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1.
IUBMB Life ; 2024 May 09.
Artigo em Inglês | MEDLINE | ID: mdl-38721892

RESUMO

Low back pain is a common clinical symptom of intervertebral disc degeneration (IVDD), which seriously affects the quality of life of the patients. The abnormal apoptosis and senescence of nucleus pulposus cells (NPCs) play important roles in the pathogenesis of IVDD. PHLDA2 is an imprinted gene related to cell apoptosis and tumour progression. However, its role in NPC degeneration is not yet clear. Therefore, this study was set to explore the effects of PHLDA2 on NPC senescence and apoptosis and the underlying mechanisms. The expression of PHLDA2 was examined in human nucleus pulposus (NP) tissues and NPCs. Immunohistochemical staining, magnetic resonance imaging imaging and western blot were performed to evaluate the phenotypes of intervertebral discs. Senescence and apoptosis of NPCs were assessed by SA-ß-galactosidase, flow cytometry and western blot. Mitochondrial function was investigated by JC-1 staining and transmission electron microscopy. It was found that the expression level of PHLDA2 was abnormally elevated in degenerated human NP tissues and NPCs. Furthermore, knockdown of PHLDA2 can significantly inhibit senescence and apoptosis of NPCs, whereas overexpression of PHLDA2 can reverse senescence and apoptosis of NPCs in vitro. In vivo experiment further confirmed that PHLDA2 knockdown could alleviate IVDD in rats. Knockdown of PHLDA2 could also reverse senescence and apoptosis in IL-1ß-treated NPCs. JC-1 staining indicated PHLDA2's knockdown impaired disruption of the mitochondrial membrane potential and also ameliorated superstructural destruction of NPCs as showed by transmission electron microscopy. Finally, we found the PHLDA2 knockdown promoted Collagen-II expression and suppressed MMP3 expression in NPCs by repressing wnt/ß-catenin pathway. In conclusion, the results of the present study showed that PHLDA2 promotes IL-1ß-induced apoptosis and senescence of NP cells via mitochondrial route by activating the Wnt/ß-catenin pathway, and suggested that therapy targeting PHLDA2 may provide valuable insights into possible IVDD therapies.

2.
Cell Death Dis ; 15(3): 236, 2024 Mar 29.
Artigo em Inglês | MEDLINE | ID: mdl-38553452

RESUMO

Metastasis is a bottleneck in cancer treatment. Studies have shown the pivotal roles of long noncoding RNAs (lncRNAs) in regulating cancer metastasis; however, our understanding of lncRNAs in gastric cancer (GC) remains limited. RNA-seq was performed on metastasis-inclined GC tissues to uncover metastasis-associated lncRNAs, revealing upregulated small nucleolar RNA host gene 26 (SNHG26) expression, which predicted poor GC patient prognosis. Functional experiments revealed that SNHG26 promoted cellular epithelial-mesenchymal transition and proliferation in vitro and in vivo. Mechanistically, SNHG26 was found to interact with nucleolin (NCL), thereby modulating c-Myc expression by increasing its translation, and in turn promoting energy metabolism via hexokinase 2 (HK2), which facilitates GC malignancy. The increase in energy metabolism supplies sufficient energy to promote c-Myc translation and expression, forming a positive feedback loop. In addition, metabolic and translation inhibitors can block this loop, thus inhibiting cell proliferation and mobility, indicating potential therapeutic prospects in GC.


Assuntos
RNA Longo não Codificante , Neoplasias Gástricas , Humanos , Linhagem Celular Tumoral , Movimento Celular/genética , Proliferação de Células/genética , Metabolismo Energético , Retroalimentação , Regulação Neoplásica da Expressão Gênica , Biossíntese de Proteínas , RNA Longo não Codificante/metabolismo , Neoplasias Gástricas/patologia
3.
Cell Mol Life Sci ; 81(1): 24, 2024 Jan 12.
Artigo em Inglês | MEDLINE | ID: mdl-38212432

