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1.
Tissue Cell ; 74: 101696, 2021 Nov 23.
Artigo em Inglês | MEDLINE | ID: mdl-34861581

RESUMO

Hepatocellular carcinoma (HCC) is a major type of liver cancer with high mortality, which is a prevalent common cancer in the world. Aberrant miRNAs contribute to the progression and development of HCC. Currently, our study demonstrated that miR-4317 was decreased in HCC patient samples tissues and HCC cell lines, which was related to poor clinical features, including tumor size, advanced TNM stage and vascular invasion. Furthermore, we confirmed that miR-4317 suppressed cell viability, proliferation, invasion and migration through loss- and gain-of-function experiment in vitro. In addition, miR-4317 inhibited tumor growth in vivo experiment. Luciferase reporter assays confirmed that ZNF436 was a direct target of miR-4317. Restoration of ZNF436 reversed the role of miR-4317 on HCC. ZNF436 expression was increased in HCC tissues and cell lines, which was negatively correlated with miR-4317 expression. ZNF436 overexpression obviously promoted the cell proliferation, viability, invasion and migration of HCC cells. ZNF436 mediated the regulatory function of miR-4317 on PI3K/AKT pathway. Overall, our data suggest that miR-4317 is a novel tumor suppressor to suppress HCC progression through PI3K/AKT pathway by targeting ZNF436, and may serve as a prognostic biomarker and therapeutic target for HCC.

2.
Phytomedicine ; : 153835, 2021 Oct 30.
Artigo em Inglês | MEDLINE | ID: mdl-34799185

RESUMO

BACKGROUND: Asthma characterized by airway remodeling is a multiple pulmonary disease, which is associated with various physiological processes including inflammation reaction, immune response, oxidative stress and autophagy. PURPOSE: This study aimed to investigate whether these processes are modulated by the total glucosides of Paeonia lactiflora Pall (TGP), and its active compound paeoniflorin (PF) with anti-inflammatory and immune-regulatory effects could alleviate ovalbumin (OVA)-induced mouse asthma. METHODS: In vivo, models of mouse asthma were established by intraperitoneally with a mixture of OVA and aluminum hydroxide, plus a single nasal injected with OVA to female C57BL/6 mice. The results were observed with PET imaging, TEM, RT-PCR, western blotting. In vitro, CD4+ T cells were isolated and detected with flow cytometry. RESULTS: TGP, either in its crude or processed form, and PF effectively ameliorated lung injury in mice induced by OVA, regulated immune/inflammatory response by inhibiting the release of pro-inflammatory cytokines, thereby decreasing Th2 cell proportion, inhibited oxidative stress by recovering mitochondrial membrane potential and regulating metabolic activity in dose-dependent manner. Moreover, PF could inhibit autophagy by regulating mitochondrial function. In addition, the therapeutic effects of TGP and PF on pulmonary injury in asthmatic mice were not affected by processing. CONCLUSION: PF may be a valuable agent in ameliorating inflammation and immune response in asthmatic mice, and the possible mechanism involved in this response rang may from oxidative stress to autophagy.

3.
J Agric Food Chem ; 2021 Nov 17.
Artigo em Inglês | MEDLINE | ID: mdl-34788040

RESUMO

High-fat diet (HFD) contributes to metabolic inflammation and glucose metabolism disorder, thereby resulting in the pathogenesis of metabolic syndrome. Accumulating evidence has revealed that some probiotics could improve HFD-induced metabolic inflammation and glucose metabolism disorder. Our previous study has discovered that Lactobacillus acidophilus NX2-6 exhibited in vitro lipid-lowering, antioxidative, and anti-inflammatory activities. This study mainly investigated whether L. acidophilus NX2-6 improved HFD-induced glucose metabolism disorder. The results exhibited that L. acidophilus NX2-6 effectively reduced blood glucose levels and improved glucose tolerance by activating the insulin signaling pathway, promoting glucose uptake, glycolysis, and intestinal gluconeogenesis and suppressing hepatic gluconeogenesis, independent of regulation of glycogen synthesis in the liver and muscle. Enhanced insulin sensitivity was associated with L. acidophilus NX2-6-mediated suppression of inflammatory cascades in the target organs. Meanwhile, L. acidophilus NX2-6 also improved hepatic energy metabolism via the FGF21/AMPKα/PGC-1α/NRF1 pathway. However, L. acidophilus NX2-6 did not affect apoptosis, pyroptosis, inflammation, and endoplasmic reticulum stress in the pancreas of HFD-fed mice. In conclusion, our results indicated that L. acidophilus NX2-6 improved glucose metabolism disorder through enhancing insulin sensitivity, suppressing metabolic inflammation, and promoting energy expenditure.

