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1.
Zhongguo Gu Shang ; 34(11): 1044-52, 2021 Jul 25.
Artigo em Chinês | MEDLINE | ID: mdl-34812023

RESUMO

OBJECTIVE: To explore the efficacy of Yishen Huoxue Tongluo() decoction containing serum on the apoptosis of human disc nucleus pulposus cells under the overload static pressure stress and its related mechanism. METHODS: Human nucleus pulposus cells were divided into three groups. The blank group had no intervention. The model group and traditional Chinese medicine serum intervention group were treated with 3 MPa compressive stress in vitro for 2, 4 and 6 hours. The changes and differences of morphology, growth status and ultrastructure of intervertebral disc nucleus pulposus cells were observed. The apoptosis rate of nucleus pulposus cells and nuclear factor kappa-B p65 (NF-κB p65), SRY-related high mobility group box 9 (SOX9), C/EBP-homologous protein (CHOP), matrix metalloprotein-13 (MMP-13) and corresponding gene expression were detected. RESULTS: At the same time, compared with the blank group, the nucleus pulposus cells in the model group were smaller in volume, less in cytoplasm and worse in growth; the nucleus pulposus cells in the traditional Chinese medicine serum intervention group were slightly larger in volume, more complete in morphology, richer in cytoplasm and better in growth. Under the same action time, the ultrastructure of nucleus pulposus cells in blank group was complete, and the structures of primary and secondary processes were not broken;and the ultrastructure of model group and traditional Chinese medicine serum intervention group were damaged, the main and secondary processes were broken to varying degrees, and there was no significant difference between the two groups. At the same time, the apoptosis rate of nucleus pulposus cells in model group was higher than that in blank group, while the apoptosis rate of nucleus pulposus cells in the traditional Chinese medicine serum intervention group was lower than that inmodel group, the difference was statistically significant (P<0.05); with the increase of action time, there was no significant difference in the apoptosis rate of nucleus pulposus cells between blank group and traditional Chinese medicine serum intervention group, and the apoptosis rate of nucleus pulposus cells in model group was increased. Compared with model group, the expression of NF-κB p65, CHOP, MMP-13 were decreased and SOX9 was increased in traditional Chinese medicine serum intervention group at the same time (P<0.05);with the increase of action time, the expression of NF-κB p65, CHOP and MMP-13 were increased, and the expression of SOX9 was decreased in blank group and model group(P<0.05), and the expression level of model group was higher than that of blank group(P<0.05). Overall observation by gene expression, under the same action time, the relative quantifications of NF-κB p65, CHOP and MMP-13 in traditional Chinese medicine serum intervention group were lower than that in model group, while SOX9 was increased (P<0.05);compared with model group, the relative quantifications of NF-κB p65, CHOP and MMP-13 in blank group were decreased(P<0.05), and the relative quantification of SOX9 was increased(P<0.05);with the increase of action time, the relative quantifications of NF-κB p65, CHOP and MMP-13 of nucleus pulposus cells in blank group and model group were increased and SOX9 was decreased(P<0.05). CONCLUSION: Yishen Huoxue Tongluo() decoction can reduce the apoptosis of nucleus pulposus cells under overload and static pressure, and has the effect of delaying the degeneration of nucleus pulposus cells. Its mechanism may be related to the decrease of CHOP, MMP-13 expression and the increase of SOX9 expression by inhibiting NF-κB p65 signal pathway of nucleus pulposus cells.


Assuntos
Degeneração do Disco Intervertebral , Disco Intervertebral , Núcleo Pulposo , Apoptose , Medicamentos de Ervas Chinesas , Humanos
2.
Front Med (Lausanne) ; 8: 744518, 2021.
Artigo em Inglês | MEDLINE | ID: mdl-34778306

