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1.
Zool Res ; 43(1): 52-63, 2022 01 18.
Artigo em Inglês | MEDLINE | ID: mdl-34821086

RESUMO

The ability to sense temperature changes is crucial for mammalian survival. Mammalian thermal sensing is primarily carried out by thermosensitive transient receptor potential channels (Thermo-TRPs). Some mammals hibernate to survive cold winter conditions, during which time their body temperature fluctuates dramatically. However, the underlying mechanisms by which these mammals regulate thermal responses remain unclear. Using quantitative real-time polymerase chain reaction (qRT-PCR) and the Western blotting, we found that Myotis ricketti bats had high levels of heat-activated TRPs (e.g., TRPV1 and TRPV4) during torpor in winter and cold-activated TRPs (e.g., TRPM8 and TRPC5) during active states in summer. We also found that laboratory mice had high mRNA levels of cold-activated TRPs (e.g., Trpm8 and Trpc5) under relatively hot conditions (i.e., 40 °C). These data suggest that small mammals up-regulate the expression of cold-activated TRPs even under warm or hot conditions. Binding site analysis showed that some homeobox (HOX) transcription factors (TFs) regulate the expression of hot- and cold-activated TRP genes and that some TFs of the Pit-Oct-Unc (POU) family regulate warm-sensitive and cold-activated TRP genes. The dual-luciferase reporter assay results demonstrated that TFs HOXA9, POU3F1, and POU5F1 regulate TRPC5 expression, suggesting that Thermo-TRP genes are regulated by multiple TFs of the HOX and POU families at different levels. This study provides insights into the adaptive mechanisms underlying thermal sensing used by bats to survive hibernation.

2.
Philos Trans A Math Phys Eng Sci ; 380(2214): 20210124, 2022 Jan 10.
Artigo em Inglês | MEDLINE | ID: mdl-34802277

RESUMO

Prolonged school closure has been adopted worldwide to control COVID-19. Indeed, UN Educational, Scientific and Cultural Organization figures show that two-thirds of an academic year was lost on average worldwide due to COVID-19 school closures. Such pre-emptive implementation was predicated on the premise that school children are a core group for COVID-19 transmission. Using surveillance data from the Chinese cities of Shenzhen and Anqing together, we inferred that compared with the elderly aged 60 and over, children aged 18 and under and adults aged 19-59 were 75% and 32% less susceptible to infection, respectively. Using transmission models parametrized with synthetic contact matrices for 177 jurisdictions around the world, we showed that the lower susceptibility of school children substantially limited the effectiveness of school closure in reducing COVID-19 transmissibility. Our results, together with recent findings that clinical severity of COVID-19 in children is lower, suggest that school closure may not be ideal as a sustained, primary intervention for controlling COVID-19. This article is part of the theme issue 'Data science approach to infectious disease surveillance'.


Assuntos
COVID-19 , Idoso , Criança , Humanos , Pessoa de Meia-Idade , SARS-CoV-2 , Instituições Acadêmicas
3.
Orthop Surg ; 2021 Nov 08.
Artigo em Inglês | MEDLINE | ID: mdl-34747564

RESUMO

OBJECTIVE: To investigate the role of autologous platelet-rich plasma (PRP) on the repair of meniscal white-white zone injury through promoting the proliferation of canine bone marrow-derived mesenchymal stem cells (BMSCs). METHODS: A total of 24 beagle dogs were selected to construct meniscal white-white zone injury models in both lateral knee joints. All subjects were divided into four groups: control, BMSCs, PRP, and PRP + BMSCs. Immunohistochemistry was applied in the expression detection of type I and type II collagens. HE staining and methylene blue staining were performed to observe the injury of cartilage of lateral femoral condyle in each group. ELISA was used to detect the osteopontin (OPN) content in cartilage of lateral femoral condyle. HE staining and magnetic resonance imaging (MRI) were used to observe the healing of meniscus in each group. Outcome measures include the expression of OPN in the synovial fluid of knee joint, the expression of type I collagen and type II collagen, the healing of meniscus injury, and the damage degree of lateral femoral condyle cartilage. RESULTS: Compared with the control group, the expressions of type I and type II collagens were enhanced in the PRP group and the PRP + BMSCs group. Compared with 1 week before modeling, the expression of OPN was elevated in the control group and the BMSCs group at 3 weeks after modeling. There were no significant differences in the above indicators between the PRP group and the PRP + BMSCs group. According to MRI and pathological section after HE staining, meniscal healing in the PRP group and the PRP + BMSCs group was significantly improved as compared to that of the control group and the BMSCs group (all P < 0.05), and there was no significant difference between the PRP group and the PRP + BMSCs group (P > 0.05). All subjects were divided into the non-healing group and the healing group in accordance with the HE staining results in previous experiment. The injury of cartilage of lateral femoral condyle was significantly heavier in the non-healing group than that in the healing group. CONCLUSION: The application of PRP alone or in combination with BMSCs could promote the clinical healing rate of meniscal white-white zone injury.

