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1.
Front Med (Lausanne) ; 11: 1399247, 2024.
Artigo em Inglês | MEDLINE | ID: mdl-39114831

RESUMO

Objective: In several randomized controlled trials (RCTs), sacrospinous hysteropexy and other forms of hysteropreservation have been compared. Nevertheless, there is no definitively best treatment. This study summarized RCT evidence for various uterine preservation surgical procedures. Methods: From each database inception to August 2023, we searched PubMed, Embase, Cochrane Library, and Web of Science for eligible RCTs. A comparison was made between sacrospinous hysteropexy and other hysteropreservation, including vaginal and abdominal surgery. For categorical and continuous variables, relative risks (RRs) and mean differences (MDs) were calculated using random-effects models. Results: We reviewed a total 1,398 studies and ultimately included five RCTs that met all inclusion criteria. These five studies included a total of 1,372 uterine POP cases all of whom received transvaginal surgery and had a follow-up period for assessment of recurrence from 12 months to 5 years. There were no significant differences between sacrospinous hysteropexy and other hysteropreservation for the incidences of recurrence (RR,1.24; 95% CI, 0.58 to 2.63; p = 0.58) or hematoma (RR,0.70; 95% CI, 0.17 to 2.92; p = 0.62). Moreover, neither sacrospinous hysteropexy nor hysteropreservation had any significant effect on the risk of mesh exposure (RR,0.34; 95% CI, 0.03 to 4.31; p = 0.41), dyspareunia (RR,0.45; 95% CI, 0.13 to1.6; p = 0.22), urinary tract infection (RR,0.66; 95% CI, 0.38 to 1.15; p = 0.15), bothersome bulge symptoms (RR,0.03; 95% CI, -0.02 to 0.08; p = 0.24), operative time (MD, -4.53; 95% CI, -12.08 to 3.01; p = 0.24), and blood loss (MD, -25.69; 95% CI, -62.28 to 10.91; p = 0.17). However, sacrospinous hysteropexy was associated with a lower probability of pain (RR,4.8; 95% CI, 0.79 to 29.26; p = 0.09) compared with other hysteropreservation. Conclusion: There was no difference between sacrospinous hysteropexy and hysteropreservation in terms of recurrence, hematoma, mesh exposure, dyspareunia, urinary tract infection, bothersome bulge symptoms, operative time, pain, and blood loss. Systematic Review Registration: PROSPERO [CRD42023470025].

2.
Bioact Mater ; 39: 206-223, 2024 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-38827172

RESUMO

Traditional treatments against advanced non-small cell lung cancer (NSCLC) with high morbidity and mortality continue to be dissatisfactory. Given this situation, there is an urgent requirement for alternative modalities that provide lower invasiveness, superior clinical effectiveness, and minimal adverse effects. The combination of photodynamic therapy (PDT) and immunotherapy gradually become a promising approach for high-grade malignant NSCLC. Nevertheless, owing to the absence of precise drug delivery techniques as well as the hypoxic and immunosuppressive characteristics of the tumor microenvironment (TME), the efficacy of this combination therapy approach is less than ideal. In this study, we construct a novel nanoplatform that indocyanine green (ICG), a photosensitizer, loads into hollow manganese dioxide (MnO2) nanospheres (NPs) (ICG@MnO2), and then encapsulated in PD-L1 monoclonal antibodies (anti-PD-L1) reprogrammed exosomes (named ICG@MnO2@Exo-anti-PD-L1), to effectively modulate the TME to oppose NSCLC by the synergy of PDT and immunotherapy modalities. The ICG@MnO2@Exo-anti-PD-L1 NPs are precisely delivered to the tumor sites by targeting specially PD-L1 highly expressed cancer cells to controllably release anti-PD-L1 in the acidic TME, thereby activating T cell response. Subsequently, upon endocytic uptake by cancer cells, MnO2 catalyzes the conversion of H2O2 to O2, thereby alleviating tumor hypoxia. Meanwhile, ICG further utilizes O2 to produce singlet oxygen (1O2) to kill tumor cells under 808 nm near-infrared (NIR) irradiation. Furthermore, a high level of intratumoral H2O2 reduces MnO2 to Mn2+, which remodels the immune microenvironment by polarizing macrophages from M2 to M1, further driving T cells. Taken together, the current study suggests that the ICG@MnO2@Exo-anti-PD-L1 NPs could act as a novel drug delivery platform for achieving multimodal therapy in treating NSCLC.

