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1.
Curr Eye Res ; : 1-7, 2022 Aug 03.
Artigo em Inglês | MEDLINE | ID: mdl-35924323

RESUMO

PURPOSE: Retinitis pigmentosa (RP) constitutes a class of common inherited retinal dystrophies. Patients with RP and comorbid primary angle-closure glaucoma (PACG) have been described, but the relationship between the diseases remains unclear. This study investigated the clinical and genetic characteristics of Chinese patients with RP and comorbid PACG. METHODS: Of 1356 patients with RP, we analyzed the genetic features of 39 RP patients with PACG using next-generation sequencing and reviewed their clinical characteristics. RESULTS: In total, 18 patients with acute PACG and 21 patients with chronic PACG were included in this study; their age at examination was 50.54 ± 12.99 years (range, 25.0-71.0 years), and their age at PACG onset was 46.04 ± 14.50 years (range, 24.9-68.0 years). Additionally, the mean lens thickness (LT) was 4.49 ± 0.44 µm, and the mean axial length (AL) was 22.63 ± 1.17 mm. Notably, the prevalence of PACG in patients with RP was 2.88%; this was higher than the prevalence in the general population. This could be explained by nanophthalmos, thickened lentis, ectopia lentis, or zonular insufficiency. Furthermore, patients with a shorter AL, a greater LT, iridociliary cysts, or nanophthalmos exhibited earlier development of PACG. Overall, 30 disease-causing variants spanning 17 genes were identified in 56.41% of the patients, and PRPH2 was the most common mutation gene. CONCLUSIONS: Our findings revealed that there is a strong association between RP and PACG. Furthermore, intraocular pressure (IOP) should be measured in patients with RP to protect them from the aggravated damage of an elevated IOP.

2.
Pulm Circ ; 12(3): e12034, 2022 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-35874853

RESUMO

The purpose of this study was to investigate the effects of sacubitril/valsartan on right ventricular (RV) function in patients with pulmonary hypertension (PH) due to heart failure with reduced ejection fraction (HFrEF). We prospectively enrolled patients with HFrEF-induced PH admitted to the Department of Cardiology between August 2018 and December 2019. Patients were randomized to receive oral treatment with sacubitril/valsartan or enalapril. Epidemiological data were recorded before treatment. Echocardiography was performed at admission and 6 months of follow-up, and all parameters were compared. Major adverse cardiac events (MACEs) were compared between baseline and 6 months follow-up. There were no significant differences in the baseline characteristics between the two groups. After 6 months of treatment, both treatment groups improved the following parameters from baseline (mean ± SD): left atrium, left ventricle, the left ventricular ejection function (LVEF), RV systolic function (the tricuspid annular plane systolic excursion [TAPSE], the systolic pulmonary artery pressure [sPAP], and TAPSE/sPAP). After 6 months, sacubitril/valsartan improved significantly the following parameters compared with enalapril (all p < 0.05): LVEF (47.07 ± 6.93% vs. 43.47 ± 7.95%); TAPSE (15.33 ± 1.31 vs. 14.78 ± 1.36 mm); sPAP (36.76 ± 14.32 vs. 42.26 ± 12.07 mmHg); and TAPSE/sPAP ratio (0.50 ± 0.23 vs. 0.39 ± 0.14), respectively. There was no difference in readmissions due to recurrent heart failure. Sacubitril/valsartan seems to provide more beneficial effects among patients with HFrEF-induced PH to improve RV function, along with a decrease in pulmonary pressure.

3.
Lab Invest ; 2022 Jul 08.
Artigo em Inglês | MEDLINE | ID: mdl-35804043

RESUMO

Glaucoma, a common cause of blindness, is characterized by the progressive loss of retinal ganglion cells (RGCs). Growing evidence suggests that nobiletin (NOB) is a promising neuroprotective drug; however, its effects on glaucomatous neurodegeneration remain unknown. Using rat models of microbead occlusion in vivo and primary RGCs model of hypoxia in vitro, we first demonstrate that NOB reduces RGC apoptosis by a TUNEL assay, Hoechst 33342 staining and FluoroGold (FG) retrograde labeling. This effect does not depend on intraocular pressure (IOP) lowering. Additionally, NOB partially restored the functional and structural damage of inner retinas, attenuated Müller glial activation and oxidative stress caused by ocular hypertension. At 2 weeks after IOP elevation, NOB further enhanced Nrf2/HO-1 pathway in RGCs to withstand the cumulative damage of ocular hypertension. With the administration of HO-1 inhibitor tin-protoporphyrin IX (SnPP), the protective effect of NOB was attenuated. Overall, these results indicate that NOB exerts an outstanding neuroprotective effect on RGCs of glaucomatous neurodegeneration. Besides, interventions to enhance activation of Nrf2/HO-1 pathway can slow the loss of RGCs and are viable therapies for glaucoma.