RESUMO

Background: Galectins, a family of ß-galactoside-binding proteins, are related to the development and progression of various human diseases such as cancer, heart failure, and chronic kidney disease. However, its role in liver diseases is unclear. Methods: The PubMed, Embase, and Cochrane Library databases were searched. Hazard ratios (HRs), odds ratios (ORs), and mean differences (MDs) with 95% CIs were pooled to evaluate the association of the galectins with the outcomes and risk of liver diseases by a random effects model. Results: Thirty three studies involving 43 cohorts and 4,168 patients with liver diseases were included. In the patients with hepatocellular carcinoma (HCC), high expression of galectin-1 and -3 in the tissues was significantly associated with worse overall survival (galectin-1: HR = 1.94, 95% CI = 1.61-2.34, p < 0.001; galectin-3: HR = 3.29, 95% CI = 1.62-6.68, p < 0.001) and positive vascular invasion (galectin-1: OR = 1.74, 95% CI = 1.18-2.58, p = 0.005; galectin-3: OR = 2.98, 95% CI = 1.58-5.60, p = 0.001); but, high expression of galectin-4 and -9 in the tissues was significantly associated with better overall survival (galectin-4: HR = 0.53, 95% CI = 0.36-0.79, p = 0.002; galectin-9: HR = 0.56, 95% CI = 0.44-0.71, p < 0.001) and negative vascular invasion (galectin-4: OR = 0.36, 95% CI = 0.19-0.72, p = 0.003; galectin-9: OR = 0.60, 95% CI = 0.37-0.97, p = 0.037). Serum galectin-3 level was significantly higher in HCC (MD = 3.06, 95% CI = 1.79-4.32, p < 0.001), liver failure (MD = 0.44, 95% CI = 0.23-0.66, p < 0.001), liver cirrhosis (MD = 1.83, 95% CI = 1.15-2.51, p < 0.001), and chronic active hepatitis B (MD = 18.95, 95% CI = 10.91-27.00, p < 0.001); serum galectin-9 level was significantly higher in HCC (MD = 3.74, 95% CI = 2.57-4.91, p < 0.001) and autoimmune hepatitis (MD = 8.80, 95% CI = 7.61-9.99, p < 0.001). Conclusion: High galectin-1 and -3 and low galectin-4 and -9 expression indicate worse outcomes of patients with HCC. Serum galectin-3 and -9 levels are positively associated with the risk of chronic liver diseases.

3.
CNS Neurosci Ther ; 2021 Nov 12.
Artigo em Inglês | MEDLINE | ID: mdl-34767694

RESUMO

AIMS: This study aimed to explore the pathomechanism of a mutation on the leucine-rich glioma inactivated 1 gene (LGI1) identified in a family having autosomal dominant lateral temporal lobe epilepsy (ADLTE), using a precise knock-in mouse model. METHODS AND RESULTS: A novel LGI1 mutation, c.152A>G; p. Asp51Gly, was identified by whole exome sequencing in a Chinese family with ADLTE. The pathomechanism of the mutation was explored by generating Lgi1D51G knock-in mice that precisely phenocopied the epileptic symptoms of human patients. The Lgi1D51G / D51G mice showed spontaneous recurrent generalized seizures and premature death. The Lgi1D51G /+ mice had partial epilepsy, with half of them displaying epileptiform discharges on electroencephalography. They also showed enhanced sensitivity to the convulsant agent pentylenetetrazole. Mechanistically, the secretion of Lgi1 was impaired in the brain of the D51G knock-in mice and the protein level was drastically reduced. Moreover, the antiepileptic drugs, carbamazepine, oxcarbazepine, and sodium valproate, could prolong the survival time of Lgi1D51G / D51G mice, and oxcarbazepine appeared to be the most effective. CONCLUSIONS: We identified a novel epilepsy-causing mutation of LGI1 in humans. The Lgi1D51G /+ mouse model, precisely phenocopying epileptic symptoms of human patients, could be a useful tool in future studies on the pathogenesis and potential therapies for epilepsy.

4.
J Environ Manage ; 302(Pt B): 114077, 2021 Nov 10.
Artigo em Inglês | MEDLINE | ID: mdl-34768038

RESUMO

Diffuse solar radiation (Rd), known as an important component of global solar radiation (Rg), is a key parameter for solar energy related applications and ecosystem photosynthesis. Some meteorological models have been developed to estimate Rd with acceptable accuracy, but their spatial scales are often small due to the limited meteorological station number. Satellite-based models provide accurate and large-scale Rg estimates. However, remote sensing estimations of Rd are often with low spatial resolutions and large uncertainties, because their methods were based on inaccurate surface and atmospheric parameters. To address these challenges, the high-spatiotemporal-resolution (half-hourly and 1-km) Rd in the United States was estimated using the top-of-atmosphere (TOA) data from the new-generation geostationary satellite Geostationary Operational Environmental Satellites (GOES-16) and the method iterative random forest (RF). The results showed that the iterative RF model had higher accuracy than the simple RF and artificial neural network (ANN) models, and using TIR (thermal infrared) bands can improve models' accuracy. The best model can estimate half-hourly Rd with the accuracy R2 = 0.88, RMSE = 37.81 W/m2, and MBE = 0.01 W/m2. Compared with the previous 0.01-degree (∼11-km) Rd product Earth Polychromatic Imaging Camera (EPIC), the GOES-16 estimated 1-km Rd had similar spatial patterns. Moreover, based on the GOES-16 estimated half-hourly and 1-km Rd in the United States, the spatiotemporal heterogeneity of Rd was quantitatively observed. The proposed approach can be used to produce more high-spatiotemporal-resolution Rd products, and these products are very helpful for many solar-related research topics and industrial applications.

