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1.
J Clin Virol ; 174: 105710, 2024 Jun 27.
Artigo em Inglês | MEDLINE | ID: mdl-38954911

RESUMO

Epstein-Barr virus (EBV) is a ubiquitous and oncogenic virus that is associated with various malignancies and non-malignant diseases and EBV DNA detection is widely used for the diagnosis and prognosis prediction for these diseases. The dried blood spots (DBS) sampling method holds great potential as an alternative to venous blood samples in geographically remote areas, for individuals with disabilities, or for newborn blood collection. Therefore, the objective of this study was to assess the viability of detecting EBV DNA load from DBS. Matched whole blood and DBS samples were collected for EBV DNA extraction and quantification detection. EBV DNA detection in DBS presented a specificity of 100 %. At different EBV DNA viral load in whole blood, the sensitivity of EBV DNA detection in DBS was 38.78 % (≥1 copies/mL), 43.18 % (≥500 copies/mL), 58.63 % (≥1000 copies/mL), 71.43 % (≥2000 copies/mL), 82.35 % (≥4000 copies/mL), and 92.86 % (≥5000 copies/mL), respectively. These results indicated that the sensitivity of EBV DNA detection in DBS increased with elevating viral load. Moreover, there was good correlation between EBV DNA levels measured in whole blood and DBS, and on average, the viral load measured in whole blood was about 6-fold higher than in DBS. Our research firstly demonstrated the feasibility of using DBS for qualitative and semi-quantitative detection of EBV DNA for diagnosis and surveillance of EBV-related diseases.

2.
PLoS One ; 19(7): e0305243, 2024.
Artigo em Inglês | MEDLINE | ID: mdl-38959186

RESUMO

BACKGROUND: Friedman's standards, developed almost 50 years ago, may no longer align with the needs of today's obstetric population and current pregnancy management practices. This study aims to analyze contemporary labor patterns and estimate labor duration in China, focusing on first-stage labor data from Chinese parturients with a spontaneous onset of labor. METHODS: This retrospective observational study utilized data from electronic medical records of a tertiary hospital in Changsha, Hunan. Out of a total of 2,689 parturients, exclusions were made for multiple gestations, preterm, post-term, or stillbirth, cesarean delivery, non-vertex presentation, and neonatal intensive care unit admission. Average labor curves were constructed by parity using repeated-measure analysis, and labor duration was estimated through interval-censored regression, stratified by cervical dilation at admission. We performed an analysis to assess the impact of oxytocin augmentation and amniotomy on labor progression and conducted a sensitivity analysis using women with complicated outcomes. RESULTS: Nulliparous women take over 180 minutes for cervical dilation from 3 to 4 cm, and the duration from 5 to 6 cm exceeds 145 minutes. Multiparous women experience shorter labor durations than nulliparous. Labor acceleration is observed after 5 cm in nulliparous, but no distinct inflection point is evident in the average labor curve. In the second stage of labor, the 95th percentile for nulliparous, with and without epidural analgesia, is 142 minutes and 127 minutes, respectively. CONCLUSIONS: These findings provide valuable insights for the reassessment of labor and delivery processes in contemporary obstetric populations, including current Chinese obstetric practice.


Assuntos
Primeira Fase do Trabalho de Parto , Humanos , Feminino , Gravidez , Primeira Fase do Trabalho de Parto/fisiologia , Estudos Retrospectivos , Adulto , China , Paridade/fisiologia , Recém-Nascido , Trabalho de Parto/fisiologia , Resultado da Gravidez , Ocitocina , População do Leste Asiático
3.
Artigo em Inglês | MEDLINE | ID: mdl-38952021

