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1.
Angew Chem Int Ed Engl ; 63(41): e202409750, 2024 Oct 07.
Artigo em Inglês | MEDLINE | ID: mdl-38982974

RESUMO

Splitting the five and seven-membered rings of azulene and embedding them separately into a conjugated backbone provides azulene-like polycyclic aromatic hydrocarbons (PAHs), which are of great interest in quantum and material chemistry. However, the synthetic accessibility poses a significant challenge. In this study, we present the synthesis of a novel azulene-like PAH, Pery-57, which can be viewed as the integration of a perylene framework into the split azulene. The compact structure of Pery-57 displays several intriguing characteristics, including NIR II absorption at 1200 nm, a substantial dipole moment of 3.5 D, and head-to-tail alternating columnar packing. Furthermore, Pery-57 exhibits remarkable redox properties. The cationic radical Pery-57⋅+ readily captures a hydrogen atom. Variable-temperature NMR (VT NMR ) and variable-temperature EPR (VT-EPR) studies reveal that the dianion Pery-572- possesses an open-shell singlet ground state and demonstrates significant global anti-aromaticity. The dication Pery-572+ is also predicted to exhibit diradical character. Despite bearing three bulky substituents, Pery-57 displays p-type transport characteristics with a mobility of 0.03 cm2 V-1 s-1, attributed to its unique azulene-like structure. Overall, this work directs interest in azulene-like PAHs, a unique member of nonalternant PAHs showcasing exceptional properties and applications.

2.
Angew Chem Int Ed Engl ; 63(29): e202407547, 2024 Jul 15.
Artigo em Inglês | MEDLINE | ID: mdl-38725308

RESUMO

We report the synthesis of a longitudinally helical molecular nanocarbon, hexabenzoheptacene (HBH), along with its dimethylated derivative (HBH-Me), which are composed of six benzene rings periodically benzannulated to both zigzag edges of a heptacene core. This benzannulation pattern endows the resulting nanocarbons with a helical heptacene core and local aromaticity, imparting enhanced solubility and stability to the system. The chiral HBH-Me adopts a more highly twisted conformation with an end-to-end twist angle of 95°, enabling the separation of the enantiomers. Both HBH and HBH-Me can be facilely oxidized into their corresponding dications, which exhibit enhanced planarity and aromaticity upon loss of electrons. Notably, both longitudinally helical nanocarbons readily promote solid state packing into two-dimensional (2D) arrangement. Single-crystal microbelts of HBH-Me show hole mobility up to 0.62 cm2 V-1 s-1, illustrating the promising potential of these longitudinally helical molecules for organic electronic devices.

3.
Int J Mol Sci ; 25(9)2024 May 02.
Artigo em Inglês | MEDLINE | ID: mdl-38732182

RESUMO

Anthocyanins are water-soluble flavonoid pigments that play a crucial role in plant growth and metabolism. They serve as attractants for animals by providing plants with red, blue, and purple pigments, facilitating pollination and seed dispersal. The fruits of solanaceous plants, tomato (Solanum lycopersicum) and eggplant (Solanum melongena), primarily accumulate anthocyanins in the fruit peels, while the ripe fruits of Atropa belladonna (Ab) have a dark purple flesh due to anthocyanin accumulation. In this study, an R2R3-MYB transcription factor (TF), AbMYB1, was identified through association analysis of gene expression and anthocyanin accumulation in different tissues of A. belladonna. Its role in regulating anthocyanin biosynthesis was investigated through gene overexpression and RNA interference (RNAi). Overexpression of AbMYB1 significantly enhanced the expression of anthocyanin biosynthesis genes, such as AbF3H, AbF3'5'H, AbDFR, AbANS, and Ab3GT, leading to increased anthocyanin production. Conversely, RNAi-mediated suppression of AbMYB1 resulted in decreased expression of most anthocyanin biosynthesis genes, as well as reduced anthocyanin contents in A. belladonna. Overall, AbMYB1 was identified as a fruit-expressed R2R3-MYB TF that positively regulated anthocyanin biosynthesis in A. belladonna. This study provides valuable insights into the regulation of anthocyanin biosynthesis in Solanaceae plants, laying the foundation for understanding anthocyanin accumulation especially in the whole fruits of solanaceous plants.


