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1.
J Nutr Biochem ; : 109034, 2022 Apr 29.
Artigo em Inglês | MEDLINE | ID: mdl-35500829

RESUMO

Autism spectrum disorder (ASD) refers to a group of neurodevelopmental disorders. The etiology and pathological mechanisms of ASD are still unknown, and its prognosis is poor. This study investigated the effects of selenium (Se) supplementation on abnormal behavior and cognitive function in ASD model mice, as well as the potential action pathways. BTBR mice were randomly assigned to either a model group (BTBR group), a model selenium supplement group (BTBR+Se group), a normal control group (B6 group) or a normal selenium supplement group (B6+Se group). Sodium selenite, at a dosage of 1 mg/kg/day, was administered to the selenium supplementation groups by gavage. The mice in the BTBR group and the B6 group received the same amount of 0.9% saline by gavage. After 4 weeks of continuous intervention, the social functions and cognitive behaviors of the mice and the selenium concentration in hippocampal tissue were assessed. Hippocampal tissue structures were observed. Changes in neurotransmitter levels, oxidative stress and neuroinflammatory indicators were detected. SelP protein expression was significantly lower in hippocampal tissue from BTBR mice than in hippocampal tissue from B6 mice. The administration of sodium selenite in BTBR mice: (1) increased the expression of SelP; (2) attenuated spatial learning, memory impairment and improved social behaviors; (3) changed the serum levels of 5-HT, DA and Glu; (4) decreased the levels of inflammatory cytokines IL-6, IL-1ß, and TNF-α in serum and hippocampal tissue; (5) reduced the ROS and MDA contents and significantly increased SOD activity, CAT activity, GSH-px activity, and antioxidant GSH levels; and (6) protected against neuronal loss in the hippocampus. Se supplementation significantly improved the social functioning, repetitive stereotyped behavior and cognitive function in BTBR mice. Se may play a protective role in the hippocampus of BTBR mice by regulating neurotransmitter levels, reducing oxidative stress, alleviating neuroinflammation and rescuing neural cell damage.

2.
JMIR Public Health Surveill ; 8(5): e31847, 2022 May 02.
Artigo em Inglês | MEDLINE | ID: mdl-35499864

RESUMO

BACKGROUND: As a young subgroup, college students have become the main users of mobile social networks. Considering that people can indiscriminately access explicit sexual content on the internet, coupled with the increase of HIV infections in male college students, the role of the internet in meeting sexual partners and its correlation to risky sexual behavior has become an important topic. OBJECTIVE: The aim of this study is to explore the effects of internet exposure on sexual partners and sexual risk behavior among sexually experienced male college students. METHODS: An institution-based cross-sectional study design was used to collect data through a paper-based questionnaire administered to male college students recruited from colleges and gay organizations in Hangzhou, Zhejiang Province, China. A total of 1045 sexually experienced male students were incorporated in our analysis, with the following information collected: sociodemographic characteristics, sexual intercourse-related behaviors, and sexually transmitted disease (STD) knowledge. Mann-Whitney U and Kruskal-Wallis tests were used to examine differences regarding basic characteristics and sexual risk behaviors between male college students who meet sexual partners via the internet and those who do not. Sequential logistic regression models were employed to examine the influence of meeting sexual partners via the internet on risky sexual behaviors after controlling for other factors. RESULTS: The mean age of the sexually experienced male students was 21.6 (SD 2.0) years. The likelihood of risky sexual behavior was varied, yet it was the highest for those who aim to meet paid sexual partners (145/192, 75.5% to 19/22, 86.4%), followed by those seeking partners for love or romance (258/435, 59.3%). Compared to non-internet partner seekers, internet partner seekers tended to have more casual intercourse (292/542, 53.9% versus 51/503, 10.1%), paid intercourse (32/542, 5.9% versus 12/503, 2.4%), and intercourse with same-sex partners (349/542, 64.4% versus 41/503, 8.2%); they were also more likely to use psychoactive drugs (125/349, 35.8% versus 5/41, 12.2%) and have more than 2 partners. With the increase of HIV and STD knowledge, the probability of having unprotected intercourse decreased for non-internet partner seekers. However, it increased for internet partner seekers with a rising HIV knowledge score. Sequential logistic regression showed that meeting sexual partners on the internet was statistically associated with sexual risk behaviors with multiple sexual partners (odds ratio 4.434; P<.001). CONCLUSIONS: Meeting sexual partners via the internet is a common behavior among sexually experienced male college students, and those who meet partners on the internet exhibited higher levels of risky sexual behaviors although they had sufficient HIV and STD knowledge; this is especially true for students who aimed to find partners for sexual intercourse. Thus, more attention should be paid to young adults to address the risky sexual behaviors that may contribute to STD spread among this population.