4.
Med Sci Monit ; 27: e932612, 2021 Oct 16.
Artigo em Inglês | MEDLINE | ID: mdl-34654795

RESUMO

BACKGROUND Postherpetic neuralgia (PHN) is a common complication of herpes zoster virus infection that is associated with intense pain. The present study aimed to investigate the use of computed tomography (CT)-guided radiofrequency ablation (RFA) of the cervical dorsal root ganglia (DRG) for treatment of cervical and occipital PHN in 27 patients at a single center. MATERIAL AND METHODS Twenty-seven patients with PHN in the cervical and/or occipital region were enrolled. After imaging the area of PHN in the patients, axial scanning was performed on the upper cervical segment in the spinal scanning mode. The puncture path was defined and then RFA therapy (90°C for 180 s) was performed by targeting the corresponding intervertebral foramen. Patients were followed 2 days later and at 1, 3, 6, and 12 months after surgery. Observation at each follow-up visit included rating of pain on a visual analog scale (VAS) and assessment of complications and adverse events. RESULTS VAS scores significantly decreased in patients with PHN after RFA compared with their scores before RFA (P<0.05). Skin sensation decreased in the area that was originally painful and allodynia significantly diminished. CONCLUSIONS The findings from this small study from a single center showed that CT-guided percutaneous RFA of cervical DRG safely and effectively reduced cervical and occipital PHN in the short term.

5.
Br J Pharmacol ; 2021 Oct 08.
Artigo em Inglês | MEDLINE | ID: mdl-34625952

RESUMO

BACKGROUND AND PURPOSE: In chronic kidney disease (CKD), patients inevitably reach end-stage renal disease and require renal transplant. Evidence suggests that CKD is associated with metabolite disorders. However, the molecular pathways targeted by metabolites remain enigmatic. Here, we describe roles of 1-hydroxypyrene in mediating renal fibrosis. EXPERIMENTAL APPROACH: We analysed 5406 urine and serum samples from patients with Stage 1-5 CKD using metabolomics, and 1-hydroxypyrene was identified and validated using longitudinal and drug intervention cohorts as well as 5/6 nephrectomised and adenine-induced rats. KEY RESULTS: We identified correlations between the urine and serum levels of 1-hydroxypyrene and the estimated GFR in patients with CKD onset and progression. Moreover, increased 1-hydroxypyrene levels in serum and kidney tissues correlated with decreased renal function in two rat models. Up-regulated mRNA expression of aryl hydrocarbon receptor and its target genes, including CYP1A1, CYP1A2 and CYP1B1, were observed in patients and rats with progressive CKD. Further we showed up-regulated mRNA expression of aryl hydrocarbon receptor and its three target genes, plus up-regulated nuclear aryl hydrocarbon receptor protein levels in mice and HK-2 cells treated with 1-hydroxypyrene, which caused accumulation of extracellular matrix components. Treatment with aryl hydrocarbon receptor short hairpin RNA or flavonoids inhibited mRNA expression of aryl hydrocarbon receptor and its target genes in 1-hydroxypyrene-induced HK-2 cells and mice. CONCLUSION AND IMPLICATIONS: Metabolite 1-hydroxypyrene was demonstrated to mediate renal fibrosis through activation of the aryl hydrocarbon receptor signalling pathway. Targeting aryl hydrocarbon receptor may be an alternative therapeutic strategy for CKD progression.

6.
BMC Bioinformatics ; 22(1): 489, 2021 Oct 10.
Artigo em Inglês | MEDLINE | ID: mdl-34629071

RESUMO

BACKGROUND: Data visualization, especially the genome track plots, is crucial for genomics researchers to discover patterns in large-scale sequencing dataset. Although existing tools works well for producing a normal view of the input data, they are not convenient when users want to create customized data representations. Such gap between the visualization and data processing, prevents the users to uncover more hidden structure of the dataset. RESULTS: We developed CoolBox-an open-source toolkit for visual analysis of genomics data. This user-friendly toolkit is highly compatible with the Python ecosystem and customizable with a well-designed user interface. It can be used in various visualization situations like a Swiss army knife. For example, to produce high-quality genome track plots or fetch commonly used genomic data files with a Python script or command line, to explore genomic data interactively within Jupyter environment or web browser. Moreover, owing to the highly extensible Application Programming Interface design, users can customize their own tracks without difficulty, which greatly facilitate analytical, comparative genomic data visualization tasks. CONCLUSIONS: CoolBox allows users to produce high-quality visualization plots and explore their data in a flexible, programmable and user-friendly way.