3.
Am J Clin Nutr ; 119(2): 406-416, 2024 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-38042409

RESUMO

BACKGROUND: Dietary patterns have been associated with several cancers, especially gastrointestinal cancer (GIC). However, whether a healthy dietary pattern could modify the risk of GIC among people with different genetic backgrounds is not clear. OBJECTIVE: The objective of the study was to investigate how dietary patterns and genetic susceptibility contribute to the risk of GIC independently and jointly. METHODS: This large-scale prospective cohort study included 105,463 participants in UK Biobank who were aged 40-72 y and cancer-free at baseline. Dietary intake (Oxford WebQ) was used to calculate dietary pattern scores including dietary approach to stop hypertension (DASH) score and healthful plant-based diet index (hPDI). Genetic risk was quantified by a polygenic risk score (PRS) comprising 129 known GIC-associated loci. Cox proportional hazards regression was performed to estimate the associations of dietary patterns and PRS with GIC incidence after adjusting for potential confounders. RESULTS: Over a median follow-up of 11.70 y, 1,661 participants were diagnosed with GIC. DASH and hPDI were associated with 20% and 36% reductions, respectively, in GIC risk. Low PRS was associated with a 30 % decrease in GIC risk (HR: 0.70; 95% CI: 0.62, 0.79). Participants with healthy dietary scores at high-genetic risk had a lower GIC risk with HR of 0.77 (95% CI: 0.60, 0.98) for DASH and 0.66 (95% CI: 0.52, 0.84) for hPDI than those with unhealthy dietary score. Participants with both high-dietary score and low-genetic risk showed the lowest risk of GIC, with HR of 0.58 (95% CI: 0.45, 0.75) for DASH and 0.45 (95% CI: 0.34, 0.58) for hPDI. CONCLUSIONS: Adherence to DASH and hPDI were associated with a lower risk of some gastrointestinal cancers, and these 2 dietary patterns may partly compensate for genetic predispositions to cancer. Our results advance the development of precision medicine strategies that consider both dietary patterns and genetics to improve gastrointestinal health.


Assuntos
Neoplasias Gastrointestinais , Hipertensão , Humanos , Estudos Prospectivos , Padrões Dietéticos , Fatores de Risco , Dieta , Neoplasias Gastrointestinais/etiologia , Neoplasias Gastrointestinais/genética , Plantas , Estratificação de Risco Genético , Predisposição Genética para Doença
4.
Adv Rheumatol ; 63(1): 42, 2023 08 18.
Artigo em Inglês | MEDLINE | ID: mdl-37596678

RESUMO

BACKGROUND: The etiology of systemic lupus erythematosus is complex and incurable. A large number of systematic reviews have studied the risk factors of it. Mendelian randomization is an analytical method that uses genetic data as tool variables to evaluate the causal relationship between exposure and outcome. OBJECTIVE: To review the systematic reviews and Mendelian randomization studies that focused on the risk factors of systemic lupus erythematosus and shed light on the development of treatments for its prevention and intervention. METHODS: From inception to January 2022, we systematically searched MEDLINE (via PubMed) and Embase for related systematic reviews and Mendelian randomization studies. Extract relevant main data for studies that meet inclusion criteria. The quality of systematic reviews was assessed by using Assessment of Multiple Systematic Reviews 2 (AMSTAR-2). Finally, the risk factors are scored comprehensively according to the results' quantity, quality, and consistency. RESULTS: Our study involved 64 systematic reviews and 12 Mendelian randomization studies. The results of systematic reviews showed that diseases (endometriosis, atopic dermatitis, allergic rhinitis), lifestyle (smoking, drinking, vaccination), and gene polymorphism influenced the incidence of systemic lupus erythematosus. The results of Mendelian randomization studies identified the role of disease (periodontitis, celiac disease), trace elements (selenium, iron), cytokines (growth differentiation factor 15), and gut microbiome in the pathogenesis of systemic lupus erythematosus. CONCLUSION: We should pay attention to preventing and treating systemic lupus erythematosus in patients with endometriosis, celiac disease, and periodontitis. Take appropriate dietary supplements to increase serum iron and selenium levels to reduce the risk of systemic lupus erythematosus. There should be no excessive intervention in lifestyles such as smoking and drinking.