Assuntos
Infecções por HIV , Doenças Sexualmente Transmissíveis , Adulto , China/epidemiologia , Estudos Transversais , Infecções por HIV/epidemiologia , Humanos , Internet , Masculino , Assunção de Riscos , Comportamento Sexual , Doenças Sexualmente Transmissíveis/epidemiologia , Estudantes , Adulto Jovem
3.
J Ethnopharmacol ; : 115341, 2022 May 09.
Artigo em Inglês | MEDLINE | ID: mdl-35551978

RESUMO

ETHNOPHARMACOLOGICAL RELEVANCE: QiruiWeishu capsule is an herbal preparation from a herbal formula prescribed by an experienced doctor at Guang'anmen Hospital of China Academy of Chinese Medical Sciences. It has been used clinically for more than 30 years. Abdominal pain, distension, and nausea are common symptoms of chronic non-atrophic gastritis with erosion dampness and heat stasis syndrome, and this herbal medicine has been used to treat them. AIM OF THE STUDY: To verify the clinical efficacy and safety of QiruiWeishu capsule in the treatment of chronic non-atrophic gastritis with damp-heat stasis syndrome. MATERIALS AND METHODS: This study was a multicenter randomized double-blind clinical trial with positive herbal drug SanjiuWeitai capsule as control and superiority test of main efficacy. A total of 477 subjects with chronic non-atrophic gastritis with erosion diagnosed by gastroscopy and pathological biopsy were randomly divided into QiruiWeishu capsule and SanjiuWeitai groups respectively in a ratio of 3:1. During the trial, subjects were required to complete medication for 28 days. The primary outcome was the disappearance rate of epigastric pain from baseline to 4weeks. At baseline, treatment at 1, 2, and 4 weeks, and follow-up at 8 and 16 weeks, the epigastric pain and traditional Chinese medicine (TCM) symptom scores were evaluated; gastroscopy, histopathology, and the helicobacter pylori test were evaluated at baseline and after 4 weeks of treatment. The safety assessment included blood routine, liver and kidney function, coagulation of laboratory tests, and electrocardiogram (ECG). RESULTS: Both groups of subjects had a high level of medication adherence (defined as treatment completion for over 80%) (346/357, 96.9% in Qirui Weishu group vs 118/120, 98.3% in Sanjiu Weitai group; p > 0.05). The QiruiWeishu capsule was significantly better than SanjiuWeitai capsule in disappearance rate of epigastric pain (64.2%, 229/357vs 46.7%, 56/120; p < 0.001),especially subgroupsubjects with moderate epigastric pain (65.0%, 89/137 vs 30.4%, 14/46; p < 0.001), grade1 erythema (67.7%, 149/220 vs 51.9%, 42/81; p = 0.011) and grade 2 erythema (57.6%, 70/121 vs37.1%, 13/35; p = 0.050) of gastroscopy, grade 2 erosion (66.7%, 118/177 vs43.9%, 25/57; p = 0.002) of gastroscopy and Helicobacter pylori negative (65.4%, 155/237 vs 42.7%, 35/82; p < 0.001) at baseline. For the scores of TCM symptoms in QiruiWeishu group were significantly lower than those in SanjiuWeitai group after 28 days of treatment (p = 0.002). The number and incidence of adverse events related to the trial drug were 14/355 (3.9%) in QiruiWeishu group, 6/118 (5.1%) in SanjiuWeitai group (p > 0.05). No serious adverse reactions occurred in the two groups. According to laboratory tests and ECG, there was no discernible effect on heart, liver, kidney, or blood coagulation function. CONCLUSION: Qirui Weishu capsule appears to be more effective in terms of symptoms than the SanjiuWeitai capsule, and its use is both safe and effective for the treatment of chronic non-atrophic gastritis. A further randomized, double-blind, placebo-control trial is warranted to verify its benefit.

