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1.
Front Public Health ; 12: 1365877, 2024.
Artículo en Inglés | MEDLINE | ID: mdl-38633240

RESUMEN

Health insurance stands as a pivotal facet of social wellbeing, with profound implications for the overarching landscape of economic development. The existing research, however, lacks consensus on the relationship between health insurance and economic performance and provides no evidence about the magnitude of the correlation. This lack of information seriously impedes the high-quality development of the healthcare system. Therefore, to scientifically elucidate the relationship between the two, this study involved a meta-analysis, analyzing 479 effect values derived from 34 independent research samples. The results reveal a strongly positive correlation between health insurance and economic performance [r = 0.429, 95% CI = (0.381, 0.475)]. Findings show that health insurance in developed countries more effectively fosters economic performance than in developing countries. Moreover, public health insurance exerts a stronger promoting effect on economic performance than commercial health insurance. The relationship between health insurance and economic performance is moderated by data type, research method, country of sample origin, literature type, journal impact factor, publication year, type of health insurance, and the research populations. Based on meta-analysis, this study not only scientifically responds to the controversy of the relationship between health insurance and economic performance, and the magnitude of a correlation, but also further reveals the inner conduction mechanism between the two. Our research findings are meaningful for policymakers to choose an appropriate healthcare strategy according to their unique attributes, propelling sustainable economic development.


Asunto(s)
Atención a la Salud , Seguro de Salud , Desarrollo Económico , Salud Pública , Proyectos de Investigación
3.
Expert Rev Gastroenterol Hepatol ; 18(1-3): 121-128, 2024.
Artículo en Inglés | MEDLINE | ID: mdl-38362663

RESUMEN

BACKGROUND: Liaoning score has been developed and validated to predict the risk of esophageal varices in liver cirrhosis. This study aimed to further modify the Liaoning score by combining clinical and laboratory parameters to predict the long-term outcome of cirrhotic patients. METHODS: First, 474 cirrhotic patients were retrospectively enrolled from Shenyang, China as the training cohort. Independent predictors for death were identified by competing risk analyses, and then a new prognostic model, called as modified Liaoning score, was developed. Its performance was externally validated at three centers from Fuzhou, China (n = 1944), Jinan, China (n = 485), and São Paulo, Brazil (n = 221). RESULTS: Age, total bilirubin (TBIL), albumin (ALB), serum creatinine (SCr), and Liaoning score were independently associated with death in the training cohort. Modified Liaoning score = 0.159×Liaoning score + 0.010×TBIL(µmol/L)+0.029×age(years)+0.011×SCr(µmol/L)-0.037×ALB(g/L). The area under curve of modified Liaoning score was 0.714 (95%CI = 0.655-0.773), which was higher than that of Child-Pugh score (0.707, 95%CI = 0.645-0.770), MELD score (0.687, 95%CI = 0.623-0.751), and Liaoning score (0.583, 95%CI = 0.513-0.654). A modified Liaoning score of ≥ 1.296 suggested a higher cumulative incidence of death in liver cirrhosis (p < 0.001). Modified Liaoning score still had the highest prognostic performance in Chinese and Brazilian validation cohorts. CONCLUSIONS: Modified Liaoning score can be considered for predicting the long-term outcome of cirrhotic patients.


Asunto(s)
Cirrosis Hepática , Humanos , Estudios Retrospectivos , Brasil , Cirrosis Hepática/complicaciones , Pronóstico , Índice de Severidad de la Enfermedad
4.
Adv Ther ; 41(3): 967-990, 2024 Mar.
Artículo en Inglés | MEDLINE | ID: mdl-38286960

RESUMEN

Liver diseases cause a significant burden on public health worldwide. In spite of great advances during recent years, there are still many challenges in the diagnosis and treatment of liver diseases. During recent years, artificial intelligence (AI) has been widely used for the diagnosis, risk stratification, and prognostic prediction of various diseases based on clinical datasets and medical images. Accumulative studies have shown its performance for diagnosing patients with nonalcoholic fatty liver disease and liver fibrosis and assessing their severity, and for predicting treatment response and recurrence of hepatocellular carcinoma, outcomes of liver transplantation recipients, and risk of drug-induced liver injury. Herein, we aim to comprehensively summarize the current evidence regarding diagnostic, prognostic, and/or therapeutic role of AI in these common liver diseases.


