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1.
Eur J Pharmacol ; : 175391, 2022 Nov 15.
Artigo em Inglês | MEDLINE | ID: mdl-36400161

RESUMO

Epilepsy is a chronic disease that affects a wide range of people. Furthermore, a third of patients suffering from epileptic seizures do not respond to antiepileptic drugs. In recent years, increasing attention has focused on the role of oxidative stress in acquired epilepsy, and adjuvant antiepileptic drugs to reduce oxidative stress may be a new therapeutic strategy. In this study ginsenoside Rh2 was resistant to oxidative stress induced by epileptic activity in vivo and in vitro. Using online databases, we identified forkhead box O3a (FOXO3a) overexpression in epilepsy tissue and validated this in vitro, in vivo, and in clinical tissues of patients with epilepsy. An in vitro epilepsy model revealed that the overexpression of FOXO3a led to more severe oxidative stress, while the knockdown of FOXO3a had a protective effect on SH-SY5Y cells. Moreover, our results showed that the positive effect of FOXO3a on oxidative stress was caused by the transcriptional activation of Kelch-like ECH-associated protein 1 (KEAP1), a negative regulator of nuclear factor erythroid 2-related factor 2 (NRF2). We also found that ginsenoside Rh2 can directly inhibit the activation of FOXO3a by selectively blocking CREB-binding protein (CBP)/p300-mediated FOXO3a acetylation and play a role in regulating the KEAP1-NRF2 pathway to resist oxidative stress.

2.
Artigo em Inglês | MEDLINE | ID: mdl-36377924

RESUMO

Ring-opening transformations of donor-acceptor (D-A) cyclopropanes enable the rapid assembly of complex molecules. However, the enantioselective formation of chiral quaternary stereocenters using substrates bearing two different acceptors remains a challenge. Herein, we describe the first palladium-catalyzed highly diastereo- and enantioselective (3+2) cycloaddition of vinyl cyclopropanes bearing two different electron-withdrawing groups, a subset of D-A cyclopropanes. The key to the success of this reaction is the remote stereoinduction through hydrogen bond from chiral ligands, which thereby addressed the aforementioned challenge. A variety of chiral five-membered heterocycles were produced in good yields and with high stereoselectivity (up to 99% yields, 99:1 er and >19:1 dr). In-depth mechanistic investigations, including control experiments and theoretical calculations, revealed the origin of the stereoselectivity and the importance of H-bonding in stereocontrol.

3.
Cell Death Dis ; 13(11): 951, 2022 Nov 10.
Artigo em Inglês | MEDLINE | ID: mdl-36357365

RESUMO

The deubiquitinating enzyme USP1 (ubiquitin-specific protease 1) plays a role in the progression of various tumors, emerging as a potential therapeutic target. This study aimed to determine the role of USP1 as a therapeutic target in hepatocellular carcinoma (HCC). We detected USP1 expression in the tumor and adjacent tissues of patients with HCC using immunohistochemical staining. We evaluated the effect of the USP1 inhibitor ML-323 on HCC cell proliferation and cell cycle using a CCK-8 cell-counting kit and plate cloning assays, and propidium iodide, respectively. Apoptosis was detected by annexin V-FITC/Propidium Iodide (PI) staining and caspase 3 (casp3) activity. Transmission electron microscopy and LC3B immunofluorescence were used to detect autophagy. Western blotting was used to detect the accumulation of ubiquitinated proteins, the expression of endoplasmic reticulum (ER) stress-related proteins, and the AMPK-ULK1/ATG13 signaling pathway. We demonstrated that ML-323 inhibits the growth of HCC cells and induces G1 phase cell cycle arrest by regulating cyclin expression. ML-323 treatment resulted in the accumulation of ubiquitinated proteins, induced ER stress, and triggered Noxa-dependent apoptosis, which was regulated by the Activating Transcription Factor 4(ATF4). Moreover, active ER stress induces protective autophagy by increasing AMPK phosphorylation; therefore, we inhibited ER stress using 4-Phenylbutyric acid (4-PBA), which resulted in ER stress reduction, apoptosis, and autophagy in ML-323-treated HCC cells. In addition, blocking autophagy using the AMPK inhibitor compound C (CC), chloroquine (CQ), or bafilomycin A1 (BafA1) enhanced the cytotoxic effect of ML-323. Our findings revealed that targeting USP1 may be a potential strategy for the treatment of HCC.


