RESUMO
Achieving high cell transfection efficiency is essential for various cell types in numerous disease applications. However, the efficient introduction of genes into natural killer (NK) cells remains a challenge. In this study, we proposed a design strategy for delivering exogenous genes into the NK cell line, NK-92, using a modified non-viral gene transfection method. Calcium phosphate/DNA nanoparticles (pDNA-CaP NPs) were prepared using co-precipitation methods and combined with low-voltage pulse electroporation to facilitate NK-92 transfection. The results demonstrated that the developed pDNA-CaP NPs exhibited a uniform diameter of approximately 393.9 nm, a DNA entrapment efficiency of 65.8%, and a loading capacity of 15.9%. Furthermore, at three days post-transfection, both the transfection efficiency and cell viability of NK-92 were significantly improved compared to standalone plasmid DNA (pDNA) electroporation or solely relying on the endocytosis pathway of pDNA-CaP NPs. This study provides valuable insights into a novel approach that combines calcium phosphate nanoparticles with low-voltage electroporation for gene delivery into NK-92 cells, offering potential advancements in cell therapy.
RESUMO
To study the influences of the degree of interdepartmental collaborative supervision on the behavioral strategy selection of pig farmers, pig slaughterers, and pork processing manufacturers in the pork supply chain system, this study established a three-party evolutionary game model involving pig farmers, pig slaughterers, and pork processing manufacturers based on the social co-governance framework by focusing on the interdepartmental information sharing mechanism and cooperative governance. Here, we examined how the degree of collaborative supervision among government departments influences the behavioral strategy selection of these parties by focusing on key mechanisms such as information sharing and interdepartmental collaborative governance. Our findings revealed that within a social co-governance system, the strategic choices of the three entities in the pork supply chain closely correlate with the coordination level of collaborative supervision among government departments, particularly through information-sharing mechanisms. Additionally, the strategies are influenced by market-based contract supervision among entities, consumer reporting intensity, and the collaborative governance capabilities of the government, market actors, and consumers. Higher levels of social co-governance are associated with fewer risky links in the pork supply chain and reduced overall risk. Key factors affecting the behavioral strategy selection of the subjects in the pork supply chain include interdepartmental collaborative governance among government departments (e.g., optimizing random inspection frequencies, adjusting economic penalties, and disclosing enterprise market credit information via information sharing mechanisms), consumer complaint probabilities, and the intensity of mutual supervision among enterprises. Therefore, to enhance pork supply chain quality and mitigate risks, it is crucial to enhance the coordination of collaborative supervision among government departments, encourage consumer reporting, and improve market-based mutual supervision mechanisms among upstream and downstream subjects in the supply chain.
RESUMO
BACKGROUND: Massive hemoptysis is characterized by its life-threatening nature, potentially leading to airway obstruction and asphyxia. The objective of this study was to evaluate the clinical effectiveness of combining endobronchial tamponade with bronchial artery embolization (BAE) in the treatment of massive hemoptysis. METHODS: Between March 2018 and March 2022, a total of 67 patients with massive hemoptysis who underwent BAE were divided into two groups: the combination group (n = 26) and the BAE group (n = 41). Technical and clinical success rates were assessed, and adverse events were monitored following the treatment. Blood gas analysis and coagulation function indicators were collected before and after the treatment, and recurrence and survival rates were recorded during the follow-up period. RESULTS: All patients achieved technical success. There were no significant differences in the clinical success rate, recurrence rates at 3 and 6 months, and mortality rates at 3 months, 6 months, and 1 year between the combination group and the BAE group. However, the hemoptysis recurrence rate at 1 year was significantly lower in the combination group compared to the BAE group (15.4% vs. 39.0%, P = 0.039). No serious adverse events were reported in either group. After treatment, the combination group showed higher levels of arterial partial pressure of oxygen (PaO2), oxygenation index (PaO2/FiO2), fibrinogen (FIB), and D-dimer (D-D) compared to the BAE group (P < 0.05). Multivariate regression analysis demonstrated a significant correlation between combined therapy and hemoptysis-free survival. CONCLUSION: Combination therapy, compared to embolization alone, exhibits superior efficacy in improving respiratory function, correcting hypoxia, stopping bleeding, and preventing recurrence. It is considered an effective and safe treatment for massive hemoptysis.