4.
J Drug Target ; : 1-15, 2021 Nov 10.
Artigo em Inglês | MEDLINE | ID: mdl-34727794

RESUMO

Hepatocellular carcinoma (HCC) is one of the most common malignant cancer in the world, which greatly threatens human health. However, the routine treatment strategies for HCC have failed to specifically eradicate the tumorigenic cells, leading to the occurrence of metastasis and recurrence. To improve treatment efficacies, the development of novel effective technologies is urgently required. Recently, nanotechnologies have gained the extensive attention in cancer targeted therapy, which could provide a promising way for HCC clinical practice. However, a successful cancer management depends on accurate diagnosis of the tumour along with precise therapeutic protocol, thereby predicting the tumour response to existing therapies. The synergistic effect of targeted therapeutic systems and imaging approaches (also called 'imaging-guided cancer treatment') may establish a more effective platform for individual cancer care. This review outlines the recent advanced nano-targeted and -traceable therapeutic strategies for HCC management. The multifunctional nano agents that have both diagnosis and therapy abilities are highlighted. Finally, we conclude with our perspectives on the future development and challenges of HCC nanotheranostics.

5.
Front Cell Dev Biol ; 9: 758220, 2021.
Artigo em Inglês | MEDLINE | ID: mdl-34746150

RESUMO

G protein-coupled receptors (GPCRs) are transmembrane receptor proteins that trigger numerous intracellular signaling pathways in response to the extracellular stimuli. The GPCRs superfamily contains enormous structural and functional diversity and mediates extensive biological processes. Until now, critical roles have been established in many diseases, including osteoarthritis (OA). Existing studies have shown that GPCRs play an important role in some OA-related pathogenesis, such as cartilage matrix degradation, synovitis, subchondral bone remodeling, and osteophyte formation. However, current pharmacological treatments are mostly symptomatic and there is a paucity of disease-modifying OA drugs so far. Targeting GPCRs is capable of inhibiting cartilage matrix degradation and synovitis and up-regulating cartilage matrix synthesis, providing a new therapeutic strategy for OA. In this review, we have comprehensively summarized the structures, biofunctions, and the novel roles of GPCRs in the pathogenesis and treatment of OA, which is expected to lay the foundation for the development of novel therapeutics against OA. Even though targeting GPCRs may ameliorate OA progression, many GPCRs-related therapeutic strategies are still in the pre-clinical stage and require further investigation.

6.
PeerJ ; 9: e12361, 2021.
Artigo em Inglês | MEDLINE | ID: mdl-34760377

RESUMO

Tooth replacement rate is an important feature related to feeding mechanics and food choices for dinosaurs. However, only a few data points are available for sauropod dinosaurs, partially due to rarity of relevant fossil material. Four somphospondylan sauropod species have been recovered from the Lower Cretaceous Aptian-Albian Haoling Formation in the Ruyang Basin, Henan Province of central China, but no cranial material has been reported except for a single crown. Here we report the discovery of the rostral portion of a left dentary with replacement teeth in its first five alveoli. Comparative anatomical study shows the partial dentary can be assigned to a member of early diverging somphospondylans. The non-destructive tooth length-based approach to estimating tooth formation time and replacement rate is adopted here. The estimated tooth replacement rate is 76 days, faster than that of Brachiosaurus (83 days) and much lower than typical late diverging lithostrotian titanosaurians (20 days). Thus, this discovery adds an intermediate tooth replacement rate in the evolution of titanosauriform sauropods and supports the idea that evolution of tooth replacement rate is clade-specific. This discovery also provides more information to understand the Ruyang sauropod assemblage, which includes one of the most giant dinosaurs to have walked our Earth (Ruyangosaurus giganteus).

