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1.
Poult Sci ; 103(7): 103797, 2024 Apr 26.
Artigo em Inglês | MEDLINE | ID: mdl-38713990

RESUMO

Previous studies here have demonstrated that the rabbit sacculus rotundus-derived antimicrobial peptides (RSRP) could alter the intestinal mucosal immune responses in specific-pathogen-free (SPF) chickens, however, the protective effects of RSRP on chickens against infection remain questionable. In the present study, eighty SPF chickens were randomly divided into five groups and challenged with very virulent infectious bursal disease virus (vvIBDV) to determine the protective effects and its underlying mechanism of RSRP. Histopathology examination found that vvIBDV-infection caused severe damage in the bursa of Fabricius, especially the bursal lymphoid follicles underwent severe necrosis, depletion, hemorrhage, and edema. Unexpectedly, RSRP intervention significantly reduced the necrosis and depletion of lymphoid follicles in the vvIBDV-infected chickens. Moreover, RSRP treatment significantly decreased the expression of Bax (P < 0.01) as well as remarkably promoted the expression of Bcl-2 (P < 0.01), concomitantly alleviated the excessive apoptosis in the immune organs such as the bursa of Fabricius during vvIBDV infection. Notably, consistent with our previous reports that increased mast cell activation and degranulation in the bursa after vvIBDV infection, RSRP administration considerably reduced the mast cell density and the expression of tryptase, a marker for activated mast cells. Collectively, the present study indicates that rabbit sacculus rotundus-derived antimicrobial peptides could effectively protect the major immune organs including the bursa of Fabricius from the damage caused by vvIBDV infection, which provides the possibility and a promising perspective for the future application of antimicrobial peptides for poultry production.

2.
iScience ; 27(5): 109807, 2024 May 17.
Artigo em Inglês | MEDLINE | ID: mdl-38766355

RESUMO

Type I interferon (IFN) production is crucial in tuberculosis pathogenesis, yet the bacterial factors initiating this process are incompletely understood. CpsA, protein of Mycobacterium marinum and Mycobacterium tuberculosis, plays a key role in maintaining bacterial virulence and inhibiting host cell LC3-associated phagocytosis. By utilizing CpsA full deletion mutant studies, we re-verified its essential role in infection-induced pathology and revealed its new role in type I IFN expression. CpsA deficiency hindered IFN production in infected macrophages in vitro as well as zebrafish and mice in vivo. This effect was linked to the cGAS-TBK1-IRF3 pathway, as evidenced by decreased TBK1 and IRF3 phosphorylation in CpsA-deficient bacterial strain-infected macrophages. Moreover, we further show that CpsA deficiency cause decreased cytosolic DNA levels, correlating with impaired phagosomal membrane rupture. Our findings reveal a new function of mycobacterial CpsA in type I IFN production and offer insight into the molecular mechanisms underlying mycobacterial infection pathology.

3.
Nat Commun ; 15(1): 2471, 2024 Mar 19.
Artigo em Inglês | MEDLINE | ID: mdl-38503787

RESUMO

The development of neuromorphic visual systems has recently gained momentum due to their potential in areas such as autonomous vehicles and robotics. However, current machine visual systems based on silicon technology usually contain photosensor arrays, format conversion, memory and processing modules. As a result, the redundant data shuttling between each unit, resulting in large latency and high-power consumption, seriously limits the performance of neuromorphic vision chips. Here, we demonstrate an artificial neural network (ANN) architecture based on an integrated 2D MoS2/Ag nanograting phototransistor array, which can simultaneously sense, pre-process and recognize optical images without latency. The pre-processing function of the device under photoelectric synergy ensures considerable improvement of efficiency and accuracy of subsequent image recognition. The comprehensive performance of the proof-of-concept device demonstrates great potential for machine vision applications in terms of large dynamic range (180 dB), high speed (500 ns) and low energy consumption per spike (2.4 × 10-17 J).

