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2.
Ther Adv Respir Dis ; 18: 17534666241271990, 2024.
Artículo en Inglés | MEDLINE | ID: mdl-39136335

RESUMEN

Pulmonary hypertension (PH) is a chronic progressive disease with high mortality. There has been more and more research focusing on the role of AMPK in PH. AMPK consists of three subunits-α, ß, and γ. The crosstalk among these subunits ultimately leads to a delicate balance to affect PH, which results in conflicting conclusions about the role of AMPK in PH. It is still unclear how these subunits interfere with each other and achieve balance to improve or deteriorate PH. Several signaling pathways are related to AMPK in the treatment of PH, including AMPK/eNOS/NO pathway, Nox4/mTORC2/AMPK pathway, AMPK/BMP/Smad pathway, and SIRT3-AMPK pathway. Among these pathways, the role and mechanism of AMPK/eNOS/NO and Nox4/mTORC2/AMPK pathways are clearer than others, while the SIRT3-AMPK pathway remains still unclear in the treatment of PH. There are drugs targeting AMPK to improve PH, such as metformin (MET), MET combination, and rhodiola extract. In addition, several novel factors target AMPK for improving PH, such as ADAMTS8, TUFM, and Salt-inducible kinases. However, more researches are needed to explore the specific AMPK signaling pathways involved in these novel factors in the future. In conclusion, AMPK plays an important role in PH.


Asunto(s)
Proteínas Quinasas Activadas por AMP , Hipertensión Pulmonar , Transducción de Señal , Humanos , Hipertensión Pulmonar/fisiopatología , Hipertensión Pulmonar/tratamiento farmacológico , Hipertensión Pulmonar/enzimología , Proteínas Quinasas Activadas por AMP/metabolismo , Animales
3.
Curr Mol Med ; 2024 May 16.
Artículo en Inglés | MEDLINE | ID: mdl-38757326

RESUMEN

Obstructive sleep apnea [OSA] is widespread in the population and affects as many as one billion people worldwide. OSA is associated with dysfunction of the brain system that controls breathing, which leads to intermittent hypoxia [IH], hypercapnia, and oxidative stress [OS]. The number of NOD-like receptor family pyrin domain-containing [NLRP3] inflammasome was increased after IH, hypercapnia, and OS. NLRP3 inflammasome is closely related to inflammation. NLRP3 inflammasome causes a series of inflammatory diseases by activating IL-1ß and IL-18. Subsequently, NLRP3 inflammasome plays an important role in the complications of OSA, including Type 2 diabetes [T2DM], coronary heart disease [CHD], hypertension, neuroinflammation, and depression. This review will introduce the basic composition and structure of the NLRP3 inflammasome and focus on the relationship between the NLRP3 inflammasome and OSA and OSA complications. We can deeply understand how NLRP3 inflammasome is strongly associated with OSA and OSA complications.