4.
World J Gastroenterol ; 28(20): 2184-2200, 2022 May 28.
Artigo em Inglês | MEDLINE | ID: mdl-35721888

RESUMO

BACKGROUND: Recent studies have emphasized the emerging importance of long noncoding RNAs (lncRNAs) in colorectal cancer (CRC). However, the functions and regulatory mechanisms of numerous lncRNAs in CRC have not been fully elucidated. AIM: To explore the functional role and underlying molecular mechanisms of lncRNA TNFRSF10A-AS1 in CRC. METHODS: TNFRSF10A-AS1 expression was measured by quantitative real-time polymerase chain reaction in CRC, and the relationship between TNFRSF10A-AS1 levels and the clinicopathological features of CRC patients was analyzed. The effect of TNFRSF10A-AS1 expression on CRC proliferation and metastasis was examined in vitro and in vivo. Mechanistically, we investigated how TNFRSF10A-AS1 is involved in CRC as a competitive endogenous RNA. RESULTS: TNFRSF10A-AS1 was expressed at a high level in CRC and the upregulation of TNFRSF10A-AS1 was associated with advanced T grade and tumor size in CRC patients. A functional investigation revealed that TNFRSF10A-AS1 enhanced the proliferation, migration ability and invasion ability of colon cancer cells in vitro and in vivo. A mechanistic analysis demonstrated that TNFRSF10A-AS1 acted as a miR-3121-3p molecular sponge to regulate HuR expression, ultimately promoting colorectal tumorigenesis and progression. CONCLUSION: TNFRSF10A-AS1 exerts a tumor-promoting function through the miR-3121-3p/HuR axis in CRC, indicating that it may be a novel target for CRC therapy.


Assuntos
Neoplasias Colorretais , MicroRNAs , RNA Longo não Codificante , Linhagem Celular Tumoral , Movimento Celular/genética , Proliferação de Células/genética , Neoplasias Colorretais/genética , Neoplasias Colorretais/patologia , Regulação Neoplásica da Expressão Gênica , Humanos , MicroRNAs/genética , MicroRNAs/metabolismo , RNA Longo não Codificante/genética , RNA Longo não Codificante/metabolismo , Regulação para Cima
5.
Cancer Cell Int ; 22(1): 190, 2022 May 16.
Artigo em Inglês | MEDLINE | ID: mdl-35578228

RESUMO

Extracellular vesicles secreted by tumor microenvironment (TME) cells are vital players in tumor progression through transferring nucleic acids and proteins. Macrophages are the main immune cells in TME and tumor associated macrophages (TAM) express M2 phenotype, which induce tumor proliferation, angiogenesis, invasion, metastasis and immune elimination, resulting in the subsequent evolution of malignancies. There are a high number of studies confirmed that tumor cells and TAM interact with each other through extracellular vesicles in various cancers, like pancreatic ductal adenocarcinoma, gastric cancer, breast cancer, ovarian cancer, colon cancer, glioblastoma, hepatocellular cancer, and lung cancer. Herein, this review summarizes the current knowledge on mechanisms of communications between tumor cells and TAM via extracellular vesicles, mainly about microRNAs, and targeting these events might represent a novel approach in the clinical implications of this knowledge into successful anti-cancer strategies.

6.
J Gastrointest Oncol ; 13(2): 695-709, 2022 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-35557592

RESUMO

Background: Colitis-associated colorectal cancer (CAC) is a serious complication of inflammatory bowel disease (IBD). microRNA-320 (miRNA-320) promotes intestinal mucosal barrier repair in IBD and inhibits tumor progression. However, the role of miRNA-320 in the progression of CAC remains to be defined. We studied the mechanisms of miRNA-320 in the progression of CAC in mice. Methods: CAC was induced in mice (C57BL/B6) by the administration of azoxymethane (AOM) and dextran sulfate sodium (DSS), and the mice were given a lentiviral vector (LV) overexpressing mmu-miRNA-320. The level of miRNA-320 was analyzed by quantitative real-time polymerase chain reaction (qPCR). Colonic inflammation, histological analysis, and tumorigenesis were evaluated. Ki-67 in colonic tissues was examined by immunohistochemistry. B-cell lymphoma-extra large (BCL-xl) and proliferating cell nuclear antigen (PCNA) expression was examined by Western blot. Furthermore, the proliferation, migration, and invasion of colorectal cancer (CRC) cells were evaluated. The levels of interleukin-6 receptor (IL-6R), signal transducer and activator of transcription 3 (STAT3), and phosphorylated-signal transducer and activator of transcription 3 (p-STAT3) were examined by Western blot and qPCR. Results: miRNA-320 was downregulated in CAC mice (0.57±0.13 vs. 1.00±0.12, t=-5.95, P<0.001). miRNA-320 decreased the disease activity index (DAI) scores, improved colonic inflammation, and inhibited tumor formation (tumor number: 8.00±2.90 vs. 13.67±2.73, t=-3.49, P<0.01) in mice with CAC. miRNA-320 suppressed the expression of BCL-xl, PCNA, and Ki-67 (0.38±0.07 vs. 0.69±0.08, t=-7.30, P<0.001). miRNA-320 inhibited colon cancer cell proliferation, migration, and invasion. miRNA-320 significantly inhibited the levels of IL-6R [colon tissue messenger RNA (mRNA): 4.06±1.44 vs. 10.05±1.55, t=-6.94, P<0.001], STAT3, and p-STAT3 in vivo and in vitro. Silencing IL-6R expression partially reversed the IL-6R/STAT3-suppressing and tumor-inhibiting effect of miRNA-320. Conclusions: miRNA-320 inhibits tumorigenesis in mice with CAC by suppressing IL-6R/STAT3 expression, and IL-6R is a target gene of miRNA-320.