Assuntos
Ecossistema , Genômica , Genoma , Software , Navegador
7.
Nanomaterials (Basel) ; 11(10)2021 Sep 24.
Artigo em Inglês | MEDLINE | ID: mdl-34684927

RESUMO

In the last 20 years, silicon quantum dots have received considerable attention from academic and industrial communities for research on readout, manipulation, storage, near-neighbor and long-range coupling of spin qubits. In this paper, we introduce how to realize a single spin qubit from Si-MOS quantum dots. First, we introduce the structure of a typical Si-MOS quantum dot and the experimental setup. Then, we show the basic properties of the quantum dot, including charge stability diagram, orbital state, valley state, lever arm, electron temperature, tunneling rate and spin lifetime. After that, we introduce the two most commonly used methods for spin-to-charge conversion, i.e., Elzerman readout and Pauli spin blockade readout. Finally, we discuss the details of how to find the resonance frequency of spin qubits and show the result of coherent manipulation, i.e., Rabi oscillation. The above processes constitute an operation guide for helping the followers enter the field of spin qubits in Si-MOS quantum dots.

8.
J Appl Toxicol ; 2021 Oct 15.
Artigo em Inglês | MEDLINE | ID: mdl-34655103

RESUMO

Asthma progression is involved in airway epithelial dysfunction, airway inflammatory response, and mucus hypersecretion. Euxanthone has been found to exhibit cytotoxic activity on several human diseases, such as neurological disorders and cancers. Our study aimed to explore the influence of euxanthone on lipopolysaccharide (LPS)-induced injury, inflammatory response, and mucin 5AC (MUC5AC) hypersecretion in human airway epithelial cells (AECs). Network pharmacology analysis was carried out to analyze the drug targets and key pathways of euxanthone against asthma. Cell injury was evaluated by CCK-8, Lactate dehydrogenase (LDH) release assay, and terminal deoxynucleotidyl transferase-mediated dUTP nick end-labeling (TUNEL) assay. The production of interleukin (IL)-6, IL-8, monocyte chemoattractant protein-1 (MCP-1), and MUC5AC was measured using enzyme-linked immunosorbent assay (ELISA). MUC5AC mRNA expression was detected by qRT-PCR. Toll-like receptor 4 (TLR4) and myeloid differentiation factor 88 (MyD88) protein expression was examined by western blot analysis. Venn diagram showed 14 overlapping targets between euxanthone and asthma. According to Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway enrichment analysis, we focused on TLR signaling pathway. LPS exposure evoked viability reduction, increased LDH release and apoptosis, and induced production of inflammatory cytokines (IL-6, IL-8, and MCP-1) and MUC5AC hypersecretion in human AECs, which were alleviated by euxanthone. Mechanistically, we validated that euxanthone attenuated LPS-induced activation of TLR4/MyD88 pathway in AECs. Moreover, inhibition of the TLR4/MyD88 pathway enhanced the inhibitory effect of euxanthone on LPS-induced cell injury, inflammatory response and MUC5AC expression. In conclusion, euxanthone attenuated LPS-induced cell injury, inflammatory response, and MUC5AC expression in AECs by inhibiting the activation of TLR4/MyD88 pathway.

9.
Artigo em Inglês | MEDLINE | ID: mdl-34528190

RESUMO

A clear understanding of the impacts of urban land expansion on ecosystem services is crucial for sustainable urban planning. Although various studies have shown that urban land expansion caused a degradation of ecosystem services, the relationship between the spatial variation of urban land expansion and ecosystem services still remains unclear. This study quantified the ecosystem services and urban land expansion indicators of Wuhan for 1990-2015 and analyzed the spatial and temporal variation characteristics of ecosystem service values (ESVs) and urban land expansion indicators. Using spatial autocorrelation analysis and linear regression, the quantitative and qualitative correlations between ecosystem services and urban land expansion indicators were explored. The total ESV of Wuhan decreased by 16.47%, representing a loss of 1636.19 million yuan. Areas with extremely low ESVs continuously expanded outward from the urban center. During 2010-2015, the urban land expansion area, intensity, damage weight, and distance peaked, which caused an enormous decrease of the total ESV. Negative correlations were found between urban land expansion and all ecosystem services; the correlation with food production was most significant, indicating that urban land expansion had the strongest impact on food production. The expansion area is the main factor causing the decline of each ecosystem service among urban land expansion indicators. This study presents the impact characteristics of urban land expansion on ecosystem services, and the results provide a reference for reasonable decision making in urban planning.

