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1.
J Toxicol Pathol ; 35(2): 193-203, 2022 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-35516842

RESUMO

Liver fibrosis results from liver inflammation and progresses to liver cirrhosis or liver cancer. It is known that nonalcoholic liver disease is mediated by the Toll-like receptor 4 (TLR4)/myeloid differentiation factor-2 (MD-2)-tumor necrosis factor-alpha (TNF-α) signaling pathway. This study aimed to investigate whether alcoholic liver disease is also mediated by this pathway. To this end, we first established rat models of liver fibrosis by administering alcohol. Next, the rats were injected with anti-TLR4 and anti-MD-2 antibodies. Real Time Quantitative PCR (RT-qPCR) and Western blotting were used to detect the activation of the TLR4/MD-2-TNF-α signaling pathway and hepatic stellate cells (HSCs). Moreover, the expression of molecules related to liver fibrosis was estimated. The morphology of rat liver tissue was observed through hematoxylin-eosin staining and Masson staining. For in vitro studies, Kupffer cells (KCs) isolated from the liver were transfected with si-TLR4 and si-MD-2 and co-cultured with HSCs to determine the activity of HSCs. It was found that alcohol treatment activated the TLR4/MD-2-TNF-α signaling pathway and upregulated the molecules associated with liver fibrosis. However, inhibition of TLR4 and MD-2 partially reversed this trend. Notably, in vitro studies indicated that knockdown of TLR4 and MD-2 in KCs partially inhibited LPS-induced activation of KCs and HSCs. Overall, this study showed that alcohol induces liver fibrosis via the LPS-TLR4/MD-2-TNF-α signaling pathway.

2.
Adv Sci (Weinh) ; : e2106071, 2022 May 07.
Artigo em Inglês | MEDLINE | ID: mdl-35524635

RESUMO

Dental caries is among the most prevalent dental diseases globally, which arises from the formation of microbial biofilm on teeth. Besides, tooth whitening represents one of the fastest-growing areas of cosmetic dentistry. It will thus be great if tooth biofilm eradication can be combined with tooth whitening. Herein, a highly efficient photodynamic dental therapy strategy is reported for tooth biofilm eradication and tooth discoloration by employing a photosensitizer (DTTPB) with aggregation-induced emission characteristics. DTTPB can efficiently inactivate S. mutans, and inhibit biofilm formation by suppressing the expression of genes associated with extracellular polymeric substance synthesis, bacterial adhesion, and superoxide reduction. Its inhibition performance can be further enhanced through combined treatment with chlorhexidine. Besides, DTTPB exhibits an excellent tooth-discoloration effect on both colored saliva-coated hydroxyapatite and clinical teeth, with short treatment time (less than 1 h), better tooth-whitening performance than 30% hydrogen peroxide, and almost no damage to the teeth. DTTPB also demonstrates excellent biocompatibility with neglectable hemolysis effect on mouse red blood cells and almost no killing effect on mammalian cells, which enables its potential applications for simultaneous tooth biofilm eradication and tooth whitening in clinical dentistry.

3.
Mol Psychiatry ; 2022 May 10.
Artigo em Inglês | MEDLINE | ID: mdl-35538193

RESUMO

Cohort studies report inconsistent associations between body mass index (BMI) and all-cause incident dementia. Furthermore, evidence on fat distribution and body composition measures are scarce and few studies estimated the association between early life adiposity and dementia risk. Here, we included 322,336 participants from UK biobank to investigate the longitudinal association between life course adiposity and risk of all-cause incident dementia and to explore the underlying mechanisms driven by metabolites, inflammatory cells and brain structures. Among the 322,336 individuals (mean (SD) age, 62.24 (5.41) years; 53.9% women) in the study, during a median 8.74 years of follow-up, 5083 all-cause incident dementia events occurred. The risk of dementia was 22% higher with plumper childhood body size (p < 0.001). A strong U-shaped association was observed between adult BMI and dementia. More fat and less fat-free mass distribution on arms were associated with a higher risk of dementia. Interestingly, similar U-shaped associations were found between BMI and four metabolites (i.e., 3-hydroxybutrate, acetone, citrate and polyunsaturated fatty acids), four inflammatory cells (i.e., neutrophil, lymphocyte, monocyte and leukocyte) and abnormalities in brain structure that were also related to dementia. The findings that adiposity is associated with metabolites, inflammatory cells and abnormalities in brain structure that were related to dementia risk might provide clues to underlying biological mechanisms. Interventions to prevent dementia should begin early in life and include not only BMI control but fat distribution and body composition.

