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1.
Sci Total Environ ; 857(Pt 1): 159427, 2023 Jan 20.
Artigo em Inglês | MEDLINE | ID: mdl-36244486

RESUMO

Quizalofop-p-ethyl is a widely used herbicide that poses a threat to human health and environmental safety. In this study, anti-quizalofop-p-ethyl monoclonal antibodies (mAbs) were prepared and used to develop a gold nanoparticle-based lateral flow immunoassay (AuNP-LFIA) for the detection of quizalofop-p-ethyl in agriproducts and environmental samples. Four hybridoma cell lines were obtained, among which 5B6D10E11 secreted mAb with the highest sensitivity, with a 50 % inhibition concentration of 4.57 ng/mL in the indirect competitive enzyme-linked immunosorbent assay. After optimization, the AuNP-LFIA strip based on the mAb (5B6D10E11) showed a visual detection limit of 10 ng/mL, and the results could be directly determined by the naked eye within 8 min. The cross-reactivity of the AuNP-LFIA for analogs of quizalofop-p-ethyl was negligible except for quizalofop-p-acid. The established AuNP-LFIA was proven to be accurate and precise based on the recovery test. Furthermore, the detection results of AuNP-LFIA were consistent with those of ultra-high-performance liquid chromatography tandem mass spectrometry.


Assuntos
Ouro , Nanopartículas Metálicas , Humanos , Ouro/química , Nanopartículas Metálicas/química , Imunoensaio/métodos , Ensaio de Imunoadsorção Enzimática/métodos , Limite de Detecção
2.
Food Chem ; 401: 134053, 2023 Feb 01.
Artigo em Inglês | MEDLINE | ID: mdl-36096008

RESUMO

Constructing robust group-specific probes and non-competitive analysis methods for small molecules in the fields of food analysis is of great significance. In this study, three diarrhetic shellfish poisons (DSPs) with high safety risks to humans were taken as models of group targets, and a non-competitive and turn-on format colorimetric aptasensor was constructed for simultaneous and highly sensitive detection of the class of DSPs. A pair of anti-DSP split aptamers were generated with group-specific binding affinity to the three targets. The split aptamers were then fabricated with a hybridization chain reaction (HCR)-enhanced AuNPs nanozyme. The aptasensor realized linear detection range of 187.5-3000 pM, high sensitivity with a limit of detection (LOD) as low as 65.36 pM, good selectivity, as well as good accuracy when analyzing the DSPs in shellfish samples. This study provides good reference for developing robust probes and facile biosensors to detect multiple small molecules in food matrix.


Assuntos
Aptâmeros de Nucleotídeos , Técnicas Biossensoriais , Nanopartículas Metálicas , Venenos , Humanos , Ouro/química , Aptâmeros de Nucleotídeos/genética , Aptâmeros de Nucleotídeos/química , Nanopartículas Metálicas/química , Hibridização de Ácido Nucleico , Colorimetria/métodos , Limite de Detecção , Técnicas Biossensoriais/métodos
3.
Mol Neurobiol ; 2022 Dec 05.
Artigo em Inglês | MEDLINE | ID: mdl-36469225

RESUMO

Electroconvulsive therapy (ECT) is an effective neuromodulatory therapy for major depressive disorder (MDD). Treatment is associated with regional changes in brain structure and function, indicating activation of neuroplastic processes. To investigate the underlying neurobiological mechanism of macroscopic reorganization following ECT, we longitudinally (before and after ECT in two centers) collected magnetic resonance images for 96 MDD patients. Similar patterns of cortical thickness (CT) changes following ECT were observed in two centers. These CT changes were spatially colocalized with a weighted combination of genes enriched for neuroplasticity-related ontology terms and pathways (e.g., synaptic pruning) as well as with a higher density of D2/3 dopamine receptors. A multiple linear regression model indicated that the region-specific gene expression and receptor density patterns explained 40% of the variance in CT changes after ECT. In conclusion, these findings suggested that dopamine signaling and neuroplasticity-related genes are associated with the ECT-induced morphological reorganization.

