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1.
J Obstet Gynaecol Can ; 46(5): 102356, 2024 Jan 11.
Artigo em Inglês | MEDLINE | ID: mdl-38215821

RESUMO

OBJECTIVE: Syphilis-related stillbirths (SRSBs) disproportionately affect marginalized women with 11% of all local stillbirths having maternal syphilis as a contributory factor in 2020. This study describes the incidence and perinatal factors associated with SRSB. METHODS: This was a retrospective cohort study of all stillbirths occurring from 1 January 2017 to 31 December 2020, at a single tertiary-level referral hospital in Winnipeg, Manitoba. Cases that met criteria for SRSB were identified from hospital records and included in the final analysis. Maternal demographics, comorbidities, prenatal care attendance, sexually transmitted infection testing, treatment, and diagnostic investigations at time of stillbirth were collected from hospital charts using a standardized data collection form. Descriptive statistics were performed to present the results. RESULTS: The proportion of SRSB increased over the period of study from 0%-11%. Eleven cases were identified as SRSB, with diagnosis occurring intrapartum in 7 cases and antenatally in 4 cases. Of the 4 antenatal cases, only 2 had identifiable treatment responses indicated by microbiological and pathology workup. Commonly identified risk factors for SRSB were homelessness, mental illness, substance use, sexually transmitted co-infections, and lack of prenatal care. CONCLUSIONS: Cases of SRSB are rising in Winnipeg with 11% of all stillbirths having maternal syphilis as a contributory factor by 2020. SRSBs disproportionately affect marginalized women. The dramatic and rapid changes in the epidemiology of syphilis in Winnipeg are likely shared by other Canadian regions and warrant increased prevention strategies to improve outcomes.

2.
Stem Cell Res Ther ; 14(1): 369, 2023 Dec 13.
Artigo em Inglês | MEDLINE | ID: mdl-38093354

RESUMO

BACKGROUNDS: Allergic airway inflammation is prevalent worldwide and imposes a considerable burden on both society and affected individuals. This study aimed to investigate the therapeutic advantages of mesenchymal stem cells (MSCs) overexpressed interleukin-10 (IL-10) for the treatment of allergic airway inflammation, as both IL-10 and MSCs possess immunosuppressive properties. METHODS: Induced pluripotent stem cell (iPSC)-derived MSCs were engineered to overexpress IL-10 via lentiviral transfection (designated as IL-10-MSCs). MSCs and IL-10-MSCs were administered intravenously to mice with allergic inflammation induced by ovalbumin (OVA), and the features of allergic inflammation including inflammatory cell infiltration, Th cells in the lungs, and T helper 2 cell (Th2) cytokine levels in bronchoalveolar lavage fluid (BALF) were examined. MSCs and IL-10-MSCs were co-cultured with CD4+ T cells from patients with allergic rhinitis (AR), and the levels of Th2 cells and corresponding type 2 cytokines were studied. RNA-sequence was performed to further investigate the potential effects of MSCs and IL-10-MSCs on CD4+ T cells. RESULTS: Stable IL-10-MSCs were established and characterised by high IL-10 expression. IL-10-MSCs significantly reduced inflammatory cell infiltration and epithelial goblet cell numbers in the lung tissues of mice with allergic airway inflammation. Inflammatory cell and cytokine levels in BALF also decreased after the administration of IL-10-MSCs. Moreover, IL-10-MSCs showed a stronger capacity to inhibit the levels of Th2 after co-cultured with CD4+ T cells from patients with AR. Furthermore, we elucidated lower levels of IL-5 and IL-13 in IL-10-MSCs treated CD4+ T cells, and blockade of IL-10 significantly reversed the inhibitory effects of IL-10-MSCs. We also reported the mRNA profiles of CD4+ T cells treated with IL-10-MSCs and MSCs, in which IL-10 played an important role. CONCLUSION: IL-10-MSCs showed positive effects in the treatment of allergic airway inflammation, providing solid support for the use of genetically engineered MSCs as a potential novel therapy for allergic airway inflammation.

