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1.
Theranostics ; 11(16): 7879-7895, 2021.
Artigo em Inglês | MEDLINE | ID: mdl-34335970

RESUMO

Rationale: Previous studies have shown that human embryonic stem cell-derived cardiomyocytes improved myocardial recovery when administered to infarcted pig and non-human primate hearts. However, the engraftment of intramyocardially delivered cells is poor and the effectiveness of clinically relevant doses of human induced pluripotent stem cell-derived cardiomyocytes (hiPSC-CMs) in large animal models of myocardial injury remains unknown. Here, we determined whether thymosin ß4 (Tb4) could improve the engraftment and reparative potency of transplanted hiPSC-CMs in a porcine model of myocardial infarction (MI). Methods: Tb4 was delivered from injected gelatin microspheres, which extended the duration of Tb4 administration for up to two weeks in vitro. After MI induction, pigs were randomly distributed into 4 treatment groups: the MI Group was injected with basal medium; the Tb4 Group received gelatin microspheres carrying Tb4; the CM Group was treated with 1.2 × 108 hiPSC-CMs; and the Tb4+CM Group received both the Tb4 microspheres and hiPSC-CMs. Myocardial recovery was assessed by cardiac magnetic resonance imaging (MRI), arrhythmogenesis was monitored with implanted loop recorders, and tumorigenesis was evaluated via whole-body MRI. Results: In vitro, 600 ng/mL of Tb4 protected cultured hiPSC-CMs from hypoxic damage by upregulating AKT activity and BcL-XL and promoted hiPSC-CM and hiPSC-EC proliferation. In infarcted pig hearts, hiPSC-CM transplantation alone had a minimal effect on myocardial recovery, but co-treatment with Tb4 significantly enhanced hiPSC-CM engraftment, induced vasculogenesis and the proliferation of cardiomyocytes and endothelial cells, improved left ventricular systolic function, and reduced infarct size. hiPSC-CM implantation did not increase incidence of ventricular arrhythmia and did not induce tumorigenesis in the immunosuppressed pigs. Conclusions: Co-treatment with Tb4-microspheres and hiPSC-CMs was safe and enhanced the reparative potency of hiPSC-CMs for myocardial repair in a large-animal model of MI.

2.
Front Cell Infect Microbiol ; 11: 581239, 2021.
Artigo em Inglês | MEDLINE | ID: mdl-34336708

RESUMO

Background: Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) is a novel coronavirus that has caused the outbreak of coronavirus disease 2019 (COVID-19) all over the world. In the absence of appropriate antiviral drugs or vaccines, developing a simple, rapid, and reliable assay for SARS-CoV-2 is necessary for the prevention and control of the COVID-19 transmission. Methods: A novel molecular diagnosis technique, named multiplex reverse transcription loop-mediated isothermal amplification, that has been linked to a nanoparticle-based lateral flow biosensor (mRT-LAMP-LFB) was applied to detect SARS-CoV-2 based on the SARS-CoV-2 RdRp and N genes, and the mRT-LAMP products were analyzed using nanoparticle-based lateral flow biosensor. The mRT-LAMP-LFB amplification conditions, including the target RNA concentration, amplification temperature, and time were optimized. The sensitivity and specificity of the mRT-LAMP-LFB method were tested in the current study, and the mRT-LAMP-LFB assay was applied to detect the SARS-CoV-2 virus from clinical samples and artificial sputum samples. Results: The SARS-CoV-2 specific primers based on the RdRp and N genes were valid for the establishment of mRT-LAMP-LFB assay to detect the SARS-CoV-2 virus. The multiple-RT-LAMP amplification condition was optimized at 63°C for 30 min. The full process, including reaction preparation, viral RNA extraction, RT-LAMP, and product identification, could be achieved in 80 min. The limit of detection (LoD) of the mRT-LAMP-LFB technology was 20 copies per reaction. The specificity of mRT-LAMP-LFB detection was 100%, and no cross-reactions to other respiratory pathogens were observed. Conclusion: The mRT-LAMP-LFB technique developed in the current study is a simple, rapid, and reliable method with great specificity and sensitivity when it comes to identifying SARS-CoV-2 virus for prevention and control of the COVID-19 disease, especially in resource-constrained regions of the world.

