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1.
Artigo em Inglês | MEDLINE | ID: mdl-38518833

RESUMO

CONTEXT: Although spiritual intervention is crucial in the care of childhood cancer patients (CCPs), its effectiveness has not yet been systematically evaluated. OBJECTIVES: To determine the effectiveness of existing spiritual interventions on psychological, spiritual outcomes, and quality of life (QoL) in CCPs. METHODS: We searched eight databases to identify relevant randomized controlled trials and quasi-experimental studies. Risk of bias was assessed using the Cochrane risk-of-bias tool for randomized trials. Results were either synthesized in a systematic narrative synthesis or a meta-analysis using a random effects model, where appropriate. The pooled treatment effect was estimated using the standardized mean difference (SMD) and 95% confidence interval (CI). RESULTS: Twelve studies with 576 CCPs were included. Eight studies showed a high risk of bias. The overall effect of existing spiritual interventions on QoL (Z = 1.05, SMD = 0.64, 95%CI = -0.15 to 1.83, P = 0.29), anxiety (Z = 1.11, SMD = -0.83, 95%CI = -2.30 to 0.64, P = 0.28) and depressive symptoms (Z = 1.06, SMD = -0.49, 95%CI = -1.40 to 0.42, P = 0.12) were statistically nonsignificant. The nonsignificant findings could be attributed to the high heterogeneity among the included studies (QoL: I2 = 85%; anxiety: I2 = 90%; depressive symptoms: I2 = 58%). CONCLUSION: Evidence to support the positive effects of existing spiritual interventions on psychological and spiritual outcomes and QoL in CCPs is insufficient. Future studies should adopt a more rigorous design and unify the outcome measures to reduce the risk of bias and heterogeneity, respectively.

2.
Foods ; 13(4)2024 Feb 07.
Artigo em Inglês | MEDLINE | ID: mdl-38397492

RESUMO

Milk proteins are well-known delivery agents; however, there is no clear understanding of the competitive interactions of milk proteins with polyphenols in mixed complex systems. Here, we investigate the preferential competitive interactions of different polyphenols present in blackcurrant extract with milk proteins by quantifying the protein-bound polyphenols and comparing the factors affecting these interactions. In addition, bioaccessibility and antioxidant activity were studied after in vitro gastric digestion. Our results indicated that polyphenols from blackcurrant extracts were preferentially bound to caseins more than whey proteins, with noncovalent interactions causing secondary structural changes in the protein. The hydrophobicity and the charge of the polyphenols were negatively and positively related to the number of polyphenols bound to casein and whey proteins, respectively. Moreover, the bioaccessibility and antioxidant activity of polyphenols were enhanced in the presence of milk proteins in milk-based blackcurrant samples when compared to polyphenol and protein-alone samples in the in vitro gastric phase. These findings underscore the critical role of milk proteins in encapsulating or delivering polyphenols. This will pave the way for boosting the bioavailability of polyphenols by complexing them with milk proteins and formulating functional dairy foods, integrating the beneficial effects of these compounds.