4.
Front Microbiol ; 15: 1329521, 2024.
Artigo em Inglês | MEDLINE | ID: mdl-38486697

RESUMO

Background: Numerous investigations have underscored the causal effect between chronic pain (CP) and gut microbiota, jointly contributing to the onset and development of widespread CP. Nonetheless, there was still uncertainty about the causal effect between gut microbiota and chronic regional pain (CRP). Methods: Genome-wide association study (GWAS) summary data of gut microbial taxa (MiBioGen Consortium: 211 microbiotas and the Dutch Microbiome Project: 207 microbiotas) and eight types of CRP were used to reveal the causal effect between persistent pain in a specific region of the body and gut microbiota. A two-sample bidirectional Mendelian randomization (MR) design was used. In order to ensure the accuracy of the results, multiple sensitivity analyses were employed. Results: This study uncovered significant causal associations between six gut microbial taxa and three types of CRP (forward: Genus Parabacteroides for general pain; Class Bacteroidia, Order Bacteroidales, and Phylum Bacteroidetes for back pain. Reverse: knee pain for Genus Howardella and Order Coriobacteriales) by forward and reverse MR analysis. These findings had been verified by a rigorous Bonferroni correction. Furthermore, this research identified 19 microbial taxa that exhibited potential correlations with four types of CRP. There are no significant or potential gut microbiotas that were associated with other types of CRP, including fascial pain, stomach or abdominal pain, and hip pain. Conclusion: This two-sample bidirectional MR analysis unveiled the causality between gut microbial taxa and eight CRP conditions. The findings reveal the interplay between CRP and 6 gut microbiotas while also delineating 19 potential specific microbial taxa corresponding to diverse locations of persistent pain.

5.
6.
Gene ; 905: 148237, 2024 May 05.
Artigo em Inglês | MEDLINE | ID: mdl-38310983

RESUMO

Approximately a quarter of Retinitis Pigmentosa (RP) is caused by mutations in transport-related genes in cilia. IFT27 (Intraflagellar Transport 27), a core component of the ciliary intraflagellar transport (IFT) system, has been implicated as a significant pathogenic gene in RP. The pathogenic mechanisms and subsequent pathology related to IFT27 mutations in RP are largely obscure. Here, we utilized TALEN technology to create an ift27 knockout (ift27-/-) zebrafish model. Electroretinography (ERG) detection showed impaired vision in this model. Histopathological examinations disclosed that ift27 mutations cause progressive degeneration of photoreceptors in zebrafish, and this degeneration was late-onset. Immunofluorescence labeling of outer segments showed that rods degenerated before cones, aligning with the conventional characterization of RP. In cultured human retinal pigment epithelial cells, we found that IFT27 was involved in maintaining ciliary morphology. Furthermore, decreased IFT27 expression resulted in the inhibition of the Hedgehog (Hh) signaling pathway, including decreased expression of key factors in the Hh pathway and abnormal localization of the ciliary mediator Gli2. In summary, we generated an ift27-/- zebrafish line with retinal degeneration which mimicked the symptoms of RP patients, highlighting IFT27's integral role in the long-term maintenance of cilia via the Hh signaling pathway. This work may furnish new insights into the treatment or delay of RP caused by IFT27 mutations.


Assuntos
Retinose Pigmentar , Proteínas de Peixe-Zebra , Peixe-Zebra , Animais , Humanos , Transporte Biológico , Cílios/genética , Proteínas Hedgehog/genética , Proteínas Hedgehog/metabolismo , Retinose Pigmentar/genética , Retinose Pigmentar/patologia , Peixe-Zebra/genética , Peixe-Zebra/metabolismo , Proteínas de Peixe-Zebra/genética
7.
Virus Evol ; 10(1): veae016, 2024.
Artigo em Inglês | MEDLINE | ID: mdl-38404965

RESUMO

Porcine reproductive and respiratory syndrome virus (PRRSV) poses a serious threat to the pig industry in China. Our previous study demonstrated that PRRSV persists with local circulations and overseas imports in China and has formed a relatively stable epidemic pattern. However, the sudden African swine fever (ASF) outbreak in 2018 caused serious damage to China's pig industry structure, which resulted in about 40 per cent of pigs being slaughtered. The pig yields recovered by the end of 2019. Thus, whether the ASF outbreak reframed PRRSV evolution with changes in pig populations and further posed new threats to the pig industry becomes a matter of concern. For this purpose, we conducted genomic surveillance and recombination, NSP2 polymorphism, population dynamics, and geographical spread analysis of PRRSV-2, which is dominant in China. The results showed that the prevalence of ASF had no significant effects on genetic diversities like lineage composition, recombination patterns, and NSP2 insertion and deletion patterns but was likely to lead to changes in PRRSV-2 recombination frequency. As for circulation of the two major sub-lineages of Lineage 1, there was no apparent transmission of NADC30-like among provinces, while NADC34-like had obvious signs of inter-provincial transmission and foreign importation during the ASF epidemic. In addition, two suspected vaccine recombinant epidemic strains suggest a slight safety issue of vaccine use. Herein, the interference of ASF to the PRRSV-2 evolutionary pattern was evaluated and vaccine safety was analyzed, in order to monitor the potential threat of PRRSV-2 to China's pig industry in the post-epidemic era of ASF.

