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1.
J Virol ; 97(1): e0184322, 2023 01 31.
Artigo em Inglês | MEDLINE | ID: mdl-36622220

RESUMO

Porcine reproductive and respiratory syndrome virus (PRRSV) is one of the most important pathogens in the global pig industry, which modulates the host's innate antiviral immunity to achieve immune evasion. RIG-I-like receptors (RLRs) sense viral RNA and activate the interferon signaling pathway. LGP2, a member of the RLR family, plays an important role in regulating innate immunity. However, the role of LGP2 in virus infection is controversial. Whether LGP2 has a role during infection with PRRSV remains unclear. Here, we found that LGP2 overexpression restrained the replication of PRRSV, while LGP2 silencing facilitated PRRSV replication. LGP2 was prone to interact with MDA5 and enhanced viral RNA enrichment and recognition by MDA5, thus promoting the activation of RIG-I/IRF3 and NF-κB signaling pathways and reinforcing the expression of proinflammatory cytokines and type I interferon during PRRSV infection. Meanwhile, there was a decreased protein expression of LGP2 upon PRRSV infection in vitro. PRRSV Nsp1 and Nsp2 interacted with LGP2 and promoted K63-linked ubiquitination of LGP2, ultimately leading to the degradation of LGP2. These novel findings indicate that LGP2 plays a role in regulating PRRSV replication through synergistic interaction with MDA5. Moreover, targeting LGP2 is responsible for PRRSV immune evasion. Our work describes a novel mechanism of virus-host interaction and provides the basis for preventing and controlling PRRSV. IMPORTANCE LGP2, a member of retinoic acid-inducible gene I (RIG-I)-like receptors (RLRs), shows higher-affinity binding to RNA and work synergism with RIG-I or MDA5. However, LGP2 has divergent responses to different viruses, which remains controversial in antiviral immune responses. Here, we present the detailed process of LGP2 in positively regulating the anti-PRRSV response. Upon PRRSV infection, LGP2 was prone to bind to MDA5 and enhanced MDA5 signaling, manifesting the enrichment of viral RNA on MDA5 and the activation of downstream IRF3 and NF-κB, which results in increased proinflammatory cytokines and type I interferon expression, ultimately inhibiting PRRSV at the early stage of infection. Moreover, PRRSV Nsp1 and Nsp2 interacted with LGP2 via ubiquitin-proteasome pathways, thus blocking LGP2-mediated immune response. This research helps us understand the host recognition and innate antiviral response to PRRSV infection by neglected pattern recognition receptors, which sheds light on the detailed mechanism of virus-host interaction.


Assuntos
Interferon Tipo I , Síndrome Respiratória e Reprodutiva Suína , Vírus da Síndrome Respiratória e Reprodutiva Suína , RNA Helicases , Animais , Imunidade Inata , NF-kappa B/metabolismo , Vírus da Síndrome Respiratória e Reprodutiva Suína/genética , RNA Helicases/metabolismo , RNA Viral/genética , Transdução de Sinais/genética , Suínos , Síndrome Respiratória e Reprodutiva Suína/imunologia
2.
Am J Hematol ; 99(5): 824-835, 2024 05.
Artigo em Inglês | MEDLINE | ID: mdl-38321864

RESUMO

Two recent guidelines, the 5th edition of the World Health Organization Classification of Haematolymphoid Tumours (WHO-HAEM5) and the International Consensus Classification (ICC), were published to refine the diagnostic criteria of acute myeloid leukemia (AML). They both consider genomic features more extensively and expand molecularly defined AML subtypes. In this study, we compared the classifications of 1135 AML cases under both criteria. According to WHO-HAEM5 and ICC, the integration of whole transcriptome sequencing, targeted gene mutation screening, and conventional cytogenetic analysis identified defining genetic abnormalities in 89% and 90% of AML patients, respectively. The classifications displayed discrepancies in 16% of AML cases after being classified using the two guidelines, respectively. Both new criteria significantly reduce the number of cases defined by morphology and differentiation. However, their clinical implementation heavily relies on comprehensive and sophisticated genomic analysis, including genome and transcriptome levels, alongside the assessment of pathogenetic somatic and germline variations. Discrepancies between WHO-HAEM5 and ICC, such as the assignment of RUNX1 mutations, the rationality of designating AML with mutated TP53 as a unique entity, and the scope of rare genetic fusions, along with the priority of concurrent AML-defining genetic abnormalities, are still pending questions requiring further research for more elucidated insights.


