Your browser doesn't support javascript.
loading
Mostrar: 20 | 50 | 100
Resultados 1 - 20 de 446
Filtrar
1.
Neural Regen Res ; 17(8): 1827-1832, 2022 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-35017445

RESUMO

Targeted muscle reinnervation (TMR) is a surgical procedure used to transfer residual peripheral nerves from amputated limbs to targeted muscles, which allows the target muscles to become sources of motor control information for function reconstruction. However, the effect of TMR on injured motor neurons is still unclear. In this study, we aimed to explore the effect of hind limb TMR surgery on injured motor neurons in the spinal cord of rats after tibial nerve transection. We found that the reduction in hind limb motor function and atrophy in mice caused by tibial nerve transection improved after TMR. TMR enhanced nerve regeneration by increasing the number of axons and myelin sheath thickness in the tibial nerve, increasing the number of anterior horn motor neurons, and increasing the number of choline acetyltransferase-positive cells and immunofluorescence intensity of synaptophysin in rat spinal cord. Our findings suggest that TMR may enable the reconnection of residual nerve fibers to target muscles, thus restoring hind limb motor function on the injured side.

2.
ACS Appl Mater Interfaces ; 14(2): 2510-2521, 2022 Jan 19.
Artigo em Inglês | MEDLINE | ID: mdl-34986639

RESUMO

The development of nanocarriers capable of codelivering antigens and immune-activating adjuvants is an emerging area of research and is relevant for cancer vaccines that target induction of antigen-specific CD8+ T-cell responses. Here, we report a system for delivery of short peptide antigens to dendritic cells for strong cellular immune responses, based on block copolymers chemically modified with a hydrophobic and self-immolative linker. After modification, micelles effectively and reversibly capture antigens and adjuvants via a covalent bond within several minutes in an aqueous solution. After uptake in antigen presenting cells, the polymer disulfide bond is cleaved by intracellular glutathione, leading to release of pristine antigens, along with the upregulated expression of costimulatory molecules. The induced antigen-specific CD8+ T cells have strong tumor cell killing efficacy in the murine B16OVA and human papilloma virus-E6/E7 subcutaneous and lung metastasis tumor models. In addition, delivery to lymph nodes can be imaged to visualize vaccine trafficking. Taken together, multifunctional self-immolative micelles represent a versatile class of a vaccine delivery system for the generation of a cellular immune response that warrants further exploration as a component of cancer immunotherapy.

3.
BMC Anesthesiol ; 22(1): 20, 2022 Jan 12.
Artigo em Inglês | MEDLINE | ID: mdl-35021994

RESUMO

OBJECTIVE: We sought to evaluate the postoperative control of pain and recovery in patients with ovarian cancer who underwent cytoreductive surgery by adding dexmedetomidine to ropivacaine in bilateral dual-transversus abdominis plane (Bd-TAP) blocks. METHODS: We enrolled 90 patients with an American Society of Anesthesiologists physical status I to III undergoing open abdominal cytoreductive surgery in this study. Patients were randomized and assigned into three groups (TAP-R, TAP-DR, or CON) of 30 participants each. All of the patients received standardized general anesthesia, and postoperative Bd-TAP blocks were performed. The TAP-R, TAP-DR, and CON groups received Bd-TAP blocks with 0.3% ropivacaine, 0.3% ropivacaine and 0.5 µg/kg of dexmedetomidine, and 0.9% normal saline, respectively. All of the patients received patient-controlled analgesia (PCA) (formula, 100 µg of sufentanil and 16 mg of ondansetron diluted with normal saline to 100 mL). Flurbiprofen axetil was used as a rescue drug if the visual analog scale (VAS) score was more than four points. The first request time for PCA bolus; the VAS scores at 0, 6, 12, 24, and 48 h after operation; and the cumulative sufentanil consumption within 24 and 48 h, respectively, were compared. Pulmonary function was evaluated preoperatively and at 24 h after the operation. The use of the rescue drug was recorded. Postoperative functional recovery, including time to stand, time to walk, time to return of bowel function, time to readiness for discharge, and postoperative complications, were recorded. RESULTS: Median values of the first request time for PCA of the TAP-R group was significantly prolonged compared to that of the CON group (median [interquartile range], 7.3 [6.5-8.0] hours vs. 3.0 [2.3-3.5] hours) (P < .001), while the TAP-DR group has the longest request time among the three groups (median [interquartile range], 13.5 [12.4-14.5] hours) (P < .001). The VAS scores at rest and upon coughing of the TAP-R group in the first 12 h were significantly lower than those of the CON group (P < 0.05), but showed no significant difference compared to those of the TAP-DR group. The VAS scores at rest and upon coughing were lower in the TAP-DR group at each time point compared to those of the CON group (P < .05). The cumulative sufentanil consumption in the TAP-DR group was significantly lower at 48 h (P = .04) after surgery than in the CON group, while there was no significant difference compared to that in the TAP-R group (P > .05). Less rescue analgesic was required by patients in the TAP-DR group than in the CON group (P < .05). Postoperative mean measured forced expiratory volume in 1 s (FEV1) and FEV1/forced vital capacity values in the TAP-DR group were significantly higher than those of the CON group (P = .009), while there was no significant difference compared to those of the TAP-R group (P = .10). There was no significantly difference in postoperative functional recovery between TAP-DR and CON group (P > 0.05). CONCLUSION: TAP blocks can provide effective pain relief up to 12 h postoperatively without a significant improvement in postoperative pulmonary function. The addition of dexmedetomidine to ropivacaine for Bd-TAP block prolonged the first bolus time of PCA when compared to that in the TAP-R group and decreased sufentanil consumption and the need of rescue analgesia relative to in the CON group at 48 h postoperative. The procedure provided better postoperative analgesia and improved postoperative pulmonary function relative to the CON group. Our results indicate that dexmedetomidine as an adjuvant of Bd-TAP can provide effective pain relief up to 48 h.