RESUMO

OBJECTIVE: This study aimed to: 1) test for the link between snack choices and BMI using a novel sensory-based classification method; and 2) elucidate the role of gustatory sensitivity in orienting snack choices. METHODS: The study employed a dual approach involving sensory and nutritional assessments. Ninety-eight European male individuals were tested for gustatory sensitivities to sweetness, saltiness, umami, and lipid perception. Participant food intake was measured over 4 days. A separate cohort of 327 participants categorized the recorded snacks based on taste patterns, enabling profiling of snack choices across body-weight groups. RESULTS: Results showed clear differentiations in snack choices across the BMI groups: Individuals with a higher BMI consumed more "Sweet" and "Sweet+Fat" snacks and less "Savory" snacks compared with the lower-BMI group (p < 0.05). Mediation analyses confirmed a significant effect of gustatory sensitivity, showing that the greater choice for "Sweet" and "Sweet+Fat" snacks among those with a higher BMI was mediated by sensitivities to sweetness and lipid perception (p = 0.008-0.044). CONCLUSIONS: Our study revealed that gustatory sensitivity can mediate the relationship between BMI and energy consumption from different snacks. These findings highlight the significance of taste perception in shaping snack choice, suggesting potential strategies for interventions aimed at addressing gustatory sensitivity to promote healthier dietary preferences.

4.
Ann Rehabil Med ; 48(3): 220-227, 2024 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-38830633

RESUMO

OBJECTIVE: To construct a prognostic model for unsuccessful removal of nasogastric tube (NGT) was the aim of our study. METHODS: This study examined patients with swallowing disorders receiving NGT feeding due to stroke or traumatic brain injury in a regional hospital. Clinical data was collected, such as age, sex, body mass index (BMI), level of activities of daily living (ADLs) dependence. Additionally, gather information regarding the enhancement in Functional Oral Intake Scale (FOIS) levels and the increase in food types according to the International Dysphagia Diet Standardization Initiative (IDDSI) after one month of swallowing training. A stepwise logistic regression analysis model was employed to predict NGT removal failure using these parameters. RESULTS: Out of 203 patients, 53 patients (26.1%) had experienced a failed removal of NGT after six months of follow-up. The strongest predictors for failed removal were age over 60 years, underweight BMI, total dependence in ADLs, and ischemic stroke. The admission prediction model categorized patients into high, moderate, and low-risk groups for removal failure. The failure rate of NGT removal was high not only in the high-risk group but also in the moderate-risk groups when there was no improvement in FOIS levels and IDDSI food types. CONCLUSION: Our predictive model categorizes patients with brain insults into risk groups for swallowing disorders, enabling advanced interventions such as percutaneous endoscopic gastrostomy for high-risk patients struggling with NGT removal, while follow-up assessments using FOIS and IDDSI aid in guiding rehabilitation decisions for those at moderate risk.

5.
Chem Biodivers ; : e202400873, 2024 Jun 20.
Artigo em Inglês | MEDLINE | ID: mdl-38900486

RESUMO

This study explores the anti-inflammatory potential of an endophytic fungus, Trametes versicolor CL-1, isolated from the fruit tissues of Rosa roxburghii. Morphological and molecular analyses confirmed the identity of CL-1. An ethyl acetate extract (CL-E) from its fermentation broth was subjected to UPLC-HRMS and GNPS molecular networking. The analysis revealed a diverse array of secondary metabolites, including 11 terpenes, 7 flavonoids, 10 cinnamic acid derivatives, 6 oligopeptides, and 9 fatty acids, as verified by LC-MS/MS. Notably, CL-E exhibited significant in vitro anti-inflammatory activity in RAW264.7 cells. Furthermore,  molecular docking studies predicted favorable binding interactions of key compounds 1 within CL-E with the NLRP3 inflammasome (PDB ID: 6NPY). These findings suggest T. versicolor CL-1 as a promising source of natural anti-inflammatory agents and unveil R. roxburghii as a potential reservoir for discovering novel bioactive metabolites.

