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1.
Cancer Epidemiol ; 75: 102020, 2021 Sep 09.
Artigo em Inglês | MEDLINE | ID: mdl-34509873

RESUMO

BACKGROUND: The aim of this study was to investigate the relationship between high-risk genotypes of Human Papilloma Virus (HPV) and cancer of different subsites of the oral cavity. MATERIAL AND METHODS: A pooled analysis of five studies included on the International Head and Neck Cancer Epidemiology (INHANCE) Consortium was conducted. HPV 16 and HPV 18 were considered. Adjusted odds ratios (ORs) and corresponding 95 % confidence intervals (CIs) for HPV and each oral cavity subsites were simultaneously estimated using multinomial logistic regression models. RESULTS: The analysis included 1157 cases and 3272 controls. This study showed a slightly higher prevalence of HPV infection among oral cancer cases than controls. In particular, an increased risk of other and not otherwise specified (NOS) sites within the oral cavity, oral tongue, palate and floor of mouth cancer was observed for overall HPV16 positivity (OR = 1.66, 95 % CI: 1.01-2.72; OR = 1.97, 95 % CI: 1.36-2.85; OR = 2.48, 95 % CI: 1.50-4.11; OR = 2.71, 95 % CI: 1.06-6.95, respectively). In particular, HPV16E7 was related to cancer of floor of mouth, oral cavity NOS and palate (OR = 2.71, 95 % CI: 1.06-6.95; OR = 3.32, 95 % CI:1.53-7.19; OR = 3.34, 95 % CI:1.38-8.06). Results were inconsistent for HPV18 due to low prevalence of infection. CONCLUSION: Our study suggests that HPV16 infection may increase the risk of developing floor of mouth, gum, tongue, and palate cancers. CLINICAL RELEVANCE: Subjects with HPV infection have a higher risk of cancer from all sites of the oral cavity.

2.
Ecotoxicol Environ Saf ; 225: 112756, 2021 Sep 08.
Artigo em Inglês | MEDLINE | ID: mdl-34507040

RESUMO

Exposure to melamine, which is ubiquitous in daily life, is linked to adverse kidney outcomes. The melamine tolerable daily intake in humans is based on the no-observed-effect-level (NOEL) established in a single-toxicant murine model. However, humans are often simultaneously exposed to multiple environmental nephrotoxicants. The NOEL of melamine during coexposure with other toxicants needs to be evaluated. Oxalate is a potentially nephrotoxic terminal metabolite, and hyperoxaluria is reportedly associated with chronic kidney disease. We explored whether these two potential nephrotoxicants can interact and enhance kidney injury. We established a Sprague-Dawley rat model of coexposure to the melamine NOEL (63 mg/kg/day) and 2% hydroxy-L-proline (HLP, an oxalate precursor) in drinking water to simulate human environmental melamine exposure. Melamine/oxalate coexposure increased proximal tubular cell mitochondrial reactive oxygen species levels, lipid peroxidation and oxidative DNA damage. The degrees of mitochondrial damage, tubular cell apoptosis, tubular atrophy, and interstitial fibrosis were elevated in coexposed rat kidneys. The evidence indicated that exposure to the melamine NOEL can cause renal tubular injury via oxidative stress and that this effect may be enhanced via interaction of melamine with other environmental factors, such as oxalate. Thus, melamine risk assessment and toxicity prevention should be conducted carefully in different susceptible populations.

3.
Int J Mol Sci ; 22(16)2021 Aug 18.
Artigo em Inglês | MEDLINE | ID: mdl-34445623

RESUMO

Human breast milk lipids have major beneficial effects: they promote infant early brain development, growth and health. To identify the relationship between human breast milk lipids and infant neurodevelopment, multivariate analyses that combined lipidomics and psychological Bayley-III scales evaluation were utilized. We identified that 9,12-octadecadiynoic acid has a significantly positive correlation with infant adaptive behavioral development, which is a crucial neurodevelopment to manage risk from environmental stress. To further clarify the biological function of 9,12-octadecadiynoic acid in regulating neurodevelopment, Caenorhabditis elegans (C. elegans) was used as a model to investigate the effect of 9,12-octadecadiynoic acid on neurobehavioral development. Supplementation with 9,12-octadecadiynoic acid from the L1 to L4 stage in larvae affected locomotive behaviors and foraging ability that were not socially interactive, implying that 9,12-octadecadiynoic acid is involved in regulating the serotonergic neuronal ability. We found that supplementary 0.1 µM 9,12-octadecadiynoic acid accelerated the locomotive ability and foraging ability via increasing the expression of serotonin transporter mod-1. Antioxidant defense genes, sod-1, sod-3 and cyp-35A2 are involved in 9,12-octadecadiynoic acid-induced motor neuronal activity. Nevertheless, supplementary 9,12-octadecadiynoic acid at concentrations above 1 µM significantly attenuated locomotive behaviors, foraging ability, serotonin synthesis, serotonin-related gene expressions and stress-related gene expression, resulting in the decreased longevity of worms in the experiment. In conclusion, our study demonstrates the biological function of 9,12-octadecadiynoic acid in governing adaptive behavioral development.