RESUMO

The accumulation of metabolites in the intervertebral disc is considered an important cause of intervertebral disc degeneration (IVDD). Lactic acid, which is a metabolite that is produced by cellular anaerobic glycolysis, has been proven to be closely associated with IVDD. However, little is known about the role of lactic acid in nucleus pulposus cells (NPCs) senescence and oxidative stress. The aim of this study was to investigate the effect of lactic acid on NPCs senescence and oxidative stress as well as the underlying mechanism. A puncture-induced disc degeneration (PIDD) model was established in rats. Metabolomics analysis revealed that lactic acid levels were significantly increased in degenerated intervertebral discs. Elimination of excessive lactic acid using a lactate oxidase (LOx)-overexpressing lentivirus alleviated the progression of IVDD. In vitro experiments showed that high concentrations of lactic acid could induce senescence and oxidative stress in NPCs. High-throughput RNA sequencing results and bioinformatic analysis demonstrated that the induction of NPCs senescence and oxidative stress by lactic acid may be related to the PI3K/Akt signaling pathway. Further study verified that high concentrations of lactic acid could induce NPCs senescence and oxidative stress by interacting with Akt and regulating its downstream Akt/p21/p27/cyclin D1 and Akt/Nrf2/HO-1 pathways. Utilizing molecular docking, site-directed mutation and microscale thermophoresis assays, we found that lactic acid could regulate Akt kinase activity by binding to the Lys39 and Leu52 residues in the PH domain of Akt. These results highlight the involvement of lactic acid in NPCs senescence and oxidative stress, and lactic acid may become a novel potential therapeutic target for the treatment of IVDD.


Assuntos
Degeneração do Disco Intervertebral , Disco Intervertebral , Núcleo Pulposo , Ratos , Animais , Degeneração do Disco Intervertebral/metabolismo , Núcleo Pulposo/metabolismo , Proteínas Proto-Oncogênicas c-akt/metabolismo , Simulação de Acoplamento Molecular , Fosfatidilinositol 3-Quinases/metabolismo , Disco Intervertebral/metabolismo , Senescência Celular
4.
Arthritis Res Ther ; 25(1): 117, 2023 07 07.
Artigo em Inglês | MEDLINE | ID: mdl-37420255

RESUMO

BACKGROUND: Intervertebral disc degeneration (IVDD) is closely associated with the structural damage in the annulus fibrosus (AF). Aberrant mechanical loading is an important inducement of annulus fibrosus cells (AFCs) apoptosis, which contributes to the AF structural damage and aggravates IVDD, but the underlying mechanism is still unclear. This study aims to investigate the mechanism of a mechanosensitive ion channel protein Piezo1 in aberrant mechanical loading-induced AFCs apoptosis and IVDD. METHODS: Rats were subjected to lumbar instability surgery to induce the unbalanced dynamic and static forces to establish the lumbar instability model. MRI and histological staining were used to evaluate the IVDD degree. A cyclic mechanical stretch (CMS)-stimulated AFCs apoptosis model was established by a Flexcell system in vitro. Tunel staining, mitochondrial membrane potential (MMP) detection, and flow cytometry were used to evaluate the apoptosis level. The activation of Piezo1 was detected using western blot and calcium fluorescent probes. Chemical activator Yoda1, chemical inhibitor GSMTx4, and a lentiviral shRNA-Piezo1 system (Lv-Piezo1) were utilized to regulate the function of Piezo1. High-throughput RNA sequencing (RNA-seq) was used to explore the mechanism of Piezo1-induced AFCs apoptosis. The Calpain activity and the activation of Calpain2/Bax/Caspase3 axis were evaluated by the Calpain activity kit and western blot with the siRNA-mediated Calapin1 or Calpain2 knockdown. Intradiscal administration of Lv-Piezo1 was utilized to evaluate the therapeutic effect of Piezo1 silencing in IVDD rats. RESULTS: Lumbar instability surgery promoted the expression of Piezo1 in AFCs and stimulated IVDD in rats 4 weeks after surgery. CMS elicited distinct apoptosis of AFCs, with enhanced Piezo1 activation. Yoda1 further promoted CMS-induced apoptosis of AFCs, while GSMTx4 and Lv-Piezo1 exhibited opposite effects. RNA-seq showed that knocking down Piezo1 inhibited the calcium signaling pathway. CMS enhanced Calpain activity and elevated the expression of BAX and cleaved-Caspase3. Calpain2, but not Calpain1 knockdown, inhibited the expression of BAX and cleaved-Caspase3 and alleviated AFCs apoptosis. Lv-Piezo1 significantly alleviated the progress of IVDD in rats after lumbar instability surgery. CONCLUSIONS: Aberrant mechanical loading induces AFCs apoptosis to promote IVDD by activating Piezo1 and downstream Calpain2/BAX/Caspase3 pathway. Piezo1 is expected to be a potential therapeutic target in treating IVDD.