5.
Signal Transduct Target Ther ; 6(1): 405, 2021 Nov 18.
Artigo em Inglês | MEDLINE | ID: mdl-34795208

RESUMO

Thalidomide induces γ-globin expression in erythroid progenitor cells, but its efficacy on patients with transfusion-dependent ß-thalassemia (TDT) remains unclear. In this phase 2, multi-center, randomized, double-blind clinical trial, we aimed to determine the safety and efficacy of thalidomide in TDT patients. A hundred patients of 14 years or older were randomly assigned to receive placebo or thalidomide for 12 weeks, followed by an extension phase of at least 36 weeks. The primary endpoint was the change of hemoglobin (Hb) level in the patients. The secondary endpoints included the red blood cell (RBC) units transfused and adverse effects. In the placebo-controlled period, Hb concentrations in patients treated with thalidomide achieved a median elevation of 14.0 (range, 2.5 to 37.5) g/L, whereas Hb in patients treated with placebo did not significantly change. Within the 12 weeks, the mean RBC transfusion volume for patients treated with thalidomide and placebo was 5.4 ± 5.0 U and 10.3 ± 6.4 U, respectively (P < 0.001). Adverse events of drowsiness, dizziness, fatigue, pyrexia, sore throat, and rash were more common with thalidomide than placebo. In the extension phase, treatment with thalidomide for 24 weeks resulted in a sustainable increase in Hb concentrations which reached 104.9 ± 19.0 g/L, without blood transfusion. Significant increase in Hb concentration and reduction in RBC transfusions were associated with non ß0/ß0 and HBS1L-MYB (rs9399137 C/T, C/C; rs4895441 A/G, G/G) genotypes. These results demonstrated that thalidomide is effective in patients with TDT.

6.
Technol Cancer Res Treat ; 20: 15330338211045204, 2021.
Artigo em Inglês | MEDLINE | ID: mdl-34605330

RESUMO

Background: Pancreatic cancer (PC) has a poor prognosis and is prone to liver metastasis. The KAI1/CD82 gene inhibits PC metastasis. This study aimed to explore differential metabolites and enrich the pathways in serum samples between PC and liver metastasis nude mouse models stably expressing KAI1/CD82. Methods: KAI1/CD82-PLV-EF1α-MCS-IRES-Puro vector and PANC1 cell line stably expressing KAI1/CD82 were constructed for the first time. This cell line was used to construct 3 PC nude mouse models and 3 liver metastasis nude mouse models. The different metabolites and Kyoto encyclopedia of genes and genomes (KEGG) and human metabolome database (HMDB) enrichment pathways were analyzed using the serum samples of the 2 groups of nude mouse models on the basis of untargeted ultra-performance liquid chromatography-tandem mass spectrometry platform. Results: KAI1/CD82-PLV-EF1α-MCS-IRES-Puro vector and PANC1 cell line stably expressing KAI1/CD82 were constructed successfully, and all nude mouse models survived and developed cancers. Among the 1233 metabolites detected, 18 metabolites (9 upregulated and 9 downregulated) showed differences. In agreement with the literature data, the most significant differences between both groups were found in the levels of bile acids (taurocholic acid, chenodeoxycholic acid), glycine, prostaglandin E2, vitamin D, guanosine monophosphate, and inosine. Bile recreation, primary bile acid biosynthesis, and purine metabolism KEGG pathways and a series of HMDB pathways (P < .05) contained differential metabolites that may be associated with liver metastasis from PC. However, the importance of these metabolites on PC liver metastases remains to be elucidated. Conclusions: Our findings suggested that the metabolomic approach may be a useful method to detect potential biomarkers in PC.