Assuntos
Doença Celíaca , Endometriose , Lúpus Eritematoso Sistêmico , Selênio , Feminino , Humanos , Análise da Randomização Mendeliana , Revisões Sistemáticas como Assunto , Fatores de Risco , Ferro , Lúpus Eritematoso Sistêmico/genética
5.
Int J Surg ; 109(11): 3631-3647, 2023 Nov 01.
Artigo em Inglês | MEDLINE | ID: mdl-37565634

RESUMO

OBJECTIVE: Previous systematic reviews demonstrated a potentially beneficial effect of probiotics on irritable bowel syndrome (IBS). However, these studies are either affected by the inclusion of insufficient trials or by the problem of dependent data across multiple outcomes, and an overall effect size has not been provided. We aimed to determine the effect of probiotics on IBS through a three-level meta-analysis and clarify potential effect moderators. METHODS: We searched MEDLINE, Embase, and Web of Science, screening for randomized controlled trials (RCTs) that examine the effect of probiotics on IBS. The primary outcome was the improvement in the severity of global IBS symptoms at the end of treatment. The secondary outcomes were the improvement in abdominal pain and the quality of life. The effect sizes of the probiotics were measured by using the standardized mean difference (SMD) and pooled by a three-level meta-analysis model. RESULTS: We included 72 RCTs in the analysis. The meta-analysis showed significantly better overall effect of probiotics than placebo on the global IBS symptoms (SMD -0.55, 95% CI -0.76 to -0.34, P <0.001), abdominal pain (SMD -0.89, 95% CI -1.29 to -0.5, P <0.001) and quality of life (SMD 0.99, 95% CI 0.45 to 1.54, P <0.001), respectively. Moderator analysis found that a treatment duration shorter than 4 weeks was associated with a larger effect size in all the outcomes, and Bacillus probiotics had better improvement on the abdominal pain. CONCLUSIONS: Probiotics had a short-term effect and a medium effect size on the global IBS symptoms. Treatment duration and types of probiotics affected the effect size of probiotics, and shorter durations and Bacillus probiotics were associated with better treatment effects. REGISTRATION: Open Science Framework.


Assuntos
Síndrome do Intestino Irritável , Probióticos , Humanos , Síndrome do Intestino Irritável/terapia , Probióticos/uso terapêutico , Dor Abdominal/etiologia , Dor Abdominal/terapia , Qualidade de Vida , Fatores de Tempo , Resultado do Tratamento
6.
Front Med (Lausanne) ; 10: 1117158, 2023.
Artigo em Inglês | MEDLINE | ID: mdl-36936202

RESUMO

Study objective: To describe the surgical technique and compare the operative outcomes of gasless and traditional robot-assisted transvaginal natural orifice transluminal endoscopic surgery (GR-vNOTES vs. TR-vNOTES) in hysterectomy. Methods: The patients undergoing hysterectomy via GR-vNOTES or TR-vNOTES between February 2020 and January 2022 in our hospital were included. Clinical data regarding patient demographics, operative time, blood loss, complications, and postoperative hospital stays were collected and analyzed. Results: Five cases underwent hysterectomy via GR-vNOTES, and nine cases via TR-vNOTES. The baseline demographics and operative outcomes were not significantly different in GR-vNOTES and TR-vNOTES groups. There was no conversion to multiport robotic laparoscopy, conventional laparoscopy or laparotomy. No complications were seen in both groups, except two cases had fever postoperatively in the TR-vNOTES group. For those with early stage cervical/endometrial cancer, no recurrence or metastasis was observed in the follow-up of six months. Conclusion: Both GR-vNOTES and TR-vNOTES were feasible and safe for hysterectomy. GR-vNOTES was a promising alternative to TR-vNOTES in hysterectomy.