Assuntos
Carcinoma Hepatocelular , Neoplasias Hepáticas , Humanos , Carcinoma Hepatocelular/tratamento farmacológico , Carcinoma Hepatocelular/genética , Carcinoma Hepatocelular/metabolismo , Agregados Proteicos , Proteínas Quinases Ativadas por AMP/metabolismo , Proteínas Ubiquitinadas , Neoplasias Hepáticas/tratamento farmacológico , Neoplasias Hepáticas/genética , Neoplasias Hepáticas/metabolismo , Propídio/farmacologia , Estresse do Retículo Endoplasmático , Autofagia , Apoptose , Linhagem Celular Tumoral , Proteases Específicas de Ubiquitina
4.
Chemosphere ; 312(Pt 1): 137169, 2022 Nov 16.
Artigo em Inglês | MEDLINE | ID: mdl-36402353

RESUMO

UV-assisted advanced oxidation processes (AOPs) are widely used and studied in degradation of bisphenol A (BPA). However, detailed information on their radical chemistry and degradation mechanisms is still lacking. In this study, degradation of BPA was comparatively evaluated to investigate the radical mechanisms, products and the toxicity variation in UV/chlorine and UV/H2O2 processes. In comparison with UV/H2O2, UV/chlorine had a higher BPA degradation efficiency and higher pH-dependency due to chlorination and the synergy of •OH and RCS. The •OH and Cl• played a pivotal role as the primary radicals in BPA degradation by UV/chlorine process at all pH investigated (6-8). The relative contributions of the secondary radicals ClO• gradually decreased with a variation of pH from 6 to 8 in this process. Presence of HCO3─ and HA inhibited BPA degradation to different extents in UV/chlorine process, while the effect of Cl─ could be neglected. According to the identified transformation products, chlorination (major), hydroxylation and breakage of the isopropylidene chain were BPA decomposition pathways in the UV/chlorine system. In the UV/H2O2 system, only hydroxylation (major) and breakage of the isopropylidene chain occurred. The toxicity analysis, based on the proposed degradation pathways, indicated that the generation of chlorinated products in the UV/chlorine system led to a higher toxicity of the resulting mixture than in the UV/H2O2 system. Although UV/chlorine has an excellent BPA degradation effect and it is cost-effective, the possible environmental risk should be carefully considered when UV/chlorine system is used to remove BPA in real waters.

5.
Cell Death Dis ; 13(11): 988, 2022 Nov 23.
Artigo em Inglês | MEDLINE | ID: mdl-36418320

RESUMO

COX7A1, a subunit of cytochrome c oxidase, holds an important position in the super-assembly which integrates into multi-unit heteromeric complexes peripherally in the mitochondrial electron transport chain (ETC). Recently, some studies indicated the significant potential of COX7A1 in cancer metabolism and therapy. However, the underlying metabolic process and therapy mechanism remain unclear. In this study, COX7A1-overexpressed cell line was established via lentivirus transduction. The relationship between COX7A1 and ferroptosis, a novel form of cell death driven by iron-dependent lipid peroxidation, was further analyzed in different human non-small-cell lung carcinoma (NSCLC) cells respectively. Our results showed that COX7A1 increased the sensitivity of NSCLC cells to the ferroptosis induced by cysteine deprivation via enhancing the tricarboxylic acid (TCA) cycle and the activity of complex IV in mitochondrial ETC. Meanwhile, COX7A1 suppressed mitochondrial dynamics as well as mitochondrial biogenesis and mitophagy through blocking autophagic flux. The autophagy activator, rapamycin, relieved the autophagic blockage and further strengthened the sensitivity to cysteine deprivation-induced ferroptosis of NSCLC cells in vitro and in vivo. Taken together, our data indicate the close association of COX7A1 with cysteine deprivation-induced ferroptosis, and provide a novel insight into the therapy mode against human NSCLC.