4.
Artigo em Inglês | MEDLINE | ID: mdl-35569794

RESUMO

As a misfolding protein, almost all of F508del-CFTR is degraded by the ubiquitin-proteasome system before its maturation, which results in no membrane expression of cystic fibrosis transmembrane conductance regulator (CFTR) and therefore, no chloride secretion across epithelial cells of cystic fibrosis (CF) patients. The conjugation of ubiquitin (Ub) chains to protein substrates is necessary for the proteasomal degradation of F508del-CFTR. Ubiquitin contains seven lysine (K) residues, all of which can be conjugated to one another, forming poly-ubiquitin chains on substrates, either by mixing together, or by only one type of lysine providing sorting signals for different pathways. Here, we report that four lysine-linked poly-Ub chains (LLPUCs) were involved in F508del-CFTR biogenesis: LLPUCs linked by K11 or K48 facilitated F508del-CFTR degradation, whereas the other two linked by K63 and K33 protected F508del-CFTR from degradation. LLPUC K11 is more potent for F508del-CFTR degradation than K48. F508del-CFTR utilizes four specific lysine-linked poly-Ub chains during its biogenesis for opposite destiny through different identification by proteasomal shuttle protein or receptors. These findings provide new insights into the CF pathogenesis and are expected to facilitate the development of therapies for this devastating disease.

5.
Neurol Ther ; 2022 May 11.
Artigo em Inglês | MEDLINE | ID: mdl-35543808

RESUMO

INTRODUCTION: Early diagnosis and etiological treatment can effectively improve the prognosis of patients with autoimmune encephalitis (AE). However, anti-neuronal antibody tests which provide the definitive diagnosis require time and are not always abnormal. By using natural language processing (NLP) technology, our study proposes an assisted diagnostic method for early clinical diagnosis of AE and compares its sensitivity with that of previously established criteria. METHODS: Our model is based on the text classification model trained by the history of present illness (HPI) in electronic medical records (EMRs) that present a definite pathological diagnosis of AE or infectious encephalitis (IE). The definitive diagnosis of IE was based on the results of traditional etiological examinations. The definitive diagnosis of AE was based on the results of neuronal antibodies, and the diagnostic criteria of definite autoimmune limbic encephalitis proposed by Graus et al. used as the reference standard for antibody-negative AE. First, we automatically recognized and extracted symptoms for all HPI texts in EMRs by training a dataset of 552 cases. Second, four text classification models trained by a dataset of 199 cases were established for differential diagnosis of AE and IE based on a post-structuring text dataset of every HPI, which was completed using symptoms in English language after the process of normalization of synonyms. The optimal model was identified by evaluating and comparing the performance of the four models. Finally, combined with three typical symptoms and the results of standard paraclinical tests such as cerebrospinal fluid (CSF), magnetic resonance imaging (MRI), or electroencephalogram (EEG) proposed from Graus criteria, an assisted early diagnostic model for AE was established on the basis of the text classification model with the best performance. RESULTS: The comparison results for the four models applied to the independent testing dataset showed the naïve Bayesian classifier with bag of words achieved the best performance, with an area under the receiver operating characteristic curve of 0.85, accuracy of 84.5% (95% confidence interval [CI] 74.0-92.0%), sensitivity of 86.7% (95% CI 69.3-96.2%), and specificity of 82.9% (95% CI 67.9-92.8%), respectively. Compared with the diagnostic criteria proposed previously, the early diagnostic sensitivity for possible AE using the assisted diagnostic model based on the independent testing dataset was improved from 73.3% (95% CI 54.1-87.7%) to 86.7% (95% CI 69.3-96.2%). CONCLUSIONS: The assisted diagnostic model could effectively increase the early diagnostic sensitivity for AE compared to previous diagnostic criteria, assist physicians in establishing the diagnosis of AE automatically after inputting the HPI and the results of standard paraclinical tests according to their narrative habits for describing symptoms, avoiding misdiagnosis and allowing for prompt initiation of specific treatment.

6.
J Healthc Eng ; 2022: 3724033, 2022.
Artigo em Inglês | MEDLINE | ID: mdl-35494526

RESUMO

Objective: The objective of this study is to investigate the effect of dysfunctional circulating follicular helper T cells (Tfh) on B cell maturation and differentiation in patients with osteosarcoma (OS). Method: Data from 30 OS patients who underwent diagnosis and treatment in our hospital, as well as those of 30 healthy subjects (HC), were collected at the same time. Flow cytometry was employed to identify proportions of CD4+CXCR5+Tfh cells and Tfh cell subtypes Tfh17, Tfh1, and Tfh2 in the patient's peripheral blood. CD40 L and IFNγ levels were detected after stimulating Tfh cells with an influenza antigen; the positive rates of CD27 and CD38 in B cells were detected before and after coculture with Tfh cells. qRT-PCR was carried out for Blimp-1 expression in B cells, and ELISA was employed to identify the levels of IgM, IgG, and IgA in B cells and IL-2, IL-10, and IL-4 in Tfh cells before and after coculture. Results: The percentage of CD4+CXCR5+Tfh cells in OS patients' peripheral blood increased significantly. The Tfh cell ratio increased along with the TNM stage, and the Tfh cell ratio in OS metastasis patients is greater than that in nonmetastatic patients. In addition, Tfh2 and Tfh17 cells increased drastically in OS patients, and no meaningful change was seen in Tfh1 cells. CD40 L levels of Tfh cells in OS patients were less than those of the HC group, and IFNγ was substantially increased. After coculturing the OS group's B cells with Tfh cells, the CD27+ and CD38+ cells of B cells were drastically greater, and Blimp-1 expression was also significantly increased. In addition, the levels of IL-21, IL-4, and IL-10 of Tfh cells in the OS group and the levels of IgA, IgG, and IgM in B cells were significantly reduced after coculture. Conclusion: Dysfunctional Tfh in OS patients can severely inhibit B cell development, maturation, and differentiation.