7.
Biomed Pharmacother ; 161: 114477, 2023 May.
Artigo em Inglês | MEDLINE | ID: mdl-36931030

RESUMO

Glioblastoma multiforme (GBM) is one of the most common primary malignant brain tumors in adults. Due to the poor prognosis of patients, the median survival time of GBM is often less than 1 year. Therefore, it is very necessary to find novel treatment options with a good prognosis for the treatment or prevention of GBM. In recent years, flavonoids are frequently used to treat cancer. It is a new attractive molecule that may achieve this promising treatment option. Flavonoids have been proved to have many biological functions, such as antioxidation, prevention of angiogenesis, anti-inflammation, inhibition of cancer cell proliferation, and protection of nerve cells. It has also shown the ability to regulate long non-coding RNA (LncRNA). Studies have confirmed that flavonoids can regulate epigenetic modification, transcription, and change microRNA (miRNA) expression of GBM through lncRNA at the gene level. It also found that flavonoids can induce apoptosis and autophagy of GBM cells by regulating lncRNA. Moreover, it can improve the metabolic abnormalities of GBM, interfere with the tumor microenvironment and related signaling pathways, and inhibit the angiogenesis of GBM cells. Eventually, flavonoids can block the tumor initiation, growth, proliferation, differentiation, invasion, and metastasis. In this review, we highlight the role of lncRNA in GBM cancer progression and the influence of flavonoids on lncRNA regulation. And emphasize their expected role in the prevention and treatment of GBM.


Assuntos
Neoplasias Encefálicas , Glioblastoma , MicroRNAs , RNA Longo não Codificante , Adulto , Humanos , Glioblastoma/tratamento farmacológico , Glioblastoma/genética , Glioblastoma/metabolismo , RNA Longo não Codificante/genética , RNA Longo não Codificante/metabolismo , Neoplasias Encefálicas/tratamento farmacológico , Neoplasias Encefálicas/genética , Neoplasias Encefálicas/metabolismo , Transformação Celular Neoplásica/genética , Apoptose/genética , Proliferação de Células/genética , MicroRNAs/genética , MicroRNAs/metabolismo , Regulação Neoplásica da Expressão Gênica , Linhagem Celular Tumoral , Microambiente Tumoral
8.
ACS Appl Mater Interfaces ; 15(13): 16539-16551, 2023 Apr 05.
Artigo em Inglês | MEDLINE | ID: mdl-36961248

RESUMO

Pancreatic cancer (PC) is the fourth leading cause of cancer death, and the 5 year survival rate is only 4%. Chemotherapy is the treatment option for the majority of PC patients diagnosed at an advanced stage, whereas the desmoplastic stroma of PC could block the perfusion of chemotherapeutic agents to tumor tissues and contribute generally to chemoresistance. Therefore, the clinical status of PC calls for an urgent exploration in the effective treatment strategy. Chemo-phototherapy is an emerging modality against malignant tumors, but owing to the low targeting ability of theranostic agents or unspecific accumulation in the tumor region, majority of chemo-phototherapy techniques have disappointing therapeutic efficiencies. Herein, we have explored CD71-specific targeting aptamers and paclitaxel (PTX)-modified polydopamine (PDA) nanospheres with the conjugation of peptidomimetic AV3 (termed Apt-PDA@PTX/AV3 bioconjugates) to specifically target and combat PC in vivo by synergistic chemo-phototherapy. After the delivery of nanotheranostic agents to the tumor microenvironment (TME) or subsequent endocytic uptake by PC cells, a simultaneous release of AV3 and PTX from Apt-PDA@PTX/AV3 bioconjugates via near-infrared (NIR) irradiation can decrease desmoplastic stroma to enhance tumor perfusion and tumor-killing effects. Meanwhile, PDA cores utilize NIR laser to create unendurable hyperthermia within TME to "cook" tumors. Taken together, the current study finally suggests that our Apt-PDA@PTX/AV3 bioconjugates could act as a novel therapeutic approach by synergistic chemo-phototherapy for the programmable inhibition of PC.


Assuntos
Hipertermia Induzida , Nanopartículas , Nanosferas , Neoplasias Pancreáticas , Humanos , Hipertermia Induzida/métodos , Fototerapia/métodos , Paclitaxel/farmacologia , Neoplasias Pancreáticas/tratamento farmacológico , Peptídeos , Perfusão , Linhagem Celular Tumoral , Doxorrubicina/farmacologia , Microambiente Tumoral , Neoplasias Pancreáticas
9.
Adv Rheumatol ; 63: 42, 2023. tab, graf
Artigo em Inglês | LILACS-Express | LILACS | ID: biblio-1513562