Assuntos
Artérias Brônquicas , Embolização Terapêutica , Hemoptise , Humanos , Hemoptise/terapia , Hemoptise/etiologia , Embolização Terapêutica/métodos , Feminino , Masculino , Pessoa de Meia-Idade , Idoso , Resultado do Tratamento , Estudos Retrospectivos , Terapia Combinada , Adulto , Recidiva , Broncoscopia/métodos , GasometriaRESUMO
OBJECTIVE: The aim of this study was to explore the effect of depression and selective serotonin reuptake inhibitors on implant osseointegration and bone healing. METHODS: Forty-eight 6- to 8-week-old SPF Sprague-Dawley male rats were randomly divided into four groups: the Control group, the Fluoxetine group, the Depression group and the De&Flu group. The rats in the Depression group and the De&Flu group were subjected to a depression modelling process, and the rats in the Control group and the Fluoxetine group were raised normally. Then, a titanium implant was placed in the right tibia of each rat. In the Fluoxetine group and De&Flu group, fluoxetine was injected subcutaneously daily, while subcutaneously injecting physiological saline in the Control group and Depression group. Collecting serum from the rats used for ELISA. The surgical area was cut for microcomputed tomography and histology observation. RESULTS: After 12 weeks, bone mineral density was lower in the De&Flu group than in the Control group, Depression group and Fluoxetine group. Bone mineral density was also lower in the Depression group and the Fluoxetine group than in the Control group. The percentage of bone-implant contact (BIC%) in De&Flu rats was lower than in the Control, Depression and Fluoxetine groups. The BIC% in the Depression group and the Fluoxetine group was lower than in the Control group. CONCLUSIONS: Depression and fluoxetine negatively affect bone density and implant osseointegration independently, and this damaging effect is exacerbated when both factors are present. The mechanism may be related to the dysregulation of the hypothalamic-pituitary-adrenal axis and inflammation in the body.
RESUMO
Currently, there are still great challenges in promoting bone defect healing, a common health problem affecting millions of people. Herein an osteoimmunity-regulating biopatch capable of promoting stem cell-based therapies for bone regeneration is developed. A totally biodegradable conjugate is first synthesized, which can self-assemble into bioactive nano micelles (PPT NMs). This nanotherapy effectively improves the osteogenesis of periodontal ligament stem cells (PDLSCs) under pathological conditions, by simultaneously regulating IL-17 signaling and ferroptosis pathways. Incorporation of PPT NMs into biodegradable electrospun nanofibers affords a bioactive patch, which notably improves bone formation in two rat bone defect models. A Janus bio patch is then engineered by integrating the bioactive patch with a stem cell sheet of PDLSCs. The obtained biopatch shows additionally potentiated bone regeneration capacity, by synergistically regulating osteoimmune microenvironment and facilitating stem cell differentiation. Further surface functionalization of the biopatch with tannic acid considerably increases its adhesion to the bone defect, prolongs local retention, and sustains bioactivities, thereby offering much better repair effects in rats with mandibular or cranial bone defects. Moreover, the engineered bioactive patches display good safety. Besides bone defects, this osteoimmunity-regulating biopatch strategy can be applied to promote stem cell therapies for spinal cord injury, wound healing, and skin burns.
RESUMO
To investigate the effect of an enhanced rehabilitation program on upper limb function in patients with abdominal pedicle flap surgery, we retrospectively analyzed 70 patients received abdominal pedicled flap surgery between 2017 and 2022. Patients were categorized into the traditional rehabilitation group (rehabilitation initiated after the stage â ¡ pedicle dissection of the abdominal pedicle flap) and the enhanced rehabilitation group (rehabilitation initiated on the first day following the stage â abdominal pedicle flap surgery). All the patients received identical rehabilitation protocols. PROM, ADL, FIM, and MMT were assessed at five days and one month following the stage â ¡ surgery. The main causes of injury were electrical burns in both groups. The hospital stay of patients in the enhanced group was significantly shorter than the traditional group. One month assessment indicated both groups showed significant improvements in the PROM of shoulder flexion, abduction, and elbow extension compared to the five days assessment. Notably, at five days assessment, the enhanced group had significantly higher PROM in shoulder abduction and elbow extension compared to the traditional group. Furthermore, the enhanced group continued to exhibit higher PROM in shoulder flexion and abduction than the traditional group at one month assessment. At one month assessment, a significant increase was observed in the ADL, FIM, and MMT of both groups compared to the five days. The study indicated the enhanced rehabilitation program immediately following the stage â surgery can effectively improve the PROM of the shoulder and elbow and reduce the length of hospital stay for patients.