4.
Plant Dis ; 2024 Feb 28.
Artículo en Inglés | MEDLINE | ID: mdl-38416046

RESUMEN

Forever Summer Hydrangea (Hydrangea macrophylla) is a common flowering plant in the Yangtze River Valley area of China, and it is widely cultivated globally (Chen et al. 2015). In July 2023, H. macrophylla leaves exhibiting visible diseased lesions were reported in a nursery in Wuhu, Anhui Province, China. The incidence reached 40% in a 0.2 ha area. The primary disease symptom was multiple irregular necrotic spots (0.5 to 1 mm in diameter) appearing on the leaves. These spots on the leaves were faded yellow around the perimeter and grayish brown in the center.). 15 leaf samples were sterilized with 75% alcohol and rinsed three times in sterile distilled water, then transferred to antibiotic-added potato dextrose agar (PDA) for incubation at 27°C. The colonies were fluffy, flocculent, or hairy, dark green, gray-green to gray-brown in color, and spreading or protruding punctate with a colorless halo on PDA. The conidiophores were brown to dark brown, smooth or rough surface, mostly unbranched, clearly differentiated, erect or curved. The conidia displayed a light brown to brown hue, lemon shape, fusiform, elongated ellipsoid or others with obvious spore markings and spore umbilicus. Genomic DNA was extracted from fungal colonies on infected leaves of three collections separately (Braun et al. 2003) and the internal transcribed spacer regions (ITS), actin (ACT) genes and partial translation elongation factor-l-alpha (EF) were amplified and sequenced using the primers ITS1/4 (Yin et al. 2012), ACT-512F/ACT-783R and EF 1-728F/986R (Carbone and Kohn 1999), respectively. DNA sequences of isolates were identical and deposited in GenBank (accession no. OR362754 for ITS, OR611929 for ACT and PP209106 for EF). The consensus sequences from ITS, EF and ACT showed 100%, 98.98% and 100% identical to Cladosporium strains (accession no. OQ186140.1, MT154169.1 and OL322092.1), respectively. To confirm the pathogenicity of the isolates, hydrangeas were planted in 15-cm pots containing commercial potting mix (one plant/pot). Three healthy plants were inoculated at the five to eight leaf stage by spraying 50 µL of the isolate conidial suspension (4 × 106 spores/mL) on healthy leaves. Three plants treated with sterile distilled water were used as controls. After inoculation, all plants were placed in a humidity chamber (>95% relative humidity, 26°C) for 48 h and then transferred to a greenhouse at 22/27°C. All inoculated leaves exhibited symptoms similar to those observed in the nursery 10 days after inoculation, while no symptoms were observed for control leaves. The fungus was re-isolated and confirmed to be C. tenuissimum. Based on the above morphological characterization and molecular identification, the causal agent for this leaf spot disease was identified as C. tenuissimum. Although C. tenuissimum has been reported to cause disease on H. paniculata in northern China (Li et al.2021), this is the first time that C. tenuissimum has been found on H. macrophylla in southern China. This new disease of H. macrophylla caused by C. tenuissimum is a threat to urban greening and is worth further investigation.

5.
Cell Adh Migr ; 17(1): 1-15, 2023 12.
Artículo en Inglés | MEDLINE | ID: mdl-37909712

RESUMEN

The mammalian Sterile 20-like kinase 1/2 (MST1/2) belongs to the serine/threonine (GC) protein kinase superfamily. Collective studies confirm the vital role MST1/2 in inflammation and immunity. MST1/2 is closely related to the progress of inflammation. Generally, MST1/2 aggravates the inflammatory injury through MST1-JNK, MST1-mROS, MST1-Foxo3, and NF-κB pathways, as well as several regulatory factors such as tumor necrosis factor-α (TNF-α), mitochondrial extension factor 1 (MIEF1), and lipopolysaccharide (LPS). Moreover, MST1/2 is also involved in the regulation of immunity to balance immune activation and tolerance by regulating MST1/2-Rac, MST1-Akt1/c-myc, MST1-Foxos, MST1-STAT, Btk pathways, and lymphocyte function-related antigen 1 (LFA-1), which subsequently prevents immunodeficiency syndrome and autoimmune diseases. This article reviews the effects of MST1/2 on inflammation and immunity.


Asunto(s)
Inflamación , Proteínas Serina-Treonina Quinasas , Animales , Humanos , Proteínas Serina-Treonina Quinasas/metabolismo , Inflamación/patología , Factor de Necrosis Tumoral alfa/metabolismo , Factor de Necrosis Tumoral alfa/farmacología , Mitocondrias/metabolismo , FN-kappa B/metabolismo , Apoptosis , Mamíferos/metabolismo , Factores de Elongación de Péptidos/metabolismo , Factores de Elongación de Péptidos/farmacología , Proteínas Mitocondriales/metabolismo , Proteínas Mitocondriales/farmacología
8.
Mater Today Bio ; 19: 100597, 2023 Apr.
Artículo en Inglés | MEDLINE | ID: mdl-36910270

