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OBJECTIVE: Previous studies have investigated the association between diabetes medications and thyroid cancer, but the results have not been conclusive. This study used a Mendelian randomization approach to investigate the causal relationship between diabetes medications and thyroid cancer (TC). METHODS: Exposures were six major diabetes medications target, while outcomes were TC and its differentiated forms, including papillary thyroid carcinoma (PTC) and follicular thyroid carcinoma (FTC). Mendelian randomization was conducted using IVW, MR-Egger, and weighted median methods. Tests for heterogeneity, horizontal pleiotropy, and leave-one-out were also performed. RESULTS: In European populations, SGLT2 inhibitors were significantly negatively associated with TC (OR 0.051, 95% CI 0.006-0.465, P = 0.0082) as well as PTC (OR 0.034, 95% CI 0.003-0.411, P = 0.0079), while no correlation was found with FTC. These findings remained consistent even after applying the Bonferroni correction. CONCLUSIONS: The evidence suggests that SGLT2 inhibitors could be potential therapeutic targets for TC, especially for PTC, in European populations. However, further large-scale randomized controlled trials are necessary to verify their ability to reduce the risk of and treat these types of cancer.
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Functional ability decline occurs with age. This study aims to investigate the associations between the lifestyle factors-exercising, food consumption, and smoking-and the functional ability of the activities of daily living (ADL) by gender. The data were obtained from the Taiwan longitudinal study on aging, a national cohort study. The cross-sectional results demonstrated that the frequency of exercising was negatively associated with ADL in both men and women. Dairy products were positively associated with ADL in men. The longitudinal results illustrated that current and consistent exercising were negatively associated with changes in ADL scores over 4- and 8-year periods in both men and women. Seafood consumption was negatively associated with changes in the subsequent 4-year ADL scores. Past smoking was positively associated with changes in subsequent 4-year ADL scores in men, while current smoking was positively associated with changes in subsequent 8-year ADL scores in women. Therefore, consistent exercising, food consumption, and smoking were associated with ADL functional ability in elderly people, and the associations differed by gender. Elders exercising consistently had good ADL performance and maintained their ADL ability better, especially women. Seafood consumption decreased the risk of ADL decline, while smoking increased the risk of ADL decline.
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Actividades Cotidianas , Envejecimiento , Ejercicio Físico , Estilo de Vida , Fumar , Humanos , Masculino , Femenino , Taiwán/epidemiología , Estudios Longitudinales , Anciano , Envejecimiento/fisiología , Estudios Transversales , Fumar/epidemiología , Anciano de 80 o más Años , Factores de Riesgo , Dieta/estadística & datos numéricos , Factores Sexuales , Alimentos MarinosRESUMEN
Citrus canker, caused by Xanthomonas citri subsp. citri (Xcc), is a severe citrus disease. Currently, copper-containing pesticides are widely used to manage this disease, posing high risks to the environment and human health. This study reports the discovery of naturally occurring anti-Xcc compounds from a deep-sea fungus, Aspergillus terreus SCSIO 41202, and the possible mode of action. The ethyl acetate extract of A. terreus was subjected to bioassay-guided isolation, resulting in the discovery of eight anti-Xcc compounds (1-8) with minimum inhibitory concentrations (MICs) ranging from 0.078 to 0.625 mg/mL. The chemical structures of these eight metabolites were determined by integrative analysis of various spectroscopic data. Among these compounds, Asperporonin A (1) and Asperporonin B (2) were identified as novel compounds with a very unusual structural skeleton. The electronic circular dichroism was used to determine the absolute configurations of 1 and 2 through quantum chemical calculation. A bioconversion pathway involving pinacol rearrangement was proposed to produce the unusual compounds (1-2). Compound 6 exhibited an excellent anti-Xcc effect with a MIC value of 0.078 mg/mL, which was significantly more potent than the positive control CuSO4 (MIC = 0.3125 mg/mL). Compound 6 inhibited cell growth by disrupting biofilm formation, destroying the cell membrane, and inducing the accumulation of reactive oxygen species. In vivo tests indicated that compound 6 is highly effective in controlling citrus canker disease. These results indicate that compounds 1-8, especially 6, have the potential as lead compounds for the development of new, environmentally friendly, and efficient anti-Xcc pesticides.
