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1.
Zhongguo Zhong Yao Za Zhi ; 49(16): 4313-4320, 2024 Aug.
Artigo em Chinês | MEDLINE | ID: mdl-39307768

RESUMO

This study aims to investigate the mechanism of Xueshuantong Injection(XST) on pulmonary fibrosis induced by bleomycin(BLM) in rats based on the coagulation cascade pathway. Sixty SD rats were randomly divided into sham surgery group,model group, pirfenidone(PFD, 50 mg·kg~(-1)) group, and 27, 54, and 81 mg·kg~(-1) XST groups. The rat model of pulmonary fibrosis was established by intratracheal injection of BLM(5 mg·kg~(-1)). After 24 hours, the administration groups were given corresponding drugs, while the sham surgery group and model group were given equal volumes of saline. On the 28th day, samples were collected,and the imaging and collagen fiber changes in the lungs of rats were observed. Immunofluorescence(IF) method was used to detect the expression level of alpha-smooth muscle actin(α-SMA), collagen Ⅰ(Col-Ⅰ), E-cadherin(E-cad), and vimentin(Vim). Western blot was used to determine the protein expression of α-SMA, Col-Ⅰ, Vim, and E-cad. Enzyme-linked immunosorbent assay(ELISA)was used to detect the levels of prothrombin fragment(F1 + 2), thrombin-antithrombin complex(TAT), soluble fibrin monomer complex(SFMC), and rat fibrinogen degradation products(FDP) in rat lung tissue. Finally, the mRNA and protein levels of protease activated receptor 1(PAR-1) were detected by RT-qPCR, western blot, and IF. Compared with the model group, the scanning of the lungs of rats receiving XST treatment also exhibited patchy and non-homogeneous shadows, but these shadows were less dense than those in the model group. At the same time, there was a significant decrease in Col-Ⅰ fibers in the lungs of rats, and XST could inhibit epithelial-mesenchymal transition(EMT) and downregulate α-SMA and Col-Ⅰ protein expression. In the aspect of the coagulation system, administration of 81 mg·kg~(-1) XST significantly reduced the levels of SFMC and FDP. Meanwhile, 81 mg·kg~(-1) XST significantly downregulated the mRNA and protein levels of PAR-1. XST has an anti-pulmonary fibrosis effect in rats, and its mechanism may be related to the downregulation of PAR-1 to rebalance the coagulation cascade pathway.


Assuntos
Bleomicina , Medicamentos de Ervas Chinesas , Fibrose Pulmonar , Ratos Sprague-Dawley , Animais , Fibrose Pulmonar/induzido quimicamente , Fibrose Pulmonar/metabolismo , Fibrose Pulmonar/tratamento farmacológico , Fibrose Pulmonar/genética , Bleomicina/efeitos adversos , Ratos , Medicamentos de Ervas Chinesas/administração & dosagem , Medicamentos de Ervas Chinesas/farmacologia , Masculino , Coagulação Sanguínea/efeitos dos fármacos , Pulmão/efeitos dos fármacos , Pulmão/metabolismo , Humanos , Actinas/metabolismo , Actinas/genética , Caderinas/genética , Caderinas/metabolismo , Colágeno Tipo I/metabolismo , Colágeno Tipo I/genética , Vimentina/metabolismo , Vimentina/genética , Injeções
2.
Biomolecules ; 14(9)2024 Sep 08.
Artigo em Inglês | MEDLINE | ID: mdl-39334901

RESUMO

Fine particulate matter (PM2.5) is a significant cause of respiratory diseases and associated cellular damage. The mechanisms behind this damage have not been fully explained. This study investigated two types of cellular damage (inflammation and pyroptosis) induced by PM2.5, focusing on their relationship with two organelles (the endoplasmic reticulum and mitochondria). Animal models have demonstrated that PM2.5 induces excessive endoplasmic reticulum stress (ER stress), which is a significant cause of lung damage in rats. This was confirmed by pretreatment with an ER stress inhibitor (4-Phenylbutyric acid, 4-PBA). We found that, in vitro, the intracellular Ca2+ ([Ca2+]i) dysregulation induced by PM2.5 in rat alveolar macrophages was associated with ER stress. Changes in mitochondria-associated membranes (MAMs) result in abnormal mitochondrial function. This further induced the massive expression of NLRP3 and GSDMD-N, which was detrimental to cell survival. In conclusion, our findings provide valuable insights into the relationship between [Ca2+]i dysregulation, mitochondrial damage, inflammation and pyroptosis under PM2.5-induced ER stress conditions. Their interactions ultimately have an impact on respiratory health.


