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1.
Proc Natl Acad Sci U S A ; 121(14): e2315982121, 2024 Apr 02.
Artículo en Inglés | MEDLINE | ID: mdl-38536757

RESUMEN

Throughout evolution, arboviruses have developed various strategies to counteract the host's innate immune defenses to maintain persistent transmission. Recent studies have shown that, in addition to bacteria and fungi, the innate Toll-Dorsal immune system also plays an essential role in preventing viral infections in invertebrates. However, whether the classical Toll immune pathway is involved in maintaining the homeostatic process to ensure the persistent and propagative transmission of arboviruses in insect vectors remain unclear. In this study, we revealed that the transcription factor Dorsal is actively involved in the antiviral defense of an insect vector (Laodelphax striatellus) by regulating the target gene, zinc finger protein 708 (LsZN708), which mediates downstream immune-related effectors against infection with the plant virus (Rice stripe virus, RSV). In contrast, an antidefense strategy involving the use of the nonstructural-protein (NS4) to antagonize host antiviral defense through competitive binding to Dorsal from the MSK2 kinase was employed by RSV; this competitive binding inhibited Dorsal phosphorylation and reduced the antiviral response of the host insect. Our study revealed the molecular mechanism through which Toll-Dorsal-ZN708 mediates the maintenance of an arbovirus homeostasis in insect vectors. Specifically, ZN708 is a newly documented zinc finger protein targeted by Dorsal that mediates the downstream antiviral response. This study will contribute to our understanding of the successful transmission and spread of arboviruses in plant or invertebrate hosts.


Asunto(s)
Arbovirus , Hemípteros , Oryza , Tenuivirus , Animales , Arbovirus/genética , Hemípteros/fisiología , Tenuivirus/fisiología , Insectos Vectores , Antivirales/metabolismo , Oryza/genética , Enfermedades de las Plantas
2.
PLoS Pathog ; 19(3): e1011266, 2023 03.
Artículo en Inglés | MEDLINE | ID: mdl-36928081

RESUMEN

The Janus kinase-signal transducer and activator of transcription (JAK-STAT) pathway is an evolutionarily conserved signaling pathway that can regulate various biological processes. However, the role of JAK-STAT pathway in the persistent viral infection in insect vectors has rarely been investigated. Here, using a system that comprised two different plant viruses, Rice stripe virus (RSV) and Rice black-streaked dwarf virus (RBSDV), as well as their insect vector small brown planthopper, we elucidated the regulatory mechanism of JAK-STAT pathway in persistent viral infection. Both RSV and RBSDV infection activated the JAK-STAT pathway and promoted the accumulation of suppressor of cytokine signaling 5 (SOCS5), an E3 ubiquitin ligase regulated by the transcription factor STAT5B. Interestingly, the virus-induced SOCS5 directly interacted with the anti-apoptotic B-cell lymphoma-2 (BCL2) to accelerate the BCL2 degradation through the 26S proteasome pathway. As a result, the activation of apoptosis facilitated persistent viral infection in their vector. Furthermore, STAT5B activation promoted virus amplification, whereas STAT5B suppression inhibited apoptosis and reduced virus accumulation. In summary, our results reveal that virus-induced JAK-STAT pathway regulates apoptosis to promote viral infection, and uncover a new regulatory mechanism of the JAK-STAT pathway in the persistent plant virus transmission by arthropod vectors.


Asunto(s)
Tenuivirus , Virosis , Animales , Quinasas Janus/metabolismo , Transducción de Señal , Factores de Transcripción STAT/metabolismo , Tenuivirus/metabolismo , Insectos Vectores , Proteínas Proto-Oncogénicas c-bcl-2/metabolismo
3.
BMC Genomics ; 25(1): 450, 2024 May 07.
Artículo en Inglés | MEDLINE | ID: mdl-38714918

RESUMEN

BACKGROUND: Circular RNAs (circRNAs) are a novel kind of non-coding RNAs proved to play crucial roles in the development of multiple diabetic complications. However, their expression and function in diabetes mellitus (DM)-impaired salivary glands are unknown. RESULTS: By using microarray technology, 663 upregulated and 999 downregulated circRNAs companied with 813 upregulated and 525 downregulated mRNAs were identified in the parotid glands (PGs) of type2 DM mice under a 2-fold change and P < 0.05 cutoff criteria. Gene ontology (GO) and kyoto encyclopedia of genes and genomes (KEGG) analysis of upregulated mRNAs showed enrichments in immune system process and peroxisome proliferator-activated receptor (PPAR) signaling pathway. Infiltration of inflammatory cells and increased inflammatory cytokines were observed in diabetic PGs. Seven differently expressed circRNAs validated by qRT-PCR were selected for coding-non-coding gene co-expression (CNC) and competing endogenous RNA (ceRNA) networks analysis. PPAR signaling pathway was primarily enriched through analysis of circRNA-mRNA networks. Moreover, the circRNA-miRNA-mRNA networks highlighted an enrichment in the regulation of actin cytoskeleton. CONCLUSION: The inflammatory response is elevated in diabetic PGs. The selected seven distinct circRNAs may attribute to the injury of diabetic PG by modulating inflammatory response through PPAR signaling pathway and actin cytoskeleton in diabetic PGs.


