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1.
J Multidiscip Healthc ; 17: 2185-2202, 2024.
Artigo em Inglês | MEDLINE | ID: mdl-38736541

RESUMO

Purpose: To recommend the classification of unilateral genital tract obstruction with ipsilateral renal anomaly (UGTOIRA) syndrome into five types based on the site of obstruction, and to analyze the clinical manifestations and precise diagnosis of the syndrome. Methods: The data, including demographic characteristics, symptoms, and precise diagnoses from 59 patients over the last decade, were retrospectively analyzed. Data analysis was conducted using the statistical software package SPSS 26.0. Results: All 59 patients diagnosed with UGTOIRA syndrome were classified into five types based on the site of obstruction: Type I (vaginal obstruction) (45, 76.3%), Type II (cervicovaginal obstruction) (7, 11.9%), Type III (cervical obstruction) (3, 5.1%), Type IV (unilateral partial cervical aplasia) (3, 5.1%), and Type V (Unilateral isthmus atresia) (1, 1.7%). Of these cases, there were 34 cases (57.6%) with communication and 25 cases (42.4%) without communication between the left and right genital tracts. The chief complaints included dysmenorrhea alone in 28 cases (47.5%), dysmenorrhea accompanied by blood dripping after menstruation in 12 cases (20.3%), blood dripping after menstruation alone in 14 cases (23.7%), purulent vaginal secretions in one case (1.7%), vaginal pain in one case (1.7%), irregular menstruation in one case (l.7%), and infertility in two cases (3.4%). The precise diagnostic criteria include the affected side, abnormalities in the kidney and ureter, the site of obstruction, the location of blood accumulation, the size of the ipsilateral genital tract, whether there is communication and its site, the type based on the site of obstruction, and the presence and type of complications. Conclusion: This classification of UGTOIRA syndrome encompasses the anatomical features of all cases reported in our study. Only by fully understanding the anatomical characteristics of this syndrome and identifying its clinical manifestations can clinicians make precise diagnoses as early as possible and provide individualized management.

2.
Nutrients ; 16(9)2024 Apr 25.
Artigo em Inglês | MEDLINE | ID: mdl-38732527

RESUMO

Ulcerative colitis (UC) is characterized by chronic inflammation and ulceration of the intestinal inner lining, resulting in various symptoms. Sea buckthorn berries contain a bioactive compound known as sea buckthorn polysaccharide (SBP). However, the precise mechanisms underlying the impact of SBP on UC remain unclear. In this study, we investigated the effects of pretreatment with SBP on colitis induced by DSS. Our findings demonstrate that SBP pretreatment effectively reduces inflammation, oxidative stress, and intestinal barrier damage associated with colitis. To further elucidate the role of SBP-modulated gut microbiota in UC, we performed fecal microbiota transplantation (FMT) on DSS-treated mice. The microbiota from SBP-treated mice exhibits notable anti-inflammatory and antioxidant effects, improves colonic barrier integrity, and increases the abundance of beneficial bacteria, as well as enhancing SCFA production. Collectively, these results strongly indicate that SBP-mediated amelioration of colitis is attributed to its impact on the gut microbiota, particularly through the promotion of SCFA-producing bacteria and subsequent elevation of SCFA levels. This study provides compelling evidence supporting the efficacy of pre-emptive SBP supplementation in alleviating colitis symptoms by modulating the gut microbiota, thereby offering novel insights into the potential of SBP as a regulator of the gut microbiota for colitis relief.