Assuntos
Cálcio , Estresse do Retículo Endoplasmático , Retículo Endoplasmático , Lesão Pulmonar , Mitocôndrias , Material Particulado , Fenilbutiratos , Animais , Fenilbutiratos/farmacologia , Mitocôndrias/metabolismo , Mitocôndrias/efeitos dos fármacos , Cálcio/metabolismo , Ratos , Estresse do Retículo Endoplasmático/efeitos dos fármacos , Material Particulado/toxicidade , Retículo Endoplasmático/metabolismo , Retículo Endoplasmático/efeitos dos fármacos , Lesão Pulmonar/metabolismo , Lesão Pulmonar/induzido quimicamente , Lesão Pulmonar/patologia , Macrófagos Alveolares/metabolismo , Macrófagos Alveolares/efeitos dos fármacos , Masculino , Piroptose/efeitos dos fármacos , Ratos Sprague-Dawley , Proteína 3 que Contém Domínio de Pirina da Família NLR/metabolismo
3.
Microorganisms ; 12(8)2024 Jul 24.
Artigo em Inglês | MEDLINE | ID: mdl-39203356

RESUMO

Sulfide is a toxic and hazardous substance in the agricultural environment, which can cause damage to humans and livestock when exposed to large amounts of air. In this study, we performed one-factor optimization of the culture conditions and culture fractions of the Cellulosimicrobium sp. strain L1 and combined it with a biological trickling filter cell for the degradation of hydrogen sulfide for 24 consecutive days. The degradation effect of strain L1 and the biological trickling filter (BTF) on hydrogen sulfide was investigated, and the changes in intermediate products in the degradation process were briefly analyzed. The results showed that strain L1 had the highest conversion efficiency when incubated with 3 g/L sucrose as the carbon source and 1 g/L NH4Cl as the nitrogen source at a temperature of 35 °C, an initial pH of 5, and a NaCl concentration of 1%. The concentration of thiosulfate increased and then decreased during the degradation process, and the concentration of sulfate increased continuously. When strain L1 was applied to the biological trickling filter, it could degrade 359.53 mg/m3 of H2S. This study provides a deeper understanding of sulfide degradation in biological trickling filters and helps promote the development of desulfurization technology and the treatment of malodorous gasses produced by the accumulation of large quantities of livestock manure.

4.
BMC Microbiol ; 24(1): 301, 2024 Aug 12.
Artigo em Inglês | MEDLINE | ID: mdl-39134942

RESUMO

BACKGROUND: Penicillium oxalicum is an important fungal agent in the composting of cattle manure, but the changes that occur in the microbial community, physicochemical factors, and potential functions of microorganisms at different time points are still unclear. To this end, the dynamic changes occurring in the microbial community and physicochemical factors and their correlations during the composting of cattle manure with Penicillium oxalicum were analysed. RESULTS: The results showed that the main phyla observed throughout the study period were Firmicutes, Actinobacteria, Proteobacteria, Bacteroidetes, Halanaerobiaeota, Apicomplexa and Ascomycota. Linear discriminant analysis effect size (LEfSe) illustrated that Chitinophagales and Eurotiomycetes were biomarker species of bacteria and eukaryote in samples from Days 40 and 35, respectively. Bacterial community composition was significantly correlated with temperature and pH, and eukaryotic microorganism community composition was significantly correlated with moisture content and NH4+-N according to redundancy analysis (RDA). The diversity of the microbial communities changed significantly, especially that of the main pathogenic microorganisms, which showed a decreasing trend or even disappeared after composting. CONCLUSIONS: In conclusion, a combination of high-throughput sequencing and physicochemical analysis was used to identify the drivers of microbial community succession and the composition of functional microbiota during cattle manure composting with Penicillium oxalicum. The results offer a theoretical framework for explaining microecological assembly during cattle manure composting with Penicillium oxalicum.


Assuntos
Bactérias , Compostagem , Esterco , Microbiota , Penicillium , Animais , Penicillium/metabolismo , Bovinos , Esterco/microbiologia , Esterco/análise , Bactérias/classificação , Bactérias/genética , Bactérias/metabolismo , Bactérias/isolamento & purificação , Temperatura , Microbiologia do Solo , Sequenciamento de Nucleotídeos em Larga Escala , Concentração de Íons de Hidrogênio , Biodiversidade , RNA Ribossômico 16S/genética
5.
Toxics ; 12(6)2024 May 25.
Artigo em Inglês | MEDLINE | ID: mdl-38922066

RESUMO

It is well known that Particulate Matter2.5 (PM2.5) has a major adverse effect on the organism. However, the health hazards of livestock farm PM2.5 to humans and animals are not yet known, and the role of miRNAs in the cellular damage induced by livestock farm PM2.5 is also unclear. Therefore, our study used cowshed PM2.5 to stimulate rat alveolar macrophage NR8383 to construct an in vitro injury model to investigate the effect of miR-122-5p on PM2.5-induced apoptosis in the NR8383. The level of apoptosis was quantified by flow cytometry and Hoechst 33342/PI double staining. Furthermore, the potential target gene Collagen type IV alpha (COL4A1) of miR-122-5p was identified through the use of bioinformatics methods. The results demonstrated a decline in cell viability and an increase in apoptosis with rising PM2.5 concentrations and exposure durations. The transfection of miR-122-5p mimics resulted in an upregulation of the pro-apoptotic protein Bcl-xL/Bcl-2 and activation of cleaved caspase-3 while inhibiting the anti-apoptotic protein B-cell lymphoma-2. The experimental data indicate that miR-122-5p is involved in the apoptotic process by targeting COL4A1. Furthermore, the overexpression of COL4A1 was observed to enhance the PM2.5-activated PI3K/AKT/NF-κB signaling pathway, which contributed to the inhibition of apoptosis. This finding offers a promising avenue for the development of therapeutic strategies aimed at mitigating cellular damage induced by PM2.5 exposure.

