interference with VEGF-mTORC1 pathway can reduce the autophagy levels and alleviate the inflammatory injury. The present study provides a new target for prevention and treatment of HLAP.


Assuntos
Pancreatite , Doença Aguda , Animais , Autofagia , Ceruletídeo/efeitos adversos , Masculino , Mamíferos/metabolismo , Alvo Mecanístico do Complexo 1 de Rapamicina , Proteínas Associadas aos Microtúbulos/metabolismo , RNA Interferente Pequeno/genética , Ratos , Ratos Sprague-Dawley , Sirolimo/efeitos adversos , Fator A de Crescimento do Endotélio Vascular/genética
7.
PLoS One ; 17(5): e0268237, 2022.
Artigo em Inglês | MEDLINE | ID: mdl-35522615

RESUMO

COVID-19 remains a challenge worldwide, and testing of asymptomatic individuals remains critical to pandemic control measures. Starting March 2020, a total of 7497 hospital employees were tested at least weekly for SARS CoV-2; the cumulative incidence of asymptomatic infections was 5.64%. Consistently over a 14-month period half of COVID-19 infections (414 of 820, total) were detected through the asymptomatic screening program, a third of whom never developed any symptoms during follow-up. Prompt detection and isolation of these cases substantially reduced the risk of potential workplace and outside of workplace transmission. COVID-19 vaccinations of the workforce were initiated in December 2020. Twenty-one individuals tested positive after being fully vaccinated (3.9 per 1000 vaccinated). Most (61.9%) remained asymptomatic and in majority (75%) the virus could not be sequenced due to low template RNA levels in swab samples. Further routine testing of vaccinated asymptomatic employees was stopped and will be redeployed if needed; routine testing for those not vaccinated continues. Asymptomatic SARS-CoV-2 testing, as a part of enhanced screening, monitors local dynamics of the COVID-19 pandemic and can provide valuable data to assess the ongoing impact of COVID-19 vaccination and SARS-CoV-2 variants, inform risk mitigation, and guide adaptive, operational planning including titration of screening strategies over time, based on infection risk modifiers such as vaccination.


Assuntos
COVID-19 , COVID-19/diagnóstico , COVID-19/epidemiologia , COVID-19/prevenção & controle , Teste para COVID-19 , Vacinas contra COVID-19 , Humanos , Pandemias/prevenção & controle , SARS-CoV-2 , Recursos Humanos
8.
Chem Biol Interact ; : 109968, 2022 May 04.
Artigo em Inglês | MEDLINE | ID: mdl-35525316

RESUMO

Gaudichaudione H (GH), a caged polyprenylated xanthone from Garcinia plants, showed anti-cancer and anti-inflammatory effects in vitro. However, the in vivo toxicity of this compound has never been reported. The present study was aimed to address the toxic effects of Gaudichaudione H using zebrafish embryos and larvae as an in vivo test model. The zebrafish embryos were treated with GH having different concentrations (0, 0.28, 0.38 and 0.57 µg/mL). The results revealed that GH induces significant embryonic mortality, decreased heartbeat, cardiotoxicity, cardiovascular defects, increased apoptosis and decreased hemoglobinization in zebrafish embryos and larvae. According to transcriptome analysis, 1841 genes were significantly differentially expressed (1185 down-regulated and 656 up-regulated) after GH treatment. The main functions of these genes were related to iron metabolism pathways. The toxicity of GH on zebrafish embryonic development and cardiovascular may due to large amounts of downregulated genes involved in metabolic pathways and DEGs related to 'Iron ion binding' and 'Heme binding' functions.