3.
J Geriatr Cardiol ; 20(11): 779-787, 2023 Nov 28.
Artigo em Inglês | MEDLINE | ID: mdl-38098467

RESUMO

BACKGROUND: The benefits of healthy lifestyles are well recognized. However, the extent to which improving unhealthy lifestyles reduces cardiovascular disease (CVD) risk needs to be discussed. We evaluated the impact of lifestyle improvement on CVD incidence using data from the China-PAR project (Prediction for Atherosclerotic Cardiovascular Disease Risk in China). METHODS: A total of 12,588 participants free of CVD were followed up for three visits after the baseline examination. Changes in four lifestyle factors (LFs) (smoking, diet, physical activity, and alcohol consumption) were assessed through questionnaires from the baseline to the first follow-up visit. Cox proportional hazard models were used to estimate hazard ratios (HRs) and corresponding 95% confidence intervals (CIs). The risk advancement periods (RAPs: the age difference between exposed and unexposed participants reaching the same incident CVD risk) and population-attributable risk percentage (PAR%) were also calculated. RESULTS: A total of 909 incident CVD cases occurred over a median follow-up of 11.14 years. Compared with maintaining 0-1 healthy LFs, maintaining 3-4 healthy LFs was associated with a 40% risk reduction of incident CVD (HR = 0.60, 95% CI: 0.45-0.79) and delayed CVD risk by 6.31 years (RAP: -6.31 [-9.92, -2.70] years). The PAR% of maintaining 3-4 unhealthy LFs was 22.0% compared to maintaining 0-1 unhealthy LFs. Besides, compared with maintaining two healthy LFs, improving healthy LFs from 2 to 3-4 was associated with a 23% lower risk of CVD (HR = 0.77, 95% CI: 0.60-0.98). CONCLUSIONS: Long-term sustenance of healthy lifestyles or improving unhealthy lifestyles can reduce and delay CVD risk.

5.
PLoS One ; 18(10): e0293327, 2023.
Artigo em Inglês | MEDLINE | ID: mdl-37883350

RESUMO

BACKGROUND: Psoriasis is a systemic immune-mediated chronic inflammatory skin disease; its systemic manifestations and periodic recurrence negatively affect a patient's quality of life. Inflammatory cytokines are known to have an important role in the onset and progression of psoriasis, however, data on the association between circulating inflammatory cytokines and psoriasis risk is inconclusive. Here, we explore the relevance of circulating proinflammatory factors to the pathogenesis of psoriasis using a meta-analysis. OBJECTIVE: To explore the association between circulating levels of inflammatory factors and psoriasis to elucidate the mechanisms underlying psoriasis and improve clinical diagnosis and treatment. METHODS: We systematically retrieved articles published in PubMed, EMBASE, the Cochrane Library and the Web of Science from the establishment of each database to January 2023. The standard mean difference (SMD) in cytokine levels of individuals with psoriasis and healthy controls was used to check for correlations between circulating inflammatory factor levels and psoriasis. RESULTS: Fifty-seven studies, with data from 2838 patients, were retrieved and included in the meta-analysis. Eleven inflammatory factors were studied (circulating interleukin-2 (IL-2), IL-4, IL-12, IL-17, IL-18, IL-22, IL-23, IL-35, IL-36, transforming growth factor-beta (TGF-ß) and gamma-interferon (IFN-γ)). Of these, IL-2 [SMD = 1.29 (95% CI: 0.61-1.97; P <0.001)], IL-17 [SMD = 0.71 (95% CI: 0.12-1.30; P = 0.018)], IL-18 [SMD = 1.27 (95% CI: 0.64-1.90; P <0.001)], and IFN-γ [SMD = 1.90 (95% CI: 1.27-2.52; P <0.001)] levels had significant correlations with psoriasis. CONCLUSION: Increased serum concentrations of the circulating inflammatory cytokines IL-2, IL-17, IL-18 and IFN-γ were significantly correlated with psoriasis.


Assuntos
Citocinas , Psoríase , Humanos , Interferon gama , Interleucina-17 , Interleucina-18 , Interleucina-2 , Psoríase/tratamento farmacológico , Qualidade de Vida
6.
Cell Rep ; 42(10): 113170, 2023 10 31.
Artigo em Inglês | MEDLINE | ID: mdl-37738124

RESUMO

Chronic stress and chronic pain are two major predisposing factors to trigger depression. Enhanced excitatory input to the lateral habenula (LHb) has been implicated in the pathophysiology of depression. However, the contribution of inhibitory transmission remains unclear. Here, we dissect an inhibitory projection from the sensory thalamic reticular nucleus (sTRN) to the LHb, which is activated by acute aversive stimuli. However, chronic restraint stress (CRS) weakens sTRN-LHb synaptic strength, and this synaptic attenuation is indispensable for CRS-induced LHb neural hyperactivity and depression onset. Moreover, artificially inhibiting the sTRN-LHb circuit induces depressive-like behaviors in healthy mice, while enhancing this circuit relieves depression induced by both chronic stress and chronic pain. Intriguingly, neither neuropathic pain nor comorbid mechanical hypersensitivity in chronic stress is affected by this pathway. Altogether, our study demonstrates an sTRN-LHb circuit in establishing and modulating depression, thus shedding light on potential therapeutic targets for preventing or managing depression.