7.
Medicine (Baltimore) ; 100(39): e27355, 2021 Oct 01.
Artigo em Inglês | MEDLINE | ID: mdl-34596143

RESUMO

ABSTRACT: To evaluate the application of virtual reality technology in a dental implant training system.A 3-dimensional model of mandible was established by Mimics17.0 software based on the Digital Imaging and Communications in Medicine data obtained from cone beam computed tomography scanning of the patient in mandibular. Thirty physicians were divided into 2 groups. The virtual reality dental implant training system was used for group A, while conventional theoretical knowledge training and clinical demonstration were performed in group B. All young physicians have a 1-month study. After training, all the physicians in groups A and B would conduct a questionnaire survey according to the training situation, which was compared between the 2 groups. The success rate of the operation was also evaluated and compared.The median scores in the 5 dimensions of postoperative assessment of group A was 9/9/9/8/8, and of group B was 6/7/6/7/7. The scores of the 5 dimensions were significantly higher than those of group B (P < .05), indicating that group A has a better grasp of the simulator. After the training of simulated mandibular implants in group A, the deviations in the 4 dimensions of mesiodistal, buccal and tongue, depth, and angle were significantly lower than those of group B (P < .05). Group A has smaller deviations in each of the 4 dimensions than those in group B, indicating group A has a higher operation success rate.We independently develop a set of virtual surgery system for dental implant training, which can be used for teaching and training, with good operability and predictability, to achieve a breakthrough in dental implant surgery training.


Assuntos
Implantação Dentária Endo-Óssea/métodos , Implantes Dentários , Treinamento por Simulação/métodos , Realidade Virtual , Humanos , Imageamento Tridimensional
8.
BMC Surg ; 21(1): 378, 2021 Oct 26.
Artigo em Inglês | MEDLINE | ID: mdl-34702227

RESUMO

BACKGROUND: It was controversial to operate on the primary site of breast cancer (BC) with bone metastasis only. We investigated the impact of surgery on BC patients with bone metastases via a SEER database retrospective analysis. METHODS: A total of 2917 BC cases with bone metastasis, first diagnosed between 2010 and 2015 in the Surveillance, Epidemiology, and Results Database (SEER) of National Cancer Institute were selected. We assessed the effect of different surgical procedures on survival and prognosis. RESULTS: Compared with the non-surgical group, the primary tumor surgical group showed longer median survival time (χ2 = 146.023, P < 0.001), and the breast-conserving subgroup showed the highest median survival time of 70 months (χ2 = 157.117, P < 0.001). Compared with the non-surgery group, the median overall survival (OS) of primary surgery group was longer (HR = 0.525, 95%CI = 0.467-0.590, P < 0.001), and the breast-conserving subgroup showed the longest median operative OS (HR = 0.394, 95%CI = 0.325-0.478, P < 0.001). CONCLUSION: This study showed that primary surgery could improve the median survival time and OS of BC patients with bone metastasis. Moreover, under the condition of low tumor burden, breast conserving surgery was a better choice.


Assuntos
Neoplasias Ósseas , Neoplasias da Mama , Neoplasias Ósseas/epidemiologia , Neoplasias Ósseas/cirurgia , Neoplasias da Mama/cirurgia , Feminino , Humanos , Mastectomia Segmentar , Prognóstico , Estudos Retrospectivos , Programa de SEER
9.
Proc Natl Acad Sci U S A ; 118(42)2021 Oct 19.
Artigo em Inglês | MEDLINE | ID: mdl-34654745

RESUMO

Information about features in the visual world is parsed by circuits in the retina and is then transmitted to the brain by distinct subtypes of retinal ganglion cells (RGCs). Axons from RGC subtypes are stratified in retinorecipient brain nuclei, such as the superior colliculus (SC), to provide a segregated relay of parallel and feature-specific visual streams. Here, we sought to identify the molecular mechanisms that direct the stereotyped laminar targeting of these axons. We focused on ipsilateral-projecting subtypes of RGCs (ipsiRGCs) whose axons target a deep SC sublamina. We identified an extracellular glycoprotein, Nephronectin (NPNT), whose expression is restricted to this ipsiRGC-targeted sublamina. SC-derived NPNT and integrin receptors expressed by ipsiRGCs are both required for the targeting of ipsiRGC axons to the deep sublamina of SC. Thus, a cell-extracellular matrix (ECM) recognition mechanism specifies precise laminar targeting of ipsiRGC axons and the assembly of eye-specific parallel visual pathways.

