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Cholangiocarcinoma (CCA) displays enhanced glycolysis, pivotal for fulfilling the heightened energy demands intrinsic to its malignant progression. Recent research has indicated that endogenous glycogen rather than exogenous glucose acts as the major carbon source for glycolysis, highlighting the need to better understand the regulation of glycogen homeostasis in CCA. Here, through comprehensive integrative analysis, we identified that glycogen phosphorylase brain form (PYGB), the main enzyme involved in glycogen homeostasis, was markedly upregulated in CCA tissues, serving as an independent prognostic indicator for human CCA patients. Moreover, elevated PYGB expression potentiated cholangiocarcinogenesis and augmented CCA cell proliferation in both organoid and xenograft models. Hypoxia stimulated PYGB activity in a phosphoglycerate kinase 1 (PGK1)-dependent manner, leading to glycogenolysis and the subsequent release of glucose-6-phosphate (G6P) and thereby facilitating aerobic glycolysis. Notably, a virtual screening pinpointed the beta-blocker carvedilol as a potent pharmacological inhibitor of PYGB that could attenuate CCA progression. Collectively, these findings position PYGB as a promising prognostic biomarker and therapeutic target for CCA.
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Recent research has uncovered a surprisingly high occurrence of aberrant expression and mutations in the genes that encode subunits of the SWI/SNF chromatin-remodeling complexes (SCRC). Nevertheless, the carcinogenic effects of aberrant expression and mutations in SWI/SNF genes have only been acknowledged in recent times, resulting in a comparatively limited understanding of these modifications. In this study, we comprehensively analyzed the expression difference, somatic mutation, potential biological pathways, stromal or immune cell infiltration, and drug sensitivity of SCRC-related genes (SCRGs) in pan-cancer. Furthermore, the evolutionary trend, prognostic signature, and immunotherapy response of SCRGs in kidney renal clear cell carcinoma (KIRC) were also evaluated. The expression of SCRGs was changed in 13 out of 14 tumor types, strongly linked to prognosis, and mutated in 30.9% of tumor patients. SCRGs were also closely associated with immune-related pathways and tumor metastasis pathways. The expression of SCRGs was positively associated with the immune score or stromal score but negatively correlated with Tumor purity. Three potential drugs (FK866, Ispinesib mesylate, and WZ3105) were identified to target the SCRGs. In KIRC, scRNA-seq analysis showed that the enrichment of SCRC and the communication frequency with immune cells were significantly declined during tumor cell progression. A prognostic signature was constructed in KIRC and was effective in predicting the prognosis for KIRC. Aberrant expression of eleven prognostic genes identified from the KIRC prognostic signature and the cytotoxicity of FK866 and Ispinesib mesylate to KIRC were verified by qRT-PCR and CCK-8 assay, respectively. Our study identified SCRGs as potential biomarker and therapeutic targets, providing new insights into SCRC for tumor-targeted therapy.
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Biomarcadores Tumorais , Montagem e Desmontagem da Cromatina , Regulação Neoplásica da Expressão Gênica , Neoplasias , Humanos , Biomarcadores Tumorais/genética , Regulação Neoplásica da Expressão Gênica/efeitos dos fármacos , Neoplasias/genética , Neoplasias/tratamento farmacológico , Neoplasias/patologia , Neoplasias/metabolismo , Prognóstico , Mutação , Proteínas Cromossômicas não Histona/genética , Proteínas Cromossômicas não Histona/metabolismo , Fatores de Transcrição/genética , Fatores de Transcrição/metabolismo , Terapia de Alvo Molecular , Perfilação da Expressão GênicaRESUMO
This study aimed to evaluate the value of low-dose dual-input computed tomography perfusion (CTP) imaging in the differential diagnosis of benign and malignant pulmonary ground-glass opacity nodules (GGO). A retrospective study was conducted in patients with GGO who underwent CTP in our hospital from January 2021 to October 2023. All nodules were confirmed via pathological analysis or disappeared during follow-up. Postprocessing analysis was conducted using the dual-input perfusion mode (pulmonary artery and bronchial artery) of the body perfusion software to measure the perfusion parameters of the pulmonary GGOs. A total of 101 patients with pulmonary GGOs were enrolled in this study, including 43 benign and 58 malignant nodules. The dose length product of the CTP (348 mGy.cm) was < 75% of the diagnostic reference level of the unenhanced chest CT (470 mGy.cm). The effective radiation dose was 4.872 mSV. The blood flow (BF), blood volume (BV), mean transit time (MTT), and flow extraction product (FEP) of malignant nodules were higher than those of the benign nodules (p < 0.05). The FEP had the highest accuracy for the diagnosis of malignant nodules (area under the curve [AUC] = 0.821, 95% confidence interval [CI]: 0.735-0.908) followed by BV (AUV = 0.713, 95% CI 0.608-0.819), BF (AUC = 0.688, 95% CI 0.587-0.797), and MTT (AUC = 0.616, 95% CI 0.506-0.726). When the FEP was ≥ 19.12 mL/100 mL/min, the sensitivity was 91.5% and the specificity was 62.8%. To distinguish between benign nodules and malignant nodules, the AUC of the combination of BV and FEP was 0.816 (95% CI 0.728-0.903), whereas the AUC of the combination of BF, BV, MTT, and FEP was 0.814 (95% CI 0.729-0.900). Low-dose dual-input perfusion CT was extremely effective in distinguishing between benign from malignant pulmonary GGOs, with FEP exhibiting the highest diagnostic capability.