6.
Life Sci ; 352: 122871, 2024 Jun 25.
Artigo em Inglês | MEDLINE | ID: mdl-38936602

RESUMO

AIMS: The gut-brain axis is the communication mechanism between the gut and the central nervous system, and the intestinal flora and lipopolysaccharide (LPS) play a crucial role in this mechanism. Exercise regulates the gut microbiota composition and metabolite production (i.e., LPS). We aimed to investigate the effects of high-intensity interval training (HIIT) and moderate-intensity continuous training (MICT) on cognitive function in C57BL/6 J mice through gut-brain axis regulation of gut microbiota composition and LPS displacement. MAIN METHODS: C57BL/6 J male mice were randomly divided into sedentary, HIIT, and MICT groups. After 12 weeks of exercise intervention, the cognitive function of the brain and mRNA levels of related inflammatory factors were measured. RNA sequencing, Golgi staining, intestinal microbial 16 s rDNA sequencing, and ELISA were performed. KEY FINDINGS: HIIT and MICT affect brain cognitive function by regulating the gut microbiota composition and its metabolite, LPS, through the gut microbiota-gut-brain axis. HIIT is suspected to have a risk: it can induce "intestinal leakage" by regulating intestinal permeability-related microbiota, resulting in excessive LPS in the blood and brain and activating M1 microglia in the brain, leading to reduced dendritic spine density and affecting cognitive function. SIGNIFICANCE: This study revealed a potential link between changes in the gut microbiota and cognitive function. It highlighted the possible risk of HIIT in reducing dendritic spine density and affecting cognitive function.

7.
Nat Prod Res ; : 1-7, 2024 May 16.
Artigo em Inglês | MEDLINE | ID: mdl-38752874

RESUMO

Two new withanolides named physaminilides L (1) and M (2), together with four known ones (3-6) were isolated from the Physalis minima L. The structures were established by analysis of the HR ESIMS, IR and NMR spectroscopic data. The absolute configurations were determined through NOESY and ECD spectra. For compounds 1-5 assayed at 20 µM and compound 6 at 10 µM, inhibition rates of hepatic fibrosis were 22.19%, 15.29%, 37.07%, 9.27%, 12.45%, and 37.03%, respectively.

8.
Infect Dis Ther ; 13(6): 1359-1378, 2024 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-38733495

RESUMO

INTRODUCTION: Listeriosis is a severe food-borne disease caused by Listeria monocytogenes infection. The data of listeriosis in Xi'an population are limited. The aim of this study is to evaluate the clinical features and fatality risk factors for listeriosis in three tertiary-care hospitals in Xi'an, China METHODS: The characteristics of demographic data, underlying diseases, clinical manifestations, laboratory indicators, cranial imaging examination, antibiotics therapeutic schemes, and clinical outcomes were collected between 2011 and 2023. Logistic regression analysis was performed. RESULTS: Seventy-one etiologically confirmed listeriosis patients were enrolled, including 12 neonatal and 59 non-neonatal cases. The majority of neonatal listeriosis presented as preterm (50%) and fetal distress (75%). The main clinical manifestations of non-neonatal listeriosis included fever (88%), headache (32%), disorder of consciousness (25%), vomiting (17%), abdominal pain (12%), and convulsions (8%). The fatality rate in neonatal cases was higher than in non-neonatal listeriosis (42 vs. 17%). Although no deaths were reported in maternal listeriosis, only two of 23 patients had an uneventful obstetrical outcome. Five maternal listeriosis delivered culture-positive neonates, three of whom decreased within 1 week post-gestation due to severe complications. Twenty-eight cases were neurolisteriosis and 43 cases were bacteremia. Neurolisteriosis had a higher fatality rate compared with bacteremia listeriosis (36 vs. 12%). The main neuroradiological images were cerebral edema/hydrocephalus, intracranial infection, and cerebral hernia. Listeria monocytogenes showed extremely low resistance to ampicillin (two isolates) and penicillin (one isolate). The fatality risk factors were the involvement of the central nervous system, hyperbilirubinemia, and hyponatremia for all enrolled subjects. Hyperuricemia contributed to the elevation of fatality risk in non-neonatal listeriosis. CONCLUSIONS: When the patients suffered with symptoms of fever and central nervous system infection, they should be alert to the possibility of listeriosis. Early administration of ampicillin- or penicillin-based therapy might be beneficial for recovery of listeriosis.