Assuntos
Anel Fibroso , Degeneração do Disco Intervertebral , Disco Intervertebral , Animais , Ratos , Anel Fibroso/metabolismo , Anel Fibroso/patologia , Apoptose/genética , Proteína X Associada a bcl-2/metabolismo , Calpaína , Disco Intervertebral/metabolismo , Degeneração do Disco Intervertebral/metabolismo , Canais Iônicos/metabolismo
5.
J Int Med Res ; 51(6): 3000605231183553, 2023 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-37382236

RESUMO

Q fever is an important zoonotic disease caused by the pathogen Coxiella burnetii, which is inhaled into the body through the respiratory tract leading to acute symptoms. Severe acute Q fever may result in complications, such as pneumonia, hepatitis, or myocarditis, and some patients may develop chronic Q fever after incomplete treatment. Local persistent C. burnetii infection may lead to chronic Q fever that often requires surgery and anti-infection treatment for several years, seriously endangering patient health and increasing the economic burden for families. The clinicians' lack of awareness of the disease may be one reason leading to a delay in treatment. Here, a case of Q fever in a 53-year-old male patient, which was diagnosed by next generation sequencing and exhibited a distinct computed tomographic feature, is reported, with the aim of improving clinical knowledge of this disease. Following diagnosis, the patient was treated with 0.1 g doxycycline, orally, twice daily, and 0.5 g chloramphenicol, orally, three times daily, leading to improvement of symptoms and discharge from hospital.


Assuntos
Nódulos Pulmonares Múltiplos , Febre Q , Masculino , Animais , Humanos , Pessoa de Meia-Idade , Febre Q/complicações , Febre Q/diagnóstico , Febre Q/tratamento farmacológico , Zoonoses , Cloranfenicol , Doxiciclina/uso terapêutico
6.
Int J Hyperthermia ; 40(1): 2223369, 2023.
Artigo em Inglês | MEDLINE | ID: mdl-37344382

RESUMO

PURPOSE: To investigate the feasibility of percutaneous intrauterine instillation of chilled saline to protect the endometrium during microwave ablation (MWA) treating types 1-3 uterine fibroids. MATERIALS AND METHODS: Twenty-six patients with types 1-3 uterine fibroids were prospectively enrolled in an intrauterine saline instillation group (study group). The same number of patients with types 1-3 uterine fibroids who previously received MWA without endometrial protection were retrospectively included in a control group. Endometrial impairment was evaluated by hysteroscopy and magnetic resonance imaging (MRI). RESULTS: In the study group, hysteroscopy revealed an intact endometrium in 17 patients, congestion and reddening of the endometrium due to heat in 8 patients, and a burnt necrosis with a size < 1 cm on the functional layer of the endometrium in 1 patient. On MRI, in the study group, there were 17 (65.4%), 6 (23.1%), and 3 (11.5%) patients with grades 0, 1, and 2 endometrial impairment, respectively, but no grade 3 endometrial impairment. In the control group, there were 8 (30.8%), 8 (30.8%), 7 (26.9%), and 3 (11.5%) patients with grades 0, 1, 2, and 3 endometrial impairment, respectively. Endometrial impairment in the study group was significantly better than that in the control group (p = 0.006). One patient had puncture tunnel bleeding and no other complications occurred in the study group. CONCLUSION: Intraoperative percutaneous intrauterine instillation of chilled saline may be effective and safe in reducing the thermal damage to the endometrium caused by MWA for treating types 1-3 uterine fibroids.


Assuntos
Leiomioma , Neoplasias Uterinas , Feminino , Gravidez , Humanos , Micro-Ondas/uso terapêutico , Estudos Retrospectivos , Endométrio/diagnóstico por imagem , Endométrio/cirurgia , Endométrio/patologia , Leiomioma/diagnóstico por imagem , Leiomioma/cirurgia , Leiomioma/complicações , Histeroscopia , Neoplasias Uterinas/cirurgia
7.
Front Pharmacol ; 14: 1081363, 2023.
Artigo em Inglês | MEDLINE | ID: mdl-37006999

RESUMO

Cinobufacini injection (CI), an aqueous extract of Cutis Bufonis, is clinically used for cancer therapy in China, but its molecular mechanism for the treatment of osteosarcoma (OS) remains unclear. We constructed U2OS ectopic subcutaneous tumor model to verify the anti-OS effect of CI in vivo. Meanwhile, cell proliferation of U2OS and MG63 cells was monitored in vitro using the CCK-8 assay, colony formation and morphological changes. Cell cycle arrest and apoptosis were detected by flow cytometry and western blot, which showed that CI significantly inhibited proliferation, induced cell cycle arrest and apoptosis in human OS cells. The further RNA-seq results identified that the Hippo signaling pathway was involved in the anti-OS effect of CI. YAP/TAZ are two major components of the Hippo pathway in breast cancer and are positively regulated by prolyl isomerase PIN1, we assessed their role in OS using both clinicopathological sections and western blots. CI also inhibited PIN1 enzyme activity in a dose-dependent manner, which resulted in impaired PIN1, YAP, and TAZ expression in vitro and in vivo. Additionally, 15 potential compounds of CI were found to occupy the PIN1 kinase domain and inhibit its activity. In summary, CI plays an anti-OS role by down-regulating the PIN1-YAP/TAZ pathway.

