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1.
Front Cell Dev Biol ; 10: 850145, 2022.
Artigo em Inglês | MEDLINE | ID: mdl-35517510

RESUMO

Overproduction of reactive oxygen species (ROS) and superlative lipid peroxidation promote tumorigenesis, and mitochondrial aldehyde dehydrogenase 2 (ALDH2) is associated with the detoxification of ROS-mediated lipid peroxidation-generated reactive aldehydes such as 4-hydroxy-2-nonenal (4-HNE), malondialdehyde, and acrolein due to tobacco smoking. ALDH2 has been demonstrated to be highly associated with the prognosis and chemoradiotherapy sensitivity of many types of cancer, including leukemia, lung cancer, head and neck cancer, esophageal cancer, hepatocellular cancer, pancreatic cancer, and ovarian cancer. In this study, we explored the possible relationship between ALDH2 and urological cancers from the aspects of ferroptosis, epigenetic alterations, proteostasis, mitochondrial dysfunction, and cellular senescence.

2.
Zhongguo Zhen Jiu ; 42(4): 473-80, 2022 Apr 12.
Artigo em Chinês | MEDLINE | ID: mdl-35403413

RESUMO

OBJECTIVE: To rank the effectiveness of various moxibustion methods on the quality of life in tumor patients, and explore the best treatment plan of moxibustion for improving the quality of life in tumor patients from the perspective of evidence-based medicine. METHODS: The Chinese and English literature of randomized controlled trial (RCT) of the effect of moxibustion on the quality of life in tumor patients were searched in PubMed, EMbase, Cochrane Library, CNKI, SinoMed, Wanfang and VIP. The retrieval time was from the establishment of the databases to October 31, 2020. The R3.6.2 and Stata15.0 software were used for network Meta-analysis based on Bayesian model. RESULTS: A total of 30 Chinese RCTs were included, including 2 169 patients, involving 16 interventions. In terms of the effectiveness of improving quality of life, the top three treatments were special moxibustion plus other therapies 1 (either of tendon acupuncture, acupoint pressing, acupoint injection, etc.), wheat-grain moxibustion and mild moxibustion. The special moxibustion methods were the combination of fire-dragon moxibustion, thunder-fire moxibustion, fuyang fire moxibustion and moxa salt-bag moxibustion. The number of literature of these four moxibustion methods was small. Considering the clinical application of moxibustion, it was concluded that wheat-grain moxibustion ranked first. CONCLUSION: The adjuvant treatment of wheat-grain moxibustion is more effective than other moxibustion methods on improving the quality of life in tumor patients, but the results needed to be further verified because the bias risk of RCT included in this study is high and the sample size is small.


Assuntos
Terapia por Acupuntura , Moxibustão , Neoplasias , Humanos , Moxibustão/métodos , Neoplasias/terapia , Metanálise em Rede , Qualidade de Vida , Ensaios Clínicos Controlados Aleatórios como Assunto
3.
J Hazard Mater ; 435: 128979, 2022 Apr 20.
Artigo em Inglês | MEDLINE | ID: mdl-35472544

RESUMO

Identification of air toxics emitted from light-duty gasoline vehicles (LDGVs) is expected to better protect human health. Here, the volatile organic compound (VOC) and intermediate VOC (IVOC) emissions in the high-emitted start stages were measured on a chassis dynamometer under normal and extreme temperatures for China 6 LDGVs. Low temperature enhanced the emission rates (ERs) of both VOCs and IVOCs. The VOC ERs were averaged 5.19 ± 2.74 times higher when the temperature dropped from 23 °C to 0 °C, and IVOCs were less sensitive to temperature change with an enlargement of 2.27 ± 0.19 times. Aromatics (46.75 ± 2.83%) and alkanes (18.46 ± 1.21%) dominated the cold start VOC emissions under normal temperature, which was quite different from hot running emission profiles. From the perspective of emission inventories, changes in the speciated composition of VOCs and IVOCs were less important than that in the actual magnitude of ERs under cold conditions. However, changes in the ERs and emission profiles were equally important at high temperatures. Furthermore, high time-resolved measurements revealed that low temperature enhanced both the emission peak and peak duration of fuel components and incomplete combustion products during cold start, while high temperature only increased the peak concentration of fuel components.