4.
Artigo em Inglês | MEDLINE | ID: mdl-34360358

RESUMO

Mask usage is an effective measure to prevent severe acute respiratory syndrome coronavirus 2 (SARS-COV-2) infection; however, mask reuse is not recommended. Studies examining the factors associated with mask reuse during the coronavirus disease (COVID-19) pandemic are limited. This nationwide survey aimed to determine the prevalence and factors associated with mask reuse among Taiwanese citizens during the pandemic. From 18 May through 31 May 2020, a computer-assisted telephone interview system was used to randomly select Taiwanese citizens for interview regarding COVID-19-preventive behaviors and knowledge on mask usage. For a total of 1075 participants, the overall mean age was 57.4 years, and 82.2% of participants reported mask reuse during the COVID-19 pandemic. After controlling for other covariates, participants who had a greater knowledge of mask usage or had a high supply of masks were less likely to reuse masks during the pandemic. Moreover, generalized estimating equations (GEE) analysis showed that, compared with the participants' mask-wearing behaviors before the COVID-19 pandemic, they were more likely to reuse masks during the pandemic. Thus, it is imperative to educate people on the correct usage of masks. Furthermore, the government should provide sufficient masks to the general population to reduce mask reuse.


Assuntos
COVID-19 , Pandemias , Humanos , Máscaras , Pessoa de Meia-Idade , Pandemias/prevenção & controle , Prevalência , SARS-CoV-2 , Taiwan/epidemiologia
5.
World J Gastroenterol ; 27(28): 4722-4737, 2021 Jul 28.
Artigo em Inglês | MEDLINE | ID: mdl-34366632

RESUMO

BACKGROUND: Dysbacteriosis may be a crucial environmental factor for ulcerative colitis (UC). Further study is required on microbiota alterations in the gastrointestinal tract of patients with UC for better clinical management and treatment. AIM: To analyze the relationship between different clinical features and the intestinal microbiota, including bacteria and fungi, in Chinese patients with UC. METHODS: Eligible inpatients were enrolled from January 1, 2018 to June 30, 2019, and stool and mucosa samples were collected. UC was diagnosed by endoscopy, pathology, Mayo Score, and Montreal classification. Gene amplicon sequencing of 16S rRNA gene and fungal internal transcribed spacer gene was used to detect the intestinal microbiota composition. Alpha diversity, principal component analysis, similarity analysis, and Metastats analysis were employed to evaluate differences among groups. RESULTS: A total of 89 patients with UC and 33 non-inflammatory bowel disease (IBD) controls were enrolled. For bacterial analysis, 72 stool and 48 mucosa samples were obtained from patients with UC and 21 stool and 12 mucosa samples were obtained from the controls. For fungal analysis, stool samples were obtained from 43 patients with UC and 15 controls. A significant difference existed between the fecal and mucosal bacteria of patients with UC. The α-diversity of intestinal bacteria and the relative abundance of some families, such as Lachnospiraceae and Ruminococcaceae, decreased with the increasing severity of bowel inflammation, while Escherichia-Shigella showed the opposite trend. More intermicrobial correlations in UC in remission than in active patients were observed. The bacteria-fungi correlations became single and uneven in patients with UC. CONCLUSION: The intestinal bacteria flora of patients with UC differs significantly in terms of various sample types and disease activities. The intermicrobial correlations change in patients with UC compared with non-IBD controls.