7.
Zhongguo Zhong Yao Za Zhi ; 47(9): 2491-2499, 2022 May.
Artigo em Chinês | MEDLINE | ID: mdl-35531696

RESUMO

The present study investigated the therapeutic effect and mechanism of Di'ao Xinxuekang(DXXK) on non-alcoholic steatohepatitis(NASH) in mice. Sixty-five C57 BL/6 J mice were randomly divided into a normal group and an experimental group for model induction with the high-fat diet for 16 weeks. Then the mice in the experimental group were randomly divided into a model group, an atorvastatin group(4 mg·kg~(-1)·d~(-1)), and high-(200 mg·kg~(-1)·d~(-1)), medium-(60 mg·kg~(-1)·d~(-1)), and low-dose(20 mg·kg~(-1)·d~(-1)) DXXK groups, with 10 mice in each group. Drugs were administered by gavage for eight weeks. Serum lipid, liver lipid, serum alanine aminotransferase(ALT), aspartate aminotransferase(AST), malondialdehyde(MDA), superoxide dismutase(SOD), and glutathione reductase(GSH-Px) were determined. Interleukin-1ß(IL-1ß) and tumor necrosis factor-α(TNF-α) were measured by enzyme-linked immunosorbent assay(ELISA). The liver index was calculated. The liver pathological change and lipid accumulation were observed by HE and oil red O staining. The liver ultrastructure was observed by the transmission electron microscope. The mRNA and protein expression of nuclear factor-erythroid 2 related factor 2(Nrf2) and heme oxygenase-1(HO-1) was detected by real-time fluorescence-based quantitative PCR and Western blot, respectively. The results showed that compared with the normal group, the model group displayed serum lipid and liver lipid metabolism disorders, elevated transaminase, lipid deposition, steatosis, and inflammation, suggesting that the NASH model in mice was properly induced. Compared with the model group, the DXXK groups showed decreased serum lipid, liver lipid, ALT, AST, MDA, IL-1ß, and TNF-α, increased SOD and GSH-Px, alleviated hepatic steatosis, ballooning, and inflammation, and up-regulated Nrf2 and HO-1 gene and protein expression. In conclusion, DXXK can significantly alleviate NASH in mice, which is related to the inhibition of oxidative stress and inflammatory damage by up-regulating the Nrf2/HO-1 signaling pathway.


Assuntos
Fator 2 Relacionado a NF-E2 , Hepatopatia Gordurosa não Alcoólica , Animais , Medicamentos de Ervas Chinesas , Inflamação/metabolismo , Lipídeos , Fígado , Camundongos , Fator 2 Relacionado a NF-E2/genética , Fator 2 Relacionado a NF-E2/metabolismo , Hepatopatia Gordurosa não Alcoólica/tratamento farmacológico , Hepatopatia Gordurosa não Alcoólica/genética , Hepatopatia Gordurosa não Alcoólica/metabolismo , Estresse Oxidativo , Transdução de Sinais , Superóxido Dismutase/genética , Superóxido Dismutase/metabolismo , Fator de Necrose Tumoral alfa/metabolismo
8.
Front Endocrinol (Lausanne) ; 13: 831859, 2022.
Artigo em Inglês | MEDLINE | ID: mdl-35418945

RESUMO

Introduction: The choice of trigger drug for the controlled ovarian hyperstimulation (COH) protocol correlates with the outcome of in vitro fertilization/intracytoplasmic sperm injection embryo transfer (IVF/ICSI-ET). The co-administration of gonadotropin releasing hormone agonist (GnRH-a) and human chorionic gonadotropin (hCG), i.e., dual trigger, for final oocyte maturation, has received much attention in recent years. This trial was designed to determine whether a dual trigger approach by lengthening the time between trigger and ovum pick-up (OPU) improves the quantity and quality of mature oocytes/top-quality embryos and pregnancy outcomes in expected normal responders with a high immature oocyte rate. Methods and Analysis: We propose a study at the Affiliated Hospital of Shandong University of Chinese Medicine. A total of 90 individuals undergoing COH use a fixed GnRH antagonist protocol. They will be assigned randomly into two groups according to the trigger method and timing: recombinant hCG (6500 IU) will be injected only 36 hours before OPU for final oocyte maturation (hCG-only trigger); co-administration of GnRH-a and hCG for final oocyte maturation, 40 and 34 hours prior to OPU, respectively (Dual trigger). The primary outcome is metaphase-II (MII) oocytes rate. Secondary outcomes are number of oocytes retrieved, fertilization rate, top-quality embryos rate, blastula formation rate, embryo implantation rate, clinical pregnancy rate, miscarriage rate, live birth rate, cumulative pregnancy/live birth rates, and ovarian hyperstimulation syndrome (OHSS) rate. Ethics and Dissemination: The reproductive ethics committee of the Affiliated Hospital of Shandong University of Traditional Chinese Medicine certified this study (Identifier: SDUTCM/2021.7.26) as ethical. All individuals will sign written informed consent. All data and biological samples will be protected according to law. The results of this study will be disseminated in a peer-reviewed scientific journal. Clinical Trial Registration: [chictr.gov.cn], identifier [ChiCTR2100049292].