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Neoplasias Pulmonares , Tomografia Computadorizada por Raios X , Humanos , Masculino , Feminino , Pessoa de Meia-Idade , Diagnóstico Diferencial , Neoplasias Pulmonares/diagnóstico por imagem , Neoplasias Pulmonares/patologia , Neoplasias Pulmonares/diagnóstico , Estudos Retrospectivos , Idoso , Tomografia Computadorizada por Raios X/métodos , Adulto , Nódulo Pulmonar Solitário/diagnóstico por imagem , Nódulo Pulmonar Solitário/patologia , Imagem de Perfusão/métodos , Nódulos Pulmonares Múltiplos/diagnóstico por imagem , Nódulos Pulmonares Múltiplos/patologia , Pulmão/diagnóstico por imagem , Pulmão/irrigação sanguínea , Pulmão/patologia , Curva ROC , Doses de RadiaçãoRESUMO
The optimization of the CRISPR-Cas9 system for enhancing editing efficiency holds significant value in scientific research. In this study, we optimized single guide RNA and Cas9 promoters of the CRISPR-Cas9 vector and established an efficient protoplast isolation and transient transformation system in Eustoma grandiflorum, and we successfully applied the modified CRISPR-Cas9 system to detect editing efficiency of the EgPDS gene. The activity of the EgU6-2 promoter in E. grandiflorum protoplasts was approximately three times higher than that of the GmU6 promoter. This promoter, along with the EgUBQ10 promoter, was applied in the CRISPR-Cas9 cassette, the modified CRISPR-Cas9 vectors that pEgU6-2::sgRNA-2/pEgUBQ10::Cas9-2 editing efficiency was 37.7%, which was 30.3% higher than that of the control, and the types of mutation are base substitutions, small fragment deletions and insertions. Finally we obtained an efficient gene editing vector for E. grandiflorum. This project provides an important technical platform for the study of gene function in E. grandiflorum.
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This study investigated 120 Chinese wines from seven regions and had two objectives: to clarify the Sr isotope ratios and elemental characteristics of each region and to develop a strategy to distinguish the geographic origin of wine without authentic samples to predict its origin. The analyzed 87Sr/86Sr values ranged from 0.708256 to 0.715148, which correlated with the geological characteristics of the regions where they were grown. The Hexi Corridor exhibited the highest ratios of Sr isotopes, while Xinjiang had the lowest. The 87Sr/86Sr values were applied to establish a prediction map which was evaluated through cross-validation. The prediction error was found to be less than 0.00074. The Sr isotope ratio could remain stable for an extended period in a specific location. This map shows the feasibility of identifying wine origin and could be applied to other food products. Adding Sr isotope ratios could improve the accuracy in tracing wine origin.