Assuntos
Colite Ulcerativa , Microbioma Gastrointestinal , China/epidemiologia , Colite Ulcerativa/diagnóstico , Disbiose , Fezes , Humanos , Mucosa Intestinal , RNA Ribossômico 16S/genética
6.
Artigo em Inglês | MEDLINE | ID: mdl-34288878

RESUMO

The goal of supervised hashing is to construct hash mappings from collections of images and semantic annotations such that semantically relevant images are embedded nearby in the learned binary hash representations. Existing deep supervised hashing approaches that employ classification frameworks with a classification training objective for learning hash codes often encode class labels as one-hot or multi-hot vectors. We argue that such label encodings do not well reflect semantic relations among classes and instead, effective class label representations ought to be learned from data, which could provide more discriminative signals for hashing. In this article, we introduce Adaptive Labeling Deep Hashing (AdaLabelHash) that learns binary hash codes based on learnable class label representations. We treat the class labels as the vertices of a K-dimensional hypercube, which are trainable variables and adapted together with network weights during the backward network training procedure. The label representations, referred to as codewords, are the target outputs of hash mapping learning. In the label space, semantically relevant images are then expressed by the codewords that are nearby regarding Hamming distances, yielding compact and discriminative binary hash representations. Furthermore, we find that the learned label representations well reflect semantic relations. Our approach is easy to realize and can simultaneously construct both the label representations and the compact binary embeddings. Quantitative and qualitative evaluations on several popular benchmarks validate the superiority of AdaLabelHash in learning effective binary codes for image search.

7.
Sci Rep ; 11(1): 13805, 2021 Jul 05.
Artigo em Inglês | MEDLINE | ID: mdl-34226613

RESUMO

Imbalances of blood biomarkers are associated with disease, and biomarkers may also vary non-pathologically across population groups. We described variation in concentrations of biomarkers of one-carbon metabolism, vitamin status, inflammation including tryptophan metabolism, and endothelial and renal function among cancer-free older adults. We analyzed 5167 cancer-free controls aged 40-80 years from 20 cohorts in the Lung Cancer Cohort Consortium (LC3). Centralized biochemical analyses of 40 biomarkers in plasma or serum were performed. We fit multivariable linear mixed effects models to quantify variation in standardized biomarker log-concentrations across four factors: age, sex, smoking status, and body mass index (BMI). Differences in most biomarkers across most factors were small, with 93% (186/200) of analyses showing an estimated difference lower than 0.25 standard-deviations, although most were statistically significant due to large sample size. The largest difference was for creatinine by sex, which was - 0.91 standard-deviations lower in women than men (95%CI - 0.98; - 0.84). The largest difference by age was for total cysteine (0.40 standard-deviation increase per 10-year increase, 95%CI 0.36; 0.43), and by BMI was for C-reactive protein (0.38 standard-deviation increase per 5-kg/m2 increase, 95%CI 0.34; 0.41). For 31 of 40 markers, the mean difference between current and never smokers was larger than between former and never smokers. A statistically significant (p < 0.05) association with time since smoking cessation was observed for 8 markers, including C-reactive protein, kynurenine, choline, and total homocysteine. We conclude that most blood biomarkers show small variations across demographic characteristics. Patterns by smoking status point to normalization of multiple physiological processes after smoking cessation.

8.
Artigo em Inglês | MEDLINE | ID: mdl-34236573

RESUMO

PURPOSE: The neutrophil-to-lymphocyte ratio (NLR) is a marker of systemic inflammation that has been reported to be associated with survival after chronic disease diagnoses, including lung cancer. We hypothesized that the inflammatory profile reflected by pre-diagnosis NLR, rather than the well-studied pre-treatment NLR at diagnosis, may be associated with increased mortality after lung cancer is diagnosed in high-risk heavy smokers. METHODS: We examined associations between pre-diagnosis methylation-derived NLR (mdNLR) and lung cancer-specific and all-cause mortality in 279 non-small lung cancer (NSCLC) and 81 small cell lung cancer (SCLC) cases from the ß-Carotene and Retinol Efficacy Trial (CARET). Cox proportional hazards models were adjusted for age, sex, smoking status, pack years, and time between blood draw and diagnosis, and stratified by stage of disease. Models were run separately by histotype. RESULTS: Among SCLC cases, those with pre-diagnosis mdNLR in the highest quartile had 2.5-fold increased mortality compared to those in the lowest quartile. For each unit increase in pre-diagnosis mdNLR, we observed 22-23% increased mortality (SCLC-specific hazard ratio [HR] = 1.23, 95% confidence interval [CI]: 1.02, 1.48; all-cause HR = 1.22, 95% CI 1.01, 1.46). SCLC associations were strongest for current smokers at blood draw (Interaction Ps = 0.03). Increasing mdNLR was not associated with mortality among NSCLC overall, nor within adenocarcinoma (N = 148) or squamous cell carcinoma (N = 115) case groups. CONCLUSION: Our findings suggest that increased mdNLR, representing a systemic inflammatory profile on average 4.5 years before a SCLC diagnosis, may be associated with mortality in heavy smokers who go on to develop SCLC but not NSCLC.

