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2.
Am J Med Sci ; 2024 Jul 05.
Artigo em Inglês | MEDLINE | ID: mdl-38972378

RESUMO

OBJECTIVES: To explore the long-term trends in unhealthy lifestyle factors and the risk sociodemographic subgroups among people with dyslipidemia. METHODS: Data extracted from the 1999 to 2018 National Health and Nutrition Examination Survey (NHANES). Lifestyle factors were smoking status, alcohol drinking, obesity, dietary quality, depression, physical activity, and sedentary behavior. A Joinpoint regression model was used to estimate trends in the log-transformed age-standardized prevalence. Multinomial logistic regression models adjusted for age, sex, and race/ethnicity were used to analyze subgroups by sociodemographic factors. RESULTS: Data for 33,680 respondents were extracted between 1999 and 2018. The prevalence of smoking and poor-quality diet decreased from 1999 to 2018 (P<0.001), while obesity significantly increased (P<0.001). The prevalence of depression marginally increased from 2005 to 2018 (P=0.074). We observed that non-Hispanic Black individuals, Hispanics, males, as well as those with lower family income-to-poverty ratios and education levels, unemployed individuals, or those lacking a spouse/live-in partner, were at elevated risk of unhealthy lifestyle factors when compared to the reference groups. CONCLUSIONS: Among NHANES respondents from 1999 to 2018 with dyslipidemia, significant reductions in the prevalence of current smoking and poor diet were observed, while the prevalence of obesity was markedly increased. There were sociodemographic differences in the management of lifestyle factors. Further initiatives to encourage people with dyslipidemia are required to reduce potential adverse outcomes.

3.
J Clin Nurs ; 2024 Jul 01.
Artigo em Inglês | MEDLINE | ID: mdl-38951120

RESUMO

AIM: We aimed to assess the level of knowledge, attitudes and practices regarding airway clearance among nurses and explore the factors affecting the knowledge, attitudes and practices. DESIGN: A questionnaire-based cross-sectional study. BACKGROUND: Airway clearance is an important method of eliminating excess secretions. In neuroscience nursing, nurses are important executors of airway management, and their knowledge, attitudes and practices can influence the effectiveness of airway clearance. METHODS: This study was conducted from July to September 2023 in four hospitals in Jiangsu Province, China. A structured questionnaire about airway clearance was designed and used to collect the data. The nurses used this questionnaire to self-rate. The STROBE checklist for cross-sectional studies was followed. RESULTS: The age, work experience, highest educational attainment and technical title of the nurses can significantly influence their knowledge. The age, highest educational attainment and technical title of the nurses can significantly impact their attitudes. Practice scores were significantly influenced by age, work experience, technical title, whether the nurses had received any training on airway clearance techniques, and whether the department developed procedures for implementing the airway clearance technology. Nurses' attitudes were significantly associated with knowledge and practice, and there was no significant correlation between knowledge and practice. CONCLUSION: This study showed that age, work experience, highest educational attainment and training were related to knowledge, attitudes and practices. These findings suggest that nursing managers can conduct airway clearance training according to age group, working experience and education level of the nurses. PATIENT OR PUBLIC CONTRIBUTION: No patient or public contribution. IMPACT: The findings show that the level of knowledge, attitudes and practices related to airway clearance in neuroscience nursing among nurses were acceptable, which means that nurses can better perform airway management on patients. These findings serve as a significant reference for designing an airway clearance education for nurses and meet the needs of nurses in clinical nursing practice.