3.
J Pharm Biomed Anal ; 242: 116023, 2024 May 15.
Artigo em Inglês | MEDLINE | ID: mdl-38395000

RESUMO

OBJECTIVE: In this study, we aimed to investigate the cytotoxicity and potential mechanisms of SC-43 by analyzing the global proteomics and metabolomics of HepG2 cells exposed to SC-43. METHODS: The effect of SC-43 on cell viability was evaluated through CCK-8 assay. Proteomics and metabolomics studies were performed on HepG2 cells exposed to SC-43, and the functions of differentially expressed proteins and metabolites were categorized. Drug affinity responsive target stability (DARTS) was utilized to identify the potential binding proteins of SC-43 in HepG2 cells. Finally, based on the KEGG pathway database, the co-regulatory mechanism of SC-43 on HepG2 cells was elucidated by conducting a joint pathway analysis on the differentially expressed proteins and metabolites using the MetaboAnalyst 5.0 platform. RESULTS: Liver cell viability is significantly impaired by continuous exposure to high concentrations of SC-43. Forty-eight dysregulated proteins (27 upregulated, 21 downregulated) were identified by proteomics analysis, and 184 dysregulated metabolites (65 upregulated, 119 downregulated) were determined by metabolomics in HepG2 cells exposed to SC-43 exposure compared with the control. A joint pathway analysis of proteomics and metabolomics data using the MetaboAnalyst 5.0 platform supported the close correlation between SC-43 toxicity toward HepG2 and the disturbances in pyrimidine metabolism, ferroptosis, mismatch repair, and ABC transporters. Specifically, SC-43 significantly affected the expression of several proteins and metabolites correlated with the above-mentioned functional pathways, such as uridine 5'-monophosphate, uridine, 3'-CMP, glutathione, γ-Glutamylcysteine, TF, MSH2, RPA1, RFC3, TAP1, and glycerol. The differential proteins suggested by the joint analysis were further selected for ELISA validation. The data showed that the RPA1 and TAP1 protein levels significantly increased in HepG2 cells exposed to SC-43 compared to the control group. The results of ELISA and joint analysis were basically in agreement. Notably, DARTS and biochemical analysis indicated that SART3 might be a potential target for SC-43 toxicity in HepG2 cells. CONCLUSION: In summary, prolonged exposure of liver cells to high concentrations of SC-43 can result in significant damage. Based on a multi-omics analysis, we identified proteins and metabolites associated with SC-43-induced hepatocellular injury and clarified the underlying mechanism, providing new insights into the toxic mechanism of SC-43.


Assuntos
Metabolômica , Proteômica , Humanos , Células Hep G2 , Metabolômica/métodos , Hepatócitos/metabolismo , Fígado , Inibidores Enzimáticos/farmacologia
4.
J Appl Microbiol ; 135(4)2024 Apr 01.
Artigo em Inglês | MEDLINE | ID: mdl-38253409

RESUMO

AIMS: To examine the influence of GED on the gut microbiota and metabolites using a bilateral ovariectomized (OVX) rat model. We tried to elucidate the underlying mechanisms of GED in the treatment of menopausal hot flashes. METHODS AND RESULTS: 16S rRNA sequencing, metabonomics, molecular biological analysis, and fecal microbiota transplantation (FMT) were conducted to elucidate the mechanisms by which GED regulates the gut microbiota. GED significantly reduced OVX-induced hot flashes and improved disturbances in the gut microbiota metabolites. Moreover, FMT validated that the gut microbiota can trigger hot flashes, while GED can alleviate hot flash symptoms by modulating the composition of the gut microbiota. Specifically, GED upregulated the abundance of Blautia, thereby increasing l(+)-ornithine levels for the treatment of menopausal hot flashes. Additionally, GED affected endothelial nitric oxide synthase and heat shock protein 70 (HSP70) levels in the hypothalamic preoptic area by changing the gut microbiota composition. CONCLUSIONS: Our study illuminated the underlying mechanisms by which GED attenuated the hot flashes through modulation of the gut microbiota and explored the regulatory role of the gut microbiota on HSP70 expression in the preoptic anterior hypothalamus, thereby establishing a foundation for further exploration of the role of the gut-brain axis in hot flashes.


Assuntos
Medicamentos de Ervas Chinesas , Microbioma Gastrointestinal , Fogachos , Menopausa , Animais , Microbioma Gastrointestinal/efeitos dos fármacos , Fogachos/metabolismo , Fogachos/tratamento farmacológico , Ratos , Feminino , Medicamentos de Ervas Chinesas/farmacologia , Transplante de Microbiota Fecal , Ovariectomia , Ratos Sprague-Dawley , RNA Ribossômico 16S/genética , Metaboloma/efeitos dos fármacos
6.
J Formos Med Assoc ; 2024 Jan 08.
Artigo em Inglês | MEDLINE | ID: mdl-38195318