Assuntos
Osteossarcoma , Células T Auxiliares Foliculares , Humanos , Imunoglobulina A/metabolismo , Imunoglobulina G/metabolismo , Imunoglobulina M/metabolismo , Interleucina-10/metabolismo , Interleucina-4/metabolismo , Osteossarcoma/metabolismo , Linfócitos T Auxiliares-Indutores/metabolismo
7.
Int J Mol Sci ; 23(9)2022 Apr 23.
Artigo em Inglês | MEDLINE | ID: mdl-35563059

RESUMO

Indoleamine 2,3-dioxygenase 1 (IDO1) is an attractive heme enzyme for its significant function in cancer immunotherapy. Potent IDO1 inhibitors have been discovered for decades, whereas no clinical drugs are used for cancer treatment up to now. With the goal of developing medically valuable IDO inhibitors, we performed a systematic study of SAR405838 analogs with a spiro-oxindole skeleton in this study. Based on the expression and purification of human IDO1, the inhibitory activity of spiro-oxindole skeleton compounds to IDO1 was evaluated by IC50 and Ki values. The results demonstrated that inhibitor 3 exhibited the highest IDO1 inhibitory activity with IC50 at 7.9 µM among all inhibitors, which is ~six-fold of the positive control (4-PI). Moreover, inhibitor 3 was found to have the most effective inhibition of IDO1 in MCF-7 cancer cells without toxic effects. Molecular docking analysis revealed that the hydrophobic interaction stabilized the binding of inhibitor 3 to the IDO1 active site and made an explanation for the uncompetitive mode of inhibitors. Therefore, this study provides valuable insights into the screen of more potent IDO1 inhibitors for cancer immunotherapy.

8.
Comput Intell Neurosci ; 2022: 7364375, 2022.
Artigo em Inglês | MEDLINE | ID: mdl-35463227

RESUMO

The judgment service rate is an important index to reflect the fairness of the judgment of legal cases in a certain area, which is of great significance to verify the accuracy of a court judgment. In this paper, a grey neural network model combining grey system theory and BP neural network algorithm is proposed to predict the index. Analyze the judgment service rate of the court judgment system, and build a prediction system based on the completion rate, completion rate, plaintiff satisfaction, defendant satisfaction, litigation time, property preservation cycle, document delivery time, implementation information disclosure rate, and other key indicators. Through example analysis, it is proved that the combined model of the grey prediction model and BP neural network has a small error and good simulation effect on the prediction of court decision-making service rate, which can better promote the development of court and society.


Assuntos
Algoritmos , Redes Neurais de Computação , Julgamento
9.
Opt Express ; 30(9): 15238-15249, 2022 Apr 25.
Artigo em Inglês | MEDLINE | ID: mdl-35473250

RESUMO

We report the development of an optical-feedback cavity-enhanced absorption spectroscopy (OF-CEAS) instrument for OH detection at 2.8 µm using a DFB diode laser. Two different approaches, symmetry analysis and wavelength modulation, were performed to achieve laser frequency locking to the cavity mode. Compared with the symmetry analysis method, the wavelength modulation method continuously locked the laser frequency to the cavity mode and eliminated decoupling the laser from the cavity mode. A detection sensitivity of 1.7×10-9 cm-1 was achieved in a 25 s sampling time and was about 3 times better than that of the symmetry analysis method. The corresponding OH detection limit was ∼ 2×108 molecule/cm3. Further improvement can be achieved by using higher reflectivity mirrors and other high-sensitivity approaches, such as frequency modulation spectroscopy and Faraday rotation spectroscopy.