Asunto(s)
Diabetes Mellitus Tipo 2 , Perfilación de la Expresión Génica , Redes Reguladoras de Genes , Glándula Parótida , ARN Circular , Animales , ARN Circular/genética , Ratones , Diabetes Mellitus Tipo 2/genética , Diabetes Mellitus Tipo 2/metabolismo , Glándula Parótida/metabolismo , ARN Mensajero/genética , ARN Mensajero/metabolismo , Receptores Activados del Proliferador del Peroxisoma/metabolismo , Receptores Activados del Proliferador del Peroxisoma/genética , Transcriptoma , Ontología de Genes , Masculino , Transducción de Señal , Diabetes Mellitus Experimental/genética , Diabetes Mellitus Experimental/metabolismo
4.
J Gen Virol ; 105(4)2024 Apr.
Artículo en Inglés | MEDLINE | ID: mdl-38602389

RESUMEN

A negative-strand symbiotic RNA virus, tentatively named Nilaparvata lugens Bunyavirus (NLBV), was identified in the brown planthopper (BPH, Nilaparvata lugens). Phylogenetic analysis indicated that NLBV is a member of the genus Mobuvirus (family Phenuiviridae, order Bunyavirales). Analysis of virus-derived small interfering RNA suggested that antiviral immunity of BPH was successfully activated by NLBV infection. Tissue-specific investigation showed that NLBV was mainly accumulated in the fat-body of BPH adults. Moreover, NLBV was detected in eggs of viruliferous female BPHs, suggesting the possibility of vertical transmission of NLBV in BPH. Additionally, no significant differences were observed for the biological properties between NLBV-infected and NLBV-free BPHs. Finally, analysis of geographic distribution indicated that NLBV may be prevalent in Southeast Asia. This study provided a comprehensive characterization on the molecular and biological properties of a symbiotic virus in BPH, which will contribute to our understanding of the increasingly discovered RNA viruses in insects.


Asunto(s)
Hemípteros , Orthobunyavirus , Virus ARN , Animales , Femenino , Filogenia , Insectos , Virus ARN/genética
5.
Small ; 20(11): e2306554, 2024 Mar.
Artículo en Inglés | MEDLINE | ID: mdl-37919862

RESUMEN

Intercalation forms heterostructures, and over 25 elements and compounds are intercalated into graphene, but the mechanism for this process is not well understood. Here, the de-intercalation of 2D Ag and Ga metals sandwiched between bilayer graphene and SiC are followed using photoemission electron microscopy (PEEM) and atomistic-scale reactive molecular dynamics simulations. By PEEM, de-intercalation "windows" (or defects) are observed in both systems, but the processes follow distinctly different dynamics. Reversible de- and re-intercalation of Ag is observed through a circular defect where the intercalation velocity front is 0.5 nm s-1 ± 0.2 nm s.-1 In contrast, the de-intercalation of Ga is irreversible with faster kinetics that are influenced by the non-circular shape of the defect. Molecular dynamics simulations support these pronounced differences and complexities between the two Ag and Ga systems. In the de-intercalating Ga model, Ga atoms first pile up between graphene layers until ultimately moving to the graphene surface. The simulations, supported by density functional theory, indicate that the Ga atoms exhibit larger binding strength to graphene, which agrees with the faster and irreversible diffusion kinetics observed. Thus, both the thermophysical properties of the metal intercalant and its interaction with defective graphene play a key role in intercalation.

6.
J Immunol ; 208(5): 1204-1213, 2022 03 01.
Artículo en Inglés | MEDLINE | ID: mdl-35173034

RESUMEN

Pancreatic ß cell apoptosis is important in the pathogenesis of type 2 diabetes mellitus (T2DM). Generally, apoptotic ß cells are phagocytosed by macrophages in a process known as "efferocytosis." Efferocytosis is critical to the resolution of inflammation and is impaired in T2DM. Advanced glycation end products (AGEs), which are increased in T2DM, are known to suppress phagocytosis function in macrophages. In this study, we found that AGEs inhibited efferocytosis of apoptotic ß cells by primary peritoneal macrophages in C57BL/6J mice or mouse macrophage cell line Raw264.7. Mechanistically, AGEs inhibit efferocytosis by blocking Ras-related C3 botulinum toxin substrate 1 activity and cytoskeletal rearrangement through receptor for advanced glycation end products/ras homolog family member A/Rho kinase signaling in macrophages. Furthermore, it was observed that AGEs decreased the secretion of anti-inflammatory factors and promoted the proinflammatory ones to modulate the inflammation function of efferocytosis. Taken together, our results indicate that AGEs inhibit efferocytosis through binding to receptor for advanced glycation end products and activating ras homolog family member A/Rho kinase signaling, thereby inhibiting the anti-inflammatory function of efferocytosis.