Assuntos
Antocianinas , Frutas , Regulação da Expressão Gênica de Plantas , Proteínas de Plantas , Fatores de Transcrição , Antocianinas/biossíntese , Antocianinas/metabolismo , Frutas/metabolismo , Frutas/genética , Fatores de Transcrição/genética , Fatores de Transcrição/metabolismo , Proteínas de Plantas/genética , Proteínas de Plantas/metabolismo , Plantas Geneticamente Modificadas/metabolismo , Plantas Geneticamente Modificadas/genética , Interferência de RNA
4.
Zhongguo Zhong Yao Za Zhi ; 49(7): 1888-1895, 2024 Apr.
Artigo em Chinês | MEDLINE | ID: mdl-38812201

RESUMO

This study observed the effects of Notoginseng Radix et Rhizoma on the phosphatidylinositol 3-kinase(PI3K)/protein kinase B(Akt)/mammalian target of rapamycin complex 1(mTORC1) signaling pathway and mitochondrial energy metabolism in the rat model of adriamycin-induced renal fibrosis with blood stasis syndrome to explore the mechanism of Notoginseng Radix et Rhizoma in protecting the kidney. Thirty male rats with adriamycin-induced renal fibrosis were randomized into model, low-, medium-, and high-dose Notoginseng Radix et Rhizoma, and positive control groups(n=6). Six clean SD male rats were selected into the normal group. The normal group and model group were administrated with normal saline, and other groups with corresponding drugs. After 8 weeks of treatment, the renal function, renal pathology, adenosine triphosphate(ATP) levels, Na~+-K~+-ATPase and Ca~(2+)-Mg~(2+)-ATPase activities, and the protein levels of ATP5B, mTORC1, 70 kDa ribosomal protein S6 kinase(P70S6K), P85, Akt, p-Akt, and SH2-containing inositol phosphatase(SHIP2) in the renal tissue were determined. Compared with the normal group, the model group showed elevated levels of blood urea nitrogen(BUN) and serum creatinine(SCr)(P<0.01). Compared with the model group, Notoginseng Radix et Rhizoma and the positive control lowered the levels of BUN and SCr, which were significant in the medium-and high-dose Noto-ginseng Radix et Rhizoma groups and the positive control group(P<0.05). Compared with the model group, Notoginseng Radix et Rhizoma and the positive control alleviated the pathological changes in the renal tissue, such as vacuolar and fibroid changes, glomerulus atrophy, cystic expansion of renal tubules, and massive infiltration of inflammatory cells. Compared with the normal group, the model group showed decreased mitochondrial ATP content and Na~+-K~+-ATPase and Ca~(2+)-Mg~(2+)-ATPase activities in the renal tissue(P<0.05), and medium-and high-dose Notoginseng Radix et Rhizoma and positive control mitigated such decreases(P<0.05). Compared with the model group, medium-and high-dose Notoginseng Radix et Rhizoma and the positive control up-regulated the protein levels of ATP5B and SHIP2 and down-regulated the protein levels of mTORC1, P70S6K, P85, Akt, and p-Akt(P<0.05 or P<0.01 or P<0.001). Notoginseng Radix et Rhizoma may exert an anti-fibrosis effect by inhibiting the activation of the PI3K/Akt/mTORC1 pathway to restore mitochondrial energy metabolism, thus protecting the kidney.


Assuntos
Medicamentos de Ervas Chinesas , Metabolismo Energético , Alvo Mecanístico do Complexo 1 de Rapamicina , Mitocôndrias , Panax notoginseng , Transdução de Sinais , Animais , Humanos , Masculino , Ratos , Medicamentos de Ervas Chinesas/farmacologia , Medicamentos de Ervas Chinesas/administração & dosagem , Metabolismo Energético/efeitos dos fármacos , Rim/efeitos dos fármacos , Rim/metabolismo , Alvo Mecanístico do Complexo 1 de Rapamicina/metabolismo , Mitocôndrias/efeitos dos fármacos , Mitocôndrias/metabolismo , Panax notoginseng/química , Fosfatidilinositol 3-Quinases/metabolismo , Fosfatidilinositol 3-Quinases/genética , Proteínas Proto-Oncogênicas c-akt/metabolismo , Proteínas Proto-Oncogênicas c-akt/genética , Ratos Sprague-Dawley , Insuficiência Renal/tratamento farmacológico , Insuficiência Renal/metabolismo , Rizoma/química , Transdução de Sinais/efeitos dos fármacos
5.
Aging (Albany NY) ; 16(10): 9251-9263, 2024 05 27.
Artigo em Inglês | MEDLINE | ID: mdl-38809508