4.
Orthop Surg ; 2022 Jan 04.
Artigo em Inglês | MEDLINE | ID: mdl-34985187

RESUMO

Studies have shown that the change in lumbar spine bone mineral density with different osteoporosis drugs had a beneficial effect on the frequency of new vertebral and nonvertebral fractures in postmenopausal females, but their results were conflicting. This meta-analysis was performed to evaluate this relationship. A systematic literature search up to May 2020 was performed and 20 studies with 73,390 postmenopausal females were included; of them, a total of 41,980 were treated with osteoporosis drugs and 31,410 with placebo. They reported relationships between the change in lumbar spine bone mineral density and the frequency of new vertebral and nonvertebral fractures in postmenopausal females. Odds ratio (OR) with 95% confidence intervals (CIs) was calculated comparing the osteoporosis drugs to placebo effect on the frequency of new vertebral and nonvertebral fractures in postmenopausal females using the dichotomous method with a random or fixed-effect model. Treatment with osteoporosis drugs had significantly lower frequency of new vertebral fractures (OR, 0.53; 95% CI, 0.45-0.63, P < 0.001) and nonvertebral fractures (OR, 0.82; 95% CI, 0.78-0.87, P < 0.001) compared to placebo in postmenopausal females. Treatment with osteoporosis drugs had a significantly lower frequency of new vertebral and nonvertebral fractures compared to placebo in postmenopausal females. This relationship forces us to recommend osteoporosis drugs in postmenopausal females to avoid any possible new fractures. A cost-effective study is recommended.

5.
J Hazard Mater ; 422: 126948, 2022 01 15.
Artigo em Inglês | MEDLINE | ID: mdl-34449349

RESUMO

Phenanthrene (PHE), as one of representative polycyclic aromatic hydrocarbons (PAHs) can cause serious adverse effects on human health, developing effective adsorbents to alleviate PHE contamination is in urgent demand. A novel Fe3O4-SiO2-Dimethoxydiphenylsilane (Fe3O4-SiO2-2DMDPS) nanocomposite was fabricated from encapsulation and grafting process. Magnetic Fe3O4 nanoparticles were served as preliminary matrix material, SiO2 was used to link the magnetic oxide and provide hydroxyl groups for proceeding the silane coupling reaction subsequently, and the aromatic rings in DMDPS could provide active sites for PHE adsorption via π-π interaction. SEM-EDS, TEM, BET, VSM, XRD, FTIR, Raman, Zeta potential, and XPS techniques were used to characterize magnetic nanocomposite. The prepared Fe3O4-SiO2-2DMDPS exhibited an excellent adsorption performance towards PHE, it could maintain 75.97% adsorption capacity after four regeneration cycles. Homogeneous adsorption acted crucial role in the whole adsorption process and film diffusion was the rate-controlling procedure. Theoretical calculations put forward the most favorable bonding modes between Fe3O4-SiO2-2DMDPS and PHE molecules, confirmed the π-π interaction was valid and it usually existed in the form of parallel-displaced. This work might aid us to develop effective modification strategy for Fe3O4 nanoparticles and expand its application in the PAHs removing field.