7.
Artigo em Inglês | MEDLINE | ID: mdl-34767133

RESUMO

PURPOSE: Endoplasmic reticulum stress (ERS) plays a crucial role in myocardial ischemia-reperfusion injury (MIRI). Cellular FLICE-inhibitory protein (cFLIP) is an essential regulator of apoptosis and plays a major role in regulating ERS. The present study aimed to investigate the effects of long isoform cFLIP (cFLIPL) on endogenous apoptosis and the mechanism of ERS in MIRI. METHODS: The cFLIPL recombinant adenovirus vector was used to infect H9c2 cells and Sprague-Dawley (SD) rats. After infection for 72 h, ischemia was induced for 30 min, and reperfusion was then performed for 2 h to establish the MIRI model in SD rats. H9c2 cells were hypoxic for 4 h and then reoxygenated for 12 h to simulate ischemia/reperfusion (I/R) injury. Model parameters were evaluated by assessing cardiomyocyte viability, cell death (apoptosis), and ERS-related protein expression. In addition, tunicamycin (TM), an ERS agonist, was also added to the medium for pretreatment. Coimmunoprecipitation (Co-IP) of cFLIPL and p38 MAPK protein was performed. RESULTS: cFLIPL expression was decreased in I/R injury and hypoxia/reoxygenation (H/R) injury, and cFLIPL overexpression reduced myocardial infarction in vivo and increased the viability of H9c2 cells in vitro. I/R and H/R upregulated the protein expression of GRP78, IRE-1, and PERK to induce ERS and apoptosis. Interestingly, overexpression of cFLIPL significantly inhibited ERS and subsequent apoptosis, which was reversed by an agonist of ERS. Moreover, Co-IP showed that cFLIPL attenuated ERS and was associated with inhibiting the activation of p38 protein. CONCLUSION: The expression of cFLIPL is significantly downregulated in MIRI, and it is accompanied by excessive ERS and apoptosis. Upregulated cFLIPL suppresses ERS to reduce myocardial apoptosis, which is associated with inhibiting the activity of p38 MAPK. Therefore, cFLIPL may be a potential intervention target for MIRI.

8.
Front Genet ; 12: 765400, 2021.
Artigo em Inglês | MEDLINE | ID: mdl-34759961

RESUMO

Rationale: Severe asthma is a heterogeneous disease with multiple molecular mechanisms. Gene expression studies of asthmatic bronchial epithelial cells have provided biological insights and underscored possible pathological mechanisms; however, the molecular basis in severe asthma is still poorly understood. Objective: The objective of this study was to identify the features of asthma and uncover the molecular basis of severe asthma in distinct molecular phenotype. Methods: The k-means clustering and differentially expressed genes (DEGs) were performed in 129 asthma individuals in the Severe Asthma Research Program. The DEG profiles were analyzed by weighted gene co-expression network analysis (WGCNA), and the expression value of each gene module in each individual was annotated by gene set variation analysis (GSVA). Results: Expression analysis defined five stable asthma subtype (AS): 1) Phagocytosis-Th2, 2) Normal-like, 3) Neutrophils, 4) Mucin-Th2, and 5) Interferon-Th1 and 15 co-expressed gene modules. "Phagocytosis-Th2" enriched for receptor-mediated endocytosis, upregulation of Toll-like receptor signal, and myeloid leukocyte activation. "Normal-like" is most similar to normal samples. "Mucin-Th2" preferentially expressed genes involved in O-glycan biosynthesis and unfolded protein response. "Interferon-Th1" displayed upregulation of genes that regulate networks involved in cell cycle, IFN gamma response, and CD8 TCR. The dysregulation of neural signal, REDOX, apoptosis, and O-glycan process were related to the severity of asthma. In non-TH2 subtype (Neutrophils and Interferon-Th1) with severe asthma individuals, the neural signals and IL26-related co-expression module were dysregulated more significantly compared to that in non-severe asthma. These data infer differences in the molecular evolution of asthma subtypes and identify opportunities for therapeutic development. Conclusions: Asthma is a heterogeneous disease. The co-expression analysis provides new insights into the biological mechanisms related to its phenotypes and the severity.