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Antibacterianos , Aspergillus , Pruebas de Sensibilidad Microbiana , Enfermedades de las Plantas , Xanthomonas , Xanthomonas/efectos de los fármacos , Aspergillus/efectos de los fármacos , Aspergillus/química , Aspergillus/metabolismo , Enfermedades de las Plantas/microbiología , Antibacterianos/farmacología , Antibacterianos/química , Citrus/química , Citrus/microbiología , Estructura MolecularRESUMEN
Ischemic stroke (IS) has attracted worldwide attention due to the high mortality and disability rate. Raw rhubarb (RR) is a traditional medicinal plant and whole-food that has been used in China for its various pharmacological activities, such as antioxidant and anti-inflammatory properties. Recent pharmacological research has shown the role of RR against IS, but its mechanism of action remains unclear, particularly in the context of the brain-gut axis. To address this gap in knowledge, the present study was conducted in the middle cerebral artery occlusion/reperfusion (MCAO/R) model with the aim of investigating the effects of RR on regulating the intestinal microbiota barrier and metabolism and thereby reducing inflammatory response so as to improve the IS. The results showed that pre-treatment of RR attenuated cerebral infarct area and inflammation response in MCAO rats. Furthermore, RR also improved intestinal barrier function, including the integrity and permeability of the intestinal barrier. Additionally, RR intervention significantly attenuated gut microbiota dysbiosis caused by ischemic stroke, especially the increased Firmicutes. Notably, the pseudo-germ-free (PGF) rats further demonstrated that the anti-stroke effect of RR might rely on intestinal microbiota. In addition, the UPLC/Q-Orbitrap-MS-Based metabolomics revealed the disrupted metabolic profiles caused by MCAO/R, and a total of 11 differential metabolites were modulated by RR administration, especially bile acids. Further correlation analysis and network pharmacology analysis also demonstrated a strong association between specific bacteria, such as Firmicutes and bile acids. In conclusion, our work demonstrated that RR could effectively ameliorate ischemic stroke by modulating the microbiota and metabolic disorders.
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Eje Cerebro-Intestino , Microbioma Gastrointestinal , Accidente Cerebrovascular Isquémico , Ratas Sprague-Dawley , Rheum , Animales , Rheum/química , Microbioma Gastrointestinal/efectos de los fármacos , Accidente Cerebrovascular Isquémico/tratamiento farmacológico , Ratas , Masculino , Eje Cerebro-Intestino/efectos de los fármacos , Metaboloma , Infarto de la Arteria Cerebral Media , Disbiosis , Modelos Animales de EnfermedadRESUMEN
With the escalating air pollution and frequent outbreaks of airborne diseases, there is a growing demand for personal protective filtration media. Melt-blown nonwovens have proven to be highly effective in capturing tiny particles, but their tightly packed fiber assemblages are more resistant to airflow and less comfortable to breathe. Here, we present a one-step melt-blown spinning process for the production of bicomponent core/sheath (BCS) crimped fibers and their application in high-efficiency, low-resistance air filtration. Fiber curl is caused by unbalanced internal stresses resulting from differences in the structure components, resulting in uneven shrinkage inside and outside the fibers. The resulting CM@S-2 filtration media features a uniform fiber curl and a porous fiber mesh structure, which reduces air filtration resistance. Under the same filtration conditions, the filtration efficiency of CM@S-2 (96.58% vs. 95.58%), filtration resistance (56.1 Pa vs. 108.0 Pa), quality factor (0.061 Pa-1vs. 0.029 Pa-1), and dust holding capacity (10.60 g m-2vs. 9.10 g m-2) were comparable to those of the single-component polypropylene filters. The filtration efficiency of the CM@S-2 remained above 94.0% after 30 days of indoor storage. Computational Fluid Dynamics (CFD) simulation demonstrated that crimped fibers effectively reduce pressure surges on the filter media caused by fiber accumulation. In comparative tests with commercial masks, the CM@S-2 cartridge masks demonstrated superior air permeability compared to commercial masks under similar filtration conditions. In conclusion, the bicomponent core/sheath melt-blown fibers significantly reduce air resistance and show excellent potential for application in protective masks.
