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1.
Environ Res ; 216(Pt 2): 114523, 2023 Jan 01.
Artigo em Inglês | MEDLINE | ID: mdl-36270534

RESUMO

Acute exposure to fresh traffic-related air pollutants (TRAPs) can be high for road users, including motorbike drivers, cyclists, and pedestrians. However, evaluating the toxicity of fresh traffic emissions from on-road vehicles is challenging since pollution properties can change dynamically within a short distance and time. This study demonstrated a mobile platform equipped with an On-Board Diagnostic II (OBDII) system, a tailor-made portable emission measurement system, and an electrostatic air-liquid interface exposure system with human monocytic THP-1 cells to characterize on-road tailpipe emissions under real driving conditions. High number concentrations up to 106-107 # cm-3 of ultrafine particles (UFPs) were observed for a gasoline engine at the cold-start stage and a diesel engine during particulate filter regeneration. In particular, a substantial fraction of freshly emitted UFPs within the size less than 23 nm were observed and should be cautioned. The potential toxicity of fresh TRAPs was quantified by cell viability, cytotoxicity, oxidative stress, and inflammatory biomarkers. Results show that the decreased cell viability, increased lactate dehydrogenase (LDH) activity, and high oxidative stress induced by the fresh TRAPs were potentially contributed by gaseous pollutants as well as particles, especially driving with the high idling frequency. Moreover, the dominant contributor to the toxicity is different for gasoline's and diesel's TRAPs. Characterizing on-road air pollutant toxicity as well as physicochemical properties using an innovative mobile platform can fill this knowledge gap.


Assuntos
Poluentes Atmosféricos , Poluição do Ar , Humanos , Material Particulado/análise , Gasolina/análise , Tamanho da Partícula , Monitoramento Ambiental/métodos , Emissões de Veículos/toxicidade , Emissões de Veículos/análise , Poluentes Atmosféricos/toxicidade , Poluentes Atmosféricos/análise , Poluição do Ar/análise , Veículos Automotores
2.
Sci Total Environ ; 858(Pt 2): 159957, 2023 Feb 01.
Artigo em Inglês | MEDLINE | ID: mdl-36343820

RESUMO

The consumption of similar diets has led to the convergence of gut microbial compositions and functions across phylogenetically distinct animals. However, given the functional redundancy in gut microbiomes, it remains unclear whether synchrony occurs in their functions only and not in their composition, even within phylogenetically close animals consuming a similar diet. In this study, we collected fresh fecal samples from a Rhinopithecus roxellana population in April 2021 (before food provisioning) and June and December 2021 (after food provisioning) and used high-throughput sequencing methods (full-length 16S rRNA gene sequencing and metagenomes) to investigate changes in the gut microbiome due to food provisioning. Combining the results from our previous studies on a wild Rhinopithecus bieti population, we found that the artificial food provisions (e.g., apples, carrots, and peanuts) affected the gut microbiome, and synchrony occurred only in its functions and antibiotic resistance gene community in both Rhinopithecus species, reflecting its ecological functional redundancy. Given the current findings (e.g., depletion in probiotic microbes, dysbiosis in the gut microbial community, and changes in the antibiotic resistance gene profile), anthropogenic disturbances (e.g., food provisioning) would have potential negative effects on host health. Therefore, human activity in animal conservation should be rethought from the standpoint of gut microbial diversity.

3.
J Sci Food Agric ; 103(1): 195-204, 2023 Jan 15.
Artigo em Inglês | MEDLINE | ID: mdl-35860991

RESUMO

BACKGROUND: Insoluble dietary fiber (IDF) has beneficial physiological effects, such as the promoting of intestinal peristalsis, the improving of intestinal flora, and the absorbing of some harmful substances. Okara, a byproduct of soybean processing, is a potential source of IDF. But the larger particle size and poor water solubility of okara IDF have adverse effects on sensory properties and functional characteristics. Therefore, we used an emerging type of physical method is electron beam irradiation (EBI) to modify okara, and investigated that the effects of EBI doses on the structure and functional properties of okara IDF. RESULTS: It was found that the electron beam treatment damaged the crystalline structure of IDF. Observation of the surface of EBI-treated IDF revealed a loose and porous morphology rather than the typical smooth structure. At a dose of 6 kGy, a smallest particle size and largest specific surface area of IDF was obtained, and these factors increased the apparent viscosity of an IDF dispersion. The water holding capacity, swelling capacity and the oil holding capacity upon irradiation at 6 kGy increased 74.13%, 84.76% and 41.62%, respectively. In addition, the capacity for adsorption of cholesterol, sodium cholate, glucose and nitrite ion were improved after electron beam treatment. CONCLUSION: The modified okara IDF showed improved particle sizes and hydration properties, and these changes correlated with an improvement to the rough taste of IDF and improvements to the texture and storage period upon supplementation into food. © 2022 Society of Chemical Industry.