Asunto(s)
Carcinoma Hepatocelular , Neoplasias Hepáticas , Enfermedad del Hígado Graso no Alcohólico , Humanos , Inteligencia Artificial , Cirrosis Hepática/complicaciones , Cirrosis Hepática/diagnóstico , Enfermedad del Hígado Graso no Alcohólico/complicaciones , Enfermedad del Hígado Graso no Alcohólico/diagnóstico , Enfermedad del Hígado Graso no Alcohólico/terapia , Neoplasias Hepáticas/diagnóstico
5.
J Pain Res ; 16: 4337-4351, 2023.
Artículo en Inglés | MEDLINE | ID: mdl-38145036

RESUMEN

Purpose: Fibromyalgia (FM) is a syndrome characterized by chronic musculoskeletal pain. Its clinical symptoms include both somatic and psychiatric symptoms, making the treatment of FM extremely challenging. The cause of FM is still unknown, and some patients do not improve their symptoms even after long-term active treatment. Thus, the development of new targeted therapies is important to reduce pain and improve quality of life for FM patients. Methods: In this study, we screened genes and secreted factors that play key roles in FM through bioinformatics and big data analysis. Furthermore, we performed CCK-8, qRT-PCR, glucose, ATP and lactate content testing, dual luciferase reporter gene assay to investigate the potential mechanism of complement factor D in fibromyalgia development. Results: In bioinformatics and big data analysis, we identified CFD was negatively correlated with the pro-inflammatory factor IL-6 and positively correlated with the anti-inflammatory factor IL-4, which suggested that CFD may be an anti-inflammatory factor. Through cellular assays, we verified that CFD reversed the decrease in IL-4 expression and the increase in IL-6 expression in BV2 cells caused by ATP. Conclusion: In summary, based on bioinformatic methods and big data mining we obtained a new target CFD for FM, and further experiments verified that CFD has significant inhibition of ATP-induced neuropathic pain. These findings provide a new theoretical basis for the clinical translation of CFD.

6.
Healthcare (Basel) ; 11(22)2023 Nov 07.
Artículo en Inglés | MEDLINE | ID: mdl-37998407

RESUMEN

The growing research interest in the relationship between health insurance and pharmaceutical innovation is driven by their significant impact on healthcare optimization and pharmaceutical development. The existing literature, however, lacks consensus on this relationship and provides no evidence of the magnitude of a correlation. In this context, this study employs meta-analysis to explore the extent to which health insurance affects pharmaceutical innovation. It analyzes 202 observations from 14 independent research samples, using the regression coefficient of health insurance on pharmaceutical innovation as the effect size. The results reveal that there is a strong positive correlation between health insurance and pharmaceutical innovation (r = 0.367, 95% CI = [0.294, 0.436]). Public health insurance exhibits a stronger promoting effect on pharmaceutical innovation than commercial health insurance. The relationship between health insurance and pharmaceutical innovation is moderated by the country of sample origin, data range, journal type, journal impact factor, type of health insurance, and research perspective. Our research findings further elucidate the relationship mechanism between health insurance and pharmaceutical innovation, providing a valuable reference for future explorations in pharmaceutical fields.