8.
iScience ; 27(3): 109204, 2024 Mar 15.
Artigo em Inglês | MEDLINE | ID: mdl-38420591

RESUMO

Pathogenic mycobacteria orchestrate the complex cell populations known as granuloma that is the hallmark of tuberculosis. Foam cells, a lipid-rich cell-type, are considered critical for granuloma formation; however, the causative factor in foam cell formation remains unclear. Atherosclerosis is a chronic inflammatory disease characterized by the abundant accumulation of lipid-laden-macrophage-derived foam cells during which cholesterol 25-hydroxylase (CH25H) is crucial in foam cell formation. Here, we show that M. marinum (Mm), a relative of M. tuberculosis, induces foam cell formation, leading to granuloma development following CH25H upregulation. Moreover, the Mm-driven increase in CH25H expression is associated with the presence of phthiocerol dimycocerosate, a determinant for Mm virulence and integrity. CH25H-null mice showed decreased foam cell formation and attenuated pathology. Atorvastatin, a recommended first-line lipid-lowering drug, promoted the elimination of M. marinum and concomitantly reduced CH25H production. These results define a previously unknown role for CH25H in controlling macrophage-derived foam cell formation and Tuberculosis pathology.

9.
Int Immunopharmacol ; 129: 111597, 2024 Mar 10.
Artigo em Inglês | MEDLINE | ID: mdl-38295543

RESUMO

Neutrophils are the most important innate immune cells in host defense against methicillin-resistant Staphylococcus aureus (MRSA). However, MRSA orchestrates precise and timely expression of a series of virulence factors, especially the chemotaxis inhibitory protein of Staphylococcus aureus (CHIPS), to evade neutrophil-mediated host defenses. Here, we demonstrated that tripterin, a plant-derived bioactive pentacyclic triterpenoid, had a low minimum inhibitory concentration (MIC) of 1.28 µg/mL and displayed excellent anti-MRSA activity in vitro and in vivo. RNA-seq and further knockdown experiments revealed that tripterin could dramatically downregulate the expression of CHIPS by regulating the SaeRS two-component regulatory system, thereby enhancing the chemotactic response of neutrophils. Furthermore, tripterin also displayed a potential inhibitory effect on biofilm components to enhance neutrophil infiltration into the interior of the biofilm. In a mouse bacteremia model, tripterin could still maintain an excellent therapeutic effect that was significantly better than that of the traditional antibiotic vancomycin. Overall, these results suggest that tripterin possesses a superior antibacterial activity via breaking CHIPS-mediated immune evasion to promote neutrophil chemotaxis, thus providing a novel strategy for combating serious pathogenic infections.


Assuntos
Staphylococcus aureus Resistente à Meticilina , Infecções Estafilocócicas , Animais , Camundongos , Staphylococcus aureus , Neutrófilos , Quimiotaxia , Evasão da Resposta Imune , Antibacterianos/farmacologia , Antibacterianos/uso terapêutico , Triterpenos Pentacíclicos/farmacologia , Triterpenos Pentacíclicos/uso terapêutico , Testes de Sensibilidade Microbiana
10.
Drug Chem Toxicol ; : 1-12, 2023 Dec 26.
Artigo em Inglês | MEDLINE | ID: mdl-38148561