8.
Materials (Basel) ; 16(8)2023 Apr 19.
Artigo em Inglês | MEDLINE | ID: mdl-37110046

RESUMO

The aim of this study is to fabricate high-strength steel with exceptional yield strength and superior ductility by employing a novel design approach of nanolamellar/equiaxial crystal "sandwich" heterostructures, utilizing rolling and electron-beam-welding techniques. The microstructural heterogeneity of the steel is manifested in the phase content and grain size, ranging from nanolamellae comprising a small quantity of martensite on both sides to the completely coarse austenite in the center, which are interconnected via gradient interfaces. The structural heterogeneity and phase-transformation-induced plasticity (TIRP) offer remarkable strength and ductility for the samples. Furthermore, the synergistic confinement of the heterogeneous structures leads to the formation of Lüders bands, which exhibit stable propagation under the TIRP effect and impede the onset of plastic instability, ultimately resulting in a significant improvement in the ductility of the high-strength steel.

9.
Se Pu ; 41(3): 281-286, 2023 Mar.
Artigo em Chinês | MEDLINE | ID: mdl-36861212

RESUMO

Two-dimensional liquid chromatography (2D-LC) has gained increased attention because of its high peak capacity for separating complex samples. However, preparative 2D-LC aimed at isolating compounds is significantly different compared with one-dimensional liquid chromatography (1D-LC) in terms of method development and system configuration; thus, it is less developed than its analytical counterpart. The use of 2D-LC in large-scale product preparation has rarely been reported. Hence, a preparative 2D-LC system was developed in this study. The system was composed of one set of preparative LC modules as a separation system, with a dilution pump, switch valves, and trap column array as the interface, to enable the simultaneous isolation of several compounds. Tobacco was used as a sample, and the developed system was applied to isolate nicotine, chlorogenic acid, rutin, and solanesol. The chromatographic conditions were developed by investigating the trapping efficiency of different types of trap column packings, and chromatographic behaviors under different overload conditions. The four compounds were isolated in one 2D-LC run with high purity. The developed system features low cost because it employs medium-pressure isolation, excellent automation owing to its use of an online column switch, high stability, and capability for large-scale production. The isolation of chemicals from tobacco leaves as pharmaceutical raw materials could aid in the development of the tobacco industry and promote the local agricultural economy.


Assuntos
Ácido Clorogênico , Nicotiana , Cromatografia Líquida , Nicotina , Folhas de Planta
10.
Ultrasonography ; 42(2): 314-322, 2023 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-36935592

RESUMO

PURPOSE: This study aimed to evaluate the diagnostic value of combined fine-needle aspiration (FNA) with core needle biopsy (CNB) in thyroid nodules. METHODS: FNA and CNB were performed simultaneously on 703 nodules. We compared the proportions of inconclusive results and the diagnostic performance for malignancy among FNA, CNB, and combined FNA/CNB for different nodule sizes. RESULTS: Combined FNA/CNB showed lower proportions of inconclusive results than CNB for all nodules (2.8% vs. 5.7%, P<0.001), nodules ≤1.0 cm (4.9% vs. 7.3%, P=0.063), nodules >1.0 cm (2.0% vs. 5.0 %, P<0.001), nodules ≤1.5 cm (3.8% vs. 7.9 %, P<0.001), and nodules >1.5 cm (2.1% vs. 3.9 %, P=0.016). The sensitivity of combined FNA/CNB in predicting malignancy was significantly higher than that of CNB (89.0% vs. 80.0%, P<0.001) and FNA (89.0% vs. 58.1%, P<0.001) for all nodules. Within American College of Radiology Thyroid and Imaging Reporting and Data System grades 4-5, in the subgroup of nodules ≤1.5 cm, combined FNA/ CNB showed the best sensitivity in predicting malignancy (91.4%), significantly higher than that of CNB (81.0%, P<0.001) and FNA (57.8%, P<0.001). However, in the subgroup of nodules >1.5 cm, the difference between combined FNA/CNB and CNB was not significant (84.2% vs. 78.9%, P=0.500). CONCLUSION: Regardless of nodule size, combined FNA/CNB tended to yield lower proportions of inconclusive results than CNB or FNA alone and exhibited higher performance in diagnosing malignancy. The combined FNA/CNB technique may be a more valuable diagnostic method for nodules ≤1.5 cm and nodules with a risk of malignancy than CNB and FNA alone.