6.
Int J Mol Sci ; 25(11)2024 May 24.
Artigo em Inglês | MEDLINE | ID: mdl-38891899

RESUMO

In aquaculture, viral diseases pose a significant threat and can lead to substantial economic losses. The primary defense against viral invasion is the innate immune system, with interferons (IFNs) playing a crucial role in mediating the immune response. With advancements in molecular biology, the role of non-coding RNA (ncRNA), particularly microRNAs (miRNAs), in gene expression has gained increasing attention. While the function of miRNAs in regulating the host immune response has been extensively studied, research on their immunomodulatory effects in teleost fish, including silver carp (Hyphthalmichthys molitrix), is limited. Therefore, this research aimed to investigate the immunomodulatory role of microRNA-30b-5p (miR-30b-5p) in the antiviral immune response of silver carp (Hypophthalmichthys molitrix) by targeting cytokine receptor family B5 (CRFB5) via the JAK/STAT signaling pathway. In this study, silver carp were stimulated with polyinosinic-polycytidylic acid (poly (I:C)), resulting in the identification of an up-regulated miRNA (miR-30b-5p). Through a dual luciferase assay, it was demonstrated that CRFB5, a receptor shared by fish type I interferon, is a novel target of miR-30b-5p. Furthermore, it was found that miR-30b-5p can suppress post-transcriptional CRFB5 expression. Importantly, this study revealed for the first time that miR-30b-5p negatively regulates the JAK/STAT signaling pathway, thereby mediating the antiviral immune response in silver carp by targeting CRFB5 and maintaining immune system stability. These findings not only contribute to the understanding of how miRNAs act as negative feedback regulators in teleost fish antiviral immunity but also suggest their potential therapeutic measures to prevent an excessive immune response.


Assuntos
Carpas , Proteínas de Peixes , MicroRNAs , Poli I-C , Transdução de Sinais , Animais , Carpas/genética , Carpas/imunologia , Carpas/virologia , Carpas/metabolismo , Doenças dos Peixes/imunologia , Doenças dos Peixes/virologia , Doenças dos Peixes/genética , Proteínas de Peixes/genética , Proteínas de Peixes/metabolismo , Regulação da Expressão Gênica/efeitos dos fármacos , Imunidade Inata/genética , Janus Quinases/metabolismo , MicroRNAs/genética , MicroRNAs/metabolismo , Poli I-C/farmacologia , Fatores de Transcrição STAT/metabolismo , Fatores de Transcrição STAT/genética
7.
Biomolecules ; 14(6)2024 Jun 14.
Artigo em Inglês | MEDLINE | ID: mdl-38927097

RESUMO

MicroRNAs (miRNAs) are highly conserved endogenous single-stranded non-coding RNA molecules that play a crucial role in regulating gene expression to maintain normal physiological functions in fish. Nevertheless, the specific physiological role of miRNAs in lower vertebrates, particularly in comparison to mammals, remains elusive. Additionally, the mechanisms underlying the control of antiviral responses triggered by viral stimulation in fish are still not fully understood. In this study, we investigated the regulatory impact of miR-1388 on the signaling pathway mediated by IFN regulatory factor 3 (IRF3). Our findings revealed that following stimulation with the viral analog poly(I:C), the expression of miR-1388 was significantly upregulated in primary immune tissues and macrophages. Through a dual luciferase reporter assay, we corroborated a direct targeting relationship between miR-1388 and tumor necrosis factor receptor (TNFR)-associated factor 3 (TRAF3). Furthermore, our study demonstrated a distinct negative post-transcriptional correlation between miR-1388 and TRAF3. We observed a significant negative post-transcriptional regulatory association between miR-1388 and the levels of antiviral genes following poly(I:C) stimulation. Utilizing reporter plasmids, we elucidated the role of miR-1388 in the antiviral signaling pathway activated by TRAF3. By intervening with siRNA-TRAF3, we validated that miR-1388 regulates the expression of antiviral genes and the production of type I interferons (IFN-Is) through its interaction with TRAF3. Collectively, our experiments highlight the regulatory influence of miR-1388 on the IRF3-mediated signaling pathway by targeting TRAF3 post poly(I:C) stimulation. These findings provide compelling evidence for enhancing our understanding of the mechanisms through which fish miRNAs participate in immune responses.


Assuntos
Carpas , MicroRNAs , Poli I-C , Fator 3 Associado a Receptor de TNF , Animais , MicroRNAs/genética , MicroRNAs/metabolismo , Poli I-C/farmacologia , Carpas/genética , Carpas/metabolismo , Carpas/virologia , Fator 3 Associado a Receptor de TNF/genética , Fator 3 Associado a Receptor de TNF/metabolismo , Regulação para Baixo/efeitos dos fármacos , Regulação para Baixo/genética , Fator Regulador 3 de Interferon/metabolismo , Fator Regulador 3 de Interferon/genética , Regulação da Expressão Gênica/efeitos dos fármacos , Proteínas de Peixes/genética , Proteínas de Peixes/metabolismo , Transdução de Sinais
8.
Toxicol Appl Pharmacol ; 487: 116976, 2024 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-38777097