Assuntos
Leucemia Mieloide Aguda , Humanos , Consenso , Mutação , Leucemia Mieloide Aguda/diagnóstico , Leucemia Mieloide Aguda/genética , Leucemia Mieloide Aguda/patologia , Genômica , Organização Mundial da Saúde
3.
Inorg Chem ; 2024 Jul 13.
Artigo em Inglês | MEDLINE | ID: mdl-39001841

RESUMO

Monitoring levels of excessive aluminum ions (Al3+) is crucial as it can harm the immune system, reduce enzyme activity, cause cell death, and damage environmental and biological systems. Developing a fast and efficient Al3+ ion determination method is the key to addressing this issue. In this work, red-emitting fluorescent copper nanoclusters (CuNCs) were synthesized using N-acetyl-l-cysteine (NAC) as a ligand and CuCl2·2H2O through a facile procedure. The NAC-CuNCs exhibited a large Stokes shift and displayed remarkable luminescence properties. A method for detecting Al3+ through a fluorescence probe was proposed. Its fluorescence mechanism was also explored. The probe showed rapid responsiveness (within 1 min) to Al3+ ion determination. The detection limit for Al3+ was found to be 19.7 nM, which is significantly lower than the WHO's value and most reports, with a linear range of 0-52.9 µM. The determination of Al3+ concentrations in actual water using the fluorescence probe yielded satisfactory outcomes. Moreover, the visual detection of Al3+ ions was also achieved through a smartphone, which can enhance its fast and practical detection.

4.
Anal Bioanal Chem ; 416(18): 4131-4141, 2024 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-38780654

RESUMO

Wax printing is the most widely used method for fabricating microfluidic paper-based analytical devices (µPADs), but it still suffers from disadvantages like discontinuation of wax printers and need for additional equipment for heating treatment. To address these issues, this work initially describes a new class of wax printing approach for high-precision, batch fabrication of µPADs using a household 3D printer. It only involves a one patterning step of printing polyethylene wax into rice paper body. Under optimized parameters, a fabrication resolution, namely the minimum hydrophilic channel width, down to ~189 ± 30 µm could be achieved. In addition, the analytical applicability of such polyethylene wax-patterned µPADs was demonstrated well with enhanced colorimetric detection of dopamine as a model analyte by combining metal-organic framework (MOF) based nanoenzymes (ZIF-67) with a smartphone (for portable quantitative readout). The developed nanosensor could linearly detect dopamine over a concentration range from 10 to 1000 µM, with a detection limit of ca. 2.75 µM (3σ). The recovery results for analyzing several real samples (i.e., pig feed, chicken feed, pork and human serum) were between 91.82 and 102.79%, further validating its good detection accuracy for potential practical applications in food safety and medical diagnosis.


Assuntos
Dopamina , Limite de Detecção , Papel , Impressão Tridimensional , Dopamina/análise , Dopamina/sangue , Animais , Humanos , Estruturas Metalorgânicas/química , Colorimetria/métodos , Colorimetria/instrumentação , Suínos , Técnicas Analíticas Microfluídicas/instrumentação , Técnicas Analíticas Microfluídicas/métodos , Dispositivos Lab-On-A-Chip , Galinhas , Ração Animal/análise , Desenho de Equipamento
5.
Anal Bioanal Chem ; 416(8): 1821-1832, 2024 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-38363308

RESUMO

This paper describes initially the application of the Tyndall effect (TE) of metal-organic framework (MOF) materials as a colorimetric signaling strategy for the sensitive detection of pyrophosphate ion (PPi). The used MOF NH2-MIL-101(Fe) was prepared with Fe3+ ions and fluorescent ligands of 2-amino terephthalic acid (NH2-BDC). The fluorescence of NH2-BDC in MOF is quenched due to the ligand-to-metal charge transfer effect, while the NH2-MIL-101(Fe) suspension shows a strong TE. In the presence of PPi analyte, the MOFs will undergo decomposition because of the competitive binding of Fe3+ by PPi over NH2-BDC, resulting in a significant decrease in the TE signal and fluorescence restoration from the released ligands. The results demonstrate that the new method only requires a laser pointer pen (for TE creation) and a smartphone (for portable quantitative readout) to detect PPi in a linear concentration range of 1.25-800 µM, with a detection limit of ~210 nM (3σ) which is ~38 times lower than that obtained from traditional fluorescence with a spectrophotometer (linear concentration range, 50-800 µM; detection limit, 8.15 µM). Moreover, the acceptable recovery of PPi in several real samples (i.e., pond water, black tea, and human serum and urine) ranges from 97.66 to 119.15%.


Assuntos
Estruturas Metalorgânicas , Humanos , Estruturas Metalorgânicas/química , Colorimetria/métodos , Difosfatos/química , Aminoácidos
6.
Environ Res ; 251(Pt 1): 118610, 2024 Jun 15.
Artigo em Inglês | MEDLINE | ID: mdl-38442811

RESUMO

Biomass-derived carbon dots (CDs) are non-toxic and fluorescently stable, making them suitable for extensive application in fluorescence sensing. The use of cheap and renewable materials not only improves the utilization rate of waste resources, but it is also drawing increasing attention to and interest in the production of biomass-derived CDs. Visual fluorescence detection based on CDs is the focus of current research. This method offers high sensitivity and accuracy and can be used for rapid and accurate determination under complex conditions. This paper describes the biomass precursors of CDs, including plants, animal remains and microorganisms. The factors affecting the use of CDs as fluorescent probes are also discussed, and a brief overview of enhancements made to the preparation process of CDs is provided. In addition, the application prospects and challenges related to biomass-derived CDs are demonstrated.