Assuntos
Microbioma Gastrointestinal , Hippophae , Polissacarídeos , Animais , Hippophae/química , Polissacarídeos/farmacologia , Microbioma Gastrointestinal/efeitos dos fármacos , Camundongos , Colite/tratamento farmacológico , Colite/induzido quimicamente , Colite/microbiologia , Colite Ulcerativa/microbiologia , Colite Ulcerativa/tratamento farmacológico , Modelos Animais de Doenças , Masculino , Camundongos Endogâmicos C57BL , Estresse Oxidativo/efeitos dos fármacos , Transplante de Microbiota Fecal , Colo/efeitos dos fármacos , Colo/microbiologia , Colo/metabolismo , Sulfato de Dextrana , Anti-Inflamatórios/farmacologia , Antioxidantes/farmacologia , Frutas/química , Ácidos Graxos Voláteis/metabolismo
3.
Mol Neurobiol ; 2024 May 10.
Artigo em Inglês | MEDLINE | ID: mdl-38727976

RESUMO

A reduction in AMPA receptor (AMPAR) expression and weakened synaptic activity is early cellular phenotypes in Alzheimer's disease (AD). However, the molecular processes leading to AMPAR downregulation are complex and remain less clear. Here, we report that the salt inducible kinase SIK1 interacts with AMPARs, leading to a reduced accumulation of AMPARs at synapses. SIK1 protein level is sensitive to amyloid beta (Aß) and shows a marked increase in the presence of Aß and in AD brains. In neurons, Aß incubation causes redistribution of SIK1 to synaptic sites and enhances SIK1-GluA1 association. SIK1 function is required for Aß-induced AMPAR reduction. Importantly, in 3xTG AD mice, knockdown of SIK1 in the brain leads to restoration of AMPAR expression and a rescue of the cognitive deficits. These findings indicate an important role for SIK1 in meditating the cellular and functional pathology in AD.

5.
Int Immunopharmacol ; 133: 112170, 2024 May 30.
Artigo em Inglês | MEDLINE | ID: mdl-38691919

RESUMO

Acute kidney injury (AKI) is characterized by a sudden decline in renal function. Traditional Chinese medicine has employed Fuzi for kidney diseases; however, concerns about neurotoxicity and cardiotoxicity have constrained its clinical use. This study explored mesaconine, derived from processed Fuzi, as a promising low-toxicity alternative for AKI treatment. In this study, we assessed the protective effects of mesaconine in gentamicin (GM)-induced NRK-52E cells and AKI rat models in vitro and in vivo, respectively. Mesaconine promotes the proliferation of damaged NRK-52E cells and down-regulates intracellular transforming growth factor ß1 (TGF-ß1) and kidney injury molecule 1 (KIM-1) to promote renal cell repair. Concurrently, mesaconine restored mitochondrial morphology and permeability transition pores, reversed the decrease in mitochondrial membrane potential, mitigated mitochondrial dysfunction, decreased ATP production, inhibited inflammatory factor release, and reduced early apoptosis rates. In vivo, GM-induced AKI rat models exhibited elevated AKI biomarkers, in which mesaconine was effectively reduced, indicating improved renal function. Mesaconine enhanced superoxide dismutase activity, reduced malondialdehyde content, alleviated inflammatory infiltrate, mitigated tubular and glomerular lesions, and downregulated NF-κB (nuclear factor-κb) p65 expression, leading to decreased tumor necrosis factor-α (TNF-α) and IL-1ß (interleukin-1ß) levels in GM-induced AKI animals. Furthermore, mesaconine inhibited the expression of renal pro-apoptotic proteins (Bax, cytochrome c, cleaved-caspase 9, and cleaved-caspase 3) and induced the release of the anti-apoptotic protein bcl-2, further suppressing apoptosis. This study highlighted the therapeutic potential of mesaconine in GM-induced AKI. Its multifaceted mechanisms, including the restoration of mitochondrial dysfunction, anti-inflammatory and antioxidant effects, and apoptosis mitigation, make mesaconine a promising candidate for further exploration in AKI management.