4.
Mol Cancer ; 21(1): 110, 2022 May 07.
Artigo em Inglês | MEDLINE | ID: mdl-35525959

RESUMO

BACKGROUND: Previous studies have confirmed the oncogenic role of HMGB2 in various cancers, but the biological functions of HMGB2-derived circRNAs remain unknown. Thus, we intended to investigate the potential role of HMGB2-derived circRNAs in lung adenocarcinomas (LUAD) and squamous cell carcinomas (LUSC). METHODS: The expression profiles of HMGB2-derived circRNAs in LUAD and LUSC tissues and matched normal tissues were assessed using qRT-PCR. The role of circHMGB2 in the progression of the LUAD and LUSC was determined in vitro by Transwell, CCK-8, flow cytometry and immunohistochemistry assays, as well as in vivo in an immunocompetent mouse model and a humanized mouse model. In addition, in vivo circRNA precipitation assays, luciferase reporter assays and RNA pulldown assays were performed to explore the underlying mechanism by which circHMGB2 promotes anti-PD-1 resistance in the LUAD and LUSC. RESULTS: The expression of circHMGB2 (hsa_circ_0071452) was significantly upregulated in NSCLC tissues, and survival analysis identified circHMGB2 as an independent indicator of poor prognosis in the LUAD and LUSC patients. We found that circHMGB2 exerted a mild effect on the proliferation of the LUAD and LUSC cells, but circHMGB2 substantially reshaped the tumor microenvironment by contributing to the exhaustion of antitumor immunity in an immunocompetent mouse model and a humanized mouse model. Mechanistically, circHMGB2 relieves the inhibition of downstream CARM1 by sponging miR-181a-5p, thus inactivating the type 1 interferon response in the LUAD and LUSC. Moreover, we found that the upregulation of circHMGB2 expression decreased the efficacy of anti-PD-1 therapy, and we revealed that the combination of the CARM1 inhibitor EZM2302 and an anti-PD-1 antibody exerted promising synergistic effects in a preclinical model. CONCLUSION: circHMGB2 overexpression promotes the LUAD and LUSC progression mainly by reshaping the tumor microenvironment and regulating anti-PD-1 resistance in the LUAD and LUSC patients. This study provides a new strategy for the LUAD and LUSC treatment.


Assuntos
Adenocarcinoma de Pulmão , Carcinoma de Células Escamosas , Neoplasias Pulmonares , MicroRNAs , Adenocarcinoma de Pulmão/patologia , Animais , Carcinoma de Células Escamosas/tratamento farmacológico , Carcinoma de Células Escamosas/genética , Carcinoma de Células Escamosas/patologia , Proliferação de Células , Regulação Neoplásica da Expressão Gênica , Proteína HMGB2/genética , Proteína HMGB2/metabolismo , Humanos , Neoplasias Pulmonares/tratamento farmacológico , Neoplasias Pulmonares/genética , Neoplasias Pulmonares/metabolismo , Camundongos , MicroRNAs/genética , MicroRNAs/metabolismo , Proteína-Arginina N-Metiltransferases , RNA Circular/genética , Microambiente Tumoral
5.
J Oncol ; 2022: 3433406, 2022.
Artigo em Inglês | MEDLINE | ID: mdl-35528235