4.
Appl Environ Microbiol ; : e0012124, 2024 Jul 09.
Artigo em Inglês | MEDLINE | ID: mdl-38980046

RESUMO

Naja atra, the Chinese cobra, is a major cause of snake envenomation in Asia, causing hundreds of thousands of clinical incidents annually. The current treatment, horse serum-derived antivenom, has unpredictable side effects and presents manufacturing challenges. This study focused on developing new-generation snake venom antidotes by using microbial phage display technology to derive nanobodies from an alpaca immunized with attenuated N. atra venom. Following confirmation of the immune response in the alpaca, we amplified VHH genes from isolated peripheral blood mononuclear cells and constructed a phage display VHH library of 1.0 × 107 transformants. After four rounds of biopanning, the enriched phages exhibited increased binding activity to N. atra venom. Four nanobody clones with high binding affinities were selected: aNAH1, aNAH6, aNAH7, and aNAH9. Specificity testing against venom from various snake species, including two Southeast Asian cobra species, revealed nanobodies specific to the genus Naja. An in vivo mouse venom neutralization assay demonstrated that all nanobodies prolonged mouse survival and aNAH6 protected 66.6% of the mice from the lethal dosage. These findings highlight the potential of phage display-derived nanobodies as valuable antidotes for N. atra venom, laying the groundwork for future applications in snakebite treatment.IMPORTANCEChinese cobra venom bites present a formidable medical challenge, and current serum treatments face unresolved issues. Our research applied microbial phage display technology to obtain a new, effective, and cost-efficient treatment approach. Despite interest among scientists in utilizing this technology to screen alpaca antibodies against toxins, the available literature is limited. This study makes a significant contribution by introducing neutralizing antibodies that are specifically tailored to Chinese cobra venom. We provide a comprehensive and unbiased account of the antibody construction process, accompanied by thorough testing of various nanobodies and an assessment of cross-reactivity with diverse snake venoms. These nanobodies represent a promising avenue for targeted antivenom development that bridges microbiology and biotechnology to address critical health needs.

5.
Food Chem ; 458: 140290, 2024 Jul 03.
Artigo em Inglês | MEDLINE | ID: mdl-38996489

RESUMO

This paper employed a physiologically based pharmacokinetic model (PBPK) to investigate the transformations of folic acid and its metabolites in vivo. Additionally, an ultra-performance liquid chromatography (UPLC) method was developed to accurately measure the body's retention rate and conversion rate of folic acid, tetrahydrofolate, and 5-methyltetrahydrofolate. Furthermore, the bioavailability of folic acid in the body was assessed by combining this method with an evaluation technique for animal models. The study found that the gastric metabolism time was 2 h, while the small intestinal metabolism duration was 4 h. The maximum conversion rate was observed in plasma and liver after 6 h, and in the brain after 8 h. This serves as a framework for creating a model to assess the bioavailability of folic acid in living organisms, to enhance the safety and efficacy of folic acid intake.

6.
Cell Host Microbe ; 2024 Jul 09.
Artigo em Inglês | MEDLINE | ID: mdl-38996548

RESUMO

Numerous studies have reported critical roles for the gut microbiota in obesity. However, the specific microbes that causally contribute to obesity and the underlying mechanisms remain undetermined. Here, we conducted shotgun metagenomic sequencing in a Chinese cohort of 631 obese subjects and 374 normal-weight controls and identified a Megamonas-dominated, enterotype-like cluster enriched in obese subjects. Among this cohort, the presence of Megamonas and polygenic risk exhibited an additive impact on obesity. Megamonas rupellensis possessed genes for myo-inositol degradation, as demonstrated in vitro and in vivo, and the addition of myo-inositol effectively inhibited fatty acid absorption in intestinal organoids. Furthermore, mice colonized with M. rupellensis or E. coli heterologously expressing the myo-inositol-degrading iolG gene exhibited enhanced intestinal lipid absorption, thereby leading to obesity. Altogether, our findings uncover roles for M. rupellensis as a myo-inositol degrader that enhances lipid absorption and obesity, suggesting potential strategies for future obesity management.

7.
BMC Public Health ; 24(1): 1780, 2024 Jul 04.
Artigo em Inglês | MEDLINE | ID: mdl-38965513

RESUMO

BACKGROUND: Nosocomial infections with heavy disease burden are becoming a major threat to the health care system around the world. Through long-term, systematic, continuous data collection and analysis, Nosocomial infection surveillance (NIS) systems are constructed in each hospital; while these data are only used as real-time surveillance but fail to realize the prediction and early warning function. Study is to screen effective predictors from the routine NIS data, through integrating the multiple risk factors and Machine learning (ML) methods, and eventually realize the trend prediction and risk threshold of Incidence of Nosocomial infection (INI). METHODS: We selected two representative hospitals in southern and northern China, and collected NIS data from 2014 to 2021. Thirty-nine factors including hospital operation volume, nosocomial infection, antibacterial drug use and outdoor temperature data, etc. Five ML methods were used to fit the INI prediction model respectively, and to evaluate and compare their performance. RESULTS: Compared with other models, Random Forest showed the best performance (5-fold AUC = 0.983) in both hospitals, followed by Support Vector Machine. Among all the factors, 12 indicators were significantly different between high-risk and low-risk groups for INI (P < 0.05). After screening the effective predictors through importance analysis, prediction model of the time trend was successfully constructed (R2 = 0.473 and 0.780, BIC = -1.537 and -0.731). CONCLUSIONS: The number of surgeries, antibiotics use density, critical disease rate and unreasonable prescription rate and other key indicators could be fitted to be the threshold predictions of INI and quantitative early warning.


