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1.
IEEE Trans Cybern ; PP2022 May 04.
Artigo em Inglês | MEDLINE | ID: mdl-35507612

RESUMO

This article studies the problem of finite-time, fixed-time, and prescribed-time stability analysis and stabilization. First, a linear time-varying (LTV) inequality-based approach is introduced for prescribed-time stability analysis. Then, it is shown that the existing nonlinear Lyapunov inequalities-based finite- and fixed-time stability criteria can be recast into the unified framework of the LTV inequality-based approach for prescribed-time stability. Finally, the unified LTV inequality-based approach is used to solve the global prescribed-time stabilization problem of the attitude control system of a rigid spacecraft with disturbance, and a bounded nonlinear time-varying controller is proposed via back stepping. Numerical simulations are presented to show the effectiveness of the proposed methods.

2.
Stem Cell Res Ther ; 13(1): 178, 2022 May 03.
Artigo em Inglês | MEDLINE | ID: mdl-35505443

RESUMO

BACKGROUND: There is unmet need for effective therapies of intrauterine adhesions (IUAs) that are common cause of menstrual disturbance and infertility, since current clinical procedures do not improve prognosis for patients with moderate to severe IUA, with a recurrence rate of 23-50%. Stem cell-based therapy has emerged as a therapeutic option with unsolved issues for IUA patients in the past few years. Primary endometrial epithelial cells for cell therapy are largely hampered with the extremely limited proliferation capacity of uterine epithelial cells. This study was to evaluate whether IUA is curable with conditionally reprogrammed (CR) endometrial epithelial cells. METHODS: Mouse endometrial epithelial cells (MEECs) were isolated from C57BL female mice, and long-term cultures of MEECs were established and maintained with conditional reprogramming (CR) method. DNA damage response analysis, soft agar assay, and matrigel 3D culture were carried out to determine the normal biological characteristics of CR-MEECs. The tissue-specific differentiation potential of MEECs was analyzed with air-liquid interface (ALI) 3D culture, hematoxylin and eosin (H&E) staining, Masson's trichrome and DAB staining, immunofluorescence assay. IUA mice were constructed and transplanted with CR-MEECs. Repair and mechanisms of MEECs transplantation in IUA mice were measured with qRT-PCR, Masson's trichrome, and DAB staining. RESULTS: We first successfully established long-term cultures of MEECs using CR approach. CR-MEECs maintained a rapid and stable proliferation in this co-culture system. Our data confirmed that CR-MEECs retained normal biological characteristics and endometrium tissue-specific differentiation potential. CR-MEECs also expressed estrogen and progesterone receptors and maintained the exquisite sensitivity to sex hormones in vitro. Most importantly, allogeneic transplantation of CR-MEECs successfully repaired the injured endometrium and significantly improved the pregnancy rate of IUA mice. CONCLUSIONS: Conditionally reprogrammed physiological endometrial epithelial cells provide a novel strategy in IUA clinics in a personalized or generalized manner and also serve as a physiological model to explore biology of endometrial epithelial cells and mechanisms of IUA.


Assuntos
Doenças Uterinas , Animais , Endométrio , Células Epiteliais , Feminino , Humanos , Camundongos , Camundongos Endogâmicos C57BL , Gravidez , Aderências Teciduais/patologia , Doenças Uterinas/patologia , Doenças Uterinas/terapia
3.
Front Genet ; 13: 842387, 2022.
Artigo em Inglês | MEDLINE | ID: mdl-35518356

RESUMO

Polyploidization plays a critical role in producing new gene functions and promoting species evolution. Effective identification of polyploid types can be helpful in exploring the evolutionary mechanism. However, current methods for detecting polyploid types have some major limitations, such as being time-consuming and strong subjectivity, etc. In order to objectively and scientifically recognize collinearity fragments and polyploid types, we developed PolyReco method, which can automatically label collinear regions and recognize polyploidy events based on the K S dotplot. Combining with whole-genome collinearity analysis, PolyReco uses DBSCAN clustering method to cluster K S dots. According to the distance information in the x-axis and y-axis directions between the categories, the clustering results are merged based on certain rules to obtain the collinear regions, automatically recognize and label collinear fragments. According to the information of the labeled collinear regions on the y-axis, the polyploidization recognition algorithm is used to exhaustively combine and obtain the genetic collinearity evaluation index of each combination, and then draw the genetic collinearity evaluation index graph. Based on the inflection point on the graph, polyploid types and related chromosomes with polyploidy signal can be detected. The validation experiments showed that the conclusions of PolyReco were consistent with the previous study, which verified the effectiveness of this method. It is expected that this approach can become a reference architecture for other polyploid types classification methods.