Assuntos
Dor Crônica , Habenula , Camundongos , Animais , Depressão/metabolismo , Neurônios/metabolismo , Habenula/fisiologia , Núcleos Talâmicos
7.
Chempluschem ; 88(11): e202300387, 2023 11.
Artigo em Inglês | MEDLINE | ID: mdl-37728035

RESUMO

Colon cancer is emerging as one of the most common cancers worldwide, ranking in the top three in morbidity and mortality. Oral methotrexate (MTX) has been employed as a first-line treatment for various cancers, such as colon, breast, and lung cancer. However, the complexity and particularity of the gastrointestinal microenvironment and the limitations of MTX itself, including severe adverse effects and instability, are the main obstacles to the safe delivery of MTX to colon tumor sites. Herein, an innovative oral administrated anticancer therapeutic MTX@Am7CD/SDS NPs equipped with both pH and temperature sensitivity, which could effectively prevent MTX@Am7CD/SDS NPs from being degraded in the acidic environment mimicking the stomach and small intestine, thus harboring the potential to accumulate at the site of colon lesions and further release intestinal drug under mild conditions. In cellular assays, compared with free MTX, MTX@Am7CD/SDS NPs showed a favorable tumor inhibition effect on three tumor cell lines, as well as excellent cell uptake and apoptosis-inducing effect on SW480 cells. Therefore, this work provides a feasible solution for the safe use of MTX in the treatment of colon cancer and even other intestinal diseases.


Assuntos
Neoplasias do Colo , Nanopartículas , Humanos , Metotrexato/farmacologia , Metotrexato/uso terapêutico , Sistemas de Liberação de Medicamentos , Preparações de Ação Retardada , Neoplasias do Colo/tratamento farmacológico , Microambiente Tumoral
8.
Nat Commun ; 14(1): 5124, 2023 08 23.
Artigo em Inglês | MEDLINE | ID: mdl-37612268

RESUMO

Chronic pain causes both physical suffering and comorbid mental symptoms such as anhedonia. However, the neural circuits and molecular mechanisms underlying these maladaptive behaviors remain elusive. Here using a mouse model, we report a pathway from vesicular glutamate transporter 3 neurons in the dorsal raphe nucleus to dopamine neurons in the ventral tegmental area (VGluT3DRN→DAVTA) wherein population-level activity in response to innocuous mechanical stimuli and sucrose consumption is inhibited by chronic neuropathic pain. Mechanistically, neuropathic pain dampens VGluT3DRN → DAVTA glutamatergic transmission and DAVTA neural excitability. VGluT3DRN → DAVTA activation alleviates neuropathic pain and comorbid anhedonia-like behavior (CAB) by releasing glutamate, which subsequently promotes DA release in the nucleus accumbens medial shell (NAcMed) and produces analgesic and anti-anhedonia effects via D2 and D1 receptors, respectively. In addition, VGluT3DRN → DAVTA inhibition produces pain-like reflexive hypersensitivity and anhedonia-like behavior in intact mice. These findings reveal a crucial role for VGluT3DRN → DAVTA → D2/D1NAcMed pathway in establishing and modulating chronic pain and CAB.