Assuntos
Infecção Hospitalar , Aprendizado de Máquina , Humanos , Infecção Hospitalar/epidemiologia , Medição de Risco/métodos , China/epidemiologia , Fatores de Risco , Incidência
8.
Sci Adv ; 10(29): eado9607, 2024 Jul 19.
Artigo em Inglês | MEDLINE | ID: mdl-39018404

RESUMO

Hydroformylation (HF) or isomerization-hydroformylation (ISO-HF) represents the most direct and practical route for producing aldehydes on an industrial scale. To resolve the issues of low activity, low linear/branched (l/b) ratio, and low stability in HF and ISO-HF, we herein reported a class of spirocyclic diphosphites. Notably, the ligand termed O-SDPhite afforded excellent catalytic activity and regioselectivity for the HF of various olefins. Excellent l/b ratio and an unprecedented turnover number of up to 17,620,000 were achieved. O-SDPhite was also found to be effective in the regioselective ISO-HF of the industrially related cheap and abundant C4 Raffinates to n-valeraldehyde produced on a multimillion-ton scale. The reaction with O-SDPhite, superior to that of benchmark Biphephos, was continuously operated for 41 days and afforded an average 38.6 l/b ratio (31 days and 14.7 l/b ratio for Biphephos).

9.
Heliyon ; 10(12): e33069, 2024 Jun 30.
Artigo em Inglês | MEDLINE | ID: mdl-39022057

RESUMO

Re-epithelialization is an important step in skin wound healing, referring to the migration, proliferation, and differentiation of keratinocytes around the wound. During this process, the edges of the wound begin to form new epithelial cells, which migrate from the periphery of the wound towards the center, gradually covering the entire wound area. These newly formed epithelial cells proliferate and differentiate, ultimately forming a protective layer over the exposed dermal surface. Wound endogenous electric fields (EFs) are known as the dominant factor to facilitate the epidermal migration to wound center. However, the precise mechanisms by which EFs promote epidermal migration remains elusive. Here, we found that in a model of cultured keratinocyte monolayer in vitro, EFs application reversed the differentiation of cells, as indicated by the reduction of the early differentiation markers K1 and K10. Genetic manipulation confirmed that EFs reversed keratinocyte differentiation through down-regulating the E-cadherin-mediated adhesion. By RNA-sequencing analysis, we screened out Snail as the transcription suppressor of E-cadherin. Snail knockdown abolished the down-regulation of E-cadherin and the reversal of differentiation induced by EFs. KEGG analysis identified PI3K/AKT signaling for Snail induction under EFs. Inhibition of PI3K by LY294002 diminished the EFs-induced AKT activation and Snail augmentation, largely restoring the level of E-cadherin reduced by EFs. Finally, in model of full-thickness skin wounds in pigs, we found that weakening of the wound endogenous EFs by the direction-reversed exogenous EFs resulted in an up-regulation of E-cadherin and earlier differentiation in newly formed epidermis in vivo. Our research suggests that electric fields (EFs) decrease E-cadherin expression by suppressing the PI3K/AKT/Snail pathway, thereby reversing the differentiation of keratinocytes. This discovery provides us with new insights into the role of electric fields in wound healing. EFs intervene in intracellular signaling pathways, inhibiting the expression of E-cadherin, which results in a lower differentiation state of keratinocytes. In this state, keratinocytes exhibit increased migratory capacity, facilitating the migration of epidermal cells and wound reepithelialization.