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Vinho , Vinho/análise , Isótopos , ChinaRESUMO
Inflammatory bowel disease (IBD) remains a global health concern with a complex and incompletely understood pathogenesis. In the course of IBD development, damage to intestinal epithelial cells and a reduction in the expression of tight junction (TJ) proteins compromise the integrity of the intestinal barrier, exacerbating inflammation. Notably, the renin-angiotensin system and angiotensin II receptor type 1 (AT1R) play a crucial role in regulating the pathological progression including vascular permeability, and immune microenvironment. Thus, Telmisartan (Tel), an AT1R inhibitor, loading thermosensitive hydrogel was constructed to investigate the potential of alleviating inflammatory bowel disease through rectal administration. The constructed hydrogel exhibits an advantageous property of rapid transformation from a solution to a gel state at 37°C, facilitating prolonged drug retention within the gut while mitigating irritation associated with rectal administration. Results indicate that Tel also exhibits a beneficial effect in ameliorating colon shortening, colon wall thickening, cup cell lacking, crypt disappearance, and inflammatory cell infiltration into the mucosa in colitis mice. Moreover, it significantly upregulates the expression of TJ proteins in colonic tissues thereby repairing the intestinal barrier damage and alleviating the ulcerative colitis (UC) disease process. In conclusion, Tel-loaded hydrogel demonstrates substantial promise as a potential treatment modality for IBD.
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Colite , Doenças Inflamatórias Intestinais , Camundongos , Animais , Telmisartan/farmacologia , Telmisartan/metabolismo , Hidrogéis/farmacologia , Mucosa Intestinal/metabolismo , Junções Íntimas/metabolismo , Junções Íntimas/patologia , Doenças Inflamatórias Intestinais/tratamento farmacológico , Doenças Inflamatórias Intestinais/patologia , Colite/patologia , Colo/metabolismo , Inflamação/metabolismo , Sulfato de Dextrana/metabolismo , Modelos Animais de Doenças , Camundongos Endogâmicos C57BLRESUMO
Mesenchymal stem cells (MSCs) have been widely used in the treatment of ischemic stroke. However, factors such as high glucose, oxidative stress, and aging can lead to the reduced function of donor MSCs. The p38 mitogen-activated protein kinase (MAPK) signaling pathway is associated with various functions, such as cell proliferation, apoptosis, senescence, differentiation, and paracrine secretion. This study examined the hypothesis that the downregulation of p38 MAPK expression in MSCs improves the prognosis of mice with ischemic stroke. Lentiviral vector-mediated short hairpin RNA (shRNA) was constructed to downregulate the expression level of p38 MAPK in mouse bone marrow-derived MSCs. The growth cycle, apoptosis, and senescence of MSCs after infection were examined. A mouse model of ischemic stroke was constructed. After MSC transplantation, the recovery of neurological function in the mice was evaluated. Lentivirus-mediated shRNA significantly downregulated the mRNA and protein expression levels of p38 MAPK. The senescence of MSCs in the p38 MAPK downregulation group was significantly reduced, but the growth cycle and apoptosis did not significantly change. Compared with the control group, the infarct volume was reduced, and the neurological function and the axonal remodeling were improved in mice with ischemic stroke after transplantation of MSCs with downregulated p38 MAPK. Immunohistochemistry confirmed that in the p38 MAPK downregulation group, apoptotic cells were reduced, and the number of neuronal precursors and the formation of white matter myelin were increased. In conclusion, downregulation of p38 MAPK expression in MSCs improves the therapeutic effect in mice with ischemic stroke, an effect that may be related to a reduction in MSC senescence. This method is expected to improve the efficacy of MSCs in patients, especially in patients with underlying diseases such as diabetes, thus providing a basis for clinical individualized treatment for cerebral infarction.
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AVC Isquêmico , Transplante de Células-Tronco Mesenquimais , Células-Tronco Mesenquimais , Acidente Vascular Cerebral , Humanos , Camundongos , Animais , Proteínas Quinases p38 Ativadas por Mitógeno/metabolismo , AVC Isquêmico/metabolismo , Diferenciação Celular/genética , RNA Interferente Pequeno , Acidente Vascular Cerebral/terapiaRESUMO
Pancreatic cancer is one of the most aggressive cancers with a median survival time of less than 5 months, and conventional chemotherapeutics are the main treatment strategy. Poly(ADP-ribose) polymerase (PARP) inhibitors have been recently approved for BRCA1/2-mutant pancreatic cancer, opening a new era for targeted therapy for this disease. However, most pancreatic cancer patients carry wild-type BRCA1/2 with resistance to PARP inhibitors. Here, we reported that mammalian target of rapamycin complex 2 (mTORC2) kinase is overexpressed in pancreatic cancer tissues and promotes pancreatic cancer cell growth and invasion. Moreover, we found that knockdown of the mTORC2 obligate subunit Rictor sensitized pancreatic cancer cells to the PARP inhibitor olaparib. Mechanistically, we showed that mTORC2 positively regulates homologous recombination (HR) repair by modulating BRCA1 recruitment to DNA double-strand breaks (DSBs). In addition, we confirmed that combination treatment with the mTORC2 inhibitor PP242 and the PARP inhibitor olaparib synergistically inhibited pancreatic cancer growth in vivo. Thus, this study provides a novel target and strategy for optimizing PARP inhibitor efficiency in pancreatic cancers.