3.
Plant Cell ; 2021 Jul 07.
Artigo em Inglês | MEDLINE | ID: mdl-34240197

RESUMO

To overcome nitrogen deficiency, legume roots establish symbiotic interactions with nitrogen-fixing rhizobia that is fostered in specialized organs (nodules). Similar to other organs, nodule formation is determined by a local maximum of the phytohormone auxin at the primordium site. However, how auxin regulates nodule development remains poorly understood. Here, we found that in soybean, (Glycine max), dynamic auxin transport driven by PIN-FORMED (PIN) transporter GmPIN1 is involved in nodule primordium formation. GmPIN1 was specifically expressed in nodule primordium cells and GmPIN1 was polarly localized in these cells. Two nodulation regulators, (iso)flavonoids trigger expanded distribution of GmPIN1b to root cortical cells, and cytokinin rearranges GmPIN1b polarity. Gmpin1abc triple mutants generated with CRISPR-Cas9 showed impaired establishment of auxin maxima in nodule meristems and aberrant divisions in the nodule primordium cells. Moreover, overexpression of GmPIN1 suppressed nodule primordium initiation. GmPIN9d, an ortholog of Arabidopsis thaliana PIN2, acts together with GmPIN1 later in nodule development to acropetally transport auxin in vascular bundles, fine-tuning the auxin supply for nodule enlargement. Our findings reveal how PIN-dependent auxin transport modulates different aspects of soybean nodule development and suggest that establishment of auxin gradient is a prerequisite for the proper interaction between legumes and rhizobia.

4.
J Mol Neurosci ; 2021 Jul 04.
Artigo em Inglês | MEDLINE | ID: mdl-34218423

RESUMO

Progressive myoclonic epilepsy is a group of neurodegenerative diseases with complex clinical and genetic heterogeneity, which is associated with spontaneous or action-induced myoclonus and progressive neurodegeneration. Since 2020, 4 families with progressive myoclonic epilepsy-11 [OMIM#618876] have been reported with a very limited spectrum of SEMA6B pathogenic variants. In our study, whole-exome sequencing was used in a proband from a nonconsanguineous Chinese family presenting with growth retardation and recurrent atonic seizures. A deletion mutation (c.1960_1978del, p.Leu654Argfs*25) in the last exon of SEMA6B was detected, which is a de novo variant and pathogenic. The new genetic evidence we reported here strengthened the gene-disease relationship, and the gene curation level between SEMA6B and progressive myoclonic epilepsy-11 became "strong" following the ClinGen SOP. Therefore, the results of this study broaden the mutation spectrum of SEMA6B in different ethnic groups and strengthen the gene-disease relationship between SEMA6B and progressive myoclonic epilepsy-11.

5.
Phys Rev Lett ; 127(3): 031102, 2021 Jul 16.
Artigo em Inglês | MEDLINE | ID: mdl-34328784

RESUMO

We report observations of gamma-ray emissions with energies in the 100-TeV energy region from the Cygnus region in our Galaxy. Two sources are significantly detected in the directions of the Cygnus OB1 and OB2 associations. Based on their positional coincidences, we associate one with a pulsar PSR J2032+4127 and the other mainly with a pulsar wind nebula PWN G75.2+0.1, with the pulsar moving away from its original birthplace situated around the centroid of the observed gamma-ray emission. This work would stimulate further studies of particle acceleration mechanisms at these gamma-ray sources.