10.
Nat Mater ; 2021 Nov 18.
Artigo em Inglês | MEDLINE | ID: mdl-34795400

RESUMO

Optically addressable spin defects in silicon carbide (SiC) are an emerging platform for quantum information processing compatible with nanofabrication processes and device control used by the semiconductor industry. System scalability towards large-scale quantum networks demands integration into nanophotonic structures with efficient spin-photon interfaces. However, degradation of the spin-optical coherence after integration in nanophotonic structures has hindered the potential of most colour centre platforms. Here, we demonstrate the implantation of silicon vacancy centres (VSi) in SiC without deterioration of their intrinsic spin-optical properties. In particular, we show nearly lifetime-limited photon emission and high spin-coherence times for single defects implanted in bulk as well as in nanophotonic waveguides created by reactive ion etching. Furthermore, we take advantage of the high spin-optical coherences of VSi centres in waveguides to demonstrate controlled operations on nearby nuclear spin qubits, which is a crucial step towards fault-tolerant quantum information distribution based on cavity quantum electrodynamics.

11.
Pathol Res Pract ; 229: 153692, 2021 Nov 19.
Artigo em Inglês | MEDLINE | ID: mdl-34847369

RESUMO

BACKGROUND: Hepatocellular carcinoma (HCC) is a substantial health concern worldwide. Increasing studies have suggested that circle RNAs (circRNAs) function as new regulators in HCC progression. The present work explored the role of hsa_circ_0007059 (circ_0007059) in the developing process of hepatocarcinogenesis. METHODS: The circ_0007059 level in HCC was determined by reverse transcriptase quantitative polymerase chain reaction (RT-qPCR) and northern blot. Its biological role in HCC cells was assessed using 3-(4,5-Dimethylthiazol-2-yl)- 2,5-diphenyltetrazolium bromide (MTT), colony formation, flow cytometry, Transwell, sphere formation and western blotting analyses. Bioinformatics analysis, luciferase reporter, and RNA immunoprecipitation (RIP) assays were used to test the regulatory mechanisms of circ_0007059. RESULTS: Our results revealed that circ_0007059 expression was downregulated in HCC samples and cells. Moreover, circ_0007059 overexpression inhibited HCC cell proliferation, migration, invasion, and stem cell-like property, and strengthened cell apoptosis. In mechanism, circ_0007059 suppressed AKT/mTOR pathway by positively regulating phosphatase and tensin homolog (PTEN) expression. Additionally, circ_0007059 acted as a positive regulator of PTEN through controlling the availability of miR-421. Rescue assays demonstrated that PTEN knockdown or SC79 (AKT agonist) eliminated the effect of circ_0007059 on HCC cell phenotypes. CONCLUSION: Circ_0007059 sponges miR-421 to inhibit oncogenic cellular process in HCC by mediating the PTEN-AKT/mTOR pathway.