9.
Artigo em Inglês | MEDLINE | ID: mdl-35564423

RESUMO

BACKGROUND: The world faces vast health challenges, and urban residents living in high-density areas have even greater demand for healthy lifestyles. METHODS: Based on the data of points of interest, a field survey, and an interview, we explored the healthy community-life circle in the downtown area of Chengdu, China from two perspectives: objective measurement and subjective perception of residents. We evaluated the coverage rate and convenience in accessing eight types of health service facilities within a 15-min walk using linear and logistics regression models to explore the degree of resident satisfaction with facilities and influencing factors. RESULTS: Results showed significant differences in coverage rates between different districts. The overall convenience in accessing health service facilities decreased gradually from the city center to the outskirts. The social environment, the layout of health service facilities, and residents' travel habits were related to health service facility satisfaction. Results also showed significant differences in various facilities' accessibility satisfaction between objective measurement and residents' perception measurement. Compared with subjective measurement, the objective measurements of accessibility for sports venues (objectively measured average minus perceived average: -1.310), sports zones (-0.740), and specialized hospitals (-1.081) were lower; those for community hospitals (0.095), clinics (1.025), and pharmacies (0.765) were higher; and facility accessibility measured by subjective perception had a more significant impact on health facility satisfaction. Pharmacies (OR: 1.932) and community hospitals (OR: 1.751) had the largest impact among the eight types of facilities. CONCLUSION: This study proposed to construct a healthy community-life circle with a category and hierarchy system.

10.
Artigo em Inglês | MEDLINE | ID: mdl-35564935

RESUMO

People with end stage renal disease and undergoing hemodialysis experience a high symptom burden that impairs quality of life. This study aimed to assess the prevalence, dynamicity and determinants of symptom burden among middle-aged and older adult hemodialysis patients. A descriptive cross-sectional study together with a longitudinal assessment was used. A total of 118 and 102 hemodialysis patients were assessed at baseline and at a 6-month follow-up. Validated questionnaires were used to assess the symptom burden, stress, illness perception and social support. Multiple linear regression analysis was used to determine the factors associated with symptom burden. The median number of symptoms experienced was 21 (Interquartile Range (IQR); 18-23) and 19 (IQR; 13-22) at baseline and 6 months, respectively. Having elevated stress (ß = 0.65, p ≤ 0.005) and illness perception (ß = 0.21, p = 0.02) were significantly predicted symptom burden at baseline (F (4, 112) = 55.29, p < 0.005, R2 = 0.664). Stress (ß = 0.28, p = 0.003), illness perception (ß = 0.2, p = 0.03), poor social support (ß = -0.22, p = 0.01) and low body weight (ß = -0.19, p = 0.03) were the determinants for symptom burden at 6 months (F (5, 93) = 4.85, p ≤ 0.005, R2 = 0.24). Elevated stress, illness perception level, poor social support and low post-dialysis body weight were found to be determinants for symptom burden. Attention should be given to psychosocial factors of hemodialysis patients while conducting assessment and delivering care to patients.

11.
Front Neurol ; 13: 694418, 2022.
Artigo em Inglês | MEDLINE | ID: mdl-35518202

RESUMO

Aims: Whether endovascular treatment (EVT) can further improve the prognosis of patients with posterior circulation ischemic stroke (PCIS) is unclear. This meta-analysis aims to compare the efficacy and safety of PCIS patients treated with EVT plus standard medical treatment (SMT) and SMT alone. Methods: We systematically searched for relevant randomized controlled trials (RCTs) and prospective cohort trials in MEDLINE, EMBASE, and the Cochrane Library up to February 2022. The primary outcome was favorable functional outcome of the modified Rankin Scale (mRS) with scores of 0-2 or 0-3; secondary outcomes included successful recanalization rate, intracranial hemorrhage (ICH), or symptomatic intracranial hemorrhage (sICH) after treatment and 90-day mortality. Results: We identified six studies including 1, 385 PCIS patients (957 with EVT plus SMT; 428 with SMT alone). EVT plus SMT substantially improved 90-day functional outcomes compared with SMT alone [mRS score of 0-2: RR=1.95, 95% CI (1.52 - 2.51), P < 0.001; mRS score of 0-3: RR = 1.85, 95% CI (1.49 - 2.30), P < 0.001, respectively]. Moreover, compared with SMT, combined treatment significantly improved the rate of successful recanalization [RR = 5.03, 95% CI (3.96-6.40), P < 0.001] and reduced 90-day mortality [RR = 0.71, 95% CI (0.63-0.79), P < 0.001] despite a higher risk of ICH [RR = 6.13, 95% CI (2.50-15.02), P < 0.001] and sICH [RR = 10.47, 95% CI [2.79-39.32), P = 0.001]. Conclusion: Low-to-moderate evidence from RCTs and non-RCTs showed that increased ICH and sICH risk of EVT plus SMT did not translate to a higher risk of unfavorable outcomes compared with SMT and could even promote independence at 90 days in a real-world cohort.