11.
Clin Hemorheol Microcirc ; 83(4): 377-386, 2023.
Artigo em Inglês | MEDLINE | ID: mdl-36744332

RESUMO

BACKGROUND: The inadequacy samples caused by the internal characteristic structure of thyroid nodules are difficult to be solved. OBJECTIVE: To evaluate the ultrasound features affecting the sample adequacy after fine-needle aspiration (FNA) of thyroid nodules with different risk stratification. METHODS: 592 thyroid nodules that underwent ultrasound-guided FNA were included in this retrospective study. The sample obtained by FNA were classified as inadequacy and adequacy according to the cytopathological results. Ultrasound features (ie., size, position, cystic predominance, composition, echo, shape, margin, and superficial annular calcification status) of the nodules were recorded and compared between the inadequacy sample group and adequacy sample group. RESULTS: Multiple logistic regression shows that preponderant cystic proportion (OR, 0.384; P = 0.041), extremely hypoechogenicity and hypoechogenicity (OR, 6.349; P = 0.006) were the independent influencing factors of inadequate samples after FNA in benign expected nodules. In addition, nodule size ≤10 mm (OR, 1.960; P = 0.010) and superficially annular calcification (OR, 4.600; P < 0.001) were independent influencing factors for inadequate samples after FNA in malignant expected nodules. CONCLUSION: The ultrasound features of hypoechogenicity or high cystic proportion in benign expected nodules and that of small size or annular calcification in malignant expected nodules were the risk factors for inadequacy samples by US-guided FNA.


Assuntos
Neoplasias da Glândula Tireoide , Nódulo da Glândula Tireoide , Humanos , Nódulo da Glândula Tireoide/diagnóstico por imagem , Nódulo da Glândula Tireoide/patologia , Biópsia por Agulha Fina/métodos , Estudos Retrospectivos , Ultrassonografia , Medição de Risco , Neoplasias da Glândula Tireoide/diagnóstico por imagem , Neoplasias da Glândula Tireoide/patologia
12.
Gene Ther ; 30(1-2): 75-87, 2023 02.
Artigo em Inglês | MEDLINE | ID: mdl-35132206

RESUMO

Traumatic brain injury (TBI) survivors suffer from long-term disability and neuropsychiatric sequelae due to irreparable brain tissue destruction. However, there are still few efficient therapies to promote neurorestoration in damaged brain tissue. This study aimed to investigate whether the pro-oncogenic gene ski can promote neurorestoration after TBI. We established a ski-overexpressing experimental TBI mouse model using adenovirus-mediated overexpression through immediate injection after injury. Hematoxylin-eosin staining, MRI-based 3D lesion volume reconstruction, neurobehavioral tests, and analyses of neuronal regeneration and astrogliosis were used to assess neurorestorative efficiency. The effects of ski overexpression on the proliferation of cultured immature neurons and astrocytes were evaluated using imaging flow cytometry. The Ski protein level increased in the perilesional region at 3 days post injury. ski overexpression further elevated Ski protein levels up to 14 days post injury. Lesion volume was attenuated by approximately 36-55% after ski overexpression, with better neurobehavioral recovery, more newborn immature and mature neurons, and less astrogliosis in the perilesional region. Imaging flow cytometry results showed that ski overexpression elevated the proliferation rate of immature neurons and reduced the proliferation rate of astrocytes. These results show that ski can be considered a novel neurorestoration-related gene that effectively promotes neurorestoration, facilitates neuronal regeneration, and reduces astrogliosis after TBI.


Assuntos
Lesões Encefálicas Traumáticas , Gliose , Camundongos , Animais , Gliose/genética , Gliose/metabolismo , Gliose/patologia , Neurônios/metabolismo , Lesões Encefálicas Traumáticas/terapia , Encéfalo/metabolismo , Regeneração
13.
Int J Mol Sci ; 23(21)2022 Nov 02.
Artigo em Inglês | MEDLINE | ID: mdl-36362159

RESUMO

Soot molecules are hazardous compounds threatening human health. Computational chemistry provides efficient tools for studying them. However, accurate quantum chemistry calculation is costly for the simulation of large-size soot molecules and high-throughput calculations. Semi-empirical (SE) quantum chemistry methods are optional choices for balancing computational costs. In this work, we validated the performances of several widely used SE methods in the description of soot formation. Our benchmark study focuses on, but is not limited to, the validation of the performances of SE methods on reactive and non-reactive MD trajectory calculations. We also examined the accuracy of SE methods of predicting soot precursor structures and energy profiles along intrinsic reaction coordinate(s) (IRC). Finally, we discussed the spin density predicted by SE methods. The SE methods validated include AM1, PM6, PM7, GFN2-xTB, DFTB2, with or without spin-polarization, and DFTB3. We found that the shape of MD trajectory profiles, the relative energy, and molecular structures predicted by SE methods are qualitatively correct. We suggest that SE methods can be used in massive reaction soot formation event sampling and primary reaction mechanism generation. Yet, they cannot be used to provide quantitatively accurate data, such as thermodynamic and reaction kinetics ones.