RESUMO

Background: Gastric cancer (GC) is a common malignancy that can be formed by methylation-induced deactivation of tumor silencer genes, which is one of the key mechanisms of tumorigenesis. SEPT9 methylation, a symptomatic marker for tumors, can downregulate gene expression. Long noncoding RNA small nucleolar host gene 3 (lncRNA SNHG3) is a new type of lncRNA related to cancer. Our study investigated the mechanism of SNHG3 regulation of SEPT9 methylation and its effects on the growth, metastasis, and spread of gastric cancer cells. Methods: Quantitative real-time PCR (qRT-PCR) was used to detect SNHG3 and miR-448 in gastric cancer, and a dual-luciferase experiment verified the effects of SNHG3, miR-448, and DNMT1. After abnormally expressing SNHG3, miR-448, and DNMT1 alone or together, methylation-specific PCR was performed to determine the methylation of SEPT9, Western blotting was performed to detect the expression of DNA methyltransferase 1 (DNMT1) and SEPT9, and Transwell, scratch, and CCK-8 assays were performed to reveal the invasion, migration, and cell growth of gastric cancer cells. Results: We found that SNHG3 was upregulated in gastric cancer and that SNHG3 knockdown or miR-448 overexpression inhibited SEP9 methylation and therefore increased its expression, thereby inhibiting the growth, metastasis, and spread of gastric cancer cells. Conclusion: Our study indicates that SNHG3 regulates SEPT9 methylation by targeting miR-448/DNMT1 and subsequently affecting the occurrence and development of gastric cancer.

6.
Am J Cancer Res ; 12(4): 1465-1483, 2022.
Artigo em Inglês | MEDLINE | ID: mdl-35530295

RESUMO

To evaluate the potential anticancer effects of 1175 FDA-approved drugs, cell viability screening was performed using 25 human cancer cell lines covering 14 human cancer types. Here, we focus on the action of paroxetine, which demonstrated greater toxicity toward human gastric adenocarcinoma cell-line AGS cells compared with the other FDA-approved drugs, exhibiting an IC50 value lower than 10 µM. Evaluation of the underlying novel mechanisms revealed that paroxetine can enhance DNA damage in gastric cancer cells and involves downregulation of Rad51, HR23B and ERCC1 expression and function, as well as nucleotide shortage. Enhancement of autophagy counteracted paroxetine-induced apoptosis but did not affect paroxetine-induced DNA damage. Paroxetine also enhanced ROS generation in AGS cells, but a ROS scavenger did not improve paroxetine-mediated DNA damage, apoptosis, or autophagy, suggesting ROS might play a minor role in paroxetine-induced cell toxicity. In contrast, paroxetine did not enhance DNA damage, apoptosis, or autophagy in another insensitive gastric adenocarcinoma cell-line MKN-45 cells. Interestingly, co-administration of paroxetine with conventional anticancer agents sensitized MKN-45 cells to these agents: co-treated cells showed increased apoptosis relative to MKN-45 cells treated with the anticancer agent alone. Unequivocally, these data suggest that for the first time that paroxetine triggers cytotoxicity and DNA damage in AGS cells at least partly by reducing the gene expression of Rad51, HR23B, and ERCC1. Our findings also suggest that paroxetine is a promising candidate anticancer agent and/or chemosensitizing agent for use in combination with other anticancer drugs in cancer therapy. The molecular mechanisms underlying the anticancer activity of co-treatment with paroxetine and chemotherapy appear to be complex and are worthy of further investigation.

7.
Drug Des Devel Ther ; 16: 1289-1300, 2022.
Artigo em Inglês | MEDLINE | ID: mdl-35531319

RESUMO

Purpose: This study aimed to explore the effects of intravenous analgesia using tramadol on postoperative depression, anxiety, and sleep in women undergoing abdominal endoscopic surgery. Patients and Methods: Two hundred female patients (100 in each group) who underwent abdominal endoscopic surgery were recruited to randomly receive intravenous analgesia with sufentanil combined with tramadol (tramadol group) or sufentanil (control group). The primary outcome was the incidence of postoperative depression, which was assessed at 1, 2, and 3 days after surgery using the 13-item Beck Depression Inventory. The secondary outcomes were the incidence of anxiety and sleep quality, which were assessed using the 20-item Self-Rating Anxiety Scale and Richards-Campbell Sleep Questionnaire. Results: The incidence of depression (Beck depression scale≥4) during the 3-day follow-up in the control group was 51%, which was significantly higher than that in the tramadol group of 28% (relative risk [RR]=0.55; 95% confidence interval [CI], 0.38-0.79; P=0.001). No difference was found in the incidence of anxiety state (Self-Rating Anxiety Scale≥40) between the tramadol and control groups (7%vs 5%; RR=1.40; 95% CI, 0.46-4.25; P=0.552). All of the Richards-Campbell sleep scales of patients in the tramadol group at 1 (77.4±15.2 vs 64.2±20.1, P<0.001), 2 (84.1±14.9 vs 71.8±18.8, P<0.001), and 3 days (87.0±12.2 vs 70.3±21.0, P<0.001) after surgery were higher than those in the control group. Conclusion: Intravenous analgesia using tramadol can effectively improve the postoperative depression and sleep status of women undergoing abdominal endoscopic surgery. Tramadol is recommended for use in postoperative analgesia when improving postoperative mood, and sleep is needed in clinical practice.