10.
Nanoscale ; 14(17): 6600-6611, 2022 May 05.
Artigo em Inglês | MEDLINE | ID: mdl-35421886

RESUMO

Fiber-based nanostructures are greatly desired for the improvement of wearable/flexible electronics, which are expected to be stretchable, conformable, flexible, and long-term. Herein, an ultra-stretchable, breathable, and highly sensitive flexible capacitive tactile sensor and triboelectric effect core-shell nanofibers are proposed. In particular, core-shell ionic TPU/PVDF-HFP nanofibers are effectively prepared by an electrospinning approach. The core-shell ionic TPU/PVDF-HFP nanofibers exhibit high performance as a capacitive flexible sensor with high sensitivity (0.718 kPa-1) in a low linear pressure range (0-1.2 kPa), an ultralow detection limit (7 Pa), a rapid response and recovery time, and excellent stability. Moreover, we assembled a self-powered pressure sensor, which has a sensitivity of 0.071 V kPa-1 in the high linear pressure range of 90 kPa to 400 kPa. The increase in the inductive charges of the nanofiber layer allows it to work as an energy harvester with a high power density (1.6 W m-2) that can light up 100 LEDs instantly. These remarkable results allow the capacitive flexible devices to be applied in various applications, such as spatial pressure mapping, bending angle detection, soft grabbing, and physiological signal monitoring.

11.
Sci Total Environ ; 831: 154881, 2022 Mar 29.
Artigo em Inglês | MEDLINE | ID: mdl-35364156

RESUMO

Widespread presence of plastic mulch has led to macroplastic (MaP) pollution. While this issue is widely explored in aquatic ecosystems, MaP pollution on land has been neglected. In 2019, we conducted a large-scale survey of MaPs in Northwest China in 0-30 cm soil with long-term mulching. Samples of MaP debris were collected from 67 sites across Gansu, east Qinghai, and north Shannxi Provinces. All visible MaP pieces for each site were separated and weighed. The mass of each MaP piece was calibrated by size measured in digital images. The MaP mass averaged 47.2 kg ha-1, and the number of MaPs averaged 266.2 pieces ha-1. The mass and number of MaPs varied from site to site. The mean size of MaPs was 19.5 cm2 piece-1 or 28.0 mg piece-1. More importantly, the number of small MaP pieces (<5 and 5-20 cm2 piece-1) accounted for 76.7% of the total number of MaPs detected, and small-sized plastic debris (<10 and 10-25 mg piece-1) were detected in 70.1% of the sampling sites. The percentage of small fragments increased before 15-year of mulching and then declined. However, the amount of medium-large debris (20-50 and >50 cm2 piece-1) showed a trend opposite to that of small fragments. The percentage of MaPs was greater in the small size group than in the medium-large size group. The arid to semi-arid area exhibited higher MaP contamination compared with the semi-arid to the semi-humid area. These observations indicate that plastic debris residing in soil tend to be fragmented, making plastic film recovery more challenging and causing severe soil pollution. Further studies are required to regulate plastic mulch methods and explore the degradation process.

12.
Front Oncol ; 12: 831345, 2022.
Artigo em Inglês | MEDLINE | ID: mdl-35433421

RESUMO

Background: To compare the efficacy and safety of pembrolizumab combined with neoadjuvant chemotherapy (neoCT) versus neoadjuvant chemoradiotherapy (neoCRT) followed by surgery for locally advanced resectable oesophageal squamous cell carcinoma (ESCC). Methods: This study is a multicentre, prospective, randomized-controlled, phase III clinical study. Eligible ESCC (staging: cT1N2M0 or cT2-3N0-2M0 (stage II/III, high-risk lesions in T2N0M0)) patients will be randomly assigned to either the experimental group (pembrolizumab with neoCT, n = 228) or the control group (neoCRT, n = 114) at a ratio of 2:1. Within 4-6 weeks after preoperative therapy, the McKeown procedure will be performed. Patients in the experimental group will also receive pembrolizumab alone as adjuvant therapy after surgery until 1 year or until the radiographically confirmed PD or other condition indicated for premature termination is observed. The primary endpoint is event-free survival (EFS). The secondary endpoints are 1-, 3-, and 5-year overall survival (OS) and disease-free survival (DFS), short-term outcomes, and quality of life. Discussion: This is the first prospectively randomized controlled trial designed to compare pembrolizumab plus chemotherapy and chemoradiotherapy as neoadjuvant therapy for resectable ESCC. According to our hypothesis, preoperative pembrolizumab combined with chemotherapy will result in a better tumour response and prolong the survival of patients, with acceptable toxicity. This study started in December 2021, and the enrolment time is estimated to be 2 years. Trial Registration: This prospective study has been registered at ClinicalTrials.gov (NCT04807673), March 2021.