Asunto(s)
Diabetes Mellitus Tipo 2/patología , Productos Finales de Glicación Avanzada/metabolismo , Células Secretoras de Insulina/metabolismo , Macrófagos Peritoneales/inmunología , Fagocitosis/fisiología , Receptor para Productos Finales de Glicación Avanzada/metabolismo , Animales , Apoptosis/fisiología , Toxinas Botulínicas/metabolismo , Línea Celular , Humanos , Inflamación/patología , Masculino , Ratones , Ratones Endogámicos C57BL , Células RAW 264.7 , Transducción de Señal/fisiología , Quinasas Asociadas a rho/metabolismo , Proteína de Unión al GTP rhoA/metabolismo
7.
J Neuroeng Rehabil ; 21(1): 85, 2024 May 28.
Artículo en Inglés | MEDLINE | ID: mdl-38807117

RESUMEN

BACKGROUND: Sensor-based interventions (SI) have been suggested as an alternative rehabilitation treatment to improve older adults' functional performance. However, the effectiveness of different sensor technologies in improving gait and balance remains unclear and requires further investigation. METHODS: Ten databases (Academic Search Premier; Cumulative Index to Nursing and Allied Health Literature, Complete; Cochrane Central Register of Controlled Trials; MEDLINE; PubMed; Web of Science; OpenDissertations; Open grey; ProQuest; and Grey literature report) were searched for relevant articles published up to December 20, 2022. Conventional functional assessments, including the Timed Up and Go (TUG) test, normal gait speed, Berg Balance Scale (BBS), 6-Minute Walk Test (6MWT), and Falling Efficacy Scale-International (FES-I), were used as the evaluation outcomes reflecting gait and balance performance. We first meta-analyzed the effectiveness of SI, which included optical sensors (OPTS), perception sensors (PCPS), and wearable sensors (WS), compared with control groups, which included non-treatment intervention (NTI) and traditional physical exercise intervention (TPEI). We further conducted sub-group analysis to compare the effectiveness of SI (OPTS, PCPS, and WS) with TPEI groups and compared each SI subtype with control (NTI and TPEI) and TPEI groups. RESULTS: We scanned 6255 articles and performed meta-analyses of 58 selected trials (sample size = 2713). The results showed that SI groups were significantly more effective than control or TPEI groups (p < 0.000) in improving gait and balance performance. The subgroup meta-analyses between OPTS groups and TPEI groups revealed clear statistically significant differences in effectiveness for TUG test (mean difference (MD) = - 0.681 s; p < 0.000), normal gait speed (MD = 4.244 cm/s; p < 0.000), BBS (MD = 2.325; p = 0.001), 6MWT (MD = 25.166 m; p < 0.000), and FES-I scores (MD = - 2.036; p = 0.036). PCPS groups also presented statistically significant differences with TPEI groups in gait and balance assessments for normal gait speed (MD = 4.382 cm/s; p = 0.034), BBS (MD = 1.874; p < 0.000), 6MWT (MD = 21.904 m; p < 0.000), and FES-I scores (MD = - 1.161; p < 0.000), except for the TUG test (MD = - 0.226 s; p = 0.106). There were no statistically significant differences in TUG test (MD = - 1.255 s; p = 0.101) or normal gait speed (MD = 6.682 cm/s; p = 0.109) between WS groups and control groups. CONCLUSIONS: SI with biofeedback has a positive effect on gait and balance improvement among a mixed population of older adults. Specifically, OPTS and PCPS groups were statistically better than TPEI groups at improving gait and balance performance, whereas only the group comparison in BBS and 6MWT can reach the minimal clinically important difference. Moreover, WS groups showed no statistically or clinically significant positive effect on gait and balance improvement compared with control groups. More studies are recommended to verify the effectiveness of specific SI. Research registration PROSPERO platform: CRD42022362817. Registered on 7/10/2022.