10.
Proc Natl Acad Sci U S A ; 121(30): e2401091121, 2024 Jul 23.
Artigo em Inglês | MEDLINE | ID: mdl-39024109

RESUMO

Achieving ligand subtype selectivity within highly homologous subtypes of G-protein-coupled receptor (GPCR) is critical yet challenging for GPCR drug discovery, primarily due to the unclear mechanism underlying ligand subtype selectivity, which hampers the rational design of subtype-selective ligands. Herein, we disclose an unusual molecular mechanism of entropy-driven ligand recognition in cannabinoid (CB) receptor subtypes, revealed through atomic-level molecular dynamics simulations, cryoelectron microscopy structure, and mutagenesis experiments. This mechanism is attributed to the distinct conformational dynamics of the receptor's orthosteric pocket, leading to variations in ligand binding entropy and consequently, differential binding affinities, which culminate in specific ligand recognition. We experimentally validated this mechanism and leveraged it to design ligands with enhanced or ablated subtype selectivity. One such ligand demonstrated favorable pharmacokinetic properties and significant efficacy in rodent inflammatory analgesic models. More importantly, it is precisely due to the high subtype selectivity obtained based on this mechanism that this ligand does not show addictive properties in animal models. Our findings elucidate the unconventional role of entropy in CB receptor subtype selectivity and suggest a strategy for rational design of ligands to achieve entropy-driven subtype selectivity for many pharmaceutically important GPCRs.


Assuntos
Entropia , Simulação de Dinâmica Molecular , Receptores Acoplados a Proteínas G , Ligantes , Animais , Receptores Acoplados a Proteínas G/metabolismo , Receptores Acoplados a Proteínas G/química , Humanos , Ligação Proteica , Camundongos , Microscopia Crioeletrônica , Receptores de Canabinoides/metabolismo , Receptores de Canabinoides/química , Sítios de Ligação
11.
Asian J Psychiatr ; 99: 104151, 2024 Jul 10.
Artigo em Inglês | MEDLINE | ID: mdl-39018700

RESUMO

Clarifying the effect size of the association between somatic symptom disorders (SSDs) and defects in emotional regulation (ER) dimensions through a meta-analysis may improve ER-related treatment for SSD patients. SSDs exhibited a lower level of adaptive ER (overall Hedge's g = -0.618, 95 %CI [0.872, -0.365]; Hedge's g for ER dimensions of Awareness, Description, Clarity, Acceptance, Tolerance, Self-efficacy belief, and Cognitive Reappraisal ranged from -0.451 to -1.344). Maladaptive ER dimensions (catastrophizing and expressive inhibition) showed no significant associations with SSDs. Psychotherapy focusing on developing adaptive ER rather than reducing maladaptive ER may be a more promising approach for treating SSD patients.

12.
Chemosphere ; : 142873, 2024 Jul 15.
Artigo em Inglês | MEDLINE | ID: mdl-39019187

RESUMO

Electro-osmosis has been valued as a promising technology to enhance the dewatering of waste sludge, stabilization and environmental remediation of soils with low permeability. However, the coefficient of electro-osmotic permeability (keo) is commonly taken as constant value which is particularly not the case in variable charge soil. As a result, the nonlinearity of the electro-osmotic flow (EOF) and the direction reverse could not be interpreted. Herein, the electro-chemical parameters were monitored in electro-osmotic experiment with natural variable charge soil. It was observed that evolutions showed significant nonlinear behavior and were correlated. The comprehensive Zeta potential model proposed by the authors was applied to simulate the nonlinear keo induced by the variable pH and electrolyte concentration. The agreement between tested and simulated flow rate variation and excess pore water pressure distribution demonstrated the reliability of the theory. The error rate of the simulations through coupling nonlinear keo and voltage gradient Ex was reduced to 29.4% from 381.9% of calculations with constant parameters. The direction reverse of EOF was innovatively interpreted. Hence, the numerical model would act as a useful tool to connect these electro-chemical parameters and provide guidance to evaluate contributions of commonly used pH conditioning measurements.