4.
Front Med (Lausanne) ; 9: 799156, 2022.
Artigo em Inglês | MEDLINE | ID: mdl-35559341

RESUMO

Background: Myoclonic movement is a very common but undesirable phenomenon during the induction of general anesthesia using etomidate. Such movement may cause unnecessary problems. Currently, there is an increasing number of drugs for preventing etomidate-induced myoclonus (EM). However, direct comparisons of various drugs are lacking, and this interferes with clinical decision-making. Our network meta-analysis (NMA) aimed to compare the efficacy of different drugs for the prevention of moderate-to-severe general myoclonus. Methods: Using several biomedical databases, randomized controlled trials (RCTs) published in English from inception to August 22, 2021 were searched. Among the various interventions, we selected nine types of intervention drugs (dexmedetomidine, etomidate, lidocaine, NMDA receptor antagonist, κ opioid receptor agonist, µ opioid receptor agonist, muscle relaxant, gabapentin, and midazolam) for comparison, according to the number of studies. Bayesian NMA was performed using STATA16 and R softwares. The relative risk of EM was assessed using risk ratios (RRs) and the corresponding 95% confidence intervals (CI). Results: A total of 31 RCTs (3209 patients) were included. NMA results showed that, compared with a placebo, etomidate (RR 4.0, 95%CI 2.1-7.8), κ opioid receptor agonist (RR 2.9, 95%CI 1.9-4.6), µ opioid receptor agonist (RR 3.1, 95%CI 2.3-4.3), NMDA receptor antagonist (RR 1.7, 95%CI 1.0-2.8), dexmedetomidine (RR 2.4, 95%CI 1.5-3.9), lidocaine (RR 2.1, 95%CI 1.2-3.9), and midazolam (RR 2.2, 95%CI 1.5-3.2) can significantly reduce the risk of EM. In contrast, the effects of muscle relaxants (RR 2.1, 95%CI 0.81-5.3) and gabapentin (RR 2.8, 95%CI 0.92-9.3) were inconclusive. Further subgroup analyses showed that preoperative low-dose etomidate, µ-opioid receptor agonist, and κ-opioid receptor agonist were significantly better than other interventions in the prevention of moderate to severe EM. Conclusion: Preoperative use of small doses of etomidate or opioids may be the most effective way to avoid EM, especially moderate and severe EM, which makes anesthesia induction safer, more stable, and aligns better with the requirements of comfortable medicine. Systematic Review Registration: [https://www.crd.york.ac.uk/prospero/], [CRD4202127706].