10.
PLoS One ; 16(10): e0258517, 2021.
Artigo em Inglês | MEDLINE | ID: mdl-34653189

RESUMO

Depression is associated with poorer outcomes in a wide spectrum of surgeries but the specific effects of depression in patients undergoing cervical spine surgery are unknown. This study aimed to evaluate the prevalence and impact of pre-surgical clinical depression on pain and other outcomes after surgery for cervical degenerative disc disease using a national representative database. Data of patients with cervical myelopathy and radiculopathy were extracted from the 2005-2014 US Nationwide Inpatient Sample (NIS) database. Included patients underwent anterior discectomy and fusion (ACDF). Acute or chronic post-surgical pain, postoperative complications, unfavorable discharge, length of stay (LOS) and hospital costs were evaluated. Totally 215,684 patients were included. Pre-surgical depression was found in 29,889 (13.86%) patients, with a prevalence nearly doubled during 2005-2014 in the US. Depression was independently associated with acute or chronic post-surgical pain (aOR: 1.432), unfavorable discharge (aOR: 1.311), prolonged LOS (aOR: 1.152), any complication (aOR: 1.232), respiratory complications/pneumonia (aOR: 1.153), dysphagia (aOR: 1.105), bleeding (aOR: 1.085), infection/sepsis (aOR: 1.529), and higher hospital costs (beta: 1080.640) compared to non-depression. No significant risk of delirium or venous thrombotic events was observed in patients with depression as compared to non-depression. Among patients receiving primary surgery, depression was independently associated with prolonged LOS (aOR: 1.150), any complication (aOR:1.233) and postoperative pain (aOR:1.927). In revision surgery, no significant associations were found for prolonged LOS, any complication or pain. In conclusion, in the US patients undergoing ACDF, pre-surgical clinical depression predicts post-surgical acute or chronic pain, a slightly prolonged LOS and the presence of any complication. Awareness of these associations may help clinicians stratify risk preoperatively and optimize patient care.

11.
Neurosci Bull ; 2021 Oct 26.
Artigo em Inglês | MEDLINE | ID: mdl-34699030

RESUMO

Astrocytes are increasingly recognized to play an active role in learning and memory, but whether neural inputs can trigger event-specific astrocytic Ca2+ dynamics in real time to participate in working memory remains unclear due to the difficulties in directly monitoring astrocytic Ca2+ dynamics in animals performing tasks. Here, using fiber photometry, we showed that population astrocytic Ca2+ dynamics in the hippocampus were gated by sensory inputs (centered at the turning point of the T-maze) and modified by the reward delivery during the encoding and retrieval phases. Notably, there was a strong inter-locked and antagonistic relationship between the astrocytic and neuronal Ca2+ dynamics with a 3-s phase difference. Furthermore, there was a robust synchronization of astrocytic Ca2+ at the population level among the hippocampus, medial prefrontal cortex, and striatum. The inter-locked, bidirectional communication between astrocytes and neurons at the population level may contribute to the modulation of information processing in working memory.

12.
Neuropharmacology ; 200: 108806, 2021 12 01.
Artigo em Inglês | MEDLINE | ID: mdl-34562441

RESUMO

Synapse pruning is essential not only for the developmental establishment of synaptic connections in the brain but also for the pathogenesis of neurodevelopmental and neurodegenerative disorders. However, there are no effective pharmacological means to regulate synaptic pruning during early development. Using the eye-specific segregation of the dorsal lateral geniculate nucleus (dLGN) as a model of synaptic pruning coupled with adenosine A2A receptor (A2AR) antagonism and knockout, we demonstrated while genetic deletion of the A2AR throughout the development attenuated eye-specific segregation with the attenuated microglial phagocytosis at postnatal day 5 (P5), selective treatment with the A2AR antagonist KW6002 at P2-P4 facilitated synaptic pruning of visual pathway with microglial activation, increased lysosomal activity in microglia and increased microglial engulfment of retinal ganglion cell (RGC) inputs in the dLGN at P5 (but not P10). Furthermore, KW6002-mediated facilitation of synaptic pruning was activity-dependent since tetrodotoxin (TTX) treatment abolished the KW6002 facilitation. Moreover, the A2AR antagonist also modulated postsynaptic proteins and synaptic density at early postnatal stages as revealed by the reduced immunoreactivity of postsynaptic proteins (Homer1 and metabotropic glutamate receptor 5) and colocalization of presynaptic VGlut2 and postsynaptic Homer1 puncta in the dLGN. These findings suggest that A2AR can control pruning by multiple actions involving the retinal wave, microglia engulfment, and postsynaptic stability. Thus, A2AR antagonists may represent a novel pharmacological strategy to modulate microglia-mediated synaptic pruning and treatment of neurodevelopmental disorders associated with dysfunctional pruning.