RESUMEN

Osteoarthritis (OA) and rheumatoid arthritis (RA) are chronic and progressive inflammatory joint diseases that affect a large population worldwide. Intra-articular administration of various therapeutics is applied to alleviate pain, prevent further progression, and promote cartilage regeneration and bone remodeling in both OA and RA. However, the effectiveness of intra-articular injection with traditional drugs is uncertain and controversial due to issues such as rapid drug clearance and the barrier afforded by the dense structure of cartilage. Nanoparticles can improve the efficacy of intra-articular injection by facilitating controlled drug release, prolonged retention time, and enhanced penetration into joint tissue. This review systematically summarizes nanoparticle-based therapies for OA and RA management. Firstly, we explore the interaction between nanoparticles and joints, including articular fluids and cells. This is followed by a comprehensive analysis of current nanoparticles designed for OA/RA, divided into two categories based on therapeutic mechanisms: direct therapeutic nanoparticles and nanoparticles-based drug delivery systems. We highlight nanoparticle design for tissue/cell targeting and controlled drug release before discussing challenges of nanoparticle-based therapies for efficient OA and RA treatment and their future clinical translation. We anticipate that rationally designed local injection of nanoparticles will be more effective, convenient, and safer than the current therapeutic approach.

9.
Biol Psychiatry ; 94(3): 262-277, 2023 08 01.
Artículo en Inglés | MEDLINE | ID: mdl-36842495

RESUMEN

BACKGROUND: The ventromedial prefrontal cortex has been viewed as a locus for storage and recall of extinction memory. However, the synaptic and cellular mechanisms underlying these processes remain elusive. METHODS: We combined transgenic mice, electrophysiological recording, activity-dependent cell labeling, and chemogenetic manipulation to analyze the role of adaptor protein APPL1 in the ventromedial prefrontal cortex in fear extinction retrieval. RESULTS: We found that both constitutive and conditional APPL1 knockout decreased NMDA receptor (NMDAR) function in the ventromedial prefrontal cortex and impaired fear extinction retrieval. Moreover, APPL1 undergoes nuclear translocation during extinction retrieval. Blocking APPL1 nucleocytoplasmic translocation reduced NMDAR currents and disrupted extinction retrieval. We also identified a prefrontal neuronal ensemble that is both necessary and sufficient for the storage of extinction memory. Inducible APPL1 knockout in this ensemble abolished NMDAR-dependent synaptic potentiation and disrupted extinction retrieval, while chemogenetic activation of this ensemble simultaneously rescued the impaired behaviors. CONCLUSIONS: Our results indicate that a prefrontal neuronal ensemble stores extinction memory, and APPL1 signaling supports these neurons in retrieving extinction memory by controlling NMDAR-dependent potentiation.


Asunto(s)
Extinción Psicológica , Miedo , Ratones , Animales , Extinción Psicológica/fisiología , Miedo/fisiología , Receptores de N-Metil-D-Aspartato/metabolismo , Neuronas/fisiología , Transducción de Señal , Corteza Prefrontal/metabolismo , Ratones Transgénicos
10.
Artículo en Chino | WPRIM (Pacífico Occidental) | ID: wpr-1027901