RESUMO
Background: The objective of this study was to investigate the association between pre-operative body mass index (BMI) and surgical infection in perihilar cholangiocarcinoma (pCCA) patients treated with curative resection. Methods: Consecutive pCCA patients were enrolled from four tertiary hospitals between 2008 and 2022. According to pre-operative BMI, the patients were divided into three groups: low BMI (≤18.4 kg/m2), normal BMI (18.5-24.9 kg/m2), and high BMI (≥25.0 kg/m2). The incidence of surgical infection among the three groups was compared. Multivariable logistic regression models were used to determine the independent risk factors associated with surgical infection. Results: A total of 371 patients were enrolled, including 283 patients (76.3%) in the normal BMI group, 30 patients (8.1%) in the low BMI group, and 58 patients (15.6%) in the high BMI group. The incidence of surgical infection was significantly higher in the patients in the low BMI and high BMI groups than in the normal BMI group. The multivariable logistic regression model showed that low BMI and high BMI were independently associated with the occurrence of surgical infection. Conclusions: The pCCA patients with a normal BMI treated with curative resection could have a lower risk of surgical infection than pCCA patients with an abnormal BMI.
RESUMO
BACKGROUND: Despite cryptorchidism being a common genital abnormality in male newborns with significant prevalence variations globally, there is a notable scarcity of epidemiological data on this condition in China. OBJECTIVE: This study aimed to delineate the prevalence pattern of cryptorchidism in Chinese population over the past 15 years using nationwide surveillance data. MATERIALS AND METHODS: Data from the China National Population-based Birth Defects Surveillance System (2007-2021) were analyzed to calculate the prevalence rates of cryptorchidism, stratified by birth year, maternal age, maternal residence, and geographic region. Adjusted prevalence rate ratios were computed using Poisson regression, while trends in prevalence and average annual percent change (AAPC) were assessed using the joinpoint regression model. RESULTS: During the study period, a total of 1,833 cases of cryptorchidism were identified among 2,565,964 full-term male births, resulting in prevalence rates of 7.14, 5.60, and 1.54 per 10,000 births for overall, isolated, and associated cryptorchidism, respectively. The overall prevalence increased from 3.86 to 11.20 per 10,000 births, with an AAPC of 7.9% (95% confidence interval: 5.5-11.0). Significant variations were observed across maternal age (< 20 years, 7.62/10,000; 20-24 years, 6.14/10,000; 25-29 years, 6.96/10,000; 30-34 years, 7.48/10,000; ≥35 years, 9.22/10,000), maternal residence (urban vs. rural, 10.99/10,000 vs. 2.86/10,000), and geographic region (eastern, 12.38/10,000; central, 2.36/10,000; western, 2.63/10,000). Approximately one-third of cryptorchidism cases were bilaterally, while two-thirds were unilateral. Commonly observed associated abnormalities included congenital hydrocele testis, as well as anomalies in the genital organs, circulatory system, and musculoskeletal system. CONCLUSION: Despite lower rates compared to other countries, the increasing trend in prevalence of cryptorchidism necessitates further investigation and intervention.