RESUMO

BACKGROUND: Senile osteoporosis may be caused by an imbalance in intestinal flora and oxidative stress. Trimethylamine-N-oxide (TMAO), a metabolite of dietary choline dependent on gut microbes, has been found to be significantly increased in osteoporosis. However, the role of TMAO in bone loss during osteoporosis remains poorly understood. In this study, we examined the impact of TMAO on osteoclast differentiation and bone resorption in an in vitro setting. METHODS: Osteoclast differentiation was induced by incubating RAW 264.7 cells in the presence of Receptor Activator for Nuclear Factor-κB Ligand (RANKL) and macrophage-stimulating factor (M-CSF). Flow cytometry, TRAP staining assay, CCK-8, and ELISA were employed to investigate the impact of TMAO on osteoclast differentiation and bone resorption activity in vitro. For mechanistic exploration, RT-PCR and Western blotting were utilized to assess the activation of the NF-κB pathway. Additionally, protein levels of secreted cytokines and growth factors were determined using suspension array technology. RESULTS: Our findings demonstrate that TMAO enhances RANKL and M-CSF-induced osteoclast formation and bone resorption in a dose-dependent manner. Mechanistically, TMAO triggers the upregulation of the NF-κB pathway and osteoclast-related genes (NFATc1, c-Fos, NF-κB p65, Traf6, and Cathepsin K). Furthermore, TMAO markedly elevated the levels of oxidative stress and inflammatory factors. CONCLUSIONS: In conclusion, TMAO enhances RANKL and M-CSF-induced osteoclast differentiation and inflammation in RAW 264.7 cells by activating the NF-κB signaling pathway. These findings offer a new rationale for further academic and clinical research on osteoporosis treatment.


Assuntos
Diferenciação Celular , Metilaminas , NF-kappa B , Osteoclastos , Estresse Oxidativo , Ligante RANK , Transdução de Sinais , Animais , Osteoclastos/efeitos dos fármacos , Osteoclastos/metabolismo , Camundongos , Metilaminas/farmacologia , Estresse Oxidativo/efeitos dos fármacos , Diferenciação Celular/efeitos dos fármacos , Células RAW 264.7 , NF-kappa B/metabolismo , Ligante RANK/metabolismo , Transdução de Sinais/efeitos dos fármacos , Fator Estimulador de Colônias de Macrófagos/metabolismo , Fator Estimulador de Colônias de Macrófagos/farmacologia , Reabsorção Óssea/metabolismo
6.
Nat Commun ; 15(1): 3623, 2024 Apr 29.
Artigo em Inglês | MEDLINE | ID: mdl-38684703

RESUMO

Solanaceous plants produce tropane alkaloids (TAs) via esterification of 3α- and 3ß-tropanol. Although littorine synthase is revealed to be responsible for 3α-tropanol esterification that leads to hyoscyamine biosynthesis, the genes associated with 3ß-tropanol esterification are unknown. Here, we report that a BAHD acyltransferase from Atropa belladonna, 3ß-tigloyloxytropane synthase (TS), catalyzes 3ß-tropanol and tigloyl-CoA to form 3ß-tigloyloxytropane, the key intermediate in calystegine biosynthesis and a potential drug for treating neurodegenerative disease. Unlike other cytosolic-localized BAHD acyltransferases, TS is localized to mitochondria. The catalytic mechanism of TS is revealed through molecular docking and site-directed mutagenesis. Subsequently, 3ß-tigloyloxytropane is synthesized in tobacco. A bacterial CoA ligase (PcICS) is found to synthesize tigloyl-CoA, an acyl donor for 3ß-tigloyloxytropane biosynthesis. By expressing TS mutant and PcICS, engineered Escherichia coli synthesizes 3ß-tigloyloxytropane from tiglic acid and 3ß-tropanol. This study helps to characterize the enzymology and chemodiversity of TAs and provides an approach for producing 3ß-tigloyloxytropane.