Assuntos
Biomassa , Carbono , Corantes Fluorescentes , Carbono/análise , Carbono/química , Pontos Quânticos/análise , Pontos Quânticos/química , Plantas , Estrutura Molecular
7.
Mol Carcinog ; 62(5): 665-675, 2023 05.
Artigo em Inglês | MEDLINE | ID: mdl-36752333

RESUMO

This study aimed to investigate the relationship between anomalous DNA nucleotidylexotransferase (DNTT) activation and the mutagenesis of gene length mutations (LMs) in acute myeloid leukemia (AML), and the relevance of their prognosis in antithymocyte globulin (ATG)-based regimen allogeneic hematopoietic stem cell transplantation (allo-HSCT). A cohort of 578 AML cases was enrolled. Next-generation sequencing was performed to screen mutations of 86 leukemia driver genes. RNA-seq was used to analyze gene expression. Prognostic analysis was investigated in 239 AML cases who underwent ATG-based regimen allo-HSCT. We report a refined subtyping algorithm of LMs (type I-IV) based on sequence anatomy considering the TdT-aided mutagenesis mechanism. GC content adjacent to LM junctions, inserted nontemplate nucleotide bases, and DNTT expression analysis supported the DNTT activation and TdT-aided mutagenesis in type II/III LMs in the total AML cohort. Both single-variate and multivariate analyses showed a better overall survival of FLT3 type III compared to type I in a subset of ATG-based regimen allo-HSCT cases. The novel LM subtyping algorithm not only deciphers the etiology of the mutagenesis of LMs but also helps to fine-tune prognosis differentiation in AML. The possible prognostic versatility of this novel LM subtyping algorithm in terms of chemotherapy, targeted therapy, and allo-HSCT merits further investigation.


Assuntos
Transplante de Células-Tronco Hematopoéticas , Leucemia Mieloide Aguda , Humanos , DNA Nucleotidilexotransferase/genética , Soro Antilinfocitário/genética , Soro Antilinfocitário/uso terapêutico , Leucemia Mieloide Aguda/terapia , Leucemia Mieloide Aguda/tratamento farmacológico , Mutação , Estudos Retrospectivos
8.
Hematol Oncol ; 41(4): 784-788, 2023 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-37132198

RESUMO

Acute promyelocytic leukemia (APL) is a unique subtype of acute myeloid leukemia (AML) which is characterized by specific clinical and biological features. Typical APL cases are caused by PML::RARA fusion gene and are exquisitely sensitive to all-trans retinoic acid (ATRA) and arsenic trioxide (ATO). Rarely, APLs are caused by atypical fusions involving RARA or, in fewer cases still, fusions involving other members of the retinoic acid receptors (RARB or RARG). To date, seven partner genes of RARG have been reported in a total of 18 cases of variant APL. Patients with RARG fusions showed distinct clinical resistance to ATRA and had poor outcomes. Here, we report PRPF19 gene as a novel partner of RARG and identify a rare interposition-type gene fusion in a variant APL patient with a rapidly fatal clinical course. The incomplete ligand-binding domain of RARG in the fusion protein may account for the clinical ATRA resistance in this patient. These results broaden the spectrum of variant APL associated molecular aberrations. Accurately and timely identification of these rare gene fusions in variant APL is essential to guide therapeutic decisions.


Assuntos
Leucemia Mieloide Aguda , Leucemia Promielocítica Aguda , Humanos , Leucemia Promielocítica Aguda/tratamento farmacológico , Leucemia Promielocítica Aguda/genética , Tretinoína , Trióxido de Arsênio/uso terapêutico , Leucemia Mieloide Aguda/genética , Receptores do Ácido Retinoico/genética , Receptores do Ácido Retinoico/uso terapêutico , Fatores de Processamento de RNA , Proteínas Nucleares/genética , Enzimas Reparadoras do DNA/uso terapêutico
9.
Wound Repair Regen ; 31(2): 227-232, 2023 03.
Artigo em Inglês | MEDLINE | ID: mdl-36541709

RESUMO

Chronic wounds have become one of the major issues in medicine today, the treatments for which include dressing changes, negative pressure wound therapy, hyperbaric oxygen, light irradiation, surgery and so forth. Nevertheless, the application of diode lasers in chronic wounds has rarely been reported. This retrospective cohort study aimed to evaluate the therapeutic effect of diode laser (810 nm) irradiation on chronic wounds. Eighty-nine patients were enrolled in the study. The control group (41 patients) received traditional dressing change therapy, while the diode laser treatment group (48 patients) were patients received additional treatment with diode laser (810 nm) irradiation for 10 min at each dressing change. Wound healing time was compared between two groups, while the pain relief index was creatively introduced to evaluate the effect of relieving wound pain, which was calculated by the difference in pain scores between the first and last dressing changes divided by the number of treatment days. The wound healing time of the diode laser treatment group was 22.71 ± 8.99 days, which was significantly shorter than that of the control group (37.44 ± 23.42 days). The pain relief index of the diode laser treatment group was 0.081 ± 0.055, which was significantly increased compared with that of the control group (0.057 ± 0.033). Our findings suggest that diode laser irradiation has the potential to promote healing in chronic wounds and relieve wound pain.