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Background & Aims: A high human cytomegalovirus (HCMV) infection rate accompanied by an increased level of bile duct damage is observed in the perinatal period. The possible mechanism was investigated. Methods: A total of 1,120 HCMV-positive and 9,297 HCMV-negative children were recruited, and depending on age, their liver biochemistry profile was compared. Fetal and infant biliary epithelial cells (F-BECs and I-BECs, respectively) were infected with HCMV, and the differences in cells were revealed by proteomic analysis. Protein-protein interactions were examined by coimmunoprecipitation and mass spectrometry analyses. A murine cytomegalovirus (MCMV) infection model was established to assess treatment effects. Results: Perinatal HCMV infection significantly increased the level of bile duct damage. Neonatal BALB/c mice inoculated with MCMV showed obvious inflammation in the portal area with an abnormal bile duct structure. Proteomics analysis showed higher CD14 expression in F-BECs than in I-BECs. CD14 siRNA administration hindered HCMV infection, and CD14-knockout mice showed lower MCMV-induced bile duct damage. HCMV infection upregulated CD55 and poly ADP-ribose polymerase-1 (PARP-1) expression in F-BECs. Coimmunoprecipitation and mass spectrometry analyses revealed formation of the CD14-CD55 complex. siRNA-mediated inhibition of CD55 expression reduced sCD14-promoted HCMV replication in F-BECs. In MCMV-infected mice, anti-mouse CD14 antibody and PARP-1 inhibitor treatment diminished cell death, ameliorated bile duct damage, and reduced mortality. Conclusions: CD14 facilitates perinatal HCMV infection in BECs via CD55, and PARP-1-mediated cell death was detected in perinatal cytomegalovirus-infected BECs. These results provide new insight into the treatment of perinatal HCMV infection with bile duct damage. Impact and implications: Perinatal human cytomegalovirus (HCMV) infection is associated with bile duct damage, but the underlying mechanism is still unknown. We discovered that CD14 expression is increased in biliary epithelial cells during perinatal HCMV infection and facilitates viral entry through CD55. We also detected PARP-1-mediated cell death in perinatal HCMV-infected biliary epithelial cells. We showed that blocking CD14 or inhibiting PARP-1 reduced bile duct damage and mortality in a mouse model of murine cytomegalovirus infection. Our findings provide a new insight into therapeutic strategies for perinatal HCMV infection.
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Most brain metastases originate from lung cancer. The majority of cases of lung cancer can be categorized into squamous carcinoma and adenocarcinoma,necessitating distinct clinical treatments and yielding diverse prognoses.Therefore,accurate preoperative evaluation of pathological types through imaging techniques is essential. The objective of this study is to assess the capability of amide proton transfer-weighted(APTw) MRI in predicting the pathological types of brain metastases in lung cancer.Additionally,it seeks to evaluate whether APTw MRI can provide additional value to diffusion-weighted imaging(DWI) at MRI·In this study,a total of 32 participants(mean age,60 ± 9 years;14 men) underwent evaluation,comprising 9 with squamous carcinoma and 23 with adenocarcinoma.Interestingly,adenocarcinoma demonstrated elevated APTw values(2.70 ± 0.81% vs 1.82 ± 0.47%;P = 0.001) and a higher apparent diffusion coefficient(ADC) value(1.00 ± 0.40 × 10-3 mm2/s vs 0.77 ± 0.13 × 10-3 mm2/s;P<0.05) in comparison to squamous carcinoma. The area under the receiver operating characteristic curve(AUC) of APTw and ADC in distinguishing between squamous carcinoma and adenocarcinoma were found to be 0.84 and 0.63,respectively.Moreover,the combined area under the receiver operating characteristic curve of the two techniques is 0.84. Amide proton transfer-weighted has the potential to predict the pathological types of brain metastases in lung cancer.