10.
Pharmacol Ther ; : 107983, 2021 Sep 02.
Artigo em Inglês | MEDLINE | ID: mdl-34480962

RESUMO

Fibrosis, which is characterized by excessive extracellular matrix (ECM) deposition, is a wound-healing response to organ injury and may promote cancer and failure in various organs, such as the heart, liver, lung, and kidney. Aging associated with oxidative stress and inflammation exacerbates cellular dysfunction, tissue failure, and body function disorders, all of which are closely related to fibrosis. Sirtuin-1 (SIRT1) is a class III histone deacetylase that regulates growth, transcription, aging, and metabolism in various organs. This protein is downregulated in organ injury and fibrosis associated with aging. Its expression and distribution change with age in different organs and play critical roles in tissue oxidative stress and inflammation. This review first described the background on fibrosis and regulatory functions of SIRT1. Second, we summarized the relationships of SIRT1 with other proteins and its protective action during fibrosis in the heart, liver, lung and kidney. Third, the activation of SIRT1 in therapies of tissue fibrosis, especially in liver fibrosis and aging-related tissue injury, was analyzed. In conclusion, SIRT1 targeting may be a new therapeutic strategy in fibrosis.

11.
Pharmacol Res Perspect ; 9(5): e00765, 2021 10.
Artigo em Inglês | MEDLINE | ID: mdl-34523246

RESUMO

Gut microbiota disorder will lead to intestinal damage. This study evaluated the influence of total diterpenoids extracted from Euphorbia pekinensis (TDEP) on gut microbiota and intestinal mucosal barrier after long-term administration, and the correlations between gut microbiota and intestinal mucosal barrier were analysed by Spearman correlation analysis. Mice were randomly divided to control group, TDEP groups (4, 8, 16 mg/kg), TDEP (16 mg/kg) + antibiotic group. Two weeks after intragastric administration, inflammatory factors (TNF-α, IL-6, IL-1ß) and LPS in serum, short chain fatty acids (SCFAs) in feces were tested by Enzyme-linked immunosorbent assay (ELISA) and high-performance liquid chromatography (HPLC), respectively. The expression of tight junction (TJ) protein in colon was measured by western blotting. Furthermore, the effects of TDEP on gut microbiota community in mice have been investigated by 16SrDNA high-throughput sequencing. The results showed TDEP significantly increased the levels of inflammatory factors in dose-dependent manners, and decreased the expression of TJ protein and SCFAs, and the composition of gut microbiota of mice in TDEP group was significantly different from that of control group. When antibiotics were added, the diversity of gut microbiota was significantly reduced, and the colon injury was more serious. Finally, through correlation analysis, we have found nine key bacteria (Barnesiella, Muribaculaceae_unclassified, Alloprevotella, Candidatus_Arthromitus, Enterorhabdus, Alistipes, Bilophila, Mucispirillum, Ruminiclostridium) that may be related to colon injury caused by TDEP. Taken together, the disturbance of gut microbiota caused by TDEP may aggravate the colon injury, and its possible mechanism may be related to the decrease of SCFAs in feces, disrupted the expression of TJ protein in colon and increasing the contents of inflammatory factors.

12.
Chin Med ; 16(1): 73, 2021 Aug 06.
Artigo em Inglês | MEDLINE | ID: mdl-34362420

RESUMO

As a Traditional Chinese Medicine, Eucommia ulmoides Oliv. has been used for the treatment of various diseases since ancient times, involving lumbar pain, knee pain, osteoporosis, hepatoprotection, paralysis, intestinal haemorrhoids, vaginal bleeding, abortion, spermatorrhoea, foot fungus, anti-aging etc. With the developing discovery of E. ulmoides extracts and its active components in various pharmacological activities, E. ulmoides has gained more and more attention. Up to now, E. ulmoides has been revealed to show remarkable therapeutic effects on hypertension, hyperglycemia, diabetes, obesity, osteoporosis, Parkinson's disease, Alzheimer's disease, sexual dysfunction. E. ulmoides has also been reported to possess antioxidant, anti-inflammatory, neuroprotective, anti-fatigue, anti-aging, anti-cancer and immunoregulation activities etc. Along these lines, this review summarizes the traditional application and modern pharmacological research of E. ulmoides, providing novel insights of E. ulmoides in the treatment of various diseases.