Assuntos
Terapia a Laser , Terapia com Luz de Baixa Intensidade , Humanos , Cicatrização/efeitos da radiação , Lasers Semicondutores/uso terapêutico , Estudos Retrospectivos , Dor
10.
BMC Neurol ; 23(1): 132, 2023 Mar 30.
Artigo em Inglês | MEDLINE | ID: mdl-36997874

RESUMO

OBJECTIVE: Stress-induced hyperglycaemia (SIH) is a frequent phenomenon that occurs in patients with acute ischaemic stroke. The aim of this study was to investigate the relationship between SIH and the prognosis of mechanical thrombectomy (MT) patients according to the stress hyperglycemia ratio (SHR) and glycaemic gap (GG) indicators, as well as explore its relationship with haemorrhagic transformation (HT). METHODS: Patients were enrolled from January 2019 to September 2021 in our centre. SHR was calculated as fasting blood glucose divided by the A1c-derived average glucose (ADAG). GG was calculated as fasting blood glucose minus ADAG. Logistic regression was used to analyse SHR, GG with outcome and HT. RESULTS: A total of 423 patients were enrolled in the study. The incidence of SIH was as follows: 191/423 of patients with SHR > 0.89, 169/423 of patients with GG > -0.53. SHR > 0.89 (OR: 2.247, 95% CI: 1.344-3.756, P = 0.002) and GG>-0.53 (OR: 2.305, 95% CI: 1.370-3.879, P = 0.002) were both associated with poor outcomes (modified Rankin Scale > 2) at Day 90 and an increase risk of HT. Additionlly, receiver operating characteristic curves were used to assess the predictive performance of the SHR and GG on outcomes. The area under the curve for SHR to predict poor outcomes was 0.691, with an optimal cut-off value of 0.89. The area under the curve for GG was 0.682, with an optimal cut-off value of -0.53. CONCLUSION: High SHR and high GG are strongly associated with poor 90-day prognosis in MT patients and an increased risk of HT.


Assuntos
Isquemia Encefálica , Hiperglicemia , Acidente Vascular Cerebral , Humanos , Hiperglicemia/diagnóstico , Hiperglicemia/epidemiologia , Glicemia , Isquemia Encefálica/complicações , Acidente Vascular Cerebral/complicações , Prognóstico , Trombectomia/efeitos adversos , Estudos Retrospectivos , Resultado do Tratamento
11.
Pol J Pathol ; 74(3): 182-193, 2023.
Artigo em Inglês | MEDLINE | ID: mdl-37955537

RESUMO

S100 calcium-binding protein A16 (S100A16) has previously been reported to play a role in tumor cells. Nevertheless, the role that S100A16 played in nephroblastoma cells remains obscure. The expression of S100A16 and DEPDC1 were detected via RT-q PCR and western blotting. Cell transfection was performed to overexpress DEPDC1 or interfere S100A16. CCK8 was applied for the assessment of cell viability. The apoptotic level and the capabilities of WiT49 cells to proliferate, invade and migrated were appraised utilizing Tunel, colony formation Transwell, and wound healing, separately. The angiogenesis was estimated through tube formation assay. Co-immunoprecipitation (CO-IP) was performed to examine the targeted binding of S100A16 to DEPDC1. The contents of PI3K/Akt/mTOR pathway-related proteins were resolved by virtue of western blot. S100A16 and DEPDC1 expression levels were significantly increased in nephroblastoma cell lines. S100A16 deletion suppressed nephroblastoma cell proliferative, invasive, migrative and angiogenetic capabilities but facilitated the apoptotic level. Moreover, S100A16 could bind DEPDC1, DEPDC1 overexpression partially reversed the inhibitory effect of S100A16 interference on nephroblastoma cell. DEPDC1 overexpression also partially counteracted the suppressive impacts of S100A16 interference on PI3K/Akt/mTOR pathway-related proteins. S100A16 synergistic with DEPDC1 promotes the progression and angiogenesis of nephroblastoma cell through the PI3K/Akt/mTOR pathway.