5.
Zhongguo Zhong Yao Za Zhi ; 47(9): 2516-2524, 2022 May.
Artigo em Chinês | MEDLINE | ID: mdl-35531699

RESUMO

This study aims to explore the effect of butyl alcohol extract of Baitouweng Decoction(BAEB) on vulvovaginal candidiasis(VVC) in mice and to clarify the mechanism from Toll-like receptors(TLRs)/MyD88 and Dectin-1/Syk signal pathways and NLRP3 inflammasome. To be specific, female KM mice were randomized into control group(i.g., normal saline), model group, fluco-nazole group(i.g., 20 mg·kg~(-1)), and low-dose, medium-dose, and high-dose BAEB groups(i.g., 20, 40, and 80 mg·kg~(-1), respectively). VVC was induced in mice except the control group. After the modeling, administration began and lasted 7 days. The ge-neral conditions and body weight of mice were recorded every day. On the 1 st, 3 rd, 7 th, and 14 th after vaginal infection by Candida albicans, the fungal load in the vaginal lavage fluid of the mice was measured with the plate method, and the morphology of C. albicans in vaginal lavage fluid was observed based on Gram staining. After the mice were killed, vaginal tissues were subjected to hematoxylin-eosin(HE) staining and periodic acid-Schiff(PAS) staining for vaginal histopathological analysis. The content of cytokines in vaginal lavage fluid, such as interleukin(IL)-1ß, IL-18, tumor necrosis factor-α(TNF-α), IL-6, and S100 a8, was determined by enzyme-linked immunosorbent assay(ELISA), and content of reactive oxygen species(ROS) in vaginal tissues by tissue ROS detection kit. The protein expression of NLRP3, ASC, caspase-1, Dectin-1, Syk, MyD88, TLR2, TLR4, and nuclear factor-κB(NF-κB) in vaginal tissues was detected by Western blot, and the levels and distribution of NLRP3, Dectin-1, Syk, MyD88, TLR2, and TLR4 in vaginal tissues were determined with the immunohistochemical method. The results show that BAEB can improve the general conditions of VVC mice, reduce the fungal load and C. albicans hyphae in vaginal secretion, decrease ROS content in vaginal tissues and content of cytokines in vaginal lavage fluid, and down-regulate the expression of NLRP3, ASC, caspase-1, Dectin-1, Syk, MyD88, TLR2, TLR4, and NF-κB in vaginal tissues. The above results indicate that BAEB exerts therapeutic effect on VVC mice by down-regulating the key proteins in the TLRs/MyD88 and Dectin-1/Syk signal pathways and NLRP3 inflammasome.


Assuntos
Candidíase Vulvovaginal , 1-Butanol/farmacologia , 1-Butanol/uso terapêutico , Animais , Candida albicans , Candidíase Vulvovaginal/tratamento farmacológico , Caspase 1/metabolismo , Citocinas/metabolismo , Feminino , Humanos , Inflamassomos/metabolismo , Camundongos , Fator 88 de Diferenciação Mieloide/genética , Fator 88 de Diferenciação Mieloide/metabolismo , NF-kappa B/genética , NF-kappa B/metabolismo , Proteína 3 que Contém Domínio de Pirina da Família NLR/genética , Proteína 3 que Contém Domínio de Pirina da Família NLR/metabolismo , Extratos Vegetais/farmacologia , Extratos Vegetais/uso terapêutico , Espécies Reativas de Oxigênio/metabolismo , Transdução de Sinais , Receptor 2 Toll-Like/metabolismo , Receptor 4 Toll-Like/metabolismo , Fator de Necrose Tumoral alfa/metabolismo
6.
Nutr Metab (Lond) ; 19(1): 34, 2022 May 07.
Artigo em Inglês | MEDLINE | ID: mdl-35525966

RESUMO

BACKGROUND: Body water measured by bioelectrical impedance analysis (BIA) predicts the outcomes of many diseases. This study aimed to evaluate the relationship between body water and the prognosis of cancer patients with sarcopenia. METHODS: This study employed 287 cancer patients with sarcopenia underwent BIA from a prospective multicenter study of patients with cancer in China from 2013 to 2020. The primary outcome of interest was all-cause mortality presented as the longest time to follow-up available. Eight indicators of body water [total body water, extracellular water, intracellular water, free fat mass, active cell mass, extracellular water/intracellular water, extracellular water/total body water (ECW/TBW), and intracellular water/total body water] were included in the research. Neutrophil-lymphocyte ratio (NLR) = neutrophil (× 109)/lymphocyte (× 109). The discriminatory ability and prediction accuracy of each factor were assessed using the C-index. The hazard ratios (HR) and 95% confidence intervals (CI) were calculated using the Cox proportional hazard model. RESULTS: The median age was 65 years old, and 138 (48%) patients were men. During a mean follow-up of 46 months, 140 deaths were recorded, resulting in a rate of 204.6 events per 1000 patient-years. ECW/TBW showed the best predictive accuracy (C-index = 0.619) compared to the other indicators [p = 0.004, adjusted HR (95% CI) 1.70 (1.18,2.44)]. In the middle tertile (0.385-0.405), ECW/TBW had a strong independent negative association with patient survival [adjusted HR (95% CI) 2.88 (1.39-5.97), p = 0.004]. Patients who had a high ECW/TBW (ECW/TBW ≥ 0.395) combined with a high NLR had 3.84-fold risk of mortality (p < 0.001, 95% CI 1.99,7.38). CONCLUSIONS: ECW/TBW was better than other indicators in predicting survival of cancer patients with sarcopenia. High ECW/TBW combined with high NLR would further increase the risk of mortality. TRIAL REGISTRATION: The Investigation on Nutrition Status and Clinical Outcome of Common Cancers (INSCOC) (Chinese Clinical Trial Registry: ChiCTR1800020329, URL of registration: http://www.chictr.org.cn/showprojen.aspx?proj=31813 ).