RESUMO

BACKGROUND: /Purpose: To achieve the World Health Organization goal of eliminating viral hepatitis by 2030, a key strategy in resource-limited areas is to identify the areas with high prevalence and to prioritize screening and treatment intervention. We hypothesized that a hospital-based laboratory database could be used to estimate the township- and village-specific anti-hepatitis C virus (HCV) prevalence. METHODS: Yunlin County Public Health Bureau has been collecting anti-HCV test data from eight major hospitals. Township- and village-specific screening testing rates and anti-HCV prevalence were calculated for residents 40 years or older. A township with a wide range of anti-HCV prevalence rates was selected for outreach universal screening and for validating the village-specific prevalence of anti-HCV in the analysis of the data from the hospitals. RESULTS: The overall anti-HCV screening testing rate in Yunlin County was 30.4 %, whereas the anti-HCV prevalence rate for persons 40 years or older was 15.4 %. The village-specific anti-HCV prevalence rates ranged from 3.8 % to 85.8 %. Community-based screening was conducted in Kouhu Township. The village-specific anti-HCV prevalence rates ranged from 0 % to 18.8 %. Three of the four villages had the highest village-specific anti-HCV prevalence in the community-based study and the hospital-based study. Additionally, 95.8 % of the new HCV cases detected by universal screening received anti-HCV therapy. CONCLUSION: The hospital-based database provided a framework for identifying the villages with high anti-HCV prevalence. Additionally, community-based universal screening should be prioritized for villages with high prevalence in hospital-based databases.

7.
Nurse Educ Pract ; 75: 103900, 2024 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-38277802

RESUMO

AIMS: Development and evaluation of the effectiveness of a Nurse Navigation programme based on Noddings' Care theory on two dependent variables which were professional identity and career planning among first-year undergraduate nursing students. BACKGROUND: First-year undergraduate nursing students generally have a low sense of professional identity and career planning, resulting in a loss of nursing power after graduation. Implemention of a Nurse Navigation program based on Noddings' Care theory may be potentially useful in cultivating their professional identity and career planning. DESIGN: A quasi-experimental study. METHODS: A convenience sample of 122 first-year undergraduate nursing students from two medical universities was recruited between September 2021 and June 2022. Students in the experimental group (n = 63) participated in the Nurse Navigation programme based on Noddings' Care theory, which contained four core components, spreading over 50 lessons. Those in the control group (n = 59) underwent a traditional training programme with five components across 44 lessons. The two groups were compared in terms of their level of professional identity by Professional identity questionnaire for nurse students (PIQNS) and career planning by Career planning questionnaire (CPQ) after the training using the t-test. RESULTS: The mean score of professional identity in the experimental group increased significantly from 51.02 ± 8.46 at baseline to 58.02 ± 8.81 after the intervention (p < 0.001), with a large effect size (Cohen's d=0.810). Also, this post-intervention score was statistically significantly higher than that (52.86 ± 9.27) in the control group (p = 0.002), with a medium effect size (Cohen's d=0.571). The mean score of career planning in the experimental group increased significantly from 81.76 ± 9.86 at baseline to 94.52 ± 10.81 after the intervention (p < 0.001), with a large effect size (Cohen's d = 1.233). Also, this post-intervention score was statistically significantly higher than that (88.25 ± 9.30) in the control group (p < 0.001), with a medium effect size (Cohen's d=0.623). CONCLUSIONS: The Nurse Navigation programme based on Noddings' Care theory showed effectiveness in enhancing professional identity and career planning among first-year undergraduate nursing students in China. Further rigorous studies are needed to examine its effectiveness and long-term impacts on these students.


Assuntos
Bacharelado em Enfermagem , Estudantes de Enfermagem , Humanos , Bacharelado em Enfermagem/métodos , Currículo , China
8.
Comb Chem High Throughput Screen ; 27(1): 90-100, 2024.
Artigo em Inglês | MEDLINE | ID: mdl-37190798