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Adenocarcinoma , Neoplasias Encefálicas , Carcinoma de Células Escamosas , Neoplasias Pulmonares , Masculino , Humanos , Persona de Mediana Edad , Anciano , Neoplasias Pulmonares/diagnóstico por imagen , Protones , Amidas , Imagen por Resonancia Magnética/métodos , Neoplasias Encefálicas/diagnóstico por imagen , Neoplasias Encefálicas/patología , Carcinoma de Células Escamosas/diagnóstico por imagenRESUMEN
BACKGROUND: Circulating tumor cell (CTC) counting may be a useful non-invasive biomarker that helps patients choose first-line treatment options. Nevertheless, the cost of CTC inspection may impose an economic burden on patients, necessitating the simultaneous consideration of both its clinical effectiveness and cost. We evaluated the cost-effectiveness of CTC count-guided chemotherapy and endocrine therapy as first-line therapy for HR+/HER2-metastatic breast cancer (MBC) from the perspective of US payers. METHODS: Based on the STIC CTC trial, a Markov model was constructed for three health states, and health outcomes were measured in quality-adjusted life years (QALYs) and incremental cost-effectiveness ratio (ICER). One-way and probabilistic sensitivity analyses were performed to assess the robustness of the incremental cost per QALY. RESULTS: The base-case analysis revealed that CTC count-driven treatment was associated with improved effectiveness by 0.07 QALYs and increased the overall cost by $9187.05 compared with clinician-driven first-line treatment choices, leading to an ICER of $138 354.15 per QALY. One-way sensitivity analysis indicated that the model was most sensitive to the cost of treatment for neutropenia and the utility for PFS; probability sensitivity analysis indicated that CTC count-driven treatment choices would be considered the cost-effective option at a willingness-to-pay threshold of $150 000 per QALY. CONCLUSIONS: The findings of this cost-effectiveness analysis suggest that, at the current price of CTC enumeration, choosing first-line treatment options based on CTC count is a cost-effectiveness approach for treating patients with HR+/HER2- MBC in the US.
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Neoplasias de la Mama , Células Neoplásicas Circulantes , Humanos , Estados Unidos , Femenino , Neoplasias de la Mama/patología , Análisis de Costo-Efectividad , Análisis Costo-Beneficio , Resultado del Tratamiento , Años de Vida Ajustados por Calidad de VidaRESUMEN
PURPOSE: The effectiveness of anastrozole for breast cancer prevention has been demonstrated. The objective of this study was to evaluate the cost-effectiveness of anastrozole for the prevention of breast cancer in women with a high risk of breast cancer and to determine whether anastrozole for the primary prevention of breast cancer can improve the quality of life of women and save health-care resources. METHODS: A decision-analytic model was used to assess the costs and effects of anastrozole prevention versus no prevention among women with a high risk of breast cancer. The key parameters of probability were derived from the IBIS-II trial, and the cost and health outcome data were derived from published literature. Costs, quality-adjusted life-years (QALYs), and incremental cost-effectiveness ratios (ICERs) were calculated for the two strategies,One-way and probabilistic sensitivity analyses were performed. RESULTS: In the base case, the incremental cost per QALY of anastrozole prevention was £125,705.38/QALY in the first 5 years compared with no prevention in the UK, above the threshold of WTP (£3,000/QALY),and in the 12-year period, the ICER was £8,313.45/QALY, less than WTP. For the US third-party payer, ICER was $134,232.13/QALY in the first 5 years and $8,843.30/QALY in the 12 years, both less than the WTP threshold ($150,000/QALY). CONCLUSION: In the UK and US, anastrozole may be a cost-effective strategy for the prevention of breast cancer in high-risk postmenopausal women. Moreover, the longer the cycle of the model, the higher the acceptability. The results of this study may provide a scientific reference for decision-making for clinicians, patients, and national medical and health care government departments.