Assuntos
Fibras na Dieta , Elétrons , Soja/química , Adsorção , Água
4.
Br J Pharmacol ; 2022 Nov 02.
Artigo em Inglês | MEDLINE | ID: mdl-36321732

RESUMO

BACKGROUND AND PURPOSE: Gut microbiota dysbiosis induced by acute pancreatitis (AP) exacerbates pancreatic injury and systemic inflammatory response. The alleviation of gut microbiota dysbiosis through fecal microbiota transplantation (FMT) is considered a potential strategy to reduce tissue damage and inflammation in many clinical disorders. Here, we aim to investigate the effect of gut microbiota and microbiota-derived metabolites on AP, and further clarify the mechanisms associated with pancreatic damage and inflammation. EXPERIMENTAL APPROACH: Acute pancreatitis models were established by administration of caerulein or sodium taurocholate in vivo. Pancreatic acinar cells were exposed to caerulein and lipopolysaccharide in vitro to simulate acute pancreatitis. KEY RESULTS: Normobiotic FMT alleviated AP-induced gut microbiota dysbiosis and ameliorated the severity of AP, including mitochondrial dysfunction, oxidative damage and inflammation. Normobiotic FMT induced higher levels of (nicotinamide adenine dinucleotide) NAD+ associated metabolites, particularly nicotinamide mononucleotide (NMN). NMN administration mitigated AP-mediated mitochondrial dysfunction, oxidative damage and inflammation by increasing pancreatic NAD+ levels. Similarly, overexpression of the NAD+ -dependent mitochondrial deacetylase SIRT3 alleviated the severity of AP. Furthermore, SIRT3 deacetylated Peroxiredoxin 5 (PRDX5) and enhanced PRDX5 protein expression, thereby promoting its antioxidant and anti-inflammatory activities in AP. Importantly, normobiotic FMT-mediated NMN metabolism induced the SIRT3-PRDX5 pathway activation during AP. CONCLUSION AND IMPLICATIONS: Gut microbiota-derived NMN alleviates the severity of AP by activating the SIRT3-PRDX5 pathway. Normobiotic FMT could be served as a potential strategy for AP treatment.

5.
JAMA Netw Open ; 5(11): e2242064, 2022 Nov 01.
Artigo em Inglês | MEDLINE | ID: mdl-36378310

RESUMO

Importance: An association between maternal preeclampsia and an increased risk of cardiovascular disease in the offspring is plausible, but evidence in this area is limited. Objective: To investigate (1) the association between maternal preeclampsia and risks of ischemic heart disease (IHD) and stroke in the offspring, (2) whether the association varies by severity or timing of onset of preeclampsia, and (3) the role of preterm birth and small for gestational age (SGA) birth, both of which are related to preeclampsia and cardiovascular diseases, in this association. Design, Setting, and Participants: This multinational population-based cohort study obtained data from Danish, Finnish, and Swedish national registries. Live singleton births from Denmark (1973-2016), Finland (1987-2014), and Sweden (1973-2014) were followed up until December 31, 2016, in Denmark and December 31, 2014, in Finland and Sweden. Data analyses were performed between September 2020 and September 2022. Exposures: Preeclampsia and its subtypes, including early onset (<34 gestational weeks) and late onset (≥34 gestational weeks), severe and mild or moderate, and with and without SGA birth. Main Outcomes and Measures: Diagnoses of IHD and stroke were extracted from patient and cause-of-death registers. Cox proportional hazards regression models and flexible parametric survival models were used to analyze the associations. Sibling analyses were conducted to control for unmeasured familial factors. Results: The cohort included of 8 475 819 births (2 668 697 [31.5%] from Denmark, 1 636 116 [19.3%] from Finland, and 4 171 006 [49.2%] from Sweden, comprising 4 350 546 boys [51.3%]). Of these offspring, 188 670 (2.2%) were exposed to maternal preeclampsia, 7446 (0.1%) were diagnosed with IHD, and 10 918 (0.1%) were diagnosed with stroke during the median (IQR) follow-up of 19.3 (9.0-28.1) years. Offspring of individuals with preeclampsia had increased risks of IHD (adjusted hazard ratio [HR], 1.33; 95% CI, 1.12-1.58) and stroke (adjusted HR, 1.34; 95% CI, 1.17-1.52). These associations were largely independent of preterm or SGA birth. Severe forms of preeclampsia were associated with a higher stroke risk than less severe forms (severe vs mild or moderate: adjusted HR, 1.81 [95% CI, 1.41-2.32] vs 1.22 [95% CI, 1.05-1.42]; early vs late onset: adjusted HR, 2.55 [95% CI, 1.97-3.28] vs 1.18 [95% CI, 1.01-1.39]; with vs without SGA birth: adjusted HR, 1.84 [95% CI, 1.44-2.34] vs 1.25 [95% CI, 1.07-1.48]). Sibling analyses suggested that the associations were partially explained by unmeasured familial factors. Conclusions and Relevance: Results of this study suggest that offspring born to individuals with preeclampsia had increased IHD and stroke risk that were not fully explained by preterm or SGA birth, and that the associated risks for stroke were higher for severe forms of preeclampsia.