Assuntos
Nanocompostos , Fenantrenos , Poluentes Químicos da Água , Adsorção , Humanos , Modelos Teóricos , Compostos de Organossilício , Dióxido de Silício , Poluentes Químicos da Água/análise
6.
World J Clin Cases ; 9(32): 10024-10032, 2021 Nov 16.
Artigo em Inglês | MEDLINE | ID: mdl-34877346

RESUMO

BACKGROUND: Mucosal-associated lymphoid tissue extranodal marginal zone (MALT) lymphoma is a low-grade tumor that rarely occurs in the urinary bladder. There is currently no consensus on the common imaging findings or most appropriate treatment in MALT lymphoma in the urinary bladder due to the limited number of reports. CASE SUMMARY: A 48-year-old woman was admitted to the hospital with a 1-year history of macroscopic hematuria. Imaging showed a large homogeneous mass with an unclear boundary and an irregular morphology in the bladder. The mass had an abundant blood supply. For further diagnosis, transurethral cystoscopic biopsy and bone marrow biopsy was performed, and the patient was finally diagnosed with primary MALT lymphoma of the bladder. R-CHOP chemotherapy was carried out. After three cycles of chemotherapy, the mass disappeared and the bladder wall thickness was only 4 mm, which indicated excellent therapeutic response to the chemotherapy. To date, the patient remains asymptomatic and she visits our hospital regularly for the completion of the remaining chemotherapy cycles. CONCLUSION: Primary MALT lymphoma of the bladder is rare, and there are certain characteristics in the ultrasonographic findings. Imaging findings play an important role in evaluating the therapeutic efficacy and are critical during long-term follow-up after therapy.

7.
Chemosphere ; : 133084, 2021 Nov 27.
Artigo em Inglês | MEDLINE | ID: mdl-34848224

RESUMO

An efficient and novel enantioseparation method was successfully developed and validated to quantify the enantiomers of cloquintocet-mexyl in soil, millet, enoki mushroom, oilseed rape, and watermelon using a modified QuEChERS technique combined with HPLC-MS/MS. This method showed reliable performances for determining both enantiomers of cloquintocet-mexyl in all five matrices. The limits of detection and limits of quantification were in the range of 0.06-0.15 µg kg-1 and 0.2-0.5 µg kg-1, respectively. Good linearities were obtained with correlation coefficients ≥0.9954. The mean recoveries were between 84.1% and 111.5%, with relative standard deviations ranging from 1.2% to 9.8% at three spiked levels. Additionally, the study of stereoselective dissipation of cloquintocet-mexyl in soil indicated that (R)-cloquintocet-mexyl was preferentially degraded. This work is the first to describe a chiral analytical method and enantioselective behavior of cloquintocet-mexyl and provide basic data for the risk evaluation of cloquintocet-mexyl in food and environmental safety.

8.
Small ; : e2104132, 2021 Dec 01.
Artigo em Inglês | MEDLINE | ID: mdl-34850550

RESUMO

Photoacoustic imaging (PA) in the second near infrared (NIR-II) window presents key advantages for deep tissue imaging owing to reduced light scattering and low background signal from biological structures. Here, a thiadiazoloquinoxaline-based semiconducting polymer (SP) with strong absorption in the NIR-II region is reported. After encapsulation of SP in Pluronic F127 (F127) followed by removal of excess surfactant, a dual functional polymer system named surfactant-stripped semiconductor polymeric micelles (SSS-micelles) are generated with water solubility, storage stability, and high photothermal conversion efficiency, permitting tumor theranostics in a mouse model. SSS-micelles have a wideband absorption in the NIR-II window, allowing for the PA imaging at both 1064 and 1300 nm wavelengths. The PA signal of the SSS-micelles can be detected through 6.5 cm of chicken breast tissue in vitro. In mice or rats, SSS-micelles can be visualized in bladder and intestine overlaid 5 cm (signal to noise ratio, SNR ≈ 17 dB) and 5.8 cm (SNR over 10 dB) chicken breast tissue, respectively. This work demonstrates the SSS-micelles as a nanoplatform for deep tissue theranostics.