8.
Aging Clin Exp Res ; 35(10): 2019-2028, 2023 Oct.
Artículo en Inglés | MEDLINE | ID: mdl-37454035

RESUMEN

BACKGROUND: In elderly patients with fractures, sarcopenia impairs recovery and even increases mortality. Both orthopedic and geriatric professionals are at the forefront of treating sarcopenic patients with fractures. However, it is not clear to what extent they have knowledge and skills to diagnose and treat sarcopenia. AIMS: This study aimed to analyze and compare knowledge, attitude, and practice regarding sarcopenia between orthopedic and geriatric professionals. METHODS: An online cross-sectional survey was conducted in June 2022 targeting professionals in orthopedic and geriatric departments in two largest tertiary general hospitals in Taizhou, southeastern China. Results on knowledge, attitude, and practice of sarcopenia were analyzed. Variables with significance were then included in a stepwise multiple linear regression analysis. RESULTS: A total of 220 professionals, 176 from orthopedic departments and 44 from geriatric departments, participated in this study. Orthopedic professionals scored lower than geriatrics in knowledge, attitude and practice (P < 0.001). The attitude score was high in both orthopedic and geriatric professionals. Stepwise multiple linear regression analysis showed that participants who had contact with sarcopenia patients had higher knowledge score (ß = 1.941, P < 0.001); participants who had attended sarcopenia training in the past 6 months (ß = 4.305, P < 0.001) had higher practice score. DISCUSSION: Orthopedic professionals have deficiencies in the screening and diagnosis of sarcopenia. Improving the knowledge and training of professionals can strengthen practice. It is necessary to formulate diagnostic criteria and improve practice of sarcopenia through training. CONCLUSION: Orthopedic professionals had limited knowledge and practice regarding sarcopenia compared with geriatric professionals. To improve sarcopenia practice, the use of diagnostic tools to formally diagnose sarcopenia and regular training on sarcopenia should be encouraged.


Asunto(s)
Geriatría , Sarcopenia , Humanos , Anciano , Sarcopenia/diagnóstico , Sarcopenia/terapia , Estudios Transversales , Conocimientos, Actitudes y Práctica en Salud , Encuestas y Cuestionarios
9.
Clin Exp Metastasis ; 40(4): 357-371, 2023 08.
Artículo en Inglés | MEDLINE | ID: mdl-37378837

RESUMEN

Lung adenocarcinoma is the most common and aggressive type of lung cancer with the highest incidence of bone metastasis. Epidermal growth factor-like domain multiple 6 (EGFL6) is an exocrine protein, and the expression of EGFL6 is correlated with survival of patient with lung adenocarcinoma. However, the association between EGFL6 expression in lung adenocarcinoma and bone metastasis has not been investigated. In this study, we found that EGFL6 levels in lung adenocarcinoma tissues correlate with bone metastasis and TNM stages in surgical patients. In vitro, overexpression of EGFL6 in lung adenocarcinoma cells promoted their proliferation, migration, and invasion ability compared with control by enhancing EMT process and activating Wnt/ß-catenin and PI3K/AKT/mTOR pathways. In the nude mouse model, overexpression of EGFL6 enhanced tumor growth and caused greater bone destruction. Moreover, the exocrine EGFL6 of human lung adenocarcinoma cells increased osteoclast differentiation of bone marrow mononuclear macrophages (BMMs) of mice via the NF-κB and c-Fos/NFATc1 signaling pathways. However, exocrine EGFL6 had no effect on osteoblast differentiation of bone marrow mesenchymal stem cells (BMSCs). In conclusion, high expression of EGFL6 in lung adenocarcinomas is associated with bone metastasis in surgical patients. The underlying mechanism may be the increased metastatic properties of lung adenocarcinoma cells with high EGFL6 level and the enhanced osteoclast differentiation and bone resorption by exocrine EGFL6 from tumors. Therefore, EGFL6 is a potential therapeutic target to reduce the ability of lung adenocarcinomas to grow and metastasize and to preserve bone mass in patients with bone metastases from lung adenocarcinomas.