Assuntos
Gonadotropina Coriônica , Síndrome de Hiperestimulação Ovariana , Feminino , Hormônio Liberador de Gonadotropina , Humanos , Oócitos , Síndrome de Hiperestimulação Ovariana/epidemiologia , Síndrome de Hiperestimulação Ovariana/prevenção & controle , Indução da Ovulação/métodos , Gravidez , Ensaios Clínicos Controlados Aleatórios como Assunto , Proteínas Recombinantes
9.
Pathol Res Pract ; 234: 153894, 2022 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-35489123

RESUMO

Macrophages substantially influence the development, progression, and complications of inflammation-driven diseases. Although numerous studies support the critical role of Notch signaling in most inflammatory diseases, there is limited data on the role of Notch signaling in TLR4-induced macrophage activation and interaction of Notch signaling with other signaling pathways in macrophages during inflammation, such as the NF-κB pathway. This study confirmed that stimulation with lipopolysaccharide (LPS), a TLR4 ligand, upregulated Notch1 expression in monocyte/macrophage-like RAW264.7 cells and bone marrow-derived macrophages (BMDMs). LPS also induced increased mRNA expression of Notch target genes Notch1 and Hes1 in macrophages, suggesting that TLR4 signaling enhances activation of the Notch pathway. The upregulation of Notch1, Notch1 intracellular domain (NICD), and Hes1 proteins by LPS treatment was inhibited by DAPT, a Notch1 inhibitor. Additionally, the increased TNF-α, IL-6, and IL-1ß expression induced by LPS was inhibited by DAPT and rescued by jagged1, a Notch1 ligand. Furthermore, suppression of Notch signaling by DAPT upregulated Cylindromatosis (CYLD) expression but downregulated TRAF6 expression, IκB kinase (IKK) α/ß phosphorylation, and subsequently, phosphorylation and degradation of IκB-α, indicating that DAPT inhibited NF-κB activation triggered by TLR-4. Interestingly, DAPT did not inhibit the increased MyD88 expression induced by LPS. Our study findings demonstrate that macrophage stimulation via the TLR4 signaling cascade triggers activation of Notch1 signaling, which regulates the expression patterns of genes involved in pro-inflammatory responses by activating NF-κB. This effect may be dependent on the CYLD-TRAF6-IKK pathway. Thus, Notch1 signaling may provide a therapeutic target against infectious and inflammation-driven diseases.


Assuntos
NF-kappa B , Receptor 4 Toll-Like , Humanos , Quinase I-kappa B/metabolismo , Inflamação/metabolismo , Ligantes , Lipopolissacarídeos/farmacologia , Macrófagos/metabolismo , NF-kappa B/metabolismo , Inibidores da Agregação Plaquetária/metabolismo , Inibidores da Agregação Plaquetária/farmacologia , Receptor Notch1/metabolismo , Fator 6 Associado a Receptor de TNF/metabolismo , Fator 6 Associado a Receptor de TNF/farmacologia , Receptor 4 Toll-Like/genética
10.
Front Genet ; 13: 850122, 2022.
Artigo em Inglês | MEDLINE | ID: mdl-35432464