Assuntos
Dor Crônica , Neuralgia , Humanos , Área Tegmentar Ventral , Núcleo Dorsal da Rafe , Anedonia , Neurônios Dopaminérgicos , Ácido Glutâmico
9.
PLoS Negl Trop Dis ; 17(8): e0011540, 2023 08.
Artigo em Inglês | MEDLINE | ID: mdl-37552670

RESUMO

BACKGROUND: Rodents are the predominant natural hosts of orthohantavirus and the source of human infection, hemorrhagic fever with renal syndrome (HFRS) caused by orthohantavirus is a severe public health problem in the Yichun region, Jiangxi Province, China. However, little information is known about the infection of orthohantavirus in humans and rodents, and the genetic characteristics of the epidemic orthohantavirus in the region. METHODS: The clinical data of HFRS cases in 2016-2021 was analyzed. Virus infection in rodents was analyzed by orthohantavirus antigen detection using immunofluorescent assay, and the species of orthohantaviruses in rodents and patients were identified by real-time RT-PCR and gene sequencing. The S and M segments of orthohantaviruses from rodents and patients were recovered and analyzed. RESULTS: A total of 1,573 HFRS cases were reported in the Yichun region from 2016 to 2021, including 11 death cases. HFRS cases peaked twice each year: in winter from November to January and early summer from May to June. Farmers constituted the predominant population suffering from HFRS. The orthohantavirus antigen was identified in five species of rodents: Apodemus agrarius (A. agrarius), Rattus norvegicus (R. norvegicus), Sorex araneus, Rattus losea (R. losea), and Niviventer confucianus (N. confucianus). The real-time RT-PCR test and genetic analysis results showed that Hantaan orthohantavirus (HTNV), Seoul orthohantavirus (SEOV), and Dabieshan orthohantavirus (DBSV) were circulated in the rodents. HTNV, SEOV, and DBSV from the rodents were distantly related to other known orthohantaviruses and belonged to novel genetic lineages. SEOV and HTNV were found in HFRS patients, but 97.8% (90/92) of the infections were caused by HTNV. Winter and early summer peaks were both caused by HTNV. The HTNV sequences recovered from HFRS cases were closely related to those from A. agrarius. CONCLUSIONS: In the Yichun region, the orthohantaviruses transmitted in rodents include HTNV, SEOV, and DBSV, which have obvious genetic characteristics and high genetic diversity. At the same time, this region is an HFRS mixed epidemic area dominated by HTNV, with two peaks every year, which deserves our high attention.


Assuntos
Infecções por Hantavirus , Febre Hemorrágica com Síndrome Renal , Orthohantavírus , Vírus Seoul , Humanos , Ratos , Animais , Roedores , Febre Hemorrágica com Síndrome Renal/epidemiologia , Febre Hemorrágica com Síndrome Renal/veterinária , Febre Hemorrágica com Síndrome Renal/diagnóstico , Orthohantavírus/genética , Vírus Seoul/genética , China/epidemiologia , Filogenia
10.
Stem Cell Res Ther ; 14(1): 180, 2023 07 24.
Artigo em Inglês | MEDLINE | ID: mdl-37488601

RESUMO

BACKGROUND: Mesenchymal stromal cells-derived small extracellular vesicles (MSC-sEVs) have recently attracted considerable attention because of their therapeutic potential in various immune diseases. We previously reported that MSC-sEVs could exert immunomodulatory roles in allergic airway inflammation by regulating group 2 innate lymphoid cell (ILC2) and dendritic cell (DC) functions. Therefore, this study aimed to investigate the indirect effects of MSC-sEVs on ILC2s from patients with allergic rhinitis (AR) via DCs. METHODS: Here, we isolated sEVs from induced pluripotent stem cells-MSCs using anion-exchange chromatography and mature DCs (mDCs) were treated with MSC-sEVs. sEV-mDCs were co-cultured with peripheral blood mononuclear cells from patients with AR or purified ILC2s. The levels of IL-13 and GATA3 in ILC2s were examined by flow cytometry. Bulk RNA sequence for mDCs and sEV-mDCs was employed to further probe the potential mechanisms, which were then validated in the co-culture systems. RESULTS: sEV-mDCs showed impaired capacity in priming the levels of IL-13 and GATA3 in ILC2s when compared with mDCs. Furthermore, there was higher PGE2 and IL-10 production from sEV-mDCs, and the blockade of them especially the former one reversed the inhibitory effects of sEV-mDCs. CONCLUSIONS: We demonstrated that MSC-sEVs were able to dampen the activating effects of mDCs on ILC2s in patients with AR. Mechanismly, the PGE2-EP2/4 axis played an essential role in the immunomodulatory effects of sEV-mDCs on ILC2s. Herein, we provided new insights into the mechanism underlying the therapeutic effects of MSC-sEVs in allergic airway inflammation.