7.
ACS Omega ; 7(15): 12661-12679, 2022 Apr 19.
Artigo em Inglês | MEDLINE | ID: mdl-35474799

RESUMO

Liquid flow is subject to head loss because of viscous force, surface tension, friction force, and so on. Part of the energy is irreversibly converted into heat, which then dissipates into the environment. Head loss intensifies in the turbulent state. At present, few studies explore the law of head loss caused by secondary flow, cavitation intensity, and turbulence intensity. In this study, the head losses in different sections of a jet pump were studied by controlling the cavitation number σ, the secondary flow rate Q s, and the inlet pressure p i. The experimental results were analyzed with the aid of computational fluid dynamics. The results show that an increase in Q s can weaken the variations of Q s and suction pressure p s in the transitional stage of cavitation. Besides, σ, Q s, and p i influence head loss to varying extents. Cavitation intensity and turbulence intensity are the main factors for head loss and jet temperature difference. In particular, the influence of Q s on head loss provides guidance both for reducing the energy loss of the quantitative adding device and jet aerator and for expanding the stable adding range of the jet. More importantly, the main factors of energy loss caused by jet cavitation were analyzed in detail, which can effectively facilitate the pipeline design to reduce the local and frictional head loss.

8.
Artigo em Inglês | MEDLINE | ID: mdl-35435489

RESUMO

OBJECTIVE: The levels of platelet-related inflammation indicators and sarcopenia have been reported to affect the survival of patients with cancer. To evaluate the prognostic influence of platelet count (PLT), platelet lymphocyte ratio (PLR), and systemic immune inflammation index (SII), and SII combined with sarcopenia on the survival of patients with gastric cancer (GC). METHODS: A total of 1133 patients with GC (812 male and 321 female, average age: 59.43 years) were evaluated. Receiver-operating characteristic curves were used to determine the best cutoff values of PLT, PLR, and SII, and univariate and multivariate Cox risk regression models were used to evaluate whether SII is an independent predictor of overall survival (OS). The prognostic SS (SII-sarcopenia) was established based on SII and sarcopenia. Finally, a comprehensive analysis of the prognostic SS was performed. RESULTS: SII had the strongest prognostic effect. The SII and OS of patients with GC were in an inverted U-shape (adjusted HR = 1.07; 95% CI 0.97-1.19; adjusted P = 0.179). In patients with SII > 1800, SII was negatively correlated with OS (adjusted HR = 0.57; 95% CI 0.29-1.12; adjusted P = 0.102), however, there is no statistical difference. Interestingly, a high SS was associated with a poorer prognosis. The higher the SS score was, the worse the OS (P < 0.001). CONCLUSION: SII is an independent prognostic indicator of GC, and high SII is related to poor prognosis. A higher SS score had worse survival. Thus, the prognostic SS is a reliable predictor of OS in patients with GC.

9.
ACS Omega ; 7(14): 12255-12267, 2022 Apr 12.
Artigo em Inglês | MEDLINE | ID: mdl-35449934

RESUMO

The dynamic cavitation characteristics of normal-temperature water flowing through a transparent jet pump under different cavitation conditions were experimentally studied by adjusting the pressure ratio. The common results are presented at different pressure ratios, including the temporal and spatial changes of the pressure and noise, together with the visual observation of the cavitation unsteady behaviors using a high-speed camera. The analyses on the measured data and images reveal that the cavitation cloud is generated by periodic oscillations of the jet traveling pressure wave and the bubble traveling pressure wave. The oscillation of the two kinds of interface waves is caused by the collapse of the bubbles, which is the main mechanism of the bubble cloud shedding. As the pressure ratio increases, the maximum length of the jet cloud and bubble cloud linearly decreases, while their oscillation frequency increases gradually. Combined with the cavitation-cloud visualization data and noise frequency analysis, it is proposed that the strong impact between the jet traveling pressure wave and the bubble traveling pressure wave is the main cause of noise. Specially, the acoustic pressure reaches the maximum when the oscillation frequency of the jet traveling pressure wave is the same as that of the bubble traveling pressure wave. Also, the jet traveling pressure wave has a great influence on the migration of bubbles in the cavity. The results can provide guidance for the optimal operating condition in cavitation applications such as jet aerator and quantitative addition.