9.
Biomolecules ; 11(7)2021 06 29.
Artigo em Inglês | MEDLINE | ID: mdl-34209859

RESUMO

Cartilage-derived stem/progenitor cells (CSPCs) are a potential choice for seed cells in osteal and chondral regeneration, and the outcomes of their survival and position distribution in vivo form the basis for the investigation of their mechanism. However, the current use of in vivo stem cell tracing techniques in laboratories is relatively limited, owing to their high operating costs and cytotoxicity. Herein, we performed tri-modal in vivo imaging of CSPCs during subcutaneous chondrogenesis using upconversion nanoparticles (UCNPs) for 28 days. Distinctive signals at accurate positions were acquired without signal noise from X-ray computed tomography, magnetic resonance imaging, and upconversion luminescence. The measured intensities were all significantly proportional to the cell numbers, thereby enabling real-time in vivo quantification of the implanted cells. However, limitations of the detectable range of cell numbers were also observed, owing to the imaging shortcomings of UCNPs, which requires further improvement of the nanoparticles. Our study explores the application value of upconversion nanomaterials in the tri-modal monitoring of implanted stem cells and provides new perspectives for future clinical translation.

10.
Nat Commun ; 12(1): 4487, 2021 07 23.
Artigo em Inglês | MEDLINE | ID: mdl-34301922

RESUMO

Testicular germ cell tumors (TGCT) are the most common tumor in young white men and have a high heritability. In this study, the international Testicular Cancer Consortium assemble 10,156 and 179,683 men with and without TGCT, respectively, for a genome-wide association study. This meta-analysis identifies 22 TGCT susceptibility loci, bringing the total to 78, which account for 44% of disease heritability. Men with a polygenic risk score (PRS) in the 95th percentile have a 6.8-fold increased risk of TGCT compared to men with median scores. Among men with independent TGCT risk factors such as cryptorchidism, the PRS may guide screening decisions with the goal of reducing treatment-related complications causing long-term morbidity in survivors. These findings emphasize the interconnected nature of two known pathways that promote TGCT susceptibility: male germ cell development within its somatic niche and regulation of chromosomal division and structure, and implicate an additional biological pathway, mRNA translation.


Assuntos
Predisposição Genética para Doença/genética , Estudo de Associação Genômica Ampla/métodos , Neoplasias Embrionárias de Células Germinativas/genética , Polimorfismo de Nucleotídeo Único , Neoplasias Testiculares/genética , Linhagem Celular Tumoral , Mapeamento Cromossômico , Redes Reguladoras de Genes/genética , Genótipo , Humanos , Desequilíbrio de Ligação , Masculino , Metanálise como Assunto , Neoplasias Embrionárias de Células Germinativas/metabolismo , Mapas de Interação de Proteínas/genética , Neoplasias Testiculares/metabolismo
11.
Cardiovasc Toxicol ; 21(9): 759-771, 2021 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-34120306

RESUMO

Pathological cardiac hypertrophy is the leading cause of heart failure, and miRNAs have been recognized as key factors in cardiac hypertrophy. This study aimed to elucidate whether miR-17-5p affects cardiac hypertrophy by targeting the mitochondrial fusion protein mitofusin 2 (Mfn2)-mediated phosphatidylinositol-3-kinase (PI3K)/AKT/mammalian target of rapamycin (mTOR) pathway and regulating autophagy. miR-17-5p expression was shown to be upregulated both in vivo and in vitro. In addition, a miR-17-5p inhibitor significantly reversed AngII-induced cell hypertrophy in neonatal rat left ventricle myocytes (NRVMs). In contrast to miR-17-5p expression, Mfn2 expression was inhibited in rat hearts at 4 weeks after transverse aortic constriction (TAC) and in an Ang II-induced cell hypertrophy model. We examined miR-17-5p targeting of Mfn2 by dual luciferase reporter and Western blot assays. In addition, we also verified the relationship between Mfn2 and the PI3K/AKT/mTOR pathway. Mfn2 overexpression attenuated miR-17-5p-induced cell hypertrophy, and in rat myocardial tissue, miR-17-5p induced autophagy inhibition. In summary, the results of the present study demonstrated that miR-17-5p inhibits Mfn2 expression, activates the PI3K/AKT/mTOR pathway and suppresses autophagy to promote cardiac hypertrophy.