4.
Front Oncol ; 12: 854253, 2022.
Artigo em Inglês | MEDLINE | ID: mdl-35433428

RESUMO

For uveal melanoma (UM) patients, it is significant to establish diagnosis and prognosis evaluation systems through imaging techniques. However, imaging examinations are short of quantitative biomarkers and it is difficult to finish early diagnosis of UM. In order to discover new molecular biomarkers for the diagnosis and prognostic evaluation of UM, six circulating miRNAs (mir-132-3p, mir-21-5p, mir-34a-5p, mir-126-3p, mir-199a-3p, mir-214-3p) were chosen as candidates for independent validation. Validation of these miRNAs was performed in a cohort of 20 patients, including 10 spindle-shaped melanoma and 10 epithelioid cell melanoma, and 10 healthy donors. Then 5 patients with metastatic UM were included to validate the performance of miRNAs in advanced UM. Serum levels of miRNAs were determined using quantitative real-time PCR. We confirmed significantly higher levels of three miRNAs in serum of UM patients in comparison to healthy controls, and miR-199a-3p had the best performance (p < 0.0001; AUC = 0.985). MiR-214-3p and miR-21-5p were significantly upregulated in serum of epithelioid cell melanoma patients compared to spindle-shaped melanoma patients and miR-132-3p and, conversely, were significantly downregulated in serum of epithelioid cell melanoma patients. MiR-21-5p shows their best performance (p < 0.0001; AUC = 0.980). Both miR-199a-3p and miR-21-5p showed great performance in advanced UM. Significantly higher levels of miR-21-5p (p < 0.001) were found in serum of metastatic UM patients compared to patients with localized spindle-shaped melanoma, and significantly higher levels of miR-199a-3p (p < 0.001) were detected in serum of metastatic UM patients compared to healthy controls. Our preliminary data indicate promising diagnostic utility of circulating miR-199a-3p and promising prognostic utility of circulating miR-21-5p in both early and advanced UM patients.

5.
Front Oncol ; 12: 858479, 2022.
Artigo em Inglês | MEDLINE | ID: mdl-35463369

RESUMO

Background: Given the age relevance of prostate cancer (PCa) and the role of mitochondrial dysfunction (MIDS) in aging, we orchestrated molecular subtypes and identified key genes for PCa from the perspective of MIDS. Methods: Cluster analysis, COX regression analysis, function analysis, and tumor immune environment were conducted. We performed all analyses using software R 3.6.3 and its suitable packages. Results: CXCL14, SFRP4, and CD38 were eventually identified to classify the PCa patients in The Cancer Genome Atlas (TCGA) database and the Gene Expression Omnibus (GEO) dataset into two distinct clusters. Patients in the cluster 2 had shorter BCR-free survival than those in the cluster 1 in terms of both TCGA database and GEO dataset. We divided the patients from the TCGA database and the GEO dataset into high- and low-risk groups according to the median of MIDS-related genetic prognostic index. For patients in the TCGA database, the biochemical recurrence (BCR) risk in high-risk group was 2.34 times higher than that in low-risk group. Similarly, for patients in the GEO dataset, the risk of BCR and metastasis in high-risk group was 2.35 and 3.04 times higher than that in low-risk group, respectively. Cluster 2 was closely associated with advanced T stage and higher Gleason score for patients undergoing radical prostatectomy or radiotherapy. For patients undergoing radical prostatectomy, the number of CD8+ T cells was significantly lower in cluster 2 than in cluster 1, while cluster 2 had significantly higher stromal score than cluster 1. For patients undergoing radical radiotherapy, cluster 2 had significantly higher level of CD8+ T cells, neutrophils, macrophages, dendritic cells, stromal score, immune score, and estimate score, but showed lower level of tumor purity than cluster 1. Conclusions: We proposed distinctly prognosis-related molecular subtypes at genetic level and related formula for PCa patients undergoing radical prostatectomy or radiotherapy, mainly to provide a roadmap for precision medicine.