6.
Anal Bioanal Chem ; 2021 Jul 02.
Artigo em Inglês | MEDLINE | ID: mdl-34212212

RESUMO

On the basis of the Griess-Saltzman (GS) reaction, an optical device for nitric oxide (NO) detection in exhaled breath and atmosphere was developed by employing the light-emitting diode (LED, 560 nm) as the light source, light-to-voltage converter (LVC) as the detector, and porous polypropylene membrane tube (PPMT) as the cuvette. The PPMT was filled with GS reagents and covered with a coaxial jacket tube for gas collection and color reaction; two ends of the PPMT were connected with the LED and LVC to detect the change of light transmissivity in the wavelength range of 530 to 590 nm mainly. A gas absorber filled with GS reagents was installed prior to another absorber filled with KMnO4 solution to eliminate the interference of coexisting NO2. Under the optimized experimental conditions, the device achieved a limit of detection (3σ/k) of 4.4 ppbv for NO detection. The linearity range of this device was divided into two segments, i.e., 25 to 100 ppbv and 50 to 1000 ppbv, with both coefficients of determination > 0.99. The relative standard deviation was 2.7% (n = 9, c = 100 ppbv), and the analytical time was 5.5 min per detection. The minimum detectable quantity was decreased to 1.18 ng, which was ~ 100 times lower than the original GS method (115 ng). The present device was applied for determination of NO in exhaled breath, vehicle exhaust, and air. In addition to satisfactory spiking recoveries (i.e., 103% and 107%), the analytical results of the present device were in agreement with the results obtained by the standard method. These results assured the practicality of the developed device for NO detection in real environmental samples.

7.
Braz J Med Biol Res ; 54(10): e11355, 2021.
Artigo em Inglês | MEDLINE | ID: mdl-34287582

RESUMO

The etiology of subacute combined degeneration (SCD) of the spinal cord is closely associated with vitamin B12 (VitB12) deficiency. The clinical manifestations of SCD are complex and vary substantially. Due to some SCD patients with atypical manifestations and concomitant autoimmune disorders, the probability of misdiagnosis and missed diagnosis is still relatively high in the early stage. We report the cases of two patients who were missed or misdiagnosed at another hospital because of the normal initial VitB12 level and partial overlap of clinical manifestations, finally diagnosed as SCD with atypical manifestations and concomitant autoimmune disorders, pharyngeal-cervical-brachial Guillain-Barre syndrome in Case 1 and SCD with autoimmune thyroiditis in Case 2. After undergoing corresponding treatment, death was reported in Case 1 and improvement in Case 2. Analysis of the clinical manifestations and investigation of the underlying pathogenesis in such patients could help improve the rate of early diagnosis and allow timely treatment of SCD, thereby preventing disease progression and poor clinical outcomes.


Assuntos
Doenças Autoimunes , Degeneração Combinada Subaguda , Doenças Autoimunes/complicações , Doenças Autoimunes/diagnóstico , Humanos , Imageamento por Ressonância Magnética , Medula Espinal , Degeneração Combinada Subaguda/complicações , Degeneração Combinada Subaguda/diagnóstico , Degeneração Combinada Subaguda/patologia , Vitamina B 12
8.
BMC Vet Res ; 17(1): 247, 2021 Jul 18.
Artigo em Inglês | MEDLINE | ID: mdl-34275451

RESUMO

BACKGROUND: Pseudorabies virus (PRV), a member of the Alphaherpesviruses, is one of the most important pathogens that harm the global pig industry. Accumulated evidence indicated that PRV could infect humans under certain circumstances, inducing severe clinical symptoms such as acute human encephalitis. Currently, there are no antiviral drugs to treat PRV infections, and vaccines available only for swine could not provide full protection. Thus, new control measures are urgently needed. RESULTS: In the present study, kaempferol exhibited anti-PRV activity in mice through improving survival rate by 22.22 %, which was higher than acyclovir (Positive control) with the survival rate of 16.67 % at 6 days post infection (dpi); meanwhile, the survival rate was 0 % at 6 dpi in the infected-untreated group. Kaempferol could inhibit the virus replication in the brain, lung, kidney, heart and spleen, especially the viral gene copies were reduced by over 700-fold in the brain, which was further confirmed by immunohistochemical examination. The pathogenic changes induced by PRV infection in these organs were also alleviated. The transcription of the only immediate-early gene IE180 in the brain was significantly inhibited by kaempferol, leading to the decreased transcriptional levels of the early genes (EPO and TK). The expression of latency-associated transcript (LAT) was also inhibited in the brain, which suggested that kaempferol could inhibit PRV latency. Kaempferol-treatment could induce higher levels of IL-1ß, IL-4, IL-6, TNF-α and IFN-γ in the serum at 3 dpi which were then declined to normal levels at 5 dpi. CONCLUSIONS: These results suggested that kaempferol was expected to be a new alternative control measure for PRV infection.