Assuntos
Doenças Cardiovasculares , Isquemia Miocárdica , Pré-Eclâmpsia , Nascimento Prematuro , Acidente Vascular Cerebral , Gravidez , Masculino , Feminino , Recém-Nascido , Humanos , Pré-Eclâmpsia/epidemiologia , Estudos de Coortes , Nascimento Prematuro/epidemiologia , Fatores de Risco , Isquemia Miocárdica/epidemiologia , Acidente Vascular Cerebral/epidemiologia
6.
Rep Prog Phys ; 2022 Nov 17.
Artigo em Inglês | MEDLINE | ID: mdl-36395499

RESUMO

The past decades witnessed the golden era of hadron physics. Many excited open heavy flavor mesons and baryons have been observed since 2017. We shall provide an updated review of the recent experimental and theoretical progresses in this active field. Besides the conventional heavy hadrons, we shall also review the recently observed open heavy flavor tetraquark states X(2900) and Tcc(3875) as well as the hidden heavy flavor multiquark states X(6900), Pcs(4459), Zcs(3985), Zcs(4000), and Zcs(4220). We will also cover the recent progresses on the glueballs and light hybrid mesons, which are the direct manifestations of the non-Abelian SU(3) gauge interaction of the Quantum Chromodynamics in the low-energy region.

7.
Orthop Surg ; 2022 Nov 21.
Artigo em Inglês | MEDLINE | ID: mdl-36411511

RESUMO

OBJECTIVE: Aseptic femoral shaft nonunion constitutes approximately 1%-10% of all femoral shaft fractures treated with intramedullary nail (IMN) fixation, possibly attributable to the lack of anti-rotational stability. Although a lateral locking plate (LP) with retainment of original IMN has shown the most success, lateral LP inflicts significant surgical trauma on patients. Therefore, the Multidimensional Cross Locking Plate (MDC-LP) was designed based on a mini-open femoral anterior approach. We aim to report and compare the technical aspects and clinical outcomes of using anterior MDC-LP or lateral LP with retention of original IMN for the treatment of aseptic femoral shaft nonunion. METHODS: In this single center retrospective cohort study, records of 49 patients who had undergone revision of femoral shaft aseptic nonunion with anterior MDC-LP or lateral LP while retaining the original IMN from January 2015 to October 2019 were retrospectively reviewed. Information on patients' demographics, clinical data, and surgical outcomes were gathered and analyzed. X-ray and CT scans were used for bone union evaluation and the lower extremity functional scale (LEFS) was used for follow-up functional evaluation. For quantitative data, the Student's t-test was used if the data were normally distributed. The Mann-Whitney U-test was used for non-normally distributed data. For qualitative data, the Chi-square test was used for comparisons. RESULTS: Twenty-seven patients were treated with anterior MDC-LP, and 22 patients were treated with lateral LP. There are no significant differences in age, sex, BMI, time since initial femoral shaft fracture, initial fracture type (close/open), nonunion type, or nonunion location between patients' group. Among patients treated with anterior MDC-LP, an average of 2-months advantage in time to union was observed (4.09 months vs. 6.8 months in the lateral LP group: P = 0.000), smaller incision was required for MDC-LP installment (7.7 cm vs 17.1 cm in lateral LP group: P = 0.000). CONCLUSIONS: For the treatment of aseptic femoral shaft nonunion with retainment of original IMN, anterior MDC-LP via mini-open femoral anterior approach described in this study is a better option than lateral LP for achieving faster bone union and satisfactory functional outcome with less surgical trauma.