13.
Sensors (Basel) ; 21(18)2021 Sep 15.
Artigo em Inglês | MEDLINE | ID: mdl-34577381

RESUMO

Atmospheric oxygen anions play an important role in medical health, clinical medicine, environmental health, and the ecological environment. Therefore, the concentration of atmospheric anions is an important index for measuring air quality. This paper proposes a monitoring system for atmospheric oxygen anions based on Beidou positioning and unmanned vehicles. This approach combines Beidou positioning technology, 4G pass-through, the unmanned capacitance suction method, electromagnetic field theory, and atmospheric detection technology. The proposed instrument can monitor the overall negative oxygen ion concentration, temperature, and humidity in a certain region over time and provide data visualization for the concentration of negative oxygen ions.


Assuntos
Poluição do Ar , Ânions/análise , Umidade , Íons , Temperatura
14.
Yonsei Med J ; 62(10): 918-927, 2021 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-34558871

RESUMO

PURPOSE: We compared the clinical outcomes of modified procedures for associating liver partition and portal vein ligation for staged hepatectomy (ALPPS) based on a risk-reduced strategy with those of classic ALPPS procedures in treating large liver carcinoma. MATERIALS AND METHODS: Short-term outcomes, increases in future liver remnant (FLR) and functional FLR (FFLR), and overall survival (OS) were compared between 45 consecutive patients treated with modified ALPPS procedures and 34 patients treated with classic ALPPS procedures. RESULTS: Clinical outcomes after the 1st-stage operation markedly improved with the modified procedures. Although the proportions of liver cirrhosis and hepatocellular carcinoma were higher in the modified group, the mortality and incidence of severe complications did not increase. FLR and FFLR hypertrophy at 1 week after the 1st-stage operation were similar in both groups; however, kinetic growth rates in the modified group were lower. OS rates were similar. CONCLUSION: Modified ALPPS procedures could be safely applied to provide long-term survival for patients with liver cirrhosis without sufficient FLR.


Assuntos
Carcinoma Hepatocelular , Neoplasias Hepáticas , Carcinoma Hepatocelular/cirurgia , Hepatectomia , Humanos , Ligadura , Fígado/cirurgia , Neoplasias Hepáticas/cirurgia , Veia Porta/cirurgia
15.
Signal Transduct Target Ther ; 6(1): 329, 2021 09 01.
Artigo em Inglês | MEDLINE | ID: mdl-34471087

RESUMO

It's a challenge for detecting the therapeutic targets of a polypharmacological drug from variations in the responsed networks in the differentiated populations with complex diseases, as stable coronary heart disease. Here, in an adaptive, 31-center, randomized, double-blind trial involving 920 patients with moderate symptomatic stable angina treated by 14-day Danhong injection(DHI), a kind of polypharmacological drug with high quality control, or placebo (0.9% saline), with 76-day following-up, we firstly confirmed that DHI could increase the proportion of patients with clinically significant changes on angina-frequency assessed by Seattle Angina Questionnaire (ΔSAQ-AF ≥ 20) (12.78% at Day 30, 95% confidence interval [CI] 5.86-19.71%, P = 0.0003, 13.82% at Day 60, 95% CI 6.82-20.82%, P = 0.0001 and 8.95% at Day 90, 95% CI 2.06-15.85%, P = 0.01). We also found that there were no significant differences in new-onset major vascular events (P = 0.8502) and serious adverse events (P = 0.9105) between DHI and placebo. After performing the RNA sequencing in 62 selected patients, we developed a systemic modular approach to identify differentially expressed modules (DEMs) of DHI with the Zsummary value less than 0 compared with the control group, calculated by weighted gene co-expression network analysis (WGCNA), and sketched out the basic framework on a modular map with 25 functional modules targeted by DHI. Furthermore, the effective therapeutic module (ETM), defined as the highest correlation value with the phenotype alteration (ΔSAQ-AF, the change in SAQ-AF at Day 30 from baseline) calculated by WGCNA, was identified in the population with the best effect (ΔSAQ-AF ≥ 40), which is related to anticoagulation and regulation of cholesterol metabolism. We assessed the modular flexibility of this ETM using the global topological D value based on Euclidean distance, which is correlated with phenotype alteration (r2: 0.8204, P = 0.019) by linear regression. Our study identified the anti-angina therapeutic module in the effective population treated by the multi-target drug. Modular methods facilitate the discovery of network pharmacological mechanisms and the advancement of precision medicine. (ClinicalTrials.gov identifier: NCT01681316).