12.
Front Plant Sci ; 12: 724559, 2021.
Artigo em Inglês | MEDLINE | ID: mdl-34804081

RESUMO

Xylem development plays an important role in the wood formation of plants. In this study, we found that xylem development was a rapid thickening process characterized by initially rapid increases in the number of tracheary elements and fiber cells and the thickness of the secondary walls that later plateaued. Transcriptome analysis showed that the xylan and lignin biosynthetic pathways, which are involved in the early rapid thickening of the xylem, were mainly upregulated in the second month. The expression of a total of 124 transcription factors (TFs), including 28 NAC TFs and 31 MYB TFs, peaked in 2- and 3-month-old plants compared with 1-month-old plants. Based on previous studies and the key cis-acting elements secondary wall NAC-binding elements, secondary wall MYB-responsive elements, W-box and TGTG[T/G/C], 10 TFs related to xylem development, 50 TFs with unknown function, 98 cell wall biosynthetic genes, and 47 programmed cell death (PCD) genes were used to construct a four-layer transcriptional regulatory network (TRN) with poplar NAC domain TFs to characterize the transcriptional regulation of cell wall biosynthesis and PCD in Populus tomentosa. The proteome revealed that post-transcriptional modification may be widely involved in lignification development. Overall, our results revealed that xylem development is a rapid thickening process in P. tomentosa, and expression patterns varied temporally from cell division to cell death.

13.
Transl Androl Urol ; 10(10): 3815-3825, 2021 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-34804824

RESUMO

Background: The diagnostic methods of prostate cancer (PCa) present major drawbacks in that serum prostate specific antigen (PSA) testing lacks specificity for PCa and prostate needle biopsy is a painful and highly invasive procedure for patients. Thus, new alternative screening methods which are specific and non-invasive both in the early detection and in the clinical definitive diagnosis of PCa are in urgent need. Long non-coding RNA MYU has been shown to promote PCa cell proliferation and migration, and is significantly upregulated both at the cellular and tumor tissue level. Therefore, long non-coding RNA MYU may be a new potential diagnostic biomarker for PCa. Methods: In the present study, we successfully developed a highly sensitive digital PCR assay to detect long non-coding RNA in clinical urine samples. dPCR was carried out using Qx200 ddPCR EvaGreen Supermix (Bio-Rad) according to the manufacturer's instructions. Results: Our results indicated that the digital PCR assay showed better linearity, repeatability, and reproducibility when compared with real-time quantitative PCR. In addition, we identified the normalized MYU level and used the digital PCR assay to measure it in 100 clinical urine samples. Our study showed that the normalized MYU level is a promising diagnostic biomarker for predicting and evaluating the malignancy of PCa. Conclusions: Our findings presented a non-invasive liquid biopsy method to detect an alternative diagnostic parameter which can assist the diagnosis of PCa in clinical practice.

14.
ACS Nano ; 2021 Nov 22.
Artigo em Inglês | MEDLINE | ID: mdl-34806870

RESUMO

The dense extracellular matrix (ECM) in tumor tissues resists drug diffusion into tumors and leads to a poor prognosis. To address this problem, glucose oxidase (GOx)-modified ferritin loaded with luminol-curcumin was fabricated. Once delivered to the tumor, this luminol-based self-illuminating nanocage could actively convert glucose to reactive oxygen species (ROS) to achieve starvation therapy. Then, excessive ROS were transmitted to luminol, thereby emitting 425 nm blue-violet light. Momentarily, light was further absorbed by curcumin and ROS production was amplified. Abundant ROS helps break down the ECM network to penetrate deep into tumors. In addition, ROS produced after cell internalization can induce apoptosis of tumor cells by decreasing the mitochondrial membrane potential and can promote ferroptosis by consuming reduced glutathione. Effective penetration and multiple pathways inducing tumor cell death contributed to the efficient antitumor effect (tumor inhibition rate of GOx-modified ferritin loaded with luminol-curcumin: 71.73%). This study developed a glucose-driven self-illuminating nanocage for active tumor penetration via ROS-mediated destruction of the ECM and provided the synergetic mechanism of apoptosis and ferroptosis.

15.
Chem Biodivers ; : e2100707, 2021 Nov 05.
Artigo em Inglês | MEDLINE | ID: mdl-34741384

RESUMO

Fifteen metabolites, including two flavonols (1-2), three lignans (3-5), and ten diterpenoids (6-15), were isolated from the leaves of Pinus yunnanensis. Among them, flavanonol (1) were identified as undescribed flavonol derivative with natural rarely B-ring fission lactone. Massive spectroscopic methods, the DP4+ probabilities and CD/ECD calculations were applied to establish the structure of component 1. Among these compounds, taxifolin (2) showed potent cytotoxicity, having IC50 values from 21.33 to 45.48 µg/mL, it also showed broad antibacterial activity against human pathogens with MIC values from 32 to 64 µg/mL.