Assuntos
Teoria Quântica , Fuligem , Humanos , Termodinâmica , Simulação por Computador , Estrutura Molecular
14.
Pharm Biol ; 60(1): 1701-1709, 2022 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-36066106

RESUMO

CONTEST: Isopsoralen, one of the main active and quality-control compounds in Psoralea corylifolia L. (Fabaceae), has antitumor and oestrogen-like effects. Previous studies demonstrated that isopsoralen induced hepatotoxicity and its long-term exposure led to cholestatic liver injury. OBJECTIVE: This study investigates the effect of three- or seven-day exposure of low dose isopsoralen (80 mg/kg) on bile acid homeostasis in C57BL/6J mice. MATERIALS AND METHODS: Forty-two C57BL/6J mice were randomly divided into control, three- and seven-day groups (n = 14 per group, half female and half male). Isopsoralen suspension was administrated intragastrically at 80 mg/kg once a day. Blood and liver samples were collected to measure biochemical indices and transport of BAs. The histopathology of the liver was also observed. HPLC-MS/MS was also used to measure the BAs profiles and transport activity. RESULTS: In the study, isopsoralen increased the levels of serum AST, ALT in three- and seven-day groups, and caused vacuolar degeneration and swelling in the liver. Canalicular efflux transporters BSEP, OSTα, MRP2, MRP3, and basolateral uptake transporters NTCP, OATP4 were inhibited after seven-day-administration. Moreover, amino acid binding enzymes (BAAT and BACS) were also inhibited after seven-day-administration. The composition of BAs changed greatly and the concentration of some unconjugated-BAs which have stronger hydrophobicity, such as CA, CDCA, was significantly increased. CONCLUSIONS: Isopsoralen (80 mg/kg) caused hepatotoxicity after short-term exposure by inhibiting the expression of efflux transporters, amino acid binding enzymes, and disrupting BAs spectrum.


Assuntos
Ácidos e Sais Biliares , Doença Hepática Crônica Induzida por Substâncias e Drogas , Animais , Feminino , Furocumarinas , Masculino , Proteínas de Membrana Transportadoras , Camundongos , Camundongos Endogâmicos C57BL , Espectrometria de Massas em Tandem
15.
Diagn Microbiol Infect Dis ; 104(4): 115801, 2022 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-36130430

RESUMO

Timely identification of respiratory pathogens guides specific treatment, reduces hospital costs and minimizes the excessive use of antibiotics. A new multiplex real-time PCR panel was developed based on an automatic molecular detection and analysis system (AutoMolec system), consisting of three separate internally controlled assays. Mycoplasma pneumoniae, Chlamydia pneumoniae, adenovirus, human metapneumovirus, influenza B virus, respiratory syncytial virus and human parainfluenza virus 1-3 may be directly detected in original samples. The system's clinical performance was evaluated by comparison with an approved commercial kit, using 517 clinical samples. The limit of detection of the AutoMolec mRT-PCR panel ranged from 4 × 10-4 ∼3.3 TCID50/mL and no cross-reaction with common respiratory pathogens was observed. The AutoMolec mRT-PCR panel had 99.09% sensitivity and 100.0% specificity and overall detection consistency was 99.61%, making it comparable to that of the commercial kit. Therefore, the AutoMolec mRT-PCR panel has great potential for routine screening of respiratory infection in China.


Assuntos
Metapneumovirus , Vírus Sincicial Respiratório Humano , Infecções Respiratórias , Humanos , Reação em Cadeia da Polimerase em Tempo Real , Reação em Cadeia da Polimerase Multiplex , Infecções Respiratórias/diagnóstico , Metapneumovirus/genética , Sensibilidade e Especificidade
16.
Stem Cell Res Ther ; 13(1): 340, 2022 07 26.
Artigo em Inglês | MEDLINE | ID: mdl-35883157