Assuntos
Vesículas Extracelulares , Rinite Alérgica , Humanos , Imunidade Inata , Dinoprostona , Interleucina-13 , Leucócitos Mononucleares , Linfócitos , Inflamação , Células Dendríticas
11.
Indian J Surg Oncol ; 14(2): 376-386, 2023 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-37324285

RESUMO

The American Joint Committee on Cancer (AJCC) 8th stage system was limited in accuracy for predicting prognosis of stage IA non-small cell lung cancer (NSCLC) patients. This study aimed to establish and validate two nomograms that predict overall survival (OS) and lung cancer-specific survival (LCSS) in surgically resected stage IA NSCLC patients. Postoperative patients with stage IA NSCLC in SEER database between 2004 and 2015 were examined. Survival and clinical information according to the inclusion and exclusion criteria were collected. All patients were randomly divided into the training cohort and validation cohort with a ratio of 7:3. Independent prognosis factors were evaluated using univariate and multivariate Cox regression analyses, and predictive nomogram was established based on these factors. Nomogram performance was measured using the C-index, calibration plots, and DCA. Patients were grouped by quartiles of nomogram scores and survival curves were plotted by Kaplan-Meier analysis. In total, 33,533 patients were included in the study. The nomogram contained 12 prognostic factors in OS and 10 prognostic factors in LCSS. In the validation set, the C-index was 0.652 for predicting OS and 0.651 for predicting LCSS. The calibration curves for the nomogram-predicted probability of OS and LCSS showed good agreement between the actual observation and nomogram prediction. DCA indicated that the clinical value of the nomograms were higher than AJCC 8th stage for predicting OS and LCSS. Nomogram scores related risk stratification revealed statistically significant difference which have better discrimination than AJCC 8th stage. The nomogram can accurately predict OS and LCSS in surgically resected patients with stage IA NSCLC. Supplementary Information: The online version contains supplementary material available at 10.1007/s13193-022-01700-w.

12.
Mol Brain ; 16(1): 54, 2023 06 27.
Artigo em Inglês | MEDLINE | ID: mdl-37370111

RESUMO

Itch is a complex aversive sensory and emotional experience. As a most upsetting symptom in many dermatological and systemic diseases, it lacks efficient treatments. The lateral habenula nucleus (LHb) encodes negative emotions in the epithalamus and has been implicated in pain and analgesia. Nevertheless, the role of the lateral habenula nucleus in the pruritic sensation and emotion remains elusive. Here we defined the crucial role of glutamatergic neurons within the lateral habenula nucleus (GluLHb) in itch modulation in mice. We established histamine-dependent and histamine-independent models of acute pruritus, as well as the acetone-ether-water (AEW) model of chronic pruritus. We first assessed the effects of pruritogen injection on neural activation in both medial and lateral divisions of LHb in vitro. We then demonstrated that the population activity of GluLHb neurons was increased during the acute itch and chronic itch-induced scratching behaviors in vivo. In addition, electrophysiological data showed that the excitability of GluLHb neurons was enhanced by chronic itch. Chemogenetic suppression of GluLHb neurons disrupted both acute and chronic itch-evoked scratching behaviors. Furthermore, itch-induced conditioned place aversion (CPA) was abolished by GluLHb neuronal inhibition. Finally, we dissected the LHb upstream brain regions. Together, these findings reveal the involvement of LHb in processing both the sensational and emotional components of pruritus and may shed new insights into itch therapy.


Assuntos
Habenula , Camundongos , Animais , Histamina , Emoções , Sensação , Prurido
13.
J Genet Couns ; 2023 Apr 27.
Artigo em Inglês | MEDLINE | ID: mdl-37106568

RESUMO

Genetic assistant positions are now widely integrated in genetic services to address genetic counselor shortages and ultimately improve efficiency. While over 40% of genetic counselors report working with a genetic assistant ("NSGC Professional Status Survey: Work Environment," 2022), there is limited information about the genetic assistant workforce. The present study surveyed 164 genetic assistants and 139 individuals with experience working with genetic assistants (specifically genetic counselors, residents, geneticists, and administrative staff). Information was collected about genetic assistant demographics, positions, roles and responsibilities, and career paths. The data revealed that the genetic assistant workforce is demographically similar to the genetic counselor workforce and that most genetic assistants intend to pursue a career in genetic counseling. The genetic assistant positions were heterogeneous in terms of the roles and responsibilities assigned, even when separated by work setting. Lastly, participants reported that there were at least 144 genetic assistants across their institutions, a number that has likely grown since the time of the survey. The findings from this study highlight important opportunities for future research and focus, especially development of a scope of practice and competencies for genetic assistants, as well as the potential to use genetic assistant positions as an avenue to improve diversity within the genetic counseling workforce.