6.
J Infect Dis ; 2022 Apr 16.
Artigo em Inglês | MEDLINE | ID: mdl-35429399

RESUMO

INTRODUCTION: This study aims to examine the worldwide prevalence of post COVID-19 condition, through a systematic review and meta-analysis. METHODS: PubMed, Embase, and iSearch were searched on July 5, 2021 with verification extending to March 13, 2022. Using a random effects framework with DerSimonian-Laird estimator, we meta-analyzed post COVID-19 condition prevalence at 28+ days from infection. RESULTS: 50 studies were included, and 41 were meta-analyzed. Global estimated pooled prevalence of post COVID-19 condition was 0.43 (95% CI: 0.39,0.46). Hospitalized and non-hospitalized patients have estimates of 0.54 (95% CI: 0.44,0.63) and 0.34 (95% CI: 0.25,0.46), respectively. Regional prevalence estimates were Asia- 0.51 (95% CI: 0.37,0.65), Europe- 0.44 (95% CI: 0.32,0.56), and North America- 0.31 (95% CI: 0.21,0.43). Global prevalence for 30, 60, 90, and 120 days after infection were estimated to be 0.37 (95% CI: 0.26,0.49), 0.25 (95% CI: 0.15,0.38), 0.32 (95% CI: 0.14,0.57) and 0.49 (95% CI: 0.40,0.59), respectively. Fatigue was the most common symptom reported with a prevalence of 0.23 (95% CI: 0.17,0.30), followed by memory problems (0.14 [95% CI: 0.10,0.19]). DISCUSSION: This study finds post COVID-19 condition prevalence is substantial; the health effects of COVID-19 appear to be prolonged and can exert stress on the healthcare system.

7.
Aquat Toxicol ; 246: 106153, 2022 May.
Artigo em Inglês | MEDLINE | ID: mdl-35381412

RESUMO

Overuse of acetochlor pollutes soil and rivers, causing threats to the ecosystem. Studies found that acetochlor exposure could damage multiple organs and tissues in fish and mammal. Tea polyphenols (TP), a natural antioxidant that extracted from tea, has been widely used in food and feed additions. However, the mechanism by which acetochlor causes tissue damage is unclear, and its mitigating agent has yet to be developed. Therefore, we established acetochlor exposure and TP mitigation models by treating Ctenopharyngodon idellus kidney (CIK) cells with 20 µM acetochlor and/or 2.5 µg/mL TP for 24 h, and detected the programmed cell death and its related pathways. The results showed that acetochlor exposure modified antioxidant enzyme activities, induced oxidative stress, resulted in the decline of MMP and ATP levels, enhanced glycolysis and lactate accumulation, and triggered apoptosis and necroptosis in CIK cells. However, TP could inhibit CYP450s expression, activate Nrf2 pathway, enhance antioxidant capacity, further effectively alleviate acetochlor-induced CIK cell death. Overall, the present study proved that acetochlor exposure triggered mitochondrial damage and lactate accumulation-mediated apoptosis and necroptosis through CYP450s/ROS/MAPK/NF-κB pathway. Furthermore, TP could alleviate effectively cell death through relieving oxidative stress and lightening Warburg-like effect.


Assuntos
Carpas , Poluentes Químicos da Água , Animais , Antioxidantes/metabolismo , Antioxidantes/farmacologia , Apoptose , Carpas/metabolismo , Ecossistema , Rim , Ácido Láctico/metabolismo , Mamíferos/metabolismo , NF-kappa B/metabolismo , Necroptose , Estresse Oxidativo , Polifenóis/farmacologia , Espécies Reativas de Oxigênio/metabolismo , Chá/metabolismo , Toluidinas , Poluentes Químicos da Água/toxicidade
8.
BMC Ophthalmol ; 22(1): 193, 2022 Apr 27.
Artigo em Inglês | MEDLINE | ID: mdl-35477375

RESUMO

BACKGROUND: To examine an effect of intravitreally applied antibodies against epidermal growth factor family members, namely epiregulin, epigen and betacellulin, on ocular axial elongation. METHODS: The experimental study included 30 guinea pigs (age:3-4 weeks) which underwent bilateral lens-induced myopization and received three intraocular injections of 20 µg of epiregulin antibody, epigen antibody and betacellulin antibody in weekly intervals into their right eyes, and of phosphate-buffered saline into their left eyes. Seven days after the last injection, the animals were sacrificed. Axial length was measured by sonographic biometry. RESULTS: At baseline, right eyes and left eyes did not differ (all P > 0.10) in axial length in neither group, nor did the interocular difference in axial length vary between the groups (P = 0.19). During the study period, right and left eyes elongated (P < 0.001) from 8.08 ± 0.07 mm to 8.59 ± 0.06 mm and from 8.08 ± 0.07 mm to 8.66 ± 0.07 mm, respectively. The interocular difference (left eye minus right eye) in axial elongation increased significantly in all three groups (epiregulin-antibody:from 0.03 ± 0.06 mm at one week after baseline to 0.16 ± 0.08 mm at three weeks after baseline;P = 0.001); epigen-antibody group:from -0.01 ± 0.06 mm to 0.06 ± 0.08 mm;P = 0.02; betacellulin antibody group:from -0.05 ± 0.05 mm to 0.02 ± 0.04 mm;P = 0.004). Correspondingly, interocular difference in axial length increased from -0.02 ± 0.04 mm to 0.13 ± 0.06 mm in the epiregulin-antibody group (P < 0.001), and from 0.01 ± 0.05 mm to 0.07 ± 0.05 mm in the epigen-antibody group (P = 0.045). In the betacellulin-antibody group the increase (0.01 ± 0.04 mm to 0.03 ± 0.03 mm) was not significant (P = 0.24). CONCLUSIONS: The EGF family members epiregulin, epigen and betacellulin may be associated with axial elongation in young guinea pigs, with the effect decreasing from epiregulin to epigen and to betacellulin.