9.
Int J Mol Sci ; 25(10)2024 May 18.
Artigo em Inglês | MEDLINE | ID: mdl-38791554

RESUMO

Rose roxburghii, a horticulturally significant species within the Rosa genus of the Rosaceae family, is renowned for its abundance of secondary metabolites and ascorbate, earning it the title 'king of vitamin C'. Despite this recognition, the mechanisms underlying the biosynthesis and regulation of triterpenoid compounds in R. roxburghii remain largely unresolved. In this study, we conducted high-performance liquid chromatography profiling across various organs of R. roxburghii, including fruit, root, stem, and leaves, revealing distinct distributions of triterpenoid compounds among different plant parts. Notably, the fruit exhibited the highest total triterpenoid content, followed by root and stem, with leaf containing the lowest levels, with leaf containing the lowest levels. Transcriptomic analysis unveiled preferential expression of members from the cytochrome P450 (CYP) and glycosyltransferase (UGT) families, likely contributing to the higher accumulation of both ascorbate and triterpenoid compounds in the fruits of R. roxburghii compared to other tissues of R. roxburghii. Transcriptomic analysis unveiled a potential gene network implicated in the biosynthesis of both ascorbate and triterpenoid compounds in R. roxburghii. These findings not only deepen our understanding of the metabolic pathways in this species but also have implications for the design of functional foods enriched with ascorbate and triterpenoids in R. roxburghii.


Assuntos
Perfilação da Expressão Gênica , Regulação da Expressão Gênica de Plantas , Redes Reguladoras de Genes , Rosa , Triterpenos , Triterpenos/metabolismo , Perfilação da Expressão Gênica/métodos , Rosa/genética , Rosa/metabolismo , Transcriptoma , Ácido Ascórbico/metabolismo , Frutas/metabolismo , Frutas/genética , Folhas de Planta/metabolismo , Folhas de Planta/genética , Sistema Enzimático do Citocromo P-450/metabolismo , Sistema Enzimático do Citocromo P-450/genética
10.
Gels ; 10(4)2024 Mar 24.
Artigo em Inglês | MEDLINE | ID: mdl-38667638

RESUMO

Bacterial infections impede the wound healing process and can trigger local or systemic inflammatory responses. Therefore, there is an urgent need to develop a dressing with antimicrobial and anti-inflammatory properties to promote the healing of infected wounds. In this study, BA/COs/NO-PL/AL hydrogels were obtained by adding brevilin A (BA) camellia oil (CO) submicron emulsion and nitric oxide (NO) to hydrogels consisting of sodium alginate (AL) and Pluronic F127 (PL). The hydrogels were characterized through dynamic viscosity analysis, differential scanning calorimetry, and rheology. They were evaluated through anti-inflammatory, antimicrobial, and wound healing property analyses. The results showed that BA/COs/NO-PL/AL hydrogels were thermo-responsive and had good ex vivo and in vivo anti-inflammatory activity, and they also exhibited strong antimicrobial activity against methicillin-resistant Staphylococcus aureus Pseudomonas aeruginosa (MRPA) and methicillin-resistant Staphylococcus aureus (MRSA). They were able to effectively promote healing of the infected wound model and reduce inflammation and bacterial burden. H&E and Masson's staining showed that BA/COs/NO-PL/AL hydrogels promoted normal epithelial formation and collagen deposition. In conclusion, BA/COs/NO-PL/AL hydrogels are promising candidates for promoting the healing of infected wounds.

11.
Mol Neurobiol ; 2024 Mar 01.
Artigo em Inglês | MEDLINE | ID: mdl-38427215

RESUMO

Lactate has a novel function different from previously known functions despite its traditional association with hypoxia in skeletal muscle. It plays various direct and indirect physiological functions. It is a vital energy source within the central nervous system (CNS) and a signal transmitter regulating crucial processes, such as angiogenesis and inflammation. Activating lactate and its associated receptors elicits effects like synaptic plasticity and angiogenesis alterations. These effects can significantly influence the astrocyte-neuron lactate shuttle, potentially impacting cognitive performance. Decreased cognitive function relates to different neurodegenerative conditions, including Alzheimer's disease (AD), ischemic brain injury, and frontotemporal dementia. Therefore, lactic acid has significant potential for treating neurodegenerative disorders. Exercise is a method that induces the production of lactic acid, which is similar to the effect of lactate injections. It is a harmless and natural way to achieve comparable results. Animal experiments demonstrate that high-intensity intermittent exercise can increase vascular endothelial growth factor (VEGF) levels, thus promoting angiogenesis. In vivo, lactate receptor-hydroxycarboxylic acid receptor 1 (HCAR1) activation can occur by various stimuli, including variations in ion concentrations, cyclic adenosine monophosphate (cAMP) level elevations, and fluctuations in the availability of energy substrates. While several articles have been published on the benefits of physical activity on developing Alzheimer's disease in the CNS, could lactic acid act as a bridge? Understanding how HCAR1 responds to these signals and initiates associated pathways remains incomplete. This review comprehensively analyzes lactate-induced signaling pathways, investigating their influence on neuroinflammation, neurodegeneration, and cognitive decline. Consequently, this study describes the unique role of lactate in the progression of Alzheimer's disease.