Assuntos
Aconitum , Injúria Renal Aguda , Apoptose , Rim , Mitocôndrias , Ratos Sprague-Dawley , Animais , Injúria Renal Aguda/tratamento farmacológico , Injúria Renal Aguda/induzido quimicamente , Injúria Renal Aguda/patologia , Apoptose/efeitos dos fármacos , Aconitum/química , Mitocôndrias/efeitos dos fármacos , Mitocôndrias/metabolismo , Masculino , Ratos , Linhagem Celular , Rim/efeitos dos fármacos , Rim/patologia , Gentamicinas/toxicidade , Medicamentos de Ervas Chinesas/uso terapêutico , Medicamentos de Ervas Chinesas/farmacologia , Aconitina/análogos & derivados , Aconitina/farmacologia , Aconitina/uso terapêutico , Modelos Animais de Doenças , Potencial da Membrana Mitocondrial/efeitos dos fármacos , Humanos , Anti-Inflamatórios/farmacologia , Anti-Inflamatórios/uso terapêutico , Diterpenos
6.
FEBS J ; 2024 May 06.
Artigo em Inglês | MEDLINE | ID: mdl-38708519

RESUMO

HER2-enriched (HER2+) breast cancers express high levels of the growth-promoting HER2 protein. Although these cancers are treated with the HER2-targeted drug, trastuzumab, resistance to treatment is common. Retinoic acid (RA) is an anti-cancer agent that has been successfully used for the treatment of leukemia and holds promise for the treatment of solid cancers, including breast cancer. The HER2 gene is frequently co-amplified with RARA, a key determinant of RA sensitivity in breast cancers. It seems surprising, therefore, that HER2+ breast cancers are refractory to RA treatment. Here, we show that MYC mediates RA resistance by suppressing the expression of cellular retinoic acid binding protein 2 (CRABP2), resulting in RARα inactivation. CRABP2 is an intracellular RA transporter that delivers RA to the nuclear receptor RARα for its activation. Our results indicate that response to RA is enhanced by MYC depletion in HER2+ breast cancer cells and that RA treatment enhances trastuzumab responsiveness. Our findings support the use of RA and trastuzumab for the treatment of subsets of patients with breast cancers that are HER2-RARα co-amplified and have low levels of MYC.

7.
Anal Chem ; 2024 May 02.
Artigo em Inglês | MEDLINE | ID: mdl-38698557

RESUMO

A fully automated online enrichment and separation system for intact glycopeptides, named AutoGP, was developed in this study by integrating three different columns in a nano-LC system. Specifically, the peptide mixture from the enzymatic digestion of a complex biological sample was first loaded on a hydrophilic interaction chromatography (HILIC) column. The nonglycopeptides in the sample were washed off the column, and the glycopeptides retained by the HILIC column were eluted to a C18 trap column to achieve an automated glycopeptide enrichment. The enriched glycopeptides were further eluted to a C18 column for separation, and the separated glycopeptides were eventually analyzed by using an orbitrap mass spectrometer (MS). The optimal operating conditions for AutoGP were systemically studied, and the performance of the fully optimized AutoGP was compared with a conventional manual system used for glycopeptide analysis. The experimental evaluation shows that the total number of glycopeptides identified is at least 1.5-fold higher, and the median coefficient of variation for the analyses is at least 50% lower by using AutoGP, as compared to the results acquired by using the manual system. In addition, AutoGP can perform effective analysis even with a 1-µg sample amount, while a 10-µg sample at least will be needed by the manual system, implying an order of magnitude better sensitivity of AutoGP. All the experimental results have consistently proven that AutoGP can be used for much better characterization of intact glycopeptides.

9.
Ecol Evol ; 14(5): e11305, 2024 May.
Artigo em Inglês | MEDLINE | ID: mdl-38711487

RESUMO

Intraspecific variation in plant functional traits and ecological strategies is typically overlooked in most studies despite its pivotal role at the local scales and along short environmental gradients. While CSR theory has been used to classify ecological strategies (competitive C; stress-tolerant, S; ruderal, R) in different plant species, its ability to explain intraspecific variation in ecological strategies remains uncertain. Here, we sought to investigate intraspecific variation in ecological strategies for Pinus massoniana, a pioneer conifer tree for ecological restoration in Changting County, southeast China. By measuring key leaf traits and canopy height of 252 individuals at different ontogenetic stages from three plots spanning distinctive stages along early ecological restoration and calculating their C, S, and R scores, we constructed an intraspecific CSR system. All individual strategies shifted across three restoration stages, with adults from higher S component to higher C component while juveniles from higher S component to higher R component. Our results suggest that while strategies of all P. massoniana individuals start with tolerance to environmental stress, as restoration proceeds, adult transition towards completion for light, whereas juveniles shift to an acquisitive resource use. The study reveals an intraspecific pattern of strategy variation during forest restoration, contributing to our understanding of how plants adapt to diverse environments.