Asunto(s)
Marcha , Equilibrio Postural , Ensayos Clínicos Controlados Aleatorios como Asunto , Humanos , Equilibrio Postural/fisiología , Anciano , Marcha/fisiología , Dispositivos Electrónicos Vestibles
8.
Phytochem Anal ; 2024 May 13.
Artículo en Inglés | MEDLINE | ID: mdl-38740517

RESUMEN

INTRODUCTION: Sulfur-fumigation of Paeoniae Radix Alba (PRA) could induce the chemical transformation of its bioactive component paeoniflorin into a sulfur-containing derivative paeoniflorin sulfite, and thus alter the quality, bioactivities, pharmacokinetics, and toxicities of PRA. However, how sulfur-fumigated PRA (S-PRA) affects the quality of PRA-containing complex preparations has not been intensively evaluated. OBJECTIVES: We intend to evaluate the influence of S-PRA on the overall quality of three kinds of Si-Wu-Tang (SWT) formulations, i.e., decoction (SWT-D), granule (SWT-G), and mixture (SWT-M). MATERIAL AND METHODS: An UPLC-DAD multi-components quantification method was used to compare the transfer rates of paeoniflorin sulfite and other 10 bioactive components between S-PRA-containing and NS-PRA-containing SWT formulations. An UPLC-QTOF-MS/MS-based target metabolomics approach was applied to explore the differential sulfur-containing derivatives in S-PRA-containing SWT formulations. RESULTS: The transfer rates of paeoniflorin sulfite in three S-PRA-containing SWT formulations were all higher than 100%. Moreover, S-PRA also increased the transfer rate of 5-hydroxymethylfurfural, 1,2,3,4,6-O-pentagalloylglucose, whereas decreased that of paeoniflorin, albiflorin, and ferulic acid in three SWT formulations. Six pinane monoterpene glucoside sulfites originally identified in S-PRA, were also detectable in three S-PRA-containing SWT formulations. In addition, seven phenolic acid sulfites including (3Z)-6-sulfite-ligustilide, (3E)-6-sulfite-ligustilide, 6,8-disulfite-ligustilide, ferulic acid sulfite, neochlorogenic acid sulfite, chlorogenic acid sulfite, and angelicide sulfite (or isomer) were newly identified in these three S-PRA-containing formulations. CONCLUSION: S-PRA could differentially affect the transfer rate of paeoniflorin sulfite and other bioactive components during the preparation of three SWT formulations and subsequently the overall quality thereof.

9.
Sensors (Basel) ; 24(10)2024 May 17.
Artículo en Inglés | MEDLINE | ID: mdl-38794055

RESUMEN

Gait and balance have emerged as a critical area of research in health technology. Gait and balance studies have been affected by the researchers' slow follow-up of research advances due to the absence of visual inspection of the study literature across decades. This study uses advanced search methods to analyse the literature on gait and balance in older adults from 1993 to 2022 in the Web of Science (WoS) database to gain a better understanding of the current status and trends in the field for the first time. The study analysed 4484 academic publications including journal articles and conference proceedings on gait and balance in older adults. Bibliometric analysis methods were applied to examine the publication year, number of publications, discipline distribution, journal distribution, research institutions, application fields, test methods, analysis theories, and influencing factors in the field of gait and balance. The results indicate that the publication of relevant research documents has been steadily increasing from 1993 to 2022. The United States (US) exhibits the highest number of publications with 1742 articles. The keyword "elderly person" exhibits a strong citation burst strength of 18.04, indicating a significant focus on research related to the health of older adults. With a burst factor of 20.46, Harvard University has made impressive strides in the subject. The University of Pittsburgh displayed high research skills in the area of gait and balance with a burst factor of 7.7 and a publication count of 103. The research on gait and balance mainly focuses on physical performance evaluation approaches, and the primary study methods include experimental investigations, computational modelling, and observational studies. The field of gait and balance research is increasingly intertwined with computer science and artificial intelligence (AI), paving the way for intelligent monitoring of gait and balance in the elderly. Moving forward, the future of gait and balance research is anticipated to highlight the importance of multidisciplinary collaboration, intelligence-driven approaches, and advanced visualization techniques.


Asunto(s)
Bibliometría , Marcha , Equilibrio Postural , Humanos , Equilibrio Postural/fisiología , Marcha/fisiología , Anciano
10.
Phys Chem Chem Phys ; 25(19): 13690-13701, 2023 May 17.
Artículo en Inglés | MEDLINE | ID: mdl-37158013