8.
Radiat Oncol ; 17(1): 188, 2022 Nov 17.
Artigo em Inglês | MEDLINE | ID: mdl-36397060

RESUMO

BACKGROUND: This study was designed to establish radiation pneumonitis (RP) prediction models using dosiomics and/or deep learning-based radiomics (DLR) features based on 3D dose distribution. METHODS: A total of 140 patients with non-small cell lung cancer who received stereotactic body radiation therapy (SBRT) were retrospectively included in this study. These patients were randomly divided into the training (n = 112) and test (n = 28) sets. Besides, 107 dosiomics features were extracted by Pyradiomics, and 1316 DLR features were extracted by ResNet50. Feature visualization was performed based on Spearman's correlation coefficients, and feature selection was performed based on the least absolute shrinkage and selection operator. Three different models were constructed based on random forest, including (1) a dosiomics model (a model constructed based on dosiomics features), (2) a DLR model (a model constructed based on DLR features), and (3) a hybrid model (a model constructed based on dosiomics and DLR features). Subsequently, the performance of these three models was compared with receiver operating characteristic curves. Finally, these dosiomics and DLR features were analyzed with Spearman's correlation coefficients. RESULTS: In the training set, the area under the curve (AUC) of the dosiomics, DLR, and hybrid models was 0.9986, 0.9992, and 0.9993, respectively; the accuracy of these three models was 0.9643, 0.9464, and 0.9642, respectively. In the test set, the AUC of these three models was 0.8462, 0.8750, and 0.9000, respectively; the accuracy of these three models was 0.8214, 0.7857, and 0.8571, respectively. The hybrid model based on dosiomics and DLR features outperformed other two models. Correlation analysis between dosiomics features and DLR features showed weak correlations. The dosiomics features that correlated DLR features with the Spearman's rho |ρ| ≥ 0.8 were all first-order features. CONCLUSION: The hybrid features based on dosiomics and DLR features from 3D dose distribution could improve the performance of RP prediction after SBRT.


Assuntos
Carcinoma Pulmonar de Células não Pequenas , Aprendizado Profundo , Neoplasias Pulmonares , Pneumonite por Radiação , Radiocirurgia , Humanos , Pneumonite por Radiação/etiologia , Radiocirurgia/efeitos adversos , Carcinoma Pulmonar de Células não Pequenas/diagnóstico por imagem , Carcinoma Pulmonar de Células não Pequenas/radioterapia , Estudos Retrospectivos , Neoplasias Pulmonares/diagnóstico por imagem , Neoplasias Pulmonares/radioterapia
9.
Eur Spine J ; 2022 Nov 19.
Artigo em Inglês | MEDLINE | ID: mdl-36400905

RESUMO

OBJECTIVE: Cervical fractures with ankylosing spondylitis (CAS) are a specific type of spinal fracture with poor stability, low healing rate, and high disability rate. Its treatment is mainly surgical, predominantly through the anterior approach, posterior approach, and the anterior-posterior approach. Although many clinical studies have been conducted on various surgical approaches, controversy still exists concerning the choice of these surgical approaches by surgeons. The authors present here a systematic evaluation and meta-analysis exploring the utility of the anterior-posterior approach versus the anterior approach and the posterior approach. METHODS: After a comprehensive literature search of PubMed, Cochrane, Web of Science, and Embase databases, 12 clinical studies were included in the final qualitative analysis and 8 in the final quantitative analysis. Of these studies, 11 conducted a comparison between the anterior-posterior approach and the anterior approach and posterior approaches, while one examined only the anterior-posterior approach. Where appropriate, statistical advantage ratios and 95% confidence intervals were calculated. RESULTS: The present meta-analysis of postoperative neurological improvement showed no statistical difference in the overall neurological improvement rate between the anterior-posterior approach and anterior approach (OR 1.70, 95% CI 0.61 to 4.75; p = 0.31). However, the mean change in postoperative neurological function was lower in patients who received the anterior approach than in those who received the anterior-posterior approach (MD 0.17, 95% CI -0.02 to 0.36; p = 0.08). There was an identical trend between the anterior-posterior approach and posterior approach, with no statistically significant difference in the overall rate of neurological improvement (OR 1.37, 95% CI 0.70 to 2.56; p = 0.38). Nevertheless, the mean change in neurological function was smaller in patients receiving the anterior-posterior approach compared with the posterior approach, but there was no statistically significant difference between the two (MD 0.17, 95% CI -0.02 to 0.36; p = 0.08). CONCLUSIONS: The results of this review and meta-analysis suggest that the benefits of the anterior-posterior approach are different from those of the anterior and posterior approaches in the treatment of ankylosing spondylitis-related cervical fractures. In a word, there is no significant difference between the cervical surgical approach and the neurological functional improvement. Therefore, surgeons should pay more attention to the type of cervical fracture, the displacement degree of cervical fracture, the spinal cord injury, the balance of cervical spine and other aspects to comprehensively consider the selection of appropriate surgical methods.