10.
Am J Transl Res ; 16(4): 1145-1154, 2024.
Artigo em Inglês | MEDLINE | ID: mdl-38715814

RESUMO

OBJECTIVE: To verify the results of three-dimensional fracture mapping of T12-L2 compression fractures by the finite element method from a biomechanical point of view, and to provide clinical reference. METHODS: This study is a retrospective study. By collecting 150 patients' computerized tomography (CT) data with thoracolumbar compression fractures (T12-L2) with AO type A. Mimics was used for three-dimensional (3D) reconstruction, and 3-Matic was used to mark fracture lines in stereo images. After standardized treatment, all fracture lines were drawn in the same 3D image, and finally fracture lines and fracture map were drawn. Constructing a 3D finite element model of thoracolumbar segment to verify the fracture thermogram results from the perspective of biomechanics. RESULTS: From the fracture map, fracture lines were mainly distributed in the upper part of the vertebral body, the leading edge of the anterior column (AC), and the lateral margin of the middle column (MC). In the finite element analysis, the stress mainly was concentrated on the edge of the anterior and middle column of the vertebral body and the upper part of the vertebral body, and the stress gradually decreased from the upper endplate to the endplate, and the stress was the least in the posterior column (PC) of the vertebral body. CONCLUSION: The results of finite element analysis further confirm the accuracy of fracture mapping and explain the distribution characteristics of fracture lines. This will provide theoretical support for the selection of clinical fracture treatment, intraoperative implants, and for a standard fracture model.

11.
Heliyon ; 10(9): e29597, 2024 May 15.
Artigo em Inglês | MEDLINE | ID: mdl-38707399

RESUMO

A diagnosis based on multiple nuclear medicine imaging (NMI) was more comprehensive in approaching the nature of pathological changes. In this research, a method to realize triple NMIs within one day was developed based on the reasonable arrangements of 68Ga-RGD PET/CT specialized on neovascularization, 99mTc-HL-91 SPECT/CT specialized on hypoxia and 18F-FDG PET/CT specialized on tumor metabolism. Feasibility was verified in evaluating the therapeutic effects of transarterial embolization (TAE) performed on rabbit models with VX2 tumor. Radiation dosimetry was carried out to record the radiation exposure from multiple injections of radiopharmaceuticals. In results, the one-day examination of triple NMIs manifested the diversity of the postoperative histological changes, including the local neovascularization induced by embolization, hypoxic state of embolized tissues, and suppression of tumor metabolism. More importantly, radiation dosage from radiopharmaceuticals was limited below 5.70 ± 0.90 mSv. In conclusion, the strong timeliness and complementarity of one-day examination of triple nuclear medicine imaging made it clinically operative and worthy of popularizing. There was flexibility in combining distinct NMIs according to the clinical demands, so as to provide comprehensive information for diagnosis.

12.
Artigo em Inglês | MEDLINE | ID: mdl-38726483

RESUMO

In clinical practice, the choice of single vs. double screw fixation for posterior malleolus fractures (PMF) is theoretically unclear, particularly concerning the size-stability relationship. This study, employing Finite Element Analysis (FEA), assesses biomechanical stability in PMF of varying sizes under both fixation methods. Utilizing a 3D model based on CT scans, we simulated fractures with 10-50% fragment sizes and applied a 600 N force to mimic the single-leg stance. Our evaluation focused on screw Von Mises stress (VMS) and fracture relative displacement (RD). Results show that stability increases with fragment size for both fixation types. Single screw fixation is comparable to double screw in fragments up to 25%, but in larger fragments, double screw significantly enhances stability. This suggests that for fragments over 25%, double screw fixation is preferable, marking a critical threshold for PMF stability.