9.
Med Phys ; 2021 Jul 26.
Artigo em Inglês | MEDLINE | ID: mdl-34309844

RESUMO

PURPOSE: To reduce the experience dependence during the orthognathic surgical planning that involves virtually simulating the corrective procedure for jaw deformities. METHODS: We introduce a geometric deep learning framework for generating reference facial bone shape models for objective guidance in surgical planning. First, we propose a surface deformation network to warp a patient's deformed bone to a set of normal bones for generating a dictionary of patient-specific normal bony shapes. Subsequently, sparse representation learning is employed to estimate a reference shape model based on the dictionary. RESULTS: We evaluated our method on a clinical dataset containing 24 patients, and compared it with a state-of-the-art method that relies on landmark-based sparse representation. Our method yields significantly higher accuracy than the competing method for estimating normal jaws, and maintains the midfaces of patients' facial bones as well as the conventional way. CONCLUSIONS: Experimental results indicate that our method generates accurate shape models that meet clinical standards.

10.
Clin Chim Acta ; 521: 131-136, 2021 Jul 08.
Artigo em Inglês | MEDLINE | ID: mdl-34245689

RESUMO

BACKGROUND: Due to the limitations like reverse causation and residual confounding commonly seen in the observational studies, the relationship between serum immunoglobulins and amyotrophic lateral sclerosis (ALS) remains unclear. METHODS: Summary statistics from large-scale genome-wide association studies (GWAS) among European ancestry populations (~15,000 individuals for serum immunoglobulins, and more than 36,000 individuals for ALS) were accessed and used in the discovery and replication phase, respectively. Polygenic risk score analysis was performed to test the polygenic association, and Mendelian randomization analysis was used to infer the causality. RESULTS: An inverse polygenic association was discovered between IgA and ALS, as well as between IgM and ALS. Such associations were however not replicated using a larger GWAS of ALS, and no causal association was observed for either IgA-ALS or IgM-ALS. For IgG and ALS, a positive polygenic association was both discovered [odds ratio (OR) = 1.18, 95% confidence interval (CI): 1.12-1.25, P = 5.9x10-7] and replicated (OR = 1.13, 95% CI: 1.06-1.20, P = 0.001). A causal association between IgG and ALS was suggested in the discovery analysis (OR = 1.06, 95 %CI: 1.02-1.10, P = 0.009), but it was not statistically significant in the replication analysis (OR = 1.07, 95 %CI: 0.90-1.24, P = 0.420). CONCLUSION: This study suggests a positive polygenic association between serum IgG and ALS.