RESUMO

INTRODUCTION: Fu-Fang-Jin-Qian-Cao is a Chinese herbal preparation used to treat urinary calculi. Fu-Fang-Jin-Qian-Cao can protect renal tubular epithelial cells from calcium oxalateinduced renal injury by inhibiting ROS-mediated autopathy. The mechanism still needs further exploration. Metabonomics is a new subject; the combination of metabolomics and network pharmacology can find pathways for drugs to act on targets more efficiently. METHODS: Comprehensive metabolomics and network pharmacology to study the mechanism of Fu-Fang-Jin-Qian-Cao inhibiting autophagy in calcium oxalate-induced renal injury. Based on UHPLC-Q-TOF-MS, combined with biochemical analysis, a mice model of Calcium oxalateinduced renal injury was established to study the therapeutic effect of Fu-Fang-Jin-Qian-Cao. Based on the network pharmacology, the target signaling pathway and the protective effect of Fu- Fang-Jin-Qian-Cao on Calcium oxalate-induced renal injury by inhibiting autophagy were explored. Autophagy-related proteins LC3-II, BECN1, ATG5, and ATG7 were studied by immunohistochemistry. RESULTS: Combining network pharmacology and metabolomics, 50 differential metabolites and 2482 targets related to these metabolites were found. Subsequently, the targets enriched in PI3KAkt, MAPK and Ras signaling pathways. LC3-II, BECN1, ATG5 and ATG7 were up-regulated in Calcium oxalate-induced renal injury. All of them could be reversed after the Fu-Fang-Jin-Qian- Cao treatment. CONCLUSIONS: Fu-Fang-Jin-Qian-Cao can reverse ROS-induced activation of the MAPK signaling pathway and inhibition of the PI3K-Akt signaling pathway, thereby reducing autophagy damage of renal tubular epithelial cells in Calcium oxalate-induced renal injury.


Assuntos
Oxalato de Cálcio , Medicamentos de Ervas Chinesas , Camundongos , Animais , Oxalato de Cálcio/metabolismo , Oxalato de Cálcio/farmacologia , Cálcio/metabolismo , Cromatografia Líquida de Alta Pressão , Farmacologia em Rede , Fosfatidilinositol 3-Quinases/metabolismo , Espécies Reativas de Oxigênio/metabolismo , Rim/metabolismo , Autofagia , Medicamentos de Ervas Chinesas/farmacologia , Medicamentos de Ervas Chinesas/metabolismo
9.
Geroscience ; 46(2): 1641-1655, 2024 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-37713088

RESUMO

Aging is a risk factor for human health and quality of life. Screening and development of novel supplements and medications to combat aging and delay the incidence of age-related diseases are of great significance. In this study, salidroside (SA), a primary natural small molecule from Rhodiola rosea, was investigated regarding its effects on life and healthspan and the underlying molecular mechanism(s) of anti-aging and antioxidation. Our results showed that SA effectively prolonged lifespan and exhibited anti-aging and antioxidative properties. Computer-assisted methods, label-free interaction analysis, and in vitro assays showed that SA directly bound heat shock protein 90 (HSP90). Furthermore, SA significantly inhibited the ATPase activity of HSP90, affecting the interaction between HSP90 and its interacting proteins and the expression of downstream genes to regulate lifespan and the oxidative stress response. Our findings provided new insights into the pharmacological properties of SA across multiple species and its potential as an anti-aging drug.


Assuntos
Glucosídeos , Longevidade , Fenóis , Qualidade de Vida , Humanos , Estresse Oxidativo , Antioxidantes/farmacologia
10.
Genes (Basel) ; 14(12)2023 Dec 02.
Artigo em Inglês | MEDLINE | ID: mdl-38136992

RESUMO

Sclerotium rolfsii is a destructive soil-borne fungal pathogen that causes stem rot in cultivated plants. However, little is known about the genetic basis of sclerotium development. In this study, we conducted de novo sequencing of genes from three different stages of S. rolfsii (mycelia, early sclerotium formation, and late sclerotium formation) using Illumina HiSeqTM 4000. We then determined differentially expressed genes (DEGs) across the three stages and annotated gene functions. STEM and weighted gene-co-expression network analysis were used to cluster DEGs with similar expression patterns. Our analysis yielded an average of 25,957,621 clean reads per sample (22,913,500-28,988,848). We identified 8929, 8453, and 3744 DEGs between sclerotium developmental stages 1 versus 2, 1 versus 3, and 2 versus 3, respectively. Additionally, four significantly altered gene expression profiles involved 220 genes related to sclerotium formation, and two modules were positively correlated with early and late sclerotium formation. These results were supported by the outcomes of qPCR and RNA-sequencing conducted on six genes. This is the first study to provide a gene expression map during sclerotial development in S. rolfsii, which can be used to reduce the re-infection ability of this pathogen and provide new insights into the scientific prevention and control of the disease. This study also provides a useful resource for further research on the genomics of S. rolfsii.