RESUMO

Purpose: The purpose of this study was to investigate the clinical and genetic characteristics of the retinitis pigmentosa GTPase regulatory factor gene (RPGR) in a Chinese cohort. Methods: A retrospective analysis was performed on 80 subjects with RPGR-retinal dystrophy (RPGR-RD) for detailed genetic and clinical characterization. The panel-based next-generation sequencing of 792 causative genes involved in common genetic eye diseases was conducted in all individuals, followed by clinical variant interpretation. Information, including age, sex, geographic distribution, family history, consanguineous marriage, age at symptom onset, disease duration, best corrected visual acuity (BCVA), and complete ophthalmologic examination results, was collected. Results: This cohort (41 men and 39 women) included 26 families (26 probands and their available family members) and 13 sporadic cases. The average age of these participants was 36.35 ± 17.68 years, and the majority of the families were from eastern China (28 families, 71.79%). The average duration of disease in the probands was 22.68 ± 15.80 years. In addition, the average BCVA values of the right and left eyes in the probands were 0.96 ± 0.77 and 1.00 ± 0.77, respectively. A total of 34 RPGR variants were identified, including 6 reported variants and 28 novel variants. Among these variants, NM_001034853.1: c.2899_2902delGAAG and c.2744_2745ins24 were considered de novo variants. The majority of the RPGR variants were classified as likely pathogenic, accounting for 70.59% of the variants (24 variants). The most common nucleotide and amino acid changes identified in this study were deletions (16 variants, 45.06%) and frameshifts (17 variants, 50.00%), respectively. Genetic analysis revealed that these RPGR variants were distributed in 10 different subregions of RPGR, and 70.59% of the RPGR variants (24 variants) were located in exon 15. Four RPGR variants, NM_001034853.1: c.2405_2406delAG, c.1345C > T, c.2218G > T and c.2236_2237delGA, occurred at a very high frequency of 28.21% (11 families) among 39 unrelated families. Conclusion: This study expands the known mutational spectrum of RPGR, and we provide a new reference for the genetic diagnosis of RPGR variants.

11.
Cancer Cell Int ; 22(1): 109, 2022 Mar 05.
Artigo em Inglês | MEDLINE | ID: mdl-35248043

RESUMO

BACKGROUND: Abnormal expression of splicing factor 3A subunit 3 (SF3A3), a component of the spliceosome, has been confirmed to be related to the occurrence and development of various cancers. However, the expression and function of SF3A3 in bladder cancer (BC) remains unclear. METHODS: The SF3A3 mRNA and protein level were measured in clinical samples and cell lines by quantitative real-time PCR, Western blot and immunofluorescence staining. Evaluate the clinical correlation between SF3A3 expression and clinicopathological characteristics through statistical analysis in BC patients. The function of SF3A3 in BC cells was determined in vitro using MTT and colony analysis. Co-immunoprecipitation (CoIP) assay was used to detected E2F6 and KDM5C interaction. Luciferase reporter and chromatin immunoprecipitation (ChIP) were used to examine the relationship between E2F6/KDM5C and SF3A3 expression. RESULTS: In the present study, we demonstrated that expression of SF3A3 was elevated in BC tissue compared to the normal bladder tissue. Importantly, the upregulation of SF3A3 in patients was correlated with poor prognosis. Additionally, overexpression of SF3A3 promoted while depletion of SF3A3 reduced the growth of BC cells in vivo and in vitro. Data from the TCGA database and clinical samples revealed that hypomethylation of the DNA promoter leads to high expression of SF3A3 in BC tissue. We found that upregulation of lysine-specific demethylase 5C (KDM5C) promotes SF3A3 expression via hypomethylation of the DNA promoter. The transcription factor E2F6 interacts with KDM5C, recruits KDM5C to the SF3A3 promoter, and demethylates the GpC island of H3K4me2, leading to high SF3A3 expression and BC progression. CONCLUSIONS: The results demonstrated that depletion of the KDM5C/SF3A3 prevents the growth of BC in vivo and in vitro. The E2F6/KDM5C/SF3A3 pathway may be a potential therapeutic target for BC treatment.

12.
Anal Chem ; 94(11): 4794-4802, 2022 03 22.
Artigo em Inglês | MEDLINE | ID: mdl-35266710

RESUMO

Investigating multiple miRNA expression patterns in living cells by DNA logic biocomputing is a valuable strategy for diagnosis and biomedical studies. The introduction of protein enzymes in DNA logic biocomputing circuits not only expands the toolbox of nucleic acid assembly techniques, but also further improves the specificity of recognizing and processing of DNA input. Herein, a polymerase-driven primer exchange reaction, acting as the sensing module, is introduced into the biocomputing system and transduces the multiple miRNAs sensing event into the intermediate triggers for activating the subsequent processing module, which further performs signal readout through DNAzyme catalytic substrate cleavage reaction. By using biomineralized zeolitic imidazolate framework-8 nanoparticles (ZIF-8 NPs) to deliver all the components of the biocomputing system, including polymerase and DNA probes, we realized polymerase-driven DNA biocomputing operations in living cells, including AND and OR gates. The results exhibited that biomineralized ZIF-8 NPs can protect the loaded cargoes against the external environment and deliver them efficiently to the cytoplasm. The polymerase-driven DNA biocomputing system based on multiple miRNAs sensing can be used for reliable cell identification and may provide a promising platform for more accurate diagnosis and programmable therapeutics.