Assuntos
Cristalino , Animais , Betacelulina , Epigen , Epirregulina , Olho , Cobaias , Humanos
9.
Artigo em Inglês | MEDLINE | ID: mdl-35405358

RESUMO

BACKGROUND: The blocking function of allergen-specific F(ab')2 [sF(ab')2] and Fab (sFab) fragment antibodies prepared from allergen immunotherapy-induced specific immunoglobulin G (sIgG) has not been fully investigated. OBJECTIVE: To investigate the inhibitory function of sIgG, sF(ab')2, and sFab antibodies in patients undergoing Dermatophagoides pteronyssinus (Der-p) subcutaneous immunotherapy (SCIT). METHODS: This study involved 10 subjects (aged 18-42 years) with house dust mite allergic rhinitis or asthma who received a 156-week course of Der-p SCIT. Total IgG levels were purified from the serum of the participants at weeks 0 and 156 by protein A affinity chromatography. Der-p sIgG was purified by affinity chromatography with Der-p as a ligand at week 156. The sF(ab')2 and sFab antibodies were prepared from Der-p sIgG by treatment with pepsin and papain, respectively. Furthermore, IgE-facilitated allergen binding assay, basophil activation inhibition test, and cytokine release inhibition assay were used to assess the inhibitory function of Der-p sIgG, sF(ab')2, and sFab antibodies. RESULTS: We found that the Der-p sIgG, sF(ab')2, and sFab antibodies markedly blocked Der-p-allergen sIgE complex binding to B cells, inhibited basophil activation, and markedly reduced the production of interleukin (IL)-5, IL-13, IL-17, and tumor necrosis factor-α by peripheral blood mononuclear cells. CONCLUSION: SCIT-induced Der-p sIgG, sF(ab')2, and sFab antibodies may block the formation of Der-p-sIgE complexes and may serve as a potential allergen-targeted biologics candidate for the treatment of allergic asthma. CLINICAL TRIAL REGISTRATION: This study was approved by the Ethics Committee of the First Affiliated Hospital of Guangzhou Medical University and registered in the Chinese Clinical Trial Registry (ChiCTR-OOC-15006207, https://www.chictr.org.cn/enindex.aspx).

10.
Chin Med ; 17(1): 50, 2022 Apr 26.
Artigo em Inglês | MEDLINE | ID: mdl-35473719

RESUMO

BACKGROUND: Rhei Radix et Rhizoma (rhubarb), as one of the typical representatives of multi-effect traditional Chinese medicines (TCMs), has been utilized in the treatment of various diseases due to its multicomponent nature. However, there are few systematic investigations for the corresponding effect of individual components in rhubarb. Hence, we aimed to develop a novel strategy to fuzzily identify bioactive components for different efficacies of rhubarb by the back propagation (BP) neural network association analysis of ultra-performance liquid chromatography/quadrupole time-of-flight mass spectrometry for every data (UPLC-Q-TOF/MSE) and integrated effects. METHODS: Through applying the fuzzy chemical identification, most components of rhubarb were classified into different chemical groups. Meanwhile the integration effect values of different efficacies can be determined by animal experiment evaluation and multi-attribute comprehensive indexes. Then the BP neural network was employed for association analysis of components and different efficacies by correlating the component contents determined from UPLC-Q-TOF/MSE profiling and the integration effect values. Finally, the effect contribution of one type of components may be totaled to demonstrate the universal and individual characters for different efficacies of rhubarb. RESULTS: It suggested that combined anthraquinones, flavanols and their polymers may be the universal character to the multi-functional properties of rhubarb. Other components contributed to the individuality of rhubarb efficacies, including stilbene glycosides, anthranones and their dimers, free anthraquinones, chromones, gallic acid and gallotannins, butyrylbenzenes and their glycosides. CONCLUSIONS: Our findings demonstrated that the bioactive components for different efficacies of rhubarb were not exactly the same and can be systematically differentiated by the network-oriented strategy. These efforts will advance our knowledge and understanding of the bioactive components in rhubarb and provide scientific evidence to support the expansion of its use in clinical applications and the further development of some products based on this medicinal herb.