Assuntos
Basidiomycota , Perfilação da Expressão Gênica , Basidiomycota/genética , Transcriptoma/genética , Análise de Sequência de RNA
11.
Front Nutr ; 10: 1199815, 2023.
Artigo em Inglês | MEDLINE | ID: mdl-37810926

RESUMO

Purpose: This study is the first systematic review and meta-analysis based on RCTs on the effects of anthocyanins on patients with type 2 diabetes mellitus (T2DM) and the effect on T2DM-related cardiovascular disease. Methods: RCTs published in English from five electronic databases were evaluated for glycated hemoglobin (HbA1c), fasting blood glucose (FBG), 2-h postprandial blood glucose, fasting insulin, model assessment for insulin resistance, triglycerides (TG), total cholesterol (TC), high-density lipoprotein (HDL) cholesterol, low-density lipoprotein (LDL) cholesterol, systolic blood pressure, and diastolic blood pressure. The quality of the studies was rated (Cochrane Risk of Bias tool) and weighted mean differences were calculated (DerSimonian-Laird model with random effects). Leave-one-out sensitivity, subgroup, and publication bias analyses were conducted. The strength of the evidence was rated according to the GRADE guidelines. Results: In all, 13 RCTs were analyzed out of the 239 identified studies, with a duration longer than 4 weeks (703 participants with T2DM). Our findings indicate that a median dose of 320 mg/day anthocyanins, either from fruit extracts or pure supplements, for a median intervention length of 8 weeks significantly reduced HbA1c [Weighted Mean Difference (WMD) -0.31, p = 0.00], FBG (WMD -0.63, p = 0.00), 2-h postprandial glucose (WMD -1.60, p = 0.00), TG (WMD -0.45, p = 0.01), and LDL (WMD -0.26 p = 0.02). However, the effects of anthocyanins on fasting insulin, HOMA-IR, TC, HDL cholesterol, systolic blood pressure, and diastolic blood pressure in patients with T2DM were not statistically significant. Anthocyanins from fruit extracts or powder exhibited a higher reduction of HbA1c compared to pure anthocyanin supplements. Conclusion: The significant improvements in glycemic parameters and lipid profile, suggest the benefits of anthocyanins, especially from fruit extract or powder, in the management of T2DM, and their ability to delay the onset of lipid disorder-related diseases such as cardiovascular disease associated with T2DM. The mechanism behind this reduction in glycemic markers could be attributed to the antioxidant and anti-inflammatory activity of anthocyanins. Further research with well-designed RCTs is required to determine the optimal dosage of anthocyanins for the treatment of T2DM and to comprehend the consequences.

12.
Nanoscale Adv ; 5(18): 4670-4674, 2023 Sep 12.
Artigo em Inglês | MEDLINE | ID: mdl-37705783

RESUMO

This work exploits the magneto-optical activity of gold nanorods for the detection of sub-micromolar concentrations of glutathione using magnetic circular dichroism spectroscopy. Modulations of the magnetoplasmonic response of nanorods serve as the basis of the sensing methodology, whereby the presence of glutathione induces the end-to-end assembly of nanorods. In particular, the nanorod self-assembly enables a localized electric field in the nanocavities with adsorbed thiol molecules, whose field strength is amplified by the external magnetic field as confirmed by finite-element modeling, enabling their high-sensitivity detection. Our simple magnetoplasmonic sensor for glutathione requires no specific chemical tags and exhibits an impressive limit of detection of 97 nM.