10.
Int Immunopharmacol ; 108: 108764, 2022 Apr 11.
Artigo em Inglês | MEDLINE | ID: mdl-35421804

RESUMO

The prevalence of avian infectious bronchitis virus (IBV) is still one of causes inducing severe losses of production in the poultry industry worldwide. Vaccination does not completely prevent IBV infection and spread due to immune failure and viral mutations. ForsythiaeFructus and its compounds have been widely used in a lot of prescriptions of the traditional Chinese medicine for a long history, and it is well-known as safety and efficiency in heat-clearing and detoxifying. This study aims to investigate the anti-IBV activity and mechanism of phillygenin. The results showed that phillygenin inhibited IBV replication by disturbing multiple stages of the virus life cycle, including viral adsorption, invasion, internalization, and release in Vero cells. After being treated with 100, 125 and 150 µg/mL phillygenin, the expression of G3BP1 was significantly increased and the phosphorylation of PKR/eIF2α was activated, which increased stress granule, thereby triggering the antiviral response in Vero cells. The anti-virus activity of PHI was decreased when G3BP1 was interfered by si-RNA, and G3BP1 was down-regulated when PKR/eIF2α was interfered by si-RNA. In conclusion, our findings indicate that phillygenin activates PKR/eIF2α pathway and induces stress granule formation to exert anti-IBV, which holds promise to develop into a novel anti-IBV drug. Further study in vivo is needed to explore phillygenin as a potential and effective drug to prevent IB in poultry.

12.
Artigo em Inglês | MEDLINE | ID: mdl-35366326

RESUMO

BACKGROUND: Various risk factors have been associated with the risk of thyroid cancer in observational studies. However, the causality of the risk factors is not clear given the susceptibility of confounding and reverse causation. A 2-sample Mendelian randomization approach was used to estimate the effect of potential risk factors on thyroid cancer risk. METHODS: Genetic instruments to proxy 55 risk factors were identified by genome-wide association studies (GWAS). Associations of these genetic variants with thyroid cancer risk were estimated in GWAS of the FinnGen Study (989 cases and 217,803 controls). A Bonferroni-corrected threshold of P=9.09×10 -4 was considered significant, and P<0.05 was considered to be suggestive of an association. RESULTS: Telomere length was significantly associated with increased thyroid cancer risk after correction for multiple testing (OR=4.68, 95%CI 2.35 to 9.31, P=1.12×10 -5). Suggestive associations with increased risk were noted for waist-to-hip ratio (OR=1.85, 95%CI 1.02 to 3.35, P=0.042) and diastolic blood pressure (OR=1.03, 95%CI 1.00 to 1.06, P=0.040). Suggestive associations were noted between hemoglobin A1c (HbA1c) (OR=0.20, 95%CI 0.05 to 0.82, P=0.025) and decreased risk of thyroid cancer. Risk of thyroid cancer was not associated with sex hormones and reproduction, developmental and growth, lipids, diet and lifestyle, or inflammatory factors (All P>0.05). CONCLUSION: Our study identified several potential targets for primary prevention of thyroid cancer, including central obesity, diastolic blood pressure, HbA1c, as well as telomere length that should inform public health policy.

13.
Artigo em Inglês | MEDLINE | ID: mdl-35387530

RESUMO

BACKGROUND: The impact of diabetes mellitus (DM) on the survival of patients with hepatocellular carcinoma (HCC) is still unclear. The present study aims to draw a firm conclusion in terms of evaluating the impact of DM on the prognosis of HCC after hepatectomy. METHODS: The pattern of recurrence for HCC was often stratified into early-stage (<2 years) and late-stage (≥2 years) recurrence. Because the early-stage recurrence was mainly attributed to aggressive tumor pathological characteristics, patients who recurrence or die within 2 years were excluded. Cumulative overall survival (OS) and recurrence-free survival (RFS) were determined by the method of Kaplan-Meier, and the independent risk factors of OS/RFS were determined by Cox regression analysis. RESULTS: A total of 426 patients were eventually included. The 3- and 5-year OS in patients with and without DM was 83.7%, 55.1%; and 90.9%, 77.4%, respectively. Multivariate analysis showed that DM was an independent risk factor for OS (HR 1.166, 95% CI 1.056-2.036, P = 0.022) and RFS (HR 1.365, 95% CI 1.043-1.787, P = 0.023). CONCLUSION: DM is an independent risk factor for long-term prognosis in patients with HCC. Patients with DM after hepatectomy for HCC, thus, need to actively control DM and closer follow-up.