11.
Fish Physiol Biochem ; 2021 Jul 29.
Artigo em Inglês | MEDLINE | ID: mdl-34324096

RESUMO

There are great differences in metabolic responses to different levels of carbohydrate among different carnivorous fish species. To explore metabolic responses of Chinese perch to moderate and high level of dietary carbohydrates, three diets containing 7.3% (LC), 17.5% (MC), and 27.5% (HC) of carbohydrates were provided to Chinese perch for 56 days. The results showed that MC and HC groups exhibited an increase in weight gain (WG) and hepatic glycogen content, and a decrease in feed conversion efficiency, compared with the LC group. The MC and HC groups also showed the increase in mRNA levels of phosphofructokinase and citrate synthase related to the aerobic oxidation pathway, which might be responsible for the increase in WG. Moreover, compared with the LC group, the HC group exhibited high levels of plasma indices (glucose, pyruvic acid, lactic acid, total triglyceride, total cholesterol, and low-density lipoprotein) and liver lipid resulting from the increased mRNA levels of fatty acid synthesis-related genes (ATP citrate lyase, acetyl-CoA carboxylase α, and fatty acid synthase), low level of crude protein caused by inhibition of TOR pathway, and liver damage induced by low antioxidant capacity and infiltration of inflammatory cells, but the MC group did not. The above results indicated that 17.5% dietary carbohydrate might be utilized effectively in Chinese perch and part carbohydrates were converted into glycogen to maintain glucose homeostasis; 27.5% dietary carbohydrate could not be fully utilized. The 27.5% carbohydrate diet induced the up-regulation of aerobic oxidation, glycogen synthesis, and fat synthesis pathways which might not be sufficient to maintain glucose homeostasis.

12.
Arch Virol ; 166(9): 2623-2625, 2021 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-34244860

RESUMO

Here, using viral metagenomics combined with conventional PCR, the complete genome sequence of a novel anellovirus (named anel-ch-zj and GenBank no. MT157223) from nasopharynx secretion specimens from hospitalized neonates was determined, and the deduced amino acid sequence of its ODF1 protein was found to be only 33.19%-39.33% identical to those of related anelloviruses with sequences available in the GenBank database, suggesting that it represents a putative new genus within the family Anelloviridae. PCR screening of 135 samples (including 45 nasopharynx secretion, 45 blood, and 45 fecal specimens collected from 45 individual hospitalized neonates) indicated that two nasopharynx secretion, two blood, and four fecal samples were positive for anel-ch-zj. Further PCR screening of 50 blood samples, 115 fecal samples, and 396 nasopharynx secretions collected from hospitalized children 1-5 years old did not yield any positive results. Whether this novel anellovirus detected in neonates is associated with specific diseases needs future investigation.

13.
Phytochemistry ; 190: 112893, 2021 Jul 28.
Artigo em Inglês | MEDLINE | ID: mdl-34332297

RESUMO

Four previously undescribed iridoid glycosides, including two bis-iridoid glycosides, and three undescribed lignans, together with 16 known analogues, were isolated from the fruits of Gardenia jasminoides Eills. Their structures were elucidated on basis of spectroscopic methods, and the absolute configurations of three of the unknown compounds were determined by interpretation of their electronic circular dichroic (ECD) and [α] [Formula: see text] data. The α-glucosidase inhibitory effects of the isolated compounds were evaluated and all the compounds exhibited slightly inhibitory activity with the values of IC50 greater than 50 µM.

14.
Cereb Cortex ; 2021 Jul 21.
Artigo em Inglês | MEDLINE | ID: mdl-34289027

RESUMO

Nociceptive processing in the human brain is complex and involves several brain structures and varies across individuals. Determining the structures that contribute to interindividual differences in nociceptive processing is likely to improve our understanding of why some individuals feel more pain than others. Here, we found specific parts of the cerebral response to nociception that are under genetic influence by employing a classic twin-design. We found genetic influences on nociceptive processing in the midcingulate cortex and bilateral posterior insula. In addition to brain activations, we found genetic contributions to large-scale functional connectivity (FC) during nociceptive processing. We conclude that additive genetics influence specific brain regions involved in nociceptive processing. The genetic influence on FC during nociceptive processing is not limited to core nociceptive brain regions, such as the dorsal posterior insula and somatosensory areas, but also involves cognitive and affective brain circuitry. These findings improve our understanding of human pain perception and increases chances to find new treatments for clinical pain.