RESUMEN

Objective:To study whether Bayesian penalized likelihood (BPL) and its optimized reconstruction algorithm can improve the reconstructed image quality of low count total-body PET.Methods:Eight patients (5 males, 3 females, age (67.2±6.3) years) who underwent hybrid 18F-FDG PET/MR total-body scans at Department of Nuclear Medicine in Union Hospital, Tongji Medical College, Huazhong University of Science and Technology were collected retrospectively from January to June in 2023. Total-body PET/MR images of them were included and list-mode data were reconstructed with four methods, namely 25% counts conventional reconstruction (group 1), 100% counts conventional reconstruction (group 2), 25% counts BPL reconstruction (group 3), and 25% counts optimized BPL reconstruction (group 4). At last, 32 total-body PET images were obtained. SUV max and SUV mean in different ROIs and tumor metabolic volume (MTV) were measured. Total lesion glycolysis (TLG) and parameters of image quality including the ratio of lesion to background (L/B) and image signal-to-noise ratio (SNR) were calculated. Then the differences in all the parameters among the four groups were analyzed by repeated measures analysis of variance and Friedman test. Quantitative differences between BPL reconstruction and optimized BPL with the 100% counts conventional reconstruction were compared respectively by using the Bland-Altman (BA) plot. Results:For the inter-group comparison, except for SUV mean in the muscle ( F=0.38, P=0.767), SUV max and SUV mean in other ROIs were statistically different ( F values: 8.15-36.08, χ2=18.15, all P<0.01), as well as MTV and L/B ( χ2 values: 10.65, 13.35, P values: 0.014, 0.004), but not for TLG ( χ2=4.95, P=0.175) or SNR ( F=2.64, P=0.076). For the pairwise comparison, the differences between group 2 and group 3 were the most significant (all P<0.05). Compared with group 2, there were no significant differences for SUV max and SUV mean of the cerebellar cortex and lesions in group 4 (all P>0.05), as well as MTV and L/B (both P>0.05). In addition, compared with group 1, SUV max of liver and muscle in group 2 were decreased (both P<0.05), while there were no significant differences in group 4 (all P>0.05). BA plots showed that the differences of SUV, MTV, and TLG between group 4 and group 2 were smaller obviously than those between group 3 and group 2. Conclusion:BPL reconstruction can improve low focus detection sensitivity induced by low counts, but it will cause significant changes for PET quantification, which can be solved by optimized BPL reconstruction.

11.
Chinese Journal of Geriatrics ; (12): 1089-1093, 2023.
Artículo en Chino | WPRIM (Pacífico Occidental) | ID: wpr-1028170

RESUMEN

Objective:To assess the usefulness of gray-scale ultrasonography and shear wave elastography in assessing the condition of skeletal muscle in people with chronic heart failure(CHF).Methods:In this prospective study, there were 50 CHF patients and another 50 healthy people undergoing physical checkups served as the control group.The rectus femoris and the gastrocnemius medialis of all participants were evaluated by shear wave elastography and gray-scale ultrasonography.Data were collected using quantitative parameters including muscle thickness, cross-sectional area, fascicle length, pinnation angle, gray value and Young's modulus.Results:Compared with the control group, the thickness(7.80±2.01)mm, cross-sectional area(3.27±0.91)cm 2 and gray value(70.07±6.06)of the rectus femoris and the thickness(12.23±2.42)mm, fascicle length(35.90±1.38)mm and pinnation angle(18.07±3.05)degrees of the gastrocnemius medialis in the CHF group were statistically different[(12.90±2.57)mm, (4.94±2.08)cm 2, 60.93±9.77]for the rectus femoris and(15.90±2.62)mm, (37.83±2.83)mm, (20.75±2.59)degrees for the gastrocnemius medialis of the control group, t=7.71, 3.78, 3.94, 4.99, 4.47, 3.06, P<0.01), but there was no significant difference in Young's modulus of the rectus femoris and the gastrocnemius medialis between the two groups( t=1.10, 0.51, P>0.05).In the CHF group, the thickness, cross-sectional area and gray value of the rectus femoris in different New York Heart Association(NYHA)heart failure grades were statistically different( F=56.36, 69.98, 55.96, P<0.01), but no difference was found in the gastrocnemius medialis with the same ultrasound parameters( P>0.05).When participants in the CHF group was divided into subgroups based on left ventricular ejection fraction(LVEF), there was no significant difference between the subgroups in values of the ultrasonic parameters for the rectus femoris and the gastrocnemius( P>0.05). Conclusions:Gray-scale ultrasound may quantitatively evaluate the skeletal muscle of CHF patients to guide early rehabilitation training to improve their prognosis.