RESUMO

Drug-induced liver injury (DILI) is characterized by hepatocyte injury, cholestasis injury, and mixed injury. The liver transplantation is required for serious clinical outcomes such as acute liver failure. Current studies have found that many mechanisms were involved in DILI, such as mitochondrial oxidative stress, apoptosis, necroptosis, autophagy, ferroptosis, etc. Ferroptosis occurs when hepatocytes die from iron-dependent lipid peroxidation and plays a key role in DILI. After entry into the liver, where some drugs or chemicals are metabolized, they convert into hepatotoxic substances, consume reduced glutathione (GSH), and decrease the reductive capacity of GSH-dependent GPX4, leading to redox imbalance in hepatocytes and increase of reactive oxygen species (ROS) and lipid peroxidation level, leading to the undermining of hepatocytes; some drugs facilitated the autophagy of ferritin, orchestrating the increased ion level and ferroptosis. The purpose of this review is to summarize the role of ferroptosis in chemical- or drug-induced liver injury (chemical/DILI) and how natural products inhibit ferroptosis to prevent chemical/DILI.

11.
Front Microbiol ; 14: 1290246, 2023.
Artigo em Inglês | MEDLINE | ID: mdl-37928686

RESUMO

Background and aim: Nutrient production by intestinal microbiota corresponds to regulate appetite while gut microbial composition was influenced by diet ingestion. However, the causal relationship between gut microbial taxa and anorexia nervosa (AN) remains unclear. Mendelian Randomization (MR) is a novel research method that effectively eliminates the interference of confounding factors and allows for the exploration of the direct causal effects between exposure and outcome. This study employs MR to explore the causal effect between AN and specific gut microbiome. Methods: Large-scale Genome Wide Association Study (GWAS) data of AN and 211 gut microbes were obtained from the IEU open GWAS project and Mibiogen Consortium. Two-sample MR was performed to determine the causal relationship between gut microbiota and AN. Furthermore, a bi-directional MR analysis was to examine the direction of the causal relations. The Bonferroni correction test was used to adjust potential correlations among microbial taxa. Result: In forward MR analysis, 10specific gut microbial taxa have an impact on the occurrence of AN (the p value of IVW <0.05). The high abundance of Genus Eubacteriumnodatumgroup ID: 11297 (OR:0.78, 95% CI:0.62-0.98, p = 0.035) and Class Melainabacteria ID: 1589 (OR:0.72, 95% CI:0.51-0.99, p = 0.045) may be considered protective factors for AN. But after Bonferroni correction, only Class Actinobacteria ID:419 (OR:1.53, 95% CI:1.19-1.96, p = 0.00089) remained significantly associated and high abundance of Class Actinobacteria ID:419 considered as a risk factor for AN. In the reverse MR analysis, AN influences 8 gut microbial taxa with none-statistically significant associations after adjustment. Conclusion: We identified a significant correlation between AN and 18 microbial taxa which have not been previously reported. Among them, 10 kinds of gut bacteria may affect the occurrence of AN, and the status of AN would affect 8 kinds of gut bacteria. After correction, the Class Actinobacteria ID:419 continued to exert an influence on AN.

12.
Front Microbiol ; 14: 1256874, 2023.
Artigo em Inglês | MEDLINE | ID: mdl-37920262

RESUMO

Background and aim: Previous studies have reported an association between gut microbiota and cirrhosis. However, the causality between intestinal flora and liver cirrhosis still remains unclear. In this study, bi-directional Mendelian randomization (MR) analysis was used to ascertain the potential causal effect between gut microbes and cirrhosis. Methods: Large-scale Genome Wide Association Study (GWAS) data of cirrhosis and gut microbes were obtained from FinnGen, Mibiogen consortium, and a GWAS meta-analysis of Alcoholic cirrhosis (ALC). Two-sample MR was performed to determine the causal relationship between gut microbiota and cirrhosis. Furthermore, a bi-directional MR analysis was employed to examine the direction of the causal relations. Result: In MR analysis, we found that 21 gut microbiotas were potentially associated with cirrhosis. In reverse MR analysis, 11 gut microbiotas displayed potentially associations between genetic liability in the gut microbiome and cirrhosis. We found that the family Lachnospiraceae (OR: 1.59, 95% CI:1.10-2.29) might be harmful in cirrhotic conditions (ICD-10: K74). Furthermore, the genus Erysipelatoclostridium might be a protective factor for cirrhosis (OR:0.55, 95% CI:0.34-0.88) and PBC (OR:0.68, 95% CI:0.52-0.89). Combining the results from the MR analysis and reverse MR analysis, we firstly identified the Genus Butyricicoccus had a bi-directional causal effect on PBC (Forward: OR: 0.37, 95% CI:0.15-0.93; Reverse: OR: 1.03, 95% CI:1.00-1.05). Conclusion: We found a new potential causal effect between cirrhosis and intestinal flora and provided new insights into the role of gut microbiota in the pathological progression of liver cirrhosis.