13.
Crit Rev Food Sci Nutr ; : 1-23, 2023 Aug 16.
Artigo em Inglês | MEDLINE | ID: mdl-37584498

RESUMO

Polyphenols have widely accepted health benefits which are limited by their low uptake, low bioavailability, and rapid degradation in the gut. While milk proteins are excellent carriers for polyphenols, the specific interactions of the polyphenols with the milk proteins, need to be understood to facilitate the utilization of these delivery systems in food and pharmaceutical applications. We have evaluated the relevance of different factors affecting milk protein-polyphenol interactions and the subsequent impact on the bioavailability and health promoting aspects of polyphenols. Hydrophobic forces are the primary binding forces of polyphenols to milk proteins. The significant factors affecting the interactions and binding affinity are the molecular weight and the hydrophobicity of the polyphenols. The interaction of polyphenols with milk proteins improved the antioxidant activity in comparison to milk proteins, while conflicting results exists for comparisons with polyphenols. In-vitro and cell line studies demonstrated enhanced bioavailability of polyphenols in the presence of milk proteins as well as higher anti-cancer and anti-allergy benefits. Overall, this work will pave the way for better understanding of polyphenol interactions with milk proteins and enable the tailoring of complexes through sustainable green processes, enabling higher bioavailability and health promoting effects of the polyphenols in food and pharmaceutical applications.

14.
Oral Dis ; 2023 Aug 08.
Artigo em Inglês | MEDLINE | ID: mdl-37551736

RESUMO

OBJECTIVE: The purpose of this study was to investigate the effectiveness of various drug therapy methods for treating oral submucous fibrosis (OSF) in terms of increasing mouth opening, reducing VAS score, decreasing lesion area, minimizing side effects, and determining effective proportion. METHOD: A database search was conducted. Only randomized clinical trials were included, and Cochrane checklist was used for assessing the risk of bias. Stata.17 software was employed and effective treatment ranking was used. RESULTS: Thirty-one RCT studies, with a total of 2986 patients, were included in the period of 2010-2022. The combination of oral Chinese herbal medicine formulas (OC) and intralesional Salvia miltiorrhiza (ISM) was found to be the most effective treatment in improving mouth opening. For reducing the burning pain, the combination of intralesional steroids (IS) and oral Salvia miltiorrhiza (OSM) was found to be more effective than the others. In terms of lesion area, IS combined with OC was more effective than the others. IS combined with ISM had the highest effective proportion while having the lowest incidence of side effects which mentioned the incidence of side effects. CONCLUSION: This study indicates that OC and SM can be employed by clinicians for treating OSF effectively.

15.
Heliyon ; 9(8): e18556, 2023 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-37520964

RESUMO

Background: Lymphocytes are generally accepted to be a key component of the immune response, and an inadequate immune response is closely associated with disease severity and adverse outcomes in hepatitis B virus (HBV)-infected patients. The present study aimed to determine and compare the prognostic values of five lymphocyte-based scores (monocyte-to-lymphocyte ratio [MLR], mean platelet volume-to-lymphocyte ratio [MPVLR], neutrophil-to-lymphocyte ratio [NLR], red cell distribution width-to-lymphocyte ratio [RLR], and C-reactive protein-to-lymphocyte ratio [CLR]) for HBV-associated decompensated cirrhosis (HBV-DC). Methods: Data were extracted from an institutional database. The outcome was 30-day mortality. Receiver operating characteristic curve analyses were conducted, and the resulting area under the curve (AUC) values were used to evaluate the predictive capabilities of the five lymphocyte-based scores for mortality in HBC-DC relative to Model for End-Stage Liver Disease (MELD) score. Results: The study included 273 patients, and the 30-day mortality was 20.9%. Lymphocyte counts were slightly lower in non-survivors than in survivors. The prognostic values of CLR, NLR, MLR, MPVLR, and RLR for mortality in HBV-DC were different. The predictive powers of NLR and MLR were superior to those of the other three scores and similar to that of MELD score. Multivariate analyses identified NLR, MLR, and MELD score as independent prognostic predictors. Conclusion: High NLR and MLR are easily accessible and reliable indicators for predicting 30-day mortality in HBV-DC and have superior prognostic ability compared with other lymphocyte-based scores.