12.
Foods ; 13(6)2024 Mar 15.
Artigo em Inglês | MEDLINE | ID: mdl-38540880

RESUMO

Extensive research suggests that COVID-19 infection can lead to persistent changes in taste and smell perception. These sensory changes have the potential to exert lasting impacts on dietary choices, nutrition, and body weight. This study aims to explore COVID-related shifts in dietary intake among New Zealand university students. We conducted a survey involving 340 university students who had experienced COVID-19 infection between 2022 and 2023. Participants reported any changes in eating behavior since before the pandemic and were asked to complete a 24-h food record. Participants' total daily energy intake, macronutrient intake, and composition were then compared with data collected from a similar cohort before the COVID-19 pandemic, spanning from 2017 to 2019. Dietary outcomes were compared using MANCOVA while controlling for individual age, gender, ethnicity, and BMI. Approximately 25% of participants reported experiencing sensory alterations with COVID-19, with those participants more likely to report changes in their experience of sweet tastes but not salty or fatty foods. Analyses of the pre- and post-COVID cohorts revealed that participants in the post-COVID group exhibited significantly higher consumption of protein and sodium. Understanding the long-term impact of COVID-19 infection may offer crucial insights into the role of chemosensory perception in dietary behavior.

13.
Appetite ; 195: 107236, 2024 04 01.
Artigo em Inglês | MEDLINE | ID: mdl-38307298

RESUMO

OBJECTIVE: The study aimed to assess potential effects of vaping on individual taste and smell perception in a sample of young adult New Zealanders. DESIGN: This cross-sectional study measured taste and smell perception using intensity and hedonic ratings to two olfactory (i.e., vanillin, methional) and two gustatory stimuli (i.e., sucrose, monosodium glutamate), representing sweet and savoury flavours. Detection sensitivities to sucrose and vanillin were also assessed using a forced choice detection paradigm aligned with the signal detection framework. MANCOVAs were employed to compare sensory perception between groups based on vaping use frequency. Additional regression analyses were conducted to identify potential predictors of intensity and hedonic sensory ratings. SETTING: Participants were recruited from the University of Otago student population and surrounding neighbourhoods of Dunedin, New Zealand in 2023. PARTICIPANTS: The study included 213 university students (98 vapers and 115 non-vapers) RESULTS: We found a significant difference in hedonic ratings for vanillin, indicating a stronger preference among non-vapers. However, no other differences between the two groups were significant. Notably, the use of tobacco and mint flavours were emerged as significant predictors for hedonic responses to the savoury smell and sweet taste stimulus, respectively. No significant differences were observed between groups in the ability to detect weak stimuli. CONCLUSIONS: Our findings suggest that vape use, particularly with specific flavours, may be associated with alterations in hedonic responses to smells. This finding may have potential implications for how vaping affects on food preferences and dietary choices.


Assuntos
Olfato , Percepção Gustatória , Vaping , Humanos , Adulto Jovem , População Australasiana , Benzaldeídos , Estudos Transversais , Aromatizantes , Preferências Alimentares/fisiologia , Nova Zelândia , Olfato/fisiologia , Sacarose , Percepção Gustatória/fisiologia
14.
J Ethnopharmacol ; 325: 117830, 2024 May 10.
Artigo em Inglês | MEDLINE | ID: mdl-38301983