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Neoplasias de la Mama , Humanos , Femenino , Anastrozol/uso terapéutico , Neoplasias de la Mama/prevención & control , Análisis de Costo-Efectividad , Posmenopausia , Calidad de Vida , Nitrilos/uso terapéutico , Triazoles/uso terapéutico , Análisis Costo-Beneficio , Reino Unido , Años de Vida Ajustados por Calidad de VidaAsunto(s)
Neoplasias Encefálicas , Neoplasias del Ventrículo Cerebral , Glioblastoma , Linfoma , Humanos , Glioblastoma/diagnóstico por imagen , Glioblastoma/patología , Neoplasias Encefálicas/diagnóstico por imagen , Neoplasias del Ventrículo Cerebral/diagnóstico por imagen , Neoplasias del Ventrículo Cerebral/patología , Linfoma/diagnóstico por imagen , Diagnóstico DiferencialRESUMEN
OBJECTIVE: To evaluate the effects of pharmacist interventions in type-2 diabetes patients by collecting and evaluating literature. METHODS: A systematic search was conducted across six databases, including CNKI, Wanfang Data, VIP, PubMed, Web of Science, and Cochrane Library, from January 2001 to January 2023. Randomized controlled trials evaluating the clinical outcomes of pharmacist interventions on type-2 diabetes patients were searched, and data were extracted and analysed by RevMan version 5.4 software. RESULTS: A total of 35 studies involving 4827 patients were included. Meta-analysis demonstrated that pharmacist interventions had an influence on improving patients' HbA1c (MD=-0.70), LDL-C (MD=-5.51), SBP (MD=-4.58), DBP (MD=-1.90], BMI (MD=-0.47) and FBG (MD=-19.82), but there was no evidence from the study that pharmacist interventions could significantly improve HDL-C (MD=-0.61), TC (MD=-5.12) or TG (MD=-3.14). In addition, medication adherence was significantly improved. CONCLUSION: Pharmacist interventions significantly improved HbA1c, BP, and LDL-C control levels, BMI, and medication adherence in type-2 diabetes patients, but there was no evidence from this study that pharmacist interventions significantly improved HDL-C, TC, or TG. PRACTICE IMPLICATIONS: Effective pharmacist interventions are important to improve type-2 diabetes patients' clinical outcomes.
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Diabetes Mellitus Tipo 2 , Farmacéuticos , Humanos , LDL-Colesterol , Hemoglobina Glucada , Diabetes Mellitus Tipo 2/tratamiento farmacológico , Cumplimiento de la Medicación , Ensayos Clínicos Controlados Aleatorios como AsuntoRESUMEN
BACKGROUND AND OBJECTIVE: Neuromyelitis optica spectrum disorder (NMOSD) is a rare immune-mediated demyelinating disease of the central nervous system (CNS). There is a lack of reports of sick sinus syndrome (SSS) associated with NMOSD; thus, we hereby report two cases of patients with NMOSD who developed SSS. CASES PRESENTATION: The patients were both male and presented with area postrema syndrome. Brain MRI showed lesions in the dorsal part of their medulla oblongata. They were diagnosed with NMOSD when aquaporin-4 antibodies were found in their serum. Slow heart rates and several episodes of syncope were also observed in case 1 during hospitalization, while Holter monitoring showed sinus pauses (10-11 s) and SSS was diagnosed. A pacemaker was fitted. Case 2 had a respiratory arrest followed by a subsequent cardiac arrest. He was successfully resuscitated with epinephrine injection and cardiopulmonary resuscitation. Through immunotherapy, their neurological functions became stable and heart rate and blood pressure returned to the baseline. CONCLUSIONS: Since sick sinus syndrome is a life-threatening complication, serious heart arrhythmias should be considered as a potential result of area postrema syndrome associated with NMOSD.