10.
Int Wound J ; 2022 Nov 19.
Artigo em Inglês | MEDLINE | ID: mdl-36401595

RESUMO

To assess the impact of a stoma on surgical site wound infection in colorectal cancer, we conducted a meta-analysis. A thorough review of the literature up to September 2022 revealed that 3223 participants had colorectal cancer at the start of the investigations; 258 of them had a stoma, while 2965 did not have a stoma. Using dichotomous or contentious methods and a random or fixed-effect model, odds ratios (OR) and mean difference (MD) with 95% confidence intervals (CIs) were estimated to evaluate the impact of a stoma on surgical site wound infection in colorectal cancer. The stoma present had significantly higher surgical site wound infections (OR, 4.37; 95% CI, 3.08-6.21; P < 0.001) with no heterogeneity (I2 = 12%) compared to stoma absent in colorectal cancer. The stoma present had significantly higher surgical site wound infections compared to the stoma absent in colorectal cancer. The low number of selected studies in the meta-analysis calls for care when analysing the results.

11.
Arthritis Res Ther ; 24(1): 249, 2022 11 04.
Artigo em Inglês | MEDLINE | ID: mdl-36333776

RESUMO

BACKGROUND: Macrophages are key innate immune cells implicated in the pathogenesis of Behçet's disease (BD), and macrophage polarization plays a pivotal role in inflammatory response. This study aimed to investigate the role of BD serum on the phenotypes and functions of macrophage polarization. METHODS: BD or HC serum-treated human monocyte-derived macrophages (HMDMs) were examined M1/M2 phenotypes using flow cytometry and ELISA. The phagocytic capacity of HMDMs and CD4+T cell differentiation facilitated by HMDMs were measured by flow cytometry. Transcriptome analysis of BD and HC serum-stimulated HMDMs was conducted to identify differentially expressed genes. NF-κB signaling was examined using western blot to explore the mechanism of macrophage polarization induced by BD serum. RESULTS: BD serum-treated macrophages expressed a higher level of CD86, IL-12, and TNF-α and a lower level of CD163, which were compatible with the M1-like phenotype. Furthermore, BD serum-treated macrophages showed enhanced phagocytic capacity and promoted more Th1 cell differentiation. Sixty-one differentially expressed genes were identified between BD and HC serum-treated macrophages and were enriched in NF-κB signaling. BD serum-treated macrophages showed upregulated p-p65 and downregulated IκBα, and NF-κB inhibitor attenuated BD serum-stimulated M1-like phenotype. CONCLUSIONS: BD serum promoted macrophage polarization toward a proinflammatory M1-like phenotype through NF-κB signaling and potentially facilitated inflammation in BD. M1 polarized macrophages may be a potential therapeutic target for BD.


Assuntos
Síndrome de Behçet , NF-kappa B , Humanos , Síndrome de Behçet/genética , Síndrome de Behçet/patologia , Ativação de Macrófagos , Macrófagos , Fenótipo
12.
Soft Robot ; 2022 Oct 31.
Artigo em Inglês | MEDLINE | ID: mdl-36318510