Asunto(s)
Adenocarcinoma del Pulmón , Neoplasias Óseas , Resorción Ósea , Neoplasias Pulmonares , Humanos , Animales , Ratones , Fosfatidilinositol 3-Quinasas , Transducción de Señal , Neoplasias Pulmonares/genética , Línea Celular Tumoral , Proteínas de Unión al Calcio , Moléculas de Adhesión Celular
10.
Int Arch Allergy Immunol ; 184(10): 966-974, 2023.
Artículo en Inglés | MEDLINE | ID: mdl-37245505

RESUMEN

INTRODUCTION: The treatment of atopic dermatitis (AD) patients with insufficient response or intolerance to topical medication remains clinical challenges, and there is a paucity of head-to-head trials comparing the efficacy of novel biological agents such as JAK inhibitor and antibody. METHODS: To compare the efficacy of selective JAK1/JAK2 inhibitor baricitinib and interleukin-4 monoclonal antibody dupilumab in the treatment of patients with moderate-to-severe AD, a retrospective cohort study method was adopted. Clinical data from June 2020 to April 2022 were systematically reviewed. Eligible patients who received baricitinib or dupilumab were screened according to the following inclusion criteria: (1) age ≥ 18 years; (2) moderate-to-severe AD: baseline investigator global assessment (IGA) score ≥ 3, baseline eczema area and severity index (EASI) score ≥ 16; (3) poor response or intolerance to at least one topical drug in the past 6 months; (4) no topical glucocorticoids were used in the past 2 weeks and no systematic treatment was given in the past 4 weeks. Patients of the baricitinib group were treated with oral baricitinib in doses of 2 mg per day for 16 weeks, and patients of the dupilumab group were treated with standardized use of dupilumab for 16 weeks, with the initial 600 mg subcutaneous injection and the following 300 mg subcutaneous injection every 2 weeks. The clinical efficacy score indexes including the IGA score, EASI score, and Itch Numeric Rating Scale (NRS) score. These scores at 0, 2, 4, 8, 12, and 16 weeks after the start of treatment were collected. RESULTS: A total of 54/45 patients treated with baricitinib/dupilumab were included. There was no significant difference in the decrease of all scores between the two groups at the 4th week (p > 0.05). There was no difference in the EASI score and Itch NRS score (p > 0.05), but the IGA score of the baricitinib group was lower at the 16th week (Z = 4.284, p < 0.001). Within the first 4 weeks, the Itch NRS score of the baricitinib group decreased rapidly, but with the prolongation of treatment time, there was no significant difference between the two groups at the 16th week (Z = 1.721, p = 0.085). CONCLUSIONS: The efficacy of baricitinib at a dose of 2 mg daily was similar to dupilumab, and the improvement in pruritus was significantly faster in the early stage of treatment (the first 4 weeks) than that of dupilumab.


Asunto(s)
Dermatitis Atópica , Humanos , Dermatitis Atópica/diagnóstico , Dermatitis Atópica/tratamiento farmacológico , Pueblos del Este de Asia , Inmunoglobulina A , Prurito , Estudios Retrospectivos , Índice de Severidad de la Enfermedad , Resultado del Tratamiento
11.
World Allergy Organ J ; 16(3): 100744, 2023 Mar.
Artículo en Inglés | MEDLINE | ID: mdl-37008533

RESUMEN

Background: The prevalence of allergic rhinitis (AR) has been increasing steadily worldwide, especially in countries with increasing industrialization such as China. However, available evidence regarding AR prevalence among Chinese adults is scarce and limited to regional data collected in earlier years. We therefore aimed to provide a more recent and robust estimate of AR prevalence using a nationwide representative cross-sectional study in China. Methods: Data of 184 326 participants aged 18 years or older were obtained from the China Chronic Disease and Risk Factor Surveillance conducted in 2018-2019. AR was determined by self-reported sneezing, nasal itching, obstruction, or rhinorrhea symptoms for at least 1 h in the absence of a cold or flu within the last 12 months. Multivariable logistic model was used to examine the risk factors of AR, and a possible non-linear relationship was further tested by restricted cubic spline. Potential additive interactions of risk factors with sex, residence, and geographic region were assessed by relative excess risk due to interaction (RERI). Results: The weighted prevalence of AR was 8.1% (95% confidence interval [CI], 7.4%-8.7%), of whom 23.7% (95% CI, 21.3%-26.0%) were aware of their diagnosis. Increased odds of AR were associated with younger age, men, living in urban area or north region, more education, smoking, underweight, and higher income. Despite the nonsignificant linear trend, the spline regression demonstrated a non-linear association between AR and sleep duration, with higher odds at both ends. Additionally, the observed associations were generally stronger among men and people living in urban area and north region, with significant RERI ranging from 0.07 (95% CI, 0.00-0.14) to 0.40 (95% CI, 0.12-0.67). Conclusions: AR is prevalent in China and the associated factors and interactions are helpful to design targeted preventive strategies towards certain subpopulations. The low awareness of AR calls for a national effort on AR screening.