16.
Front Neurol ; 14: 1164600, 2023.
Artigo em Inglês | MEDLINE | ID: mdl-37483438

RESUMO

Introduction: Previous studies have revealed structural, functional, and metabolic changes in brain regions inside the cortico-striatal-thalamo-cortical (CSTC) loop in patients with paroxysmal kinesigenic dyskinesia (PKD), whereas no quantitative susceptibility mapping (QSM)-related studies have explored brain iron deposition in these areas. Methods: A total of eight familial PKD patients and 10 of their healthy family members (normal controls) were recruited and underwent QSM on a 3T magnetic resonance imaging system. Magnetic susceptibility maps were reconstructed using a multi-scale dipole inversion algorithm. Thereafter, we specifically analyzed changes in local mean susceptibility values in cortical regions and subcortical nuclei inside the motor CSTC loop. Results: Compared with normal controls, PKD patients had altered brain iron levels. In the cortical gray matter area involved with the motor CSTC loop, susceptibility values were generally elevated, especially in the bilateral M1 and PMv regions. In the subcortical nuclei regions involved with the motor CSTC loop, susceptibility values were generally lower, especially in the bilateral substantia nigra regions. Conclusion: Our results provide new evidence for the neuropathogenesis of PKD and suggest that an imbalance in brain iron levels may play a role in PKD.

17.
J Med Virol ; 95(7): e28954, 2023 07.
Artigo em Inglês | MEDLINE | ID: mdl-37493180

RESUMO

At present, the horse or human rabies immunoglobulin (RIG) used for postexposure prevention of human rabies (PEP) has high cost and limited availability. It is strongly encouraged to replace RIG with equivalent or more effective and safer products. Mouse and human monoclonal antibodies have been shown to protect rodents from lethal rabies virus (RABV) attacks. In this study, we reported a human-mouse chimeric monoclonal antibody, 12-2A12, which showed a strong neutralization potency and a wide breadth against multiple street viruses of RABV in vitro. The antibody binded the viral glycoprotein (G) with nanomolar affinity. The complex structure of 12-2A12 bound to RABV G revealed that the antibody recognizes an epitope that partially overlaps with the recognition region for the nicotinic acetylcholine receptor (nAChR). The antibody therefore would interfere with the nAChR/G interaction to block the viral receptor binding. In addition, comparison of our complex structure with the G structure in the acidic state reveals a clear steric clash, highlighting that the antibody would further prevent the conformational changes of the viral glycoprotein that are essential for membrane fusion. In light of these functional and structural data, we believe that 12-2A12 might be developed to be included in an antibody cocktail for potential use in human rabies PEP.


Assuntos
Vírus da Raiva , Raiva , Humanos , Animais , Camundongos , Cavalos , Raiva/prevenção & controle , Anticorpos Antivirais , Glicoproteínas , Anticorpos Monoclonais , Fatores Imunológicos/metabolismo , Imunossupressores
18.
Biochem Biophys Res Commun ; 674: 147-153, 2023 09 24.
Artigo em Inglês | MEDLINE | ID: mdl-37419036

RESUMO

The age-related hearing loss allele (Cdh23ahl) of the cadherin 23 gene leads to a more severe hearing loss phenotype through additive effects with risk alleles for hearing loss. In this study, we genome edited the Cdh23ahl allele to the wild-type Cdh23+ allele in outbred ICR mice and inbred NOD/Shi mice established from ICR mice and investigated their effects on hearing phenotypes. Several hearing tests confirmed that ICR mice developed early onset high-frequency hearing loss and exhibited individual differences in hearing loss onset times. Severe loss of cochlear hair cells was also detected in the high-frequency areas in ICR mice. These phenotypes were rescued by genome editing the Cdh23ahl allele to Cdh23+, suggesting that abnormal hearing phenotypes develop because of the interaction of the Cdh23ahl and risk alleles in the genetic background of ICR mice. NOD/Shi mice developed more severe hearing loss and hair cell degeneration than ICR mice. Hearing loss was detected at 1 month old. Hair cell loss, including degeneration of cell bodies and stereocilia, was observed in all regions of the cochlea in NOD/Shi mice. Although these phenotypes were partially rescued by genome editing to the Cdh23+ allele, the phenotypes associated with high-frequency hearing were mostly unrecovered in NOD/Shi mice. These results strongly suggest that the genetic background of NOD/Shi mice contain a potential risk allele for the acceleration of early onset high-frequency hearing loss.