12.
BMC Neurol ; 21(1): 238, 2021 Jun 24.
Artigo em Inglês | MEDLINE | ID: mdl-34167467

RESUMO

BACKGROUND AND PURPOSE: The purpose of our study was to analyse endovascular treatment (EVT) in patients presenting acute anterior circulation ischemic stroke with large-vessel occlusion (AIS-LVO) during the pandemic and post-epidemic periods. METHODS: Patients with AIS-LVO of the anterior circulation who underwent EVT were enrolled. According to the times of Wuhan closure and reopening, patients were divided into a pre-pandemic group (from November 8, 2019, to January 22, 2020), pandemic group (from January 23, 2020, to April 8, 2020) and post-epidemic group (from April 9, 2020, to June 24, 2020). The primary endpoints were the time delay among symptom onset to arriving hospital door, to groining puncture and to vascular reperfusion. Secondary endpoints were the functional outcomes evaluated by 90-day modified Rankin scale (mRS) score. RESULTS: In total, the times from onset to reperfusion (OTR, median 356 min vs. 310 min, p = 0.041) and onset to door (OTD, median 238 min vs. 167 min, p = 0.017) were prolonged in the pandemic group compared to the pre-pandemic group, and the delay continue in the post-epidemic period. In the subgroup analysis, the time from door to imaging (DTI) was significantly prolonged during the pandemic period. Interestingly, the prolonged DTI was corrected in the directly admitted subgroup during post-epidemic period. In addition, the functional outcomes showed no significant differences across the three periods. CONCLUSIONS: Total time and prehospital time were prolonged during the pandemic and post-epidemic periods. Urgent public education and improved in-hospital screening processes are necessary to decrease time delays.


Assuntos
COVID-19 , Procedimentos Endovasculares/métodos , AVC Isquêmico/terapia , Idoso , Idoso de 80 Anos ou mais , Isquemia Encefálica/terapia , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Reperfusão/métodos , Estudos Retrospectivos , Resultado do Tratamento
13.
Orthop Surg ; 13(5): 1628-1638, 2021 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-34152699

RESUMO

OBJECTIVE: To assess the clinical efficacy and share the technique notes of Wiltse Approach TLIF for the treating single segment degenerative lumbar spinal disease. METHOD: In this retrospective controlled study, 780 patients with single segment degenerative lumbar disease who were operated in our hospital from January 2016 to December 2020 were analyzed retrospectively. The patients were randomly assigned to Wiltse approach group (group A, 410 cases) and conventional open approach group (group B, 370 cases). Patient's assessment of pain and disability were evaluated by the visual analogue scale (VAS) and the Oswestry disability index (ODI) before and after surgery. The incision length, operative time, exposure time, intraoperative blood loss, hidden blood loss, time to ambulation, total length of hospitalization, serum creatine kinase, X-rays, CT and MRI were also evaluated. RESULTS: There were no differences in sex, age, pre-operative ODI score, VAS score between the two groups (P > 0.05). The Wiltse approach group had a shorter incision length with 7.69 ± 0.44 cm compared to the conventional group with 11.13 ± 0.36 cm (P < 0.01). The average operative time was 119.20 ± 14.64 min with exposure time of 16.20 ± 3.42 min in the Wiltse approach group and 145.65 ± 16.98 min with 29.20 ± 3.42 min in the conventional group (P < 0.05, P < 0.01). Comparing the intraoperative blood loss, hidden blood loss, serum creatine kinase, time to ambulation, total length of hospitalization, the Wiltse approach group was less than the conventional open approach group (P < 0.05). The VAS score of the two groups decreased significantly with time, and the VAS score of the Wiltse group was significantly lower than that of the conventional open approach group (P < 0.05). At last investigation after operation, ODI scores of the two groups were significantly decreased compared with that before operation. Wiltse approach group was significantly lower than that of the conventional open approach group (P < 0.05). The multifidus of the two groups of patients had a certain degree of atrophy. But the Wiltse approach group multifidus muscle atrophy rate is significantly lower than the conventional open approach group. CONCLUSION: The Wiltse approach TLIF significantly reduces the damage to the paravertebral muscles and the postoperative incidence of chronic low back pain.