RESUMO

Staff and animals in livestock buildings are constantly exposed to fine particulate matter (PM2.5), which affects their respiratory health. However, its exact pathogenic mechanism remains unclear. Regulator of G-protein signaling 2 (RGS2) has been reported to play a regulatory role in pneumonia. The aim of this study was to explore the therapeutic potential of RGS2 in cowshed PM2.5-induced respiratory damage. PM2.5 was collected from a cattle farm, and the alveolar macrophages (NR8383) of the model animal rat were stimulated with different treatment conditions of cowshed PM2.5. The RGS2 overexpression vector was constructed and transfected it into cells. Compared with the control group, cowshed PM2.5 significantly induced a decrease in cell viability and increased the levels of apoptosis and proinflammatory factor expression. Overexpression of RGS2 ameliorated the above-mentioned cellular changes induced by cowshed PM2.5. In addition, PM2.5 has significantly induced intracellular Ca2+ dysregulation. Affinity inhibition of Gq/11 by RGS2 attenuated the cytosolic calcium signaling pathway mediated by PLCß/IP3R. To further investigate the causes and mechanisms of action of differential RGS2 expression, the possible effects of oxidative stress and TLR2/4 activation were investigated. The results have shown that RGS2 expression was not only regulated by oxidative stress-induced nitric oxide during cowshed PM2.5 cells stimulation but the activation of TLR2/4 had also an important inhibitory effect on its protein expression. The present study demonstrates the intracellular Ca2+ regulatory role of RGS2 during cellular injury, which could be a potential target for the prevention and treatment of PM2.5-induced respiratory injury.


Assuntos
Macrófagos Alveolares , Material Particulado , Proteínas RGS , Receptor 2 Toll-Like , Receptor 4 Toll-Like , Animais , Proteínas RGS/genética , Proteínas RGS/metabolismo , Material Particulado/toxicidade , Receptor 4 Toll-Like/metabolismo , Receptor 4 Toll-Like/genética , Ratos , Macrófagos Alveolares/efeitos dos fármacos , Macrófagos Alveolares/metabolismo , Bovinos , Receptor 2 Toll-Like/metabolismo , Receptor 2 Toll-Like/genética , Subunidades alfa Gq-G11 de Proteínas de Ligação ao GTP/metabolismo , Subunidades alfa Gq-G11 de Proteínas de Ligação ao GTP/genética , Linhagem Celular , Sinalização do Cálcio/efeitos dos fármacos , Cálcio/metabolismo , Apoptose/efeitos dos fármacos , Poluentes Atmosféricos/toxicidade
9.
PLoS One ; 19(5): e0304113, 2024.
Artigo em Inglês | MEDLINE | ID: mdl-38820335

RESUMO

Microbial degradation of tylosin (TYL) is a safe and environmentally friendly technology for remediating environmental pollution. Kurthia gibsonii (TYL-A1) and Klebsiella pneumonia (TYL-B2) were isolated from wastewater; degradation efficiency of the two strains combined was significantly greater than either alone and resulted in degradation products that were less toxic than TYL. With Polyvinyl alcohol (PVA)-sodium alginate (SA)-activated carbon (AC) used to form a bacterial immobilization carrier, the immobilized bacterial alliance reached 95.9% degradation efficiency in 1 d and could be reused for four cycles, with > 93% degradation efficiency per cycle. In a wastewater application, the immobilized bacterial alliance degraded 67.0% TYL in 9 d. There were significant advantages for the immobilized bacterial alliance at pH 5 or 9, with 20 or 40 g/L NaCl, or with 10 or 50 mg/L doxycycline. In summary, in this study, a bacterial consortium with TYL degradation ability was constructed using PVA-SA-AC as an immobilized carrier, and the application effect was evaluated on farm wastewater with a view to providing application guidance in environmental remediation.


Assuntos
Biodegradação Ambiental , Células Imobilizadas , Álcool de Polivinil , Tilosina , Águas Residuárias , Águas Residuárias/química , Águas Residuárias/microbiologia , Álcool de Polivinil/química , Células Imobilizadas/metabolismo , Alginatos/química , Alginatos/metabolismo , Poluentes Químicos da Água/metabolismo , Klebsiella pneumoniae/metabolismo , Antibacterianos , Carvão Vegetal/química
10.
Ecotoxicol Environ Saf ; 278: 116381, 2024 Jun 15.
Artigo em Inglês | MEDLINE | ID: mdl-38676963

RESUMO

Bioaerosols produced during animal production have potential adverse effects on the health of workers and animals. Our objective was to investigate characteristics, antibiotic-resistance genes (ARGs), and health risks of bioaerosols in various animal barns. Poultry and swine barns had high concentrations of airborne bacteria (11156 and 10917 CFU/m3, respectively). Acinetobacter, Clostridium sensu stricto, Corynebacterium, Pseudomonas, Psychrobacter, Streptococcus, and Staphylococcus were dominant pathogenic bacteria in animal barns, with Firmicutes being the most abundant bacterial phylum. Based on linear discriminant analysis effect size (LEfSe), there were more discriminative biomarkers in cattle barns than in poultry or swine barns, although the latter had the highest abundance of bacterial pathogens and high abundances of ARGs (including tetM, tetO, tetQ, tetW sul1, sul2, ermA, ermB) and intI1). Based on network analyses, there were higher co-occurrence patterns between bacteria and ARGs in bioaerosol from swine barns. Furthermore, in these barns, relative abundance of bacteria in bioaerosol samples was greatly affected by environmental factors, mainly temperature, relative humidity, and concentrations of CO2, NH3, and PM2.5. This study provided novel data regarding airborne bio-contaminants in animal enclosures and an impetus to improve management to reduce potential health impacts on humans and animals.