9.
Front Microbiol ; 12: 761579, 2021.
Artigo em Inglês | MEDLINE | ID: mdl-34917049

RESUMO

The microbial community of acid mine drainage (AMD) fascinates researchers by their adaption and roles in shaping the environment. Molecular surveys have recently helped to enhance the understanding of the distribution, adaption strategy, and ecological function of microbial communities in extreme AMD environments. However, the interactions between the environment and microbial community of extremely acidic AMD (pH <3) from different mining areas kept unanswered questions. Here, we measured physicochemical parameters and profiled the microbial community of AMD collected from four mining areas with different mineral types to provide a better understanding of biogeochemical processes within the extremely acidic water environment. The prominent physicochemical differences across the four mining areas were in SO4 2-, metal ions, and temperature, and distinct microbial diversity and community assemblages were also discovered in these areas. Mg2+ and SO4 2- were the predominant factors determining the microbial structure and prevalence of dominant taxa in AMD. Leptospirillum, Ferroplasma, and Acidithiobacillus were abundant but showed different occurrence patterns in AMD from different mining areas. More diverse communities and functional redundancy were identified in AMD of polymetallic mining areas compared with AMD of copper mining areas. Functional prediction revealed iron, sulfur, nitrogen, and carbon metabolisms driven by microorganisms were significantly correlated with Mg2+ and SO4 2-, Ca2+, temperature, and Fe2+, which distinguish microbial communities of copper mine AMD from that of polymetallic mine AMD. In summary, microbial diversity, composition, and metabolic potential were mainly shaped by Mg2+ and SO4 2- concentrations of AMD, suggesting that the substrate concentrations may contribute to the distinct microbiological profiles of AMD from different mining areas. These findings highlight the microbial community structure in extremely acidic AMD forming by types of minerals and the interactions of physicochemical parameters and microbiology, providing more clues of the microbial ecological function and adaptation mechanisms in the extremely acidic environment.

10.
J Healthc Eng ; 2021: 7168397, 2021.
Artigo em Inglês | MEDLINE | ID: mdl-34931140

RESUMO

Background: Increasing evidence has shown that apoptosis in the hippocampus is closely related to depressive-like behavior. We previously reported that helicid had good antidepressant activities, which manifested as the alleviation of depression-like behaviors and the reversal of the high expression of neurocalcin delta (NCALD) in chronic unpredictable mild stress (CUMS) rats. The aim of this study was, therefore, to characterize the antidepressant-like effects and underlying mechanism of helicid on CUMS rats by silencing NCALD and using rescue experiments. Methods: We developed the CUMS rat model using CUMS stimulation from week 0 to week 6. The rats were treated with helicid, or NCALD silenced, then we overexpressed NCALD using adeno-associated virus. We also measured the protein levels of sGCα1, sGCß1, PKG1/2, and cleaved caspase-3 in hippocampal tissues using western blotting and measured cGMP using an ELISA. Results: Treating CUMS rats by silencing NCALD or by the administration of helicid improved the depressive-like behavior. The levels of proteins, including sGC, PKG, cleaved caspase-3, and cGMP, in hippocampus all decreased. NCALD overexpression reversed these decreases and reversed the alleviation of depression-like behaviors in CUMS rats. Limitation. We only detected the antidepressant effects of helicid in the hippocampus; therefore, other parts of brain should also be studied. Conclusions: Inhibition of NCALD, as well as helicid administration, alleviated antidepressant-like behavior by regulating the expressions of apoptotic cytokines and the sGC/cGMP/PKG signaling pathway. Overexpressing NCALD reversed the amelioration effects of silenced NCALD and helicid administration.