RESUMO
Preterm birth (PTB) is a leading cause of neonatal morbidity and mortality worldwide, yet the cellular and molecular mechanisms driving this condition remain undeciphered, thus limiting discovery of new therapies. In-depth analyses of human and mouse tissues associated with PTB, in combination with cellular studies, indicated that aberrantly high-expressed neutrophil cytoplasmic factor (NCF) 1 leads to oxidative distress, recruitment, and pro-inflammatory activation of neutrophils and macrophages, while sequentially overexpressed pro-inflammatory mediators induce contractions of uterine smooth muscle cells (USMCs) as well as apoptosis of USMCs and amniotic epithelial cells, thereby causing PTB. According to these new findings, we rationally engineered an amphiphilic macromolecular conjugate LPA by covalently integrating low-molecular-weight heparin, a reactive oxygen species-responsive/scavenging component, and an anti-inflammatory peptide. This bioengineered macromolecular conjugate can self-assemble into multi-bioactive nanoparticles (LPA NP). In a mouse model of PTB, LPA NP effectively delayed PTB and inhibited adverse pregnancy outcomes, by regulating NCF1-mediated oxidative-inflammatory cascades, i.e., attenuating oxidative stress, inhibiting inflammatory cell activation, reducing local inflammation, and decreasing contraction/apoptosis of myometrial cells. Packaging LPA NP into temperature-responsive, self-healing, and bioadhesive hydrogel further potentiated its in vivo efficacies after intravaginal delivery, by prolonging retention time, sustaining nanotherapy release, and increasing bioavailability in the placenta/uterus. Importantly, both the conjugate/nanotherapy and hydrogel formulations exhibited excellent safety profiles in pregnant mice, with negligible side effects on the mother and offspring.
RESUMO
BACKGROUND: The long-term survival benefit of immune checkpoint inhibitors (ICIs) in neoadjuvant and adjuvant settings is unclear for colorectal cancers (CRC) and gastric cancers (GC) with deficiency of mismatch repair (dMMR) or microsatellite instability-high (MSI-H). METHODS: This retrospective study enrolled patients with dMMR/MSI-H CRC and GC who received at least one dose of neoadjuvant ICIs (neoadjuvant cohort, NAC) or adjuvant ICIs (adjuvant cohort, AC) at 17 centers in China. Patients with stage IV disease were also eligible if all tumor lesions were radically resectable. RESULTS: In NAC (n = 124), objective response rates were 75.7% and 55.4%, respectively, in CRC and GC, and pathological complete response rates were 73.4% and 47.7%, respectively. The 3-year disease-free survival (DFS) and overall survival (OS) rates were 96% (95%CI 90-100%) and 100% for CRC (median follow-up [mFU] 29.4 months), respectively, and were 84% (72-96%) and 93% (85-100%) for GC (mFU 33.0 months), respectively. In AC (n = 48), the 3-year DFS and OS rates were 94% (84-100%) and 100% for CRC (mFU 35.5 months), respectively, and were 92% (82-100%) and 96% (88-100%) for GC (mFU 40.4 months), respectively. Among the seven patients with distant relapse, four received dual blockade of PD1 and CTLA4 combined with or without chemo- and targeted drugs, with three partial response and one progressive disease. CONCLUSION: With a relatively long follow-up, this study demonstrated that neoadjuvant and adjuvant ICIs might be both associated with promising DFS and OS in dMMR/MSI-H CRC and GC, which should be confirmed in further randomized clinical trials.
Assuntos
Neoplasias Colorretais , Inibidores de Checkpoint Imunológico , Instabilidade de Microssatélites , Terapia Neoadjuvante , Neoplasias Gástricas , Humanos , Neoplasias Gástricas/tratamento farmacológico , Neoplasias Gástricas/mortalidade , Neoplasias Gástricas/patologia , Feminino , Inibidores de Checkpoint Imunológico/uso terapêutico , Masculino , Terapia Neoadjuvante/métodos , Pessoa de Meia-Idade , Neoplasias Colorretais/tratamento farmacológico , Neoplasias Colorretais/mortalidade , Neoplasias Colorretais/patologia , Estudos Retrospectivos , Idoso , Adulto , Reparo de Erro de Pareamento de DNA , Quimioterapia Adjuvante/métodos , SeguimentosRESUMO
Fructus hippophae (Hippophae rhamnoides spp. mongolica×Hippophae rhamnoides sinensis), a hybrid variety of sea buckthorn that Hippophae rhamnoides spp. mongolica serves as the female parent and Hippophae rhamnoides sinensis serves as the male parent, is a traditional plant with great potentials of economic and medical values. Herein, we gained a chromosome-level genome of Fructus hippophae about 918.59 Mb, with the scaffolds N50 reaching 83.65 Mb. Then, we anchored 440 contigs with 97.17% of the total genome sequences onto 12 pseudochromosomes. Next, de-novo, homology and transcriptome assembly strategies were adopted for gene structure prediction. This predicted 36475 protein-coding genes, of which 36226 genes could be functionally annotated. Simultaneously, various strategies were used for quality assessment, both the complete BUSCO value (98.80%) and the mapping rate indicated the high assembly quality. Repetitive elements, which occupied 63.68% of the genome, and 1483600 bp of non-coding RNA were annotated. Here, we provide genomic information on female plants of a popular variety, which can provide data for pan-genomic construction of sea buckthorn and for the resolution of the mechanism of sex differentiation.