13.
Huan Jing Ke Xue ; 45(7): 4218-4227, 2024 Jul 08.
Artigo em Chinês | MEDLINE | ID: mdl-39022968

RESUMO

The potato planting area of Guizhou Province ranks second in China. However, due to factors such as climatic conditions and unbalanced fertilization, soil organic matter in potato fields is consumed rapidly and has a large deficit, which affects soil biological function and soil fertility. Biochar and organic fertilizer are effective ways to supplement foreign aid organic matter to improve soil quality. However, the differences in soil fertility and microbial community structure and their relationships under the conditions of organic fertilizer or biochar combined with chemical fertilizer are not clear. In this study, three treatments of conventional fertilization (NPK), increased application of biochar (NPKB), and increased application of organic fertilizer (NPKO) were set up to investigate the characteristics of potato rhizosphere soil, bacterial community composition, and diversity; to analyze the effects of these factors on the soil integrated fertility index; and to explore the direct and indirect effects of IFI on soil fertility and bacterial community structure differences between treatments and their driving factors. The results showed that soil pH, available phosphorus (AP), available potassium (AK), total nitrogen (TN), organic carbon (SOC), and C/N ratio were significantly higher in the NPKB and NPKO treatments than in the NPK treatment (P<0.05). Soil IFI was greatest for NPKO, followed by NPKB and least for the NPK treatment. A total of 8 214 ASVs were obtained from all the soil samples, belonging to 26 phyla, 75 classes, 165 orders, 176 families, and 251 genera (excluding unidentified fungi). Proteobacteria, Actinobacteria, and Chloroflexi were the dominant phyla, accounting for 54.85% of all ASVs. Compared to that in the NPK and NPKB treatments, the NPKO treatment had the highest bacterial diversity and number of significantly different taxa, and soil AN, AP, AK, SOC, TN, and IFI were significant correlates of bacterial diversity index (P<0.05). Additionally, pH, TN, and SOC were significant influencers of bacterial taxa differences (P<0.05), with importance ranked as TN (70.59%) > SOC (49.42%) > pH (27.08%). Structural equations suggested that pH-related soil properties and bacterial community diversity were the direct pathways influencing IFI, and soil pH-related soil characteristics could also indirectly affect IFI by affecting bacterial Shannon diversity. These results indicate that soil fertility and bacterial community structure were significantly different and correlated between the biochar and organic fertilizer addition treatments and that pH and bacterial community diversity were the key factors influencing IFI, with the NPKO treatment in particular having the best effect on improving IFI. Considering the effect of soil fertilization and the functional group of bacteria, NPKO is the recommended combination for the best synergistic effect of soil fertilization, that is, N 150 kg·hm-2+P2O5 135 kg·hm-2+K2O 135 kg·hm-2+organic fertilizer 6.6 t·hm-2.


Assuntos
Carbono , Carvão Vegetal , Fertilizantes , Microbiologia do Solo , Solo , Carvão Vegetal/química , Solo/química , Solanum tuberosum/crescimento & desenvolvimento , Bactérias/classificação , Bactérias/crescimento & desenvolvimento , China , Nitrogênio , Rizosfera , Compostos Orgânicos , Microbiota/efeitos dos fármacos , Fósforo
14.
J Environ Manage ; 365: 121522, 2024 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-38909576

RESUMO

Ofloxacin (OFL) is a commonly used antibiotic that can enter wastewater treatment plants and be adsorbed by the sludge, resulting in a high OFL concentration in sludge and affecting the subsequent sludge anaerobic digestion process. However, the micro mechanisms involved in this process have not been thoroughly studied. Therefore, this study focuses on the effect of OFL on the sludge anaerobic digestion of sludge to provide such support. The experimental results showed that the maximal methane yield decreased from 277.7 to 164.7 mL/g VSS with the OFL concentration increased from 0 to 300 mg/L. Additionally, OFL hindered the intermediate biochemical processes of hydrolysis, acidogenesis, acetogenesis, and acetoclastic methanogenesis. However, it promoted hydrogenotrophic methanogenesis process, using H2 as substrate, with the concentration of 300 mg/L OFL was 5.54 fold methane production of that in the control. Further investigation revealed that the negative effect of OFL was likely due to the induction of reactive oxygen species, which led to a decrease in cell activity and interference with the activity of key enzymes. Microbiological analysis revealed that OFL reduced the relative abundance of hydrolysis and acidogenesis bacteria, and Methanosaeta archaea, while increasing the relative abundance of hydrogenotrophic methanogenesis microorganism from 36.54% to 51.48% as the OFL concentration increase from 0 to 300 mg/L.