Assuntos
DNA Catalítico , MicroRNAs , Nanopartículas , Zeolitas , DNA
13.
Front Pharmacol ; 13: 825667, 2022.
Artigo em Inglês | MEDLINE | ID: mdl-35222040

RESUMO

Pulmonary fibrosis (PF) is a clinically common disease caused by many factors, which will lead to lung function decline and even respiratory failure. Jingyin granule has been confirmed to have anti-inflammatory and antiviral effects by former studies, and has been recommended for combating H1N1 influenza A virus (H1N1) infection and Coronavirus disease 2019 (COVID-19) in China. At present, studies have shown that patients with severe COVID-19 infection developed lung fibrotic lesions. Although Jingyin granule can improve symptoms in COVID-19 patients, no study has yet reported whether it can attenuate the process of PF. Here, we explored the underlying mechanism of Jingyin granule against PF by network pharmacology combined with in vitro experimental validation. In the present study, the active ingredients as well as the corresponding action targets of Jingyin granule were firstly collected by TCMSP and literature data, and the disease target genes of PF were retrieved by disease database. Then, the common targets were subjected to Gene Ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) enrichment analyses, and then a PPI network and an ingredient-target network were constructed. Next, UPLC-MS was used to isolate and identify selected representative components in Jingyin granule. Finally, LPS was used to induce the A549 cell fibrosis model to verify the anti-PF effect of Jingyin granule in vitro. Our results indicated that STAT3, JUN, RELA, MAPK3, TNF, MAPK1, IL-6, and AKT1 were core targets of action and bound with good affinity to selected components, and Jingyin granule may alleviate PF progression by Janus kinase 2/signal transducers and activators of transcription (JAK2/STAT3), the mammalian nuclear factor-κB (NF-κB), the phosphatidylinositol 3-kinase (PI3K)/protein kinase B (Akt), tumor necrosis factor (TNF), and the extracellular signal-regulated kinases 1 and 2 (ERK1/2) signaling pathways. Overall, these results provide future therapeutic strategies into the mechanism study of Jingyin granule on PF.

14.
Microorganisms ; 10(2)2022 Feb 05.
Artigo em Inglês | MEDLINE | ID: mdl-35208826

RESUMO

Soil microorganisms play an indispensable role in the forest ecosystem. It is necessary to study the soil microorganisms in Pinus sylvestris var. mongolica, which is one of the afforestation species widely planted in the northern sandy region of China. We collected soil samples of P. sylvestris at large spatial scales and analyzed bacterial and fungal community composition differences using high-throughput sequencing techniques. The results showed that: (1) the richness index of different sandy lands was significantly different. The α-diversity of bacteria was the highest in Mu Us Sandy Land, and the α-diversity of fungi was the highest in Horqin Sandy Land. (2) The dominant phyla of bacteria were Actinobacteria, Proteobacteria, Chloroflexi and Acidobacteria, while the dominant phyla of fungi were Ascomycota and Basidiomycota. The relative abundance of dominant phyla was different. (3) Temperature and precipitation were the main driving factors of bacterial and fungal community change at large spatial scale. In addition, bacteria were also affected by total nitrogen, soil organic carbon and pH content; fungal community was affected by pH. The microorganisms showed obvious differences in geographical distribution, which could provide ideas for promoting sustainable management of P. sylvestris stand.

15.
World J Clin Cases ; 10(1): 275-282, 2022 Jan 07.
Artigo em Inglês | MEDLINE | ID: mdl-35071528

RESUMO

BACKGROUND: Postmenopausal bleeding (PMB) is a common gynecologic complaint among elderly women, and endometrial hyperplasia is a common cause of this bleeding. Ovarian fibromas are the most common type of ovarian sex cord-stromal tumor (SCST). They arise from non-functioning stroma, rarely show estrogenic activity, and stimulate endometrial hyperplasia, causing abnormal vaginal bleeding. CASE SUMMARY: We report herein the case of a 64-year-old Chinese woman who presented with recurrent PMB. A sex hormone test revealed that her estrogen level was significantly higher than normal, and other causes of hyperestrogenism had been excluded. The patient had undergone four curettage and hysteroscopy procedures in the past 7 years due to recurrent PMB and endometrial hyperplasia. The culprit behind the increase in estrogen level-an ovarian cellular fibroma with estrogenic activity-was eventually found during the fifth operation. CONCLUSION: Ovarian cellular fibromas occur insidiously, and some may have endocrine functions. Postmenopausal patients with recurrent PMB and endometrial thickening observed on ultrasonography are recommended to undergo sex hormone testing while waiting for results regarding the pathology of the endometrium. If the estrogen level remains elevated, the clinician should consider the possibility of an ovarian SCST and follow-up the patient closely, even if the imaging results do not indicate ovarian tumors. Once the tumor is found, it should be removed as soon as possible no matter the size to avoid endometrial lesions due to long-term estrogen stimulation. More studies are needed to confirm whether preventive total hysterectomy with bilateral salpingo-oophorectomy should be recommended for women with recurrent PMB exhibiting elevated estrogen levels, despite the auxiliary examination results not indicating ovarian mass. The physical and psychological burden caused by repeated curettage could be prevented using this technique.