RESUMO

The evolution of wearable technologies has led to the development of novel types of sensors customized for a wide range of applications. Wearable sensors need to possess a low form factor and be ergonomic, causing minimal impediment of the user's natural movement. Various principles have been explored to meet these requirements, ranging from optical, magnetic, resistive flex sensing to 3D printed sensors and liquid metals such as those using eutectic gallium-indium. However, manufacturing techniques for most current wearable sensors tend to be complex and difficult to scale. Challenges also exist in achieving high sensitivity with noise resistance and robustness to false detections, especially in capacitive sensors. In this research, a novel ultralow-latency soft tactile and pressure sensor developed using off-the-shelf e-textiles is proposed, which overcomes some of these limitations. The sensor does not use any specialized equipment or materials for manufacture. A human-in-loop (HIL) sensing technique is demonstrated, which provides high sensitivity, high sensing bandwidth, as well as ultralow latency, which makes it ideal as a wearable input device. In addition, the HIL method provides other advantages such as high noise rejection and resistance to accidental triggers that could be caused by other humans or environmental factors owing to its high signal to noise ratio. Finally, two applications-a wearable keyboard and gaming input device-were demonstrated using these sensors.

13.
iScience ; 25(11): 105446, 2022 Nov 18.
Artigo em Inglês | MEDLINE | ID: mdl-36388955

RESUMO

Transmembrane protein 16A (TMEM16A) localizes at plasma membrane and controls chloride influx in various type of cells. We here showed an intracellular localization pattern of TMEM16A molecules. In myoblasts, TMEM16A was primarily localized to the cytosolic compartment and partially co-localized with intracellular organelles. The global deletion of TMEM16A led to severe skeletal muscle developmental defect. In vitro observation showed that the proliferation of Tmem16a-/- myoblasts was significantly promoted along with activated ERK1/2 and Cyclin D expression; the myogenic differentiation was impaired accompanied by the enhanced caspase 12/3 activation, implying enhanced endoplasmic reticulum (ER) stress. Interestingly, the bradykinin-induced Ca2+ release from ER calcium store was significantly enhanced after TMEM16A deletion. This suggested a suppressing role of intracellular TMEM16A in ER calcium release whereby regulating the flux of chloride ion across the ER membrane. Our findings reveal a unique location pattern of TMEM16A in undifferentiated myoblasts and its role in myogenesis.

14.
BMC Psychiatry ; 22(1): 733, 2022 Nov 24.
Artigo em Inglês | MEDLINE | ID: mdl-36434598

RESUMO

BACKGROUND: Bodily distress syndrome (BDS) is a new, empirical-based diagnosis of functional somatic symptoms. This study aimed to explore the prevalence of BDS and its association with psychosocial variables in a Chinese clinical population. METHODS: A multicentre cross-sectional study of 1269 patients was conducted in 9 different Chinese tertiary outpatient hospitals. The BDS was identified by trained interviewers face-to face, based on a brief version of the Schedules for Assessment in Neuropsychiatry (RIFD) and the BDS Checklist-25. Sociodemographic data and further information were characterised from psychometric questionnaires (The Patient Health Questionnaire-15, the Patient Health Questionnaire-9, the General Anxiety Disorder-7, the Whiteley scale-8) . RESULTS: Complete data were available for 697 patients. The prevalence of BDS was 26.8% (95% confidence interval (CI): 23.5-30.1). Among the participants, 5.8% (95% CI: 4.1-7.6) fulfilled the criteria for single-organ BDS, while 20.9% (95%CI: 17.9-24.0) had multi-organ BDS. Comparison of the PHQ-15, PHQ-9, GAD-7, and WI-8 scores revealed higher scores on all dimensions for patients with BDS. In a binary logistic regression analysis, BDS was significantly associated with increased health-related anxiety (WI-8) and depression (PHQ-9). The explained variance was Nagelkerke's R2 = 0.42. CONCLUSIONS: In China, the BDS is a common clinical condition in tertiary outpatient hospital settings with high prevalence, and is associated with health anxiety and depressive symptoms. In this clinical population, the severe multi-organ subtype of BDS was the most frequent.


Assuntos
Hospitais , Pacientes Ambulatoriais , Humanos , Prevalência , Estudos Transversais , Síndrome
15.
Ecotoxicol Environ Saf ; 247: 114266, 2022 Dec 01.
Artigo em Inglês | MEDLINE | ID: mdl-36334339