14.
Oncol Rep ; 46(2)2021 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-34165168

RESUMO

MicroRNA (miRNA or miR)­10b is an oncogenic miRNA associated with metastasis that is present in various types of tumor, including lung cancer. However, whether miR­10b is involved in different malignant characteristics, such as drug resistance or stemness, remains unclear. Therefore, the present study investigated whether miR­10b is an upstream regulator of p53. Ectopic expression of miR­10b­agomir decreased the expression of p53 and its downstream effectors, such as Bax and p53 upregulated modulator of apoptosis. Two non­canonical sites, including 1,580­1,587 and 2,029­2,035, located in p53 3'­untranslated region (UTR) were affected by the presence of miR­10b. In functional assays, upregulation of the p53 signaling pathway following cisplatin treatment was associated with decreased levels of miR­10b and upregulation of the luciferase activity of wild­type, but not 1,584, 2,032­dual­mutant, p53 3'­UTR. The ectopic expression of miR­10b­agomir attenuated the stability of p53 3'­UTR and the expression of p53 and its downstream effectors induced by cisplatin. By contrast, the knockdown of miR­10b induced the stability of p53 3'­UTR and increased levels of p53 and the sensitivity of A549 cells to cisplatin treatment. Similar results were also observed for Beas 2B cells. In the clinical investigation, p53 exhibited two distinct associations (cocurrent and countercurrent) with miR­10b in patients with lung cancer. Patients with lung cancer with low p53 and high miR­10b levels exhibited the poorest prognosis, while those with high p53 and low miR­10b exhibited the most favorable prognosis. These findings indicate a novel pathway in which cisplatin induces the levels of p53 by increasing mRNA stability via miR­10b, indicating a novel oncogenic role of miR­10b in promoting the malignant characteristics of non­small cell lung carcinoma.

15.
J Neuroinflammation ; 18(1): 143, 2021 Jun 24.
Artigo em Inglês | MEDLINE | ID: mdl-34162400

RESUMO

BACKGROUND: Hemorrhagic transformation (HT) is a critical issue in thrombolytic therapy in acute ischemic stroke. Damage-associated molecular pattern (DAMP)-stimulated sterile neuroinflammation plays a crucial role in the development of thrombolysis-associated HT. Our previous study showed that the phthalide derivative CD21 attenuated neuroinflammation and brain injury in rodent models of ischemic stroke. The present study explored the effects and underlying mechanism of action of CD21 on tissue plasminogen activator (tPA)-induced HT in a mouse model of transient middle cerebral artery occlusion (tMCAO) and cultured primary microglial cells. METHODS: The tMCAO model was induced by 2 h occlusion of the left middle cerebral artery with polylysine-coated sutures in wildtype (WT) mice and macrophage scavenger receptor 1 knockout (MSR1-/-) mice. At the onset of reperfusion, tPA (10 mg/kg) was intravenously administered within 30 min, followed by an intravenous injection of CD21 (13.79 mg/kg/day). Neuropathological changes were detected in mice 3 days after surgery. The effect of CD21 on phagocytosis of the DAMP peroxiredoxin 1 (Prx1) in lysosomes was observed in cultured primary microglial cells from brain tissues of WT and MSR1-/- mice. RESULTS: Seventy-two hours after brain ischemia, CD21 significantly attenuated neurobehavioral dysfunction and infarct volume. The tPA-infused group exhibited more severe brain dysfunction and hemorrhage. Compared with tPA alone, combined treatment with tPA and CD21 significantly attenuated ischemic brain injury and hemorrhage. Combined treatment significantly decreased Evans blue extravasation, matrix metalloproteinase 9 expression and activity, extracellular Prx1 content, proinflammatory cytokine mRNA levels, glial cells, and Toll-like receptor 4 (TLR4)/nuclear factor κB (NF-κB) pathway activation and increased the expression of tight junction proteins (zonula occludens-1 and claudin-5), V-maf musculoaponeurotic fibrosarcoma oncogene homolog B, and MSR1. MSR1 knockout significantly abolished the protective effect of CD21 against tPA-induced HT in tMCAO mice. Moreover, the CD21-induced phagocytosis of Prx1 was MSR1-dependent in cultured primary microglial cells from WT and MSR1-/- mice, respectively. CONCLUSION: The phthalide derivative CD21 attenuated tPA-induced HT in acute ischemic stroke by promoting MSR1-induced DAMP (Prx1) clearance and inhibition of the TLR4/NF-κB pathway and neuroinflammation.