Assuntos
Analgesia , Tramadol , Analgesia Controlada pelo Paciente , Analgésicos Opioides/uso terapêutico , Depressão/tratamento farmacológico , Método Duplo-Cego , Feminino , Humanos , Dor Pós-Operatória/tratamento farmacológico , Dor Pós-Operatória/epidemiologia , Complicações Pós-Operatórias/tratamento farmacológico , Sufentanil/uso terapêutico , Tramadol/uso terapêutico
8.
J Plant Res ; 2022 May 09.
Artigo em Inglês | MEDLINE | ID: mdl-35534649

RESUMO

MicroRNAs (miRNAs) are known to play vital roles in coloration of leaves, flowers, and fruits in plants. However, their functions in spathe coloration are poorly known. Anthurium andraeanum is a popular ornamental plant with various spathe colors. In this study, small RNA and degradome libraries from three A. andraeanum cultivars with different-colored spathes were constructed and sequenced. Illumina sequencing resulted in 94 conserved miRNAs, and 34 novel miRNAs in total were then identified based on precursor sequences and hairpin structures. Differential expression analysis showed that 52, 51, and 49 miRNAs were differentially expressed in comparisons of orange- versus white-colored spathe, purple- versus white-colored spathe, and purple- versus orange-colored spathe, respectively. The expression patterns of miRNAs and their corresponding targets involved in spathe coloration were further analyzed, and displayed that miR156b and miR529 were highly abundant in the spathes with higher anthocyanin content. These two miRNAs co-targeted a gene encoding SPL17, which may function as a negative regulator in anthocyanin accumulation. In addition, miR408 was also abundantly expressed in purple- and orange-colored spathes, and its typical targets were also identified. This comprehensive integrated analysis provides insight into the miRNA-mediated genetic regulation in spathe coloration of A. andraeanum.

9.
Endocrinology ; 2022 May 02.
Artigo em Inglês | MEDLINE | ID: mdl-35511048

RESUMO

Ovulation is a dramatic remodeling process that includes rupture of blood capillaries and clotting, but coagulation is not thought to directly regulate this process. Herein, we report remarkable increases of coagulation factors V (f5, ~3145-fold) and tissue factor (f3a, ~120-fold) in zebrafish ovarian follicle cells during ovulation. This increase was mediated through the nuclear progestin receptor (Pgr), which is essential for ovulation in zebrafish, and was totally abolished in ovarian follicular cells from pgr-/- mutants. In addition, promoter activities of f5 and f3a were significantly enhanced by progestin (DHP) via Pgr. Similar regulation of human F5 promoter activity was induced via human PGRB, suggesting a conserved mechanism. Site-directed mutagenesis of the zebrafish f5 promoter further demonstrated a direct regulation of coagulation factors via progestin response elements. Moreover, a stark increase of erythrocytes occurred in capillaries meshed in wildtype preovulatory follicles but was absent in pgr-/- mutants. Interestingly, anticoagulants significantly inhibited ovulation both in vitro and in vivo, respectively. Furthermore, reduced fecundity was observed in f5+/- female zebrafish. Taken together, our study provides plausible evidence for steroid regulation of coagulation factors, and a new hypothesis for blood clotting triggered ovulation in vertebrates.