RESUMO

Particulate matter 2.5 (PM2.5) is a widely known atmospheric pollutant which can induce the aging-related pulmonary diseases such as acute respiratory distress syndrome (ARDS), chronic obstructive pulmonary disease (COPD) and interstitial pulmonary fibrosis (IPF). In recent years, with the increasing atmospheric pollution, airborne fine PM2.5, which is an integral part of air pollutants, has become a thorny problem. Hence, this study focused on the effect of PM2.5 on cellular senescence in the lung, identifying which inflammatory pathway mediated PM2.5-induced cellular senescence and how to play a protective role against this issue. Our data suggested that PM2.5 induced time- and concentration-dependent increasement in the senescence of A549 cells. Using an inhibitor of cGAS (PF-06928215) and an inhibitor of NF-κB (BAY 11-7082), it was revealed that PM2.5-induced senescence was regulated by inflammatory response, which was closely related to the cGAS/STING/NF-κB pathway activated by DNA damage. Moreover, our study also showed that the pretreatment with selenomethionine (Se-Met) could inhibit inflammatory response and prevent cellular senescence by hindering cGAS/STING/NF-κB pathway in A549 cells exposed to PM2.5. Furthermore, in vivo C57BL/6J mice model demonstrated that aging of mouse lung tissue caused by PM2.5 was attenuated by decreasing cGAS expression after Se-Met treatment. Our findings indicated that selenium made a defense capability for PM2.5-induced cellular senescence in the lung, which provided a novel insight for resisting the harm of PM2.5 to human health.


Assuntos
NF-kappa B , Selenometionina , Animais , Humanos , Camundongos , Antioxidantes , Senescência Celular , Pulmão , Camundongos Endogâmicos C57BL , Nucleotidiltransferases , Material Particulado/toxicidade
16.
Exp Cell Res ; 422(1): 113427, 2022 Nov 15.
Artigo em Inglês | MEDLINE | ID: mdl-36400183

RESUMO

Protein kinase C epsilon (PKCε) belongs to a family of serine/threonine kinases that control cell proliferation, differentiation and survival. Aberrant PKCε activation and overexpression is a frequent feature of numerous cancers. However, its role in regulation of lipid metabolism in cancer cells remains elusive. Here we report a novel function of PKCε in regulating of prostate cancer cell proliferation by modulation of PKM2-mediated de novo lipogenesis. We show that PKCε promotes de novo lipogenesis and tumor cell proliferation via upregulation of lipogenic enzymes and lipid contents in prostate cancer cells. Mechanistically, PKCε interacts with NABD (1-388) domain of C-terminal deletion on pyruvate kinase isoform M2 (PKM2) and enhances the Tyr105 phosphorylation of PKM2, leading to its nuclear localization. Moreover, forced expression of mutant Tyr105 (Y105F) or PKM2 inhibition suppressed de novo lipogenesis and cell proliferation induced by overexpression of PKCε in prostate cancer cells. In a murine tumor model, inhibitor of PKM2 antagonizes lipogenic enzymes expression and prostate cancer growth induced by overexpression of PKCε in vivo. These data indicate that PKCε is a critical regulator of de novo lipogenesis, which may represent a potential therapeutic target for the treatment of prostate cancer.

18.
Clin Lung Cancer ; 2022 Sep 30.
Artigo em Inglês | MEDLINE | ID: mdl-36333268

RESUMO

INTRODUCTION: Epidermal growth factor receptor (EGFR) mutations are well-known genetic alterations in advanced non-small cell lung cancer (NSCLC) which are associated with remarkable survival benefits from first-line treatment with EGFR-tyrosine kinase inhibitors (EGFR-TKIs). However, around 30% of patients exhibit primary resistance to EGFR-TKIs therapy. Co-existing MET amplification/over-expression has showed shorter time to progression on EGFR-TKI monotherapy. Osimertinib (TAGRISSO, AZD9291) has been recommended in EGFR-mutant advanced NSCLC patients as first-line treatment. Savolitinib (AZD6094, HMPL-504) is a highly selective MET-TKI which has demonstrated anti-tumor activity in various cancers with MET alterations. METHODS: This FLOWERS study, a phase II, randomized, open-label, 2-cohort multicenter trial aimed to evaluate the efficacy and safety of osimertinib with or without savolitinib as first-line therapy in patients with de novo MET amplified/over-expressed, EGFR-mutant positive, locally advanced or metastatic NSCLC. Approximately 44 patients will be randomized to receive osimertinib (80 mg once daily) monotherapy or osimertinib (80 mg once daily) and savolitinib (300 mg twice daily) combination therapy; patients in osimertinib monotherapy cohort confirmed as MET positive (MET-amplified/over-expressed) after disease progression will have the opportunity to receive the cross-over combination therapy as second-line treatment. Primary endpoint will be objective response rate. Key secondary endpoints will be progression-free survival, duration of response, disease control rate, overall survival, safety and tolerability. CONCLUSION: The results of the study will provide better perspectives on the efficacy and safety of EGFR-TKI plus MET-TKI combination therapy (osimertinib plus savolitinib) in patients with de novo MET-amplified/over-expressed, EGFR-mutant positive, treatment naïve, advanced NSCLC and offer a meaningful guidance in clinical practice (NCT05163249).