15.
Radiologia (Engl Ed) ; 63(4): 345-357, 2021.
Artigo em Inglês | MEDLINE | ID: mdl-34246425

RESUMO

Interventional radiology is playing an increasingly important role in the local treatment of bone metastases; this treatment is usually done with palliative intent, although in selected patients it can be done with curative intent. Two main groups of techniques are available. The first group, centered on bone consolidation, includes osteoplasty/vertebroplasty, in which polymethyl methacrylate (PMMA) is injected to reinforce the bone and relieve pain, and percutaneous osteosynthesis, in which fractures with nondisplaced or minimally bone fragments are fixed in place with screws. The second group centers on tumor ablation. tumor ablation refers to the destruction of tumor tissue by the instillation of alcohol or by other means. Thermoablation is the preferred technique in musculoskeletal tumors because it allows for greater control of ablation. Thermoablation can be done with radiofrequency, in which the application of a high frequency (450 Hz-600 Hz) alternating wave to the tumor-bone interface achieves high temperatures, resulting in coagulative necrosis. Another thermoablation technique uses microwaves, applying electromagnetic waves in an approximate range of 900 MHz-2450 MHz through an antenna that is placed directly in the core of the tumor, stimulating the movement of molecules to generate heat and thus resulting in coagulative necrosis. Cryoablation destroys tumor tissue by applying extreme cold. A more recent, noninvasive technique, magnetic resonance-guided focused ultrasound surgery (MRgFUS), focuses an ultrasound beam from a transducer placed on the patient's skin on the target lesion, where the waves' mechanical energy is converted into thermal energy (65 °C-85 °C). Treatment should be planned by a multidisciplinary team. Treatment can be done with curative or palliative intent. Once the patient is selected, a preprocedural workup should be done to determine the most appropriate technique based on a series of factors. During the procedure, protective measures must be taken and the patient must be closely monitored. After the procedure, patients must be followed up.

16.
Pathol Oncol Res ; 27: 1609753, 2021.
Artigo em Inglês | MEDLINE | ID: mdl-34257614

RESUMO

Background: Chemotherapy failure causes high breast cancer recurrence and poor patient prognosis. Thus, we studied a cohort of novel biomarkers to predict chemotherapeutic response in breast cancer. In this study, miRNA expression profiling was performed on 10 breast cancer punctured specimens sensitive to chemotherapy (MP grade 4, 5) and 10 chemotherapy resistant (MP grade 1). Differentially expressed miRNAs were verified by qRT-PCR in 60 initial samples, 59 validated samples and 71 independent samples. A miRNA signature was generated using a Logistic regression model. A receiver operating characteristic (ROC) test was used to assess specificity and sensitivity of single miRNA and miRNA signature. Target genes regulated by miRNAs and their involved signaling pathways were analyzed using GO enrichment and KEGG software. MiRNAs expression were separately compared with ER, PR, HER2 immunohistochemical staining and different drugs. qRT-PCR showed that the high expression of miR-23a-3p, miR-200c-3p, miR-214-3p and the low expression of miR-451a and miR-638 were closely related to chemoresistance. According to the formula for calculating the drug resistance risk, patients in the high-risk group were more likely to develop chemotherapy resistance than the low-risk group. Bioinformatics analysis showed that 5 miRNAs and target genes are mainly involved in p53, ubiquitin-mediated proteolysis, mTOR, Wnt, cells skeletal protein regulation, cell adhesion and ErbB signaling pathways. miR-451a expression was associated with ER, HER-2 status and anthracyclines. A miRNA signature of chemotherapeutic response may be clinically valuable for improving current chemotherapy regimens of individual treatment for patients with breast cancer.