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Antineoplásicos , Neoplasias Pancreáticas , Humanos , Inibidores de Poli(ADP-Ribose) Polimerases/farmacologia , Inibidores de Poli(ADP-Ribose) Polimerases/uso terapêutico , Proteína BRCA1/genética , Linhagem Celular Tumoral , Proteína BRCA2 , Poli(ADP-Ribose) Polimerases , Neoplasias Pancreáticas/tratamento farmacológico , Neoplasias Pancreáticas/genéticaRESUMO
Chemotherapy-induced adaptive resistance is a significant factor that contributes to low therapeutic efficacy in tumor cells. The unfolded protein response (UPR) is a key mechanism in the development of drug resistance and serves as a critical reactive system for endoplasmic reticulum stress. Cu(II) can reduce the abundance of 60S ribosomal subunits and inhibit rRNA processing, leading to a decrease in the translation efficiency of the GRP78/BiP mRNA, which serves as a primary sensor for UPR activation. In this study, CuET-Lipid@Cela, composed of CuET and tripterine (Cela), demonstrates a significant synergistic antitumor effect on cholangiocarcinoma (CCA) cells. RNA-Seq is used to investigate the underlying mechanism, which suggests that the transmembrane protein 2 (TMX2) gene may be crucial in Cu(II) regulation of UPR by inhibiting the activation of GRP78/BiP and PERK/eIF2α. The synergistic antitumor efficacy of CuET-Lipid@Cela via inhibition of TMX2 is also confirmed in a myrAKT/YapS127A plasmid-induced primary CCA mouse model, providing new insights into the reversal of acquired chemotherapy-induced resistance in CCA.
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Antineoplásicos , Neoplasias dos Ductos Biliares , Colangiocarcinoma , Animais , Camundongos , Cobre , Chaperona BiP do Retículo Endoplasmático , Colangiocarcinoma/tratamento farmacológico , Colangiocarcinoma/patologia , Ductos Biliares Intra-Hepáticos/patologia , Neoplasias dos Ductos Biliares/tratamento farmacológico , Neoplasias dos Ductos Biliares/patologia , Antineoplásicos/farmacologia , LipídeosRESUMO
Lignin is one of the most important secondary metabolites and essential to the formation of cell walls. Changes in lignin biosynthesis have been reported to be associated with environmental variations and can influence plant fitness and their adaptation to abiotic stresses. However, the molecular mechanisms underlying this association remain unclear. In this study, we evaluated the relations between the lignin biosynthesis and environmental factors and explored the role of epigenetic modification (DNA methylation) in contributing to these relations if any in natural birch. Significantly negative correlations were observed between the lignin content and temperature ranges. Analyzing the transcriptomes of birches in two habitats with different temperature ranges showed that the expressions of genes and transcription factors (TFs) involving lignin biosynthesis were significantly reduced at higher temperature ranges. Whole-genome bisulfite sequencing revealed that promoter DNA methylation of two NAC-domain TFs, BpNST1/2 and BpSND1, may be involved in the inhibition of these gene expressions, and thereby reduced the content of lignin. Based on these results we proposed a DNA methylation-mediated lignin biosynthesis model which responds to environmental factors. Overall, this study suggests the possibility of environmental signals to induce epigenetic variations that result in changes in lignin content, which can aid to develop resilient plants to combat ongoing climate changes or to manipulate secondary metabolite biosynthesis for agricultural, medicinal, or industrial values.