RESUMO

ETHNOPHARMACOLOGICAL RELEVANCE: Physalis angulata L., a traditional Chinese medicine called "Kuzhi" in China, was used traditionally to treat liver diseases (eg. icterus, hepatitis) as well as malaria, asthma, and rheumatism. AIM OF THE STUDY: Our study aimed to investigate the withanolides with anti-hepatic fibrosis effect from P. angulate. MATERIALS AND METHODS: Withanolides were obtained from the EtOH extract of P. angulate by bioassay-molecular networking analysis-guided isolation using column chromatography and normal/reversed-phase semipreparative HPLC. The structures of new withanolides were elucidated by combinations of spectroscopic techniques with NMR and ECD calculations. MTT cell viability assay, AO/EB staining method, cell wound healing assay, ELISA and Western blot experiments were employed to evaluate the anti-hepatic fibrosis activity and to uncover related mechanism. Molecular docking analysis and cellular thermal shift assay were used to evaluate and verify the interaction between the active withanolides and their potential targets. RESULTS: Eight unreported withanolides, withagulides A-H (1-8), along with twenty-eight known ones were obtained from P. angulate. Withanolides 6, 9, 10, 24, 27, and 29-32 showed marked anti-hepatic fibrosis effect with COL1A1 expression inhibition above 50 %. Physalin F (9), the main component in the active fraction, significantly decreased the TGF ß1-stimulated expressions of collagen I and α-SMA in LX-2 cells. Mechanism study revealed that physalin F exerted its anti-hepatic fibrosis effect via the PI3K/AKT/mTOR signaling pathway. CONCLUSION: This study suggested that withanolides were an important class of natural products with marked anti-hepatic fibrosis effect. The main withanolide physalin F might be a promising candidate for hepatic fibrosis treatment. The work provided experimental foundation for the use of P. angulate to treat hepatic fibrosis.


Assuntos
Physalis , Vitanolídeos , Vitanolídeos/farmacologia , Vitanolídeos/uso terapêutico , Vitanolídeos/química , Physalis/química , Simulação de Acoplamento Molecular , Fosfatidilinositol 3-Quinases , Cirrose Hepática/induzido quimicamente , Cirrose Hepática/tratamento farmacológico , Extratos Vegetais/farmacologia , Extratos Vegetais/uso terapêutico , Extratos Vegetais/química
15.
Thromb Res ; 236: 22-29, 2024 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-38387300

RESUMO

OBJECTIVE: The purpose was to evaluate pregnancy outcomes and risk factors associated with fetal complications in Chinese pregnant women with mechanical heart valves (MHVs) taking low-dose warfarin, aiming to fill in the research gap of this area. METHODS: Between June 2010 and Aug 2023, 122 patients with MHVs who had 151 pregnancies and received warfarin throughout pregnancy were included. We compared them with 302 paired pregnancies without warfarin treatment. Binary logistic regression analyses were performed to explore risk predictors of fetal complications. RESULTS: Pregnancy loss rate was 37.1 % in women taking warfarin, compared to only 4.6 % for those without warfarin exposure in pregnancy (RR = 8.00, 95 % CI: 4.61-13.90). In pregnant women with MHVs, there were 34 spontaneous abortions, 22 stillbirths and 1 neonatal malformation. In the first, second and third pregnant trimesters of women with MHVs, fetal complication incidences were 19.2 %, 9.9 % and 8.0 %, respectively. 86.0 % of fetal complications occurred in women taking a warfarin dose ≤5 mg/d, accounting for 94.0 % of the total population. The newborns' birth weight, gestational age and 1-minute Apgar score were significantly lower in pregnancies treated with warfarin compared to those without warfarin exposure. Only 2.0 % of postpartum hemorrhage and no thrombosis or maternal mortality data were collected in pregnant women on warfarin in this study. CONCLUSION: Most Chinese pregnant women take a warfarin daily dose ≤5 mg and they might have only around 60 % chance of giving birth to a live baby without maternal complications.


Assuntos
Aborto Espontâneo , Complicações Cardiovasculares na Gravidez , Gravidez , Feminino , Humanos , Recém-Nascido , Lactente , Resultado da Gravidez , Varfarina/efeitos adversos , Anticoagulantes/efeitos adversos , Complicações Cardiovasculares na Gravidez/tratamento farmacológico , Valvas Cardíacas , China/epidemiologia
16.
NPJ Genom Med ; 9(1): 4, 2024 Jan 09.
Artigo em Inglês | MEDLINE | ID: mdl-38195571