Assuntos
Aciltransferases , Mitocôndrias , Tropanos , Aciltransferases/metabolismo , Aciltransferases/genética , Mitocôndrias/metabolismo , Mitocôndrias/enzimologia , Tropanos/metabolismo , Escherichia coli/genética , Escherichia coli/metabolismo , Nicotiana/genética , Nicotiana/metabolismo , Simulação de Acoplamento Molecular , Proteínas de Plantas/metabolismo , Proteínas de Plantas/genética , Mutagênese Sítio-Dirigida
7.
J Agric Food Chem ; 72(14): 7749-7764, 2024 Apr 10.
Artigo em Inglês | MEDLINE | ID: mdl-38537104

RESUMO

Fusarium wilt is a severe fungal disease caused by Fusarium oxysporum in sweet potato. We conducted transcriptome analysis to explore the resistance mechanism of sweet potato against F. oxysporum. Our findings highlighted the role of scopoletin, a hydroxycoumarin, in enhancing resistance. In vitro experiments confirmed that scopoletin and umbelliferone had inhibitory effects on the F. oxysporum growth. We identified hydroxycoumarin synthase genes IbF6'H2 and IbCOSY that are responsible for scopoletin production in sweet potatoes. The co-overexpression of IbF6'H2 and IbCOSY in tobacco plants produced the highest scopoletin levels and disease resistance. This study provides insights into the molecular basis of sweet potato defense against Fusarium wilt and identifies valuable genes for breeding wilt-resistant cultivars.


Assuntos
Fusarium , Ipomoea batatas , Ipomoea batatas/genética , Escopoletina/farmacologia , Fusarium/genética , Melhoramento Vegetal , Doenças das Plantas/microbiologia
8.
iScience ; 27(2): 108955, 2024 Feb 16.
Artigo em Inglês | MEDLINE | ID: mdl-38322996

RESUMO

Hepatocellular carcinoma (HCC) is a highly malignant tumor with rich blood supply. HCC-derived exosomes containing hereditary substances including microRNAs (miRNAs) were involved in regulating tumor angiogenesis and metastasis. Subsequently, series experiments were performed to evaluate the effect of exosomal miR-3174 on HCC angiogenesis and metastasis. HCC-derived exosomal miR-3174 was ingested by human umbilical vein endothelial cells (HUVECs) in which HIPK3 was targeted and silenced, causing subsequent inhibition of Fas and p53 signaling pathways. Furthermore, exosomal miR-3174 induced permeability and angiogenesis of HUVECs to enhance HCC progression and metastasis. Under hypoxia, upregulated HIF-1α further promoted the transcription of miR-3174. Moreover, HNRNPA1 augmented the package of miR-3174 into exosomes. Clinical data analysis confirmed that HCC patients with high-level miR-3174 were correlated with worse prognosis. Thus, exosomal miR-3174 induced by hypoxia promotes angiogenesis and metastasis of HCC by inhibiting HIPK3/p53 and HIPK3/Fas signaling pathways. Our findings might provide potential targets for anti-tumor therapy.

9.
Plant Physiol Biochem ; 208: 108439, 2024 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-38408396

RESUMO

Putrescine, produced via the arginine decarboxylase (ADC)/ornithine decarboxylase (ODC)-mediated pathway, is an initial precursor for polyamines metabolism and the root-specific biosynthesis of medicinal tropane alkaloids (TAs). These alkaloids are widely used as muscarinic acetylcholine antagonists in clinics. Although the functions of ODC in biosynthesis of polyamines and TAs have been well investigated, the role of ADC is still poorly understood. In this study, enzyme inhibitor treatment showed that ADC was involved in the biosynthesis of putrescine-derived metabolites and root growth in Atropa belladonna. Further analysis found that there were six ADC unigenes in the A. belladonna transcriptome, with two of them, AbADC1 and AbADC2, exhibiting high expression in the roots. To investigate their roles in TAs/polyamines metabolism and root growth, RNA interference (RNAi) was used to suppress either AbADC1 or AbADC2 expression in A. belladonna hairy roots. Suppression of the AbADC1 expression resulted in a significant reduction in the putrescine content and hairy root biomass. However, it had no noticeable effect on the levels of N-methylputrescine and the TAs hyoscyamine, anisodamine, and scopolamine. On the other hand, suppression of AbADC2 expression markedly reduced the levels of putrescine, N-methylputrescine, and TAs, but had no significant effect on hairy root biomass. According to ß-glucuronidase (GUS) staining assays, AbADC1 was mainly expressed in the root elongation and division region while AbADC2 was mainly expressed in the cylinder of the root maturation region. These differences in expression led to functional divergence, with AbADC1 primarily regulating root growth and AbADC2 contributing to TA biosynthesis.