Assuntos
Aerossóis , Microbiologia do Ar , Bactérias , Animais , Aerossóis/análise , Suínos , Bactérias/isolamento & purificação , Bactérias/classificação , Bactérias/genética , Bovinos , Monitoramento Ambiental , Criação de Animais Domésticos , Aves Domésticas , Abrigo para Animais , Humanos , Material Particulado/análise , Resistência Microbiana a Medicamentos/genética , Poluição do Ar em Ambientes Fechados/análise
11.
Toxicology ; 504: 153797, 2024 May.
Artigo em Inglês | MEDLINE | ID: mdl-38583737

RESUMO

Particulate matter 2.5 (PM2.5) is a highly hazardous airborne particulate matter that poses a significant risk to humans and animals. Urban airborne particulate matter contributes to the increased incidence and mortality of respiratory diseases, such as asthma and chronic obstructive pulmonary disease (COPD), in humans. However, the specific mechanism by which PM2.5 affects animals in barn environments is yet to be elucidated. In this study, we investigated the effect of exposure to cow barn PM2.5 on rat alveolar macrophages (NR8383) and found that it induced apoptosis via the miR-212-5p/RASSF1 pathway. We found that lnc-Clic5 expression was downregulated in NR8383 cells exposed to cow barn PM2.5. Lnc-Clic5 plays a competitive endogenous RNA (ceRNA) regulatory role by sponging miR-212-5p to attenuate the regulation of RASSF1. Moreover, lnc-Clic5 overexpression inhibited NR8383 apoptosis by targeting the miR-212-5p/RASSF1 pathway. Co-treatment with miR-212-5p and lnc-Clic5 in the presence of cow barn PM2.5 revealed that lnc-Clic5 reversed NR8383 cell apoptosis induced by PM2.5 when miR-212-5p was overexpressed. These findings contribute to the study of ncRNAs and ceRNAs regulating PM2.5-induced apoptosis in animal farms, provide therapeutic targets for lung macrophage apoptosis, and may be useful for further evaluating the toxicological effects of PM2.5 in farmhouses on the respiratory systems of humans and animals.


Assuntos
Apoptose , Macrófagos Alveolares , MicroRNAs , Material Particulado , Animais , MicroRNAs/genética , MicroRNAs/metabolismo , Macrófagos Alveolares/efeitos dos fármacos , Macrófagos Alveolares/metabolismo , Apoptose/efeitos dos fármacos , Ratos , Material Particulado/toxicidade , Bovinos , Linhagem Celular , RNA Longo não Codificante/genética , RNA Longo não Codificante/metabolismo , Poluentes Atmosféricos/toxicidade
12.
Animals (Basel) ; 14(2)2024 Jan 17.
Artigo em Inglês | MEDLINE | ID: mdl-38254454

RESUMO

The ubiquitous Gram-negative bacterial pathogen Aeromonas veronii (A. veronii) can easily cause inflammatory reactions in aquatic organisms, resulting in high mortality and huge economic losses. MicroRNAs (miRNAs) participate in immune regulation and have certain conserved properties. MiRNAs are involved in the immune responses of a variety of teleost fish infected with bacteria, whereas there is no related report in silver carp (Hypophthalmichthys molitrix). Therefore, we identified the expression profiles of miRNA in silver carp stimulated by A. veronii and LPS. Among them, the quantity of differentially expressed miRNAs (DEmiRNAs) obtained in the silver carp challenge group was 73 (A. veronii) and 90 (LPS). The GO enrichment and analysis of KEGG pathways have shown that the predicted target genes are mainly associated with lipid metabolism and the immune response in silver carp. This indicates the possibility that miRNAs play a role in regulating immune-related pathways. In addition, a total of eight DEmiRNAs validated the accuracy of the sequencing result via quantitative real-time PCR (qRT-PCR). Finally, we selected the silver carp head kidney macrophage cells (HKCs) as model cells and proved that miR-30b-5p can regulate the inflammatory response in silver carp HKCs. This study lays the foundation for exploring miRNA regulation in silver carp during pathogenic bacterial infection. In addition, it provides a reference for the future development of non-coding RNA antibacterial drugs.