14.
Ther Adv Med Oncol ; 15: 17588359231167818, 2023.
Artigo em Inglês | MEDLINE | ID: mdl-37113733

RESUMO

Background: Circulating tumor cells (CTCs) are prognostic biomarker in non-small-cell lung cancer (NSCLC). CTCs could also be used as predictor of efficacy of systemic treatments in advanced NSCLC. Objectives: We described the dynamic changes of CTCs during first-line platinum-based chemotherapy in advanced NSCLC and clarified the correlation between CTC counts and efficacy of chemotherapy. Design: Chemotherapy is administered and blood specimens are collected at four time points from baseline to disease progression for CTC detection. Methods: This multicenter prospective study enrolled patients with previously untreated stage III or IV NSCLC fit for standard platinum-based chemotherapy. Bloods were sampled as per standard operating procedures at baseline, cycle 1 and cycle 4 of chemotherapy, and at disease progression for CTC analysis using the CellSearch system. Results: Among 150 patients enrolled, median overall survival (OS) was 13.8, 8.4, and 7.9 months in patients with CTC-, KIT-CTC, and KIT+CTC at baseline (p = 0.002). Patients with persistent negative CTC (46.0%) had longer progression-free survival [5.7 months, 95% confidence interval (CI): 5.0-6.5 versus 3.0 months, 0.6-5.4; hazard ratio (HR): 0.34, 95% CI: 0.18-0.67) and OS (13.1 months, 10.9-15.3 versus 5.6 months, 4.1-7.1; HR: 0.17, 0.08-0.36) compared with patients with persistent positive CTC (10.7%), which was not impacted by chemotherapy. Chemotherapy decreased CTC from 36.0% (54/150) to 13.7% (13/95). Conclusions: CTC persistent presence during treatment represents poor prognosis and resistance to chemotherapy in advanced NSCLC. Chemotherapy could effectively eliminate CTCs. Molecular characterization and the functionalization of CTC will be warranted for further intensive investigation. Trial registration: NCT01740804.

15.
Sheng Li Xue Bao ; 75(1): 1-9, 2023 Feb 25.
Artigo em Chinês | MEDLINE | ID: mdl-36859829

RESUMO

This study was designed to evaluate the protective effect of CPD1, a novel phosphodiesterase 5 inhibitor, on renal interstitial fibrosis after unilateral renal ischemia-reperfusion injury (UIRI). Male BALB/c mice were subjected to UIRI, and treated with CPD1 once daily (i.g, 5 mg/kg). Contralateral nephrectomy was performed on day 10 after UIRI, and the UIRI kidneys were harvested on day 11. Hematoxylin-eosin (HE), Masson trichrome and Sirius Red staining methods were used to observe the renal tissue structural lesions and fibrosis. Immunohistochemical staining and Western blot were used to detect the expression of proteins related to fibrosis. HE, Sirius Red and Masson trichrome staining showed that CPD1-treated UIRI mice had lower extent of tubular epithelial cell injury and deposition of extracellular matrix (ECM) in renal interstitium compared with those in the fibrotic mouse kidneys. The results from immunohistochemistry and Western blot assay indicated significantly decreased protein expressions of type I collagen, fibronectin, plasminogen activator inhibitor-1 (PAI-1) and α-smooth muscle actin (α-SMA) after CPD1 treatment. In addition, CPD1 dose-dependently inhibited the expression of ECM-related proteins induced by transforming growth factor ß1 (TGF-ß1) in normal rat kidney interstitial fibroblasts (NRK-49F) and human renal tubular epithelial cell line (HK-2). In summary, the novel PDE inhibitor, CPD1, displays strong protective effects against UIRI and fibrosis by suppressing TGF-ß signaling pathway and regulating the balance between ECM synthesis and degradation through PAI-1.