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BACKGROUND AND OBJECTIVE: There is a considerable survival benefit of alpelisib in patients with PIK3CA-mutated, hormone receptor-positive and human epidermal growth factor receptor 2-negative advanced breast cancer (HR+/HER2- ABC), yet the financial burden may limit its use. Therefore, this study evaluated the cost-effectiveness of alpelisib plus fulvestrant in patients with PIK3CA-mutated, HR+/HER2- ABC in the USA. METHODS: A Markov model was constructed to simulate the progression of PIK3CA-mutated, HR+/HER2- ABC. Efficacy and safety data were derived from the SOLAR-1 trial. A parametric survival model was used to explore the long-term effect. From a US payer perspective, only direct medical costs were considered. The cost data were estimated based on local pricing and relevant literature. The health outcomes were expressed in quality-adjusted life years (QALYs). Model stability was assessed using one-way sensitivity analysis and probability sensitivity analysis. Subgroup analyses were performed to explore cost-effectiveness outcomes for patients with different clinical characteristics. RESULTS: The QALY increased by 0.28 with alpelisib plus fulvestrant with an additional cost of $94,345.87 compared with placebo plus fulvestrant, leading to an incremental cost-effectiveness ratio (ICER) of $340,153.30/QALY gained. Sensitivity analyses suggested that the model is most sensitive to the price of alpelisib. At a willingness-to-pay (WTP) threshold of $150,000/QALY, alpelisib plus fulvestrant was cost effective when the cost of alpelisib was less than $71 per 300 mg (36.5 % of the original price), whereas this cost would be less than $168 per 300 mg (86.5 % of the original price) at a WTP threshold of $300,000/QALY. In addition, alpelisib + fulvestrant was not cost effective in all subgroups compared with placebo + fulvestrant at the WTP threshold of $150,000/QALY. In contrast, at the WTP threshold of $300,000/QALY, alpelisib + fulvestrant was cost effective in nearly all subgroups except for endocrine-sensitive patients. CONCLUSION: At current drug prices, alpelisib plus fulvestrant is not cost effective for patients with PIK3CA-mutated, HR+/HER2- ABC from a US payer perspective. Given the considerable progression-free survival (PFS) and overall survival (OS) benefits observed with alpelisib in this setting, further discussion and negotiation of the price of alpelisib are warranted to provide more favorable economic outcomes and thereby increase the value of the alpelisib plus fulvestrant regimen in patients.
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Neoplasias de la Mama , Humanos , Femenino , Fulvestrant , Neoplasias de la Mama/tratamiento farmacológico , Neoplasias de la Mama/genética , Análisis Costo-Beneficio , Fosfatidilinositol 3-Quinasa Clase I/genética , Mutación , Protocolos de Quimioterapia Combinada Antineoplásica/uso terapéutico , Receptor ErbB-2/genética , Receptor ErbB-2/metabolismoRESUMEN
Subacute combined degeneration (SCD) is a neurological disorder caused by vitamin B12 deficiency, prevalent in the cervical and thoracic medullas, with an insidious onset and a lack of characteristic clinical manifestations. The present study describes a case of a 36-year-old female patient with SCD who demonstrated abnormal changes in the white matter of the brain. The laboratory test results showed a decrease in serum vitamin B12 levels and an increase in homocysteine levels. Magnetic resonance imaging (MRI) of the brain showed that, in addition to abnormal signals in the cervical and thoracic spine, speckled and short-striped abnormal signals were present, symmetrically distributed in the centrum semiovale. After 6 months of follow-up treatment, cranial MRI showed a significant attenuation of the symmetrical speckled and short-striped abnormal signals in the centrum semiovale. Homocysteine and serum vitamin B12 levels of the patient were within the expected range. Although, to the best of our knowledge, there have been no previous reports of alterations in the brain of patients with SCD, if these patients report neurological symptoms, clinicians should consider that these symptoms may be accompanied by inflammatory demyelination of the brain.
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Gannan navel orange is a famous brand in China but the isolation of its endophytic fungi was rarely reported. In this study, a total of 54 strains of endophytic fungi were successfully isolated from the pulp, peel, twig, and leaf of Gannan navel orange; they were successfully identified to belong to 17 species of 12 genera. All these strains were fermented using potato-dextrose agar (PDA) medium, and their secondary metabolites were then extracted with ethyl acetate (EtOAc). The antibacterial assays of Escherichia coli (E. coli), methicillin-resistant Staphylococcus aureus (MRSA), and Xanthomonas citri subsp. citri (Xcc) were also performed for the EtOAc extracts of these strains. As a result, the extracts of both Geotrichum sp. (gc-1-127-30) and Diaporthe biconispora (gc-1-128-79) demonstrated significant antibacterial activities against Xcc, and the MIC value for the extract of Colletotrichum gloeosporioides against MRSA was low to 62.5 µg/mL. Moreover, the chemical components of the extracts of Colletotrichum sp., Diaporthe biconispora, and Annulohypoxylon atroroseum were primarily investigated, and they successfully led to the isolation of 24 compounds involving a new botryane sesquiterpene. Among the isolated products, compound 2 showed significant inhibitory activities toward SA, MRSA, E. coli, and Xcc with MIC values of 12.5, 3.1, 125, and 12.5 µg/mL, respectively. This study revealed that the endophytic fungi of Gannan navel orange showed high potency to produce secondary metabolites with significant antibacterial effects.