Assuntos
Metano , Ofloxacino , Esgotos , Esgotos/microbiologia , Metano/metabolismo , Anaerobiose , Hidrogênio/metabolismo , Archaea/metabolismo , Reatores Biológicos , Águas Residuárias
15.
Opt Express ; 32(8): 14521-14531, 2024 Apr 08.
Artigo em Inglês | MEDLINE | ID: mdl-38859394

RESUMO

A topological photonic crystal InGaAsP/InP core-shell nanowire array laser with bulk states operating in the 1550 nm band is proposed and simulated. By optimizing the structure parameters, high Q factor of 1.2 × 105 and side-mode suppression ratio of 13.2 dB are obtained, which are 28.6 and 4.6 times that of a uniform nanowire array, respectively. The threshold and maximum output are 17% lower and 613% higher than that of the uniform nanowire array laser, respectively, due to the narrower nanowire slits and stronger optical confinement. In addition, a low beam divergence angle of 2° is obtained due to the topological protection. This work may pave the way for the development of high-output, low-threshold, low-beam-divergence nanolasers.

16.
Adv Mater ; : e2406366, 2024 Jun 13.
Artigo em Inglês | MEDLINE | ID: mdl-38870394

RESUMO

Alkaline zinc-iron flow batteries (AZIFBs) are well suited for energy storage because of their good safety, high cell voltage, and low cost. However, the occurrence of irreversible anodic parasitic reactions results in a diminished coulombic efficiency (CE), unbalanced charge state of catholyte/anolyte and subsequently, a poor cycling performance. Here, we report a universal CE compensation strategy centered around the oxygen evolution reaction (OER) on the cathodic side. This strategy aims to equalize the charge state of the [Fe(CN)6]3-/4--based catholyte and counteract pH fluctuations. The OER process can be implemented either directly on the electrode through electrochemical reaction or in an external catalytic reactor column via a redox-mediated process. This innovative approach effectively mitigates the gradual accumulation of [Fe(CN)6]3- in discharged catholyte and [Zn(OH)4]2- in charged anolyte by consuming the extra OH- during continuous cycling process. As a result, AZIFBs demonstrated exceptional cycling performance with an extremely low capacity fading rate of 0.0128%/day (or 0.0005%/cycle) over 600 cycles at 80% state of charge (SOC). The proposed CE compensation strategy not only provides an effective way to address the CE loss issue for AZIFBs but can also be applied to diverse battery technologies encountering CE loss caused by water/oxygen-induced parasitic reactions. This article is protected by copyright. All rights reserved.

18.
Small ; : e2402925, 2024 Jun 14.
Artigo em Inglês | MEDLINE | ID: mdl-38874069

RESUMO

Aqueous Zn metal batteries are attracting tremendous interest as promising energy storage systems due to their intrinsic safety and cost-effectiveness. Nevertheless, the reversibility of Zn metal anodes (ZMAs) is hindered by water-induced parasitic reactions and dendrite growth. Herein, a novel hydrated eutectic electrolyte (HEE) consisting of Zn(BF4)2·xH2O and sulfolane (SL) is developed to prevent the side reactions and achieve the outstanding cyclability of ZMAs. The strong coordination between Zn2+ and SL triggers the eutectic feature, enabling the low-temperature availability of HEEs. The restriction of BF4 - hydrolysis in the eutectic system can realize favorable compatibility between Zn(BF4)2-based electrolyte and ZMAs. Besides, the newly-established solvation structure with the participation of SL, H2O, and BF4 -, can induce in situ formation of desirable SEI with gradient structure consisting of B,O-rich species, ZnS, and ZnF2, to offer satisfactory protection toward ZMAs. Consequently, the HEE allows the Zn||Zn symmetric cell to cycle over 1650 h at 2 mA cm-2 and 1 mA h cm-2. Moreover, the Zn||NH4V4O10 full batteries can deliver a prolonged lifespan for 1000 cycles with a high capacity retention of 83.4%. This work represents a feasible approach toward the elaborate design of advanced electrolyte systems for next-generation batteries.