14.
J Thorac Dis ; 14(1): 123-134, 2022 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-35242374

RESUMO

BACKGROUND: Antimicrobial resistance (AMR) has become a worldwide public health problem. Abuse of antibiotic in acute respiratory tract infections (ARI) contributes to the increasing AMR. C-reactive protein (CRP) testing may help reduce antibiotic overprescribing, but the available evidence quality varies widely. There is no meta-analysis of CRP testing to guide the antibiotic prescribing for adult ARI. Therefore, we conducted this meta-analysis to determine the effectiveness of CRP testing to guide antibiotic prescribing in adult ARI. METHODS: We searched the Cochrane Library, PubMed, and EMBASE databases for randomized controlled trials (RCTs) involving our meta-analysis from the establishment of these databases until January 16, 2021. Two reviewers extracted the data separately and pooled the data using RevMan5.3. The evidence quality was appraised strictly with GRADE system. RESULTS: Seven studies included with 3,614 patients. Compared with routine care, CRP testing reduced antibiotic prescribing rate at the index consultation significantly [risk ratio (RR) =0.76; 95% confidence interval (CI): 0.68-0.85; P<0.00001], and during 28 days follow-up (RR =0.77; 95% CI: 0.73-0.81; P<0.00001). There were no significant differences between CRP testing and routine care in clinical recovery of patients within 7 days (RR =0.95; 95% CI: 0.90-1.01; P=0.08). Moreover, adverse events were not significantly different between CRP testing and routine care. DISCUSSION: CRP testing can reduce the antibiotic prescribing rate at index consultation and during 28 days follow-up. These findings support the conclusion that CRP testing is valuable to guide the antibiotic prescribing for adult ARI.

15.
J Ethnopharmacol ; 292: 115212, 2022 Jun 28.
Artigo em Inglês | MEDLINE | ID: mdl-35331876

RESUMO

ETHNOPHARMACOLOGICAL RELEVANCE: Huang Bai Jian Pi (HBJP) decoction, a Chinese herbal formula based on the Pulsatilla decoction (PD) and Si Junzi decoction, is efficacy to treat clinical diarrhea in calves. AIM OF THE STUDY: The mechanism of HBJP decoction to treat calf diarrhea remains unclear. This study was to investigate the therapeutic effect and anti-inflammatory mechanism of HBJP decoction on diarrhea in rats. MATERIALS AND METHODS: Thirty-six Sprague Dawley rats were randomly divided into control group, model group, PD group and three treated groups with HBJP decoction. The diarrheal model in rats was established by multiple factors including high-sugar and fat diet, high temperature and dampness environment, biological pathogenic factors. The diarrheal animals were treated with HBJP decoction or PD for 5 days. The inflammatory model of the intestinal epithelioid cell line 6 (IEC-6) was induced by TNF-α. The clinical symptoms, blood routine and biochemistry parameters, histopathology of main organs were detected. The proteins associated with PI3K/Akt/NF-κB pathway and the expression levels of cytokines associated with inflammation were detected in vivo and in vitro by Western blot and ELISA. RESULTS: The model rats showed obvious diarrheal symptoms, and the obvious systemic inflammatory response accompanied with abnormal change in blood routine, biochemistry parameters and histopathology. HBJP decoction alleviated obviously the clinical symptoms, and pathological changes of the liver, colon and lung, and abnormal blood routine and biochemistry indexes in rats. The expression of P-PI3K, P-Akt, P-NF-κB, IL-1ß, IL-6 was significantly increased, and the expression of IL-10 was markedly decreased in diarrheal rats and IEC-6 with inflammation. HBJP decoction significantly inhibited the PI3K/AKT/NF-κB signal pathway and adjusted the expression of these inflammatory cytokines. CONCLUSIONS: The finding suggested that HBJP decoction alleviate the inflammation in diarrhea through inhibiting the PI3K/Akt/NF-κB signal pathway, which provides scientific evidences for the clinical application of HBJP decoction in diarrhea.