Assuntos
Proteínas Proto-Oncogênicas c-akt , Tumor de Wilms , Humanos , Proteínas Proto-Oncogênicas c-akt/metabolismo , Fosfatidilinositol 3-Quinases/metabolismo , Linhagem Celular Tumoral , Serina-Treonina Quinases TOR/metabolismo , Tumor de Wilms/genética , Proteínas de Neoplasias/metabolismo , Proteínas Ativadoras de GTPase/metabolismo , Proteínas S100/metabolismo
12.
Int J Mol Sci ; 24(3)2023 Jan 21.
Artigo em Inglês | MEDLINE | ID: mdl-36768459

RESUMO

Rapeseed (Brassica napus L.) is not only one of the most important oil crops in the world, but it is also an important vegetable crop with a high value nutrients and metabolites. However, rapeseed is often severely damaged by adverse stresses, such as low temperature, pathogen infection and so on. Glyoxalase I (GLYI) and glyoxalase II (GLYII) are two enzymes responsible for the detoxification of a cytotoxic metabolite methylglyoxal (MG) into the nontoxic S-D-lactoylglutathione, which plays crucial roles in stress tolerance in plants. Considering the important roles of glyoxalases, the GLY gene families have been analyzed in higher plans, such as rice, soybean and Chinese cabbage; however, little is known about the presence, distribution, localizations and expression of glyoxalase genes in rapeseed, a young allotetraploid. In this study, a total of 35 BnaGLYI and 30 BnaGLYII genes were identified in the B. napus genome and were clustered into six and eight subfamilies, respectively. The classification, chromosomal distribution, gene structure and conserved motif were identified or predicted. BnaGLYI and BnaGLYII proteins were mainly localized in chloroplast and cytoplasm. By using publicly available RNA-seq data and a quantitative real-time PCR analysis (qRT-PCR), the expression profiling of these genes of different tissues was demonstrated in different developmental stages as well as under stresses. The results indicated that their expression profiles varied among different tissues. Some members are highly expressed in specific tissues, BnaGLYI11 and BnaGLYI27 expressed in flowers and germinating seed. At the same time, the two genes were significantly up-regulated under heat, cold and freezing stresses. Notably, a number of BnaGLY genes showed responses to Plasmodiophora brassicae infection. Overexpression of BnGLYI11 gene in Arabidopsis thaliana seedlings confirmed that this gene conferred freezing tolerance. This study provides insight of the BnaGLYI and BnaGLYII gene families in allotetraploid B. napus and their roles in stress resistance, and important information and gene resources for developing stress resistant vegetable and rapeseed oil.


Assuntos
Brassica napus , Brassica rapa , Lactoilglutationa Liase , Lactoilglutationa Liase/genética , Lactoilglutationa Liase/metabolismo , Brassica napus/metabolismo , Perfilação da Expressão Gênica/métodos , Genoma de Planta , Brassica rapa/genética , Filogenia , Estresse Fisiológico/genética , Regulação da Expressão Gênica de Plantas , Proteínas de Plantas/metabolismo
13.
Pak J Med Sci ; 39(1): 17-22, 2023.
Artigo em Inglês | MEDLINE | ID: mdl-36694748

RESUMO

Objectives: To evaluate the effects of paroxetine hydrochloride combined with idebenone on inflammatory factors and antioxidant molecules in the treatment of depression after ischemic stroke. Methods: Randomized controlled trial was adopted on 80 patients with depression after ischemic stroke were randomly divided into two groups, with 40 patients in each group at Xingtai Sanli Health Quannan Clinic from March 17, 2019 to December 20, 2021. Both groups were given basic treatment. On this basis, the control group was treated with paroxetine hydrochloride, while the study group was treated with paroxetine hydrochloride combined with idebenone. The clinical efficacy was evaluated using the Hamilton Rating Scale for Depression (HRSD) before and after treatment. Additionally, the difference in HRSD score after treatment and the improvement in inflammatory factors and antioxidant molecules were compared and analyzed between the two groups. Results: After treatment, the HRSD score of the study group was significantly improved compared with that of the control group (p= 0.00). The effective rate was 82.5% in the study group, which was significantly higher than 62.5% in the control group (p= 0.04). After treatment, TNF-a, CRP and IL-6 in the study group were significantly lower than those in the control group (p= 0.00). Serum SOD, TAC and CAT levels in the study group were significantly higher than those in the control group after treatment (SOD and TAC, p= 0.00; CAT, p= 0.01). The incidence of adverse reactions was 37.5% in the study group and 25% in the control group. Although the incidence of adverse reactions in the study group was higher than that in the control group, the difference was not statistically significant (p= 0.23). Conclusion: Paroxetine hydrochloride combined with idebenone in the treatment of depression after ischemic stroke can significantly improve HRSD score, enhance clinical efficacy, reduce the levels of inflammatory factors, and increase the levels of antioxidant factors, without a significant increase in adverse reactions. Therefore, it is a safe and effective treatment method.