13.
Drug Des Devel Ther ; 17: 3723-3748, 2023.
Artigo em Inglês | MEDLINE | ID: mdl-38107658

RESUMO

Purpose: This study aimed to investigate the main pharmacological action and underlying mechanisms of Jin Gu Lian Capsule (JGL) against rheumatoid arthritis (RA) based on network pharmacology and experimental verification. Methods: Network pharmacology approaches were performed to explore the core active compounds of JGL, key therapeutic targets, and signaling pathways. Molecular docking was used to predict the binding affinity of compounds with targets. In vivo experiments were undertaken to validate the findings from network analysis. Results: A total of 52 targets were identified as candidate JGL targets for RA. Sixteen ingredients were identified as the core active compounds, including, quercetin, myricetin, salidroside, etc. Interleukin-1 beta (IL1B), transcription factor AP-1 (JUN), growth-regulated alpha protein (CXCL1), C-X-C motif chemokine (CXCL)3, CXCL2, signal transducer and activator of transcription 1 (STAT1), prostaglandin G/H synthase 2 (PTGS2), matrix metalloproteinase (MMP)1, inhibitor of nuclear factor kappa-B kinase subunit beta (IKBKB) and transcription factor p65 (RELA) were obtained as the key therapeutic targets. Gene Ontology and Kyoto Encyclopedia of Genes and Genomes pathway enrichment analysis showed that the efficacy of JGL was functionally involved in regulating immune-mediated inflammation, in which IL-17/NF-κB signaling was recommended as one of the main pathways. Molecular docking suggested that the core active compounds bound strongly to their respective targets. Experimentally, JGL treatment mitigated inflammation, showed analgesic activity, and ameliorated collagen-induced arthritis. Enzyme-linked immunosorbent assay showed that JGL effectively reduced the serum levels of cytokines, chemokines, and MMPs. Immunohistochemistry staining showed that JGL markedly reduced the expression of the targets in IL-17/NF-κB pathway including IL-17A, IL-17RA, NF-κB p65, C-X-C motif ligand 2, MMP1 and MMP13. Conclusion: This investigation provided evidence that JGL may alleviate RA symptoms by partially inhibiting the immune-mediated inflammation via IL-17/NF-κB pathway.


Assuntos
Artrite Reumatoide , Medicamentos de Ervas Chinesas , Humanos , NF-kappa B , Fator de Transcrição RelA , Interleucina-17 , Simulação de Acoplamento Molecular , Farmacologia em Rede , Artrite Reumatoide/tratamento farmacológico , Inflamação/tratamento farmacológico , Medicamentos de Ervas Chinesas/farmacologia
14.
Toxics ; 11(12)2023 Dec 03.
Artigo em Inglês | MEDLINE | ID: mdl-38133382

RESUMO

Objective: To investigate the role of miR-212-5p-targeted ARAF during the apoptosis of rat alveolar macrophages induced by cowshed PM2.5. Methods: miRNA and related target genes and pathways were predicted using the KEGG, TargetScan, and other prediction websites. NR8383 macrophages were treated with cowshed PM2.5 to establish an in vitro lung injury model in rats; meanwhile, for the assessment of cell viability, apoptosis, intracellular calcium ions, and mitochondrial membrane potential in NR8383 cells, RT-qPCR was used to detect the expression of miR-212-5p and the target gene ARAF. Results: The bioinformatic analyses showed that miR-212-5p and ARAF were involved in PM2.5-associated cellular damage. Exposure to different concentrations (0 µg/mL, 60 µg/mL, 180 µg/mL, 300 µg/mL) with different durations (0 h, 12 h, 24 h, 48 h) of cowshed PM2.5 resulted in apoptosis, increased intracellular calcium ions, and decreased mitochondrial membrane potential. The miR-212-5p mimic group showed an up-regulation of Bax and cleaved Caspase 3 expression but decreased Bcl2 expression compared to the NC group, and overexpression of ARAF up-regulated the expression of p-MEK1/2 and p-ERK1/2 and simultaneously reversed the above phenomena. Conclusions: miR-212-5p targets ARAF to affect the cowshed PM2.5-induced apoptosis through the MEK/ERK signaling pathway, providing a potential target for relevant farming industry and pathology studies.

15.
BMC Biotechnol ; 23(1): 48, 2023 11 03.
Artigo em Inglês | MEDLINE | ID: mdl-37924095

RESUMO

BACKGROUND: A lot of kitchen waste oil is produced every day worldwide, leading to serious environmental pollution. As one of the environmental protection methods, microorganisms are widely used treating of various wastes. Lipase, as one of the cleaning agents can effectively degrade kitchen waste oil. The composting process of pig carcasses produces many lipase producing microorganisms, rendering compost products an excellent source for isolating lipase producing microorganisms. To our knowledge, there are no reports isolating of lipase producing strains from the high temperature phase of pig carcass compost. METHODOLOGY: Lipase producing strains were isolated using a triglyceride medium and identified by 16S rRNA gene sequencing. The optimal fermentation conditions for maximum lipase yield were gradually optimized by single-factor tests. The extracellular lipase was purified by ammonium sulfate precipitation and Sephadex G-75 gel isolation chromatography. Amino acid sequence analysis, structure prediction, and molecular docking of the purified protein were performed. The pure lipase's enzymatic properties and application potential were evaluated by characterizing its biochemical properties. RESULTS: In this study, a lipase producing strain of Bacillus sp. ZF2 was isolated from pig carcass compost products, the optimal fermentation conditions of lipase: sucrose 3 g/L, ammonium sulfate 7 g/L, Mn2+ 1.0 mmol/L, initial pH 6, inoculum 5%, temperature 25 ℃, and fermentation time 48 h. After purification, the specific activity of the purified lipase reached 317.59 U/mg, a 9.78-fold improvement. Lipase had the highest similarity to the GH family 46 chitosanase and molecular docking showed that lipase binds to fat via two hydrogen bonds at Gln146 (A) and Glu203 (A). Under different conditions (temperature, metal ions, organic solvents, and surfactants), lipase can maintain enzymatic activity. Under different types of kitchen oils, lipase has low activity only for 'chicken oil', in treating other substrates, the enzyme activity can exceed 50%. CONCLUSIONS: This study reveals the potential of lipase for waste oil removal, and future research will be devoted to the application of lipase.