Assuntos
Alcaloides , Atropa belladonna , Carboxiliases , Atropa belladonna/genética , Atropa belladonna/metabolismo , Putrescina/metabolismo , Tropanos/metabolismo
10.
Sci Total Environ ; 918: 170515, 2024 Mar 25.
Artigo em Inglês | MEDLINE | ID: mdl-38309344

RESUMO

The Great Wall, a World Heritage Site and a vertical wall habitat, is under threat of soil erosion. The role of vascular plants and biocrust in controlling soil erosion has attracted attention, yet our knowledge of the underlying mechanism is limited, and there is a lack of systematic strategies for erosion prevention and control. In this study, we quantified the vascular plant community functional composition (including species diversity, functional diversity, and community-weighted mean), biocrust coverage, and soil erosion levels associated with seven different zones (lower, middle, and upper zones on East and West faces, plus wall crest) of the Great Wall. We then employed a combination of linear regression analysis, random forest model, and structural equation model to evaluate the individual and combined effects, as well as the direction and relative importance of these factors in reducing soil erosion. The results indicated that the vascular plant species richness, species diversity, functional richness, community-weighted mean, and moss crust coverage decreased significantly from the crest to the lower zone of the Great Wall (P < 0.05), and were negatively correlated with the soil erosion area and depth on both sides of the Great Wall (P < 0.05). This suggests that higher zones on the wall favored the colonization and growth of biocrusts and vascular plants and that biocrusts and vascular plants reduced soil erosion on the wall. Based on these findings, we propose a "restoration framework" for managing soil erosion on walls, based on biocrust and vascular plant communities (namely target species selection, plant community construction, biocrust inoculation, and maintenance of community stability), which aims to address the urgent need for more effective soil erosion prevention and control strategies on the Great Wall and provide practical methods that practitioners can utilize.


Assuntos
Briófitas , Traqueófitas , Erosão do Solo , Solo/química , Ecossistema , Microbiologia do Solo
11.
Cell Prolif ; 57(3): e13558, 2024 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-37807299

RESUMO

Human organoids recapitulate the cell type diversity and function of their primary organs holding tremendous potentials for basic and translational research. Advances in single-cell RNA sequencing (scRNA-seq) technology and genome-wide association study (GWAS) have accelerated the biological and therapeutic interpretation of trait-relevant cell types or states. Here, we constructed a computational framework to integrate atlas-level organoid scRNA-seq data, GWAS summary statistics, expression quantitative trait loci, and gene-drug interaction data for distinguishing critical cell populations and drug targets relevant to coronavirus disease 2019 (COVID-19) severity. We found that 39 cell types across eight kinds of organoids were significantly associated with COVID-19 outcomes. Notably, subset of lung mesenchymal stem cells increased proximity with fibroblasts predisposed to repair COVID-19-damaged lung tissue. Brain endothelial cell subset exhibited significant associations with severe COVID-19, and this cell subset showed a notable increase in cell-to-cell interactions with other brain cell types, including microglia. We repurposed 33 druggable genes, including IFNAR2, TYK2, and VIPR2, and their interacting drugs for COVID-19 in a cell-type-specific manner. Overall, our results showcase that host genetic determinants have cellular-specific contribution to COVID-19 severity, and identification of cell type-specific drug targets may facilitate to develop effective therapeutics for treating severe COVID-19 and its complications.


Assuntos
COVID-19 , Estudo de Associação Genômica Ampla , Humanos , COVID-19/genética , Organoides , Perfilação da Expressão Gênica , Genética Humana
12.
Int Wound J ; 2023 Oct 17.
Artigo em Inglês | MEDLINE | ID: mdl-37849027

RESUMO

In this study, a meta-analysis was conducted to comprehensively assess the effectiveness of nursing intervention in the operating room to prevent pressure ulcers and wound infections in patients with intertrochanteric fractures. A computerised search of PubMed, Cochrane Library, Embase, China National Knowledge Infrastructure (CNKI), VIP Database of Chinese Technical Periodicals, and Wanfang databases was performed to identify randomised controlled studies (RCTs) on the effectiveness of nursing intervention in the operating room for patients undergoing intertrochanteric fractures from the time of construction of the respective databases to June 2023. Two researchers independently searched and screened the literature, extracted information and performed quality assessments of the included literature. The meta-analysis was performed using RevMan 5.4 software. Eighteen studies were finally included, including 1517 patients, with 757 in the intervention group and 760 in the control group. The results showed that nursing intervention in the operating room significantly reduced the incidence of postoperative pressure ulcers in patients with intertrochanteric femoral fractures compared to the control group (1.69% vs. 6.01%, odds ratio [OR]: 0.32, 95% confidence interval [CI]: 0.18-0.57, p < 0.001) and reduced the incidence of surgical site wound infection (1.00% vs. 6.15%, OR: 0.23, 95% CI: 0.11-0.50, p < 0.001). Current evidence suggests that nursing intervention in the operating room is superior to routine care in reducing the incidence of pressure ulcers and wound infections in patients with intertrochanteric fractures and that such interventions should be promoted for clinical use.