10.
Biochem Biophys Res Commun ; 612: 91-98, 2022 Apr 25.
Artigo em Inglês | MEDLINE | ID: mdl-35512462

RESUMO

Nephrotoxicity is a major adverse reaction of cisplatin-based chemotherapy. Organic cation transporter 2 (OCT2) which is located on the basement membrane of human proximal renal tubules is responsible for the renal accumulation of cisplatin and its nephrotoxicity. This study aimed to investigate the protective effect of PPIs to CP-induced nephrotoxicity. Three kinds of PPIs including lansoprazole, omeprazole and rabeprazole (Rab) were co-administrated with CP to mice. In addition, OCT2-overexpressed HEK293, HK-2 and A549 cells were co-incubated with CP and PPIs. The results showed that PPIs can attenuate CP-induced increase of CRE, BUN and histological damage of kidney. Among the three PPIs, Rab was found with a superior protective effect. It significantly reduced the accumulation of CP in OCT2-overexpressed HEK293 cells and in the renal cortex tissues of mice, but not in HK-2 cells. Moreover, Rab reduced the expression levels of cleaved-caspase-3, RIPK1, RIPK3, MLKL and p-MLKL and the apoptosis rate of renal tubular cells induced by CP in vivo, but not in HK-2 cells. However, Rab increased the viability of CP-treated cells in a concentration-dependent manner and attenuated CP-induced apoptosis and necroptosis in OCT2 over-expressed HEK293 cells. Finally, we demonstrated that Rab have no influence on the antitumor effect of CP. In conclusion, Rab attenuate CP-induced nephrotoxicity mainly through inhibiting OCT2-mediated CP uptake, without interfering with its anti-tumor property of inducing apoptosis and necroptosis.

11.
J Ethnopharmacol ; : 115316, 2022 May 02.
Artigo em Inglês | MEDLINE | ID: mdl-35513214

RESUMO

ETHNOPHARMACOLOGICAL RELEVANCE: Many studies have demonstrated the powerful neuroprotection abilities of multiple traditional Chinese medicines (TCMs) against NLRP3 inflammasome-mediated ischemic cerebral injury. These TCMs may be in the form of TCM prescriptions, Chinese herbal medicines and their extracts, and TCM monomers. AIM OF THE STUDY: This review aimed to analyze and summarize the existing knowledge on the assembly and activation of the NLRP3 inflammasome and its role in the pathogenesis of ischemic stroke (IS). We also summarized the mechanism of action of the various TCMs on the NLRP3 inflammasome, which may provide new insights for the management of IS. MATERIALS AND METHODS: We reviewed recently published articles by setting the keywords "NLRP3 inflammasome" and "traditional Chinese medicines" along with "ischemic stroke"; "NLRP3 inflammasome" and "ischemic stroke" along with "natural products" and so on in Pubmed and GeenMedical. RESULTS: According to recent studies, 16 TCM prescriptions (officially authorized products and clinically effective TCM prescriptions), 7 Chinese herbal extracts, and 29 TCM monomers show protective effects against IS through anti-inflammatory, anti-oxidative stress, anti-apoptotic, and anti-mitochondrial autophagy effects. CONCLUSIONS: In this review, we analyzed studies on the involvement of NLRP3 in IS therapy. Further, we comprehensively and systematically summarized the current knowledge to provide a reference for the further application of TCMs in the treatment of IS.

12.
Artif Organs ; 2022 May 02.
Artigo em Inglês | MEDLINE | ID: mdl-35491962

RESUMO

OBJECTIVE: To evaluate whether septic shock patients with pulmonary infection and life-threatening hypoxemia can benefit from V-V ECMO. METHODS: Retrospective clinical data analysis on patients who suffered septic shock with pulmonary infection, categorized into V-V ECMO and control groups.The propensity score matching (PSM) method was used to screen patients matched for age, gender, and disease severity.The primary outcome was 30- and 90-day mortality after diagnosis of septic shock. RESULTS: After PSM, 31 pairs of patients were enrolled in this study, and there were no significant differences between the two groups in terms of gender, age, chronic disease, Acute Physiological and Chronic Health Evaluation II (APACHE II) score, and Sequential Organ Failure Assessment (SOFA) score. Within 28 days after the diagnosis of septic shock, the median time of renal replacement therapy-free days was longer in the V-V ECMO group than in the control group (27 days versus 9 days ; P=0.044).Kaplan-Meier analysis showed that 30-day mortality was lower in the V-V ECMO group than in the control group (38.7% versus 61.3%; HR 0.488; 95% CI 0.240-0.992; P=0.043,by Log-rank test); 90-day mortality was not significantly different between the two groups (51.6% versus 67.7%; P=0.097). CONCLUSION: Patients receiving V-V ECMO support had lower 30-day mortality and faster recovery of renal function within 28 days compared with those receiving conventional therapy. However, V-V ECMO did not improve 90-day survival in septic shock patients with pulmonary infection.