Assuntos
Carcinoma Pulmonar de Células não Pequenas , Ferroptose , Neoplasias Pulmonares , Humanos , Carcinoma Pulmonar de Células não Pequenas/patologia , Cistina/metabolismo , Cisteína , Neoplasias Pulmonares/patologia , Complexo IV da Cadeia de Transporte de Elétrons/metabolismo
6.
Front Plant Sci ; 13: 988485, 2022.
Artigo em Inglês | MEDLINE | ID: mdl-36340378

RESUMO

The plant microbiome profoundly affects many aspects of host performance; however, the ecological processes by which plant hosts govern microbiome assembly, function, and dispersal remain largely unknown. Here, we investigated the bacterial and fungal communities in multiple compartment niches (bulk soil, rhizosphere soil, root endosphere, phylloplane, and leaf endosphere) of Casuarina equisetifolia L. at three developmental stages in Hainan Province, China. We found that microbiome assemblages along the soil-plant continuum were shaped by the compartment niches. Bacterial diversity and richness decreased from the soils to roots to leaves, with the highest network complexity found in the roots and the lowest found in the phylloplane. However, fungal diversity gradually increased from the soils to roots to phyllosphere, whereas fungal richness decreased from the soils to roots but increased from the roots to phyllosphere; the greatest network complexity was found in bulk soils and the lowest was found in the roots. Different biomarker taxa occurred in the different ecological niches. Bacterial and fungal communities exhibited distinct ecological functions; the former played important roles in maintaining plant growth and providing nutrients, whereas the latter predominantly decomposed organic matter. The bacterial community of C. equisetifolia mostly originated from bulk soil, whereas the fungal community was mainly derived from rhizosphere soil and air. Leaf endophytes were positively correlated with organic carbon, and root and soil microorganisms were positively correlated with total nitrogen, total phosphorus, and total potassium. Our findings provide empirical evidence for plant-microbiome interactions and contribute to future research on non-crop management and the manipulation of non-crop microbiomes.

7.
Plant Commun ; : 100472, 2022 Nov 08.
Artigo em Inglês | MEDLINE | ID: mdl-36352792

RESUMO

Wheat powdery mildew, caused by Blumeria graminis f. sp. tritici (Bgt), is a devastating disease threatening wheat production worldwide. Pm12, which originated from Aegilops speltoides, a wild relative of wheat, confers strong resistance to powdery mildew and therefore has potential use in wheat breeding. Using susceptible mutants induced by gamma irradiation, we physically mapped and isolated Pm12 and showed it to be orthologous to Pm21 from Dasypyrum villosum, also a wild relative of wheat. The resistance function of Pm12 was validated via EMS mutagenesis, virus-induced gene silencing, and stable genetic transformation. Evolutionary analysis indicates that the Pm12/Pm21 loci in wheat species are relatively conserved, but dynamic. Here, we demonstrated that the two orthologous genes, Pm12 and Pm21, possess differential resistance against the same set of Bgt isolates. Overexpression of the coiled-coil domains of PM12 and PM21 both induce cell death in Nicotiana benthamiana leaves. However, their full-length forms display different cell death-inducing activities caused by their distinct intramolecular interactions. Cloning of Pm12 will facilitate its application in wheat breeding programs. This study also gives new insight into the two orthologous resistance genes, Pm12 and Pm21, that show different race specificities and intramolecular interaction patterns.

8.
Front Genet ; 13: 1051800, 2022.
Artigo em Inglês | MEDLINE | ID: mdl-36353119

RESUMO

Colon adenocarcinoma (COAD) is a common malignancy and has a high mortality rate. However, the current tumor node metastasis (TNM) staging system is inadequate for prognostic assessment of COAD patients. Therefore, there is an urgent need to identify reliable biomarkers for the prognosis COAD patients. The aberrant expression of necroptosis-related genes (NRGs) is reported to be associated with tumorigenesis and metastasis. In the present work, we compared the expression profiles of NRGs between COAD patients and normal individuals. Based on seven differentially expressed NRGs, a risk score was defined to predict the prognosis of COAD patients. The validation results from both training and independent external cohorts demonstrated that the risk score is able to distinguish the high and low risk COAD patients with higher accuracies, and is independent of the other clinical factors. To facilitate its clinical use, by integrating the proposed risk score, a nomogram was built to predict the risk of individual COAD patients. The C-index of the nomogram is 0.75, indicating the reliability of the nomogram in predicting survival rates. Furthermore, two candidate drugs, namely dapsone and xanthohumol, were screed out and validated by molecular docking, which hold the potential for the treatment of COAD. These results will provide novel clues for the diagnosis and treatment of COAD.