4.
Artigo em Inglês | MEDLINE | ID: mdl-36331735

RESUMO

Soil selenium (Se) is mainly inorganic including selenate and selenite but organic forms such as selenomethionine (SeMet) and selenocystine (SeCys2) are commonly present. Although organic Se is bioavailable or potentially bioavailable to plants, whether the effects of the organic Se on uptake and accumulation of Se in winter wheat differ in forms is still not clear. Both hydroponic experiments and a pot trial of whole plant growth stage were conducted to investigate the effects of SeMet and L-selenocystine (SeCys2) on uptake and accumulation of Se in winter wheat (Triticum aestivum L. cv. Xinong 979). Not only metabolic inhibitor (carbonyl cyanide m-chlorophenylhydrazone (CCCP)) inhibited SeMet (44%) influx into wheat roots but also aquaporin inhibitor (AgNO3) or putative inhibitor (H2SiO4 and H3BO3) suppressed 83%, 62%, or 64% SeMet influx into the roots. However, these inhibitors had insignificant effects on SeCys2 influx into the roots. Wheat grain possessed more effective Se accumulation under SeCys2 treatments than under SeMet treatments, which was contributed to more efficiently translocation of Se from husk to grain, more remobilization of tissue Se to grain, and significantly higher concentration of soluble Se (SOL-Se) and exchangeable and carbonate-bound Se (EXC-Se) in the rhizosphere of winter wheat. The present study indicated that the effects of organic Se on uptake and accumulation of Se in winter wheat differed in forms and that SeCys2 exhibited the potential to increase grain Se concentration in winter wheat. The results from the present study will replenish information about the effects and related mechanisms of SeMet or SeCys2 on uptake and accumulation of Se in winter wheat and provide insights of effects of organic Se on wheat grain Se accumulation.

5.
G3 (Bethesda) ; 2022 Nov 07.
Artigo em Inglês | MEDLINE | ID: mdl-36342187

RESUMO

Flavonoids are rich in tea plants (Camellia sinensis), and responsible for the flavor and healthful benefits of tea beverage. The anthocyanin levels in the purple tender shoots are higher than in the general green leaves of tea plant, which provide special materials to search metabolic mechanisms of flavonoid enrichment in plant. In this work, flavonoid differences between purple and green shoots from tea cultivars 'Zijuan' (ZJ) and 'Yunkang10' (YK-10) were investigated through metabolomic analysis, and mechanisms for their difference were surveyed by comparative transcriptomic and proteomic analysis. Levels of 34 flavonoids were different between ZJ and YK-10 shoots. Among them, eight and six were marker metabolites in ZJ and YK-10, respectively. The differentially expressed genes (DEGs), proteins (DEPs) and different-level metabolites (DLMs) between ZJ and YK-10 were researched, respectively; and interactions including DEG-DLM, DEP-DLM, DEG-DEP and DEG-DEP-DLM were analyzed; the contents of 18 characteristic flavonoids in tea leaves and expressions of 34 flavonoid metabolic genes were measured to verify the omics results. Integrated above analyses, a proposed model of flavonoids biosynthesis in tea shoots were established. The differential expression of the leucoanthocyanidin reductase (LAR), anthocyanidin synthase (ANS), anthocyanidin reductase (ANR), UDPG-flavonoid glucosyltransferase (UGT) 75L12 and 94P1 at gene level, and the ANS, ANR and UGT78A15 at protein level, were closely associated with differences in flavonoids between ZJ and YK-10 shoot. Together, this study provides new information on the flavonoid accumulation mechanism in tea plant.