13.
Heliyon ; 10(7): e28693, 2024 Apr 15.
Artigo em Inglês | MEDLINE | ID: mdl-38571642

RESUMO

Background: Hepatic fibrosis is caused by various liver diseases and eventually develops into liver cancer. There is no specific drug approved for the treatment of hepatic fibrosis in the world. Acacetin (AC), a natural flavonoid, is widely present in nature in various plants, such as black locust, Damiana, Silver birch. It has been reported that acacetin can inhibit the proliferation of cancer cells and induce apoptosis. Purpose: In this study, we investigated the effect of acacetin on hepatic stellate cell apoptosis, thereby improving hepatic fibrosis, and combined experimental validation and molecular docking to reveal the underlying mechanism. Result: First, we discovered that acacetin inhibited hepatic stellate cell proliferation as well as the expression of fibrosis-related proteins α-smooth muscle actin (α-SMA) and collagen type I 1 gene (COL1A1) in LX2 cells. Acacetin was then found to promote apoptosis of hepatic stellate cells through the caspase cascade pathway. Network pharmacology screening showed that TP53, CASP3, CASP8, BCL2, PARP1, and BAX were the most important targets related to apoptosis in the PPI network. GO and KEGG analyses of these six important targets were performed, and the top 10 enriched biological processes and related signaling pathways were revealed. Further network pharmacology analysis proved that apoptosis was involved in the biological process of acacetin's action against hepatic stellate cells. Finally, molecular docking revealed that acacetin binds to the active sites of six apoptotic targets. In vitro experiments further confirmed that acacetin could promote the apoptosis of LX2 cells by inducing the activation of P53, thereby improving hepatic fibrosis. Conclusion: acacetin induces P53 activation and promotes apoptosis of hepatic stellate cells thereby ameliorating hepatic fibrosis.

14.
Heliyon ; 10(7): e28582, 2024 Apr 15.
Artigo em Inglês | MEDLINE | ID: mdl-38586416

RESUMO

The combination of Chaidangbo (CDB) is an antidepressant traditional Chinese medicine (TCM) prescription simplified by Xiaoyaosan (a classic antidepressant TCM prescription) through dismantling research, which has the effect of dispersing stagnated liver qi and nourishing blood in TCM theory. Although the antidepressant effect of CBD has been confirmed in animal studies, the material basis and possible molecular mechanism for antidepressant activity in CBD have not been clearly elucidated. Herein, we investigated the effects and potential mechanisms of CDB antidepressant fraction (petroleum ether fraction of CDB, PEFC) on chronic unpredictable mild stress (CUMS)-induced depression-like behavior in mice using network pharmacology and metabolomics. First, a UPLC-QE/MS was employed to identify the components of PEFC. To extract active ingredients, SwissADME screening was used to the real PEFC components that were found. Potential PEFC antidepressant targets were predicted based on a network pharmacology approach, and a pathway enrichment analysis was performed for the predicted targets. Afterward, a CUMS mouse depression model was established and LC-MS-based untargeted hippocampal metabolomics was performed to identify differential metabolites, and related metabolic pathways. Finally, the protein expressions in mouse hippocampi were determined by Western blot to validate the network pharmacology and metabolomics deduction. A total of 16 active compounds were screened in SwissADME that acted on 73 core targets of depression, including STAT3, MAPKs, and NR3C1; KEGG enrichment analysis showed that PEFC modulated signaling pathways such as PI3K-Akt signaling pathway, endocrine resistance, and MAPK to exert antidepressant effects. PEFC significantly reversed abnormalities of hippocampus metabolites in CUMS mice, mainly affecting the synthesis and metabolism of glycine, serine, and threonine, impacting catecholamine transfer and cholinergic synapses and regulating the activity of the mTOR signaling pathway. Furthermore, Western blot analysis confirmed that PEFC significantly influenced the main protein levels of the PI3K/Akt/mTOR signaling pathways in the hippocampus of mice subjected to CUMS. This study integrated metabolomics, network pharmacology and biological verification to explore the potential mechanism of PEFC in treating depression, which is related to the regulation of amino acid metabolism dysfunction and the activation of PI3K/Akt/mTOR signaling pathways in the hippocampus. The comprehensive strategy also provided a reasonable way for unveiling the pharmacodynamic mechanisms of multi-components, multi-targets, and multi-pathways in TCM with antidepressant effect.