11.
BMC Bioinformatics ; 22(1): 589, 2021 Dec 13.
Artigo em Inglês | MEDLINE | ID: mdl-34903170

RESUMO

BACKGROUND: More and more Cas9 variants with higher specificity are developed to avoid the off-target effect, which brings a significant volume of experimental data. Conventional machine learning performs poorly on these datasets, while the methods based on deep learning often lack interpretability, which makes researchers have to trade-off accuracy and interpretability. It is necessary to develop a method that can not only match deep learning-based methods in performance but also with good interpretability that can be comparable to conventional machine learning methods. RESULTS: To overcome these problems, we propose an intrinsically interpretable method called AttCRISPR based on deep learning to predict the on-target activity. The advantage of AttCRISPR lies in using the ensemble learning strategy to stack available encoding-based methods and embedding-based methods with strong interpretability. Comparison with the state-of-the-art methods using WT-SpCas9, eSpCas9(1.1), SpCas9-HF1 datasets, AttCRISPR can achieve an average Spearman value of 0.872, 0.867, 0.867, respectively on several public datasets, which is superior to these methods. Furthermore, benefits from two attention modules-one spatial and one temporal, AttCRISPR has good interpretability. Through these modules, we can understand the decisions made by AttCRISPR at both global and local levels without other post hoc explanations techniques. CONCLUSION: With the trained models, we reveal the preference for each position-dependent nucleotide on the sgRNA (short guide RNA) sequence in each dataset at a global level. And at a local level, we prove that the interpretability of AttCRISPR can be used to guide the researchers to design sgRNA with higher activity.


Assuntos
Aprendizado de Máquina , RNA Guia , Sistemas CRISPR-Cas/genética
12.
J Clin Lab Anal ; : e24189, 2021 Dec 24.
Artigo em Inglês | MEDLINE | ID: mdl-34953081

RESUMO

BACKGROUND: Gastric cancer is the third leading cause of cancer-related death in the world. The purpose of the present study is to investigate the expression and prognostic significance of 6-phosphogluconolactonase (PGLS) in gastric cancer. METHODS: The protein extracted from a panel of four pairs of gastric cancer tissues and adjacent tissues, labeled with iTRAQ (8-plex) reagents, and followed by LC-ESI-MS/MS. The expressions of proteins were further validated by immunohistochemistry analysis. The expression levels of mRNA were analyzed and validated in the Oncomine database. The correlations of PGLS with prognostic outcomes were evaluated with Kaplan-Meier plotter database. RESULTS: The present study found that PGLS was significantly up-regulated in gastric cancer by using iTRAQ-based proteomics and immunohistochemistry analysis. The sensitivity of PGLS in gastric cancer was 72.9%. The high expression of PGLS was significantly correlated with TNM staging in gastric cancer (p = 0.02). The overexpression of PGLS predicts worse overall survival (OS) and post-progression survival (PPS) for gastric cancer (OS, HR = 1.48, p = 2.1e-05; PPS, HR = 1.35, p = 0.015). Specifically, the high PGLS expression predicts poor OS, PPS in male gastric cancer patients, in patients with lymph node metastasis and in patients with Her-2 (-). CONCLUSIONS: These findings suggested that PGLS was aberrantly expressed in gastric cancer and predicts poor overall survival, post-progression survival for gastric cancer patients. The present study collectively supported that PGLS is an important target for early determining and follow-up monitoring for gastric cancer.

13.
Front Microbiol ; 12: 768283, 2021.
Artigo em Inglês | MEDLINE | ID: mdl-34721370

RESUMO

The order Sulfolobales (phylum Crenarchaeota) is a group of thermoacidophilic archaea. The first member of the Sulfolobales was discovered in 1972, and current 23 species are validly named under the International Code of Nomenclature of Prokaryotes. The majority of members of the Sulfolobales is obligately or facultatively chemolithoautotrophic. When they grow autotrophically, elemental sulfur or reduced inorganic sulfur compounds are their energy sources. Therefore, sulfur metabolism is the most important physiological characteristic of the Sulfolobales. The functions of some enzymes and proteins involved in sulfur reduction, sulfur oxidation, sulfide oxidation, thiosulfate oxidation, sulfite oxidation, tetrathionate hydrolysis, and sulfur trafficking have been determined. In this review, we describe current knowledge about the physiology, taxonomy, and sulfur metabolism of the Sulfolobales, and note future challenges in this field.