13.
Front Bioeng Biotechnol ; 11: 1239246, 2023.
Artigo em Inglês | MEDLINE | ID: mdl-37767108

RESUMO

Background: Flat foot deformity is a prevalent and challenging condition often leading to various clinical complications. Accurate identification of abnormal foot types is essential for appropriate interventions. Method: A dataset consisting of 1573 plantar pressure images from 125 individuals was collected. The performance of the You Only Look Once v5 (YOLO-v5) model, improved YOLO-v5 model, and multi-label classification model was evaluated for foot type identification using the collected images. A new dataset was also collected to verify and compare the models. Results: The multi-label classification algorithm based on ResNet-50 outperformed other algorithms. The improved YOLO-v5 model with Squeeze-and-Excitation (SE), the improved YOLO-v5 model with Convolutional Block Attention Module (CBAM), and the multilabel classification model based on ResNet-50 achieved an accuracy of 0.652, 0.717, and 0.826, respectively, which is significantly higher than those obtained using the ordinary plantar-pressure system and the standard YOLO-v5 model. Conclusion: These results indicate that the proposed DL-based multilabel classification model based on ResNet-50 is superior in flat foot type detection and can be used to evaluate the clinical rehabilitation status of patients with abnormal foot types and various foot pathologies when more data on patients with various diseases are available for training.

14.
Cell Genom ; 3(9): 100383, 2023 Sep 13.
Artigo em Inglês | MEDLINE | ID: mdl-37719150

RESUMO

Advances in single-cell RNA sequencing (scRNA-seq) techniques have accelerated functional interpretation of disease-associated variants discovered from genome-wide association studies (GWASs). However, identification of trait-relevant cell populations is often impeded by inherent technical noise and high sparsity in scRNA-seq data. Here, we developed scPagwas, a computational approach that uncovers trait-relevant cellular context by integrating pathway activation transformation of scRNA-seq data and GWAS summary statistics. scPagwas effectively prioritizes trait-relevant genes, which facilitates identification of trait-relevant cell types/populations with high accuracy in extensive simulated and real datasets. Cellular-level association results identified a novel subpopulation of naive CD8+ T cells related to COVID-19 severity and oligodendrocyte progenitor cell and microglia subsets with critical pathways by which genetic variants influence Alzheimer's disease. Overall, our approach provides new insights for the discovery of trait-relevant cell types and improves the mechanistic understanding of disease variants from a pathway perspective.

15.
Chin J Physiol ; 66(4): 220-227, 2023.
Artigo em Inglês | MEDLINE | ID: mdl-37635481

RESUMO

Lijie Capsules (LJJN) are a classical Chinese herbal formula adopted to treat rheumatoid arthritis (RA) clinically, yet the regulatory mechanism underlying the protection of LJJN against RA has not been fully elucidated. Here, the animal model of RA was established by complete Freund's adjuvant administration in mice. About 60 mg/ml of LJJN was used for treatment. The histological change of ankle joint was measured by hematoxylin and eosin staining. The inflammatory cytokines were detected using ELISA kits. The protein associated with inflammation and GLUD2 was detected using Western blot. The mice feces were analyzed by 16S rRNA sequencing. The levels of glutamate (Glu) and α-ketoglutarate (α-KG) were detected using their detection kits. In addition, fibroblast-like synoviocytes (FLSs) were stimulated by Glu to induce an injured synoviocytes model in vitro, with or without LJJN treatment for 48 h. It was demonstrated that LJJN alleviated ankle joint swelling and synovial injury in RA mice. Meanwhile, LJJN inactivated nuclear factor kappa B signaling and suppressed inflammation of RA mice. The disordered gut microbiota composition in RA mice was partly restored by LJJN. Bacteroides-mediated Glu metabolism was impacted in RA mice, and LJJN contributed to the conversion of Glu to α-KG in RA mice. In addition, the in vitro results revealed that LJJN could block Glu-induced inflammation in FLSs but had no direct influence on α-KG and GLUD2 levels. In summary, LJJN exerted a protective role against ankle joint injury and inflammation in RA, which might be partly associated with gut microbiota-mediated Glu metabolism.