11.
Immunology ; 2022 Mar 10.
Artigo em Inglês | MEDLINE | ID: mdl-35271752

RESUMO

We developed an immune-related gene prognostic index (IGPI) associated with progression and provided new insights into the tumour immune microenvironment (TIME) for prostate cancer (PCA) patients undergoing radical prostatectomy. All analyses were conducted with R software (version 3.6.3) and its suitable packages. Meta-analysis was performed with STATA 16.0. TUBB3, WDR62 and PPARGC1A were finally identified to establish the IGPI score. The IGPI score increased with the augment of the Gleason score and T stage, as well as biochemical recurrence (BCR) and prostate specific antigen (PSA). Patients with a higher IGPI score were at a higher risk of progress (HR: 2·88; 95%CI: 95%CI: 1·80-4·61). Gene set enrichment analysis indicated that patients in high-risk group were positively associated with mismatch repair, cell cycle, DNA replication, base excision repair, nucleotide excision repair, homologous recombination and pyrimidine metabolism. We observed that patients in the high-risk group had significantly higher tumour mutation burden score and microsatellite instability score than those in the low-risk group. For analysis of immune checkpoint, ADORA2A, CD80, TNFRSF4, TNFRSF18 and TNFRSF25 were differentially expressed between no progress and progress groups and were significantly associated with progress free survival. We observed positive correlations between the IGPI score and lymphoid immune cells, macrophages M2 and immune score, while negative association between the IGPI score and dendritic cells, fibroblasts, stromal score and microenvironment score. In conclusion, the IGPI score constructed in this study might serve as an independent risk factor associated with PCA progression. ADORA2A, CD80, TNFRSF4, TNFRSF18 and TNFRSF25 might be the potential targets in the treatment of PCA.

12.
Front Immunol ; 13: 839362, 2022.
Artigo em Inglês | MEDLINE | ID: mdl-35280985

RESUMO

Background: We aimed to construct and validate an energy metabolism-related gene prognostic index (EMRGPI) to predict biochemical recurrence (BCR) in patients undergoing radical prostatectomy. Methods: We used Lasso and COX regression analysis to orchestrate the EMRGPI in the TCGA database, and the prognostic value of EMRGPI was further validated externally using the GSE46602. All analyses were conducted with R version 3.6.3 and its suitable packages. Results: SDC1 and ADH1B were finally used to construct the risk formula. We classified the 430 tumor patients in the TCGA database into two groups, and patients in the high-risk group had a higher risk of BCR than those in the low-risk group (HR: 1.98, 95%CI: 1.18-3.32, p=0.01). Moreover, in the GSE46602, we confirmed that the BCR risk in the high-risk group was 3.86 times higher than that in the low-risk group (95%CI: 1.61-9.24, p=0.001). We found that patients in the high-risk group had significantly higher proportions of residual tumor, older age, and T stage. SDC1 and ADH1B were significantly expressed low in the normal tissues when compared to the tumor tissues, which were opposite at the protein level. The spearman analysis showed that EMRGPI was significantly associated with B cells, CD4+ T cells, CD8+ T cells, neutrophils, macrophages, dendritic cells, stromal score, immune score, and estimate score. In addition, the EMRGPI was positively associated with the 54 immune checkpoints, among which CD80, ADORA2A, CD160, and TNFRSF25 were significantly related to the BCR-free survival of PCa patients undergoing RP. Conclusions: The EMRGPI established in this study might serve as an independent risk factor for PCa patients undergoing radical prostatectomy.