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PURPOSE: The purpose of this meta-analysis was to compare the efficacy and imaging parameters of kinematic alignment (KA) and mechanical alignment (MA) in total knee arthroplasty (TKA) and to evaluate whether patients undergoing KA-TKA benefited more than those undergoing MA-TKA. METHODS: Studies comparing the efficacy of KA-TKA and MA-TKA were included after searching and screening in the database, including PubMed, Embase, Web of Science and Cochrane Database Library. A total of 1420 patients were enrolled in the study, with 736 MA-TKA and 738 KA-TKA. The primary outcomes were postoperative knee function scores including KSS series, WOMAC, KOOS and OKS. Secondary outcomes included the operative time, the length of hospital stay, knee extension/flexion angle, and some imaging parameters. The risk of bias for included studies was assessed using the Cochrane Collaborative risk-of-bias assessment tool or the Newcastle-Ottawa Scale(NOS). RESULTS: Sixteen studies were included in this meta-analysis (11 randomized controlled studies and 5 cohort studies). Primary outcomes: Knee Society score (KSS, MD = 8.36, 95% Cl: 0.83-15.90) and combined KSS (MD = 15.24, 95% CI: 5.41-25.07) were higher in KA-TKA than in MA-TKA, and other functional scores were not statistically significant in KA-TKA and MA-TKA, including knee injury and osteoarthritis outcome score (KOOS), Oxford knee score (OKS), Knee Function score (KFS) and Western Ontario and McMaster Universities Osteoarthritis Index (WOMAC). Secondary outcomes: KA-TKA resulted in smaller medial proximal tibial angle (MPTA) and lateral distal femoral angle (LDFA) compared to MA-TKA. For other outcome measures, KA-TKA showed similar results compared to MA-TKA, including hip-knee-ankle (HKA) angle, extension/flexion angle, tibial component slope angle, joint line orientation angle (JLOA), the operation time, the length of hospital stay and ligament release rate. CONCLUSIONS: In our analysis results, patients undergoing KA-TKA benefit as much as patients undergoing MA-TKA. KA may be a viable reference in total knee replacement.
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Artroplastia do Joelho , Prótese do Joelho , Osteoartrite do Joelho , Artroplastia do Joelho/métodos , Fenômenos Biomecânicos , Humanos , Articulação do Joelho/diagnóstico por imagem , Articulação do Joelho/cirurgia , Osteoartrite do Joelho/diagnóstico por imagem , Osteoartrite do Joelho/cirurgiaRESUMO
CRISPR/dCas9 is an important DNA modification tool in which a disarmed Cas9 protein with no nuclease activity is fused with a specific DNA modifying enzyme. A previous study reported that overexpression of the TET1 catalytic domain (TET1cd) reduces genome-wide methylation in Arabidopsis. A spontaneous naturally occurring methylation region (NMR19-4) was identified in the promoter region of the PPH (Pheophytin Pheophorbide Hydrolase) gene, which encodes an enzyme that can degrade chlorophyll and accelerate leaf senescence. The methylation status of NMR19-4 is associated with PPH expression and leaf senescence in Arabidopsis natural accessions. In this study, we show that the CRISPR/dCas9-TET1cd system can be used to target the methylation of hypermethylated NMR19-4 region to reduce the level of methylation, thereby increasing the expression of PPH and accelerating leaf senescence. Furthermore, hybridization between transgenic demethylated plants and hypermethylated ecotypes showed that the demethylation status of edited NMR19-4, along with the enhanced PPH expression and accelerated leaf senescence, showed Mendelian inheritance in F1 and F2 progeny, indicating that spontaneous epialleles are stably transmitted trans-generationally after demethylation editing. Our results provide a rational approach for future editing of spontaneously mutated epialleles and provide insights into the epigenetic mechanisms that control plant leaf senescence.
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Arabidopsis , Arabidopsis/genética , Proteína 9 Associada à CRISPR/genética , Sistemas CRISPR-Cas/genética , Domínio Catalítico , Desmetilação do DNA , Metilação de DNA/genética , Epigênese Genética , Edição de Genes/métodos , FeofitinasRESUMO
Based on the knowledge of the previous film, the CT scan was used to diagnose the disease of women and men after the diagnosis of atherosclerosis by scanning the CT microscope. This article first examines the existing medical procedures in China, highlighting the advantages and disadvantages of various systems in terms of usability and user experience. Combined with the actual needs of hospitals, this paper developed a set of preoperative intelligent measurement system (MIPS) based on pattern recognition for total skeletal joint replacement. It is beneficial for doctors to better observe the lesions of patients before surgery and carry out necessary operations in the PATIENT DR film. In the process, the model is used to identify the patient, and the patient is given a fake score based on the characteristics of the DR film. In nonsymptomatic patients, 13.5% had muscle contraction > 50%, 2.0% had muscle contraction 70%, and the mean pelvic area was 23.48%. The left ventricular muscle has a 45.0% contraction rate, the left ventricle has a 70% contraction, and the median contraction rate is 47.58%. The right muscle, which is inserted between the right artery and the inner lymphatic artery, is the most common type of compression of the right muscle, accounting for 59.26%. In terms of the mean muscle contraction rate on the right side, patients with DVT with right muscles were higher than patients with DVT with left ventricles (48.54% to 22.29%, P < 0.001). The mean incidence of left ventricular DVT patients was higher than that of right ventricular DVT patients (71.88% versus 45.83% P < 0.0011).