15.
Clin Rehabil ; : 2692155241239881, 2024 Apr 17.
Artigo em Inglês | MEDLINE | ID: mdl-38629433

RESUMO

OBJECTIVE: Assessing rehabilitation effectiveness for persistent symptoms post-infection with emerging viral respiratory diseases. DATA SOURCES: Systematic review of seven databases (MEDLINE, EMBASE, Cochrane Library, PEDro, MedRxiv, CNKI, Wanfang) until 30 December 2023. REVIEW METHODS: Evaluated 101 studies (9593 participants) on respiratory function, exercise capacity, and quality of life. Methodological quality was assessed using the Cochrane Collaboration's Risk of Bias tool for randomized controlled trials (RCTs), the Newcastle-Ottawa Scale (NOS) for observational studies and non-RCTs, and the NIH Quality Assessment Tools for before-after studies. RESULTS: The most common rehabilitation program combined breathing exercises with aerobic exercise or strength training. Rehabilitation interventions significantly enhanced respiratory function, as evidenced by improvements on the Borg Scale (MD, -1.85; 95% CI, -3.00 to -0.70, low certainty), the mMRC Dyspnea Scale (MD, -0.45; 95% CI, -0.72 to -0.18, low certainty), and the Multidimensional Dyspnoea-12 Scale (MD, -4.64; 95% CI, -6.54 to -2.74, moderate certainty). Exercise capacity also improved, demonstrated by results from the Six-Minute Walk Test (MD, 38.18; 95% CI, 25.33-51.03, moderate certainty) and the Sit-to-Stand Test (MD, 3.04; 95% CI, 1.07-5.01, low certainty). CONCLUSION: Rehabilitation interventions are promising for survivors of viral respiratory diseases, yet gaps in research remain. Future investigations should focus on personalizing rehabilitation efforts, utilizing remote technology-assisted programs, improving research quality, and identifying specific subgroups for customized rehabilitation strategies to achieve the best outcomes for survivors.

16.
MedComm (2020) ; 5(4): e540, 2024 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-38606360

RESUMO

Senile plaque, composed of amyloid ß protein (Aß) aggregates, is a critical pathological feature in Alzheimer's disease (AD), leading to cognitive dysfunction. However, how Aß aggregates exert age-dependent toxicity and temporal cognitive dysfunction in APP/PS1 mice remains incompletely understood. In this study, we investigated AD pathogenesis and dynamic alterations in lysosomal pathways within the hippocampus of age-gradient male mice using transcriptome sequencing, molecular biology assays, and histopathological analyses. We observed high levels of ß-amyloid precursor protein (APP) protein expression in the hippocampus at an early stage and age-dependent Aß deposition. Transcriptome sequencing revealed the enrichment of differential genes related to the lysosome pathway. Furthermore, the protein expression of ATP6V0d2 and CTSD associated with lysosomal functions exhibited dynamic changes with age, increasing in the early stage and decreasing later. Similar age-dependent patterns were observed for the endosome function, autophagy pathway, and SGK1/FOXO3a pathway. Nissl and Golgi staining in the hippocampal region showed age-dependent neuronal loss and synaptic damage, respectively. These findings clearly define the age-gradient changes in the autophagy-lysosome system, the endosome/lysosome system, and the SGK1/FOXO3a pathway in the hippocampus of APP/PS1 mice, providing new perspectives and clues for understanding the possible mechanisms of AD, especially the transition from compensatory to decompensated state.