RESUMO

Abstract Background The etiology of systemic lupus erythematosus is complex and incurable. A large number of systematic reviews have studied the risk factors of it. Mendelian randomization is an analytical method that uses genetic data as tool variables to evaluate the causal relationship between exposure and outcome. Objective To review the systematic reviews and Mendelian randomization studies that focused on the risk factors of systemic lupus erythematosus and shed light on the development of treatments for its prevention and intervention. Methods From inception to January 2022, we systematically searched MEDLINE (via PubMed) and Embase for related systematic reviews and Mendelian randomization studies. Extract relevant main data for studies that meet inclusion criteria. The quality of systematic reviews was assessed by using Assessment of Multiple Systematic Reviews 2 (AMSTAR-2). Finally, the risk factors are scored comprehensively according to the results' quantity, quality, and consistency. Results Our study involved 64 systematic reviews and 12 Mendelian randomization studies. The results of systematic reviews showed that diseases (endometriosis, atopic dermatitis, allergic rhinitis), lifestyle (smoking, drinking, vaccination), and gene polymorphism influenced the incidence of systemic lupus erythematosus. The results of Mendelian randomization studies identified the role of disease (periodontitis, celiac disease), trace elements (selenium, iron), cytokines (growth differentiation factor 15), and gut microbiome in the pathogenesis of systemic lupus erythematosus. Conclusion We should pay attention to preventing and treating systemic lupus erythematosus in patients with endometriosis, celiac disease, and periodontitis. Take appropriate dietary supplements to increase serum iron and selenium levels to reduce the risk of systemic lupus erythematosus. There should be no excessive intervention in lifestyles such as smoking and drinking.

10.
Nutrients ; 14(23)2022 Nov 23.
Artigo em Inglês | MEDLINE | ID: mdl-36501003

RESUMO

Limited evidence investigated the combined influence of early-adulthood weight change and later physical activity on the risk of cardiovascular (CVD) and all-cause mortality. The aim of this study is to explore the associations of early-adulthood weight change and later physical activity with CVD and all-cause mortality. This is a cohort study of 23,193 US adults aged 40 to 85 years from the National Health and Nutrition Examination Survey (NHANES) 1999 to 2014. Cox proportional hazards regression was used to calculate hazard ratios (HRs) with 95% confidence intervals (CIs) of CVD and all-cause mortality associated with early-adulthood weight change and later physical activity. During a median follow-up of 9.2 years, there were 533 and 2734 cases of CVD and all-cause deaths. Compared with being physically inactive, the HRs of the CVD mortality of being physically active were 0.44 (0.26 to 0.73), 0.58 (0.19 to 1.82), 0.38 (0.17 to 0.86) and 0.46 (0.21 to 1.02) among individuals with stable normal, stable obese, non-obese to obese and maximum overweight early-adulthood weight change patterns. Using stable normal patterns that were physically active later as the reference, other early-adulthood weight change patterns did not show a significantly higher risk of CVD mortality when participants were physically active in later life; later physically inactive participants had a significantly increased risk of CVD mortality, with HRs of 2.17 (1.30 to 3.63), 5.32 (2.51 to 11.28), 2.59 (1.29 to 5.18) and 2.63 (1.32 to 5.26) in the stable normal, stable obese, non-obese to obese and maximum overweight groups, respectively. Similar results can be seen in the analyses for all-cause mortality. Our findings suggest that inadequate physical activity worsens the negative impact of unhealthy early-adulthood weight change patterns, which is worthy of being noted in the improvement of public health.


Assuntos
Doenças Cardiovasculares , Adulto , Humanos , Inquéritos Nutricionais , Estudos de Coortes , Fatores de Risco , Exercício Físico , Obesidade/complicações , Sobrepeso/epidemiologia , Sobrepeso/complicações
11.
Molecules ; 27(22)2022 Nov 17.
Artigo em Inglês | MEDLINE | ID: mdl-36432062

RESUMO

Ischemic stroke (IS) is an acute cerebrovascular disease caused by sudden arterial occlusion, which is characterized by a high morbidity, mortality, and disability rate. It is one of the most important causes of nervous system morbidity and mortality in the world. In recent years, the search for new medicine for the treatment of IS has become an attractive research focus. Due to the extremely limited time window of traditional medicine treatment, some side effects may occur, and accompanied by the occurrence of adverse reactions, the frequency of exploration with natural medicine is significantly increased. Phosphatidylinositol-3-kinase/Protein kinase B (PI3K/Akt) signaling pathway is a classical pathway for cell metabolism, growth, apoptosis, and other physiological activities. There is considerable research on medicine that treats various diseases through this pathway. This review focuses on how natural medicines (including herbs and insects) regulate important pathophysiological processes such as inflammation, oxidative stress, apoptosis, and autophagy through the PI3K/Akt signaling pathway, and the role it plays in improving IS. We found that many kinds of herbal medicine and insect medicine can alleviate the damage caused by IS through the PI3K/Akt signaling pathway. Moreover, the prescription after their combination can also achieve certain results. Therefore, this review provides a new candidate category for medicine development in the treatment of IS.