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Veia Femoral , Trombose Venosa , Feminino , Veia Femoral/patologia , Humanos , Masculino , Tomografia Computadorizada por Raios X , Trombose Venosa/diagnóstico por imagem , Trombose Venosa/etiologiaRESUMO
Flower color, which is determined by various chemical pigments, is a vital trait for ornamental plants, in which anthocyanin is a major component. However, the epigenetic regulation of anthocyanin biosynthesis remains poorly understood. During chrysanthemum cultivation, we found a heterochromatic chrysanthemum accession (YP) whose progeny generated by asexual reproduction contained both yellow-flowered (YP-Y) and pink-flowered (YP-P) plants. In this study, we aimed to elucidate the epigenetic mechanisms of different flower colors in the YP plant progeny. Metabolome and transcriptome analyses revealed that the difference in flower color between YP-Y and YP-P was caused by expression variation of the anthocyanin biosynthesis gene CmMYB6. Bisulfite sequencing revealed that methylation at the CmMYB6 promoter, especially in the CHH context, was higher in YP-Y than YP-P. After demethylation of the CmMYB6 promoter using the dCas9-TET1cd system, the flower color returned from yellow to pink. Furthermore, the methylation status of the CmMYB6 promoter was higher in YP-Y over three consecutive generations, indicating that this methylation status was heritable mitotically. Finally, investigation of other chrysanthemum cultivars showed that the methylation of CmMYB6 decreased gradually with the increase in anthocyanin content. These results lay an epigenetic foundation for the improvement of flower color in horticultural plants.
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Chrysanthemum , Antocianinas/metabolismo , Chrysanthemum/genética , Chrysanthemum/metabolismo , Cor , Epigênese Genética , Flores/metabolismo , Regulação da Expressão Gênica de Plantas , Pigmentação/genética , Proteínas de Plantas/genética , Proteínas de Plantas/metabolismoRESUMO
Numerous studies have evaluated the association between air pollution and gestational diabetes mellitus (GDM), but the findings were inconsistent. This meta-analysis aimed to provide higher grade evidence on the association of air pollution with GDM based on previous studies. PubMed, Web of science, China National Knowledge Infrastructure (CNKI), and Wanfang Data Knowledge Service Platform (Wanfang) were searched comprehensively up to September 2021. Totally, 20 eligible cohort studies were finally included, for which the pooled RR and 95% CIs were estimated. Stratified analyses by study regions and units of pollutant increase were conducted for further investigation. Sensitivity analyses were also performed to assess the robustness. The finding showed that PM2.5, PM10, NO2, and SO2 exposure increased the risk of GDM, while O3 exposure reduced GDM risk. Specifically, PM2.5 exposure in the first and second trimesters, NO2 and SO2 exposure in the first trimester significantly increased the risk of GDM, with the RR ranging from 1.015 to 1.032. In addition, the elevation of GDM risk induced by PM2.5, PM10, and O3 exposure was more pronounced in Asian subjects than in American subjects. The meta-analysis provides high-quality evidence on the effect of maternal air pollution exposure on GDM in each exposure period.