19.
Front Psychiatry ; 13: 935597, 2022.
Artigo em Inglês | MEDLINE | ID: mdl-36339843

RESUMO

Objective: This study investigates the diagnostic accuracy of the PHQ-15, SSS-8, SSD-12 and Whitley 8 and their combination in detecting DSM-5 somatic symptom disorder in general hospitals. Methods: In our former multicenter cross-sectional study enrolling 699 outpatients from different departments in five cities in China, SCID-5 for SSD was administered to diagnose SSD and instruments including PHQ-15, SSS-8, SSD-12 and WI-8 were used to evaluate the SSD A and B criteria. In this secondary analysis study, we investigate which instrument or combination of instrument has best accuracy for detecting SSD in outpatients. Receiver operator curves were created, and area under the curve (AUC) analyses were assessed. The sensitivity and specificity were calculated for the optimal individual cut points. Results: Data from n = 694 patients [38.6% male, mean age: 42.89 years (SD = 14.24)] were analyzed. A total of 33.9% of patients fulfilled the SSD criteria. Diagnostic accuracy was moderate or good for each questionnaire (PHQ-15: AUC = 0.72; 95% CI = 0.68-0.75; SSS-8: AUC = 0.73; 95% CI = 0.69-0.76; SSD-12: AUC = 0.84; 95% CI = 0.81-0.86; WI-8: AUC = 0.81; 95% CI = 0.78-0.84). SSD-12 and WI-8 were significantly better at predicting SSD diagnoses. Combining PHQ-15 or SSS-8 with SSD-12 or WI-8 showed similar diagnostic accuracy to SSD-12 or WI-8 alone (PHQ-15 + SSD-12: AUC = 0.84; 95% CI = 0.81-0.87; PHQ-15 + WI-8: AUC = 0.82; 95% CI = 0.79-0.85; SSS-8 + SSD-12: AUC = 0.84; 95% CI = 0.81-0.87; SSS-8 + WI-8: AUC = 0.82; 95% CI = 0.79-0.84). In the efficiency analysis, both SSD-12 and WI-8 showed good efficiency, SSD-12 slightly more efficient than WI-8; however, within the range of good sensitivity, the PHQ-15 and SSS-8 delivered rather poor specificity. For a priority of sensitivity over specificity, the cutoff points of ≥13 for SSD-12 (sensitivity and specificity = 80 and 72%) and ≥17 for WI-8 (sensitivity and specificity = 80 and 67%) are recommended. Conclusions: In general hospital settings, SSD-12 or WI-8 alone may be sufficient for detecting somatic symptom disorder, as effective as when combined with the PHQ-15 or SSS-8 for evaluating physical burden.

20.
Plant Genome ; : e20279, 2022 Nov 10.
Artigo em Inglês | MEDLINE | ID: mdl-36366733

RESUMO

Breeding crop plants with increased yield potential and improved tolerance to stressful environments is critical for global food security. Drought stress (DS) adversely affects agricultural productivity worldwide and is expected to rise in the coming years. Therefore, it is vital to understand the physiological, biochemical, molecular, and ecological mechanisms associated with DS. This review examines recent advances in plant responses to DS to expand our understanding of DS-associated mechanisms. Suboptimal water sources adversely affect crop growth and yields through physical impairments, physiological disturbances, biochemical modifications, and molecular adjustments. To control the devastating effect of DS in crop plants, it is important to understand its consequences, mechanisms, and the agronomic and genetic basis of DS for sustainable production. In addition to plant responses, we highlight several mitigation options such as omics approaches, transgenics breeding, genome editing, and biochemical to mechanical methods (foliar treatments, seed priming, and conventional agronomic practices). Further, we have also presented the scope of conventional and speed breeding platforms in helping to develop the drought-smart future crops. In short, we recommend incorporating several approaches, such as multi-omics, genome editing, speed breeding, and traditional mechanical strategies, to develop drought-smart cultivars to achieve the 'zero hunger' goal.

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