16.
Malar J ; 20(1): 374, 2021 Sep 19.
Artigo em Inglês | MEDLINE | ID: mdl-34538247

RESUMO

BACKGROUND: Plasmodium falciparum erythrocyte binding antigen-175 (PfEBA-175) is a candidate antigen for a blood-stage malaria vaccine, while various polymorphisms and dimorphism have prevented to development of effective vaccines based on this gene. This study aimed to investigate the dimorphism of PfEBA-175 on both the Bioko Island and continent of Equatorial Guinea, as well as the genetic polymorphism and natural selection of global PfEBA-175. METHODS: The allelic dimorphism of PfEBA-175 region II of 297 bloods samples from Equatorial Guinea in 2018 and 2019 were investigated by nested polymerase chain reaction and sequencing. Polymorphic characteristics and the effect of natural selection were analyzed using MEGA 7.0, DnaSP 6.0 and PopART programs. Protein function prediction of new amino acid mutation sites was performed using PolyPhen-2 and Foldx program. RESULTS: Both Bioko Island and Bata district populations, the frequency of the F-fragment was higher than that of the C-fragment of PfEBA-175 gene. The PfEBA-175 of Bioko Island and Bata district isolates showed a high degree of genetic variability and heterogeneity, with π values of 0.00407 & 0.00411 and Hd values of 0.958 & 0.976 for nucleotide diversity, respectively. The values of Tajima's D of PfEBA-175 on Bata district and Bioko Island were 0.56395 and - 0.27018, respectively. Globally, PfEBA-175 isolates from Asia were more diverse than those from Africa and South America, and genetic differentiation quantified by the fixation index between Asian and South American countries populations was significant (FST > 0.15, P < 0.05). A total of 310 global isolates clustered in 92 haplotypes, and only one cluster contained isolates from three continents. The mutations A34T, K109E, D278Y, K301N, L305V and D329N were predicted as probably damaging. CONCLUSIONS: This study demonstrated that the dimorphism of F-fragment PfEBA-175 was remarkably predominant in the study area. The distribution patterns and genetic diversity of PfEBA-175 in Equatorial Guinea isolates were similar another region isolates. And the levels of recombination events suggested that natural selection and intragenic recombination might be the main drivers of genetic diversity in global PfEBA-175. These results have important reference value for the development of blood-stage malaria vaccine based on this antigen.


Assuntos
Antígenos de Protozoários/genética , Plasmodium falciparum/genética , Polimorfismo Genético , Proteínas de Protozoários/genética , Seleção Genética , Adolescente , Adulto , Idoso , Criança , Pré-Escolar , Guiné Equatorial , Humanos , Lactente , Malária Falciparum/parasitologia , Pessoa de Meia-Idade , Adulto Jovem
17.
Exp Eye Res ; 212: 108758, 2021 Nov.
Artigo em Inglês | MEDLINE | ID: mdl-34506801

RESUMO

Myopia is the most common cause of a visual refractive error worldwide. Cyclic adenosine monophosphate (cAMP)-linked signaling pathways contribute to the regulation of myopia development, and increases in cAMP accumulation promote myopia progression. To pinpoint the underlying mechanisms by which cAMP modulates myopia progression, we performed scleral transcriptome sequencing analysis in form-deprived mice, a well-established model of myopia development. Form deprivation significantly inhibited the expression levels of genes in the cAMP catabolic pathway. Quantitative real-time polymerase chain reaction analysis validated that the gene expression level of phosphodiesterase 4B (PDE4B), a cAMP hydrolase, was downregulated in form-deprived mouse eyes. Under visually unobstructed conditions, loss of PDE4B function in Pde4b-knockout mice increased the myopic shift in refraction, -3.661 ± 1.071 diopters, more than that in the Pde4b-wildtype littermates (P < 0.05). This suggests that downregulation and inhibition of PDE4B gives rise to myopia. In guinea pigs, subconjunctival injection of rolipram, a selective inhibitor of PDE4, led to myopia in normal eyes, and it also enhanced form-deprivation myopia (FDM). Subconjunctival injection of dibutyryl-cyclic adenosine monophosphate, a cAMP analog, induced only a myopic shift in the normal visually unobstructed eyes, but it did not enhance FDM. As myopia developed, axial elongation occurred during scleral remodeling that was correlated with changes in collagen fibril thickness and distribution. The median collagen fibril diameter in the FDM + rolipram group, 55.09 ± 1.83 nm, was thinner than in the FDM + vehicle group, 59.33 ± 2.06 nm (P = 0.011). Thus, inhibition of PDE4 activity with rolipram thinned the collagen fibril diameter relative to the vehicle treatment in form-deprived eyes. Rolipram also inhibited increases in collagen synthesis induced by TGF-ß2 in cultured human scleral fibroblasts. The current results further support a role for PDE enzymes such as PDE4B in the regulation of normal refractive development and myopia because either loss or inhibition of PDE4B function increased myopia and FDM development through declines in the scleral collagen fibril diameter.