Assuntos
Artrite Reumatoide , Microbioma Gastrointestinal , Sinoviócitos , Animais , Camundongos , RNA Ribossômico 16S/metabolismo , Artrite Reumatoide/tratamento farmacológico , Artrite Reumatoide/metabolismo , Artrite Reumatoide/patologia , Sinoviócitos/metabolismo , Sinoviócitos/patologia , Inflamação , Fibroblastos/metabolismo , Fibroblastos/patologia , Células Cultivadas , Proliferação de Células
16.
J Headache Pain ; 24(1): 50, 2023 May 10.
Artigo em Inglês | MEDLINE | ID: mdl-37165344

RESUMO

BACKGROUND: Dental treatment associated with unadaptable occlusal alteration can cause chronic primary myofascial orofacial pain. The serotonin (5-HT) pathway from the rostral ventromedial medulla (RVM) exerts descending modulation on nociceptive transmission in the spinal trigeminal nucleus (Sp5) and facilitates chronic pain. The aim of this study was to investigate whether descending 5-HT modulation from the RVM to the Sp5 is involved in the maintenance of primary myofascial orofacial hyperalgesia after persistent experimental occlusal interference (PEOI) or after delayed removal of experimental occlusal interference (REOI). METHODS: Expressions of 5-HT3A and 5-HT3B receptor subtypes in the Sp5 were assessed by immunofluorescence staining and Western blotting. The release and metabolism of 5-HT in the Sp5 were measured by high-performance liquid chromatography. Changes in the pain behavior of these rats were examined after specific pharmacologic antagonism of the 5-HT3 receptor, chemogenetic manipulation of the RVM 5-HT neurons, or selective down-regulation of 5-HT synthesis in the RVM. RESULTS: Upregulation of the 5-HT3B receptor subtype in the Sp5 was found in REOI and PEOI rats. The concentration of 5-HT in Sp5 increased significantly only in REOI rats. Intrathecal administration of Y-25130 (a selective 5-HT3 receptor antagonist) dose-dependently reversed the hyperalgesia in REOI rats but only transiently reversed the hyperalgesia in PEOI rats. Chemogenetic inhibition of the RVM 5-HT neurons reversed the hyperalgesia in REOI rats; selective down-regulation of 5-HT in advance also prevented the development of hyperalgesia in REOI rats; the above two manipulations did not affect the hyperalgesia in PEOI rats. However, chemogenetic activation of the RVM 5-HT neurons exacerbated the hyperalgesia both in REOI and PEOI rats. CONCLUSIONS: These results provide several lines of evidence that the descending pathway from 5-HT neurons in the RVM to 5-HT3 receptors in the Sp5, plays an important role in facilitating the maintained orofacial hyperalgesia after delayed EOI removal, but has a limited role in that after persistent EOI.


Assuntos
Dor Crônica , Hiperalgesia , Ratos , Animais , Hiperalgesia/induzido quimicamente , Núcleo Espinal do Trigêmeo/metabolismo , Receptores 5-HT3 de Serotonina/metabolismo , Receptores 5-HT3 de Serotonina/uso terapêutico , Serotonina/metabolismo , Ratos Sprague-Dawley , Dor Facial/etiologia , Dor Crônica/etiologia
17.
Nat Commun ; 14(1): 1446, 2023 03 15.
Artigo em Inglês | MEDLINE | ID: mdl-36922496

RESUMO

Tropane alkaloids (TAs) are widely distributed in the Solanaceae, while some important medicinal tropane alkaloids (mTAs), such as hyoscyamine and scopolamine, are restricted to certain species/tribes in this family. Little is known about the genomic basis and evolution of TAs biosynthesis and specialization in the Solanaceae. Here, we present chromosome-level genomes of two representative mTAs-producing species: Atropa belladonna and Datura stramonium. Our results reveal that the two species employ a conserved biosynthetic pathway to produce mTAs despite being distantly related within the nightshade family. A conserved gene cluster combined with gene duplication underlies the wide distribution of TAs in this family. We also provide evidence that branching genes leading to mTAs likely have evolved in early ancestral Solanaceae species but have been lost in most of the lineages, with A. belladonna and D. stramonium being exceptions. Furthermore, we identify a cytochrome P450 that modifies hyoscyamine into norhyoscyamine. Our results provide a genomic basis for evolutionary insights into the biosynthesis of TAs in the Solanaceae and will be useful for biotechnological production of mTAs via synthetic biology approaches.