Assuntos
AVC Isquêmico , Proteínas Proto-Oncogênicas c-akt , Humanos , Proteínas Proto-Oncogênicas c-akt/metabolismo , Fosfatidilinositol 3-Quinases/metabolismo , AVC Isquêmico/tratamento farmacológico , Transdução de Sinais , Fosfatidilinositol 3-Quinase/metabolismo
12.
Front Nutr ; 9: 848400, 2022.
Artigo em Inglês | MEDLINE | ID: mdl-35369090

RESUMO

The integrity of intestinal barrier determines intestinal homeostasis, which could be affected by various factors, like physical, chemical, and biological stimuli. Therefore, it is of considerable interest and importance to maintain intestinal barrier function. Fortunately, many plant polyphenols, including resveratrol, could affect the health of intestinal barrier. Resveratrol has many biological functions, such as antioxidant, anti-inflammation, anti-tumor, and anti-cardiovascular diseases. Accumulating studies have shown that resveratrol affects intestinal tight junction, microbial composition, and inflammation. In this review, we summarize the effects of resveratrol on intestinal barriers as well as the potential mechanisms (e.g., inhibiting the growth of pathogenic bacteria and fungi, regulating the expression of tight junction proteins, and increasing anti-inflammatory T cells while reducing pro-inflammatory T cells), and highlight the applications of resveratrol in ameliorating various intestinal diseases.

13.
Front Med (Lausanne) ; 9: 760722, 2022.
Artigo em Inglês | MEDLINE | ID: mdl-35308537

RESUMO

Pyroptosis, a novel pro-inflammatory type of programmed cell death, is involved in the tumorigenesis of various cancers. Recent findings have implicated long non-coding RNAs (lncRNAs) in the serial steps of cancer development. However, the expression and prognostic signatures of pyroptosis-related lncRNAs in hepatocellular carcinoma (HCC) remain largely unknown. Therefore, a pyroptosis-related lncRNA prognostic model was constructed for HCC. Thirty-four pyroptosis-related genes were obtained from previous reviews, and gene expression data were collected from The Cancer Genome Atlas (TCGA) database. Spearman's correlation test was used to identify potential pyroptosis-related lncRNAs. Cox and LASSO regression analyses were used to construct a prognostic model. Subsequently, receiver operating characteristic (ROC) curves were constructed to assess the model's predictive ability for the overall survival (OS) of HCC patients. CytoHubba was used to screen out the potential hub gene, whose expression was verified using clinical samples from HCC patients. Finally, nine pyroptosis-related differentially expressed lncRNAs in HCC were identified, and a prognostic model with four pyroptosis-related lncRNAs was constructed with an area under the ROC curve (AUC) of approximately 0.734. Single-sample gene set enrichment analysis and TCGA revealed different immune infiltration and immune checkpoints between the two risk groups. Moreover, these lncRNAs are closely related to the pyroptosis-related gene, NLRP6, which may be considered a hub gene. NLRP6 was lower-expressed in HCC samples, and patients with lower expression of NLRP6 had the longer OS. In conclusion, NLRP6-dependent pyroptosis-related lncRNAs play important roles in tumor immunity and may be potential predictors and therapeutic targets for HCC.