9.
Zhonghua Yi Xue Yi Chuan Xue Za Zhi ; 39(10): 1093-1098, 2022 Oct 10.
Artigo em Chinês | MEDLINE | ID: mdl-36184090

RESUMO

OBJECTIVE: To explore the genetic basis for a child with metachromatic leukodystrophy (MLD). METHODS: Clinical data of the patient was collected. Genomic DNA was extracted from peripheral blood samples of the child and his family members. Potential variant was screened by whole exome sequencing (WES), and candidate variant was verified by Sanger sequencing. The pathogenicity the variant was analyzed by multiple sequence alignment of the amino acid sequence and three-dimensional model prediction of its protein product. RESULTS: The child was found to harbor compound heterozygous variants c.257G>A (p.R86Q) and c.467del (p.G156Afs*6) of the ARSA gene, among which the c.467del (p.G156Afs*6) frameshift variation was unreported previously. Multiple sequence alignment showed that the site of the c.257G>A (p.R86Q) missense variant is highly conserved. Three-dimensional structure modeling analysis showed that the partial deletion due to the p.G156Afs*6 variant may cause significant alteration of the structure of ARSA protein. CONCLUSION: The discovery of novel variant in ARSA has enriched the mutational spectrum of MLD and may facilitate the understanding of the genotype-phenotype correlation of MLD.


Assuntos
Cerebrosídeo Sulfatase , Leucodistrofia Metacromática , Cerebrosídeo Sulfatase/genética , DNA , Estudos de Associação Genética , Humanos , Leucodistrofia Metacromática/genética , Mutação
10.
Front Plant Sci ; 13: 988442, 2022.
Artigo em Inglês | MEDLINE | ID: mdl-36212345

RESUMO

Rhizosphere bacterial diversity and community structure are important factors involving in plant growth. However, the exact process of how plant rhizosphere bacterial community structures is assembled remains unclear. To investigate the role of bacterial chemotaxis to rhizosphere secretions in the establishment of rhizosphere microbial community in Casuarina equisetifolia, we screened bacteria strains derived from the rhizosphere of Casuarina equisetifolia L. using top three chemicals of the plant root exudates (2,4-di-tert-butylphenol, methyl stearate, and arginine) as chemoattractant. Among 72 bacterial strains, five showed strong chemotaxis to 2,4-di-tert-butylphenol, six to methyl stearate, and eleven to arginine, with the highest bacterial chemotaxis occurring at a concentration of 60 µM. This indicates that arginine is a more important chemoattractant than 2,4-di-tert-butylphenol, methyl stearate in the establishment of rhizosphere microbial community in Casuarina equisetifolia. Bacterial community assembly analysis using different chemoattractants and chemoattractants-plus-bacteria combinations were then performed by burying laboratory prepared bags of sterlized soil into C. equisetifolia forest. Bacteria diversity and enrichment analyses using 16S rDNA sequencing at 7 and 14 days after burying showed that arginine-plus-Ochrobactrum sp. and Pantoea sp. treatment exhibited the greatest similarity to the natural forest bacterial community. Our date provides new insights into how chemoattractants and chemotactic bacteria strains shape the rhizosphere microbial community of C. equisetifolia, which constitutes foundational information for future management of these communities.

11.
Front Psychol ; 13: 1010197, 2022.
Artigo em Inglês | MEDLINE | ID: mdl-36237695

RESUMO

Although a large number of literatures have explored the relationship between electronic communication during nonwork time and individual perception and behavior under the Western culture background, we still have some limitations on this topic under the cultural background of collectivism, dedication and "Guanxi" in China. Different from Western organizations, Chinese employees tend to put work first and are more inclusive of handling work tasks during nonwork time. This type of communication during nonwork time can significantly affect employees' cognition, emotion and behavior. From the perspective of Job Demands-Resources theory, this study constructs a double-edged (U-shaped) model between electronic communication during nonwork time and employee withdrawal behavior. Sample data were collected from 516 employees with clear working time boundaries in China. The results indicate that electronic communication during nonwork time has a U-shaped effect on employee withdrawal behavior and an inverted U-shaped effect on employee's cognition, namely job engagement. Job engagement plays a mediating role between them. Moreover, regulatory emotional self-efficacy has a moderating effect on the relationship between electronic communication during nonwork time and job engagement. These findings not only provide theoretical and practical implications for managers and employees on how to reduce withdrawal behaviors, but also advance our understanding of electronic communication during nonwork time in Chinese cultural context.