6.
Reprod Biol Endocrinol ; 20(1): 160, 2022 Nov 21.
Artigo em Inglês | MEDLINE | ID: mdl-36411450

RESUMO

BACKGROUND: MicroRNAs (miRNAs) are considered potential biomarkers for various diseases. This study investigated whether hsa-miR-320a-3p and hsa-miR-483-5p levels in human ovarian granulosa cells derived from follicular fluids are associated with embryo developmental competence. METHODS: We collected 195 granulosa cells samples and analyzed the treatment outcomes in patients undergoing in vitro fertilization (n = 147) or intracytoplasmic sperm injection (n = 48) cycles. The hsa-miR-320a-3p and hsa-miR-483-5p levels in granulosa cells were measured using quantitative reverse transcription-polymerase chain reaction. RESULTS: Patients were subdivided into four groups according to the granulosa cells hsa-miR-320a-3p and hsa-miR-483-5p levels quartiles (Q1-Q4). Embryo developmental competence was compared using the chi-square test. Patients in Q3 were less likely to achieve a normal fertilization rate for in vitro fertilization and blastocyst formation than those in Q1 as they expressed high levels of hsa-miR-320a-3p and hsa-miR-483-5p (P < 0.05). Patients in Q3 and Q4 were less likely to achieve a good-quality embryo as they expressed high levels of hsa-miR-483-5p and hsa-miR-320a-3p (P < 0.05). The hsa-miR-320a-3p and hsa-miR-483-5p levels were not associated with clinical pregnancy. However, multiple regression analysis indicated that in Q3 and Q4 intervals had experienced a decreased chance of live birth due to high expression levels of hsa-miR-320a-3p and hsa-miR-483-5p levels. The relative hsa-miR-320a-3p expression levels in granulosa cells were weakly and positively correlated with the patient age (P = 0.0033). Moreover, both the basal follicle stimulating hormone (P = 0.0003) and ovarian stimulation protocols (P = 0.006 and P = 0.004) significantly and positively affected hsa-miR-320a-3p levels. The days of stimulation was negatively correlated with the relative hsa-miR-320a-3p expression level (P = 0.047). CONCLUSIONS: The hsa-miR-320a-3p and hsa-miR-483-5p levels in human granulosa cells negatively correlated with the good-quality embryo rate and live birth, indicating that hsa-miR-320a-3p and hsa-miR-483-5p can be used as potential negative indicators to predict good-quality embryos and live births.


Assuntos
Nascido Vivo , MicroRNAs , Feminino , Gravidez , Humanos , Masculino , Nascido Vivo/genética , Injeções de Esperma Intracitoplásmicas , Sêmen/metabolismo , MicroRNAs/genética , MicroRNAs/metabolismo , Células da Granulosa/metabolismo , Biomarcadores
7.
Stem Cell Rev Rep ; 2022 Nov 25.
Artigo em Inglês | MEDLINE | ID: mdl-36434300

RESUMO

Type 1 diabetes (T1D) is a chronic, lifelong metabolic disease. It is characterised by the autoimmune-mediated loss of insulin-producing pancreatic ß cells in the islets of Langerhans (ß-islets), resulting in disrupted glucose homeostasis. Administration of exogenous insulin is the most common management method for T1D, but this requires lifelong reliance on insulin injections and invasive blood glucose monitoring. Replacement therapies with beta cells are being developed as an advanced curative treatment for T1D. Unfortunately, this approach is limited by the lack of donated pancreatic tissue, the difficulties in beta cell isolation and viability maintenance, the longevity of the transplanted cells in vivo, and consequently high costs. Emerging approaches to address these limitations are under intensive investigations, including the production of insulin-producing beta cells from various stem cells, and the development of bioengineered devices including nanotechnologies for improving islet transplantation efficacy without the need for recipients taking toxic anti-rejection drugs. These emerging approaches present promising prospects, while the challenges with the new techniques need to be tackled for ultimately clinical treatment of T1D. This review discussed the benefits and limitations of the cell-based therapies for beta cell replacement as potential curative treatment for T1D, and the applications of bioengineered devices including nanotechnology to overcome the challenges associated with beta cell transplantation.

8.
Cerebellum ; 2022 Nov 25.
Artigo em Inglês | MEDLINE | ID: mdl-36434494

RESUMO

Primary autoimmune cerebellar ataxia (PACA) is an idiopathic sporadic cerebellar ataxia that is thought to be immune-mediated but lacks biomarkers or a known cause. Here, we report two cases of immune-mediated cerebellar ataxia that responded favorably to immunotherapy, in which tissue-based indirect immunofluorescence test for serum or cerebrospinal fluid (CSF) samples yielded positive results. Case 1 was a 78-year-old man who presented with subacute progressive gait ataxia with truncal instability and dysarthria in response to steroids. Case 2 was a 62-year-old man who presented with relapses and remissions of acute progressive cerebellar ataxia occurring 1-2 times per year. Despite a favorable response to steroid treatment, he relapsed repeatedly in the absence of long-term immunosuppression. In the case of "idiopathic" cerebellar ataxia, immune-mediated causes should be investigated, and immunotherapy may have therapeutic effects.