12.
J Am Chem Soc ; 144(34): 15718-15726, 2022 Aug 31.
Artículo en Inglés | MEDLINE | ID: mdl-35975916

RESUMEN

"Spin" has been recently reported as an important degree of electronic freedom to improve the performance of electrocatalysts and photocatalysts. This work demonstrates the manipulations of spin-polarized electrons in CsPbBr3 halide perovskite nanoplates (NPLs) to boost the photocatalytic CO2 reduction reaction (CO2RR) efficiencies by doping manganese cations (Mn2+) and applying an external magnetic field. Mn-doped CsPbBr3 (Mn-CsPbBr3) NPLs exhibit an outstanding photocatalytic CO2RR compared to pristine CsPbBr3 NPLs due to creating spin-polarized electrons after Mn doping. Notably, the photocatalytic CO2RR of Mn-CsPbBr3 NPLs is significantly enhanced by applying an external magnetic field. Mn-CsPbBr3 NPLs exhibit 5.7 times improved performance of photocatalytic CO2RR under a magnetic field of 300 mT with a permanent magnet compared to pristine CsPbBr3 NPLs. The corresponding mechanism is systematically investigated by magnetic circular dichroism spectroscopy, ultrafast transient absorption spectroscopy, and density functional theory simulation. The origin of enhanced photocatalytic CO2RR efficiencies of Mn-CsPbBr3 NPLs is due to the increased number of spin-polarized photoexcited carriers by synergistic doping of the magnetic elements and applying a magnetic field, resulting in prolonged carrier lifetime and suppressed charge recombination. Our result shows that manipulating spin-polarized electrons in photocatalytic semiconductors provides an effective strategy to boost photocatalytic CO2RR efficiencies.

13.
Inorg Chem ; 61(26): 9897-9905, 2022 Jul 04.
Artículo en Inglés | MEDLINE | ID: mdl-35730617

RESUMEN

A substituent decorating strategy for modification of the functional cavity is of great importance in the design of metal-organic frameworks (MOFs). Herein, three new isostructural cationic MOFs, [Cu3(Xpip)2]·NO3·nH2O (Xpip stands for X-substituted phenylimidazophenanthroline, where X = adm (SCNU-2), f (SCNU-3), and none for SCNU-4), have been successfully synthesized and shown gyroidal utc-c topology and large pore sizes which can be adjusted by different substituents (-N(CH3)2, -F, and -H). Interestingly, the differences of the substituents (sizes and proton donor/acceptor) show essential effects on the adsorption abilities of carbon dioxide and dyes, where SCNU-4 exhibits the highest CO2 affinity and the biggest adsorption capacity for anionic dyes Fluorescein Sodium, and SCNU-3 adsorbs the largest amount (1503.6 mg/g) of Acid Fuchsin to date for the reported porous materials. The detailed studies in adsorption kinetics, adsorption isotherms, and theoretical calculation of the binding energies between the structures and dye molecules confirm that the electric properties of the frameworks (cationic) and substituents directed to the pore surface are two important factors dramatically affecting the selective dye adsorption.

14.
Entropy (Basel) ; 24(3)2022 Feb 26.
Artículo en Inglés | MEDLINE | ID: mdl-35327850

RESUMEN

The Navier-Stokes equation can be written in a form of Poisson equation. For laminar flow in a channel (plane Poiseuille flow), the Navier-Stokes equation has a non-zero source term (∇2u(x, y, z) = Fx (x, y, z, t) and a non-zero solution within the domain. For transitional flow, the velocity profile is distorted, and an inflection point or kink appears on the velocity profile, at a sufficiently high Reynolds number and large disturbance. In the vicinity of the inflection point or kink on the distorted velocity profile, we can always find a point where ∇2u(x, y, z) = 0. At this point, the Poisson equation is singular, due to the zero source term, and has no solution at this point due to singularity. It is concluded that there exists no smooth orphysically reasonable solutions of the Navier-Stokes equation for transitional flow and turbulence in the global domain due to singularity.