14.
Front Pharmacol ; 13: 1079953, 2022.
Artigo em Inglês | MEDLINE | ID: mdl-36618924

RESUMO

Background: Previous studies suggested that anti-TNF drugs might be repurposed as a preventive treatment for colorectal cancer. We aimed to examine whether genetically proxied inhibition of tumor necrosis factor receptor 1 (TNFR1) reduces the absolute risk of colorectal cancer through mendelian randomization (MR) analysis. Methods: We obtained 28 single nucleotide polymorphisms (SNPs) that were located within a ±15 kilobase window of the TNFRSF1A-the gene that encodes the TNFR1 protein, and we used genetic data from three GWAS studies of circulating levels of TNFR1, C-reactive protein (CRP), and white blood counts (WBC) to screen SNPs that proxied the inhibition of TNFR1. Positive control analyses were then performed by using another three GWAS data from the ulcerative colitis cohort (n = 45,975), Crohn's disease cohort (n = 40,266), and multiple sclerosis cohort (n = 115,803) to confirm the effect of the included SNPs. A two-sample mendelian randomization analysis was performed to examine the association between TNFR1 inhibition and the absolute risk reduction (ARR) of colorectal cancer. Results: We finally included seven SNPs to proxy the anti-TNF effect, and these SNPs caused lower levels of TNFR1, CRP, and white blood counts. In positive control analyses, the included SNPs caused lower odds ratio of ulcerative colitis and Crohn's disease but a higher odds ratio of multiple sclerosis, consistent with drug mechanistic actions and previous trial evidence. By using the inverse-variance weighted analyses to combine the effects of the seven SNPs, we found that the anti-TNF effect was associated with a 0.988 (95%CI 0.985-0.991) mg/L decrease in CRP levels and a reduction in the risk of colorectal cancer (absolute risk reduction -2.1%, 95%CI -3.8% to -0.4%, p = 0.01). Conclusion: Our study confirmed that anti-TNF drugs were associated with a risk reduction in colorectal cancer. Physicians could consider using anti-TNF drugs for the prevention of colorectal cancer, especially in patients with high risks of developing cancer.

15.
Zhong Yao Cai ; 35(2): 300-3, 2012 Feb.
Artigo em Chinês | MEDLINE | ID: mdl-22822678

RESUMO

OBJECTIVE: To study the extraction conditions of Sapindus mukorossi oil by Supercritical CO2 Extraction and identify its components. METHODS: Optimized SFE-CO2 Extraction by response surface methodology and used GC-MS to analysie Sapindus mukorossi oil compounds. RESULTS: Established the model of an equation for the extraction rate of Sapindus mukorossi oil by Supercritical CO2 Extraction, and the optimal parameters for the Supercritical CO2 Extraction determined by the equation were: the extraction pressure was 30 MPa, temperature was 40 degrees C; The separation I pressure was 14 MPa, temperature was 45 degrees C; The separation II pressure was 6 MPa, temperature was 40 degrees C; The extraction time was 60 min and the extraction rate of Sapindus mukorossi oil of 17.58%. 22 main compounds of Sapindus mukorossi oil extracted by supercritical CO2 were identified by GC-MS, unsaturated fatty acids were 86.59%. CONCLUSION: This process is reliable, safe and with simple operation, and can be used for the extraction of Sapindus mukorossi oil.


Assuntos
Ácidos Graxos Insaturados/análise , Óleos de Plantas/química , Óleos de Plantas/isolamento & purificação , Sapindus/química , Sementes/química , Dióxido de Carbono , Cromatografia com Fluido Supercrítico/métodos , Cromatografia Gasosa-Espectrometria de Massas , Pressão , Projetos de Pesquisa , Temperatura
16.
Zhong Yao Cai ; 34(5): 789-94, 2011 May.
Artigo em Chinês | MEDLINE | ID: mdl-21954569

RESUMO

The orthogonal test and the supercritical carbon dioxide fluid extraction were used for optimizing the extraction of the essential oil from Plumeria rubra var. actifolia for the first time. Compared with the steam distillation, the optimal operation parameter of extraction was as follows: extraction pressure 25 MPa, extraction temperature 45 degrees C; separator I pressure 12 MPa, separator I temperature 55 degrees C; separator II pressure 6 MPa, separator II temperature 30 degrees C. Under this condition the yield of the essential oil was 5.8927%. The components were separated and identified by GC-MS. 53 components of Plumeria rubra var. actifolia measured by SFE method were identified and determined by normalization method. The main components were 1, 6, 10-dodecatrien-3-ol, 3, 7, 11-trimethyl, benzoic acid, 2-hydroxy-, phenylmethyl ester, 1, 2-benzenedicarboxylic acid, bis(2-methylpropyl) ester,etc.. 1, 2-Benzenedicarboxylic acid, bis (2-methylpropyl) este. took up 66.11% of the total amount, and there was much difference of the results from SD method.


Assuntos
Apocynaceae/química , Cromatografia com Fluido Supercrítico/métodos , Flores/química , Óleos Voláteis/isolamento & purificação , Álcoois/análise , Álcoois/química , Dióxido de Carbono , Ésteres/análise , Ésteres/química , Cromatografia Gasosa-Espectrometria de Massas , Laos , Estrutura Molecular , Óleos Voláteis/química , Pressão , Temperatura
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