12.
Curr Drug Metab ; 24(3): 223-237, 2023.
Artículo en Inglés | MEDLINE | ID: mdl-37114779

RESUMEN

BACKGROUND: Benzodiazepines (BZDs) are compounds that contain one diazepine ring and two benzene rings, and are widely used to treat central nervous system diseases. However, drug abuse and BZDs' illegal addition may affect normal life and even lead to grave social harm. As BZDs may be metabolized and eliminated quickly, it is of great theoretical and practical significance to clarify their metabolic profile. OBJECTIVE: In this paper, LC-Q-TOF/MS-based fragmentation behavior has been investigated for nine benzodiazepine drugs available and widely used in clinical treatment (diazepam, nitrazepam, clonazepam, oxazepam, lorazepam, alprazolam, estazolam, triazolam, and midazolam), and their metabolic profile has been studied by using in vitro human liver microsomal incubation. METHODS: A regular human liver microsomal system was used to investigate the potential biotransformation of the nine benzodiazepines in vitro, and an LC-Q/TOF-MS was used to perform fragmentation behavior studies and metabolite identification. RESULTS: As a result, characteristic fragmentation pathway and diagnostic fragment ions of the nine BZDs were analyzed, and 19 metabolites of the 9 benzodiazepines were found and identified, with glucuronidation and hydroxylation considered as their most important metabolic pathways. CONCLUSION: These experimental data add to our knowledge of the nine benzodiazepine drugs and their metabolism study, which could provide useful information and evidence of their in vivo metabolic profile prediction and help promote their monitoring in both clinical use and social/illegal abuse.


Asunto(s)
Benzodiazepinas , Midazolam , Humanos , Espectrometría de Masas , Cromatografía Liquida
15.
Int Arch Allergy Immunol ; 184(2): 199-201, 2023.
Artículo en Inglés | MEDLINE | ID: mdl-36327946

RESUMEN

BACKGROUND: Anaphylaxis is a life-threatening systemic allergic reaction. Omalizumab (OMA) is an established treatment in chronic urticaria (CU), but experience in anaphylaxis is limited. OBJECTIVES: The objective was to evaluate the efficacy and safety of OMA on anaphylaxis in patients with CU who are resistant to antihistamine therapy and have a history of anaphylaxis. METHOD: Patients with antihistamine-resistant CU and a history of anaphylaxis were eligible. OMA was given 300 mg/150 mg every 4 weeks. Urticaria control test (UCT) scores, the episodes of anaphylaxis, and adverse events were recorded during the OMA treatment. RESULTS: A total of 7 adults were included. After starting OMA, all of them achieved a complete control (UCT = 16) after 3 months of OMA treatment; 6 of them did not suffer any attack of anaphylaxis in the follow-up periods (5 patients for more than 12 months and 1 patient for 4 months). No adverse events were observed. CONCLUSION: The study indicated the efficacy and safety of OMA for antihistamine-resistant CU patients with a history of anaphylaxis and its potential as a prevention option for anaphylaxis.