RESUMEN

Benzene (C6H6) and 1,3-cyclopentadiene (c-C5H6) are critical intermediate species in the combustion of fossil fuel and the formation of polycyclic aromatic hydrocarbons (PAHs). This study investigates the underlying mechanisms of pyrolysis and oxidation of C6H6 and c-C5H6 in the presence of O2, NO and NO2, respectively, under combustion conditions via ReaxFF molecular dynamics simulations. The size growth in the pyrolysis system is accompanied by an amorphous nature as well as an increase in the C/H ratio. In the oxidation sytems, NO2 is the most effective in the oxidation of both C6H6 and c-C5H6, followed by NO and O2. In the presence of NOx, O and N radicals generated in the high-temperature decomposition reactions of NO and NO2 are actively involved in the addition and H-abstraction reactions of C6H6 and c-C5H6. Remarkably, the decomposition of NO2 dramatically increases the number of O radicals in the system, which significantly accelerates the ring-opening of C6H6 and c-C5H6 by O-addition and forms linear-C6H6O and C5H6O species, respectively. Afterwards, the formation of -CH2- by H-transfer plays an essential role in the decomposition of linear-C6H6O and -C5H6O. Reaction pathways of O and N radicals with C6H6 and c-C5H6 are reported in detail. The O and N-addition of C6H6 facilitate the decomposition to resonance-stabilized cyclopentadienyl radicals after the restructuring of the C-C bond.

11.
Oral Dis ; 29(5): 2086-2095, 2023 Jul.
Artículo en Inglés | MEDLINE | ID: mdl-35472254

RESUMEN

OBJECTIVES: Tight junctions (TJs) are involved in the regulation of salivary secretion via paracellular pathway. Botulinum toxin type A (BTXA) is widely used for the treatment of hypersecretion diseases such as sialorrhea. This study aimed to investigate the role of TJs in BTXA-inhibited secretion of the submandibular gland (SMG). MATERIALS AND METHODS: BTXA was injected into the SMGs of rats, and the same amount of saline was injected as a control. Western blot, real-time PCR, and immunofluorescence staining were used to detect the expression and distribution of TJ proteins. Paracellular permeability was evaluated using the transepithelial electrical resistance (TER) measurements and fluorescent tracer detection in BTXA-stimulated SMG-C6 cells. RESULTS: BTXA injection into the SMGs of rats led to increased expression of claudin (Cldn) -1 and Cldn3. Immunofluorescence staining showed no significant changes in the distribution of TJ proteins. In vitro, BTXA increased the TER values and significantly reduced the permeability of fluorescent tracer, suggesting that BTXA decreased the paracellular permeability. The expression levels of Cldn1, Cldn3, and Cldn4 were upregulated after BTXA treatment. CONCLUSION: The expression of TJ proteins changed in both animal models and SMG-C6 cells after BTXA treatment, which may contribute to the inhibition of salivary secretion.


Asunto(s)
Toxinas Botulínicas Tipo A , Uniones Estrechas , Ratas , Animales , Uniones Estrechas/fisiología , Toxinas Botulínicas Tipo A/farmacología , Toxinas Botulínicas Tipo A/metabolismo , Salivación , Glándula Submandibular/metabolismo
12.
Microsc Microanal ; 29(4): 1357-1372, 2023 Jul 25.
Artículo en Inglés | MEDLINE | ID: mdl-37488828

RESUMEN

Monazite is one of the most important dating accessory minerals for deciphering geological processes. The growth history of monazite can be identified by its internal structure; thus, high-resolution imaging is necessary for in situ U-Th-Pb dating. In this study, cathodoluminescence (CL) techniques were optimized via the key parameters of working distance, accelerating voltage, and beam current and were then applied to monazites from igneous and metamorphic rocks. The CL images of igneous monazites show concentric oscillatory zoning, whereas those of metamorphic monazites clearly show homogeneous, patchy, or core-rim structures. CL imaging is a more effective approach than back-scattered electron (BSE) imaging for the observation of the internal structure of monazite and may yield additional information. CL can add to the interpretation of X-ray maps and the two techniques that may complement each other. The CL spectra of monazite consist of broad peaks and sets of narrow emission rare earth element 3+ (REE3+) peaks (Gd3+, Tb3+, Dy3+, and Sm3+). The microstructures observed via CL imaging techniques can show a certain relationship between light REE (LREE) and U, Th, and Si in some igneous monazites and heavy REE (HREE) variation in some metamorphic monazites.