Assuntos
Compostagem , Suínos , Animais , Sulfato de Amônio , RNA Ribossômico 16S/genética , Simulação de Acoplamento Molecular , Concentração de Íons de Hidrogênio , Lipase/química , Temperatura
16.
PLoS One ; 18(10): e0291955, 2023.
Artigo em Inglês | MEDLINE | ID: mdl-37824519

RESUMO

In geese breeding, due to the frequent influence of drugs and environmental and other factors, geese are extremely prone to oxidative stress, which adversely affects growth and development, geese meat quality, down production, and severely affects the development of the geese industry. Ferulic acid from plant extracts can be used as a feed additive, which is safe and non-toxic, and it can exert certain therapeutic effects on oxidative stress in geese. This experiment investigated the effect of ferulic acid on the growth performance, organs indices, and intestinal oxidative indices of Jilin white geese under lipopolysaccharide-induced oxidative stress. Geese were randomly divided into six groups: C (blank control), L (lipopolysaccharide control), F1 (60 mg/kg ferulic acid), F2 (120 mg/kg ferulic acid), F3 (180 mg/kg ferulic acid), and F4 (240 mg/kg ferulic acid). Groups L and F1-F4 were injected intraperitoneally with 0.5 mg/kg lipopolysaccharide and group C with an equivalent volume of normal saline on days 14,17 and 20, and 10 animals from each group were randomly selected for slaughter on day 21. The results showed that: 1) On day 14, the final body weight and average daily feed intake were significantly higher in group F3 than in group L, and on day 21, the final body weight was significantly higher in group F3 than in group L. 2) The thymus index was significantly higher in group F4 than in group L. 4) In the duodenum, MDA activity was reduced in group C compared with that in group L. 5) In the jejunum and ileum, MDA was significantly lower in group F3 than in group L. These results show that the addition of 180 mg/kg of ferulic acid to the diet can promote the growth of geese and alleviate the damage caused by oxidative stress in all intestinal segments.


Assuntos
Gansos , Lipopolissacarídeos , Animais , Ração Animal/análise , Peso Corporal , Dieta , Estresse Oxidativo , Melhoramento Vegetal
17.
Microb Cell Fact ; 22(1): 116, 2023 Jun 27.
Artigo em Inglês | MEDLINE | ID: mdl-37370116

RESUMO

BACKGROUND: 17ß-estradiol (E2) residues exhibit harmful effects both for human and animals and have got global attention of the scientific community. Microbial enzymes are considered as one of the effective strategies having great potential for removal E2 residues from the environment. However, limited literature is available on the removal of E2 from wastewater using short-chain dehydrogenase. RESULTS: In this study, 17ß-estradiol degrading enzyme (17ß-HSD-0095) was expressed and purified from Microbacterium sp. MZT7. The optimal pH and temperature for reaction was 7 and 40 °C, respectively. Molecular docking studies have shown that the ARG215 residue form a hydrogen bond with oxygen atom of the substrate E2. Likewise, the point mutation results have revealed that the ARG215 residue play an important role in the E2 degradation by 17ß-HSD-0095. In addition, 17ß-HSD-0095 could remediate E2 contamination in synthetic livestock wastewater. CONCLUSIONS: These findings offer some fresh perspectives on the molecular process of E2 degradation and the creation of enzyme preparations that can degrade E2.


Assuntos
Microbacterium , Águas Residuárias , Animais , Humanos , Microbacterium/metabolismo , Simulação de Acoplamento Molecular , Estradiol/metabolismo
18.
Int J Mol Sci ; 24(10)2023 May 22.
Artigo em Inglês | MEDLINE | ID: mdl-37240435

RESUMO

Antibiotic tolerance has become an increasingly serious crisis that has seriously threatened global public health. However, little is known about the exogenous factors that can trigger the development of antibiotic tolerance, both in vivo and in vitro. Herein, we found that the addition of citric acid, which is used in many fields, obviously weakened the bactericidal activity of antibiotics against various bacterial pathogens. This mechanistic study shows that citric acid activated the glyoxylate cycle by inhibiting ATP production in bacteria, reduced cell respiration levels, and inhibited the bacterial tricarboxylic acid cycle (TCA cycle). In addition, citric acid reduced the oxidative stress ability of bacteria, which led to an imbalance in the bacterial oxidation-antioxidant system. These effects together induced the bacteria to produce antibiotic tolerance. Surprisingly, the addition of succinic acid and xanthine could reverse the antibiotic tolerance induced by citric acid in vitro and in animal infection models. In conclusion, these findings provide new insights into the potential risks of citric acid usage and the relationship between antibiotic tolerance and bacterial metabolism.


Assuntos
Antibacterianos , Estresse Oxidativo , Animais , Antibacterianos/farmacologia , Bactérias , Ciclo do Ácido Cítrico
19.
Front Pharmacol ; 14: 1133982, 2023.
Artigo em Inglês | MEDLINE | ID: mdl-36874008