18.
Int J Gen Med ; 14: 5287-5299, 2021.
Artigo em Inglês | MEDLINE | ID: mdl-34522128

RESUMO

Background: Presently, no study reported the function of cathepsin H (CTSH) in thyroid carcinoma (THCA). The aim of present study was to initially explore the factors affecting CTSH expression, and association between CTSH expression and survival rate in THCA. Methods: We explored mRNA expression of CTSH in normal and BRCA tissues, and evaluated prognostic impact of CTSH expression on the overall survival of THCA patients. Then, related factors influencing CTSH mRNA expression in THCA were analyzed. Functional enrichment analysis was performed to reveal the potential function of CTSH involved in THCA. We also constructed PPI network among co-expressed genes of CTSH to determine hub genes, followed by association analysis on hub genes with CTSH. Results: (1) CTSH mRNA was highly expressed in THCA compared with normal group (P<0.001). High expression of CTSH was conducive to the overall survival of THCA patients (P=0.0027). CTSH was then determined as an independent prognostic factor in THCA (P=0.024). (2) The mRNA expression of CTSH was statistically related to patient's histological type, N stage, T stage, tumor stage and sample type (all P<0.001). CTSH copy number variation and methylation also influenced its mRNA expression (all P<0.001). (3) Pathway analysis indicated that CTSH mainly participated in cancer-related pathways, such as hedgehog signaling pathway, cytokine-cytokine receptor interaction and JAK-STAT signaling pathway (all P<0.05). (4) The top 10 co-expressed genes in whole PPI network showed significant correlation with CTSH expression (all P<0.001). Conclusion: CTSH higher expression was observed in THCA, which caused a good prognosis of patients. CTSH expression might be regulated by multiple factors including clinical characteristic, methylation, copy number and other genes. This study demonstrated the clinical significance of CTSH in THCA, as well as revealed the potential pathway associated with CTSH involved in thyroid cancer.

19.
Front Microbiol ; 12: 731379, 2021.
Artigo em Inglês | MEDLINE | ID: mdl-34557176

RESUMO

Norovirus (NoV) is the main non-bacterial pathogen causing outbreaks of gastroenteritis and is considered to be the leading cause of foodborne illness. This study aims to determine whether lettuce-encapsulated bacteria can express histo-blood group antigen (HBGA)-like substances to bind to NoV and, if so, to explore its role in protecting NoV from disinfection practices. Fifteen bacterial strains (HBGA-SEBs) were isolated from the lettuce microbiome and studied as they were proved to have the ability to express HBGA-like substances through indirect ELISA detection. By using attachment assay, HBGA-SEBs showed great abilities in carrying NoVs regarding the evaluation of binding capacity, especially for the top four strains from genera Wautersiella, Sphingobacterium, and Brachybacterium, which could absorb more than 60% of free-flowing NoVs. Meanwhile, the direct viral-bacterial binding between HBGA-like substance-expressing bacteria (HBGA-SEB) and NoVs was observed by TEM. Subsequently, results of simulated environmental experiments showed that the binding of NoVs with HBGA-SEBs did have detrimental effects on NoV reduction, which were evident in short-time high-temperature treatment (90°C) and UV exposure. Finally, by considering the relative abundance of homologous microorganisms of HBGA-SEBs in the lettuce microbiome (ca. 36.49%) and the reduction of NoVs in the simulated environments, we suggested putting extra attention on the daily disinfection of foodborne-pathogen carriers to overcome the detrimental effects of direct viral-bacterial interactions on the reduction of NoVs.

20.
J Nat Med ; 2021 Aug 21.
Artigo em Inglês | MEDLINE | ID: mdl-34417964

RESUMO

One new compound, crocusatin M (1), and three new glycosidic compounds, crocusatins N-P (2-4), along with nine known compounds were isolated from the dried stigmas of Crocus sativus. The structures of new compounds were elucidated on the basis of spectroscopic analysis, and the absolute configurations of 1, 2, and 3 were unambiguously assigned by the comparison of experimental and calculated ECD data. This is the first report of the isolation of 4 with the HMG moiety from the genus Crocus. Compounds 1 and 4 exhibited weak anti-inflammatory activities on inhibiting lipopolysaccharide (LPS)-induced NO production.

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