Assuntos
Cromossomos de Plantas , Genoma de Planta , Hippophae , Hippophae/genética , Cromossomos de Plantas/genética , Transcriptoma , Anotação de Sequência MolecularRESUMO
In the last few decades, tear-based biosensors for continuous glucose monitoring (CGM) have provided new avenues for the diagnosis of diabetes. The tear CGMs constructed from nanomaterials have been extensively demonstrated by various research activities in this field and are gradually witnessing their most prosperous period. A timely and comprehensive review of the development of tear CGMs in a compartmentalized manner from a nanomaterials perspective would greatly broaden this area of research. However, to our knowledge, there is a lack of specialized reviews and comprehensive cohesive reports in this area. First, this paper describes the principles and development of electrochemical glucose sensors. Then, a comprehensive summary of various advanced nanomaterials recently reported for potential applications and construction strategies in tear CGMs is presented in a compartmentalized manner, focusing on sensing properties. Finally, the challenges, strategies, and perspectives used to design tear CGM materials are emphasized, providing valuable insights and guidance for the construction of tear CGMs from nanomaterials in the future.
Assuntos
Técnicas Biossensoriais , Técnicas Eletroquímicas , Nanoestruturas , Lágrimas , Dispositivos Eletrônicos Vestíveis , Nanoestruturas/química , Humanos , Lágrimas/química , Glucose/análiseRESUMO
BACKGROUND: Due to the close correlation between choline, L-carnitine, betaine and their intestinal microbial metabolites, including trimethylamine (TMA) and trimethylamine N-oxide (TMAO), and creatinine, there has been an increasing interest in the study of these compounds in vivo. METHODS: In this study, a rapid stable isotope dilution (SID)-UHPLC-MS/MS method was developed for the simultaneous determination of choline, L-carnitine, betaine, TMA, TMAO and creatinine in plasma, liver and feces of rats. The method was validated using quality control (QC) samples spiked at low, medium and high levels. Second, we applied the method to quantify the effects of Rosa Roxburghii Tratt juice (RRTJ) on plasma, liver, and fecal levels of choline, L-carnitine, betaine, TMA, TMAO, and creatinine in high-fat diet-induced hyperlipidemic rats, demonstrating the utility of the method. RESULTS: The limits of detection (LOD) were 0.04-0.027 µM and the limits of quantification (LOQ) were 0.009-0.094 µM. The linear ranges for each metabolite in plasma were choline1.50-96 µM; L-carnitine: 2-128 µM; betaine: 3-192 µM; TMA: 0.01-40.96 µM; TMAO: 0.06-61.44 µM and creatinine: 1-64 µM (R2 ≥ 0.9954). The linear ranges for each metabolite in liver were Choline: 12-768 µM; L-carnitine: 1.5-96 µM; betaine: 10-640 µM; TMA: 0.5-32 µM; TMAO: 0.02-81.92 µM and creatinine: 0.2-204.8 µM (R2 ≥ 0.9938). The linear ranges for each metabolite in feces were choline: 1.5-96 µM; L-carnitine: 0.01-40.96 µM; Betaine: 1.5-96 µM; TMA: 1-64 µM; TMAO: 0.02-81.92 µM and Creatinine: 0.02-81.92 µM (R2 ≥ 0.998). The intra-day and inter-day coefficients of variation were < 8 % for all analytes. The samples were stabilized after multiple freeze-thaw cycles (3 freeze-thaw cycles), 24 h at room temperature, 24 h at 4 °C and 20 days at -80 °C. The samples were stable. The average recovery was 89 %-99 %. This method was used to quantify TMAO and its related metabolites and creatinine levels in hyperlipidemic rats. The results showed that high-fat diet led to the disorder of TMAO and its related metabolites and creatinine in rats, which was effectively improved after the intervention of Rosa Roxburghii Tratt juiceï¼RRTJï¼. CONCLUSIONS: A method for the determination of choline, L-carnitine, betaine, TMA, TMAO and creatinine in plasma, liver and feces samples was established, which is simple, time-saving, high precision, accuracy and recovery.