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Poluentes Atmosféricos , Poluição do Ar , Diabetes Gestacional , Poluentes Atmosféricos/análise , Poluição do Ar/análise , Estudos de Coortes , Diabetes Gestacional/induzido quimicamente , Diabetes Gestacional/epidemiologia , Feminino , Humanos , Exposição Materna , Dióxido de Nitrogênio/análise , Material Particulado/análise , GravidezRESUMO
PURPOSE: To evaluate the impact of discectomy on back muscles (e.g. multifidus muscle (MM)) morphology in patients with lumbar disc herniation (LDH) following discectomy surgery, address the association of back muscles morphology with pain score preoperatively and post-operatively, and investigate the relationships between the changes from pre- to post-operative back muscles measurements and pain score (primary outcome) and disability score (secondary outcome) change following discectomy if any. METHODS: We searched three online databases for randomized controlled trials (RCTs) and observational studies. In LDH patients, eligible for discectomy surgery, pre- and post-operative and the changes from pre- to post-operative of back and/or leg pain with Visual Analogue Scale (VAS) and multifidus muscle morphology, were considered as primary outcomes. Cochrane Risk-of-Bias 2 tool and Newcastle-Ottawa Scale (NOS) were used to assess the methodological quality of RCTs and observational studies, respectively. Standardize mean difference (SMD) with 95% confidence intervals (CI) was evaluated. A meta-regression analysis was conducted. GRADE approach was used to summarize the strength of evidence. RESULTS: One RCT and five observational studies were included in the analysis of 489 patients with LDH undergoing discectomy surgery. The mean overall follow-up was 64.9 weeks (6 to 148.7 weeks). There was a significant negative relationship between the change from pre- to post-operative cross-sectional area (CSA) in MM and change in VAS back pain [regression coefficient = -0.01, (95% CI = -0.02, -0.01), p = 0.044] after discectomy surgery. No significant relationship between preoperative CSA in MM and preoperative/post-operative clinical (any of the follow-up periods) scores could be established. CONCLUSION: The results of this study found very low-quality grade evidence for an association between higher reduction of CSA in MM and less reductions of back pain scores following discectomy surgery for patients with LDH. Due to the heterogeneity and methodological limitations, further studies will improve understanding and aid preoperative counselling.
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Deslocamento do Disco Intervertebral , Dor nas Costas/cirurgia , Discotomia/efeitos adversos , Discotomia/métodos , Humanos , Deslocamento do Disco Intervertebral/complicações , Deslocamento do Disco Intervertebral/cirurgia , Vértebras Lombares/diagnóstico por imagem , Vértebras Lombares/cirurgia , Músculos ParaespinaisRESUMO
OBJECTIVE: Most hepatocellular carcinoma (HCC) patients in China have some degree of liver cirrhosis. The effect of cirrhosis on the long-term prognosis of HCC patients after hepatectomy is still unclear. This study aimed to investigate the effect of liver cirrhosis on the prognosis of HCC patients after hepatectomy. METHODS: Data from patients who underwent hepatectomy and had pathologically confirmed HCC were retrospectively collected. The patients' clinical pathological data were recorded. Propensity score matching (PSM) was used to eliminate the influence of potential confounding factors. The Kaplan-Meier method was used to calculate the recurrence-free survival (RFS) and overall survival (OS) rates, and Cox regression analysis was used to screen for independent risk factors affecting OS and RFS. RESULTS: A total of 1381 HCC patients who were initially treated with hepatectomy were included, including 797 patients with liver cirrhosis. The RFS and OS rates in the group with cirrhosis were significantly lower than those in the group without cirrhosis (after PSM, RFS: P < 0.001; OS: P = 0.001). Subgroup analysis showed that among patients with Barcelona Clinic Liver Cancer (BCLC) stage 0-B disease, RFS and OS were significantly lower in those with cirrhosis than in those without cirrhosis (both P < 0.05); while in patients with stage C disease, there was no significant difference between those with and without cirrhosis. In the group with cirrhosis, alpha-fetoprotein (AFP) > 400, intraoperative blood loss, tumor diameter > 5 cm, satellite lesions, and large vessel invasion were independent risk factors for RFS, while albumin-bilirubin (ALBI) grade, neutrophil-to-lymphocyte ratio (NLR), tumor diameter > 5 cm, satellite lesions, microvascular invasion, and macrovascular invasion were independent risk factors for OS. CONCLUSION: HCC with liver cirrhosis has specific characteristics. Compared with patients without cirrhosis, patients with cirrhosis have worse long-term survival after surgery. In addition, the independent risk factors for RFS and OS are different between patients with cirrhosis and without cirrhosis; liver cirrhosis is an independent risk factor for the long-term prognosis of HCC patients, especially patients with BCLC stage 0-B disease after hepatectomy.