13.
Front Cardiovasc Med ; 9: 859771, 2022.
Artigo em Inglês | MEDLINE | ID: mdl-35497979

RESUMO

Background: Multiparametric models have shown better risk stratification in Brugada syndrome. Recently, these models have been validated in different populations. Aims: To perform a systematic review and meta-analysis of the predictive performance of three validated multiparametric models (Delise model, Sieria model, and Shanghai score). Methods: We searched PubMed, Embase, MEDLINE, Web of Science, and Ovid for studies validating the risk multiparametric model. A Sieria score > 2 and Shanghai score ≥ 4 were considered to indicate higher risk. Performance estimates were summarized using a random-effects model. Results: Seven studies were included, with sample sizes of 111-1,613. The follow-up duration was 3.3-10.18 years. The Sieria model had a pooled area under the curve (AUC), sensitivity, and specificity of 0.71 [95% confidence interval (CI): 0.67-0.75], 57% (95% CI: 35-76), and 71% (95% CI: 62-79), respectively. The Shanghai score had an AUC of 0.63-0.71, 68.97-90.67% sensitivity, and 43.53-63.43% specificity. The AUC of the Delise model was 0.77-0.87; however, the optimal cut-off was not identified. Conclusions: The three models exhibited moderate discriminatory ability for Brugada syndrome. The Sieria model has poor sensitivity and moderate specificity, whereas the Shanghai score has poor specificity and moderate sensitivity.

14.
Artigo em Inglês | MEDLINE | ID: mdl-35381090

RESUMO

BACKGROUND: The relationship between maternal thyroid function and pregnancy outcomes remains controversial and the safe range of TSH is still unclear in women planning pregnancy. METHODS: This population-based cohort study enrolled Chinese women who became pregnant subsequently in 30 provinces from 2010 to 2012 from the National Free Preconception Checkups Project. The maternal TSH level within 6 months before pregnancy and different pregnancy outcomes were collected and analyzed using restricted cubic spline regression model for dose-response relationship and potential optimal cut-off values. Logistic regression was used to reveal the relationship between different TSH groups and the risk of adverse outcomes. RESULTS: Among 175112 women, a J-shaped association was revealed between TSH and LGA (P < 0.001). When TSH was lower than 1.27 or 0.91 mIU/L, lower TSH was associated with higher OR of LBW (P = 0.003) or preterm delivery (P < 0.001). There was no significant association of preconception TSH with SGA, macrosomia, fetal anomalies, stillbirth, natural or induced abortion, and cesarean delivery. The range of TSH for OR lower than 1.0 was within 0.91-1.82 mIU/L in dose-response association. Compared with TSH 0.91-1.82 mIU/L, TSH low (<0.40 mIU/L and 0.40-0.90 mIU/L) and high (1.83-2.49 mIU/L, 2.50-3.99 mIU/L and >4.00 mIU/L) were associated with higher risk of preterm delivery and LGA. There was no significant association between TSH groups and the risk of LBW except for TSH <0.40 mIU/L. CONCLUSION: Preconception TSH was associated with preterm delivery, LGA, and LBW. Preconception TSH had a bidirectional effect on LGA, indicating a potential mechanism regarding influence of TSH on birth weight. TSH within 0.91-1.82mIU/L was the potential safe range for preconception women.