13.
Front Cell Dev Biol ; 9: 706375, 2021.
Artigo em Inglês | MEDLINE | ID: mdl-34368157

RESUMO

Human papillomavirus (HPV) integration is the major contributor to cervical cancer (CC) development by inducing structural variations (SVs) in the human genome. SVs are directly associated with the three-dimensional (3D) genome structure leading to cancer development. The detection of SVs is not a trivial task, and several genome-wide techniques have greatly helped in the identification of SVs in the cancerous genome. However, in cervical cancer, precise prediction of SVs mainly translocations and their effects on 3D-genome and gene expression still need to be explored. Here, we have used high-throughput chromosome conformation capture (Hi-C) data of cervical cancer to detect the SVs, especially the translocations, and validated it through whole-genome sequencing (WGS) data. We found that the cervical cancer 3D-genome architecture rearranges itself as compared to that in the normal tissue, and 24% of the total genome switches their A/B compartments. Moreover, translocation detection from Hi-C data showed the presence of high-resolution t(4;7) (q13.1; q31.32) and t(1;16) (q21.2; q22.1) translocations, which disrupted the expression of the genes located at and nearby positions. Enrichment analysis suggested that the disrupted genes were mainly involved in controlling cervical cancer-related pathways. In summary, we detect the novel SVs through Hi-C data and unfold the association among genome-reorganization, translocations, and gene expression regulation. The results help understand the underlying pathogenicity mechanism of SVs in cervical cancer development and identify the targeted therapeutics against cervical cancer.

14.
Front Pharmacol ; 12: 630319, 2021.
Artigo em Inglês | MEDLINE | ID: mdl-34434104

RESUMO

Siegesbeckia orientalis L. (SO) is a commonly used Chinese medicinal herb. It has long been used as a remedy in traditional Chinese medicine (TCM) for symptoms that resemble inflammatory joint disorders. However, it is slightly toxic. According to the TCM theory, processing can reduce the toxicity of the herbs. Here, we performed metabolomics to determine whether processing with rice wine reduces the toxicity of raw SO, and to explore the mechanisms underlying the raw SO-induced toxicity and the toxicity-reducing effect of processing. Our results showed that raw SO has long-term toxicity in rats. It significantly elevated the serum level of LDH and caused histopathological damages in the lung tissues. It is worth noting that the LDH level in the PSO group was lower than that in the raw SO group, and the damages in lung tissues were relatively mild in PSO-treated rats, suggesting that processing reduces the pulmonary toxicity of the raw. Moreover, a total of 32 significantly changed metabolites were identified. Based on the MetaboAnalyst pathway analysis, we found that two characteristic metabolic pathways including alanine, aspartate and glutamate metabolism and glycerophospholipid metabolism were only changed in the raw SO group, while histidine metabolism was only changed in the PSO group, which suggests that induction of oxidative stress contributes to raw SO-induced pulmonary toxicity, and free radical scavenging might be responsible for the toxicity-reducing effect of processing. Our data shed new light on how raw SO induces pulmonary toxicity and how the toxicity can be reduced by processing. This study not only provides scientific justifications for the traditional processing theory of SO, but also helps to optimize the processing protocol and the clinical drug combination of SO.

15.
J Biochem Mol Toxicol ; 35(9): e22852, 2021 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-34396630

RESUMO

Colon adenocarcinoma (COAD) is a common malignant tumor of the digestive tract that threatens human health seriously. Thus, it is urgent to explore biomarkers that can be used to evaluate a patient's survival prognosis overall as a supplementary treatment. RNA-seq expression profiles were downloaded from The Cancer Genome Atlas and Gene Expression Omnibus, and Lasso and multivariate Cox regression analyses were used for developing the prognostic model. Finally, a nomogram comprising the prognostic model was established to evaluate survival overall. A risk model comprised of a total of 12 immune-related gene pairs was constructed. Further analysis revealed the model's independent prognostic ability in relation to other clinical characteristics. This model's nomogram could help clinicians choose personalized treatment for COAD patients. This model has significant potential to complement COAD's clinical identifying characteristics, and also provide new insights into the identification of colon cancer patients with a high risk of death.