9.
J Med Chem ; 65(22): 15227-15237, 2022 Nov 24.
Artigo em Inglês | MEDLINE | ID: mdl-36356292

RESUMO

Severe acute respiratory syndrome-coronavirus-1/2 (SARS-CoV-1/2) macrodomain 3 (Mac3) is critical for replication and transcription of the viral genome and is therefore a potential therapeutic target. Here, we solved the crystal structure of SARS-CoV-2 Mac3, which reveals a small-molecule binding pocket. Two low-molecular-weight drugs, oxaprozin and meclomen, induced different patterns of nuclear magnetic resonance (NMR) chemical shift perturbations (CSPs). Meclomen binds to site I of SARS-CoV-2 Mac3 with binding pose determined by NMR CSP and transferred paramagnetic relaxation enhancement, while oxaprozin binds to site II as revealed by the crystal structure. Interestingly, oxaprozin and meclomen both perturb residues in site I of SARS-CoV Mac3. Fluorescence polarization experiments further demonstrated that oxaprozin and meclomen inhibited the binding of DNA-G4s to SARS-CoV-2 Mac3. Our work identified two adjacent ligand-binding sites of SARS-CoV-2 Mac3 that shall facilitate structure-guided fragment linking of these compounds for more potent inhibitors.


Assuntos
COVID-19 , Proteases Semelhantes à Papaína de Coronavírus , SARS-CoV-2 , Humanos , Sítios de Ligação , COVID-19/tratamento farmacológico , Ácido Meclofenâmico , Oxaprozina , Proteínas não Estruturais Virais/metabolismo , Proteases Semelhantes à Papaína de Coronavírus/química
10.
Anal Chem ; 94(47): 16282-16289, 2022 Nov 29.
Artigo em Inglês | MEDLINE | ID: mdl-36322695

RESUMO

Researchers have been looking for ways to fix the structural stability of aptamers so as to achieve the high affinity of aptamers and thus the high sensitivity of analytical methods. Herein, we report a post-selection strategy to facilitate the formation of aptameric structures and enhance their affinity. Key fragments containing crucial bases of parent aptamers were identified and evolved by iterative embedding to form chimeras. The termini of the optimized chimera were then fixed by hybridization to limit their flexibility. Robust aptamers with more stable structures and higher affinity were thus engineered. An anti-okadaic acid aptamer, anti-dinophysistoxin aptamer, and anti-phosphatidylserine (PS) aptamer were engineered in this way, with the affinity enhanced by 160.5-fold, 50.36-fold, and 39.28-fold over that of the parent aptamers, respectively. Furthermore, the practicability of the anti-PS aptamer was validated with a polyA-nanotetrahedron-assisted electrochemical aptasensor. The aptasensor achieved high sensitivity, with the limit of detection as low as 1.741 nM, good accuracy, and good selectivity when monitoring PS in real biosynthesis samples. This study offers a facile and efficient approach to generate robust aptamers and aptasensors for real-world applications.


Assuntos
Aptâmeros de Nucleotídeos , Técnicas Biossensoriais , Aptâmeros de Nucleotídeos/química , Técnicas Biossensoriais/métodos , Ácido Okadáico , Limite de Detecção
11.
Clin Transl Med ; 12(11): e1116, 2022 Nov.
Artigo em Inglês | MEDLINE | ID: mdl-36437506

RESUMO

BACKGROUND: The potential of circulating tumour DNA (ctDNA) as a reliable biomarker for relapse/metastasis early detection and prognosis in esophageal squamous cell carcinoma (ESCC) after radiotherapy/chemoradiotherapy (RT/CRT) initiation requires comprehensive investigation. METHODS: Treatment-naive locally advanced ESCC patients with available baseline plasma samples were prospectively enrolled from November 2018 to January 2020. RT/CRT was delivered with a simultaneous integrated boost of radiation dose. Serial plasma samples were collected at baseline (T0 ), week 4 of RT/CRT (T1 ), 1-3 (T2 ) and 3-6 months post-RT/CRT (T3 ). ctDNA was analysed using next-generation sequencing of 474 cancer-relevant genes. RESULTS: A total of 128 plasma samples from 40 eligible patients were analysed (median age: 64 [range: 40-78], 88% males, 95% stage III/IV), and the median follow-up time was 20.6 months (range: 12.2-33.3). During the post-RT/CRT surveillance including 36 patients, radiological progression was observed in 16 patients, and 69% (11/16) had detectable post-RT/CRT ctDNA prior to radiological progression, with a median lead time of 4.4 months compared with radiological imaging. ctDNA positivity at T1 (hazard ratio, HR: 3.60, 95% confidence interval, CI: 1.30-10.01) or T2 (HR: 5.45, 95% CI: 1.72-17.26) indicated inferior progression-free survival (PFS). ctDNA clearance between T0 -T1 (HR: 0.31, 95% CI: 0.08-1.13) or T0 -T2 (HR: 0.11; 95% CI: 0.02-0.61) was associated with relatively favourable PFS. Similar results were obtained when focusing on patients without esophagectomy after RT/CRT. Notably, detectable ctDNA at T1 was a potential indicator of high local recurrence risks (HR: 4.43, 95% CI: 1.31-15.04). CONCLUSIONS: ctDNA was identified as a robust biomarker for early detection of disease progression and post-RT/CRT prognosis stratification in ESCC. Detectable ctDNA at week 4 of RT/CRT might indicate higher local recurrence risks, implying the potential clinical utility of ctDNA tests in guiding post-RT/CRT treatments for locoregional control in ESCC.