14.
Zhong Nan Da Xue Xue Bao Yi Xue Ban ; 48(3): 369-375, 2023 Mar 28.
Artigo em Inglês, Zh | MEDLINE | ID: mdl-37164920

RESUMO

OBJECTIVES: Tanshinone IIA has a wide range of myocardial protective effects. AK003290 is a long noncoding RNA (lncRNA) that is highly expressed in myocardial tissue, and its expression is down-regulated when myocardial injury occurs. This study aims to explore the mechanism for tanshinone IIA in alleviating myocardial cell damage induced by oxygen glucose deprivation (OGD). METHODS: OGD model was established in rat H9C2 cardiomyocytes. siRNA was transfected to reduce AK003290 expression. H9C2 cells were divided into 6 groups: A control group, a tanshinone IIA (TAN) group, an OGD group, a tanshinone IIA+OGD (TAN+OGD) group, a scrambled siRNA transfection+tanshinone IIA+OGD (scrambled siRNA+TAN+OGD) group, and a AK003290 siRNA transfection+tanshinone IIA+OGD (AK003290 siRNA+TAN+OGD) group. H9C2 cells in the TAN group were treated with 40 µmol/L tanshinone IIA for 12 h. The TAN+OGD group was treated with 40 µmol/L tanshinone IIA for 12 h, followed by OGD treatment for 12 h. The scrambled siRNA+TAN+OGD group and AK003290 siRNA+TAN+OGD group were transfected with the scrambled siRNA or AK003290 siRNA. Twenty-four hours later, the cells were treated with tanshinone IIA and OGD. Real-time RT-PCR was used to detect the expression of AK003290. Spectrophotometry was used to detect the content of lactate dehydrogenase (LDH) in cell culture medium to reflect LDH leakage rate, and enzyme-linked immunosorbent assay (ELISA) was used to detect the content of interleukin-1ß (IL-1ß) and interleukin-18 (IL-18). Western blotting was used to detect the protein expression of phospho-nuclear factor- κB (p-NF-κB). RESULTS: Compared with the control group, the leakage rate of LDH, the content of IL-1ß and IL-18 in culture medium, and the protein expression level of p-NF-κB were increased in the OGD group (P<0.01 or P<0.001). Compared with the OGD group, the leakage rate of LDH, the content of IL-1ß and IL-18 in culture medium, and the protein expression level of p-NF-κB were decreased in the TAN+OGD group (P<0.05 or P<0.01). Compared with the control group, the AK003290 expression was increased in the TAN group (P<0.01) and it was decreased in the OGD group (P<0.05). Compared with the OGD group, the AK003290 expression was increased in the TAN+OGD group (P<0.05). Compared with the scrambled siRNA+TAN+OGD group, the leakage rate of LDH, the content of IL-1ß and IL-18 in culture medium, and the protein expression level of p-NF-κB were increased in the AK003290 siRNA+TAN+OGD group (P<0.05 or P<0.01). CONCLUSIONS: Tanshinone IIA inhibits NF-κB activity and attenuates OGD-induced inflammatory injury of cardiomyocytes through up-regulating AK003290.


Assuntos
Miócitos Cardíacos , NF-kappa B , Ratos , Animais , Miócitos Cardíacos/metabolismo , NF-kappa B/metabolismo , Transdução de Sinais , Interleucina-18/metabolismo , Interleucina-18/farmacologia , Oxigênio/metabolismo , Glucose/metabolismo , RNA Interferente Pequeno/genética
15.
Cell Mol Biol (Noisy-le-grand) ; 68(10): 136-140, 2022 Sep 30.
Artigo em Inglês | MEDLINE | ID: mdl-37114258

RESUMO

This experiment was carried out to investigate changes in lymphocyte subpopulation, immunoglobulins (Igs), and complements, and also to explore the relationship between these immune indices and C-reactive protein and erythrocyte sedimentation rate in 61 patients with erythema nodosum. For this aim, a 4-year, retrospective study contained 61 patients with erythema nodosum, and 61 healthy control subjects were included from the out-patient clinic. The subpopulation of the T, B and natural killer lymphocytes and levels of IgA, IgG, IgM, complement C3, complement C4, C-reactive protein, and erythrocyte sedimentation rate from peripheral blood of them were detected. A correlation analysis was done between lymphocyte subpopulation, levels of IgA, IgG, and IgM, complement C3, complement C4 and C-reactive protein level and erythrocyte sedimentation rate in the patient group. Results showed that the percentage of CD4+ cells, CD4+/CD8+ ratio, the level of C-reactive protein and the erythrocyte sedimentation rate in the patients were higher than in controls (P<0.05). While the percentage of CD8+ cells and the serum levels of complement C3 were lower than in controls (P<0.05). There were no differences in the percentages of CD3+, B and natural killer cells and the serum levels of IgA, IgG and IgM, and complement C4 between the patients and the controls (P>0.05). IgM level was positively correlated with C-reactive protein (P<0.05) but did not correlate with an erythrocyte sedimentation rate (P>0.05). There was no correlation between lymphocyte subpopulation, levels of IgA, IgG, complement C3, complement C4 and C-reactive protein level and erythrocyte sedimentation rate (P>0.05). In conclusion, there was dysregulation of both cellular immunity and humoral immunity in patients with erythema nodosum. IgM level has a positive correlation with C-reactive protein.