12.
BMC Med ; 20(1): 369, 2022 10 25.
Artigo em Inglês | MEDLINE | ID: mdl-36280874

RESUMO

BACKGROUND: Circulating tumor DNA (ctDNA) has been proven to be a promising tumor-specific biomarker in solid tumors, but its clinical utility in risk stratification and early prediction of relapse for diffuse large B cell lymphoma (DLBCL) has not been well explored. METHODS: Here, using a lymphoma-specific sequencing panel, we assessed the prognostic and predictive utilities of ctDNA measurements before, during, and after first-line therapy in 73 Chinese DLBCL patients. RESULTS: The pretreatment ctDNA level serving as an independent prognostic factor for both progression-free survival (PFS, adjusted HR 2.47; p = 0.004) and overall survival (OS, adjusted HR 2.49; p = 0.011) was confirmed in our cohort. Furthermore, the patients classified as molecular responders who presented a larger decrease in ctDNA levels after the initial two treatment cycles had more favorable PFS (unreached vs. 6.25 months; HR 5.348; p = 0.0015) and OS (unreached vs. 25.87; HR 4.0; p = 0.028) than non-responders. In addition, interim ctDNA clearance may be an alternative noninvasive method of positron emission tomography and computed tomography (PET-CT) for predicting better PFS (HR 3.65; p = 0.0033) and OS (HR 3.536; p = 0.016). We also demonstrated that posttreatment ctDNA was a sensitive indicator for detecting minimal residual disease (MRD) in patients with a high risk of recurrence (HR 6.471; p = 0.014), who were otherwise claimed to achieve radiographic CR (complete remission). CONCLUSIONS: CtDNA is a promising noninvasive tool for prognosis prediction, response assessment, and early relapse prediction of first-line treatment in DLBCL patients.


Assuntos
DNA Tumoral Circulante , Linfoma Difuso de Grandes Células B , Humanos , DNA Tumoral Circulante/genética , Tomografia por Emissão de Pósitrons combinada à Tomografia Computadorizada , Recidiva Local de Neoplasia , Linfoma Difuso de Grandes Células B/diagnóstico , Linfoma Difuso de Grandes Células B/tratamento farmacológico , Linfoma Difuso de Grandes Células B/genética , Prognóstico , Biomarcadores Tumorais/genética
13.
Front Med (Lausanne) ; 9: 965836, 2022.
Artigo em Inglês | MEDLINE | ID: mdl-36106325

RESUMO

Objectives: We investigated the prevalence of pretreatment drug resistance (PDR), the molecular transmission network among HIV-positive individuals, and the impact of virological failure on those who received antiretroviral therapy (ART) in China. Methods: Based on the World Health Organization (WHO) surveillance guidelines for PDR, a baseline survey and follow-up were conducted in 2018 and 2021, respectively. Demographic information and plasma samples were obtained from all participants. HIV pol gene region sequences were used to analyze the PDR and molecular transmission networks using the Stanford HIV database algorithm and HIV-TRACE, respectively. This study assessed the odds ratios (OR) of PDR to virological failure (viral load ≥ 50 copies/mL) after 3 years of ART using multivariable logistic regression. Results: Of the 4,084 individuals, 370 (9.1%) had PDR. The prevalence of PDR to non-nucleoside reverse transcriptase inhibitors (5.2%) was notably higher than that to nucleoside reverse transcriptase inhibitors (0.7%, p < 0.001), protease inhibitors (3.0%, p < 0.001), and multidrug resistance (0.3%, p < 0.001). A total of 1,339 (32.8%) individuals from 361 clusters were enrolled in the molecular transmission network. Of the 361 clusters, 22 included two or more individuals with PDR. The prevalence of virological failure among HIV-positive individuals after 3 years of ART without PDR, those with PDR to Chinese listed drugs, and those with PDR to other drugs was 7.9, 14.3, and 12.6%, respectively. Compared with that in HIV-positive individuals without PDR, virological failure after 3 years of ART was significantly higher (OR: 2.02, 95% confidence interval (CI): 1.25-3.27) and not significantly different (OR: 1.72, 95% CI: 0.87-3.43) in individuals with PDR to Chinese listed drugs and those with PDR to other drugs, respectively. Missed doses in the past month were significantly associated with virological failure (OR, 2.82; 95% CI: 4.08-5.89). Conclusion: The overall prevalence of PDR was close to a high level and had an impact on virological failure after 3 years of ART. Moreover, HIV drug-resistant strains were transmitted in the molecular transmission network. These results illustrate the importance of monitoring PDR and ensuring virological suppression through drug adherence.