12.
Artigo em Inglês | MEDLINE | ID: mdl-35457676

RESUMO

This paper introduces an interactive music tempo control with closed-loop heart rate feedback to yield a sportsperson with better physio-psychological states. A total of 23 participants (13 men, 10 women; 16-32 years, mean = 20.04 years) who are professionals or school team members further guide a sportsperson to amend their physical tempo to harmonize their psychological and physical states. The self-tuning mechanism between the surroundings and the human can be amplified using interactive music tempo control. The experiments showed that listening to interactive music had a significant effect on the heart rate and rating of perceived exertion (RPE) of the basketball player compared to those listening to asynchronous music or no music during exercise (p < 0.01). Synchronized interactive music allows athletes to increase their heart rate and decrease RPE during exercise and does not require a multitude of preplanned playlists. All self-selected songs can be converted into sports-oriented music using algorithms. The algorithms of synchronous and asynchronous modes in this study can be adjusted and applied to other sports fields or recovery after exercise. In the future, other musical parameters should be adjusted in real-time based on physiological signals, such as tonality, beats, chords, and orchestration.


Assuntos
Basquetebol , Música , Exercício Físico/fisiologia , Retroalimentação , Feminino , Frequência Cardíaca/fisiologia , Humanos , Masculino
13.
Food Funct ; 13(9): 5381-5395, 2022 May 10.
Artigo em Inglês | MEDLINE | ID: mdl-35470823

RESUMO

Dietary interventions with probiotics have been widely reported to be effective in regulating obesity, and the intestinal microbiota is considered to be an important environmental factor. However, few reports focus on the interactions of microbiota-metabolites-phenotypic variables in ob/ob mice, and they have not been characterized in great detail. In this study, we investigated the effects of Bacillus amyloliquefaciens SC06 on obesity, the intestinal microbiota and the bile acid metabolism of ob/ob mice using biochemical testing, histochemical staining, high-throughput sequencing of the 16S rRNA gene, LC-MS/MS analysis and qRT-PCR. The results showed that SC06 ameliorated the fat mass percentage, hepatic steatosis and liver lipid metabolism disorders and reshaped the gut microbiota and metabolites in male ob/ob mice, specifically deceasing f_S24-7, p_TM7, s_Alistipes massiliensis, f_Rikenellaceae, f_Prevotellaceae, f_Lactobacillaceae, g_Alistipes, g_Flexispira, g_Lactobacillus, g_Odoribacter, g_AF12 and g_Prevotella and increasing f_Bacteroidaceae, g_Bacteroides and f_Desulfovibrionaceae. Meanwhile, SC06 treatment groups had lower ibuprofen and higher glycodeoxycholic acid and 7-dehydrocholesterol. Correlation analysis further clarified the relationships between compositional changes in the microbiota and alterations in the metabolites and phenotypes of ob/ob mice. Moreover, SC06 downregulated bile acid synthesis, export and re-absorption in the liver and increased ileum re-absorption into the blood in ob/ob mice, which may be mediated by the FXR-SHP/FGF15 signaling pathway. These results suggest that Bacillus amyloliquefaciens SC06 can ameliorate obesity in male ob/ob mice by reshaping the intestinal microbial composition, changing metabolites and regulating bile acid metabolism via the FXR signaling pathway.


Assuntos
Bacillus amyloliquefaciens , Microbioma Gastrointestinal , Animais , Ácidos e Sais Biliares/farmacologia , Cromatografia Líquida , Metabolismo dos Lipídeos , Masculino , Camundongos , Camundongos Endogâmicos C57BL , Camundongos Endogâmicos , Obesidade/tratamento farmacológico , RNA Ribossômico 16S , Espectrometria de Massas em Tandem
14.
Mol Nutr Food Res ; : e2101094, 2022 Apr 27.
Artigo em Inglês | MEDLINE | ID: mdl-35475592