Assuntos
Complemento C3 , Eritema Nodoso , Humanos , Estudos Retrospectivos , Complemento C3/análise , Proteína C-Reativa/análise , Sedimentação Sanguínea , Imunoglobulinas , Complemento C4/análise , Imunoglobulina A , Imunoglobulina G , Imunoglobulina M
16.
BMC Surg ; 22(1): 183, 2022 May 14.
Artigo em Inglês | MEDLINE | ID: mdl-35568851

RESUMO

BACKGROUND: Previous studies reported that transnasal ileus tube was a new and useful method for rapid relief of small intestinal obstruction. However, no study reported the impacts of the transnasal ileus tube for Crohn's disease combined with intestinal obstruction. We aimed to describe the strategy to the small intestine obstruction caused by Crohn's disease on the basis of transnasal ileus tube insertion. METHODS: From November 2019 to November 2021, the data of 6 hospitalized patients with CD, diagnosed and conservatively treated in The Second Hospital of Nanjing, were not relived and retrospectively collected. After the insertion of transnasal ileus tube, demographic information, clinical features and treatment data were extracted from medical records. RESULTS: Six Crohn's disease patients with intestinal obstruction were included. Half of them were male. The patients aged from 29 to 70 years. Five patients had chronic intestinal obstruction more than one year. Three patients had intestinal surgery history. One patient had colonic abdominal fistula and anastomotic fistula, when she took intermittent usage of sulfsalazine and steroid. On admission, all the patients had abdominal pain, distention and mass. Five patients had anemia, low albumin and cholinesterase. All CDAI scores were more than 400. Compared to 19 patients with incomplete intestinal obstruction improved by nasogastric decompression tube, 6 patients with intestinal obstruction catheter had significant difference in time for relieving abdominal pain and distension (p = 0.003), time for alleviating abnormal mass (p ≤ 0.01), drainage volume (p = 0.004), and preoperative CDAI score (p = 0.001). Compared with X-ray image before insertion, complete remission of obstruction of 5 patients were observed in intestinal cavity after insertion. After 1-2 months nutrition, all the patients had small intestine resection and ileostomy, half of them underwent colectomy and fistula repair, and 4 patients were performed enterolysis at the same time, the residual small intestine length ranging from 250 to 400 cm. 1 patient had permanent ileostomy;1 patient had abdominal infection after operation. The typical manifestations of acute and chronic inflammation, transmural inflammation, pseudopolyps and serous fiber hyperplasia could be seen in pathological findings of patients 1 to 5. All the patients continued enteral nutrition after surgery. Four patients were treated with infliximab or vedolizumab. CONCLUSION: The current intestinal obstruction catheter which is used to treat patients with Crohn's combined obstruction can afford quick clinical remission, longer nutrition time, and suitable preoperative CDAI score for operation, which is worthy of wildly being used.


Assuntos
Doença de Crohn , Íleus , Obstrução Intestinal , Dor Abdominal , Doença de Crohn/complicações , Feminino , Humanos , Inflamação , Obstrução Intestinal/etiologia , Obstrução Intestinal/cirurgia , Intestino Delgado/cirurgia , Masculino , Estudos Retrospectivos
17.
BMC Med Educ ; 22(1): 656, 2022 Sep 02.
Artigo em Inglês | MEDLINE | ID: mdl-36056389

RESUMO

OBJECTIVE: This study aimed to determine whether a combination of case-based learning (CBL) and problem-based learning (PBL) methods in teaching can improve the academic performance and recruitment of medical students for neurosurgery. METHODS: Four classes of fourth-year medical students were randomly divided into two groups. The traditional model group received the traditional teaching method, and the CBL-PBL group received the combined teaching methods of CBL and PBL. After the courses, the differences between the two groups in self-perceived competence, satisfaction with the course, post-class test scores, and clinical practice abilities were compared, and the proportions of neurosurgery major selection in pre- and post-curriculum between the two groups were also analyzed. RESULTS: Self-perceived competence, post-class test scores, and clinical practice abilities in the CBL-PBL group were better than those in the traditional model group. The students in the CBL-PBL group showed a higher degree of satisfaction with the course than those in the traditional model group (χ2 = 12.03, P = 0.007). At the end of the semester, the proportion of students who chose neurosurgery majors in the CBL-PBL group was 13.3%, more than the 3.4% in the traditional model group (χ2 = 3.93, P = 0.048). CONCLUSION: Compared with the traditional teaching method, the CBL and PBL integrated method is more effective for improving the performance of medical students and enhancing their clinical capabilities in neurosurgery teaching. The CBL-PBL method effectively improved students' interests in neurosurgery, potentially contributing to increasing medical student recruitment into neurosurgery.