Assuntos
Nefropatias , Inibidores da Fosfodiesterase 5 , Animais , Humanos , Masculino , Camundongos , Ratos , Proteínas da Matriz Extracelular , Fibrose , Rim , Inibidor 1 de Ativador de Plasminogênio
16.
Opt Lett ; 48(4): 1004-1007, 2023 Feb 15.
Artigo em Inglês | MEDLINE | ID: mdl-36790990

RESUMO

This Letter proposes a highly birefringent one-air-hole panda fiber, which is fabricated by corroding a single stress zone of the traditional panda-type polarization-maintaining fiber (PMF). An additional geometric asymmetry is induced in the fiber to increase the birefringence effect and enhance the light-matter interaction, which improves the performance of the sensor and the device applications of the special fiber. A theoretical and experimental analysis of the one-air-hole panda fiber demonstrates that the birefringence of the fiber can be of the order of 10-3, which is one order of magnitude higher than that of the traditional panda-type fiber. The corroded region provides a microchannel to be filled with a functional material to compose optical fiber sensors; a sample of a salt solution was filled into the microchannel to measure the refractive index with a sensitivity of 3760 nm/RIU (refractive index units).

17.
Oxid Med Cell Longev ; 2023: 9554457, 2023.
Artigo em Inglês | MEDLINE | ID: mdl-36644575

RESUMO

Disturbed structure and dysfunction of the retinal pigment epithelium (RPE) lead to degenerative diseases of the retina. Excessive accumulation of reactive oxygen species (ROS) in the RPE is thought to play an important role in RPE dysfunction and degeneration. Autophagy is a generally low-activity degradation process of cellular components that increases significantly when high levels of oxidative stress are present. Agents with antioxidant properties may decrease autophagy and provide protection against RPE dysfunction and damage caused by ROS. Lycium barbarum polysaccharide (LBP) has been widely studied as an antioxidant and cell-protective agent. Therefore, we designed this study to investigate the effects of LBP, which inhibits miR-181, on autophagy in retinal pigment epithelium (RPE) with oxidative stress in vitro and in vivo. In the current study, we found that the highly expressed miR-181 downregulated the expression of Bcl-2 in hydrogen peroxide- (H2O2-) induced ARPE-19 cells, resulting in an increase in ROS, apoptosis, and autophagy flux. LBP inhibited the expression of miR-181, decreased the levels of ROS, apoptosis, and autophagy flux, and increased cell viability in H2O2-induced ARPE-19 cells, suggesting that LBP provides protection against oxidative damage in ARPE-19 cells. We also found that LBP decreased RPE atrophy and autophagy flux in rd10 mice. Taken together, the results showed that LBP has a protective effect for RPE under oxidative stress by inhibiting miR-181 and affecting the Bcl-2/Beclin1 autophagy signaling pathway.


Assuntos
Lycium , MicroRNAs , Animais , Camundongos , Antioxidantes/farmacologia , Apoptose , Autofagia , Peróxido de Hidrogênio/farmacologia , Lycium/metabolismo , MicroRNAs/genética , MicroRNAs/metabolismo , Estresse Oxidativo , Polissacarídeos/farmacologia , Espécies Reativas de Oxigênio/metabolismo , Epitélio Pigmentado da Retina/metabolismo , Humanos
18.
Sci Total Environ ; 857(Pt 1): 159205, 2023 Jan 20.
Artigo em Inglês | MEDLINE | ID: mdl-36202352

RESUMO

Prenatal triclosan (TCS) exposure has been reported to be associated with various birth outcomes and thyroid function, while the study of TCS exposure for congenital heart disease (CHD) patients is limited. In the present study, paired mother-fetus blood samples from CHD and healthy participants were collected to measure TCS exposure levels, and then check their relationship. Coupled with the concentrations of thyroid function biomarkers [free thyroxine (FT4), free triiodothyronine (FT3), thyroid-stimulating hormone (TSH), and thyroid antibodies (TgAb)] in maternal blood, we aimed to investigate whether the hormone-disrupting properties of TCS will affect its association with CHD. Our results indicated that the maternal TCS concentrations in the CHD group (median 0.31 ng/mL) were significantly lower than those in the control group (0.48 ng/mL, Mann Whitney U test, p = 0.01). Higher interquartile of TCS levels in maternal blood was associated with decrease odds of CHD (adjusted OR = 0.61, 95%CI: 0.41-0.91, p = 0.02). Maternal blood TCS higher than the cut-off value (25th quantile, 0.17 ng/mL) was significantly negatively associated with CHD risk (adjusted OR = 0.24, 95%CI: 0.09-0.62, p < 0.01). Besides, none of the thyroid biomarkers were significantly associated with maternal TCS exposure. However, maternal FT4 concentrations were positively correlated with TCS transplacental transfer rate and cord blood TCS levels (general linear regression, both p < 0.01). The results of molecular docking and dynamics simulation suggested that these correlations might be related to the transthyretin, a thyroid hormone-binding protein involved in the placental thyroid hormone transport system. Overall, our findings indicated that at normal exposure levels, the increase of maternal blood TCS concentration may have an inverse association with CHD, which merits further investigation.