13.
ACS Biomater Sci Eng ; 8(5): 2066-2075, 2022 May 09.
Artigo em Inglês | MEDLINE | ID: mdl-35394755

RESUMO

Cryopreservation of red blood cells (RBCs) plays a vital role in preserving rare blood and serologic testing, which is essential for clinical transfusion medicine. The main difficulties of the current cryopreservation technique are the high glycerol concentration and the tedious deglycerolization procedure after thawing. In this study, we explored a microencapsulation method for cryopreservation. RBC-hydrogel microcapsules with a diameter of approximately 2.184 ± 0.061 mm were generated by an electrostatic spraying device. Then, 0.7 M trehalose was used as a cryoprotective agent (CPA), and microcapsules were adhered to a stainless steel grid for liquid nitrogen freezing. The results show that compared with the RBCs frozen by cryovials, the recovery of RBCs after microencapsulation is significantly improved, up to a maximum of more than 85%. Additionally, the washing process can be completed using only 0.9% NaCl. After washing, the RBCs maintained their morphology and adenosine 5'-triphosphate (ATP) levels and met clinical transfusion standards. The microencapsulation method provides a promising, referenceable, and more practical strategy for future clinical transfusion medicine.


Assuntos
Preservação de Sangue , Trealose , Preservação de Sangue/métodos , Cápsulas , Criopreservação/métodos , Eritrócitos , Hidrogéis/farmacologia , Trealose/farmacologia
14.
RSC Adv ; 12(15): 9051-9057, 2022 Mar 21.
Artigo em Inglês | MEDLINE | ID: mdl-35424856

RESUMO

The development of low-cost, high-efficiency, and stable bifunctional electrocatalysts for large-scale water electrolysis is very important for the sustainable development of energy. In this paper, the nickel cobalt phosphide (CoNiP) microstructure was prepared by the "in situ growth-ion exchange-phosphating" method. Due to the flake structure and the synergistic effect of the bimetal, the synthesized CoNiP microstructure exhibited high electrocatalytic activity and stability for hydrogen and oxygen evolution in alkaline electrolyte. The optimized CoNiP showed low overpotential of 116 mV at 10 mA cm-2 for hydrogen evolution reaction and 400 mV at 50 mA cm-2 for oxygen evolution reaction in KOH solution. In addition, it exhibited long-term stability at a high constant current density of 100 mA cm-2 for 48 hours at room temperature and for 65 hours at 80 °C without significant degradation. Theoretical results showed that the introduction of Co and P atoms could reduce the reaction barrier and improve the electron transfer ability. This work provides a simple and economical way for the synthesis of electrocatalytic bimetal phosphide catalysts.

15.
Kaohsiung J Med Sci ; 2022 Apr 09.
Artigo em Inglês | MEDLINE | ID: mdl-35396910

RESUMO

Excessive proliferation and migration of airway smooth muscle cell (ASMC) contribute to asthma pathogenesis. Long noncoding RNAs (lncRNAs) are reported to take part in asthma pathogenesis. This study is targeted at deciphering the role of the lncRNA antisense noncoding RNA in the INK4 locus (ANRIL) in ASMC proliferation, migration and extracellular matrix (ECM) deposition. qRT-PCR was performed to determine ANRIL, miR-98-5p, and cyclin D1 (CCND1) mRNA expression levels in transforming growth factor-ß1 (TGF-ß1)-treated ASMCs. CCK-8 and Transwell assays were employed to examine ASMC proliferation and migration, respectively. Dual-luciferase reporter gene assay and RNA immunoprecipitation assay were carried out for analyzing the targeted relationship of miR-98-5p with ANRIL or CCND1 mRNA 3'-UTR. The levels of CCND1 and ECM proteins (such as fibronectin, COL3A1, and COL1A2) in ASMCs were detected through Western blot. In this work, we found that ANRIL and CCND1 were up-regulated in TGF-ß1-treated ASMCs, whereas miR-98-5p was down-regulated. ANRIL overexpression facilitated the proliferation, ECM deposition and migration of TGF-ß1-induced ASMCs, while knocking down ANRIL had the opposite effect. Furthermore, ANRIL targeted miR-98-5p directly, and CCND1 was miR-98-5p's downstream target. ANRIL indirectly increased CCND1 expression in ASMCs via competitively binding to miR-98-5p. MiR-98-5p inhibition or CCND1 overexpression counteracted the inhibiting effect that ANRIL knockdown had on TGF-ß1-stimulated ASMC proliferation, migration and ECM deposition. In conclusion, ANRIL indirectly up-regulates CCND1 expression by targeting miR-98-5p to promote ASMC proliferation, migration and ECM deposition, thus facilitating the pathogenesis of asthma.