RESUMO

Our study presents a 319-gene panel targeting inherited retinal dystrophy (IRD) genes. Through a multi-center retrospective cohort study, we validated the assay's effectiveness and clinical utility and characterized the mutation spectrum of Taiwanese IRD patients. Between January 2018 and May 2022, 493 patients in 425 unrelated families, all initially suspected of having IRD without prior genetic diagnoses, underwent detailed ophthalmic and physical examinations (with extra-ocular features recorded) and genetic testing with our customized panel. Disease-causing variants were identified by segregation analysis and clinical interpretation, with validation via Sanger sequencing. We achieved a read depth of >200× for 94.2% of the targeted 1.2 Mb region. 68.5% (291/425) of the probands received molecular diagnoses, with 53.9% (229/425) resolved cases. Retinitis pigmentosa (RP) is the most prevalent initial clinical impression (64.2%), and 90.8% of the cohort have the five most prevalent phenotypes (RP, cone-rod syndrome, Usher's syndrome, Leber's congenital amaurosis, Bietti crystalline dystrophy). The most commonly mutated genes of probands that received molecular diagnosis are USH2A (13.7% of the cohort), EYS (11.3%), CYP4V2 (4.8%), ABCA4 (4.5%), RPGR (3.4%), and RP1 (3.1%), collectively accounted for 40.8% of diagnoses. We identify 87 unique unreported variants previously not associated with IRD and refine clinical diagnoses for 21 patients (7.22% of positive cases). We developed a customized gene panel and tested it on the largest Taiwanese cohort, showing that it provides excellent coverage for diverse IRD phenotypes.

17.
Molecules ; 29(2)2024 Jan 15.
Artigo em Inglês | MEDLINE | ID: mdl-38257331

RESUMO

Liver fibrosis is the initial pathological process of many chronic liver diseases. Targeting hepatic stellate cell (HSC) activation is an available strategy for the therapy of liver fibrosis. We aimed to explore the anti-liver fibrosis activity and potential mechanism of phomopsterone B (PB) in human HSCs. The results showed that PB effectively attenuated the proliferation of TGF-ß1-stimulated LX-2 cells in a concentration-dependent manner at doses of 1, 2, and 4 µM. Quantitative real-time PCR and Western blot assays displayed that PB significantly reduced the expression levels of α-SMA and collagen I/III. AO/EB and Hoechst33342 staining and flow cytometry assays exhibited that PB promoted the cells' apoptosis. Meanwhile, PB diminished the number of autophagic vesicles and vacuolated structures, and the LC3B fluorescent spots indicated that PB could effectively inhibit the accretion of autophagosomes in LX-2 cells. Moreover, rapamycin and MHY1485 were utilized to further investigate the effect of mTOR in autophagy and apoptosis. The results demonstrated that PB regulated autophagy and apoptosis via the mTOR-dependent pathway in LX-2 cells. In summary, this is the first evidence that PB effectively alleviates liver fibrosis in TGF-ß1-stimulated LX-2 cells, and PB may be a promising candidate for the prevention of liver fibrosis.


Assuntos
Autofagia , Fator de Crescimento Transformador beta1 , Humanos , Cirrose Hepática/tratamento farmacológico , Autofagossomos , Apoptose
18.
Org Biomol Chem ; 22(7): 1453-1457, 2024 Feb 14.
Artigo em Inglês | MEDLINE | ID: mdl-38276970

RESUMO

With dimethyl sulfoxide (DMSO) as the methylthio source, a KF-catalyzed strategy was employed for the direct thiomethylation of carboxylic acids with DMSO for the preparation of methyl thioesters. In this process, a wide range of methyl thioesters were obtained in moderate to excellent yields. This novel strategy features the first use of DMSO as a methylthiolating agent for the construction of methyl thioesters, transition metal-free conditions, inexpensive reagents, easy workup, broad substrate scope and sustainability. Additionally, this procedure can be readily scaled up to a gram scale.