Assuntos
Adenocarcinoma , Neoplasias do Colo , Bases de Dados de Ácidos Nucleicos , Regulação Neoplásica da Expressão Gênica , RNA-Seq , Adenocarcinoma/genética , Adenocarcinoma/metabolismo , Adenocarcinoma/mortalidade , Neoplasias do Colo/genética , Neoplasias do Colo/metabolismo , Neoplasias do Colo/mortalidade , Intervalo Livre de Doença , Feminino , Humanos , Masculino , Taxa de Sobrevida
16.
mSystems ; 6(4): e0078321, 2021 Aug 31.
Artigo em Inglês | MEDLINE | ID: mdl-34402643

RESUMO

Mycobacterium tuberculosis can invade different cells with distinct persistence fates because cells are equipped with different host restriction factors. However, the underlying mechanisms remain elusive. Here, we infected THP1 and Raw264.7 macrophages cell lines, A549 epithelial cell line, and hBMEC and bEnd.3 endothelial cell lines with M. tuberculosis and demonstrated that M. tuberculosis significantly inhibited lysosome acidification in THP1, hBMEC, A549, and Raw264.7 cells, while, in bEnd.3 cells, M. tuberculosis was mainly delivered into acidified phagolysosomes and auto-lysosomes. The systematic gene profile analysis of different cells and intracellular M. tuberculosis showed that the phagosome autophagy-pathway-related genes itgb3 and atg3 were highly expressed in bEnd.3 cells. Knockdown of these genes significantly increased the number of viable intracellular M. tuberculosis bacilli by altering phagosomal trafficking in bEnd.3 cells. Treatment with itgb3 agonist significantly decreased M. tuberculosis survival in vivo. These findings could facilitate the identification of anti-M. tuberculosis host genes and guide M. tuberculosis-resistant livestock breeding. IMPORTANCE As an intracellular pathogen, Mycobacterium tuberculosis could avoid host cell immune clearance using multiple strategies for its long-term survival. Understanding these processes could facilitate the development of new approaches to restrict intracellular M. tuberculosis survival. Here, we characterized the detailed molecular events occurring during intracellular trafficking of M. tuberculosis in macrophage, epithelial, and endothelial cell lines and found that ITGB3 facilitates M. tuberculosis clearance in endothelial cells through altering phagosomal trafficking. Meanwhile, the treatment with ITGB3 agonist could reduce bacterial load in vivo. Our results identified new anti-M. tuberculosis restriction factors and illuminated a new anti-M. tuberculosis defense mechanism.

17.
Pain Physician ; 24(4): E425-E432, 2021 07.
Artigo em Inglês | MEDLINE | ID: mdl-34213867

RESUMO

BACKGROUND: Percutaneous radiofrequency ablation (RFA) of the trigeminal Gasserian ganglion via the foramen ovale is still one of the classic treatments for primary trigeminal neuralgia. However, the Gasserian ganglion is deep in the middle cranial fossa. Although it is a structure outside the brain tissue, the puncture needle must enter the encephalic to reach the Gasserian ganglion and so it is difficult to completely avoid the risk of intracranial hemorrhage and infection caused by puncture damage to intracranial blood vessels. It is not clear whether if it is possible for RFA at the extracranial non-gasserian-ganglion site via the exit of the cranial channel (foramen ovale) for patients with V3 trigeminal neuralgia (TN). STUDY DESIGN: Prospective, clinical research study. SETTING: Department of Anesthesiology and Pain Medical Center, Jiaxing, China. METHODS: One hundred and seven patients with isolated mandibular branch trigeminal neuralgia were included. Radiofrequency thermocoagulation was performed by CT-guided percutaneous puncture through the foramen ovale. The puncture target was the midpoint of the horizontal transverse diameter of the oval foramen. If the tingling sensation in the mandibular nerve innervation area could be detected, the radiofrequency thermocoagulation (90°C, 120 sec) under intravenous anesthesia would be performed. We investigated the inclination angle, puncture angle and depth, puncture operation time, intraoperative complications and short-term and long-term results after operation. RESULTS: After radiofrequency thermocoagulation, the pain in the mandibular branch dominant area was completely diminished in 104 patients. Two patients were cured after the second radiofrequency treatment. No intracranial hemorrhage not infection complications occurred, except for facial hematoma during operation in 21 cases. After 12-24 months of follow-up, 9 patients had recurrence and were still effective after receiving additional extracranial radiofrequency treatment. LIMITATIONS: A control group should be established and more clinical data should be collected in future work. CONCLUSION: Extracranial non-Gasserian-ganglion RF can achieve satisfactory results and improve the safety of radiofrequency treatment for trigeminal neuralgia.