14.
Front Endocrinol (Lausanne) ; 14: 1251838, 2023.
Artigo em Inglês | MEDLINE | ID: mdl-37842299

RESUMO

Background: Osteoporosis (OP) is a systemic metabolic skeletal disorder characterized by a decrease in bone mineral density (BMD) and an increase in the risk of fracture. The level of selenium (Se) in serum is associated with BMD. However, the relationship between dietary and total selenium intake and parameters such as osteoporosis and BMD is unclear. By conducting National Health and Nutritional Examination Surveys (NHANES), in this study, we assessed the association of Se intake with BMD and the risk of OP among general middle-aged and elderly people. Methods: The data were collected from three cycles of NHANES [2009-2010, 2013-2014, and 2017-2020]. Information on the dietary and supplementary Se intake was obtained from 24-h dietary recall interviews. Additionally, dual-energy X-ray absorptiometry (DXA) was performed to measure BMD, which was later transformed into T-scores; OP was diagnosed when the T-score was ≤ -2.5. We constructed a logistic regression model for the association between selenium intake and the risk of OP based on the estimated odds ratios (ORs) and the 95% confidence intervals (CIs). We also constructed a multivariable linear regression model to analyze the relationship between selenium intake and BMD. Results: In this study, 3,250 individuals (average age: 60.01 ± 10.09 years; 51.88% females) participated. The incidence of OP was 9.35% (3.30% for males and 17.75% for females). In the logistic regression model adjusted for every interested covariate, a higher quartile of dietary Se intake (OR for quartile 4 vs. quartile 1: 0.63; 95% CI: 0.41-0.96; P for trend = 0.027) was related to a lower risk of OP relative to the lowest quartile. The total selenium intake also exhibited a consistent trend (OR for quartile 4 vs. quartile 1: 0.67; 95% CI: 0.44-1.01; P for trend = 0.049). The results of the adjusted multivariate linear regression model showed that the participants with the highest quartile of dietary Se intake (Q4) had higher BMD in the total femur (ß = 0.069, P = 0.001; P for trend = 0.001), femoral neck (ß = 0.064, P = 0.001; P for trend = 0.001), and total spine (ß = 0.030, P = 0.136; P for trend = 0.064) compared to those in quintile 1 (Q1). A similar trend of associations was observed for the total selenium intake with BMD, which was more prominent among females, as determined by the subgroup analysis. Conclusion: In this study, the dietary intake and total intake of selenium were positively associated with BMD, whereas they were negatively associated with the risk of OP among adults in the US. Further studies are required to verify our results and elucidate the associated biological mechanism.


Assuntos
Osteoporose , Selênio , Adulto , Idoso , Masculino , Pessoa de Meia-Idade , Feminino , Humanos , Densidade Óssea , Inquéritos Nutricionais , Osteoporose/epidemiologia , Osteoporose/etiologia , Estado Nutricional
15.
Front Endocrinol (Lausanne) ; 14: 1202463, 2023.
Artigo em Inglês | MEDLINE | ID: mdl-37600700

RESUMO

Neutrophil extracellular traps (NETs) are known as extracellular fibers networks consisting of antimicrobial proteins and decondensated chromatin DNA released by activated neutrophils. NETosis is a NETs-induced neutrophilic cell death which is unique from necrosis or apoptosis. Besides its neutralizing pathogen, NETosis plays a crucial role in diabetes and diabetes-related complications. In patients with diabetes, NETs-releasing products are significantly elevated in blood, and these findings confirm the association of NETosis and diabetic complications, including diabetic wound healing, diabetic retinopathy, and atherosclerosis. This article briefly summarizes the mechanisms of NETosis and discusses its contribution to the pathogenesis of diabetes-related complications and suggests new therapeutic targets by some small molecule compounds.