16.
Environ Int ; 156: 106652, 2021 11.
Artigo em Inglês | MEDLINE | ID: mdl-34034116

RESUMO

Environmental melamine exposure has been associated with deteriorating kidney function in early-stage chronic kidney disease patients. In this study, a benchmark dose (BMD) approach was used to establish melamine exposure threshold in 293 patients with eGFR≥30 ml/min per 1.73 m2. The patients were enrolled 2006-2010 and followed-up for a median of 7.0 years to monitor kidney outcomes. Average daily intakes (AvDI) of melamine were estimated using one-spot urine samples collected at enrollment. BMDs and corresponding one-sided 95% lower bound (BMDLs) were derived using established dose-response models relating estimated AvDIs and dichotomous kidney outcomes: doubling of serum creatine levels, eGFR decreased > 3 ml/min per 1.73 m2 per year, and >30% decline in eGFR during the first 2 years. In addition, survival time to doubling of serum creatinine and eGFR decline over time were assessed as continuous endpoints. Given a benchmark response of 0.10, BMDLs ranged from 0.74 to 2.03 µg/kg_bw/day after Bayesian model averaging, a range one to two orders lower than the current WHO recommended tolerable daily intake of 200 µg/kg_bw/day and the US FDA's 63 µg/kg_bw/day. Our results suggest that early-stage CKD patients should strictly refrain from using melamine tableware and related melamine-made products.


Assuntos
Benchmarking , Insuficiência Renal Crônica , Teorema de Bayes , Humanos , Rim , Triazinas/toxicidade
17.
Am J Clin Nutr ; 114(2): 450-461, 2021 08 02.
Artigo em Inglês | MEDLINE | ID: mdl-33964859

RESUMO

BACKGROUND: Epidemiologic studies examining the relations between dairy product and calcium intakes and breast cancer have been inconclusive, especially for tumor subtypes. OBJECTIVE: To evaluate the associations between intakes of specific dairy products and calcium and risk of breast cancer overall and for subtypes defined by estrogen receptor (ER) status. METHOD: We pooled the individual-level data of over 1 million women who were followed for a maximum of 8-20 years across studies. Associations were evaluated for dairy product and calcium intakes and risk of incident invasive breast cancer overall (n = 37,861 cases) and by subtypes defined by ER status. Study-specific multivariable hazard ratios (HRs) were estimated and then combined using random-effects models. RESULTS: Overall, no clear association was observed between the consumption of specific dairy foods, dietary (from foods only) calcium, and total (from foods and supplements) calcium, and risk of overall breast cancer. Although each dairy product showed a null or very weak inverse association with risk of overall breast cancer (P, test for trend >0.05 for all), differences by ER status were suggested for yogurt and cottage/ricotta cheese with associations observed for ER-negative tumors only (pooled HR = 0.90, 95% CI: 0.83, 0.98 comparing ≥60 g/d with <1 g/d of yogurt and 0.85, 95% CI: 0.76, 0.95 comparing ≥25 g/d with <1 g/d of cottage/ricotta cheese). Dietary calcium intake was only weakly associated with breast cancer risk (pooled HR = 0.98, 95% CI: 0.97, 0.99 per 350 mg/d). CONCLUSION: Our study shows that adult dairy or calcium consumption is unlikely to associate with a higher risk of breast cancer and that higher yogurt and cottage/ricotta cheese intakes were inversely associated with the risk of ER-negative breast cancer, a less hormonally dependent subtype with poor prognosis. Future studies on fermented dairy products, earlier life exposures, ER-negative breast cancer, and different racial/ethnic populations may further elucidate the relation.


Assuntos
Neoplasias da Mama/prevenção & controle , Cálcio/administração & dosagem , Laticínios , Receptores de Estrogênio/metabolismo , Estudos de Coortes , Feminino , Humanos , Análise Multivariada , Receptores de Estrogênio/genética , Fatores de Risco
18.
Mol Neurobiol ; 58(8): 4122-4133, 2021 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-33939165

RESUMO

Alzheimer's disease (AD) is the most common cause of dementia, which affects more than 5 million individuals in the USA. Unfortunately, no effective therapies are currently available to prevent development of AD or to halt progression of the disease. It has been proposed that monoacylglycerol lipase (MAGL), the key enzyme degrading the endocannabinoid 2-arachidonoylglycerol (2-AG) in the brain, is a therapeutic target for AD based on the studies using the APP transgenic models of AD. While inhibition of 2-AG metabolism mitigates ß-amyloid (Aß) neuropathology, it is still not clear whether inactivation of MAGL alleviates tauopathies as accumulation and deposition of intracellular hyperphosphorylated tau protein are the neuropathological hallmark of AD. Here we show that JZL184, a potent MAGL inhibitor, significantly reduced proinflammatory cytokines, astrogliosis, phosphorylated GSK3ß and tau, cleaved caspase-3, and phosphorylated NF-kB while it elevated PPARγ in P301S/PS19 mice, a tau mouse model of AD. Importantly, tau transgenic mice treated with JZL184 displayed improvements in spatial learning and memory retention. In addition, inactivation of MAGL ameliorates deteriorations in expression of synaptic proteins in P301S/PS19 mice. Our results provide further evidence that MAGL is a promising therapeutic target for AD.