14.
Front Psychol ; 13: 885384, 2022.
Artigo em Inglês | MEDLINE | ID: mdl-36118456

RESUMO

Social rejection is cold and hurtful, but how and why it is formed remains under-investigated. Our study offers one possible explanation from the rejector's perspective by developing a moderated mediation model on the emotional antecedent and consequence of social rejection. Specifically, envious individuals use social rejection to complement their inferiority, further triggering their negative affect. Drawing on social comparison theory, we conducted an experience sampling methodology (ESM) investigation of 55 frontline workers through a 10-workday-survey (Level 1 n = 515). As predicted, daily envy is positively associated with daily social rejection. Daily social rejection is positively related to daily negative affect. Furthermore, daily social rejection mediates the relationship between daily envy and daily negative affect. These effects are more robust for females than males, including the impact of envy on social rejection and the impact of envy on negative affect via social rejection. We suggest the recipient and the rejector make psychological and behavioral adjustments accordingly. We also recommend that future research extend our current study methodologically and theoretically.

15.
Front Oncol ; 12: 989258, 2022.
Artigo em Inglês | MEDLINE | ID: mdl-36072805

RESUMO

Patients with lymphoma who are also infected with Hepatitis B virus (HBV) have a poor prognosis. This could be partly explained by the delay or premature termination of anti-tumor treatment because of HBV reactivation. However, there is limited data on the survival outcome of patients HBV-related lymphoma in the era of prophylactic antivirals. Data for 128 patients with HBV surface antigen-positive diffuse large B-cell lymphoma was collected. The median age was 54 years and the ratio of men to women was 1.2:1. All patients received immune-chemotherapy and prophylactic antiviral therapy. The median number of cycles of immune-chemotherapy was six. The overall response rate was 82%, with a complete remission rate of 75%. With a median follow-up of 58.4 months, the 5-year progression-free survival and overall survival rates were 75.7% and 74.7%, respectively. Nine patients experienced HBV reactivation but none experienced HBV-associated hepatitis. Patients with low and high HBV DNA loads had comparable survival outcomes. In conclusion, HBV infection had no negative effect on the prognosis of DLBCL in the era of prophylactic antiviral therapy.

16.
J Environ Public Health ; 2022: 3329174, 2022.
Artigo em Inglês | MEDLINE | ID: mdl-36124244

RESUMO

The rapid development of social economy will promote the development of sports industry and then have an impact on sports economy. By using the regression analysis method, this paper compares the influencing factors of sports industry development, aiming at exploring the influence of sports industry development on economic development and its future development trend. This paper takes 12 industries of sports industry development from January 2020 to January 2022 as research objects, compares the development of sports industry of different research objects, and determines the factors affecting sports industry. We compare the promotion of different factors to sports economy and provide support for the formulation of sports industry development measures. The results show that economic growth, sports industry types, the degree of integration between sports industry and economic development, sports industry action time, and sports industry scale are the main factors affecting sports industry and promote the development of sports economy. The above indexes can improve the economic level of sports industry, and the improvement degree is about 10∼20%. Therefore, local governments and sports organizations should formulate measures to promote the economic development of sports industry from the aspects of economic growth, sports industry types, integration degree between sports industry and economic development, action time of sports industry, and scale of sports industry.