16.
Appl Environ Microbiol ; : AEM0192121, 2021 Nov 24.
Artigo em Inglês | MEDLINE | ID: mdl-34818106

RESUMO

Legionella pneumophila (LP) widely exists in natural and artificial water environments, which facilitates LP to infect people. LP infection causes Legionnaires' disease (LD), which is an important but relatively uncommon respiratory infection. Approximately 90% of LD is caused by L. pneumophila serogroup 1 (Lp1). Meteorological conditions may affect the infectivity and virulence of Lp1, but the exact relationship between them is still unclear. In this study, we evaluated the virulence of Lp1 by screening of total 156 Lp1 strains isolated from cooling tower water in different region of China by detecting their abilities to activate NF-κB signaling pathway in vitro. In addition, we screened the distribution of some selected virulence genes in these strains. The virulence, virulence gene distribution and the meteorological factors were analyzed. We found that both the virulence and the distribution of virulence genes had a certain regional and meteorological correlation. Although loss of several virulence genes showed significant effects on the virulence of Lp1 strains, the distribution of virulence genes had very limited effects on the virulence of Lp1. IMPORTANCE LD is likely to be under-recognized in many countries. Due to the widespread existence of LP in natural and artificial water environments, and to the lack of cross-protection against different strains, LP is a potentially serious threat to human health. Therefore, effective monitoring of the virulence of LP in the water environment is very important to prevent and control the prevalence of LD. Understanding the virulence of LP can not only help us to predict the risk of possible outbreaks in advance, but can also enable more targeted clinical treatment. This study highlights the importance of understanding the epidemiology and ecology of LP isolated from public facilities in terms of public health and biology. Due to the potential for water sources to harbor and disseminate LP, and to the fact that geographical conditions influence the virulence of LP, timely and accurate LP virulence surveillance is urgently needed.

17.
Talanta ; : 123088, 2021 Nov 23.
Artigo em Inglês | MEDLINE | ID: mdl-34838324

RESUMO

Both single-atom nanozymes (SAzymes) and protein-template metal nanoparticles have attracted comprehensive attention in several respects owing to their excellent catalytic performance, green facile synthesis process, and robustness. Herein, the peroxidase-like activity of single-atom copper anchored on bovine hemoglobin-template gadolinium nanoparticles (Cu,Gd@BHbFITC NPs) were successfully synthesized and two sensitive turn-on fluorescence strategies for tyrosinase (TYR) activity sensing were proposed for the first time. For strategy Ⅰ, TYR sensing was carried out from 1.00 to 7.80 U/mL with the detection limit (LOD) of 0.20 U/mL based on the fluorescence resonance energy transfer (FRET) between the fluorescein isothiocyanate (FITC) and the in situ generated polydopamine dots (PDA-dots). For strategy Ⅱ, The LOD of TYR was 0.05 U/mL with the linear range of 0.40-19.70 U/mL based on the elimination of inner-filter effect (IEF) between FITC and the reaction product (RC) of phenol and 4-Aminoantipyrine (AAP). The smartphone-assisted sensing platform was applied to construct the on-site detection of TYR with both strategies. The developed probe possessed good selectivity and was successfully utilized to TYR detection in serum samples.