17.
Foods ; 13(7)2024 Mar 22.
Artigo em Inglês | MEDLINE | ID: mdl-38611279

RESUMO

The detection of the storage state of frozen meat, especially meat frozen-thawed several times, has always been important for food safety inspections. Hyperspectral imaging (HSI) is widely applied to detect the freshness and quality of meat or meat products. This study investigated the feasibility of the low-cost HSI system, combined with the chemometrics method, to classify beef cuts among fresh (F), frozen-stored (F-S), frozen-thawed three times (F-T-3) and frozen-thawed five times (F-T-5). A compact, low-cost HSI system was designed and calibrated for beef sample measurement. The classification model was developed for meat analysis with a method to distinguish fat and muscle, a CARS algorithm to extract the optimal wavelength subset and three classifiers to identify each beef cut among different freezing processes. The results demonstrated that classification models based on feature variables extracted from differentiated tissue spectra achieved better performances, with ACCs of 92.75% for PLS-DA, 97.83% for SVM and 95.03% for BP-ANN. A visualization map was proposed to provide detailed information about the changes in freshness of beef cuts after freeze-thawing. Furthermore, this study demonstrated the potential of implementing a reasonably priced HSI system in the food industry.

18.
Lett Appl Microbiol ; 77(4)2024 Apr 08.
Artigo em Inglês | MEDLINE | ID: mdl-38573829

RESUMO

Bacterial wilt is a widespread and devastating disease that impacts the production of numerous crucial crops worldwide. The main causative agent of the disease is Ralstonia solanacearum. Due to the pathogen's broad host range and prolonged survival in the soil, it is challenging to control the disease with conventional strategies. Therefore, it is of great importance to develop effective alternative disease control strategies. In recent years, phage therapy has emerged as an environmentally friendly and sustainable biocontrol alternative, demonstrating significant potential in controlling this severe disease. This paper summarized basic information about isolated phages that infect R. solanacearum, and presented some examples of their application in the biocontrol of bacterial wilt. The risks of phage application and future prospect in this area were also discussed. Overall, R. solanacearum phages have been isolated from various regions and environments worldwide. These phages belong mainly to the Inoviridae, Autographiviridae, Peduoviridae, and Cystoviridae families, with some being unclassified. Studies on the application of these phages have demonstrated their ability to reduce pathogenicity of R. solanacearum through direct lysis or indirect alteration of the pathogen's physiological properties. These findings suggested bacteriophage is a promising tool for biocontrol of bacterial wilt in plants.

19.
Discov Med ; 36(183): 753-764, 2024 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-38665024

RESUMO

BACKGROUND: Dental fluorosis is a discoloration of the teeth caused by the excessive consumption of fluoride. It represents a distinct manifestation of chronic fluorosis in dental tissues, exerting adverse effects on the human body, particularly on teeth. The transmembrane protein 16a (TMEM16A) is expressed at the junction of the endoplasmic reticulum and the plasma membrane. Alterations in its channel activity can disrupt endoplasmic reticulum calcium homeostasis and intracellular calcium ion concentration, thereby inducing endoplasmic reticulum stress (ERS). This study aims to investigate the influence of calcium supplements and TMEM16A on ERS in dental fluorosis. METHODS: C57BL/6 mice exhibiting dental fluorosis were subjected to an eight-week treatment with varying calcium concentrations: low (0.071%), medium (0.79%), and high (6.61%). Various assays, including Hematoxylin and Eosin (HE) staining, immunohistochemistry, real-time fluorescence quantitative polymerase chain reaction (qPCR), and Western blot, were employed to assess the impact of calcium supplements on fluoride content, ameloblast morphology, TMEM16A expression, and endoplasmic reticulum stress-related proteins (calreticulin (CRT), glucose-regulated protein 78 (GRP78), inositol requiring kinase 1α (IRE1α), PKR-like ER kinase (PERK), activating transcription factor 6 (ATF6)) in the incisors of mice affected by dental fluorosis. Furthermore, mice with dental fluorosis were treated with the TMEM16A inhibitor T16Ainh-A01 along with a medium-dose calcium to investigate the influence of TMEM16A on fluoride content, ameloblast morphology, and endoplasmic reticulum stress-related proteins in the context of mouse incisor fluorosis. RESULTS: In comparison to the model mice, the fluoride content in incisors significantly decreased following calcium supplements (p < 0.01). Moreover, the expression of TMEM16A, CRT, GRP78, IRE1α, PERK, and ATF6 were also exhibited a substantial reduction (p < 0.01), with the most pronounced effect observed in the medium-dose calcium group. Additionally, the fluoride content (p < 0.05) and the expression of CRT, GRP78, IRE1α, PERK, and ATF6 (p < 0.01) were further diminished following concurrent treatment with the TMEM16A inhibitor T16Ainh-A01 and a medium dose of calcium. CONCLUSIONS: The supplementation of calcium or the inhibition of TMEM16A expression appears to mitigate the detrimental effects of fluorosis by suppressing endoplasmic reticulum stress. These findings hold implications for identifying potential therapeutic targets in addressing dental fluorosis.