16.
Artigo em Inglês | MEDLINE | ID: mdl-35397657

RESUMO

INTRODUCTION: In the reconstruction of distal radioulnar ligaments (DRULs), interference screws can be used for antegrade or retrograde fixation of grafts to the ulna. However, the biomechanics of interference screw fixation are currently unknown. This study aimed to determine the biomechanical effects of these two fixations on the distal radioulnar joint (DRUJ) in a cadaveric model and to investigate the appropriate initial tension. MATERIALS AND METHODS: A total of 30 human cadaver upper extremities were used, and the DRULs were reconstructed according to Adams' procedure. First, eight specimens were randomly divided into two groups: antegrade and retrograde, followed by translational testing and load testing. Then, the other eight specimens were divided into the two groups above, and the contact mechanics, including forces, areas, and pressures, were measured. Finally, to investigate the appropriate initial tension, the remaining 14 specimens were fixed with interference screws under different tensions in an antegrade way, and the translational testing was repeated as before. RESULTS: In the neutral position, antegrade fixation exhibited less translation than retrograde fixation (7.21 ± 0.17 mm versus 10.77 ± 1.68 mm, respectively). The maximum failure load was 70.45 ± 6.20 N in antegrade fixation, while that in retrograde fixation was 35.17 ± 2.95 N (P < 0.0001). Antegrade fixation exhibited a larger increase in contact force than retrograde fixation (99.72% ± 23.88% versus 28.18% ± 10.43%) (P = 0.001). The relationship between tension and displacement was nonlinear (Y = - 1.877 ln(x) + 7.94, R2 = 0.868, P < 0.0001). CONCLUSIONS: Compared with retrograde fixation, the antegrade fixation of interference screws may be a more reliable surgical technique, as it shows a higher failure load and stability. In addition, to avoid the risk of potential arthritis caused by anterograde fixation, we propose an equation to determine the appropriate initial tension in DRUL reconstruction.

17.
Environ Int ; 163: 107218, 2022 May.
Artigo em Inglês | MEDLINE | ID: mdl-35378443

RESUMO

AIMS: Although previous studies have linked short-term exposure to fine particulate matter (PM2.5) air pollution with various molecular biomarkers of cardiovascular system, limited evidence is available for indicators at clinical or subclinical levels. We examined the associations between short-term PM2.5 exposure and a range of clinical or subclinical indicators of cardiovascular health in general population. METHODS AND RESULTS: A longitudinal repeated-measure study was conducted among 247,640 participants who repeatedly visited health examination centers in 15 typical cities across China from 2013 to 2020. A total of 19 well-established indicators of cardiovascular risk or injury were evaluated and air quality data at nearest fixed-site monitors were collected. Linear mixed-effects models with distributed lag models were used to analyze the potentially lagged effects of PM2.5. The average daily PM2.5 concentration was 48 µg/m3 during the study period. PM2.5 exposure was associated with significant changes of 16 indicators with the effects generally peaked on lag 0 to 3 day. For an interquartile range (IQR) elevation (37 µg/m3) in PM2.5 concentrations over lag 0-7 day, the cumulative percentage changes were 0.50% to 1.27% in heart rates and blood pressure, 0.10% to 5.04% in inflammatory markers, -0.29% to 1.39% in blood viscosity parameters, -0.67% to 3.45% in blood lipids, 0.89% in blood homocysteine, 0.13% to 0.78% in myocardial enzymes, and 3.03% in pulse wave velocity. These associations were not substantially changed after adjusting concomitant exposures to gaseous pollutants. CONCLUSION: Short-term exposure to PM2.5 may induce early cardiovascular effects in general population, including acute inflammation, myocardial injury, increased blood viscosity, vascular stiffness and hyperlipidemia.