Assuntos
DNA Tumoral Circulante , Neoplasias Esofágicas , Carcinoma de Células Escamosas do Esôfago , Masculino , Humanos , Pessoa de Meia-Idade , Feminino , Carcinoma de Células Escamosas do Esôfago/diagnóstico , Carcinoma de Células Escamosas do Esôfago/genética , Carcinoma de Células Escamosas do Esôfago/radioterapia , DNA Tumoral Circulante/genética , Prognóstico , Neoplasias Esofágicas/diagnóstico , Neoplasias Esofágicas/genética , Neoplasias Esofágicas/radioterapia , Recidiva Local de Neoplasia/genética , Recidiva Local de Neoplasia/radioterapia
12.
Cell Syst ; 13(11): 932-944.e5, 2022 Nov 16.
Artigo em Inglês | MEDLINE | ID: mdl-36356577

RESUMO

Expression of the non-coding RNA XIST is essential for initiating X chromosome inactivation (XCI) during early development in female mammals. As the main function of XCI is to enable dosage compensation of chromosome X genes between the sexes, XCI and XIST expression are generally absent in male normal tissues, except in germ cells and in individuals with supernumerary X chromosomes. Via a systematic analysis of public sequencing data of both cancerous and normal tissues, we report that XIST is somatically activated in a subset of male human cancers across diverse lineages. Some of these cancers display hallmarks of XCI, including silencing of gene expression, reduced chromatin accessibility, and increased DNA methylation across chromosome X, suggesting that the developmentally restricted, female-specific program of XCI can be somatically accessed in male cancers.


Assuntos
Neoplasias , RNA Longo não Codificante , Animais , Humanos , Masculino , Feminino , Inativação do Cromossomo X/genética , RNA Longo não Codificante/genética , RNA Longo não Codificante/metabolismo , Cromossomo X/metabolismo , Compensação de Dosagem (Genética) , Mamíferos/genética , Neoplasias/genética
13.
Clin Exp Med ; 2022 Nov 08.
Artigo em Inglês | MEDLINE | ID: mdl-36348126

RESUMO

The aim of the present study was to investigate the factors influencing the short-term response to the initial radioiodine therapy (RT) course in patients with intermediate- and high-risk papillary thyroid carcinoma (PTC). A total of 182 patients with intermediate- and high-risk PTC who underwent RT in our hospital from March 2018 to October 2020 were retrospectively enrolled. The patients were divided into incomplete response (IR) and nonincomplete response (Non-IR) groups according to the response observed in clinical follow-up within 6-12 months after RT. Univariate and multivariate logistic regression analyses were used to investigate the effects of 15 observed factors on the response to RT. Receiver operating characteristic (ROC) curve analysis was used to determine the value of factors found to be significant in multivariate analyses for predicting an IR. A total of 182 patients with intermediate- and high-risk PTC were analyzed; the percentage of patients with a Non-IR was 61.54% (112/182), and the percentage of patients with an IR was 38.46% (70/182). The CD4+ T-cell percentage (t = 4.757, P = 0.000), CD4/CD8 (z = - 2.632, P = 0.008), stimulated thyroglobulin (sTg) level (z = - 8.273, P = 0.000) and M stage (χ2 = 17.823, P = 0.000) of the two groups were significantly different. Multivariate analysis showed that only the sTg level (OR: 1.116, 95% CI 1.068-1.165, P < 0.001) and CD4+ T-cell percentage (OR: 0.909, 95% CI 0.854-0.968, P = 0.003) were independent factors associated with the therapeutic response to RT. The cutoff sTg level and CD4+ T-cell percentage for predicting an IR were 7.62 µg/L and 40.95%, respectively. The sTg level and CD4+ T-cell percentage were verified to be independent predictive factors of RT response. Higher sTg levels and lower CD4+ T-cell percentages were related to an IR in patients with intermediate- and high-risk PTC.