14.
Front Cell Dev Biol ; 9: 756340, 2021.
Artigo em Inglês | MEDLINE | ID: mdl-34805165

RESUMO

Lung cancer remains the leading cause of cancer death globally, with lung adenocarcinoma (LUAD) being its most prevalent subtype. Due to the heterogeneity of LUAD, patients given the same treatment regimen may have different responses and clinical outcomes. Therefore, identifying new subtypes of LUAD is important for predicting prognosis and providing personalized treatment for patients. Pyroptosis-related genes play an essential role in anticancer, but there is limited research investigating pyroptosis in LUAD. In this study, 33 pyroptosis gene expression profiles and clinical information were collected from The Cancer Genome Atlas (TCGA) and Gene Expression Omnibus (GEO) databases. By bioinformatics and machine learning analyses, we identified novel subtypes of LUAD based on 10 pyroptosis-related genes and further validated them in the GEO dataset, with machine learning models performing up to an AUC of 1 for classifying in GEO. A web-based tool was established for clinicians to use our clustering model (http://www.aimedicallab.com/tool/aiml-subphe-luad.html). LUAD patients were clustered into 3 subtypes (A, B, and C), and survival analysis showed that B had the best survival outcome and C had the worst survival outcome. The relationships between pyroptosis gene expression and clinical characteristics were further analyzed in the three molecular subtypes. Immune profiling revealed significant differences in immune cell infiltration among the three molecular subtypes. GO enrichment and KEGG pathway analyses were performed based on the differential genes of the three subtypes, indicating that differentially expressed genes (DEGs) were involved in multiple cellular and biological functions, including RNA catabolic process, mRNA catabolic process, and pathways of neurodegeneration-multiple diseases. Finally, we developed an 8-gene prognostic model that accurately predicted 1-, 3-, and 5-year overall survival. In conclusion, pyroptosis-related genes may play a critical role in LUAD, and provide new insights into the underlying mechanisms of LUAD.

15.
Adv Mater ; : e2105829, 2021 Oct 02.
Artigo em Inglês | MEDLINE | ID: mdl-34599781

RESUMO

Lightweight polymeric materials are highly attractive platforms for many potential industrial applications in aerospace, soft robots, and biological engineering fields. For these real-world applications, it is vital for them to exhibit a desirable combination of great toughness, large ductility, and high strength together with desired healability and biocompatibility. However, existing material design strategies usually fail to achieve such a performance portfolio owing to their different and even mutually exclusive governing mechanisms. To overcome these hurdles, herein, for the first time a dynamic hydrogen-bonded nanoconfinement concept is proposed, and the design of highly stretchable and supratough biocompatible poly(vinyl alcohol) (PVA) with well-dispersed dynamic nanoconfinement phases induced by hydrogen-bond (H-bond) crosslinking is demonstrated. Because of H-bond crosslinking and dynamic nanoconfinement, the as-prepared PVA nanocomposite film exhibits a world-record toughness of 425 ± 31 MJ m-3 in combination with a tensile strength of 98 MPa and a large break strain of 550%, representing the best of its kind and even outperforming most natural and artificial materials. In addition, the final polymer exhibits a good self-healing ability and biocompatibility. This work affords new opportunities for creating mechanically robust, healable, and biocompatible polymeric materials, which hold great promise for applications, such as soft robots and artificial ligaments.

16.
Chin J Nat Med ; 19(10): 750-757, 2021 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-34688465

RESUMO

Tripterygium wilfordii multiglycoside (GTW) is a commonly used compound for the treatment of rheumatoid arthritis (RA) and immune diseases in clinical practice. However, it can induce liver injury and the mechanism of hepatotoxicity is still not clear. This study was designed to investigate GTW-induced hepatotoxicity in zebrafish larvae and explore the mechanism involved. The 72 hpf (hours post fertilization) zebrafish larvae were administered with different concentrations of GTW for three days and their mortality, malformation rate, morphological changes in the liver, transaminase levels, and histopathological changes in the liver of zebrafish larvae were detected. The reverse transcription-polymerase chain reaction (RT-PCR) was used to examine the levels of microRNA-122 (miR-122) and genes related to inflammation, apoptosis, cell proliferation and liver function. The results showed that GTW increased the mortality of zebrafish larvae, while significant malformations and liver damage occurred. The main manifestations were elevated levels of alanine aminotransferase (ALT) and aspartate aminotransferase (AST), significant liver atrophy, vacuoles in liver tissue, sparse cytoplasm, and unclear hepatocyte contours. RT-PCR results showed that the expression of miR-122 significantly decreased by GTW; the mRNA levels of inflammation-related genes il1ß, il6, tnfα, il10, cox2 and ptges significantly increased; the mRNA level of tgfß significantly decreased; the mRNA levels of apoptosis-related genes, caspase-8 and caspase-9, significantly increased; the mRNA level of bcl2 significantly decreased; the mRNA levels of cell proliferation-related genes, top2α and uhrf1, significantly reduced; the mRNA levels of liver function-related genes, alr and cyp3c1, significantly increased; and the mRNA level of cyp3a65 significantly decreased. In zebrafish, GTW can cause increased inflammation, enhanced apoptosis, decreased cell proliferation, and abnormal expression of liver function-related genes, leading to abnormal liver structure and function and resulting in hepatotoxicity.