Asunto(s)
Anafilaxia , Antialérgicos , Urticaria Crónica , Urticaria , Adulto , Humanos , Omalizumab/efectos adversos , Anafilaxia/prevención & control , Urticaria Crónica/tratamiento farmacológico , Urticaria/tratamiento farmacológico , Antagonistas de los Receptores Histamínicos H1 , Enfermedad Crónica , Resultado del Tratamiento
16.
BMC Musculoskelet Disord ; 23(1): 1134, 2022 Dec 27.
Artículo en Inglés | MEDLINE | ID: mdl-36575424

RESUMEN

OBJECTIVES: The extension of diffuse idiopathic skeletal hyperostosis (DISH) from the low thoracic spine to the lumbar spine result in adjustment of spinal sagittal alignment in surgical patients. The aim of this study was to investigate changes in sagittal alignment and back pain in the thoracolumbar spine in nonsurgical DISH and control participants selected from a radiological database. METHODS: Participants in the DISH and the control group were selected by searching for "DISH or degenerative changes in the thoracic spine" in the radiology database of Taizhou Hospital between 2018 and 2021 using Resnick and Niwayama's criteria. The subjects with spinal tumors, previous spinal surgery, vertebral fractures, inflammatory diseases, poor-quality radiographs, or loss of follow-up were excluded. Demographic and clinical characteristics were recorded retrospectively via the hospital information system and telephone follow-up. Segmental disc angles (SDAs), lumbar lordosis (LL), and bridge scores were analyzed using images of three-dimensional CT. RESULTS: The final participants consisted of 51 individuals with DISH (DISH group) and 102 individuals without DISH (control group). Depending on the presence of thoracolumbar pain, the DISH group was divided into the DISH group with thoracolumbar pain (DISH+Pain) and the DISH group without thoracolumbar pain (DISH-Pain). The LL and SDAs of T11-T12 and T12-L1 were significantly greater in the DISH group than in the control group. In addition, the SDA of L1-L2 was significantly smaller in the DISH+Pain group than in the DISH-Pain group, whereas there was no significant difference in lumbar lordosis between the DISH+Pain group and the DISH-Pain group. The bridge scores in DISH+Pain group was larger in T10-T11 (p = 0.01) and L1-L2 (p < 0.01) spine segments than those in DISH-Pain group. CONCLUSION: The extension of DISH from thoracic to lumbar spine may increase lumbar lordosis and SDAs in the thoracolumbar spine. The DISH patients with more bony bridging and small L1-L2 SDA may be more likely have thoracolumbar pain. Adjustment of sagittal alignment of the spine in the development of DISH may be of clinical importance.


Asunto(s)
Hiperostosis Esquelética Difusa Idiopática , Lordosis , Humanos , Lordosis/diagnóstico por imagen , Hiperostosis Esquelética Difusa Idiopática/complicaciones , Hiperostosis Esquelética Difusa Idiopática/diagnóstico por imagen , Estudios Retrospectivos , Vértebras Lumbares/diagnóstico por imagen , Vértebras Lumbares/cirugía , Dolor , Vértebras Torácicas/diagnóstico por imagen , Vértebras Torácicas/cirugía
17.
J Phys Chem Lett ; 13(37): 8635-8640, 2022 Sep 22.
Artículo en Inglés | MEDLINE | ID: mdl-36083044

RESUMEN

We constructed a single-molecule fluorescence imaging technique to monitor the spatiotemporal distribution of the hydroxyl radical (•OH) on TiO2-attached multiwalled carbon nanotubes (TiO2-MWCNTs) in aqueous. We found the heterogeneous distribution of •OH is closely related to the composition and heterostructure of the catalysts. The dynamic •OH production rate was evaluated by counting the single-molecule fluorescent bursts. We further confirmed the production of •OH on TiO2-MWCNTs mainly occurred via electron reduction during the aqueous photocatalytic process. Our study reveals the mechanism of reactive oxygen species involved photocatalytic reaction and guides the design of advanced semiconductor photocatalysts.