Assuntos
Desenvolvimento Econômico , Esportes , Indústrias
17.
Zhongguo Zhong Yao Za Zhi ; 47(15): 4248-4255, 2022 Aug.
Artigo em Chinês | MEDLINE | ID: mdl-36046915

RESUMO

This study analyzed and reported the basic information and clinical evidence of Chinese patent medicines for digestive system diseases in children in a scoping review manner. Based on the drug instructions, the basic information of Chinese patent medicines for digestive system diseases in children was obtained by searching the three lists of national medicines. At the same time, the relevant clinical literatures from the first day of establishment to March 7, 2022 were obtained from Chinese and English databases. According to the screening criteria, 39 Chinese patent medicines were included, involving 8 dosage forms. Eight Chinese medicines including Crataegi Fructus, Poria, Citri Reticulatae Pericarpium, Hordei Fructus Germinatus, Arecae Semen, Massa Medicata Fermentata, Dioscoreae Rhizoma, and Atractylodis Macrocephalae Rhizoma were frequently used, and the main effects were invigorating spleen, checking diarrhea, promoting digestion, clearing heat, and harmonizing stomach. The indications for Chinese patent medicines were mainly diarrhea, anorexia, food accumulation, dyspepsia, and rotavirus enteritis in children. Among all drug instructions, only 4 mentioned adverse reactions and 6 mentioned contraindications. Ninety-two clinical studies were included ultimately, including 84 randomized controlled studies, 2 systematic reviews/Meta-analysis, 1 retrospective study, and 5 case series. The literatures only covered 21 kinds of Chinese patent medicines, with the most studies related to Xingpi Yanger Granules, accounting for 32.6% of the total literature volume. The sample size in the literatures was mainly focused on 51-200 cases, and 51-100 cases were selected by the most literatures, accounting for 34.45%. The interventions of the experimental group were mainly Chinese patent medicines or Chinese patent medicines combined with western medicines. The literatures with treatment course of 0-7 d accounted for the largest proportion(51.10%). The effective rate and symptom improvement time were used as the indexes to evaluate the results. The main adverse reactions were vomiting, constipation, nausea, rash, cold, diarrhea, redness of the skin around the umbilicus, or red itchy skin. The analysis of this study found that Chinese patent medicines have good curative effect and research prospects in the treatment of digestive system diseases in children. However, most clinical evidence has problems, such as limited indexes to evaluate the results, lack of traditional Chinese medicine characteristics, uneven quantity and low quality of Chinese patent medicine literatures, and insufficient specification of instructions. In the future, high-quality clinical studies on this field should be actively carried out, and economic studies and clinical comprehensive evaluation of Chinese patent medicines should be strengthened to explore the characteristics and advantages of its treatment, so as to provide decision-making basis for finding the accurate clinical positioning and promoting the rational clinical application of Chinese patent medicines for treating digestive system diseases in children.


Assuntos
Doenças do Sistema Digestório , Medicamentos de Ervas Chinesas , Criança , China , Diarreia/tratamento farmacológico , Doenças do Sistema Digestório/tratamento farmacológico , Medicamentos de Ervas Chinesas/efeitos adversos , Humanos , Medicina Tradicional Chinesa , Medicamentos sem Prescrição/efeitos adversos , Estudos Retrospectivos
18.
Neuropathol Appl Neurobiol ; : e12850, 2022 Sep 27.
Artigo em Inglês | MEDLINE | ID: mdl-36168302

RESUMO

OBJECTIVES: Several reports suggest that epigenetic therapy may be a potential method for treating epilepsy, and circular RNAs (circRNAs) play important roles in mediating the epigenetic mechanisms associated with epilepsy; however, currently there are no effective treatment methods to prevent the progression of epileptogenesis. The circRNA serine/arginine repetitive matrix 4 (circSRRM4) was found to exert regulatory effects in temporal lobe epilepsy (TLE); however, the mechanisms involved are still unknown. MATERIALS AND METHODS: To elucidate the molecular mechanism of circSRRM4, we investigated human epileptic brain tissue, epileptic rats, neuron and astrocyte cell lines using RT-qPCR, western blot, fluorescence in situ hybridisation, immunofluorescence staining, Nissl stain, micro-PET-CT, RNA-pulldown, liquid chromatography-mass spectrometry, and RBP immunoprecipitation techniques. Furthermore, we evaluated the pyruvate kinase M1/2 (PKM) expression patterns in the human and rat models of TLE. RESULTS: We detected the increased circSRRM4 expression in the hypometabolic lesions of patients with TLE and discovered that circSrrm4 has specific spatiotemporal characteristics in rats with kainic acid-induced epilepsy. The decreased PKM1 expression and increased PKM2 expression were similar to the Warburg effect in tumours. Notably, circSrrm4 silencing reduced the incidence and frequency of epilepsy, improved local hypometabolism, and prevented neuronal loss and astrocyte activation. CONCLUSION: PKM2 promotes lactic acid production in the astrocytes by inducing glycolysis, thereby contributing to the energy source for epileptic seizures. Notably, circSRRM4 combines with and inhibits serine and arginine rich splicing factor 3 (SRSF3) from joining the ubiquitin-proteasome pathway, improving the SRSF3-regulated alternative splicing of PKM, and consequently stimulating glycolysis in cells.