19.
Stem Cell Res Ther ; 12(1): 243, 2021 04 15.
Artigo em Inglês | MEDLINE | ID: mdl-33858504

RESUMO

BACKGROUND: The regeneration response of the skin to mechanical stretching in vivo has been explored in reconstructive surgery to repair large-scale deformities. The ability of the skin to regenerate limits the reconstructive outcome. Here, we propose an approach in which autologous stromal vascular fraction (SVF) cells and mechanical stretching are combined to overcome this limitation and promote skin regeneration. METHODS: This randomized, blinded, placebo-controlled clinical trial screened 22 participants undergoing tissue expansion with exhausted regeneration. Twenty eligible participants received intradermal injections of the SVF or placebo treatments. Follow-ups were conducted at 4, 8, and 12 weeks to assess efficacy and at 2 years to assess safety. The primary endpoint was the expanded skin thickness at 12 weeks. The secondary endpoints included skin thickness at 4 and 8 weeks, the expansion index (EI), and the skin texture score at 12 weeks. RESULTS: The skin thickness of the SVF group was significantly higher than that of the control group at both 8 weeks (mean difference 0.78 [95% CI - 1.43 to - 0.11]; p = 0.018) and 12 weeks (0.65 [95% CI - 1.30 to - 0.01]; p = 0.046). In the SVF group, the increase in skin thickness was significant at 4 weeks (0.49 [95% CI - 0.80 to - 0.06]; p = 0.010) to 8 weeks (0.45 [95% CI - 0.92 to 0.02]; p = 0.026) and maintained after 12 weeks, whereas that in the control group was reduced after 8 weeks (0.42 [95% CI - 0.07 to 0.91]; p = 0.037). The SVF group showed greater EI increases than the control group (0.50 [95% CI - 0.00 to 0.99]; p = 0.047). The skin texture scores in the SVF group were greater than those in the control group at 12 weeks. Histologically, SVF-treated expanded skin showed more proliferating cells and blood vessels, and the extracellular matrix volume increased. No severe adverse events occurred. CONCLUSIONS: Transplantation of SVF cells can expedite the potency of mechanical stretch-induced skin regeneration and provide clinical reconstruction with plentiful tissue. TRIAL REGISTRATION: This trial was registered with the Chinese Clinical Trial Registry, ChiCTR2000039317 (registered 23 October 2020-retrospectively registered).


Assuntos
Tecido Adiposo , Células Estromais , Humanos , Pele , Transplante Autólogo
20.
J Mater Chem B ; 9(16): 3450-3483, 2021 04 28.
Artigo em Inglês | MEDLINE | ID: mdl-33909746

RESUMO

Cancer nanomedicine is the best option to face the limits of conventional chemotherapy and phototherapy methods, and thus the intensive quest for new nanomaterials to improve therapeutic efficacy and safety is still underway. Owing to their low density, well-defined structures, large surface area, finely tunable pore size, and metal ion free features, covalent organic frameworks (COFs) have been extensively studied in many research fields. The recent great interest in nanoscale COFs to improve the properties of bulk COFs has led to broadening of their applicability in the biomedical field, such as nanocarriers with an outstanding loading capacity and efficient delivery of therapeutic agents, smart theranostic nanoplatforms with excellent stability, high ROS generation, light-to-heat conversion capabilities, and different response and diagnostic characteristics. The COFs and related nanoplatforms with a wide variety of designability and functionalization have opened up a new avenue for exciting opportunities in cancer therapy. Herein we review the state-of-the-art technical and scientific developments in this emerging field, focusing on the overall progress addressed so far in building versatile COF-based nanoplatforms to enhance chemotherapy, photodynamic/photothermal therapy, and combination. Future perspectives for achieving the synergistic effect of cancer elimination and clinical translation are further discussed to motivate future contributions and explore new possibilities.


Assuntos
Antineoplásicos/uso terapêutico , Estruturas Metalorgânicas/uso terapêutico , Nanopartículas/química , Neoplasias/tratamento farmacológico , Antineoplásicos/química , Humanos , Estruturas Metalorgânicas/química , Fototerapia
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