Assuntos
Aterosclerose , Diabetes Mellitus , Retinopatia Diabética , Armadilhas Extracelulares , Humanos , Neutrófilos , Apoptose , Diabetes Mellitus/etiologia
16.
Virol Sin ; 38(3): 363-372, 2023 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-37146717

RESUMO

Human respiratory syncytial virus (RSV) is a severe threat to children and a main cause of acute lower respiratory tract infections. Nevertheless, the intra-host evolution and inter-regional diffusion of RSV are little known. In this study, we performed a systematic surveillance in hospitalized children in Hubei during 2020-2021, in which 106 RSV-positive samples were detected both clinically and by metagenomic next generation sequencing (mNGS). RSV-A and RSV-B groups co-circulated during surveillance with RSV-B being predominant. About 46 high-quality genomes were used for further analyses. A total of 163 intra-host nucleotide variation (iSNV) sites distributed in 34 samples were detected, and glycoprotein (G) gene was the most enriched gene for iSNVs, with non-synonymous substitutions more than synonymous substitutions. Evolutionary dynamic analysis showed that the evolutionary rates of G and NS2 genes were higher, and the population size of RSV groups changed over time. We also found evidences of inter-regional diffusion from Europe and Oceania to Hubei for RSV-A and RSV-B, respectively. This study highlighted the intra-host and inter-host evolution of RSV, and provided some evidences for understanding the evolution of RSV.


Assuntos
Infecções por Vírus Respiratório Sincicial , Vírus Sincicial Respiratório Humano , Infecções Respiratórias , Criança , Humanos , Lactente , Vírus Sincicial Respiratório Humano/genética , Infecções por Vírus Respiratório Sincicial/epidemiologia , Prevalência , Evolução Molecular , Filogenia , China/epidemiologia , Genótipo
17.
Chemistry ; 29(33): e202300861, 2023 Jun 13.
Artigo em Inglês | MEDLINE | ID: mdl-36988136

RESUMO

Laser-free photodynamic therapy (PDT) is a promising noninvasive therapeutic modality for deep-seated tumor, yet is constrained by low efficiency due to the limited stimulation strategies. Herein, a novel miRNA-responsive laser-free PDT was developed through metal-organic frameworks (MOFs)-mediated chemiluminescence resonance energy transfer (CRET) nanoplatform. The photosensitizer chlorin e6 (Ce6)-loaded MOFs were functionalized with hairpin nucleic acids for sensitive responsiveness of tumor biomarker miRNA through catalytic hairpin assembly (CHA), which enabled the amplified assembly of horseradish peroxidase (HRP)-mimicking hemin/G-quadruplex DNAzyme on MOFs. Simultaneously, the on-MOF assembled DNAzymes efficiently catalyzed chemiluminescence reaction to stimulate adjacent Ce6 in the presence of luminol and H2 O2 , thus allowing the CRET-mediated Ce6 luminescence and reactive oxygen species (ROS) generation for self-illuminating PDT. The CRET nanoplatform achieved significant malignant cell apoptosis and tumor inhibition effects without external laser irradiation. It is envisioned that the miRNA-amplified CRET nanoplatform might be a selective and highly efficient antitumor nanomedicine for precise theranostic.


Assuntos
DNA Catalítico , Estruturas Metalorgânicas , MicroRNAs , Neoplasias , Fotoquimioterapia , Porfirinas , Humanos , Luminescência , Transferência de Energia , Fármacos Fotossensibilizantes/farmacologia , Neoplasias/tratamento farmacológico , Linhagem Celular Tumoral , Porfirinas/farmacologia
18.
Front Microbiol ; 14: 1301141, 2023.
Artigo em Inglês | MEDLINE | ID: mdl-38235425