Assuntos
Cálcio , Suplementos Nutricionais , Fluorose Dentária , Animais , Masculino , Camundongos , Fator 6 Ativador da Transcrição/metabolismo , Adenina/análogos & derivados , Ameloblastos/metabolismo , Ameloblastos/patologia , Ameloblastos/efeitos dos fármacos , Anoctamina-1/metabolismo , Anoctamina-1/antagonistas & inibidores , Anoctamina-1/genética , Cálcio/metabolismo , Modelos Animais de Doenças , eIF-2 Quinase/metabolismo , eIF-2 Quinase/genética , Chaperona BiP do Retículo Endoplasmático , Estresse do Retículo Endoplasmático/efeitos dos fármacos , Endorribonucleases/metabolismo , Fluoretos/toxicidade , Fluoretos/efeitos adversos , Fluorose Dentária/patologia , Fluorose Dentária/metabolismo , Fluorose Dentária/etiologia , Indóis , Camundongos Endogâmicos C57BL , Proteínas Serina-Treonina Quinases/metabolismo , Proteínas Serina-Treonina Quinases/genética , Proteínas Serina-Treonina Quinases/antagonistas & inibidores
20.
Ann Hematol ; 103(6): 2103-2111, 2024 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-38656370

RESUMO

OBJECTIVE: This study aimed to investigate the prognosis of unrelated umbilical cord blood transplantation (UCBT) using low-dose anti-thymocyte globulin (ATG) in children diagnosed with severe aplastic anemia (SAA). METHODS: This retrospective case series study was conducted involving pediatric SAA patients treated at the Capital Institute of Pediatrics from January 2020 to February 2023. All patients underwent a reduced-intensity conditioning (RIC) regimen alongside low-dose ATG. RESULTS: The study comprised nine patients (five males) with a median age of 5 years (range: 1.7 to 7 years). The median follow-up duration was 799 days (range: 367 to 1481 days), during which all patients survived. The median time interval from diagnosis to transplantation was 3 months (range: 1 to 9 months). The median dosage of ATG administered was 5 mg/kg (range: 2.5 to 7.5 mg/kg). The median durations for granulocyte and platelet engraftment were 15 days (range: 12 to 23 days) and 26 days (range: 12 to 41 days), respectively. Three patients experienced grade 2-4 acute graft-versus-host disease (aGVHD). Epstein-Barr virus (EBV) reactivation was observed in three patients, while cytomegalovirus (CMV) reactivation occurred in seven patients, with no cases of CMV disease or post-transplant lymphoproliferative disorder (PTLD). One patient experienced recurrence 15 months after transplantation due to influenza A infection. CONCLUSION: These findings indicate that SAA patients may attain a favorable prognosis following UCBT with a RIC regimen combined with low-dose ATG.


Assuntos
Anemia Aplástica , Soro Antilinfocitário , Transplante de Células-Tronco de Sangue do Cordão Umbilical , Humanos , Anemia Aplástica/terapia , Soro Antilinfocitário/administração & dosagem , Soro Antilinfocitário/uso terapêutico , Masculino , Feminino , Pré-Escolar , Criança , Estudos Retrospectivos , Lactente , Doença Enxerto-Hospedeiro/etiologia , Condicionamento Pré-Transplante/métodos , Doadores não Relacionados
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