Assuntos
Surdez , Perda Auditiva de Alta Frequência , Camundongos , Animais , Alelos , Camundongos Endogâmicos NOD , Perda Auditiva de Alta Frequência/genética , Camundongos Endogâmicos ICR , Camundongos Endogâmicos C57BL , Surdez/genética , Caderinas/genética
19.
Front Microbiol ; 14: 1180368, 2023.
Artigo em Inglês | MEDLINE | ID: mdl-37303806

RESUMO

Introduction: The ecological balance of the plant microbiome, as a barrier against pathogens, is very important for host health. Coptis chinensis is one of the important medicinal plants in China. In recent years, Illumina Miseq high-throughput sequencing technology was frequently used to analyze root rot pathogens and the effects of root rot on rhizosphere microorganisms of C. chinensis. But the effects of root rot infection on rhizosphere microecological balance of C. chinensis have received little attention. Methods: In this study, Illumina Miseq high-throughput sequencing technology was applied to analyze the impact on microbial composition and diversity of C. chinensis by root rot. Results: The results showed that root rot infection had significant impact on bacterial α-diversity in rhizome samples, but had no significant effect on that in leaf samples and rhizosphere soil samples, while root rot infection exhibited significant impact on the fungal α-diversity in leaf samples and rhizosphere soil samples, and no significant impact on that in rhizome samples. PCoA analysis showed that the root rot infection had a greater impact on the fungal community structure in the rhizosphere soil, rhizome, and leaf samples of C. chinensis than on the bacterial community structure. Root rot infection destroyed the microecological balance of the original microbiomes in the rhizosphere soil, rhizome, and leaf samples of C. chinensis, which may also be one of the reasons for the serious root rot of C. chinensis. Discussion: In conclusion, our findings suggested that root rot infection with C. chinensis disrupts microecological balance of rhizosphere soil and endophytic microbiomes. The results of this study can provide theoretical basis for the prevention and control of C. chinensis root rot by microecological regulation.

20.
Front Microbiol ; 14: 1152865, 2023.
Artigo em Inglês | MEDLINE | ID: mdl-37323912

RESUMO

Introduction: Sclerotium rolfsii Sacc. is a globally dispersed pathogenic fungus that causes southern blight disease in many crops and Chinese herbal medicine. The high degree of variation and diversity in the fungi altered population genetic structure. Therefore, the important factors of variation within the pathogen population should be considered during the development of management strategies for the disease. Methods: In this study, S. rolfsii isolates from 13 hosts in 7 provinces of China were collected and analyzed to identify their morphological features and perform molecular characterization. To develop EST-SSR primers, transcriptome sequencing was performed on isolated CB1, and its SSR loci were comprehensively analyzed. In addition, we analyzed the polymorphisms among different populations based on screened EST-SSR primers. Results: The results showed that all of these clean reads with total 36,165,475 assembled bases were clustered into 28,158 unigenes, ranged from 201 bp to 16,402 bp on the length, of which the average length was 1,284 bp. Of these, the SSR sequence appeared at an average interval of 15.43 kB, and the frequency of SSR was 0.0648 SSR/kB. Polymorphism of 9 primers was observed among 22 populations, and was verified by the Shannon's index (average = 1.414) and polymorphic information index (> 0.50). The genetic diversity analysis revealed diversity in all host populations and geographical populations. Further, molecular variance analysis (AMOVA) showed that the differences between groups were mainly related to geographical location. Based on cluster analysis, the 7 populations were roughly divided into 3 groups, and the results were highly consistent with those based on the geographical location, ultimately aligning with the results of STRUCTURE analysis. Discussion: The findings build on current knowledge of the distribution of S. rolfsii in the southwest area of China, adding value to current knowledge base on the population structure and genetic diversity of S. rolfsii, specifically in the context of Chinese herbal medicine cultivation in China. Overall, our findings may provide valuable information for breeding of crops with enhanced resistance toward S. rolfsii.

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