Assuntos
Poluentes Atmosféricos , Poluição do Ar , Sistema Cardiovascular , Poluentes Atmosféricos/análise , Poluentes Atmosféricos/toxicidade , Poluição do Ar/análise , Poluição do Ar/estatística & dados numéricos , Biomarcadores , China/epidemiologia , Cidades , Exposição Ambiental/análise , Exposição Ambiental/estatística & dados numéricos , Humanos , Estudos Longitudinais , Material Particulado/análise , Material Particulado/toxicidade , Análise de Onda de Pulso
18.
Front Nutr ; 9: 785999, 2022.
Artigo em Inglês | MEDLINE | ID: mdl-35360693

RESUMO

On an organismal level, metabolism needs to react in a well-orchestrated manner to metabolic challenges such as nutrient uptake. Key metabolic hubs in human blood are pyruvate and lactate, both of which are constantly interconverted by very fast exchange fluxes. The quantitative contribution of different food sources to these metabolite pools remains unclear. Here, we applied in vivo stable isotope labeling to determine postprandial metabolic fluxes in response to two carbohydrate sources of different complexity. Depending on the ingested carbohydrate source, glucose or wheat flour, the net direction of the lactate dehydrogenase, and the alanine amino transferase fluxes were adjusted in a way to ensure sufficient availability, while, at the same time, preventing an overflow in the respective metabolite pools. The systemic lactate pool acts as a metabolic buffer which is fueled in the early- and depleted in the late-postprandial phase and thus plays a key role for systemic metabolic homeostasis.

19.
J Investig Med ; 2022 Apr 04.
Artigo em Inglês | MEDLINE | ID: mdl-35379700

RESUMO

This study aimed to explore the clinical adverse effects of anthracyclines on patients undergoing chemotherapy after breast cancer surgery. A total of 118 patients who received anthracycline chemotherapy after breast cancer surgery were selected as the research object, and the changes of echocardiogram, ECG, myocardial enzymes and blood biochemical indices before, during and after chemotherapy were studied. SPSS V.20 was used to conduct statistical analysis. The differences in heart rate, ST-segment abnormalities, creatine kinase, lactate dehydrogenase, hemoglobin, albumin, triglycerides and high-density lipoprotein were statistically significant. Heart rate and triglycerides increased significantly in the early stage of chemotherapy; ST-segment abnormality increased during the entire chemotherapy period; creatine kinase and lactate dehydrogenase increased significantly in the late stage of chemotherapy; hemoglobin and albumin decreased in the early stage of chemotherapy. The magnitude is large; high-density lipoprotein decreases throughout the chemotherapy period. In anthracycline chemotherapy regimens, bone marrow suppression and dyslipidemia occur in the early stage of chemotherapy, and the risk of cardiotoxicity is higher in the late stage of chemotherapy.

20.
J Healthc Eng ; 2022: 2270777, 2022.
Artigo em Inglês | MEDLINE | ID: mdl-35310196

RESUMO

The aim of this research was to assess the function of microribonucleic acid (miR)-195 in the apoptosis and proliferation of oral squamous cell carcinoma (OSCC) cells as well as its action mechanism. The downstream target protein of miR-195 was predicted using the biological software. A quantitative polymerase chain reaction (qPCR) was implemented to examine the changes in expressions of miR-195 and its target protein toll-like receptor 4 (TLR4) in OSCC cell lines (TSCCA, Tca8223, Tb3.1, and CAL-27) and normal adult human gingival fibroblasts (HGFs), and the relation between their expressions was assessed. The expressions of phosphorylated proteins in nuclear factor-κB (NF-κB) pathway were determined through western blotting. miR-195 was expressed at a noticeably lower level in four OSCC cells than in HGFs, and the lowest level appeared in CAL-27 cells. Compared with miR-195 control, the miR-195 mimic could obviously raise the expression of miR-195. In CAL-27 cells with high expression of miR-195, the proliferation was inhibited and the apoptosis was evidently enhanced. OSCC cells exhibited evidently reduced protein and mRNA expression of TLR4, and miR-195 expression was inversely associated with TLR4 expression. It was uncovered from the dual-luciferase reporter assay that cells with wild-type TLR4 had prominently weakened luciferase activity relative to cells with mutant-type TLR4, revealing that the direct target of miR-195 is TLR4. The NF-κB pathway was impeded in cells that lowly expressed TLR4. miR-195 blocks the NF-κB pathway via inhibiting the expression of TLR4 in OSCC cells, thereby exerting an antitumor effect.


Assuntos
Carcinoma de Células Escamosas , Neoplasias de Cabeça e Pescoço , MicroRNAs , Neoplasias Bucais , Adulto , Apoptose/genética , Carcinoma de Células Escamosas/genética , Proliferação de Células , Humanos , MicroRNAs/genética , MicroRNAs/metabolismo , Neoplasias Bucais/genética , NF-kappa B/metabolismo , NF-kappa B/farmacologia , Transdução de Sinais , Carcinoma de Células Escamosas de Cabeça e Pescoço , Receptor 4 Toll-Like/genética , Receptor 4 Toll-Like/metabolismo
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