14.
World J Clin Cases ; 10(32): 11898-11907, 2022 Nov 16.
Artigo em Inglês | MEDLINE | ID: mdl-36405256

RESUMO

BACKGROUND: Pulmonary hypertension (PH) is a severe complication of bronchopulmonary dysplasia (BPD) in premature neonates and is closely related to prognosis. However, there is no effective and safe treatment for PH due to BPD in infants. Successful treatment for cases of BPD-associated PH with Tadalafil combined with bosentan is rare. This case may make a significant contribution to the literature because PH is difficult to manage as a serious complication of BPD in preterm infants. Mortality is high, especially when it is complicated by heart failure. CASE SUMMARY: An extremely premature neonate with a gestational age of 26+5 wk and birth weight of 0.83 kg was diagnosed with BPD associated with PH; oral sildenafil did not improve the PH. The infant experienced sudden cardiac arrest and serious heart failure with severe PH. After a series of treatments, including cardiopulmonary resuscitation, mechanical ventilation, and inhaled nitric oxide (iNO), the respiratory and circulatory status improved but the pulmonary artery pressure remained high. Then oral sildenafil was replaced with oral tadalafil and bosentan; pulmonary artery pressure improved, and the infant recovered at our hospital. After 2 years of follow-up, she is in good condition, without any cardiovascular complications. CONCLUSION: INO can effectively improve the respiratory and circulatory status of infants with PH associated with premature BPD. B-type natriuretic peptide should be routinely measured during hospitalization to evaluate the risk and prognosis of BPD-associated PH in preterm infants. Tadalafil combined with bosentan for the treatment of PH associated with premature BPD was better than sildenafil in this case. Further studies are needed to explore the efficacy and safety of different vasodilators in the treatment of PH associated with premature BPD.

15.
Orthop Surg ; 2022 Nov 21.
Artigo em Inglês | MEDLINE | ID: mdl-36411536

RESUMO

OBJECTIVE: Musculoskeletal pain is the most prominent clinical manifestation of more than 150 musculoskeletal disease conditions, and its effective long-term management poses a great challenge to healthcare systems globally. For this, it is important to understand current research progress on musculoskeletal pain management. The purpose of the present study is to provide a comprehensive insight into the current state of research and global trends in musculoskeletal pain management. METHODS: Publications on musculoskeletal pain management from 1972 to 2021 were retrieved from the Science Citation Index-Expanded (SCIE) database. Included articles were any article type related to aspects of musculoskeletal pain management, including etiology, mechanisms, epidemiology, treatment, outcomes, side effects, and patient compliance. Publication data were analyzed using bibliometric methods. The software VOSviewer was employed to perform bibliographic coupling, co-authorship, co-citation, and co-occurrence analysis, and to visualize publication tendencies in musculoskeletal pain management. RESULTS: A total of 5475 articles were included in this study. The number of global publications on musculoskeletal pain management has escalated annually. Based on the number of publications and citations from the published literature, as well as the H-index, the United States led global contributions in this area. The institutions making the highest contributions were the League of European Research Universities (LERU), the University of Sydney, and Harvard University. The journal BMC Musculoskeletal Disorders published the highest number of articles in this area. The published studies fall under six groups: "Prevention and rehabilitation," "Etiology and diagnosis," "Clinical study," "Epidemiology," "Mental health," and "Education." High-quality primary studies and epidemiology are predicted to be the next prevailing topics in this field of research. CONCLUSIONS: Based on current global trends, the number of publications on musculoskeletal pain management will continue to increase. Future studies will likely place more emphasis on high-quality randomized controlled trials (RCTs) and epidemiological studies.