RESUMO

SCOPE: Dietary isothiocyanates (ITCs) from cruciferous vegetables have shown potent anti-breast cancer activities in preclinical models, but their anticancer effects in vivo in breast cancer patients remain elusive. A proof-of-principle, presurgical window of opportunity trial is conducted to assess the anticancer effects of dietary ITCs in breast cancer patients. METHODS AND RESULTS: Thirty postmenopausal breast cancer patients are randomly assigned to receive ITC-rich broccoli sprout extract (BSE) (200 µmol ITC per day) or a placebo for 2 weeks. Expression of biomarkers related to ITCs functions are measured in breast cancer tissue specimens at pre- and post-interventions using immunohistochemistry staining. First morning urine samples are collected at both timepoints for proteomic analysis. Overall, the study shows high compliance (100%) and low toxicity (no grade 4 adverse event). Trends of increase in cleaved caspase 3 and tumor-infiltrating lymphocytes (TILs) and trends of decrease in Ki-67 and nuclear to cytoplasm ratio of estrogen receptor (ER)-α are observed in the BSE arm only, consistent with the significantly altered signaling pathways identified in urinary proteomic analysis. CONCLUSIONS: Anticancer activities of ITCs are observed in breast cancer patients, supporting the potential beneficial roles of ITC-containing cruciferous vegetables in breast cancer prognosis.

15.
Science ; 376(6589): 199-203, 2022 04 08.
Artigo em Inglês | MEDLINE | ID: mdl-35389780

RESUMO

Despite quantum electrodynamics (QED) being one of the most stringently tested theories underpinning modern physics, recent precision atomic spectroscopy measurements have uncovered several small discrepancies between experiment and theory. One particularly powerful experimental observable that tests QED independently of traditional energy level measurements is the "tune-out" frequency, where the dynamic polarizability vanishes and the atom does not interact with applied laser light. In this work, we measure the tune-out frequency for the 23S1 state of helium between transitions to the 23P and 33P manifolds and compare it with new theoretical QED calculations. The experimentally determined value of 725,736,700(260) megahertz differs from theory [725,736,252(9) megahertz] by 1.7 times the measurement uncertainty and resolves both the QED contributions and retardation corrections.

16.
Front Med (Lausanne) ; 9: 835621, 2022.
Artigo em Inglês | MEDLINE | ID: mdl-35402469

RESUMO

Background: Microphthalmos (MCO) is a rare developmental defect characterized by small malformed eyes. Our study aimed to describe the clinical characteristics of posterior microphthalmos syndrome caused by a novel variant in MFRP gene in a Chinese patient. Methods: Complete ophthalmologic examinations were performed for the proband and proband's family members. Whole exon sequencing (WES) and Sanger sequencing were used to identify the mutated genes, and bioinformatic analysis was undertaken to predict the effect of this variant. Results: Clinical analysis showed that the proband had reduced axial length (17.95 and 17.98 mm) with normal-size corneas and shallow anterior chamber depth. Fundus photography showed scattered yellowish-white spots in the whole retina with cup-to-disc ratios of 0.95 in both eyes. Retinoschisis in the inner nuclear layer and reduced outer retina thickness were apparent on OCT examination, and optic nerve drusen demonstrated increased autofluorescence in fundus autofluorescence (FAF). Perimeter examination revealed a tubular visual field for the right eye, and electroretinography (ERG) revealed a moderately reduced rod response combined with compromised cone response. Ocular examinations of the patient's family members were unremarkable. WES revealed that the proband had homozygous mutations in c.55-1 (IVS1) G>A in intron 1 for the MFRP gene. Both the proband's parents and offspring were confirmed to be heterozygous by Sanger sequencing. Bioinformatic analysis showed this mutation was deleterious. Conclusion: We reported autosomal recessive posterior microphthalmia, atypical retinitis pigmentosa, and retinoschisis caused by a novel mutation in the MFRP gene in this consanguineous marriage family. Our study further broadens the mutation and phenotype spectrum of the MFRP gene in microphthalmia.