19.
PLoS One ; 19(6): e0305903, 2024.
Artigo em Inglês | MEDLINE | ID: mdl-38913698

RESUMO

BACKGROUND: Pulmonary fibrosis (PF) is a common interstitial pneumonia disease, also occurred in post-COVID-19 survivors. The mechanism underlying the anti-PF effect of Qing Fei Hua Xian Decotion (QFHXD), a traditional Chinese medicine formula applied for treating PF in COVID-19 survivors, is unclear. This study aimed to uncover the mechanisms related to the anti-PF effect of QFHXD through analysis of network pharmacology and experimental verification. METHODS: The candidate chemical compounds of QFHXD and its putative targets for treating PF were achieved from public databases, thereby we established the corresponding "herb-compound-target" network of QFHXD. The protein-protein interaction network of potential targets was also constructed to screen the core targets. Furthermore, Gene ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway enrichment analysis were used to predict targets, and pathways, then validated by in vivo experiments. RESULTS: A total of 188 active compounds in QFHXD and 50 target genes were identified from databases. The key therapeutic targets of QFHXD, such as PI3K/Akt, IL-6, TNF, IL-1ß, STAT3, MMP-9, and TGF-ß1 were identified by KEGG and GO analysis. Anti-PF effects of QFHXD (in a dose-dependent manner) and prednisone were confirmed by HE, Masson staining, and Sirius red staining as well as in vivo Micro-CT and immunohistochemical analysis in a rat model of bleomycin-induced PF. Besides, QFXHD remarkably inhibits the activity of PI3K/Akt/NF-κB and TGF-ß1/Smad2/3. CONCLUSIONS: QFXHD significantly attenuated bleomycin-induced PF via inhibiting inflammation and epithelial-mesenchymal transition. PI3K/Akt/NF-κB and TGF-ß1/Smad2/3 pathways might be the potential therapeutic effects of QFHXD for treating PF.


Assuntos
Medicamentos de Ervas Chinesas , Farmacologia em Rede , Mapas de Interação de Proteínas , Fibrose Pulmonar , Fibrose Pulmonar/tratamento farmacológico , Fibrose Pulmonar/induzido quimicamente , Fibrose Pulmonar/metabolismo , Fibrose Pulmonar/patologia , Medicamentos de Ervas Chinesas/farmacologia , Medicamentos de Ervas Chinesas/uso terapêutico , Animais , Ratos , Masculino , Mapas de Interação de Proteínas/efeitos dos fármacos , Bleomicina , Fator de Crescimento Transformador beta1/metabolismo , Ratos Sprague-Dawley , Transdução de Sinais/efeitos dos fármacos , Humanos , COVID-19/metabolismo , Transição Epitelial-Mesenquimal/efeitos dos fármacos , Medicina Tradicional Chinesa/métodos , Tratamento Farmacológico da COVID-19
20.
Breast Cancer Res ; 26(1): 99, 2024 Jun 12.
Artigo em Inglês | MEDLINE | ID: mdl-38867302

RESUMO

In this study, we prepared a bionic nanosystem of trastuzumab-functionalized SK-BR-3 cell membrane hybrid liposome-coated pyrotinib (Ptb-M-Lip-Her) for the treatment of HER2-positive breast cancer. Transmission electron microscopy, dynamic light scattering, polyacrylamide gel electrophoresis (SDS-PAGE) and western blotting were used to verify the successful preparation of Ptb-M-Lip-Her. In vitro drug release experiments proved that Ptb-M-Lip-Her had a sustained release effect. Cell uptake experiments and in vivo imaging experiments proved that Ptb-M-Lip-Her had good targeting ability to homologous tumor cells (SK-BR-3). The results of cell experiments such as MTT, flow cytometry, immunofluorescence staining and in vivo antitumor experiments showed that Ptb-M-Lip-Her could significantly promote apoptosis and inhibit the proliferation of SK-BR-3 cells. These results clearly indicated that Ptb-M-Lip-Her may be a promising biomimetic nanosystem for targeted therapy of HER2-positive breast cancer.


Assuntos
Apoptose , Neoplasias da Mama , Lipossomos , Receptor ErbB-2 , Trastuzumab , Ensaios Antitumorais Modelo de Xenoenxerto , Humanos , Feminino , Lipossomos/química , Trastuzumab/administração & dosagem , Trastuzumab/farmacologia , Neoplasias da Mama/tratamento farmacológico , Neoplasias da Mama/patologia , Neoplasias da Mama/metabolismo , Receptor ErbB-2/metabolismo , Animais , Linhagem Celular Tumoral , Camundongos , Apoptose/efeitos dos fármacos , Proliferação de Células/efeitos dos fármacos , Liberação Controlada de Fármacos , Sistemas de Liberação de Medicamentos , Terapia de Alvo Molecular , Acrilamidas , Aminoquinolinas
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