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A convenient one-pot assembly of 4-(imidazol-1-yl)indole derivatives from easily accessible o-alkynylanilines and imidazoles has been developed. The sequential dearomatization and Ag(I)-catalyzed cyclization/Cs2CO3-mediated conjugate addition/aromatization cascade reactions exhibit high efficiency and excellent selectivity. The combined use of a silver(I) salt and cesium carbonate is significant for facilitating this domino transformation. The 4-(imidazol-1-yl)indole products could be easily converted to the corresponding derivatives and might be valuable in biological chemistry and medicinal science.
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Citrus canker disease caused by Xanthomonas citri subsp. citri (Xac) severely influences the quality and quantity of citrus fruits. The current management of this disease mainly relies on the application of copper-associated chemicals, which poses a threat to human health and the environment. The present study isolated an endophytic fungus HT-79 from the healthy navel orange tree, whose crude fermentation product significantly inhibited the growth of Xac. The strain HT-79 was identified as a species of the Diaporthe genus. The petroleum ether extract (PEE) of the crude fermentation product of HT-79 exhibited remarkable activity against Xac with a MIC (minimum inhibitory concentration) value of 0.0625 mg/mL, significantly better than the positive control CuSO4 (MIC = 0.125 mg/mL). Bioassay-guided isolation of PEE resulted in the discovery of one highly potent anti-Xac subfraction, namely fraction 5 (MIC = 0.0156 mg/mL). Gas chromatography-mass spectrometry (GC-MS) analysis revealed that fraction 5 mainly consisted of palmitic acid (18.17%), ethyl palmitate (15.66%), linoleic acid (6.80%), oleic acid (18.32%), ethyl linoleate (21.58%), ethyl oleate (15.87%), and ethyl stearate (3.60%). Among these seven compounds, linoleic acid (MIC = 0.0078 mg/mL) was found to be the most potent against Xac, followed by oleic acid (MIC = 0.0156 mg/mL), while all others were less pronounced than CuSO4. Linoleic acid highly inhibited the growth of Xac via the destruction of the cell membrane and overproduction of reactive oxygen species (ROS). A preliminary in vivo experiment revealed that linoleic acid was effective in the control of citrus canker disease.
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Citrus , Xanthomonas , Humanos , Especies Reactivas de Oxígeno/metabolismo , Ácido Linoleico/farmacología , Ácido Linoleico/metabolismo , Ácido Oléico/metabolismo , Ácido Oléico/farmacología , Membrana Celular , Hongos , Enfermedades de las Plantas/prevención & control , Enfermedades de las Plantas/microbiología , Citrus/microbiologíaRESUMEN
Neuronal damage after ischemic stroke (IS) is frequently due to ferroptosis, contributing significantly to ischemic injury. However, the mechanism against ferroptosis in IS remained unclear. The aim of this study was to investigate the potential mechanism of Danhong injection (DHI) and the critical transcription factor SATB1 in preventing neuronal ferroptosis after ischemic stroke in vivo and in vitro. The results showed that DHI treatment significantly reduced the infarct area and associated damage in the brains of the pMCAO mice, and enhanced the viability of OGD-injured neurons. And several characteristic indicators of ferroptosis, such as mitochondrial necrosis and iron accumulation, were regulated by DHI after IS. Importantly, we found that the expression and activity of SATB1 were decreased in the pMCAO mice, especially in neuron cells. Meanwhile, the SATB1/SLC7A11/HO-1 signaling pathway was activated after DHI treatment in ischemic stroke and was found to improve neuronal ferroptosis. Inhibition of SATB1 significantly reduced SLC7A11-HO-1 and significantly attenuated the anti-ferroptosis effects of DHI in the OGD model. These findings indicate that neuronal ferroptosis after IS can be alleviated by DHI through SATB1/SLC7A11/HO-1 pathway, and SATB1 may be an attractive therapeutic target for treating ischemic stroke.