Assuntos
Antígeno Prostático Específico , Neoplasias da Próstata , Metabolismo Energético , Humanos , Masculino , Recidiva Local de Neoplasia/genética , Recidiva Local de Neoplasia/patologia , Prognóstico , Antígeno Prostático Específico/metabolismo , Prostatectomia , Neoplasias da Próstata/genética , Neoplasias da Próstata/metabolismo , Neoplasias da Próstata/cirurgia
13.
Bioengineered ; 13(4): 8538-8547, 2022 04.
Artigo em Inglês | MEDLINE | ID: mdl-35331081

RESUMO

This study aimed to investigate the roles of the lysine (K)-specific demethylase 5C (KDM5C)-bone morphogenetic protein-7 (BMP-7) signaling pathway in the pathogenesis of severe preeclampsia (sPE). A total of 180 pregnant patients were enrolled in the study and classified into three groups: an early-onset sPE group (EOsPE) (n = 60), a late-onset sPE group (LOsPE) (n = 60), and a control group (normal pregnancy; n = 60). The messenger RNA (mRNA) and protein expression levels of bone morphogenetic protein receptor II (BMPRII), BMP-7, and KDM5C were detected in placenta samples from the two sPE groups, and their sites were evaluated using immunohistochemistry (IHC). The sPE groups showed an increased KDM5C mRNA expression, and the EOsPE group showed a decreased BMP-7 and BMPRII mRNA expression compared with the LOsPE group. However, contradictory results were discovered in terms of protein expression. Immunostaining of KDM5C, BMP-7, and BMPRII was observed in villous trophoblast and extravillous trophoblast cells. Compared with the control group, the staining intensity of KDM5C in the placental tissue trophoblast cell nucleus and vascular endothelial cells of the sPE groups was weaker, while that of BMP-7 and BMPRII was stronger, and the staining intensity was more subjective in the LOsPE group. Consistent findings were obtained by IHC and Western blot analysis. KDM5C nuclear-cytoplasmic translocation may regulate sPE through BMP-7 and its receptors. The KDM5C-BMP-7 signaling pathway may also lead to less invasion and increased apoptosis of the trophoblast cells, which is involved in the pathogenesis of sPE.


Assuntos
Proteína Morfogenética Óssea 7 , Receptores de Proteínas Morfogenéticas Ósseas Tipo II , Histona Desmetilases , Pré-Eclâmpsia , Proteína Morfogenética Óssea 7/genética , Receptores de Proteínas Morfogenéticas Ósseas Tipo II/genética , Células Endoteliais/metabolismo , Feminino , Histona Desmetilases/genética , Humanos , Incidência , Lisina , Placenta/metabolismo , Pré-Eclâmpsia/genética , Gravidez , RNA Mensageiro/genética
14.
Sci Rep ; 12(1): 4982, 2022 03 23.
Artigo em Inglês | MEDLINE | ID: mdl-35322094

RESUMO

Although cyanide's biological effects are pleiotropic, its most obvious effects are as a metabolic poison. Cyanide potently inhibits cytochrome c oxidase and potentially other metabolic enzymes, thereby unleashing a cascade of metabolic perturbations that are believed to cause lethality. From systematic screens of human metabolites using a zebrafish model of cyanide toxicity, we have identified the TCA-derived small molecule glyoxylate as a potential cyanide countermeasure. Following cyanide exposure, treatment with glyoxylate in both mammalian and non-mammalian animal models confers resistance to cyanide toxicity with greater efficacy and faster kinetics than known cyanide scavengers. Glyoxylate-mediated cyanide resistance is accompanied by rapid pyruvate consumption without an accompanying increase in lactate concentration. Lactate dehydrogenase is required for this effect which distinguishes the mechanism of glyoxylate rescue as distinct from countermeasures based solely on chemical cyanide scavenging. Our metabolic data together support the hypothesis that glyoxylate confers survival at least in part by reversing the cyanide-induced redox imbalances in the cytosol and mitochondria. The data presented herein represent the identification of a potential cyanide countermeasure operating through a novel mechanism of metabolic modulation.


Assuntos
Glioxilatos , Peixe-Zebra , Animais , Cianetos/toxicidade , Mamíferos , Ácido Pirúvico
15.
Biofactors ; 2022 Mar 14.
Artigo em Inglês | MEDLINE | ID: mdl-35286732

RESUMO

Cadmium (Cd), a common toxic heavy metal, is believed as a risk factor for the induction and progression of cardiovascular disease. Autophagy is a highly ordered intracellular lysosomal-mediated degradation pathway that is crucial for protein and organelle quality control. Autophagy dysfunction could develop exacerbated cardiac dysfunction. However, the role of autophagy in Cd exposure-induced cardiotoxicity remains largely unknown. In this study, the Cd-induced swine cardiotoxicity model was established by feeding with a CdCl2 suppled diet (20 mg Cd/kg diet). The results showed that Cd exposure increased the expression of endoplasmic reticulum stress-related genes (GRP78, GRP94, IRE1, XBP1, PERK, ATF4, and ATF6), increased the expression of Ca2+ release channels IP3R and RYR1 and decreased the expression of Ca2+ uptake pump SERCA1. Cd exposure upregulated the expression of autophagy-related genes (CAMKKII, AMPK, ATG5, ATG7, ATG12, Beclin1, LC3-II, and P62) and downregulated mTOR expression. Cd exposure inhibited the expression of V-ATPase and cathepsins (CTSB and CTSD), and increased the expression of cathepsins in cytoplasm. Cd exposure decreased the colocalization of autophagosome and lysosome. This study revealed that autophagy flux inhibition caused by lysosomal dysfunction participates in the cardiotoxicity induced by Cd exposure in swine.