RESUMO

BACKGROUND: Nucleus pulposus mesenchymal stem cells (NPMSCs) transplantation is a promising treatment for intervertebral disc degeneration (IVDD). However, the transplanted NPMSCs exhibited weak cell proliferation, high cell apoptosis, and a low ability to resist the harsh microenvironment of the degenerated intervertebral disc. There is an urgent need to explore feasible methods to enhance the therapeutic efficacy of NPMSCs transplantation. OBJECTIVE: To identify the optimal concentration for NPMSCs pretreatment with hydrogen peroxide (H2O2) and explore the therapeutic efficacy of NPMSCs transplantation using H2O2 pretreatment in IVDD. METHODS: Rat NPMSCs were pretreated with different concentrations (range from 25 to 300 µM) of H2O2. The proliferation, reactive oxygen species (ROS) level, and apoptosis of NPMSCs were detected by cell counting kit-8 (CCK-8) assay, 5-ethynyl-2'-deoxyuridine (EdU) staining, and flow cytometry in vitro. The underlying signalling pathways were explored utilizing Western blotting. A rat needle puncture-stimulated IVDD model was established. X-ray, histological staining, and a multimode small animal live imaging system were used to evaluate the therapeutic effect of H2O2-pretreated NPMSCs in vivo. RESULTS: NPMSCs pretreated with 75 µM H2O2 demonstrated the strongest elevated cell proliferation by inhibiting the Hippo pathway (P < 0.01). Meanwhile, 75 µM H2O2-pretreated NPMSCs exhibited significantly enhanced antioxidative stress ability (P < 0.01), which is related to downregulated Brd4 and Keap1 and upregulated Nrf2. NPMSCs pretreated with 75 µM H2O2 also exhibited distinctly decreased apoptosis (P < 0.01). In vivo experiments verified that 75 µM H2O2-pretreated NPMSCs-transplanted rats exhibited an enhanced disc height index (DHI% = 90.00 ± 4.55, P < 0.01) and better histological morphology (histological score = 13.5 ± 0.5, P < 0.01), which means 75 µM H2O2-pretreated NPMSCs can better adapt to the environment of degenerative intervertebral discs and promote the repair of IVDD. CONCLUSIONS: Pretreatment with 75 µM H2O2 was the optimal concentration to improve the proliferation, antioxidative stress, and antiapoptotic ability of transplanted NPMSCs, which is expected to provide a new feasible method to improve the stem cell therapy efficacy of IVDD.


Assuntos
Degeneração do Disco Intervertebral , Disco Intervertebral , Células-Tronco Mesenquimais , Núcleo Pulposo , Animais , Apoptose , Peróxido de Hidrogênio/farmacologia , Disco Intervertebral/patologia , Degeneração do Disco Intervertebral/patologia , Proteína 1 Associada a ECH Semelhante a Kelch , Células-Tronco Mesenquimais/metabolismo , Fator 2 Relacionado a NF-E2/genética , Fator 2 Relacionado a NF-E2/metabolismo , Proteínas Nucleares/metabolismo , Núcleo Pulposo/metabolismo , Ratos
17.
Front Oncol ; 12: 860257, 2022.
Artigo em Inglês | MEDLINE | ID: mdl-35686112

RESUMO

Objective: To design a multidisciplinary enhanced recovery after surgery (ERAS) protocol for glioma patients undergoing elective craniotomy and evaluate its clinical efficacy and safety after implementation in a tertiary neurosurgical center in China. Methods: ERAS protocol for glioma patients was developed and modified based on the best available evidence. Patients undergoing elective craniotomy for treatment of glioma between September 2019 to May 2021 were enrolled in a randomized clinical trial comparing a conventional neurosurgical perioperative care (control group) to an ERAS protocol (ERAS group). The primary outcome was postoperative hospital length of stay (LOS). Secondary outcomes were 30-day readmission rate, postoperative complications, duration of the drainage tube, time to first oral fluid intake, time to ambulation and functional recovery status. Results: A total of 151 patients were enrolled (ERAS group: n = 80; control group: n = 71). Compared with the control group, postoperative LOS was significantly shorter in the ERAS group (median: 5 days vs. 7 days, p<0.0001). No 30-day readmission or reoperation occurred in either group. The time of first oral intake, urinary catheter removal within 24 h and early ambulation on postoperative day (POD) 1 were earlier and shorter in the ERAS group compared with the control group (p<0.001). No statistical difference was observed between the two groups in terms of surgical- and nonsurgical-related complications. Functional recovery in terms of Karnofsky Performance Status (KPS) scores both at discharge and 30-day follow-up was similar in the two groups. Moreover, no significant difference was found between the two groups in the Hospital Anxiety and Depression Scale (HADS) scores. Conclusion: The implementation of the ERAS protocol for glioma patients offers significant benefits over conventional neurosurgical perioperative management, as it is associated with enhancing postoperative recovery, without additional perioperative complications and risks. Clinical Trial Registration: Chinese Clinical Trial Registry (http://www.chictr.org.cn/showproj.aspx?proj=42016), identifier ChiCTR1900025108.