Assuntos
NF-kappa B , Proteínas Proto-Oncogênicas c-akt , Animais , Bovinos , Citocinas , Diarreia/tratamento farmacológico , Medicamentos de Ervas Chinesas , Inflamação/tratamento farmacológico , NF-kappa B/metabolismo , Fosfatidilinositol 3-Quinases/metabolismo , Proteínas Proto-Oncogênicas c-akt/metabolismo , Ratos , Ratos Sprague-Dawley
16.
Front Genet ; 13: 819699, 2022.
Artigo em Inglês | MEDLINE | ID: mdl-35309127

RESUMO

Objective: Esophageal squamous cell carcinoma (ESCC) presents high morbidity and mortality. It was demonstrated that blood-derived vesicles can facilitate ESCC development and transmit regulating signals. However, the molecular mechanism of vesicle miRNA secreted by tumor cells affecting ESCC progression has not been explored. Methods: The mRNA-related signaling pathways and differentially expressed genes were screened out in TCGA dataset. The levels of miRNA-105-5p and SPARCL1 were determined by qRT-PCR. Protein level determination was processed using Western blot. The interaction between the two genes was verified with the dual-luciferase method. A transmission electron microscope was utilized to further identify extracellular vesicles (EVs), and co-culture assay was performed to validate the intake of EVs. In vitro experiments were conducted to evaluate cell function changes in ESCC. A mice tumor formation experiment was carried out to observe tumor growth in vivo. Results: MiRNA-105-5p expression was increased in ESCC, while SPARCL1 was less expressed. MiRNA-105-5p facilitated cell behaviors in ESCC through targeting SPARCL1 and regulating the focal adhesion kinase (FAK)/Akt signaling pathway. Blood-derived external vesicles containing miRNA-105-5p and EVs could be internalized by ESCC cells. Then, miRNA-105-5p could be transferred to ESCC cells to foster tumorigenesis as well as cell behaviors. Conclusion: EV-carried miRNA-105-5p entered ESCC cells and promoted tumor-relevant functions by mediating SPARCL1 and the FAK/Akt signaling pathway, which indicated that the treatment of ESCC via serum EVs might be a novel therapy and that miRNA-105-5p can be a molecular target for ESCC therapy.

17.
Front Vet Sci ; 9: 703051, 2022.
Artigo em Inglês | MEDLINE | ID: mdl-35242833

RESUMO

Dampness-heat diarrhea (DHD), a common syndrome in Chinese dairy farms, is mainly resulted from digestive system disorders, and accompanied with metabolic disorders in some cases. However, the underlying mechanisms in the intestinal microbiome and plasma metabolome in calves with DHD remain unclear. In order to investigate the pathogenesis of DHD in calves, multi-omics techniques including the 16S rDNA gene sequencing and metabolomics were used to analyze gut microbial compositions and plasma metabolic changes in calves. The results indicated that DHD had a significant effect on the intestinal microbial compositions in calves, which was confirmed by changes in microbial population and distribution. A total of 14 genera were changed, including Escherichia-Shigella, Bacteroides, and Fournierella, in calves with DHD (P < 0.05). Functional analysis based on the Kyoto Encyclopedia of Genes and Genomes (KEGG) annotations indicated that 11 metabolic functions (level 2) were significantly enriched in DHD cases. The untargeted metabolomics analysis showed that 440 metabolites including bilineurin, phosphatidylcholine, and glutamate were significantly different between two groups (VIP > 1 and P < 0.05), and they were related to 67 signal pathways. Eight signal pathways including alpha-linolenic acid, linoleic acid, and glycerophospholipid metabolism were significantly enriched (P < 0.05), which may be potential biomarkers of plasma in calves with DHD. Further, 107 pairs of intestinal microbiota-plasma metabolite correlations were determined, e.g., Escherichia-Shigella was significantly associated with changes of sulfamethazine, butyrylcarnitine, and 14 other metabolites, which reflected that metabolic activity was influenced by the microbiome. These microbiota-metabolite pairs might have a relationship with DHD in calves. In conclusion, the findings revealed that DHD had effect on intestinal microbial compositions and plasma metabolome in calves, and the altered metabolic pathways and microorganisms might serve as diagnostic markers and potential therapeutic targets for DHD in calves.