Assuntos
Doença Hepática Induzida por Substâncias e Drogas , Tripterygium , Animais , Apoptose , Doença Hepática Induzida por Substâncias e Drogas/genética , Inflamação/induzido quimicamente , Inflamação/genética , Transativadores , Peixe-Zebra/genética , Proteínas de Peixe-Zebra
17.
Int J Med Sci ; 18(15): 3437-3451, 2021.
Artigo em Inglês | MEDLINE | ID: mdl-34522170

RESUMO

Aurora-A has attracted a great deal of interest as a potential therapeutic target for patients with CRC. However, the outcomes of inhibitors targeting Aurora-A are not as favorable as expected, and the basis behind the ineffectiveness remains unknown. Here, we found that signal transducer and activator of transcription 1 (STAT1) was highly expressed in colorectal cancer (CRC) xenograft mouse models that were resistant to alisertib, an Aurora-A inhibitor. Unexpectedly, we found that alisertib disrupted Aurora-A binding with ubiquitin-like with plant homeodomain and ring finger domain 1 (UHRF1), leading to UHRF1 mediated ubiquitination and degradation of DNA methyltransferase 1 (DNMT1), which in turn resulted in demethylation of CpG islands of STAT1 promoter and STAT1 overexpression. Simultaneous silencing Aurora-A and UHRF1 prevented STAT1 overexpression and effectively inhibited CRC growth. Hence, concomitant targeting Aurora-A and UHRF1 can be a promising therapeutic strategy for CRC.

18.
Zhongguo Xiu Fu Chong Jian Wai Ke Za Zhi ; 35(9): 1086-1092, 2021 Sep 15.
Artigo em Chinês | MEDLINE | ID: mdl-34523271

RESUMO

Objective: To formulate the classification criteria of femoral intertrochanteric fractures based on irreducibility or not in order to predict the difficulty of fracture recovery. Methods: A clinical data of 244 patients with closed femoral intertrochanteric fractures admitted between January 2017 and March 2020 was retrospectively analyzed. There were 116 males and 128 females with an average age of 77.9 years (range, 45-100 years). The cause of injury included falling in 190 cases, traffic accident in 36 cases, smashing in 13 cases, and falling from height in 5 cases. The time from injury to operation was 1-14 days (mean, 3.6 days). According toAO/Orthopaedic Trauma Association (AO/OTA) classification, the fractures were classified as type 31-A1 in 38 cases, type 31-A2 in 160 cases, and type 31-A3 in 46 cases. According to whether the recovery difficulty occurred after intraoperative closed traction reset, the patients were divided into reducible-group and irreducible-group; combined with the literature and preoperative imaging data of two groups, the classification criteria of femoral intertrochanteric fractures was formulated based on the irreducibility or not. The 244 fractures were classified by the doctors who did not attend the operation according to the classification criteria, predicted the difficulty of fracture reduction, and compared with the actual intraoperative reduction situation. Results: The 244 patients were divided into reducible-group ( n=164, 67.21%) and irreducible-group ( n=80, 32.79%) according to the intraoperative difficulty of reduction. Comparing the imaging data and characteristics of the two groups, and formulating the classification criteria of femoral intertrochanteric fractures based on irreducibility or not, the fractures were mainly divided into two categories of irreducibility and reducibility. The fractures of irreducibility category was divided into typesⅠ-Ⅴ, among which type Ⅲ was divided into subtypes 1-4; the fractures of reducibility category was divided into typesⅠand Ⅱ. Compared with the actual intraoperative evaluation results, the total accuracy rate of the doctors who did not attend the operation was 81.15% (198/244) based on the classification criteria of femoral intertrochanteric fractures. The accuracy rate of irreducibility category was 65.74% (71/108), and the reducibility category was 93.38% (127/136). All patients were followed up 13-25 months, with an average of 17.6 months. All fractures healed except 2 cases died of infection. Conclusion: The classification criteria of femoral intertrochanteric fractures based on irreducibility or not can accurately predict the reducible cases preoperatively, and most of the irreducible cases can be correctly predicted in a wider way. But the classification criteria still need to be further improved and supplemented.