15.
J Exp Clin Cancer Res ; 41(1): 153, 2022 Apr 23.
Artigo em Inglês | MEDLINE | ID: mdl-35459186

RESUMO

BACKGROUND: Chemoresistance of pancreatic cancer is the main reason for the poor treatment effect of pancreatic cancer patients. Exploring chemotherapy resistance-related genes has been a difficult and hot topic of oncology. Numerous studies implicate the key roles of circular RNAs (circRNAs) in the development of pancreatic cancer. However, the regulation of circRNAs in the process of pancreatic ductal adenocarcinoma (PDAC) chemotherapy resistance is not yet fully clear. METHODS: Based on the cross-analysis of the Gene Expression Omnibus (GEO) database and the data of our center, we explored a new molecule, hsa_circ_0078297 (circ-MTHFD1L), related to chemotherapy resistance. QRT-PCR was used to detect the expression of circRNAs, miRNAs, and mRNAs in human PDAC tissues and their matched normal tissues. The interaction between circ-MTHFD1L and miR-615-3p/RPN6 signal axis was confirmed by a series of experiments such as Dual-luciferase reporter assay, fluorescence in situ hybridization (FISH) RNA immunoprecipitation (RIP) assays. RESULTS: Circ-MTHFD1L was significantly increased in PDAC tissues and cells. And in PDAC patients, the higher the expression level of circ-MTHFD1L, the worse the prognosis. Mechanism analysis showed that circ-MTHFD1L, as an endogenous miR-615-3p sponge, upregulates the expression of RPN6, thereby promoting DNA damage repair and exerting its effect on enhancing gemcitabine chemotherapy resistance. More importantly, we also found that Silencing circ-MTHFD1L combined with olaparib can increase the sensitivity of pancreatic cancer to gemcitabine. CONCLUSION: Circ-MTHFD1L maintains PDAC gemcitabine resistance through the miR-615-3p/RPN6 signal axis. Circ-MTHFD1L may be a molecular marker for the effective treatment of PDAC.


Assuntos
Carcinoma Ductal Pancreático , MicroRNAs , Neoplasias Pancreáticas , Carcinoma Ductal Pancreático/tratamento farmacológico , Carcinoma Ductal Pancreático/genética , Carcinoma Ductal Pancreático/metabolismo , Linhagem Celular Tumoral , Proliferação de Células , Desoxicitidina/análogos & derivados , Humanos , Hibridização in Situ Fluorescente , MicroRNAs/genética , MicroRNAs/metabolismo , Neoplasias Pancreáticas/tratamento farmacológico , Neoplasias Pancreáticas/genética , Neoplasias Pancreáticas/metabolismo , RNA Circular/genética
16.
BMC Med ; 20(1): 132, 2022 Apr 25.
Artigo em Inglês | MEDLINE | ID: mdl-35462547

RESUMO

BACKGROUND: Data on the association between free-living daytime sunlight exposure and incident dementia are scarce. The objective is to evaluate whether the time spent in outdoor light is related to the dementia risk and to investigate whether the optimal duration varies with clinical parameters. METHODS: Data were from a prospective cohort of 362,094 UK Biobank participants. A questionnaire survey was conducted to investigate how many hours the participants spent outdoors on typical summer and winter days. A restricted cubic spline (RCS) was performed to explore the potential nonlinear relationship between sunlight exposure and the risk of dementia. We used multivariate Cox proportional hazard regression models to estimate the hazard ratios (HRs) for the associations between sunlight exposure and dementia outcomes, with the change points as a reference. RESULTS: After a median follow-up of 9.0 years, 4149 (1.15%) individuals were diagnosed with dementia. RCS showed a J-shaped relationship between time spent in outdoor light and the dementia risk, with the lowest risk at three change points (1.5 h/day on average, 2 h/day in summer, and 1 h/day in winter). Cox hazard regression models showed a marked increase in risk at low exposure (HR=1.287, 95%CI 1.094-1.515) but a relatively slow increase at higher exposure (HR=1.070, 95%CI 1.031-1.10). Results are more pronounced among participants over 60 years old, females, and those with exactly 7 h of sleep every night. CONCLUSIONS: Sunlight exposure had a J-shaped association with dementia risk. Giving detailed guidance on sunlight exposure can effectively prevent dementia.


Assuntos
Demência , Sono , Estudos de Coortes , Demência/diagnóstico , Demência/epidemiologia , Demência/etiologia , Feminino , Humanos , Pessoa de Meia-Idade , Estudos Prospectivos , Fatores de Risco
17.
Artigo em Inglês | MEDLINE | ID: mdl-35463097