16.
ArXiv ; 2022 Mar 23.
Artigo em Inglês | MEDLINE | ID: mdl-35350548

RESUMO

The test-negative design (TND) has become a standard approach to evaluate vaccine effectiveness against the risk of acquiring infectious diseases in real-world settings, such as Influenza, Rotavirus, Dengue fever, and more recently COVID-19. In a TND study, individuals who experience symptoms and seek care are recruited and tested for the infectious disease which defines cases and controls. Despite TND's potential to reduce unobserved differences in healthcare seeking behavior (HSB) between vaccinated and unvaccinated subjects, it remains subject to various potential biases. First, residual confounding bias may remain due to unobserved HSB, occupation as healthcare worker, or previous infection history. Second, because selection into the TND sample is a common consequence of infection and HSB, collider stratification bias may exist when conditioning the analysis on testing, which further induces confounding by latent HSB. In this paper, we present a novel approach to identify and estimate vaccine effectiveness in the target population by carefully leveraging a pair of negative control exposure and outcome variables to account for potential hidden bias in TND studies. We illustrate our proposed method with extensive simulation and an application to study COVID-19 vaccine effectiveness using data from the University of Michigan Health System.

17.
Biol Trace Elem Res ; 2022 Feb 03.
Artigo em Inglês | MEDLINE | ID: mdl-35118606

RESUMO

Cadmium (Cd) is a type of toxic substance, which widely exists in nature. However, the effect of Cd exposure on the toxicity of swine lungs and its underlying mechanism involved have not yet been reported. In our study, we divided swine into two groups, including a control group (C group) and Cd-exposed group. Swine in the C group were fed a basic diet, whereas swine in the Cd group were fed a 20 mg Cd/kg diet. Immunofluorescence, qRT-PCR, western blot analysis, and H&E staining were performed to detect necroptosis-related indicators. Our results found that after Cd exposure, Th1/Th2 imbalance occurred, miR-181-5p was down-regulated, TNF-α expression was increased, and the NF-κB/NLRP3 and JAK/STAT pathways and RIPK1/RIPK3/MLKL axis were activated. Furthermore, histopathological examination showed necrosis in swine lung after Cd exposure. Together, the above-mentioned results indicate that subacute Cd exposure is closely linked with necroptosis in swine lung. Our study provided evidence that Cd may act through miR-181-5p/TNF-α to induce necroptosis in swine lung. The findings of this study supplement the toxicological study of Cd and provide a reference for comparative medicine.

18.
Oxf Med Case Reports ; 2022(2): omac002, 2022 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-35198225

RESUMO

Diagnosis of an acute abdomen during an episode of diabetic ketoacidosis (DKA) is crucial for providing appropriate treatments and obtaining favourable outcomes, but may be difficult due to its considerable overlap with multiple intra-abdominal diseases in terms of clinical course and laboratory findings. In this study, we presented a case showing signs of an acute abdomen with sharp rises in serum pancreatic biochemical markers during the treatment of DKA with pyelonephritis. Contrast-enhanced computed tomography (CT) was performed to confirm the onset of acute pancreatitis; however, pneumatosis intestinalis and poor enhancement of the rectal wall were detected, indicating the presence of rectal infarction. Hartmann's procedure was immediately performed, and histological examination of the resected specimen revealed gangrenous ischaemic colitis. The present case highlights DKA as a risk factor of ischaemic colitis and the role of contrast-enhanced CT in the differential diagnosis of an acute abdomen in hyperglycaemic crisis.