RESUMO

Background: A. chinense frequently used in Miao medicine to treat rheumatic diseases. However, as a famous toxic herb, Alangium chinense and its representative components exhibit ineluctable neurotoxicity, thus creating significant challenges for clinical application. The combined application with compatible herbs in Jin-Gu-Lian formula attenuates such neurotoxicity according to the compatible principle of traditional Chinese medicines. Purpose: We aimed to investigate the detoxification of the compatible herbs in Jin-Gu-Lian formula on A. chinense-induced neurotoxicity and investigate its mechanism. Methods: Neurobehavioral and pathohistological analysis were used to determine the neurotoxicity in rats administered with A. chinense extract (AC), extract of compatible herbs in Jin-Gu-Lian formula (CH) and combination of AC with CH for 14 days. The mechanism underlying the reduction of toxicity by combination with CH was assessed by enzyme-linked immunosorbent assays, spectrophotometric assays, liquid chromatography tandem-mass spectrometry and real-time reverse transcription-quantitative polymerase chain reaction. Results: Compatible herbs attenuated the AC-induced neurotoxicity as evidenced by increased locomotor activity, enhanced grip strength, the decreased frequency of AC-induced morphological damage in neurons, as well as a reduction of neuron-specific enolase (NSE) and neurofilament light chain (NEFL) levels. The combination of AC and CH ameliorated AC-induced oxidative damage by modulating the activities of superoxide dismutase (SOD) and glutathione peroxidase (GSH-Px), and total antioxidant capacity (T-AOC). AC treatment significantly reduced the levels of monoamine and acetylcholine neurotransmitters in the brains of rats, including acetylcholine (Ach), dopamine (DA), 3,4-dihydroxyphenylacetic acid (DOPAC), homovanillic acid (HVA), norepinephrine (NE), and serotonin (5-HT). Combined AC and CH treatment regulated the abnormal concentrations and metabolisms of neurotransmitters. Pharmacokinetic studies showed that the co-administration of AC and CH significantly decreased plasma exposure levels of two main components of AC, as evidenced by the reduction of maximum plasma concentration (Cmax), area under the plasma concentration-time curve (AUC) compared to AC. In addition, the AC-induced downregulation in mRNA expression of cytochrome P450 enzymes was significantly reduced in response to combined AC and CH treatment. Conclusion: Compatible herbs in Jin-Gu-Lian formula alleviated the neurotoxicity induced by A. chinense by ameliorating oxidative damage, preventing abnormality of neurotransmitters and modulating pharmacokinetics.

20.
BMC Complement Med Ther ; 23(1): 62, 2023 Feb 21.
Artigo em Inglês | MEDLINE | ID: mdl-36810081

RESUMO

BACKGROUND: Systemic sclerosis (SSc; also known as "scleroderma") is an autoimmune disorder characterized by extensive fibrosis, vascular changes, and immunologic dysregulation. Baicalein (phenolic flavonoid derived from Scutellaria baicalensis Georgi) has been used to treat the pathological processes of various fibrotic and inflammatory diseases. In this study, we investigated the effect of baicalein on the major pathologic characteristics of SSc: fibrosis, B-cell abnormalities, and inflammation. METHODS: The effect of baicalein on collagen accumulation and expression of fibrogenic markers in human dermal fibroblasts were analyzed. SSc mice were produced by injecting bleomycin and treated with baicalein (25, 50, or 100 mg/kg). The antifibrotic features of baicalein and its mechanisms were investigated by histologic examination, hydroxyproline assay, enzyme-linked immunosorbent assay, western blotting and flow cytometry. RESULTS: Baicalein (5-120 µM) significantly inhibited the accumulation of the extracellular matrix and fibroblast activation in transforming growth factor (TGF)-ß1- and platelet derived growth factor (PDGF)-induced human dermal fibroblasts, as evidenced by abrogated deposition of total collagen, decreased secretion of soluble collagen, reduced collagen contraction capability and downregulation of various fibrogenesis molecules. In a bleomycin-induced model of dermal fibrosis in mice, baicalein (25-100 mg/kg) restored dermal architecture, ameliorated inflammatory infiltrates, and attenuated dermal thickness and collagen accumulation in a dose-dependent manner. According to flow cytometry, baicalein reduced the proportion of B cells (B220+ lymphocytes) and increased the proportion of memory B cells (B220+CD27+ lymphocytes) in the spleens of bleomycin-induced mice. Baicalein treatment potently attenuated serum levels of cytokines (interleukin (IL)-1ß, IL-2, IL-4, IL-6, IL-17A, tumor necrosis factor-α), chemokines (monocyte chemoattractant protein-1, macrophage inflammatory protein-1 beta) and autoantibodies (anti-scleroderma 70 (Scl-70), anti-polymyositis-scleroderma (PM-Scl), anti-centromeres, anti-double stranded DNA (dsDNA). In addition, baicalein treatment can significantly inhibit the activation of TGF-ß1 signaling in dermal fibroblasts and bleomycin-induce mice of SSc, evidenced by reducing the expression of TGF-ß1 and IL-11, as well as inhibiting both small mother against decapentaplegic homolog 3 (SMAD3) and extracellular signal-related kinase (ERK) activation. CONCLUSIONS: These findings suggest that baicalein has therapeutic potential against SSc, exerting modulating B-cell abnormalities, anti-inflammatory effects, and antifibrosis.


Assuntos
Linfócitos B , Flavanonas , Escleroderma Sistêmico , Animais , Humanos , Camundongos , Bleomicina/efeitos adversos , Colágeno/metabolismo , Fibrose , Inflamação , Escleroderma Sistêmico/tratamento farmacológico , Escleroderma Sistêmico/metabolismo , Fator de Crescimento Transformador beta1/metabolismo , Flavanonas/farmacologia , Linfócitos B/efeitos dos fármacos
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