Assuntos
Forame Oval , Neuralgia do Trigêmeo , Eletrocoagulação , Forame Oval/cirurgia , Humanos , Estudos Prospectivos , Gânglio Trigeminal/cirurgia , Neuralgia do Trigêmeo/cirurgia
18.
Front Microbiol ; 12: 658637, 2021.
Artigo em Inglês | MEDLINE | ID: mdl-34276592

RESUMO

Tuberculosis (TB) is a debilitating infectious disease responsible for more than one million deaths per year. The emergence of drug-resistant TB poses an urgent need for the development of new anti-TB drugs. In this study, we screened a library of over 4,000 small molecules and found that orbifloxacin and the peptide AK15 possess significant bactericidal activity against Mycobacterium tuberculosis (Mtb) in vitro. Orbifloxacin also showed an effective ability on the clearance of intracellular Mtb and protect mice from a strong inflammatory response but not AK15. Moreover, we identified 17 nucleotide mutations responsible for orbifloxacin resistance by whole-genome sequencing. A critical point mutation (D94G) of the DNA gyrase (gyrA) gene was found to be the key role of resistance to orbifloxacin. The computational docking revealed that GyrA D94G point mutation can disrupt the orbifloxacin-protein gyrase interactions mediated by magnesium ion bridge. Overall, this study indicated the potential ability of orbifloxacin as an anti-tuberculosis drug, which can be used either alone or in combination with first-line antibiotics to achieve more effective therapy on TB.

19.
Int Immunopharmacol ; 98: 107873, 2021 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-34182246

RESUMO

Osteoarthritis (OA) is a chronic age-related progressive joint disorder. Degradation of the cartilage extracellular matrix (ECM) is considered a hallmark of OA and may be a target for new therapeutic methods. Schisandrae Fructus (SF) has been shown to be effective in treating OA. The major active components of SF are lignans. However, the targets of SF and the pharmacological mechanisms underlying the effects of SF lignans in the treatment of OA have not been elucidated. Therefore, based on network pharmacology, this research predicted the treatment targets of six lignans in SF, constructed a protein-protein interaction network and identified 15 hub genes in the OA-target protein-protein interaction network. Through Gene Ontology function and pathway analyses, the gene functions of lignans in the treatment of OA were determined. Finally, the anti-OA effects of lignans and underlying mechanisms identified in the network pharmacology analysis were verified by molecular docking, real-time PCR and western blotting in vitro. The biological processes of the genes and proteins targeted by lignans in the treatment of OA included the immune response, inflammatory response, cell signal transduction and phospholipid metabolism. Moreover, 20 metabolic pathways were enriched. Network pharmacology, molecular docking and in vitro and in vivo experimental results revealed that SF, schisanhenol and gamma-schisandrin inhibited EGFR and MAPK14 gene expression by inhibiting SRC gene expression and activity and then decreased MMP 13 and collagen II protein and gene expression. This research provides a basis for further study of the anti-OA effects and mechanisms of SF, schisanhenol and gamma-schisandrin.

20.
Sci Adv ; 7(26)2021 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-34162542

RESUMO

Like most DNA viruses, herpesviruses precisely deliver their genomes into the sophisticatedly organized nuclei of the infected host cells to initiate subsequent transcription and replication. However, it remains elusive how the viral genome specifically interacts with the host genome and hijacks host transcription machinery. Using pseudorabies virus (PRV) as model virus, we performed chromosome conformation capture assays to demonstrate a genome-wide specific trans-species chromatin interaction between the virus and host. Our data show that the PRV genome is delivered by the host DNA binding protein RUNX1 into the open chromatin and active transcription zone. This facilitates virus hijacking host RNAPII to efficiently transcribe viral genes, which is significantly inhibited by either a RUNX1 inhibitor or RNA interference. Together, these findings provide insights into the chromatin interaction between viral and host genomes and identify new areas of research to advance the understanding of herpesvirus genome transcription.

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