13.
Phytochem Anal ; 34(2): 198-208, 2023 Mar.
Artículo en Inglés | MEDLINE | ID: mdl-36494085

RESUMEN

INTRODUCTION: Prunellae Spica (PS) is a commonly used medicinal herb in China. Secondary metabolites and saccharides are major bioactive components of PS. However, holistic quality consistency of commercial PS is ambiguous due to lack of comprehensive evaluation methods and reliable quality control markers. OBJECTIVES: Integrating multiple chromatographic and chemometric methods to comprehensively evaluate the holistic quality of PS. MATERIAL AND METHODS: Ultrahigh-performance liquid chromatography coupled with triple-quadrupole tandem mass spectrometry (UPLC-TQ-MS/MS) was applied to quantify 12 secondary metabolites of PS. High-performance liquid chromatography coupled with photodiode array/evaporative light scattering detection (HPLC-PDA/ELSD) and high-performance gel permeation chromatography (HPGPC) methods were used to characterise the saccharides. Multivariate statistical analysis was adopted to evaluate the quality consistency of commercial PS and explore the potential quality control markers. RESULTS: The contents of secondary metabolites and saccharides were significantly different among commercial PS. All samples could be classified into three groups with ferulic acid, protocatechualdehyde, gallic acid, ursolic acid/oleanolic acid, sucrose, p-coumaric acid, chlorogenic acid as the major contributing components responsible for the difference. The content of rosmarinic acid was correlated with that of betulinic acid, hyperposide, chlorogenic acid, rutin, caffeic acid, p-coumaric acid and glucose, whereas polysaccharides, ferulic acid, protocatechualdehyde and ursolic acid/oleanolic acid, quercetin, sucrose and majority monosaccharides were not. CONCLUSION: The holistic quality of commercial PS was inconsistent. Together with rosmarinic acid, ferulic acid, protocatechualdehyde, ursolic acid/oleanolic acid, polysaccharides and sucrose might be recommended as potential quality control markers for the holistic quality control of PS.


Asunto(s)
Ácido Oleanólico , Triterpenos , Espectrometría de Masas en Tándem/métodos , Triterpenos/análisis , Polisacáridos , Sacarosa , Cromatografía Líquida de Alta Presión/métodos , Ácido Rosmarínico , Ácido Ursólico
14.
Toxicol Appl Pharmacol ; 434: 115798, 2022 01 01.
Artículo en Inglés | MEDLINE | ID: mdl-34793778

RESUMEN

Local anesthetics (LAs) are widely used for intraoperative anesthesia and postoperative analgesia. However, LAs (e.g. Bupivacaine) can evoke myotoxicity that closely associated to mitochondrial damage. PGC1a is a mast co-factor for mitochondrial quality control. We have recently demonstrated that PGC1a can be activated by HSPA12A in hepatocytes, suggesting a possibility that HSPA12A protects from LAs myotoxicity through activating PGC1α-mediated mitochondrial integrity. Here, we reported that HSPA12A was downregulated during Bupivacaine-induced myotoxicity in skeletal muscles of mice in vivo and C2c12 myoblast cultures in vitro. Intriguingly, overexpression of HSPA12A attenuated the Bupivacaine-induced C2c12 cell death. We also noticed that the Bupivacaine-induced decrease of glucose consumption and ATP production was improved by HSPA12A overexpression. Moreover, overexpression of HSPA12A in C2c12 cells attenuated the Bupivacaine-induced decrease of mitochondrial contents and increase of mitochondrial fragmentation. The Bupivacaine-induced reduction of PGC1α expression and nuclear localization was markedly attenuated by HSPA12A overexpression. Importantly, pretreatment with a selective PGC1α inhibitor (SR-18292) abolished the protection of HSPA12A from Bupivacaine-induced death and mitochondrial loss in C2c12 cells. Altogether, the findings indicate that downregulation of HSPA12A underlies myotoxicity of Local anesthetic agent Bupivacaine through inhibiting PGC1α-mediated Mitochondrial Integrity. Thus, HSPA12A might represent a viable strategy for preventing myotoxicity of LAs.


Asunto(s)
Bupivacaína/toxicidad , Regulación de la Expresión Génica/efectos de los fármacos , Mitocondrias/efectos de los fármacos , Enfermedades Musculares/inducido químicamente , Coactivador 1-alfa del Receptor Activado por Proliferadores de Peroxisomas gamma/metabolismo , Anestésicos Locales/toxicidad , Animales , Línea Celular , Supervivencia Celular/efectos de los fármacos , Regulación hacia Abajo/efectos de los fármacos , Proteínas HSP70 de Choque Térmico , Ratones , Ratones Endogámicos C57BL , Mitocondrias/metabolismo , Enfermedades Musculares/metabolismo , Enfermedades Musculares/patología , Coactivador 1-alfa del Receptor Activado por Proliferadores de Peroxisomas gamma/genética
15.
PLoS Comput Biol ; 17(8): e1009291, 2021 08.
Artículo en Inglés | MEDLINE | ID: mdl-34437528

RESUMEN

Secondary structure plays an important role in determining the function of noncoding RNAs. Hence, identifying RNA secondary structures is of great value to research. Computational prediction is a mainstream approach for predicting RNA secondary structure. Unfortunately, even though new methods have been proposed over the past 40 years, the performance of computational prediction methods has stagnated in the last decade. Recently, with the increasing availability of RNA structure data, new methods based on machine learning (ML) technologies, especially deep learning, have alleviated the issue. In this review, we provide a comprehensive overview of RNA secondary structure prediction methods based on ML technologies and a tabularized summary of the most important methods in this field. The current pending challenges in the field of RNA secondary structure prediction and future trends are also discussed.