Assuntos
Alcaloides , Atropa belladonna , Hiosciamina , Solanaceae , Solanaceae/genética , Solanaceae/metabolismo , Hiosciamina/genética , Hiosciamina/metabolismo , Tropanos/metabolismo , Escopolamina/metabolismo , Atropa belladonna/genética , Atropa belladonna/metabolismo
18.
Gels ; 9(2)2023 Feb 08.
Artigo em Inglês | MEDLINE | ID: mdl-36826314

RESUMO

Articular cartilage (AC), which covers the ends of bones in joints, particularly the knee joints, provides a robust interface to maintain frictionless movement during daily life due to its remarkable lubricating and load-bearing capacities. However, osteoarthritis (OA), characterized by the progressive degradation of AC, compromises the properties of AC and thus leads to frayed and rough interfaces between the bones, which subsequently accelerates the progression of OA. Hydrogels, composed of highly hydrated and interconnected polymer chains, are potential candidates for AC replacement due to their physical and chemical properties being similar to those of AC. In this review, we summarize the recent progress of hydrogel-based synthetic cartilage, or cartilage-like hydrogels, with a particular focus on their lubrication and load-bearing properties. The different formulations, current limitations, and challenges of such hydrogels are also discussed. Moreover, we discuss the future directions of hydrogel-based synthetic cartilage to repair and even regenerate the damaged AC.

19.
Appl Radiat Isot ; 195: 110738, 2023 May.
Artigo em Inglês | MEDLINE | ID: mdl-36842414

RESUMO

The scintillator detectors such as LaCl3(Ce) play an important role in some fields of scientific research, environment, safeguards, medicine, security and industry due to its superior energy resolution and exceptional luminescence properties, etc. However, Cl element in a LaCl3 crystal produces uncertainty of determining oil saturation in pulsed neutron logging because of the background spectrum caused by secondary gamma ray from the reaction of Cl nuclei with the neutron. In this paper, we employed Monte Carlo method to simulate secondary gamma ray generated LaCl3 crystal induced by thermal neutron with different borehole and formation conditions and establish a reference spectrum of Cl element. The relations between elemental window or peak areas counts and borehole and formation conditions were also investigated. The background was obtained by combining the reaction rate derived from thermal neutron capture cross section for Cl element and neutron flux with the reference spectrum. The results indicate that the contribution of secondary gamma ray to measuring spectrum decreases with formation porosity, limestone content, borehole diameter, and water salinity increasing. Nevertheless, the relative peak areas of Cl at different energies remain constant, indicating that the logging conditions have less of an effect on the background spectrum shape. As evidenced by the measured spectra in the sandstone and limestone calibration wells processed, the peaks of Si and Ca elements are enhanced while the peaks of Cl element are weakened. After subtracting detector background, the computations of oil saturation based on calibration wells are 38% more accurate than the original method.

20.
Arch Gerontol Geriatr ; 106: 104879, 2023 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-36462246

RESUMO

OBJECTIVE: To systematically assess the association between osteoporosis and cognitive impairment, and to provide new light on the prevention of cognitive impairment in patients with osteoporosis. METHOD: A comprehensive research of Embase, Cochrane Library, PubMed, Web of Science, CNKI, Wangfang Data and VIP was performed from inception to January 2022, using the search term 'osteoporosis' and 'cognitive impairment'. Literature screening, data extraction and quality evaluation were conducted by two reviewers independently, and meta-analysis was performed by RevMan 5.4 software. RESULTS: A total of 8 studies (136222 participants) were included. Meta-analysis showed that patients with osteoporosis had an increased risk of cognitive impairment [OR=2.01, 95% CI(1.63-2.48), P<0.01]. This initial meta-analysis had significant heterogeneity, and subgroup analysis suggested that potential heterogeneity in different study types, age and outcome indicators. CONCLUSION: Patients with osteoporosis are at increased risk of cognitive impairment, and osteoporosis intervention could prevent or delay the onset of cognitive impairment for those at risk.


Assuntos
Disfunção Cognitiva , Humanos , Disfunção Cognitiva/epidemiologia , Disfunção Cognitiva/etiologia , Cognição
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