16.
Dis Markers ; 2022: 5389162, 2022.
Artigo em Inglês | MEDLINE | ID: mdl-35082930

RESUMO

OBJECTIVE: Spinal cord injury (SCI) has become popular in recent years, and cognitive decline is a common complication. Adiponectin is a common protein hormone involved in the course of many diseases, but its relationship with SCI has not yet been elucidated. The purpose of our prospective study is to explore whether adiponectin can be used as a biomarker of cognitive decline in SCI. METHODS: A total of 64 healthy volunteers and 92 patients with acute SCI were recruited by us. Serum adiponectin levels, demographic data (age and gender), lifestyle (smoking and drinking), medical history (diabetes and hypertension), and clinical baseline data (low-density lipoprotein, high-density lipoprotein, and fasting blood glucose) were recorded. Three months after enrollment, we used the Montreal Cognitive Assessment (MoCA) to evaluate cognitive function. Based on a quarter of the serum adiponectin levels, SCI patients were divided into 4 groups, and the differences in their MoCA scores were compared. In addition, we used multivariate linear regression to predict the risk factors of the MoCA score. RESULTS: The serum adiponectin level (6.1 ± 1.1 µg/ml) of SCI patients was significantly lower than that of the healthy control group (6.7 ± 0.9 µg/ml), and there was a significant difference between the two (p < 0.001). The group with higher serum adiponectin levels after 3 months of spinal cord injury had higher MoCA scores. Multivariate regression analysis showed that serum adiponectin level is a protective factor for cognitive function after SCI (ß = 0.210, p = 0.043). CONCLUSIONS: Serum adiponectin levels can be used as an independent predictor of cognitive function in patients with acute SCI.


Assuntos
Adiponectina/sangue , Disfunção Cognitiva/sangue , Índice de Gravidade de Doença , Traumatismos da Medula Espinal/sangue , Adulto , Biomarcadores/sangue , Estudos de Casos e Controles , Disfunção Cognitiva/etiologia , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Prognóstico , Estudos Prospectivos , Fatores de Risco , Traumatismos da Medula Espinal/fisiopatologia
17.
Acta Pharmacol Sin ; 43(4): 1072-1081, 2022 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-34183756

RESUMO

Jingyin granules, a marketed antiviral herbal medicine, have been recommended for treating H1N1 influenza A virus infection and Coronavirus disease 2019 (COVID-19) in China. To fight viral diseases in a more efficient way, Jingyin granules are frequently co-administered in clinical settings with a variety of therapeutic agents, including antiviral drugs, anti-inflammatory drugs, and other Western medicines. However, it is unclear whether Jingyin granules modulate the pharmacokinetics of Western drugs or trigger clinically significant herb-drug interactions. This study aims to assess the inhibitory potency of the herbal extract of Jingyin granules (HEJG) against human drug-metabolizing enzymes and to clarify whether HEJG can modulate the pharmacokinetic profiles of Western drug(s) in vivo. The results clearly demonstrated that HEJG dose-dependently inhibited human CES1A, CES2A, CYPs1A, 2A6, 2C8, 2C9, 2D6, and 2E1; this herbal medicine also time- and NADPH-dependently inhibited human CYP2C19 and CYP3A. In vivo tests showed that HEJG significantly increased the plasma exposure of lopinavir (a CYP3A-substrate drug) by 2.43-fold and strongly prolonged its half-life by 1.91-fold when HEJG (3 g/kg) was co-administered with lopinavir to rats. Further investigation revealed licochalcone A, licochalcone B, licochalcone C and echinatin in Radix Glycyrrhizae, as well as quercetin and kaempferol in Folium Llicis Purpureae, to be time-dependent CYP3A inhibitors. Collectively, our findings reveal that HEJG modulates the pharmacokinetics of CYP substrate-drug(s) by inactivating CYP3A, providing key information for both clinicians and patients to use herb-drug combinations for antiviral therapy in a scientific and reasonable way.


Assuntos
COVID-19 , Vírus da Influenza A Subtipo H1N1 , Animais , Antivirais/farmacologia , COVID-19/tratamento farmacológico , Inibidores do Citocromo P-450 CYP3A , Interações Ervas-Drogas , Humanos , Microssomos Hepáticos , Ratos
18.
Pest Manag Sci ; 78(3): 1018-1028, 2022 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-34773351

RESUMO

BACKGROUND: Bactrocera dorsalis is a devastating pest on fruits and vegetables because the adult female is the key factor that determines the population density of offspring and the degree of host damage. Unfortunately, there is still a lack of effective female attractants for behavioral control. Males of B. dorsalis fed on methyl eugenol (ME) were shown to be more sexually attracted to females and, therefore, were more successful in mating over ME-deprived males. RESULTS: In the current study, we demonstrated that (E)-coniferyl alcohol (E-CF), one of the ME metabolites in males, was highly attractive to sexually-mature females in laboratory bioassays. During the dusk courtship period, mature females showed the highest response to E-CF. However, there were no significant differences in olfactory responses to E-CF between virgin and mated mature females. Moreover, no obvious signs and symptoms of toxicity or death were observed in mice during a 14-day acute oral toxicity test. Toxicologically, no significant changes were observed in body weight, water intake, food consumption and absolute and relative organ weights between control and treated groups of healthy-looking mice, implying that E-CF could be regarded as non-toxic. Furthermore, cytotoxicity assessment revealed that E-CF was non-toxic against human fetal lung fibroblast 1 (HFL1), human breast cancer (MDA-MB-231), mouse embryonic hepatocytes (BNL-CL.2) and Spodoptera frugiperda ovary (SF-9) cell lines. CONCLUSIONS: E-CF proved to be an effective, promising and eco-friendly lure to B. dorsalis females. Therefore, this study may facilitate the development of novel control strategies against B. dorsalis in the field.