Assuntos
Fraturas do Fêmur , Fixação Intramedular de Fraturas , Fraturas do Quadril , Idoso , Pinos Ortopédicos , Feminino , Fraturas do Fêmur/cirurgia , Fraturas do Quadril/cirurgia , Humanos , Masculino , Estudos Retrospectivos , Resultado do Tratamento
19.
Ann Transl Med ; 9(15): 1251, 2021 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-34532388

RESUMO

Background: Patients with difficult weaning who undergo mechanical ventilation are more likely to be at risk of reintubation and the sequential use of oxygen therapy after extubation is a concern for clinicians. Therefore, the aim of the present study was to compare the effects of transnasal high-flow nasal cannula (HFNC) oxygen therapy and non-invasive positive-pressure ventilation (NIV) on respiratory mechanics in patients with difficult weaning. Methods: The present study was a single-center, retrospective, observational study. Twenty-nine patients with difficult weaning off invasive mechanical ventilation from the Department of Critical Care Medicine, The First Affiliated Hospital of Guangzhou Medical University, from December 2018 to April 2021, were included. Within 48 h after extubation, alternate respiratory support with HFNC and NIV was provided. Relevant indicators were recorded after each support mode had been maintained for at least 60 min. These included esophageal pressure (Pes), gastric pressure (Pga), transdiaphragmatic pressure (Pdi), pressure-time product of Pes (PTPes), pressure-time product of Pga (PTPga), pressure-time product of Pdi (PTPdi), ratio of the PTPdi to the PTPes (PTPdi/PTPes), and ratio of the Pes to the Pdi (Pes/Pdi), diaphragmatic electromyogram (EMGdi), percentage of esophageal pressure coefficient of variation (CVes%),diaphragmatic electromyogram coefficient of variation (CVEMG),inspiratory time (Ti), expiratory time (Te) and respiratory cycle time (Ttot). Results: Of the 29 patients included, 22 were males and 7 were females [age: 63.97±15.34 years, Acute Physiological and Chronic Health Estimation II (APACHE II) score: 18.00±5.63]. The CVes% and the Pes/Pdi were significantly higher in patients with NIV than HFNC using 40 L/min, CVes%: 9 (-6, 20) vs. -7 (-23, 6) and Pes/Pdi: 0.17 (-0.1, 0.53), vs. -0.12 (-0.43, 0.08) (P<0.05). The remaining indicators were not statistically different. Conclusions: The sequential NIV and HFNC can be tolerated in patients with such difficult weaning off mechanical ventilation after extubation, and more patients tend to choose HFNC subjectively. Compared with HFNC, NIV reduces the work of adjunctive respiratory muscle, but the patient's Pes dispersion is high when NIV is used, and it is necessary to pay attention to patient-ventilator coordination in clinical practice. We recommend alternating HFNC and NIV during the sequential respiratory therapy after extubation.

20.
Biomed Res Int ; 2021: 7561645, 2021.
Artigo em Inglês | MEDLINE | ID: mdl-34552988

RESUMO

Background: Nonalcoholic steatohepatitis (NASH) can progress to cirrhosis and hepatic carcinoma and is closely associated with changes in the neurological environment. The discovery of new biomarkers would aid in the treatment of NASH. Methods: Data GSE89632 were downloaded from the Gene Expression Omnibus (GEO) database, and R package "limma" was used to identify differentially expressed genes (DEGs) for NASH vs. normal tissues. The STRING database was used to construct a protein-protein interaction (PPI) network, and the Cytoscape software program (Version 3.80) was used to visualize the PPI network and identify key genes. The immune infiltration of NASH was determined using the R package "CIBERSORT". Results: We screened 41 DEGs. GO and KEGG enrichment analyses of the DEGs revealed the enrichment of pathways related to NAFLD steatosis and inflammation. A PPI network analysis was also performed on the DEGs, and seven genes (MYC, CXCL8, FOS, SOCS1, SOCS3, IL6, and PTGS2) were identified as hub genes. An immune infiltration assessment revealed that macrophages M2, memory resting CD4+ T cells, and Î³Δ T cells play important roles in the immune microenvironment of NASH, which may be mediated by the seven identified hub genes.

SELEÇÃO DE REFERÊNCIAS
DETALHE DA PESQUISA
...