Asunto(s)
Aprendizaje Automático , Conformación de Ácido Nucleico , ARN/química , Biología Computacional/métodos
16.
Biotechnol Appl Biochem ; 69(6): 2617-2623, 2022 Dec.
Artículo en Inglés | MEDLINE | ID: mdl-34981870

RESUMEN

Elevated serum high-sensitivity C-reactive protein (hs-CRP) and lipoprotein(a) (Lp(a)) levels are associated with the development of native coronary atherosclerosis. We aimed to establish a new method for the simultaneous detection of hs-CRP and Lp(a) to predict the development of atherosclerosis. A one-step time-resolved fluorescence immunoassay (TRFIA) with europium(III) (Eu3+ ) or samarium(III) (Sm3+ ) labels was established, and the performance of this TRFIA (in terms of sensitivity, specificity, accuracy, and cutoff values) was evaluated using clinical serum samples and compared with those of registered kits. The sensitivity was 0.052 µg/ml for hs-CRP and 0.64 µg/ml for Lp(a). The intra-assay and inter-assay cross-reactivities (CVs) were very low, ranging from 2.05% to 4.67% for hs-CRP and from 2.42% to 6.43% for Lp(a). The CVs were very low (<0.34% and <2.65%, respectively) with five interferents. Additionally, there was a high Pearson coefficient between the present TRFIA method and the registered kits (R2 = 0.9967 and 0.9906, respectively). These data indicate that this study developed a TRFIA method that can be used for the quantitative detection of hs-CRP and Lp(a) in serum with high sensitivity, specificity, and accuracy. This TRFIA provides a new method for predicting the development of atherosclerosis.


Asunto(s)
Aterosclerosis , Enfermedad de la Arteria Coronaria , Humanos , Proteína C-Reactiva , Lipoproteína(a) , Fluoroinmunoensayo/métodos , Sensibilidad y Especificidad
17.
Molecules ; 27(22)2022 Nov 08.
Artículo en Inglés | MEDLINE | ID: mdl-36431784

RESUMEN

Cicadae Periostracum (CP) is a traditional Chinese medicinal herb derived from the slough that is molted from the nymph of the insect Cryptotympana pustulata Fabricius. Washing with water to remove residual silt is a primary processing method of CP that is recommended by the Chinese Pharmacopoeia, but how washing methods affect the quality and bioactivity of CP is unknown. In this study, the quality and bioactivity of non-washed CP (CP-NW), post-molting-washed CP (CP-WAT), and pre-molting-washed CP (CP-WBT) were comparatively investigated. The quality of these CP samples was evaluated in terms of the UPLC-QTOF-MS/MS-based chemical profiling and semi-quantification of 39 N-acetyldopamine oligomers (belonging to six chemical types), the HPLC-UV-based quantification of 17 amino acids, the ICP-MS-based quantification of four heavy metals, and the contents of ash; the bioactivities of the samples were compared regarding their anti-oxidant and anti-inflammatory activities. It was found that, compared with CP-NW, both CP-WBT and CP-WAT had significantly lower contents of ash and heavy metals. Moreover, compared with CP-WAT, CP-WBT contained lower levels of total ash, acid-insoluble ash, and heavy metals and higher contents of N-acetyldopamine oligomers and amino acids. It also had enhanced anti-oxidant and anti-inflammatory activities. A Spearman's correlation analysis found that the contents of N-acetyldopamine oligomers and free amino acids were positively correlated with the anti-oxidant/-inflammatory activities of CP. All these results suggest that pre-molting washing can not only remove the residual silt but can also avoid the loss of the bioactive components and assure higher bioactivities. It is concluded that pre-molting washing could enhance the quality and bioactivity of CP and should be a superior alternative method for the primary processing of qualified CP.


Asunto(s)
Antioxidantes , Metales Pesados , Antioxidantes/farmacología , Oxidantes , Espectrometría de Masas en Tándem , Muda , Antiinflamatorios/farmacología , Metales Pesados/análisis , Aminoácidos
18.
Crit Rev Food Sci Nutr ; 61(12): 2061-2077, 2021.
Artículo en Inglés | MEDLINE | ID: mdl-32462901

RESUMEN

In recent years, obesity has become a global public health issue. It is closely associated with the occurrence of several chronic diseases, such as diabetes and cardiovascular diseases. Some edible and medicinal plants show anti-obesity activity, such as fruits, vegetables, spices, legumes, edible flowers, mushrooms, and medicinal plants. Numerous studies have indicated that these plants are potential candidates for the prevention and management of obesity. The major anti-obesity mechanisms of plants include suppressing appetite, reducing the absorption of lipids and carbohydrates, inhibiting adipogenesis and lipogenesis, regulating lipid metabolism, increasing energy expenditure, regulating gut microbiota, and improving obesity-related inflammation. In this review, the anti-obesity activity of edible and medicinal plants was summarized based on epidemiological, experimental, and clinical studies, with related mechanisms discussed, which provided the basis for the research and development of slimming products. Further studies should focus on the exploration of safer plants with anti-obesity activity and the identification of specific anti-obesity mechanisms.