Assuntos
Betaína , Carnitina , Colina , Creatinina , Fezes , Hiperlipidemias , Limite de Detecção , Fígado , Metilaminas , Ratos Sprague-Dawley , Espectrometria de Massas em Tandem , Animais , Ratos , Metilaminas/sangue , Metilaminas/análise , Espectrometria de Massas em Tandem/métodos , Cromatografia Líquida de Alta Pressão/métodos , Fezes/química , Colina/sangue , Colina/análise , Colina/metabolismo , Carnitina/sangue , Carnitina/análise , Carnitina/metabolismo , Masculino , Fígado/metabolismo , Fígado/química , Creatinina/sangue , Creatinina/análise , Hiperlipidemias/metabolismo , Hiperlipidemias/sangue , Betaína/sangue , Betaína/análise , Modelos Lineares , Reprodutibilidade dos Testes , Sucos de Frutas e Vegetais/análiseRESUMO
BACKGROUND: Additional resection for invasive cancer at perihilar cholangiocarcinoma (pCCA) resection margins has become a consensus. However, controversy still exists regarding whether additional resection is necessary for residual biliary intraepithelial neoplasia (BilIN). METHOD: Consecutive patients with pCCA from two hospitals were enrolled. The incidence and pattern of resection margin BilIN were summarized. Prognosis between patients with negative margins (R0) and BilIN margins were analyzed. Cox regression with a forest plot was used to identify independent risk factors associated with overall survival (OS) and recurrence-free survival (RFS). Subgroup analysis was performed based on BilIN features and tumor characteristics. RESULTS: 306 pCCA patients receiving curative resection were included. 255 had R0 margins and 51 had BilIN margins. There was no significant difference in OS (P = 0.264) or RFS (P = 0.149) between the two group. Specifically, 19 patients with BilIN at distal bile ducts and 32 at proximal bile ducts. 42 patients showed low-grade BilIN, and 9 showed high-grade. Further analysis revealed no significant difference in long-term survival between different locations (P = 0.354), or between different grades (P = 0.772). Portal vein invasion, poor differentiation and lymph node metastasis were considered independent risk factors for OS and RFS, while BilIN was not. Subgroup analysis showed no significant difference in long-term survival between the lymph node metastasis subgroup, or between the portal vein invasion subgroup. CONCLUSION: For pCCA patients underwent curative resection, residual BilIN at resection margin is acceptable. Additional resection is not necessary for such patients to achieve absolute R0 margin.
Assuntos
Neoplasias dos Ductos Biliares , Tumor de Klatskin , Margens de Excisão , Humanos , Masculino , Feminino , Neoplasias dos Ductos Biliares/cirurgia , Neoplasias dos Ductos Biliares/patologia , Neoplasias dos Ductos Biliares/mortalidade , Estudos Retrospectivos , Tumor de Klatskin/cirurgia , Tumor de Klatskin/patologia , Tumor de Klatskin/mortalidade , Pessoa de Meia-Idade , Idoso , Prognóstico , Seguimentos , Taxa de Sobrevida , Carcinoma in Situ/cirurgia , Carcinoma in Situ/patologia , Neoplasia Residual/patologia , Neoplasia Residual/cirurgia , Adulto , Transformação Celular Neoplásica/patologia , Recidiva Local de Neoplasia/patologia , Recidiva Local de Neoplasia/cirurgia , Recidiva Local de Neoplasia/epidemiologia , Hepatectomia/métodos , Hepatectomia/mortalidade , Idoso de 80 Anos ou maisRESUMO
Postoperative tissue adhesion and poor tendon healing are major clinical problems associated with tendon surgery. To avoid postoperative adhesion and promote tendon healing, we developed and synthesized a membrane to wrap the surgical site after tendon suturing. The bilayer-structured porous membrane comprised an outer layer [1,4-butanediol diglycidyl ether cross-linked with carboxymethyl cellulose (CX)] and an inner layer [1,4-butanediol diglycidyl ether cross-linked with Bletilla striata polysaccharides and carboxymethyl cellulose (CXB)]. The morphology, chemical functional groups, and membrane structure were determined. In vitro experiments revealed that the CX/CXB membrane demonstrated good biosafety and biodegradability, promoted tenocyte proliferation and migration, and exhibited low cell attachment and anti-inflammatory effects. Furthermore, in in vivo animal study, the CX/CXB membrane effectively reduced postoperative tendon-peripheral tissue adhesion and improved tendon repair, downregulating inflammatory cytokines in the tendon tissue at the surgical site, which ultimately increased tendon strength by 54% after 4 weeks.