RESUMO

Traditional Chinese medicine (TCM) has been used successfully to treat rheumatoid arthritis (RA). QingreHuoxue treatment (QingreHuoxue decoction [QRHXD]/QingreHuoxue external preparation [QRHXEP]) is a Chinese medicine treatment for RA. To date, very few studies have compared the long-term effects of QRHXD with those of conventional disease-modifying antirheumatic drugs on RA disease activity and radiological progression. QRHXD delayed the radiological progression and showed long-term clinical efficacy of RA. In clinical experiments, the clinical evidence of delaying the radiological progression of RA patients was obtained. A portion of the patients who participated in the "Traditional Chinese Medicine QingreHuoxue Treatment vs. the Combination of Methotrexate and Hydroxychloroquine for Active Rheumatoid Arthritis" study were followed up for 52 weeks, and intention-to-treat (ITT) and compliance protocol (PP) analyses were used to collect and compare the clinical indicators and imaging data between baseline and week 52. Two radiologists who were blind to treatment scored the images independently. Of the 468 subjects, 141 completed the 52-week follow-up. There were no significant differences among the three groups: the traditional Chinese medicine comprehensive treatment group, the Western medicine treatment group, and the integrated traditional Chinese and Western medicine treatment group. There were no differences in the total Sharp score, joint space stenosis score, and joint erosion score at baseline or 52 weeks. In the comparison of the estimated annual radiographic progression (EARP) and the actual annual Sharp total score changes among the three groups, the actual changes were much lower than the EARP at baseline. The radiological progress in all three groups was well controlled. Results of the ITT and PP data sets showed that the disease activity score 28 level of the three groups at 52 weeks was significantly lower than that at baseline. During the 52-week treatment period, the clearance of heat and promotion of blood circulation controlled disease activity and delayed the radiological progress of active RA.

18.
Int J Ophthalmol ; 15(4): 591-597, 2022.
Artigo em Inglês | MEDLINE | ID: mdl-35450171

RESUMO

AIM: To identify the predictive factors and laser photocoagulation associated with the use of silicone oil as endotamponade during primary diabetic vitrectomy. METHODS: The medical and surgical records of 690 patients (798 eyes) who underwent primary diabetic vitrectomy at a tertiary eye hospital in China from January 2018 to December 2018 were reviewed in this retrospective cohort study. The patients' baseline characteristics and preoperative treatments were recorded. The binary Logistic regression model was used to evaluate the risk factors for the use of silicone oil as endotamponade agent during primary vitrectomy for proliferative diabetic retinopathy (PDR)-related complications. RESULTS: Among 690 patients with mean age of 52.1±10.5y (range: 18-85y), 299/690 (43.3%) were female. The 31.6% of the eyes received preoperative laser treatment, and 72.4% of the eyes received preoperative anti-VEGF adjuvant therapy. Non-clearing vitreous haemorrhage (VH) alone or combined with retinal detachment was the main surgical indication (89.5%) for primary vitrectomy. Silicone oil was used as endotamponade in 313 (39.2%) eyes. Lack of preoperative laser treatment [odds ratio (OR) 0.66, 95% confidence interval (CI): 0.48-0.92; P=0.015] and older age (OR 0.96, 95%CI: 0.95-0.98; P<0.001) were predictors of silicone oil tamponade during primary vitrectomy for PDR. CONCLUSION: The lack of preoperative laser treatment is a significant predictor of silicone oil tamponade during primary vitrectomy for PDR. However, the severity of PDR relevant to silicone oil use should be further evaluated.

20.
Nat Plants ; 8(4): 373-388, 2022 04.
Artigo em Inglês | MEDLINE | ID: mdl-35449401

RESUMO

To improve our understanding of the origin and evolution of mycoheterotrophic plants, we here present the chromosome-scale genome assemblies of two sibling orchid species: partially mycoheterotrophic Platanthera zijinensis and holomycoheterotrophic Platanthera guangdongensis. Comparative analysis shows that mycoheterotrophy is associated with increased substitution rates and gene loss, and the deletion of most photoreceptor genes and auxin transporter genes might be linked to the unique phenotypes of fully mycoheterotrophic orchids. Conversely, trehalase genes that catalyse the conversion of trehalose into glucose have expanded in most sequenced orchids, in line with the fact that the germination of orchid non-endosperm seeds needs carbohydrates from fungi during the protocorm stage. We further show that the mature plant of P. guangdongensis, different from photosynthetic orchids, keeps expressing trehalase genes to hijack trehalose from fungi. Therefore, we propose that mycoheterotrophy in mature orchids is a continuation of the protocorm stage by sustaining the expression of trehalase genes. Our results shed light on the molecular mechanism underlying initial, partial and full mycoheterotrophy.


Assuntos
Micorrizas , Orchidaceae , Micorrizas/genética , Orchidaceae/genética , Orchidaceae/metabolismo , Orchidaceae/microbiologia , Simbiose , Trealase/metabolismo , Trealose/metabolismo
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