18.
World J Clin Cases ; 10(2): 458-468, 2022 Jan 14.
Artigo em Inglês | MEDLINE | ID: mdl-35097070

RESUMO

BACKGROUND: Gastric leiomyomas and gastric stromal tumors are the most common types of gastric tumors encountered. In recent years, the incidence of the two types of tumors has been increasing, but the differential diagnosis is still a challenge in clinical work. However, as there are many reports on stromal tumors and inflammation-related indicators are gradually being paid attention to as important factors in predicting tumor prognosis, the two main purposes of this study were to explore the inflammation-related differences between the two types of tumors and to develop a nomogram as a predictive model. AIM: To explore the differences in platelet-lymphocyte ratio (PLR), neutrophil-lymphocyte ratio (NLR), lymphocyte mononuclear cell ratio (LMR), and SII between the two types of tumors, and simultaneously create the nomogram model. METHODS: This study enrolled 88 patients in the gastric stromal tumor group and 56 patients in the gastric leiomyoma group, and the relevant data of the two groups were entered into the system for an integrated analysis. The primary objective of this study was to identify the differences in the inflammation index between the two types of tumors. RESULTS: There were statistically significant differences between the two groups in sex, age, and tumor location. In comparison, gastric leiomyomas seem to be more common in women, young patients, and gastric cardia, which is in line with our previous research; the groups showed the following statistical differences: PLR (158.2% vs 134.3%, P = 0.028), NLR (2.35 vs 1.68, P = 0.000), LMR (5.75 vs 10.8, P = 0.004), and SII (546.2 vs 384.3, P = 0.003). The results of the multivariate logistic regression analysis showed that sex, age, tumor location, and LMR were independent risk factors for the identification of the two types of tumors. After considering the risk factors selected by the above analysis into the predictive model, a predictive model for distinguishing gastrointestinal stromal tumors from gastric leiomyomas was established as the nomogram. CONCLUSION: Gastric leiomyomas and gastric stromal tumors are not only different in factors such as age of the patient, but also in inflammatory indicators such as LMR and PLR. We have established a predictive model related to the laboratory indicators and are looking forward to further research conducted in this clinical area.

19.
Inorg Chem ; 60(24): 19328-19335, 2021 Dec 20.
Artigo em Inglês | MEDLINE | ID: mdl-34865466

RESUMO

Ethylene (C2H4) is one of the most significant substances in the petrochemical industry; however, the capture of acetylene (C2H2) in about 1% from C2H2/C2H4 mixtures is a difficult task because of the similarity of their physical properties. With the aggravation of the energy crisis, using metal-organic framework (MOF) materials to purify C2H4 through adsorptive separation is a promising way to save energy and reduce emission. Pore-space partition (PSP) with the aim of enhancing the density of the binding sites and the strength of the host-guest interactions is an effective means to promote a solution for the challenging gas separation problems. Herein, we report a new embedding metal-carboxylate chain-induced topology upgrade strategy within a MOF to realize PSP and separation of C2H2/C2H4 mixtures. As a proof of concept, we construct a microporous MOF (NUM-12) utilizing the in situ insertion of cobalt terephthalic chains into a pretargeted ant-type framework during synthesis. Because of the attainment of an elaborately tuned aperture size and a specific pore environment through this strategy, NUM-12a (activated NUM-12) not only has a remarkable gas sorption capacity and strong interactions for C2H2 but also possesses an excellent purification performance for C2H2/C2H4 mixtures. Both experiments and simulation calculations clearly reveal that NUM-12 is a promising candidate for the separation of C2H2/C2H4, proving the feasibility of this new strategy for developing newly fashioned MOFs with adjustable structure and performance.

20.
Nanomaterials (Basel) ; 11(9)2021 Sep 10.
Artigo em Inglês | MEDLINE | ID: mdl-34578669

RESUMO

Martensite transformation and grain refinement can make austenitic stainless steel stronger, but this comes at a dramatic loss of both ductility and corrosion resistance. Here we report a novel gradient structure in 301 stainless steel sheets, which enables an unprecedented combination of high strength, improved ductility and good corrosion resistance. After producing inter-layer microstructure gradient by surface mechanical attrition treatment, the sheet was annealed at high temperature for a short duration, during which partial reverse transformation occurred to form recrystallized austenitic nano-grains in the surface layer, i.e., introducing extra intra-layer heterogeneity. Such 3D microstructure heterogeneity activates inter-layer and inter-phase interactions during deformation, thereby producing back stress for high yield strength and hetero-deformation induced (HDI) hardening for high ductility. Importantly, the recrystallized austenitic nano-grains significantly ameliorates the corrosion resistance. These findings suggest an effective route for evading the strength-ductility and strength-corrosion tradeoffs in stainless steels simultaneously.

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