19.
Front Immunol ; 13: 777724, 2022.
Artigo em Inglês | MEDLINE | ID: mdl-35154101

RESUMO

Background: Currently, the impact of the circadian rhythm on the tumorigenesis and progression of prostate cancer (PCA) has yet to be understood. In this study, we first established a novel nomogram to predict PCA progression based on circadian clock (CIC)-related genes and provided insights into the tumor immune microenvironment. Methods: The TCGA and Genecards databases were used to identify potential candidate genes. Lasso and Cox regression analyses were applied to develop a CIC-related gene signature. The tumor immune microenvironment was evaluated through appropriate statistical methods and the GSCALite database. Results: Ten genes were identified to construct a gene signature to predict progression probability for patients with PCA. Patients with high-risk scores were more prone to progress than those with low-risk scores (hazard ratio (HR): 4.11, 95% CI: 2.66-6.37; risk score cut-off: 1.194). CLOCK, PER (1, 2, 3), CRY2, NPAS2, RORA, and ARNTL showed a higher correlation with anti-oncogenes, while CSNK1D and CSNK1E presented a greater relationship with oncogenes. Overall, patients with higher risk scores showed lower mRNA expression of PER1, PER2, and CRY2 and higher expression of CSNK1E. In general, tumor samples presented higher infiltration levels of macrophages, T cells and myeloid dendritic cells than normal samples. In addition, tumor samples had higher immune scores, lower stroma scores and lower microenvironment scores than normal samples. Notably, patients with higher risk scores were associated with significantly lower levels of neutrophils, NK cells, T helper type 1, and mast cells. There was a positive correlation between the risk score and the tumor mutation burden (TMB) score, and patients with higher TMB scores were more prone to progress than those with lower TMB scores. Likewise, we observed similar results regarding the correlation between the microsatellite instability (MSI) score and the risk score and the impact of the MSI score on the progression-free interval. We observed that anti-oncogenes presented a significantly positive correlation with PD-L1, PD-L2, TIGIT and SIGLEC15, especially PD-L2. Conclusion: We identified ten prognosis-related genes as a promising tool for risk stratification in PCA patients from the fresh perspective of CIC.


Assuntos
Relógios Circadianos/genética , Nomogramas , Neoplasias da Próstata/genética , Neoplasias da Próstata/imunologia , Transcriptoma , Microambiente Tumoral/imunologia , Biomarcadores Tumorais/genética , Ritmo Circadiano/genética , Ritmo Circadiano/fisiologia , Perfilação da Expressão Gênica , Regulação Neoplásica da Expressão Gênica , Humanos , Masculino , Oncogenes , Prognóstico , Neoplasias da Próstata/fisiopatologia , Fatores de Risco
20.
J Am Heart Assoc ; 11(4): e024169, 2022 02 15.
Artigo em Inglês | MEDLINE | ID: mdl-35156416

RESUMO

Background Despite good evidence that the prevalence of sleep-disordered breathing (SDB) is increasing in the general population, no data are available about trends in poststroke SDB. We therefore sought to assess changes in poststroke SDB over a 10-year period (2010-2019). Methods and Results Participants in the BASIC (Brain Attack Surveillance in Corpus Christi) project were offered a home sleep apnea test to assess for SDB after stroke. SDB assessment procedures remained unchanged throughout the study period. Respiratory event index was calculated as the sum of apneas and hypopneas per hour of recording. SDB was defined as respiratory event index ≥10/h for optimal sensitivity and specificity of the home sleep apnea test device compared with in-laboratory polysomnography. Regression models were used to test associations between SDB prevalence and severity and time, with adjustment for multiple potential confounders. Among the 1215 participants who completed objective sleep apnea testing, the prevalence of SDB grew from 61% in the first year of the study to 76% in the last, with 1.1 times higher odds each year (95% CI, 1.07-1.19), after adjustment. A linear association was identified between time and respiratory event index (average annual respiratory event index increase of 0.56/h; 95% CI, 0.20/h-0.91/h), after adjustment. There was no difference in time trends by sex or ethnicity. Conclusions The prevalence and severity of SDB after ischemic stroke has increased over the past 10 years in this population-based cohort. These data highlight the need to determine whether SDB treatment improves stroke outcomes.


Assuntos
Isquemia Encefálica , AVC Isquêmico , Síndromes da Apneia do Sono , Acidente Vascular Cerebral , Isquemia Encefálica/complicações , Isquemia Encefálica/diagnóstico , Isquemia Encefálica/epidemiologia , Humanos , AVC Isquêmico/diagnóstico , AVC Isquêmico/epidemiologia , Polissonografia/métodos , Síndromes da Apneia do Sono/diagnóstico , Síndromes da Apneia do Sono/epidemiologia , Acidente Vascular Cerebral/complicações , Acidente Vascular Cerebral/diagnóstico , Acidente Vascular Cerebral/epidemiologia
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