16.
J Virol ; 96(22): e0130922, 2022 Nov 23.
Artigo em Inglês | MEDLINE | ID: mdl-36317881

RESUMO

Respiratory syncytial virus (RSV) is a major pathogen that can cause acute respiratory infectious diseases of the upper and lower respiratory tract, especially in children, elderly individuals, and immunocompromised people. Generally, following viral infection, respiratory epithelial cells secrete cytokines and chemokines to recruit immune cells and initiate innate and/or adaptive immune responses. However, whether chemokines affect viral replication in nonimmune cells is rarely clear. In this study, we detected that chemokine CCL5 was highly expressed, while expression of its receptor, CCR1, was downregulated in respiratory epithelial cells after RSV infection. When we overexpressed CCR1 on respiratory epithelial cells in vivo or in vitro, viral load was significantly suppressed, which can be restored by the neutralizing antibody for CCR1. Interestingly, the antiviral effect of CCR1 was not related to type I interferon (IFN-I), apoptosis induction, or viral adhesion or entry inhibition. In contrast, it was related to the preferential recruitment and activation of the adaptor Gαi, which promoted inositol 1,4,5-triphosphate receptor type 3 (ITPR3) expression, leading to inhibited STAT3 phosphorylation; explicitly, phosphorylated STAT3 (p-STAT3) was verified to be among the important factors regulating the activity of HSP90, which has been previously reported to be a chaperone of RSV RNA polymerase. In summary, we are the first to reveal that CCR1 on the surface of nonimmune cells regulates RSV replication through a previously unknown mechanism that does not involve IFN-I induction. IMPORTANCE Our results revealed a novel mechanism by which RSV escapes innate immunity. That is, although it induces high CCL5 expression, RSV might attenuate the binding of CCL5 by downregulating the expression of CCR1 in respiratory epithelial cells to weaken the inhibitory effect of CCR1 on HSP90 activity and thereby facilitate RSV replication in nonimmune cells. This study provides a new target for the development of co-antiviral inhibitors against other components of the host and co-molecular chaperone/HSP90 and provides a scientific basis for the search for effective broad-spectrum antiviral drugs.


Assuntos
Receptores CCR1 , Infecções por Vírus Respiratório Sincicial , Vírus Sincicial Respiratório Humano , Replicação Viral , Humanos , Quimiocinas , Receptores CCR1/genética , Receptores CCR1/metabolismo , Vírus Sincicial Respiratório Humano/fisiologia , Subunidades alfa de Proteínas de Ligação ao GTP/genética , Subunidades alfa de Proteínas de Ligação ao GTP/metabolismo
17.
J Gastrointest Oncol ; 13(5): 2366-2374, 2022 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-36388693

RESUMO

Background: Neoadjuvant chemoradiotherapy is recommended for locally advanced rectal cancer, allowing preoperative down-staging of the primary tumor to facilitate complete surgical removal. However, further investigation is warranted for identifying whether radiotherapy is necessary for rectal mucinous adenocarcinoma (RMAC). Thus, this study was designed to explore the relationship between mFOLFOX6 with or without preoperative radiotherapy and therapeutic efficacy in locally advanced RMAC. Methods: A total of 81 patients were retrospectively enrolled, with MRI-defined clinical stage II/III RMAC received neoadjuvant treatment with mFOLFOX6 alone (group A) or mFOLFOX6 plus radiation (group B), followed by total mesorectal excision. Tumor down-staging and tumor response were assessed based on post-treatment MRI-defined radiographical and pathological findings. Follow-up data were retrieved, and the Kaplan-Meier curve was used to determine the relationship between the 3-year disease-free survival (DFS) and overall survival (OS) in the two groups. Results: There were no significant differences in the clinical baseline characteristics of patients between group A and group B. The sphincter preservation rate in group B was 60.9%, higher than in group A (20.0%) (P=0.031). The rate of pathological complete response (pCR) was 14.0% in group B, while no patients had pCR in group A (P=0.029), and the tumor response rate in group B was higher than in group A (52.0% vs. 16.1%, P=0.001). The 3-year probability of OS in group A and B was 77.4% and 72.0% (P=0.509), and 3-year DFS was 58.1% and 56.0% (P=0.592), respectively. Conclusions: Neoadjuvant mFOLFOX6-based chemoradiotherapy could be a promising therapeutic option for patients with RMAC, which was associated with a high rate of pCR and sphincter preservation in comparison to treated with mFOLFOX6 alone.