18.
J Mol Med (Berl) ; 100(11): 1599-1616, 2022 11.
Artículo en Inglés | MEDLINE | ID: mdl-36112153

RESUMEN

Hormonal homeostasis is essential in bone remodeling. Recent studies have shown that the treatment of intestinal inflammation can result in the regulation of bone resorption in distant bones. Increased intestinal permeability may lead to systemic inflammation and bone loss, also known as gut-bone axis. However, the underlying mechanism remains to be elucidated. Lipopolysaccharide (LPS) is a component of gram-negative bacteria that can increase osteoclastic differentiation in vitro. Acyloxyacyl hydrolase (AOAH) is a specific degrading enzyme of LPS, but little is known about the role of AOAH in bone metabolism. In this study, adult Aoah-/- mice showed a chronic inflammatory state and osteopenic phenotype analyzed by micro-CT and HE staining. Tartrate-resistant acid phosphatase (TRAP) staining of femurs showed an increase in TRAP-positive cells from Aoah-/- mice. AOAH depletion enhanced the osteoclast differentiation and bone resorption capacity of bone marrow-derived macrophages (BMMs). The enhanced osteoclast differentiation and bone resorption capacity of Aoah-/- BMMs were reversed by rAOAH. In conclusion, the chronic inflammatory state of adult Aoah-/- mice promotes bone resorption. AOAH participates in bone metabolism, which is mainly mediated by inhibiting osteoclast differentiation. LPS may be a key mediator of the gut-bone axis, and targeting AOAH may represent a feasible strategy for the treatment of chronic inflammatory bone resorption. KEY MESSAGES : AOAH knockout mice exhibited chronic inflammation mediated by LPS, and LPS may also serve as an important mediator in the regulation of bone metabolism in the gut-bone axis. AOAH regulated bone resorption by blocking the osteoclast differentiation via classical ERK and JNK pathways. rAOAH could rescue the enhanced osteoclast differentiation caused by AOAH deficiency.


Asunto(s)
Resorción Ósea , Lipopolisacáridos , Ratones , Masculino , Animales , Lipopolisacáridos/farmacología , Fosfatasa Ácida Tartratorresistente/genética , Inflamación , Ratones Noqueados , Osteoclastos/metabolismo , Diferenciación Celular
19.
Microbiol Spectr ; 10(5): e0054422, 2022 10 26.
Artículo en Inglés | MEDLINE | ID: mdl-36069576

RESUMEN

Treatment of osteomyelitis is still challenging, as conventional antibiotic therapy is limited by the emergence of resistant strains and the formation of biofilms. Sonoantimicrobial chemotherapy (SACT) is a novel therapy of low-frequency and low-intensity ultrasound (LFLIU) combined with a sonosensitizer. Therefore, in our study, a sonosensitizer named emodin (EM) was proposed to be combined with LFLIU to relieve acute osteomyelitis caused by methicillin-resistant Staphylococcus aureus (MRSA) through antibacterial and antibiofilm effects. The efficiencies of different intensities of ultrasound, including single (S-LFLIU, 15 min) and multiple ultrasound (M-LFLIU, 3 times for 5 min at 4-h intervals), against bacteria and biofilms were compared, contributing to developing the best treatment regimen. Our results demonstrated that EM plus S-LFLIU or M-LFLIU (EM+S-LFLIU or EM+M-LFLIU) had significant combined bactericidal and antibiofilm effects, with EM+M-LFLIU in particular exhibiting superior antibiofilm performance. Furthermore, it was suggested that EM+M-LFLIU could produce a large amount of reactive oxygen species (ROS), destroy the integrity of the bacterial membrane and cell wall, and downregulate the expression of genes involved in oxidative stress, membrane wall synthesis, and bacterial virulence, as well as that of other related genes (agrB, pbp3, sgtB, gmk, zwf, and msrA). In vivo studies, micro-computed tomography (micro-CT), hematoxylin and eosin (H&E) staining, enzyme-linked immunosorbent assay (ELISA), and bacterial quantification of bone tissue indicated that EM+M-LFLIU could also relieve osteomyelitis due to MRSA infection. Our work proffers an original approach to bacterial osteomyelitis treatment that weakens drug-resistant bacteria and suppresses and degrades biofilm formation through SACT, which may provide new prospects for clinical treatment. IMPORTANCE Antibiotic therapy is the first choice for clinical treatment of osteomyelitis, but the formation of bacterial biofilms and the emergence of many drug-resistant strains also create an urgent need to find an alternative treatment to effectively eliminate the infection. Recently, LFLIU has come to be considered a safe and promising method of debridement and antibacterial therapy. In this study, we found that ultrasound and EM have a significant combined antibacterial effect in vivo and in vitro, which may play an antibacterial role by stimulating the production of ROS, destroying the bacterial cell wall, and inhibiting the expression of related genes. Our study expands the body of knowledge on the antibacterial effect of drugs-specifically emodin (EM)-through combined physiotherapy. If successfully integrated into clinical practice, these methods may reduce the burden of high concentrations of drugs needed to treat bacterial biofilms and avoid the growing resistance of bacteria to antibiotics.