Assuntos
Tephritidae , Animais , Drosophila , Feminino , Masculino , Camundongos , Fenóis , Reprodução
19.
Int J Hyperthermia ; 39(1): 8-14, 2022.
Artigo em Inglês | MEDLINE | ID: mdl-34936851

RESUMO

PURPOSE: To assess the absorption rate and factors related to the development of benign thyroid nodules (BTNs) following image-guided microwave ablation (MWA). MATERIALS AND METHODS: This retrospective study reviewed nodule efficacy in patients who underwent MWA of BTNs between January 2016 and January 2018. The endpoint was a third-year follow-up. Nodules were categorized into those showing complete absorption (volumes with less than 100% volume reduction ratio (VRR) and those showing partial absorption (100% VRR)). Univariable and multivariable regression analyses were carried out to identify variables that were associated with nodule absorption rates. RESULTS: A total of 173 BTNs (median volume= 4.23 ml; 25-75 percentiles= 2.27-9.00 ml) from 173 patients were evaluated. 49.7% (86/173) of patients had nodules that became completely absorbed. The mean VRRs of all BTNs were 18.0%, 78.7%, 89.0%, 94.5%, and 97.1% at the 1-, 6-,12-, 24- and 36- month follow-ups. At the 3-year follow-up time point, nodule characteristics related to nodule VRR included nodule volume (adjusted odds ratio [AOR], 1.1 [95% CI: 1.0, 1.2]; p = 0.03) and nodule margin (AOR, 5.3 [95% CI: 1.8, 16.0]; p < 0.01). Treatment-related characteristics included energy per ml in nodular volume (AOR, 1.0 [95% CI: 1.0, 1.0]; p < 0.01) and blockage of peripheral flow (AOR, 3.3 [95% CI: 1.3 8.3]; p = 0.01). CONCLUSIONS: US-guided image-guided MWA results in satisfactory long-term outcomes for the patients with BTNs. Factors related to nodule absorption rate were the volume and margin of the nodule, energy per ml in nodular volume and blockage of peripheral flow.


Assuntos
Ablação por Cateter , Nódulo da Glândula Tireoide , Ablação por Cateter/métodos , Seguimentos , Humanos , Micro-Ondas/uso terapêutico , Estudos Retrospectivos , Nódulo da Glândula Tireoide/diagnóstico por imagem , Nódulo da Glândula Tireoide/cirurgia , Resultado do Tratamento
20.
Dis Markers ; 2021: 3532716, 2021.
Artigo em Inglês | MEDLINE | ID: mdl-34876931

RESUMO

OBJECTIVE: Angiopoietin-like protein 4 (ANGPTL4), encoding a glycosylated secreted protein, has been reported to be closely related to many kinds of diseases, including diabetes, tumor, and some musculoskeletal pathologies, such as rheumatoid arthritis, osteoarthritis, and osteoporosis. The aim of the current study is to investigate the role of ANGPTL4 in intervertebral disc degeneration and analyze the association of ANGPTL4 expression with Pfirrmann grades. METHODS: A total of 162 nucleus pulposus tissues were collected from lumbar intervertebral disc herniation patients undergoing interforaminal endoscopic surgery. Real-time quantitative PCR and western blot were performed to determine the mRNA and protein expression of ANGPTL4 in nucleus pulposus samples. Statistical analysis was performed to analyze the association of ANGPTL4 expression with Pfirrmann grades. RESULTS: Based on the clinical data of 162 patients, results showed that Pfirrmann grades were significantly associated with patients' age (r = 0.162, P = 0.047) and were not significantly associated with patients' gender (P > 0.05). RT-qPCR and western blot results showed that the mRNA (r = 0.287, P < 0.05) and protein (r = 0.356, P < 0.05) expressions of ANGPTL4 were both closely associated with Pfirrmann grades. The expression of ANGPTL4 was remarkably increased in the groups of high IVDD Pfirrmann grades. CONCLUSION: The results demonstrated that ANGPTL4 expression was positively associated with the Pfirrmann grades and the severity of intervertebral disc degeneration. ANGPTL4 may be served as a candidate biomarker for intervertebral disc degeneration.


Assuntos
/metabolismo , Degeneração do Disco Intervertebral/metabolismo , Núcleo Pulposo/metabolismo , Adolescente , Adulto , Western Blotting , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , RNA Mensageiro/genética , Reação em Cadeia da Polimerase em Tempo Real , Adulto Jovem
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