19.
J Ethnopharmacol ; 325: 117619, 2024 May 10.
Artigo em Inglês | MEDLINE | ID: mdl-38272103

RESUMO

ETHNOPHARMACOLOGICAL RELEVANCE: Calcium oxalate (CaOx) kidney stones are widely acknowledged as the most prevalent type of urinary stones, with high incidence and recurrence rates. Incarvillea diffusa Royle (ID) is a traditionally used medicinal herb in the Miao Minzu of Guizhou province, China, for treating urolithiasis. However, the active components and the underlying mechanism of its pharmacodynamic effects remain unclear. AIM OF THE STUDY: This study aimed to investigate the potential inhibitory effect of the active component of ID on the formation of CaOx nephrolithiasis and elucidate the underlying mechanism. MATERIALS AND METHODS: In vivo, a CaOx kidney stone model was induced in Sprague-Dawley (SD) rats using an ethylene glycol and ammonium chloride protocol for four weeks. Forty-eight male SD rats were randomly assigned to 6 groups (n = 8): blank group, model group, apocynin group, and low, medium, and high dose of ID's active component (IDW) groups. After three weeks of administration, rat urine, serum, and kidney tissues were collected. Renal tissue damage and crystallization, Ox, BUN, Ca2+, CRE, GSH, MDA, SOD contents, and levels of IL-1ß, IL-18, MCP-1, caspase-1, IL-6, and TNF-α in urine, serum, and kidney tissue were assessed using HE staining and relevant assay kits, respectively. Protein expression of Nrf2, HO-1, p38, p65, and Toll-4 in kidney tissues was quantified via Western blot. The antioxidant capacities of major compounds were evaluated through DPPH, O2·-, and ·OH radical scavenging assays, along with their effects on intracellular ROS production in CaOx-induced HK-2 cells. RESULTS: We found that IDW could significantly reduce the levels of CRE, GSH, MDA, Ox, and BUN, and enhancing SOD activity. Moreover, it could inhibit the secretion of TNF-α, IL-1ß, IL-18, MCP-1, caspase-1, and decreased protein expression of Nrf2, HO-1, p38, p65, and Toll-4 in renal tissue. Three major compounds isolated from IDW exhibited promising antioxidant activities and inhibited intracellular ROS production in CaOx-induced HK-2 cells. CONCLUSIONS: IDW facilitated the excretion of supersaturated Ca2+ and decreased the production of Ox, BUN in SD rat urine, and mitigated renal tissue damage by regulating Nrf2/HO-1 signaling pathway. Importantly, the three major compounds identified as active components of IDW contributed to the inhibition of CaOx nephrolithiasis formation. Overall, IDW holds significant potential for treating CaOx nephrolithiasis.


Assuntos
Oxalato de Cálcio , Nefrolitíase , Ratos , Masculino , Animais , Oxalato de Cálcio/urina , Espécies Reativas de Oxigênio/metabolismo , Interleucina-18/efeitos adversos , Interleucina-18/metabolismo , Fator 2 Relacionado a NF-E2/metabolismo , Antioxidantes/efeitos adversos , Ratos Sprague-Dawley , Fator de Necrose Tumoral alfa/metabolismo , Nefrolitíase/induzido quimicamente , Nefrolitíase/tratamento farmacológico , Rim/metabolismo , Superóxido Dismutase/metabolismo , Caspases/metabolismo
20.
Risk Anal ; 44(2): 285-294, 2024 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-37340675

RESUMO

Humans live in social groups; thus, infectious diseases may threaten human health and safety. Do individuals exhibit ingroup favoritism or ingroup devaluation when faced with varying risks of infectious diseases? We generated relatively realistic disease scenarios to examine this question. We reported the results from three experiments in which we tested individuals' perceived disease risk from ingroup and outgroup members under high- and low-risk conditions. Experiment 1 used a realistic influenza scenario, and Experiments 2 and 3 used a realistic scenario of exposure to coronavirus disease 2019 (COVID-19). All three experiments showed that perceived disease risk was significantly lower from ingroup members than from outgroup members and significantly lower in low-risk conditions than in high-risk conditions. Furthermore, the perceived disease risk was significantly lower from ingroup members than from outgroup members in high-risk conditions but did not significantly differ in low-risk conditions, as in Experiment 1's influenza scenario and Experiment 2's COVID-19 vaccination scenario. This suggests that ingroup favoritism is flexible. The results support ingroup favoritism and the functional flexibility principle in response to disease threats according to perceived disease risk.


Assuntos
COVID-19 , Doenças Transmissíveis , Influenza Humana , Humanos , Relações Interpessoais , Influenza Humana/epidemiologia , Vacinas contra COVID-19 , Processos Grupais , Identificação Social , Doenças Transmissíveis/epidemiologia , COVID-19/epidemiologia
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