18.
Biomicrofluidics ; 16(6): 061502, 2022 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-36389273

RESUMO

The liver is the largest internal organ in the human body with largest mass of glandular tissue. Modeling the liver has been challenging due to its variety of major functions, including processing nutrients and vitamins, detoxification, and regulating body metabolism. The intrinsic shortfalls of conventional two-dimensional (2D) cell culture methods for studying pharmacokinetics in parenchymal cells (hepatocytes) have contributed to suboptimal outcomes in clinical trials and drug development. This prompts the development of highly automated, biomimetic liver-on-a-chip (LOC) devices to simulate native liver structure and function, with the aid of recent progress in microfluidics. LOC offers a cost-effective and accurate model for pharmacokinetics, pharmacodynamics, and toxicity studies. This review provides a critical update on recent developments in designing LOCs and fabrication strategies. We highlight biomimetic design approaches for LOCs, including mimicking liver structure and function, and their diverse applications in areas such as drug screening, toxicity assessment, and real-time biosensing. We capture the newest ideas in the field to advance the field of LOCs and address current challenges.

19.
Int J Mol Sci ; 23(21)2022 Nov 01.
Artigo em Inglês | MEDLINE | ID: mdl-36362097

RESUMO

Chlorine dioxide is widely used for pulp bleaching because of its high delignification selectivity. However, efficient and clean chlorine dioxide bleaching is limited by the complexity of the lignin structure. Herein, the oxidation reactions of phenolic (vanillyl alcohol) and non-phenolic (veratryl alcohol) lignin model species were modulated using chlorine dioxide. The effects of chlorine dioxide concentration, reaction temperature, and reaction time on the consumption rate of the model species were also investigated. The optimal consumption rate for the phenolic species was obtained at a chlorine dioxide concentration of 30 mmol·L-1, a reaction temperature of 40 °C, and a reaction time of 10 min, resulting in the consumption of 96.3% of vanillyl alcohol. Its consumption remained essentially unchanged compared with that of traditional chlorine dioxide oxidation. However, the consumption rate of veratryl alcohol was significantly reduced from 78.0% to 17.3%. Additionally, the production of chlorobenzene via the chlorine dioxide oxidation of veratryl alcohol was inhibited. The structural changes in lignin before and after different treatments were analyzed. The overall structure of lignin remained stable during the optimization of the chlorine dioxide oxidation treatment. The signal intensities of several phenolic units were reduced. The effects of the selective oxidation of lignin by chlorine dioxide on the pulp properties were analyzed. Pulp viscosity significantly increased owing to the preferential oxidation of phenolic lignin by chlorine dioxide. The pollution load of bleached effluent was considerably reduced at similar pulp brightness levels. This study provides a new approach to chlorine dioxide bleaching. An efficient and clean bleaching process of the pulp was developed.


Assuntos
Compostos Clorados , Lignina , Lignina/química , Compostos Clorados/farmacologia , Compostos Clorados/química , Fenóis/farmacologia , Ácido Hipocloroso , Cloro/química , Papel
20.
Heliyon ; 8(11): e11622, 2022 Nov.
Artigo em Inglês | MEDLINE | ID: mdl-36411899

RESUMO

Background: Acteoside, a water-soluble active constituent of diverse valuable medicinal vegetation, has shown strong anti-inflammatory property. However, studies on the anti-inflammatory property of acteoside in complement-induced acute lung injury (ALI) are limited. Therefore, this study aims to evaluate the anti-inflammatory activity of acteoside in cobra venom factor (CVF)-stimulated human microvascular endothelial cells (HMEC) and in ALI mice model. Methods: In this study, we investigated the effects of acteoside (20, 10, and 5 µg/mL) in vitro in CVF induced HMECs and the activity of acteoside (100, 50, and 20 mg/kg/day bodyweight) in vivo in CVF induced ALI mice. Each eight male mice were orally administered acteoside or the positive drug PDTC (100 mg/kg/day) for 7 days before CVF (35 µg/kg) injection. After injection for 1 h, the pharmacological effects of acteoside were investigated by spectrophotometry, pathological examination, enzyme-linked immunosorbent assay, and immunohistochemistry. Results: In vitro, acteoside (20, 10, and 5 µg/mL) reduced the protein expression of adhesion molecules and pro-inflammatory cytokines and transcriptional activity of NF-κB (P < 0.01). In vivo studies showed that acteoside dose-dependently alleviated lung histopathologic lesion, inhibited the production of the protein content of BALF, leukocyte cell number, lung MPO activity, and expression levels of IL-6, TNF-α, and ICAM-1, and suppressed the C5b-9 deposition and NF-κB activation in CVF-induced acute lung inflammation in mice (P < 0.05, 0.01). Conclusion: This study demonstrates that acteoside exerts strong anti-inflammatory activities in the CVF-induced acute lung inflammation model and suggests that acteoside is a potential therapeutic agent for complement-related inflammatory diseases.

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