Assuntos
Cardiopatias Congênitas , Triclosan , Humanos , Feminino , Gravidez , Triclosan/toxicidade , Sangue Fetal/química , Simulação de Acoplamento Molecular , Placenta/química , Tireotropina , Exposição Materna , Cardiopatias Congênitas/induzido quimicamente , Tiroxina
19.
Chin J Integr Med ; 29(5): 441-447, 2023 May.
Artigo em Inglês | MEDLINE | ID: mdl-35723812

RESUMO

OBJECTIVE: To derive the Chinese medicine (CM) syndrome classification and subgroup syndrome characteristics of ischemic stroke patients. METHODS: By extracting the CM clinical electronic medical records (EMRs) of 7,170 hospitalized patients with ischemic stroke from 2016 to 2018 at Weifang Hospital of Traditional Chinese Medicine, Shandong Province, China, a patient similarity network (PSN) was constructed based on the symptomatic phenotype of the patients. Thereafter the efficient community detection method BGLL was used to identify subgroups of patients. Finally, subgroups with a large number of cases were selected to analyze the specific manifestations of clinical symptoms and CM syndromes in each subgroup. RESULTS: Seven main subgroups of patients with specific symptom characteristics were identified, including M3, M2, M1, M5, M0, M29 and M4. M3 and M0 subgroups had prominent posterior circulatory symptoms, while M3 was associated with autonomic disorders, and M4 manifested as anxiety; M2 and M4 had motor and motor coordination disorders; M1 had sensory disorders; M5 had more obvious lung infections; M29 had a disorder of consciousness. The specificity of CM syndromes of each subgroup was as follows. M3, M2, M1, M0, M29 and M4 all had the same syndrome as wind phlegm pattern; M3 and M0 both showed hyperactivity of Gan (Liver) yang pattern; M2 and M29 had similar syndromes, which corresponded to intertwined phlegm and blood stasis pattern and phlegm-stasis obstructing meridians pattern, respectively. The manifestations of CM syndromes often appeared in a combination of 2 or more syndrome elements. The most common combination of these 7 subgroups was wind-phlegm. The 7 subgroups of CM syndrome elements were specifically manifested as pathogenic wind, pathogenic phlegm, and deficiency pathogens. CONCLUSIONS: There were 7 main symptom similarity-based subgroups in ischemic stroke patients, and their specific characteristics were obvious. The main syndromes were wind phlegm pattern and hyperactivity of Gan yang pattern.


Assuntos
AVC Isquêmico , Humanos , Síndrome , Medicina Tradicional Chinesa , Fígado , Fenótipo
20.
Food Chem X ; 15: 100412, 2022 Oct 30.
Artigo em Inglês | MEDLINE | ID: mdl-36211744

RESUMO

We studied the effects of conjugated linoleic acid (CLA) on the amount of nutrients, flavour substances, and healthcare fatty acids, the physicochemical properties, and the potential molecular mechanisms in the muscles of sub-adult grass carp (Ctenopharyngodon idella). Fish were fed graded levels of CLA (0.0, 3.1, 6.4, 9.6, 12.7, and 15.9 g/kg diets) for 60 days. Protein, glutamic acid, alanine, inosine monophosphate (IMP), eicosapentaenoic acid (EPA; 20:5n-3), docosahexaenoic acid (DHA; 22:6n-3), and total CLA contents (p < 0.05) increased in CLA 3.1 âˆ¼ 12.7, 6.4 âˆ¼ 9.6, 6.4 âˆ¼ 9.6, 6.4 âˆ¼ 15.9, 3.1 âˆ¼ 9.6, 3.1 âˆ¼ 9.6, and 3.1 âˆ¼ 15.9 g/kg diet, respectively (p < 0.05). In addition, optimal CLA significantly increased pH24, shear force, collagen content, and myofibre density in the muscle (P < 0.05); however, it decreased myofibre diameter (p < 0.05). We concluded that 6-9 g/kg CLA in the diet could improve the flesh quality of sub-adult grass carp.

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