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Medicamentos Herbarios Chinos , Ferroptosis , Accidente Cerebrovascular Isquémico , Neuronas , Animales , Ratones , Accidente Cerebrovascular Isquémico/tratamiento farmacológico , Accidente Cerebrovascular Isquémico/metabolismo , Proteínas de Unión a la Región de Fijación a la Matriz/metabolismo , Neuronas/efectos de los fármacos , Neuronas/metabolismo , Factores de Transcripción/metabolismo , Medicamentos Herbarios Chinos/farmacología , Sistema de Transporte de Aminoácidos y+/metabolismo , Hemo-Oxigenasa 1/metabolismoRESUMEN
Background: The maintenance of marginal bone levels around dental implants is an important criterion for evaluating the success of implants. Although computer-aided design/computer-aided manufacturing (CAD/CAM) customized abutments (CAs) provide more flexible solutions, compared with the original preformed stock abutments (PAs), there are dimensional tolerances and underlying drawbacks in the production of CAD/CAM CAs, which may change the tightness and seamless connection between fixtures and abutments set by the manufacturer and then affect the long-term stability of the abutments. This study aimed to examine the change in both mesial and distal bone levels using digital periapical radiographs to evaluate the difference between CAD/CAM CAs and original PAs.Material and methods: Radiographs were taken before delivery; after functional loading for 1 month; and after 3, 6, and 12 months; and the vertical marginal bone levels (vMBLs) of both the mesial and distal surrounding implant bones were measured. All data are presented as means ± standard errors and were analyzed using Student's t-test. A p-value < 0.05 was judged to represent a significant difference. Results: A total of 57 implants in 50 patients were divided into 22 CAD/CAM CAs and 35 original stock abutments. The PAs appeared to have a more stable bone level. By contrast, the amount of bone level change in the CAs was higher than that in the PAs. The change in the vMBL of the CAs was significantly more than that of the PAs after functional loading for 1 month (p = 0.006), 3 months (p = 0.013), 6 months (p = 0.014), and 12 months (p = 0.002). In contrast, the distal marginal bone level was lower than the mesial marginal bone level in any period. Nevertheless, the bone levels of the CAs and PAs in any period were comparable with no significant difference. Conclusions: Significant differences were found between the mesial and distal bone levels in the PAs. The CAD/CAM CAs showed a significantly greater bone level change than the original stock abutments after functional loading.
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Ischemic/reperfusion (IR) can cause adverse reactions including apoptosis, oxidative stress, and inflammation, but the existing therapeutic strategies have been limited. Moreover, the regulation of microglia plays an important role in brain injury after reperfusion. Hence, it is imperative to find new and effective drugs for modulating microglia to treat IR brain injury. Cyclic peptide compound cyclo-(Phe-Tyr) (Sparganin C, SC) is a compound isolated from Sparganii Rhizoma. However, the protective effects of SC on the central nervous system are rather unclear. In an attempt to elucidate the protective effects and mechanism of SC on cerebral damage induced by the IR, we used a middle cerebral artery occlusion reperfusion (MCAO/R) model in rats and discovered that SC significantly decreased the size of cerebral infarcts, improved neurological scores, and blocked inflammatory and oxidative factor release. Using RNA-Seq and metabolomics association analyses, SC was shown to have a protective impact through the JUNB and SOX5-related pathways. Metabolomic analysis revealed twenty-eight differentially expressed biomarkers. In addition, the detection of SC content in brain tissue using LC/MS revealed that SC had blood-brain barrier penetration. To investigate the mechanism, we established an in vitro BV2 cell oxygen-glucose deprivation/reperfusion (OGD/R) model and used siRNA as well as an inhibitor. The protective effects of SC were dependent on the JUNB and SOX5 to inhibit inflammation and apoptosis in microglia. Our findings revealed for the first that SC against IR injury by reducing inflammation and apoptosis while simultaneously acting as potential therapeutic lead compound for ischemic stroke.