18.
Artigo em Inglês | MEDLINE | ID: mdl-34721625

RESUMO

Distraction osteogenesis (DO) is an efficient strategy that is employed for the treatment of large bone defects in craniomaxillofacial surgery. Despite its utility, however, DO is associated with a prolonged consolidation phase and a high complication rate that hinder its more widespread utilization. Panax notoginseng saponin (PNS) is a traditional Chinese medicine that is frequently administered for the treatment of a range of conditions. Herein, we explored the ability of PNS treatment to influence osteogenic differentiation using both rabbit bone marrow mesenchymal cells (BMSCs) and a model of mandibular DO. BMSC proliferation was assessed via CCK-8 assay, while osteogenic differentiation was monitored through ALP and alizarin red S staining. A PCR approach was used to evaluate the expression of genes associated with osteogenesis (ALP, Runx2, and OCN) and genes linked to the TGF pathway (TßR-II, SMAD2, SMAD3, and PPM1A). For in vivo experiments, treated BMSCs were locally injected into the DO gap, with PNS being injected into treated rabbits every other day throughout the experimental period. The quality of the regenerative process was assessed via scanning electron microscopy (SEM), energy dispersive spectroscopy (EDS), X-ray imaging, and hematoxylin and eosin (H&E) staining. These analyses revealed that PNS was able to promote BMSC osteogenesis and mandibular generation, driving the upregulation of osteogenesis-related genes at the mRNA levels through the modulation of the TGF-ß1/Smad pathway. Consistently, the overexpression or silencing of TßR-II in PNS-treated BMSCs was sufficient to modulate their osteogenic potential. Analyses of in vivo mandibular DO outcomes revealed significantly augmented new bone growth in the PNS-treated group relative to control animals, with maximal osteogenesis in the group overexpressing rabbit TßR-II. Together, these results highlight the PNS as a promising and cost-effective therapeutic tool with the potential to enhance bone regeneration in clinical contexts through the modulation of the TGF-ß1/Smad pathway.

19.
Dis Markers ; 2021: 1986159, 2021.
Artigo em Inglês | MEDLINE | ID: mdl-34721731

RESUMO

Objective: Dysregulation of cell cycle progression (CCP) is one of the hallmarks of cancer. Here, our study is aimed at developing a CCP-derived gene signature for predicting high-risk population of hepatocellular carcinoma (HCC). Methods: Our study retrospectively analyzed the transcriptome profiling and clinical information of HCC patients from The Cancer Genome Atlas (TCGA) and International Cancer Genome Consortium (ICGC) projects. Uni- and multivariate cox regression models were conducted for identifying which hallmarks of cancer were risk factors of HCC. CCP-derived gene signature was developed with LASSO method. The predictive efficacy was verified by ROC curves and subgroup analyses. A nomogram was then generated and validated by ROC, calibration, and decisive curves. Immune cell infiltration was estimated with ssGSEA method. Potential small molecular compounds were predicted via CTRP and CMap analyses. The response to chemotherapeutic agents was evaluated based on the GDSC project. Results: Among hallmarks of cancer, CCP was identified as a dominant risk factor for HCC prognosis. CCP-derived gene signature displayed the favorable predictive efficacy in HCC prognosis independent of other clinicopathological parameters. A nomogram was generated for optimizing risk stratification and quantifying risk evaluation. CCP-derived signature was in relation to immune cell infiltration, HLA, and immune checkpoint expression. Combining CTRP and CMap analyses, fluvastatin was identified as a promising therapeutic agent against HCC. Furthermore, CCP-derived signature might be applied for predicting the response to doxorubicin and gemcitabine. Conclusion: Collectively, CCP-derived gene signature was a promising marker in prediction of survival outcomes and therapeutic responses for HCC patients.

20.
Anim Reprod ; 18(3): e20210031, 2021.
Artigo em Inglês | MEDLINE | ID: mdl-34840610

RESUMO

Porcine somatic cell nuclear transfer (SCNT) plays an important role in many areas of research. However, the low efficiency of SCNT in porcine embryos limits its applications. Porcine embryos contain high concentrations of lipid, which makes them vulnerable to oxidative stress. Some studies have used melatonin to reduce reactive oxygen species damage. At present there are many reports concerning the effect of exogenous melatonin on porcine SCNT. Some studies suggest that the addition of melatonin can increase the number of blastocyst cells, while others indicate that melatonin can reduce the number of blastocyst cells. Therefore, a meta-analysis was carried out to resolve the contradiction. In this study, a total of 63 articles from the past 30 years were analyzed, and six papers were finally selected. Through the analysis, it was found that the blastocyst rate was increased by adding exogenous melatonin. Melatonin had no effect on cleavage rate or the number of blastocyst cells, but did decrease the number of apoptotic cells. This result is crucial for future research on embryo implantation.

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