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Carcinoma Hepatocelular , Neoplasias Hepáticas , Carcinoma Hepatocelular/complicações , Carcinoma Hepatocelular/cirurgia , Humanos , Cirrose Hepática/complicações , Neoplasias Hepáticas/complicações , Neoplasias Hepáticas/cirurgia , Pontuação de Propensão , Estudos Retrospectivos , Análise de SobrevidaRESUMO
Maize (Zea mays L.) is sensitive to a minor decrease in temperature at early growth stages, resulting in deteriorated growth at later stages. Although there are significant variations in maize germplasm in response to cold stress, the metabolic responses as stress tolerance mechanisms are largely unknown. Therefore, this study aimed at providing insight into the metabolic responses under cold stress at the early growth stages of maize. Two inbred lines, tolerant (B144) and susceptible (Q319), were subjected to cold stress at the seedling stage, and their corresponding metabolic profiles were explored. The study identified differentially accumulated metabolites in both cultivars in response to induced cold stress with nine core conserved cold-responsive metabolites. Guanosine 3',5'-cyclic monophosphate was detected as a potential biomarker metabolite to differentiate cold tolerant and sensitive maize genotypes. Furthermore, Quercetin-3-O-(2â³'-p-coumaroyl)sophoroside-7-O-glucoside, Phloretin, Phloretin-2'-O-glucoside, Naringenin-7-O-Rutinoside, L-Lysine, L-phenylalanine, L-Glutamine, Sinapyl alcohol, and Feruloyltartaric acid were regulated explicitly in B144 and could be important cold-tolerance metabolites. These results increase our understanding of cold-mediated metabolic responses in maize that can be further utilized to enhance cold tolerance in this significant crop.
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To explore the biological activity of transmembrane prostateandrogen induced RNA (PMEPA1) in human pancreatic cancer (hPAC) cells and its drug sensitivity to gemcitabine (GEM) and cisplatin (DDP). Gene Expression Profiling Interactive Analysis (GEPIA) and Cancer Cell Line Encyclopedia (CCLE) were consulted to indicate the expression of PMEPA1 in hPAC tissues and cells. Quantitative real-time PCR (RT-qPCR) and western blot were performed to verify the indication. RT-qPCR and western blot also detected the expressions of PTEN/PI3K/AKT before and after transfection of PMEPA1 siRNA plasmids. Cell counting Kit-8 (CCK-8) and EdU staining were performed to examine cell proliferation before and after transfection of phosphatase and tensin homologue delet2ed on chromosome ten (PTEN) siRNA plasmids. Transwell and wound healing detected the invasion and migration of hPAC cells. The expressions of MMP-2 and MMP-9 were detected by western blot. After GEM or DDP treatment, cell viability was observed by commercial kits and cell apoptosis by flow cytometry. GEPIA and CCLE predicted increased expression of PMEPA1 in hPAC tissues and cells, which was confirmed by quantitative reverse transcription polymerase chain reaction (RT-qPCR) and western blot. PMEPA1 was also shown to be associated with disease-free survival. Transfection of PMEPA1 siRNA plasmids affected the expressions of PTEN/PI3K/AKT. PMEPA1 interference inhibited the proliferation, invasion and migration of hPAC cells. Furthermore, PMEPA1 interference also enhanced the sensitivity of hPAC cells to GEM and DDP via PTEN interference. PMEPA1 interference inhibits the proliferation, invasion and migration of pancreatic cancer cells and enhances the sensitivity to GEM and cisplatin by activating PTEN/PI3K/AKT signaling.
Assuntos
Neoplasias Pancreáticas , Fosfatidilinositol 3-Quinases , Apoptose , Linhagem Celular Tumoral , Movimento Celular , Proliferação de Células , Cisplatino/farmacologia , Desoxicitidina/análogos & derivados , Humanos , Proteínas de Membrana , PTEN Fosfo-Hidrolase/genética , Neoplasias Pancreáticas/tratamento farmacológico , Neoplasias Pancreáticas/genética , Neoplasias Pancreáticas/metabolismo , Fosfatidilinositol 3-Quinases/metabolismo , Proteínas Proto-Oncogênicas c-akt/metabolismo , GencitabinaRESUMO
Soybean is one of the most important legumes, providing high-quality protein for humans. The caffeic acid O-methyltransferase (COMT) gene has previously been demonstrated to be a critical gene that regulates lignin production in plant cell walls and plays an important function in plant growth and development. However, the COMT gene family has not been studied in soybeans. In this study, 55 COMT family genes in soybean were identified by phylogenetic analysis and divided into two groups, I and II. The analysis of conserved domains showed that all GmCOMTs genes contained Methyltransferase-2 domains. Further prediction of cis-acting elements showed that GmCOMTs genes were associated with growth, light, stress, and hormonal responses. Eventually, based on the genomic data of soybean under different stresses, the results showed that the expression of GmCOMTs genes was different under different stresses, such as salt and drought stress. This study has identified and characterized the COMT gene family in soybean, which provides an important theoretical basis for further research on the biological functions of COMT genes and promotes revealing the role of GmCOMTs genes under stress resistance.