15.
Ann Transl Med ; 10(3): 147, 2022 Feb.
Artículo en Inglés | MEDLINE | ID: mdl-35284549

RESUMEN

Background: Osteoarthritis (OA) is one of the most common diseases in elderly people; however, the correlation between molecular alterations and the occurrence and progression of OA are still not well understood. We conducted this study to investigate the molecular changes in OA via the competing endogenous ribonucleic acid (ceRNA) network. Methods: We downloaded the messenger RNA (mRNA) data set, GSE48556, the microRNA (miRNA) data set, GSE105027, and the long non-coding (lncRNA) data set, GSE126963 from the Gene Expression Omnibus (GEO) database, and examined the differentially expressed genes (DEGs) in these data sets. Further, we constructed a ceRNA network of the differentially expressed miRNAs, mRNAs, and lncRNAs. To determine the biological functions of the ceRNA network, we performed Gene Ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) functional enrichment analyses. Finally, we conducted an immune cell infiltration analysisusing single-sample gene set enrichment analysis to examine the abundance of immune cells in healthy and OA patients, and compared the infiltration of 28 immune cells between the healthy and OA samples. We also analyzed the relationship between the abundance of immune cells and mRNA expression levels in the ceRNA network. Results: Ultimately hsa-mir-425-3p, dual specificity phosphatase 1, and 24 lncRNAs were identified in the ceRNA network. The functional enrichment analyses showed that these lncRNAs, miRNAs, and mRNAs are involved in various significant biological process, such as the regulation of leukocyte migration, Mitogen-Activated Protein (MAP) kinase tyrosine/serine/threonine phosphatase activity, the interleukin-17 signaling pathway, the tumor necrosis factor signaling pathway, and osteoclast differentiation, and can also have a strong effect on immune cell infiltration. Conclusions: The dual-specificity phosphatase 1-specific ceRNA network can be used as a diagnostic tool to assess the progression of OA patients.

16.
ACS Appl Mater Interfaces ; 14(9): 11895-11902, 2022 Mar 09.
Artículo en Inglés | MEDLINE | ID: mdl-35191691

RESUMEN

Broadband modulation of magnetic circular dichroism (MCD) using a relatively low magnetic field or by producing a field-free magnetoplasmonic effect in the remnant magnetic state was achieved by the integration of the noble metals (NMs) Au and Ag and the perpendicular magnetic anisotropy of Co with ZnO nanowires (NWs) used as the template. The samples containing NMs revealed MCD sign reversals and enhancements when compared with the original Co/ZnO NWs. The magnetoplasmonic effect of Au close to the visible light spectrum could induce the CD change in the visible region. Notably, the ultraviolet (UV) CD in Ag/Co/ZnO NWs is 12.5 times larger under a magnetic field (∼0.2 T) and 10 times greater in the remnant state (field-free) than those of the original Co/ZnO NWs because of the magnetoplasmonic effect of Ag in the UV spectrum. These results are attributable to the coupling of the remnant magnetic state of Co magnetization, the magnetoplasmons of the NMs, and the excitons of the ZnO NWs. The findings are potentially applicable in magneto-optical recording, biosensing, and energy contexts involving magnetoplasmonic functionalization.