18.
Front Pharmacol ; 13: 814883, 2022.
Artigo em Inglês | MEDLINE | ID: mdl-35295335

RESUMO

Vulvovaginal candidiasis (VVC) is an inflammatory disease of the vagina mainly caused by Candida albicans (C. albicans), which affects around three-quarters of all women during their reproductive age. Although some antifungal drugs such as azoles have been applied clinically for many years, their therapeutic value is very limited due to the emergence of drug-resistant strains. Previous studies have shown that the adhesion of C. albicans to vaginal epithelial cells is essential for the pathogenesis of VVC. Therefore, preventing the adhesion of C. albicans to vaginal epithelial cells may be one of the most effective strategies for the treatment of VVC. Berberine (BBR) is a biologically active herbal alkaloid that was used to treat VVC. However, so far, its mechanism has remained unclear. This study shows BBR significantly inhibits the adhesion of C. albicans to vaginal epithelial cells by reducing the expressions of ICAM-1, mucin1, and mucin4 in vaginal epithelial cells, which play the most important role in modulating the adhesion of C. albicans to host cells, and balancing IL-2 and IL-4 expressions, which play a key effect on regulating the inflammatory response caused by C. albicans infection. Hence, our findings demonstrate that BBR may be a potential therapeutic agent for VVC by interfering with the adhesion of C. albicans to vaginal epithelial cells and represents a new pathway for developing antifungal therapies agents from natural herbs.

19.
MedComm (2020) ; 3(1): e126, 2022 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-35317190

RESUMO

New genetic variants of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) constantly emerge through unmitigated spread of the virus in the ongoing Coronavirus disease 2019 pandemic. Omicron (B.1.1.529), the latest variant of concern (VOC), has so far shown exceptional spread and infectivity and has established itself as the dominant variant in recent months. The SARS-CoV-2 spike glycoprotein is a key component for the recognition and binding to host cell angiotensin-converting enzyme 2 receptors. The Omicron variant harbors a cluster of substitutions/deletions/insertions, and more than 30 mutations are located in spike. Some noticeable mutations, including K417N, T478K, N501Y, and P681H, are shared with the previous VOCs Alpha, Beta, Gamma, or Delta variants and have been proven to be associated with higher transmissibility, viral infectivity, and immune evasion potential. Studies have revealed that the Omicron variant is partially resistant to the neutralizing activity of therapeutic antibodies and convalescent sera, which poses significant challenges for the clinical effectiveness of the current vaccines and therapeutic antibodies. We provide a comprehensive analysis and summary of the epidemiology and immune escape mechanisms of the Omicron variant. We also suggest some therapeutic strategies against the Omicron variant. This review, therefore, aims to provide information for further research efforts to prevent and contain the impact of new VOCs during the ongoing pandemic.

20.
J Neurol ; 2022 Mar 03.
Artigo em Inglês | MEDLINE | ID: mdl-35239007

RESUMO

BACKGROUND: This study aims to determine the genetic and clinical features of TARDBP-mutated patients in our cohort of Chinese patients with amyotrophic lateral sclerosis (ALS) combined with data in the literature. METHODS: We performed TARDBP mutation screening in 1258 Chinese ALS patients, including 1204 sporadic ALS (sALS) and 54 familial ALS (fALS) patients. A systematic literature review was conducted by searching TARDBP-mutated patients from China in the online databases. RESULTS: In our cohort, the mutant frequency of TARDBP variants was 0.3% (4/1258), with two recurrent variants (p.G294V, p.G298V) and one novel variant (p.S332G) identified. Combining with data in the literature review, the TARDBP-mutant frequency in the Chinese population was 1.4% (83/5998), with 0.8% (46/5470) in sALS and 7.0% (37/528) in fALS. Most patients had limb onset (63.0%), with an average life expectancy of 4.3 years (range 0.5-13). Disease durations significantly differed (p = 0.002), with p.M337V showing the longest duration (80 months) and p.N378D showing the shortest duration (16.7 months). CONCLUSION: Our study found that TARDBP mutation was not rare in Chinese fALS patients. Different TARDBP mutations were associated with specific features in phenotypes.

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