RESUMO

Introduction: Granulomas, the pathological hallmark of Mycobacterium tuberculosis (Mtb) infection, are formed by different cell populations. Across various stages of tuberculosis conditions, most granulomas are classical caseous granulomas. They are composed of a necrotic center surrounded by multilayers of histocytes, with the outermost layer encircled by fibrosis. Although fibrosis characterizes the architecture of granulomas, little is known about the detailed parameters of fibrosis during this process. Methods: In this study, samples were collected from patients with tuberculosis (spanning 16 organ types), and Mtb-infected marmosets and fibrotic collagen were characterized by second harmonic generation (SHG)/two-photon excited fluorescence (TPEF) microscopy using a stain-free, fully automated analysis program. Results: Histopathological examination revealed that most granulomas share common features, including necrosis, solitary and compact structure, and especially the presence of multinuclear giant cells. Masson's trichrome staining showed that different granuloma types have varying degrees of fibrosis. SHG imaging uncovered a higher proportion (4%~13%) of aggregated collagens than of disseminated type collagens (2%~5%) in granulomas from matched tissues. Furthermore, most of the aggregated collagen presented as short and thick clusters (200~620 µm), unlike the long and thick (200~300 µm) disseminated collagens within the matched tissues. Matrix metalloproteinase-9, which is involved in fibrosis and granuloma formation, was strongly expressed in the granulomas in different tissues. Discussion: Our data illustrated that different tuberculosis granulomas have some degree of fibrosis in which collagen strings are short and thick. Moreover, this study revealed that the SHG imaging program could contribute to uncovering the fibrosis characteristics of tuberculosis granulomas.

19.
Animals (Basel) ; 12(18)2022 Sep 10.
Artigo em Inglês | MEDLINE | ID: mdl-36139225

RESUMO

Understanding the genetic composition of indigenous goats is essential to promote the scientific conservation and sustainable utilization of these breeds. The Jianchang Black (JC) goat, a Chinese native breed, is solid black and exhibits crude feed tolerance, but is characterized by a low growth rate and small body size. Based on the whole-genome sequencing data for 30 JC, 41 Jintang Black (JT), and 40 Yunshang Black (YS) goats, and 21 Bezoar ibexes, here, we investigated the genetic composition of JC goats by conducting analyses of the population structure, runs of homozygosity (ROH), genomic inbreeding, and selection signature. Our results revealed that JT and YS showed a close genetic relationship with a non-negligible amount of gene flows but were genetically distant from JC, apart from Bezoars. An average of 2039 ROHs were present in the autosomal genome per individual. The ROH-based inbreeding estimates in JC goats generally showed moderate values ranging from 0.134 to 0.264, mainly due to rapid declines in the effective population size during recent generations. The annotated genes (e.g., IL2, IL7, and KIT) overlapping with ROH islands were significantly enriched in immune-related biological processes. Further, we found 61 genes (e.g., STIM1, MYO9A, and KHDRBS2) under positive selection in JC goats via three complementary approaches, which may underly genetic adaptations to local environmental conditions. Our findings provided references for the conservation and sustainable utilization of JC goats.

20.
J Cosmet Dermatol ; 21(12): 7090-7099, 2022 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-36099014

RESUMO

BACKGROUND: Glycyrrhiza is one of the most widely used traditional Chinese medicines in China. Its main bioactive ingredient glycyrrhizic acid (GA) has the potential to be used as a treatment for atopic dermatitis (AD) because it has similar actions to steroids, but with relatively few side effects. AIMS: The objective of this study was to explore the potential mechanisms of GA on AD mice model. METHODS: Calcipotriol, a vitamin D3 analogue (MC903) was applied topically to establish AD mouse model. Mice were intraperitoneally administrated with 2 mg/kg dexamethasone (DEX), 25 or 50 mg/kg GA for 15 days. After mice were executed, skin tissues were collected and detected the expression levels of IL-4, IFN-γ, TNF-α and thymic stromal lymphopoietin (TSLP). The percentages of Th1, Th2, Th17, langerhans cells (LCs) in draining lymph nodes (dLNs) were measured by flow cytometry. RESULTS: Our data demonstrated that GA improved the symptoms of AD by exerting anti-inflammatory and anti-allergic functions in vivo. We found that GA treatment decreased the level of total IgE in serum, suppressed ear swelling, reduced the infiltration of mast cells in skin lesions and decreased expressions of IL-4, IFN-γ, TNF-α and TSLP in skin lesions. Furthermore, our experimental results demonstrated that GA suppressed the Th1/Th2/Th17-immune responses in the dLNs, inhibited the migration of LCs in dLNs. CONCLUSIONS: In conclusion, our findings suggested potential therapeutic effects of GA against MC903-induced AD-like skin lesions in mice.


Assuntos
Dermatite Atópica , Camundongos , Animais , Ácido Glicirrízico/efeitos adversos , Fator de Necrose Tumoral alfa/metabolismo , Interleucina-4/efeitos adversos , Citocinas/metabolismo , Pele , Linfopoietina do Estroma do Timo
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