19.
Sci Rep ; 12(1): 15279, 2022 09 10.
Artigo em Inglês | MEDLINE | ID: mdl-36088403

RESUMO

Recently, a human mutation of OPG was identified to be associated with familial forms of osteoarthritis. This missense mutation (c.1205A = > T; p.Stop402Leu) occurs on the stop codon of OPG, which results in a 19-residue appendage to the C-terminus (OPG+19). The biochemical consequence of this unusual sequence alteration remains unknown. Here we expressed OPG+19 in 293 cells and the mutant OPG was purified to homogeneity by heparin affinity chromatography and size exclusion chromatography. We found that in sharp contrast to wildtype OPG, which mainly exists in dimeric form, OPG+19 had a strong tendency to form higher-order oligomers. To our surprise, the hyper-oligomerization of OPG+19 had no impact on how it binds cell surface heparan sulfate, how it inhibits RANKL-induced osteoclastogenesis and TRAIL-induced chondrocytes apoptosis. Our data suggest that in biological contexts where OPG is known to play a role, OPG+19 functions equivalently as wildtype OPG. The disease-causing mechanism of OPG+19 likely involves an unknown function of OPG in cartilage homeostasis and mineralization. By demonstrating the biochemical nature of this disease-causing OPG mutant, our study will likely help elucidating the biological roles of OPG in cartilage biology.


Assuntos
Osteoprotegerina/química , Ligante Indutor de Apoptose Relacionado a TNF , Apoptose , Condrócitos/metabolismo , Heparitina Sulfato/metabolismo , Humanos , Osteoprotegerina/genética , Osteoprotegerina/metabolismo , Ligante Indutor de Apoptose Relacionado a TNF/metabolismo
20.
Viruses ; 14(9)2022 09 07.
Artigo em Inglês | MEDLINE | ID: mdl-36146788

RESUMO

Visual loop-mediated isothermal amplification (LAMP) is qualified to be applied in the field to detect pathogens due to its simplicity, rapidity and cost saving. However, the color changes in currently reported visual reverse transcription LAMP (RT-LAMP) for foot-and-mouth disease virus (FMDV) detection are not so obvious to the naked eye, so interpretation of results is troublesome. In this study, a new naked-eye visual RT-LAMP to detect all seven distinct serotypes of FMDV was established based on the 3D genes by using pH-sensitive neutral red as the indicator, rendering a sharp contrast of color changes between the negative (light orange) and the positive (pink). Analytical sensitivity tests showed that the detection limit of the visual RT-LAMP was 104 copies/µL while those were 103 and 104 copies/µL for the RT-qPCR and conventional RT-PCR methods, respectively. Specificity tests proved that the established visual RT-LAMP assay had no cross-reactivity with other common livestock viruses. Furthermore, the analysis of 59 clinical samples showed 98.31% and 100% concordance with the RT-qPCR and the RT-PCR, respectively. The pan-serotypic FMD visual RT-LAMP assay could be suitable for a pen-side test of all seven serotypes of FMDV because the results could be easily distinguished by the naked eye without the requirement of complicated instruments and professional technicians. Hence, the novel method may have a promising prospect in field tests which exert an important role in monitoring, preventing, and controlling FMD, especially in regions with no PCR or qPCR instrument available.


Assuntos
Vírus da Febre Aftosa , Febre Aftosa , Animais , Febre Aftosa/diagnóstico , Vírus da Febre Aftosa/genética , Técnicas de Diagnóstico Molecular , Vermelho Neutro , Técnicas de Amplificação de Ácido Nucleico/métodos , Reação em Cadeia da Polimerase em Tempo Real/métodos , Transcrição Reversa , Sensibilidade e Especificidade
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