17.
Artículo en Inglés | WPRIM (Pacífico Occidental) | ID: wpr-928594

RESUMEN

OBJECTIVES@#To explore the optimal maintenance dose of caffeine citrate for preterm infants requiring assisted ventilation and caffeine citrate treatment.@*METHODS@#A retrospective analysis was performed on the medical data of 566 preterm infants (gestational age ≤34 weeks) who were treated and required assisted ventilation and caffeine citrate treatment in the neonatal intensive care unit of 30 tertiary hospitals in Jiangsu Province of China between January 1 and December 31, 2019. The 405 preterm infants receiving high-dose (10 mg/kg per day) caffeine citrate after a loading dose of 20 mg/kg within 24 hours after birth were enrolled as the high-dose group. The 161 preterm infants receiving low-dose (5 mg/kg per day) caffeine citrate were enrolled as the low-dose group.@*RESULTS@#Compared with the low-dose group, the high-dose group had significant reductions in the need for high-concentration oxygen during assisted ventilation (P=0.044), the duration of oxygen inhalation after weaning from noninvasive ventilation (P<0.01), total oxygen inhalation time during hospitalization (P<0.01), the proportion of preterm infants requiring noninvasive ventilation again (P<0.01), the rate of use of pulmonary surfactant and budesonide (P<0.05), and the incidence rates of apnea and bronchopulmonary dysplasia (P<0.01), but the high-dose group had a significantly increased incidence rate of feeding intolerance (P=0.032). There were no significant differences between the two groups in the body weight change, the incidence rates of retinopathy of prematurity, intraventricular hemorrhage or necrotizing enterocolitis, the mortality rate, and the duration of caffeine use (P>0.05).@*CONCLUSIONS@#This pilot multicenter study shows that the high maintenance dose (10 mg/kg per day) is generally beneficial to preterm infants in China and does not increase the incidence rate of common adverse reactions. For the risk of feeding intolerance, further research is needed to eliminate the interference of confounding factors as far as possible.


Asunto(s)
Humanos , Lactante , Recién Nacido , Cafeína/uso terapéutico , Citratos , Recien Nacido Prematuro , Respiración Artificial , Estudios Retrospectivos
18.
Transl Pediatr ; 10(7): 1851-1866, 2021 Jul.
Artículo en Inglés | MEDLINE | ID: mdl-34430433

RESUMEN

BACKGROUND: The immune microenvironment plays an essential role in osteosarcoma (OSs); however, differences in immune-related long non-coding ribonucleic acids (irlncRNAs) in children with localized OSs and metastatic OSs have not yet been investigated. METHODS: The clinical data and the transcriptome of OSs were obtained from the Therapeutically Applicable Research to Generate Effective Treatments (TARGET) database, and the immune-related genes were derived from the imported dataset. The correlations between immune-related genes and lncRNAs were examined. Next, the differential expressions of the irlncRNA pairs (IRLPs) in localized OSs and distant metastatic OSs were analyzed, and a prognostic model was constructed based on the significant differentially expressed IRLPs. We also analyzed the association between the IRLPs' signature risk score and the infiltration of the immune cells. Finally, we investigated the correlation between risk score and drug resistance. RESULTS: Thirty upregulated and 22 downregulated lncRNAs were identified in the localized and metastatic OSs samples. Univariate and multivariate cox regression analyses were undertaken to select 6 lncRNA pairs to establish the prognostic signature, the model was valuable in predicting OSs prognosis. Further, the expression of the finally selected irlncRNAs indicated that VPS9D1-AS1 (P=0.031), AP003086.2 (P=0.041), AL031847.1 (P=0.008), AL020997.3 (P=0.020), AC011444.1 (P=0.025), and AC006449.2 (P=0.003) were significantly upregulated in metastasis patients, but USP27X-AS1 (P=0.046), AL008721.2 (P=0.005), AC002091.1 (P=0.033), and AL118558.4 (P=0.049) were significantly overexpressed in localized patients. The overexpression of AC002091.1 (P=0.038) and AL118558.4 (P=0.004) resulted in better overall survival, but the upregulation of AC011444.1 (P=0.045), AL031847.1 (P=0.020), VPS9D1-AS1 (P=0.039), and AC006449.2 (0.006) led to a poor outcome. Differences in immune cell infiltration indicated that metastatic patients and localized have significant difference of 4 (CD4) T cells (P=0.006), monocytes (P=0.029), activated mast cells (P=0.018), and neutrophils (P=0.026), and a high abundance of activated dendritic cells (P=0.010) and activated mast cells (P=0.049) resulted in poor prognosis. Patients in the high-risk-score group were resistant to axitinib, but sensitive to dasatinib, bortezomib, and cisplatin. CONCLUSIONS: In the present study, IRLPs were used to construct a novel and practical model for predicting the prognosis of localized and metastatic OSs in children.