RESUMO
Acute lung injury, a fatal condition characterized by a high mortality rate, necessitates urgent exploration of treatment modalities. Utilizing UHPLS-Q-Exactive Orbitrap/MS, our study scrutinized the active constituents present in Rosa roxburghii-fermented juice (RRFJ) while also assessing its protective efficacy against LPS-induced ALI in mice through lung histopathological analysis, cytokine profiling, and oxidative stress assessment. The protective mechanism of RRFJ against ALI in mice was elucidated utilizing metabolomics, network pharmacology, and molecular docking methodologies. Our experimental findings demonstrate that RRFJ markedly ameliorates pathological injuries in ALI-afflicted mice, mitigates systemic inflammation and oxidative stress, enhances energy metabolism, and restores dysregulated amino acid and arachidonic acid metabolic pathways. This study indicates that RRFJ can serve as a functional food for adjuvant treatment of ALI.
Assuntos
Lesão Pulmonar Aguda , Sucos de Frutas e Vegetais , Lipopolissacarídeos , Metabolômica , Estresse Oxidativo , Rosa , Animais , Lesão Pulmonar Aguda/tratamento farmacológico , Lesão Pulmonar Aguda/induzido quimicamente , Lesão Pulmonar Aguda/metabolismo , Lesão Pulmonar Aguda/prevenção & controle , Rosa/química , Metabolômica/métodos , Camundongos , Masculino , Estresse Oxidativo/efeitos dos fármacos , Farmacologia em Rede , Fermentação , Pulmão/efeitos dos fármacos , Pulmão/patologia , Pulmão/metabolismo , Modelos Animais de Doenças , Simulação de Acoplamento Molecular , Extratos Vegetais/farmacologia , Citocinas/metabolismo , Metabolismo Energético/efeitos dos fármacosRESUMO
BACKGROUND: Understanding the impact of CYP2D6 metabolism on paroxetine, a widely used antidepressant, is essential for precision dosing. METHODS: We conducted an 8-week, multi-center, single-drug, 2-week wash period prospective cohort study in 921 Chinese Han patients with depressive or anxiety disorders (ChiCTR2000038462). We performed CYP2D6 genotyping (single nucleotide variant and copy number variant) to derive the CYP2D6 activity score and evaluated paroxetine treatment outcomes including steady-state concentration, treatment efficacy, and adverse reaction. CYP2D6 metabolizer status was categorized into poor metabolizers (PMs), intermediate metabolizers (IMs), extensive metabolizers (EMs), and ultrarapid metabolizers (UMs). The influence of CYP2D6 metabolic phenotype on paroxetine treatment outcomes was examined using multiple regression analysis and cross-ethnic meta-analysis. The therapeutic reference range of paroxetine was estimated by receiver operating characteristic (ROC) analyses. FINDINGS: After adjusting for demographic factors, the steady-state concentrations of paroxetine in PMs, IMs, and UMs were 2.50, 1.12, and 0.39 times that of EMs, with PM and UM effects being statistically significant (multiple linear regression, P = 0.03 and P = 0.04). Sex and ethnicity influenced the comparison between IMs and EMs. Moreover, poor efficacy of paroxetine was associated with UM, and a higher risk of developing adverse reactions was associated with lower CYP2D6 activity score. Lastly, cross-ethnic meta-analysis suggested dose adjustments for PMs, IMs, EMs, and UMs in the East Asian population to be 35%, 40%, 143%, and 241% of the manufacturer's recommended dose, and 62%, 68%, 131%, and 159% in the non-East Asian population. INTERPRETATION: Our findings advocate for precision dosing based on the CYP2D6 metabolic phenotype, with sex and ethnicity being crucial considerations in this approach. FUNDING: National Natural Science Foundation of China; Academy of Medical Sciences Research Unit.