18.
Ann Surg Oncol ; 2022 Apr 03.
Artigo em Inglês | MEDLINE | ID: mdl-35368219

RESUMO

PURPOSE: The aim of this study was to define a threshold of minimal clinically important improvement (MCII) for interpreting patient condition following video-assisted thoracoscopic surgery (VATS). METHODS: Patients undergoing VATS were recruited for this multicenter, prospective, observational cohort study. Symptoms were measured using the MD Anderson Symptom Inventory-Lung Cancer Module perioperatively. To define MCIIs, we first identified index symptoms, defined as the most severe symptoms showing the largest reduction from day 1 post-surgery to discharge. MCIIs for each index symptom were then obtained via an anchor-based approach. Symptom recovery was defined as an MCII after post-surgery day 1. Cox regression models were used to identify risk factors for unrecovered index symptoms. RESULTS: Using 366 patients, we identified pain and fatigue as index symptoms after VATS. MCII was defined as a 30% reduction in pain or fatigue. At discharge, 22.6% of patients had not recovered from pain and 22.4% had not recovered from fatigue. Cox models found that risk factors for unrecovered pain were Charlson Comorbidity Index score ≥1 (hazard ratio [HR] 1.36, 95% confidence interval [CI] 1.04-1.77; p = 0.02) and preoperative neoadjuvant therapy (HR 2.78, 95% CI 1.13-6.83; p = 0.02). Malignancy was a risk factor for unrecovered fatigue (HR 1.47, 95% CI 1.02-2.13; p = 0.04). CONCLUSION: Pain and fatigue can be used as index measures for symptom recovery in patients following VATS. A 30% MCII represented meaningful recovery after VATS and could identify patients who may need extensive care after discharge.

19.
Int J Immunopathol Pharmacol ; 36: 3946320221084835, 2022.
Artigo em Inglês | MEDLINE | ID: mdl-35377256

RESUMO

INTRODUCTION: Patients with bipolar disorder (BD) exhibit an inflamed condition that is associated with metabolic disturbance and cognitive impairment. Whether inflammation, represented by C-reactive protein (CRP), is causally associated with BD and influences treatment outcome has not been established. METHODS: We examined whether CRP is a causal factor for the risk of BD in drug-naïve, depressed BD patients and investigated whether polymorphisms in CRP and life event changes influence cognitive function in BD patients receiving valproate (VPA) treatment. RESULTS: Our results showed that BD patients had significantly higher CRP levels and worse cognitive function than the controls, while the frequencies of CRP single nucleotide polymorphisms in BD patients and in controls were not different. In addition, the life event scale score was higher for BD patients than for controls. Furthermore, the genotypes of CRP polymorphisms and the interactions between polymorphisms of CRP and life event scale score had a significant influence on cognitive performance in BD patients after 12 weeks of VPA treatment. CONCLUSION: Our study demonstrated the clinical utility of the application of functional genetics in clarifying the interactions among CRP, life event stress, and BD and suggested the important roles of CRP gene-environment interactions in developing treatment strategies for BD.


Assuntos
Transtorno Bipolar , Ácido Valproico , Transtorno Bipolar/complicações , Transtorno Bipolar/tratamento farmacológico , Transtorno Bipolar/genética , Proteína C-Reativa/genética , Proteína C-Reativa/metabolismo , Cognição , Humanos , Ácido Valproico/efeitos adversos
20.
Sci Total Environ ; 832: 155006, 2022 Apr 02.
Artigo em Inglês | MEDLINE | ID: mdl-35381246

RESUMO

OsNRAMP5 is a transporter responsible for cadmium (Cd) and manganese (Mn) uptake and root-to-shoot translocation of Mn in rice plants. Knockout of OsNRAMP5 is regarded as an effective approach to minimize Cd uptake and accumulation in rice. It is vital to evaluate the effects of knocking out OsNRAMP5 on Cd and Mn accumulation, as well as Cd tolerance of rice plants in response to varying environmental Cd concentrations, and to uncover the underlying mechanism, which until now, has remained largely unexplored. This study showed that knockout of OsNRAMP5 decreased Cd uptake, but simultaneously facilitated Cd translocation from roots to shoots. The effect of OsNRAMP5 knockout on reducing root Cd uptake weakened, however its effect on improving root-to-shoot Cd translocation was constant with increasing environmental Cd concentrations. As a result, its mutation dramatically reduced Cd accumulation in shoots under low and moderate Cd stress, but inversely increased that under high Cd conditions. Interestingly, Cd tolerance of its knockout mutants was persistently enhanced, irrespective of lower or higher Cd concentrations in shoots, compared with that of wild-type plants. Knockout of OsNRAMP5 mitigated Cd toxicity by dramatically diminishing Cd uptake at low or moderate external Cd concentrations. Remarkably, its knockout effectively complemented deficient mineral nutrients in shoots, thereby indirectly enhancing rice tolerance to severe Cd stress. Additionally, its mutation conferred preferential delivery of Mn to young leaves and grains. These results have important implications for the application of the OsNRAMP5 mutation in mitigating Cd toxicity and lowering the risk of excessive Cd accumulation in rice grains.

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