Assuntos
Neurocirurgia , Estudantes de Medicina , Currículo , Humanos , Aprendizagem Baseada em Problemas/métodos , Inquéritos e Questionários , Ensino
18.
Pak J Pharm Sci ; 35(3(Special)): 931-936, 2022 May.
Artigo em Inglês | MEDLINE | ID: mdl-35791590

RESUMO

To explore the effect of atorvastatin combined with Zishen Qingqi Granules on the immune function and liver function of patients with mild to moderate activity systemic lupus erythematosus. The data of 120 patients with mild to moderate activity systemic lupus erythematosus admitted to our hospital from February 2019 to February 2020 were retrospectively analyzed and they were divided into experimental group (n=60) and the control group (n=60) according to the order of admission; the control group was treated with atorvastatin, and the experimental group was treated with Zishen Qingqi Granules plus. The immune function, liver function, TCM syndrome score and systemic lupus erythematosus disease activity index (SLEDAI) were compared between the two groups. The experimental group after treatment was superior to the control group with respect to immune function indexes, liver function indexes, SLEDAI and TCM syndromes (all P<0.001). Atorvastatin combined with Zishen Qingqi Granules can improve the liver function of patients with mild to moderate activity systemic lupus erythematosus, enhance their immunity, and relieve their clinical symptoms.


Assuntos
Lúpus Eritematoso Sistêmico , Atorvastatina/uso terapêutico , Humanos , Imunidade , Fígado , Lúpus Eritematoso Sistêmico/tratamento farmacológico , Estudos Retrospectivos , Síndrome
19.
Bioorg Med Chem Lett ; 38: 127880, 2021 04 15.
Artigo em Inglês | MEDLINE | ID: mdl-33636303

RESUMO

Based on our previous research, thirty new 5-amino-1H-1,2,4-triazoles possessing 3,4,5-trimethoxyphenyl moiety were synthesized, and evaluated for antiproliferative activities. Among them, compounds IIa, IIIh, and IIIm demonstrated significant antiproliferative activities against a panel of tumor cell lines, and the promising compound IIIm dose-dependently caused G2/M phase arrest in HeLa cells. Furthermore, analogue IIa exhibited the most potent tubulinpolymerization inhibitory activity with an IC50 value of 9.4 µM, and molecular modeling studies revealed that IIa formed stable interactions in the colchicine-binding site of tubulin, suggesting that 5-amino-1H-1,2,4-triazole scaffold has potential for further investigation to develop novel tubulin polymerization inhibitors with anticancer activity.


Assuntos
Antineoplásicos/farmacologia , Triazóis/farmacologia , Moduladores de Tubulina/farmacologia , Tubulina (Proteína)/metabolismo , Antineoplásicos/síntese química , Antineoplásicos/química , Pontos de Checagem do Ciclo Celular/efeitos dos fármacos , Proliferação de Células/efeitos dos fármacos , Relação Dose-Resposta a Droga , Ensaios de Seleção de Medicamentos Antitumorais , Células HeLa , Humanos , Estrutura Molecular , Polimerização/efeitos dos fármacos , Relação Estrutura-Atividade , Triazóis/síntese química , Triazóis/química , Moduladores de Tubulina/síntese química , Moduladores de Tubulina/química
20.
BMC Neurol ; 21(1): 238, 2021 Jun 24.
Artigo em Inglês | MEDLINE | ID: mdl-34167467

RESUMO

BACKGROUND AND PURPOSE: The purpose of our study was to analyse endovascular treatment (EVT) in patients presenting acute anterior circulation ischemic stroke with large-vessel occlusion (AIS-LVO) during the pandemic and post-epidemic periods. METHODS: Patients with AIS-LVO of the anterior circulation who underwent EVT were enrolled. According to the times of Wuhan closure and reopening, patients were divided into a pre-pandemic group (from November 8, 2019, to January 22, 2020), pandemic group (from January 23, 2020, to April 8, 2020) and post-epidemic group (from April 9, 2020, to June 24, 2020). The primary endpoints were the time delay among symptom onset to arriving hospital door, to groining puncture and to vascular reperfusion. Secondary endpoints were the functional outcomes evaluated by 90-day modified Rankin scale (mRS) score. RESULTS: In total, the times from onset to reperfusion (OTR, median 356 min vs. 310 min, p = 0.041) and onset to door (OTD, median 238 min vs. 167 min, p = 0.017) were prolonged in the pandemic group compared to the pre-pandemic group, and the delay continue in the post-epidemic period. In the subgroup analysis, the time from door to imaging (DTI) was significantly prolonged during the pandemic period. Interestingly, the prolonged DTI was corrected in the directly admitted subgroup during post-epidemic period. In addition, the functional outcomes showed no significant differences across the three periods. CONCLUSIONS: Total time and prehospital time were prolonged during the pandemic and post-epidemic periods. Urgent public education and improved in-hospital screening processes are necessary to decrease time delays.


Assuntos
COVID-19 , Procedimentos Endovasculares/métodos , AVC Isquêmico/terapia , Idoso , Idoso de 80 Anos ou mais , Isquemia Encefálica/terapia , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Reperfusão/métodos , Estudos Retrospectivos , Resultado do Tratamento
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