Asunto(s)
Fármacos Antiobesidad , Plantas Medicinales , Metabolismo Energético , Humanos , Metabolismo de los Lípidos , Obesidad/tratamiento farmacológico , Obesidad/prevención & control , Plantas Comestibles
19.
J Fluoresc ; 31(6): 1771-1777, 2021 Nov.
Artículo en Inglés | MEDLINE | ID: mdl-34495467

RESUMEN

Currently, atherosclerosis accounts for the majority of cardiovascular morbidity and mortality worldwide, and predicting the stability of atherosclerotic plaque is the main method to prevent atherosclerotic death. This study aims to establish a dual-label time-resolved fluorescence immunoassay (TRFIA) of matrix metalloprotein-9 (MMP-9) and lipoprotein-associated phospholipaseA2 (Lp-PLA2) to predict atherosclerotic plaque stability. A dual-label TRFIA was introduced for the simultaneous quantification of MMP-9 and Lp-PLA2 using fluorescent lanthanide (Eu3+ and Sm3+) chelates. The performance (sensitivity, specificity, accuracy, precision and reference intervals in different subjects) of this TRFIA was evaluated and compared with commercial kit. The sensitivity of the TRFIA for MMP-9 was 0.85 ng/mL and for Lp-PLA2 was 0.68 ng/mL with high affinity and specificity. The average recoveries were 94.58% to 109.82%, and 104.32% to 109.26%, respectively. All intra- and inter-assay CVs ranged from 3.10% to 5.46%. For the normal subjects, the cutoff value was 160.70 ng/mL for MMP-9 and 183.73 ng/mL for LP-PLA2; for the subjects with stable plaque, the cutoff value was 181.98~309.22 ng/mL for MMP-9 and 194.73~337.89 ng/mL for LP-PLA2; for the subjects with unstable plaque, the cutoff value was 330.43 ng/mL for MMP-9 and 343.23 ng/mL for LP-PLA2. This TRFIA detection results agreed well with the results of commercial kit (R2=0.9567 and R2=0.9771, respectively) in clinical serum samples. The TRFIA developed has a wide detection range and good sensitivity for the high-throughput simultaneous detection of MMP-9 and Lp-PLA2 in serum, which provides a new method for predicting the stability of atherosclerotic plaque.


Asunto(s)
1-Alquil-2-acetilglicerofosfocolina Esterasa/sangre , Fluoroinmunoensayo , Metaloproteinasa 9 de la Matriz/sangre , 1-Alquil-2-acetilglicerofosfocolina Esterasa/metabolismo , Europio/química , Humanos , Metaloproteinasa 9 de la Matriz/metabolismo , Samario/química , Factores de Tiempo
20.
Oral Dis ; 27(5): 1171-1183, 2021 Jul.
Artículo en Inglés | MEDLINE | ID: mdl-32892462

RESUMEN

OBJECTIVE: In this study, we sought to determine the expression profiles of long non-coding RNAs (lncRNAs) and messenger RNAs (mRNAs) and construct functional networks to analyze their potential roles following botulinum toxin type A (BTXA)-mediated inhibition of salivary secretion. METHODS: The submandibular gland of rats in the BTXA and control groups was injected with BTXA and saline, respectively. Microarray analysis was used to identify the differentially expressed lncRNAs and mRNAs. Gene ontology and pathway analysis were performed to examine the biological functions. Functional networks, including lncRNA-mRNA co-expression and competing endogenous RNA (ceRNA) networks, were constructed to reveal the interaction between the coding and non-coding genes. RESULTS: Microarray analysis revealed that 254 lncRNAs and 631 mRNAs were differentially expressed between the BTXA and control groups. Bioinformatic analysis revealed that most of the mRNAs were closely related to transmembrane transporter activity. lncRNA-mRNA co-expression and ceRNA networks were constructed, and several critical mRNA-lncRNA axes and key microRNAs related to salivary secretion were identified. CONCLUSIONS: Our study identified differentially expressed lncRNAs and mRNAs through microarray analysis and explored the interactions between the coding and non-coding genes through bioinformatic analysis. These findings provide new insights into the mechanism of BTXA-mediated inhibition of salivary secretion.


Asunto(s)
Toxinas Botulínicas Tipo A , MicroARNs , ARN Largo no Codificante , Animales , Redes Reguladoras de Genes , ARN Largo no Codificante/genética , ARN Mensajero/genética , Ratas
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