19.
Nanomaterials (Basel) ; 11(7)2021 Jul 19.
Artículo en Inglés | MEDLINE | ID: mdl-34361246

RESUMEN

Extracellular vesicles (EVs) are membrane-bound lipid particles that are secreted by all cell types and function as cell-to-cell communicators through their cargos of protein, nucleic acid, lipids, and metabolites, which are derived from their parent cells. There is limited information on the isolation and the emerging therapeutic role of periodontal and dental pulp cell-derived small EVs (sEVs, <200 nm, or exosome). In this review, we discuss the biogenesis of three EV subtypes (sEVs, microvesicles and apoptotic bodies) and the emerging role of sEVs from periodontal ligament (stem) cells, gingival fibroblasts (or gingival mesenchymal stem cells) and dental pulp cells, and their therapeutic potential in vitro and in vivo. A review of the relevant methodology found that precipitation-based kits and ultracentrifugation are the two most common methods to isolate periodontal (dental pulp) cell sEVs. Periodontal (and pulp) cell sEVs range in size, from 40 nm to 2 µm, due to a lack of standardized isolation protocols. Nevertheless, our review found that these EVs possess anti-inflammatory, osteo/odontogenic, angiogenic and immunomodulatory functions in vitro and in vivo, via reported EV cargos of EV-miRNAs, EV-circRNAs, EV-mRNAs and EV-lncRNAs. This review highlights the considerable therapeutic potential of periodontal and dental pulp cell-derived sEVs in various regenerative applications.

20.
Biosci Rep ; 41(8)2021 08 27.
Artículo en Inglés | MEDLINE | ID: mdl-34350461

RESUMEN

Periodontitis is a series of inflammatory processes caused by bacterial infection. Parathyroid hormone (PTH) plays a critical role in bone remodeling. The present study aimed to investigate the influences of PTH on human bone marrow mesenchymal stem cells (HBMSCs) pretreated with lipopolysaccharide (LPS). The proliferative ability was measured using cell counting kit-8 (CCK-8) and flow cytometry. The optimal concentrations of PTH and LPS were determined using alkaline phosphatase (ALP) activity assay, ALP staining, and Alizarin Red staining. Osteogenic differentiation was further assessed by quantitative reverse-transcription polymerase chain reaction (RT-qPCR), Western blot analysis, and immunofluorescence staining. PTH had no effects on the proliferation of HBMSCs. Also, 100 ng/ml LPS significantly inhibited HBMSC osteogenesis, while 10-9 mol/l PTH was considered as the optimal concentration to reverse the adverse effects. Mechanistically, c-Jun N-terminal kinase (JNK) phosphorylation was activated by PTH in LPS-induced HBMSCs. SP600125, a selective inhibitor targeting JNK mitogen-activated protein kinase (MAPK) signaling, weakened the effects of PTH. Taken together, the findings revealed the role and mechanism of PTH and JNK pathway in promoting the osteogenic differentiation of LPS-induced HBMSCs, which offered an alternative for treating periodontal diseases.


Asunto(s)
Diferenciación Celular/efectos de los fármacos , Proteínas Quinasas JNK Activadas por Mitógenos/metabolismo , Lipopolisacáridos/farmacología , Células Madre Mesenquimatosas/efectos de los fármacos , Osteogénesis/efectos de los fármacos , Hormona Paratiroidea/farmacología , Periodontitis/tratamiento farmacológico , Adulto , Células Cultivadas , Humanos , Células Madre Mesenquimatosas/enzimología , Células Madre Mesenquimatosas/patología , Periodontitis/enzimología , Periodontitis/patología , Fosforilación , Transducción de Señal , Adulto Joven
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