17.
J Colloid Interface Sci ; 603: 615-632, 2021 Jun 15.
Artigo em Inglês | MEDLINE | ID: mdl-34225068

RESUMO

Antibiotic resistanceand biofilm formation are the main challenges of bacterial infectious diseases, and enhancing the permeability of drugs to biofilms may be a promising strategy. Herein, we constructed a cationic chitosan coated ruthenium dioxide nanozyme (QCS-RuO2@RBT, SRT NSs)。RuO2 nanosheets (RuO2 NSs) are modified with positively charged Quaternary ammonium-chitosan (QCS) to improve biocompatibility, and enhance the interaction between RuO2 nanozymes and bacterial membranes. An antibacterial drug, [Ru(bpy)2(tip)]2+ (RBT) can be loaded onto QCS-RuO2 by π-π stacking and hydrophobic interaction. SRT NSs exhibit NIR light enhanced peroxidase-like catalytic activity, thereby effectively fighting against planktonic bacteria and damaging biofilms. In the biofilm, extracellular DNA (eDNA) was cleaved by high levels of hydroxyl radicals (•OH) catalyzed by SRT NSs, thereby disrupting the rigid biofilm. In addition, in vivo studies demonstrate that SRT NSs can significantly rescue skin wound infections and the chronic lung infection in mice caused by P. aeruginosa, and hold the same therapeutic efficacy as first-line clinically anchored anti P. aeruginosa drug ciprofloxacin. Accordingly, the research work has realized the efficient production of ·OH, and the permeability of drugs to biofilms.it provides a promising response strategy for the management of biofilm-associated infections, including chronic lung infection.

18.
Aging Cell ; : e13430, 2021 Jul 18.
Artigo em Inglês | MEDLINE | ID: mdl-34278704

RESUMO

Dental pulp stem cells (DPSCs) play a vital role in tooth restoration, regeneration, and homeostasis. The link between DPSC senescence and tooth aging has been well-recognized. ROR2 plays an important role in aging-related gene expression. However, the expression and function of ROR2 in DPSC aging remain largely unknown. In this study, we found that ROR2 expression was significantly decreased in aged pulp tissues and DPSCs. The depletion of ROR2 in young DPSCs inhibits their self-renewal capacity, while its overexpression in aged DPSCs restores their self-renewal capacity. Interestingly, we found that sphingomyelin (SM) is involved in the senescence of DPSCs regulated by ROR2. Mechanistically, we confirmed that ROR2 inhibited the phosphorylation of STK4, which promoted the translocation of Forkhead Box O1 (FOXO1) to the nucleus. STK4 inhibition or knockdown of FOXO1 markedly increased the proliferation of DPSCs and upregulated the expression of SMS1, which catalyzed SM biogenesis. Moreover, FOXO1 directly bound to the SMS1 promoter, repressing its transcription. Our findings demonstrated the critical role of the ROR2/STK4-FOXO1/SMS1 axis in the regulation of SM biogenesis and DPSC senescence, providing a novel target for antagonizing tooth aging.

19.
Microb Pathog ; : 105099, 2021 Jul 17.
Artigo em Inglês | MEDLINE | ID: mdl-34284087

RESUMO

BACKGROUND: Human papillomavirus (HPV) infection, especially persistent high risk HPV infection stands as the leading reason for cervical cancer morbidity. P53 protein can activate multiple tumor suppressor genes, leading to cervical cancer progression. In recent years, the relationship between P53 gene rs1042522 polymorphism and HPV infection has been investigated. However, their conclusions were contradictory and ambiguous. OBJECTIVES: The present meta-analysis is to estimate whether P53 rs1042522 polymorphism confers risk to HPV infection in cervical specimens. METHODS: Relevant literatures were searched by searching databases including Pubmed, Embase, the Cochrane library, China National Knowledge Infrastructure (CNKI). Search time is from database foundation to January 2021. RESULTS: Eight literatures were enrolled in the present meta-analysis. Positive finding between HPV infection of cervical specimens and P53 rs1042522 polymorphism was found in Brazilian population by allele contrast (Pro versus. Arg: OR = 0.52, 95%CI = 0.35-0.79), homozygote comparison (Pro/Pro versus. Arg/Arg: OR = 0.43, 95%CI = 0.20-0.94), and dominate genetic model (Pro/Pro + Arg/Pro versus. Arg/Arg: OR = 0.29, 95%CI = 0.09-0.93). The similar phenomenon was also found in Arabian population. CONCLUSION: We conclude that P53 rs1042522 polymorphism contributed a decreased risk to HPV infection in Brazilian and Arabian population.

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