Asunto(s)
Emodina , Staphylococcus aureus Resistente a Meticilina , Osteomielitis , Humanos , Staphylococcus aureus Resistente a Meticilina/genética , Emodina/farmacología , Emodina/uso terapéutico , Especies Reactivas de Oxígeno/farmacología , Especies Reactivas de Oxígeno/uso terapéutico , Pruebas de Sensibilidad Microbiana , Microtomografía por Rayos X , Eosina Amarillenta-(YS)/farmacología , Eosina Amarillenta-(YS)/uso terapéutico , Hematoxilina/farmacología , Hematoxilina/uso terapéutico , Osteomielitis/diagnóstico por imagen , Osteomielitis/tratamiento farmacológico , Osteomielitis/microbiología , Biopelículas , Antibacterianos/farmacología , Antibacterianos/uso terapéutico
20.
Microbiome ; 10(1): 122, 2022 08 09.
Artículo en Inglés | MEDLINE | ID: mdl-35941695

RESUMEN

BACKGROUND: Hyperglycaemia in pregnancy (HIP) is a common metabolic disorder that not only poses risks to maternal health but also associates with an increased risk of diabetes among offspring. Vertical transmission of microbiota may influence the offspring microbiome and subsequent glucose metabolism. However, the mechanism by which maternal gut microbiota may influence glucose metabolism of the offspring remains unclear and whether intervening microbiota vertical transmission could be used as a strategy to prevent diabetes in the offspring of mothers with HIP has not been investigated. So we blocked vertical transmission to investigate its effect on glucose metabolism in the offspring. RESULTS: We established a murine HIP model with a high-fat diet (HFD) and investigated the importance of vertical transmission of gut microbiota on the glucose metabolism of offspring via birth and nursing by blocking these events through caesarean section (C-section) and cross-fostering. After weaning, all offspring were fed a normal diet. Based on multi-omics analysis, biochemical and transcriptional assays, we found that the glucometabolic deficits in the mothers were subsequently 'transmitted' to the offspring. Meanwhile, the partial change in mothers' gut microbial community induced by HIP could be transmitted to offspring, supported by the closed clustering of the microbial structure and composition between the offspring and their mothers. Further study showed that the microbiota vertical transmission was blocked by C-section and cross-fostering, which resulted in improved insulin sensitivity and islet function of the offspring of the mothers with HIP. These effects were correlated with changes in the relative abundances of specific bacteria and their metabolites, such as increased relative abundances of Bifidobacterium and short-chain fatty acids. In particular, gut microbial communities of offspring were closely related to those of their foster mothers but not their biological mothers, and the effect of cross-fostering on the offspring's gut microbiota was more profound than that of C-section. CONCLUSION: Our study demonstrates that the gut microbiota transmitted via birth and nursing are important contributors to the glucose metabolism phenotype in offspring. Video Abstract.


Asunto(s)
Diabetes Mellitus , Microbioma Gastrointestinal , Hiperglucemia , Efectos Tardíos de la Exposición Prenatal , Animales , Cesárea , Dieta Alta en Grasa/efectos adversos , Femenino , Glucosa , Humanos , Ratones , Embarazo , Efectos Tardíos de la Exposición Prenatal/microbiología
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