Esophageal squamous cell carcinoma (ESCC) is one of the dominant malignances worldwide, but currently there is less focus on the microbiota with ESCC and its precancerous lesions.
Paired esophageal ...biopsy and swab specimens were obtained from 236 participants in Linzhou, China. Data from 16S ribosomal RNA gene sequencing were processed using quantitative insights into microbial ecology (QIIME2) and R Studio to evaluate differences. The Wilcoxon rank sum test and Kruskal-Wallis rank sum test were used to compare diversity and characteristic genera by specimens and participant groups. Ordinal logistic regression model was used to build microbiol prediction model.
Microbial diversity was similar between biopsy and swab specimens, including operational taxonomic unit (OTU) numbers and Shannon index. There were variations and similarities of esophageal microbiota among different pathological characteristics of ESCC. Top 10 relative abundance genera in all groups include
,
,
,
,
,
,
,
,
and
. Genus
,
,
and
showed significantly difference in disease groups when compared to normal control, whereas
showed an increasing tendency with the progression of ESCC and others showed a decreasing tendency. About models based on all combinations of characteristic genera, only taken
and
into model, the prediction performance was the ideal one, of which the area under the curve (AUC) was 0.738.
Esophageal biopsy and swab specimens could yield similar microbial characterization. The combination of
and
has the potential to predict the progression of ESCC, which is needed to confirm by large-scale, prospective cohort studies.
•Resveratrol prevented the CUMS-induced behavioral abnormalities.•Resveratrol prevented the elevated serum corticosterone levels in stressed rats.•Resveratrol exhibits antidepressant-like effects via ...ERK–CREB–BDNF pathway.
Depression is one of the most common neuropsychiatric disorders and has been associated with the neuroendocrine system and alterations in specific brain proteins. Resveratrol is a natural polyphenol enriched in polygonum cuspidatum and has diverse biological activities, including potent antidepressant-like effects. The present study attempts to explore the mechanisms underlying the antidepressant-like action of resveratrol by measuring serum corticosterone levels and the content of brain derived neurotrophic factor (BDNF) in the hippocampus and amygdala of rats exposed to the chronic unpredictable mild stress (CUMS). Male Wistar rats were subjected to the CUMS protocol for a period of 5 weeks to induce depressive-like behavior. Resveratrol treatment (20, 40 and 80mg/kg/i.p. 5 weeks) significantly reversed the CUMS-induced behavioral abnormalities (reduced sucrose preference, increased immobility time and decreased locomotor activity) and the elevated serum corticosterone levels observed in stressed rats. Additionally, 5-weeks of CUMS exposure significantly decreased BDNF levels in the hippocampus and amygdala, and was accompanied by decreased phosphorylation of extracellular signal-regulated kinase (pERK) and cAMP response element-binding protein (pCREB), while resveratrol treatment normalized these levels. All of these effects of resveratrol were essentially identical to that observed with the established antidepressant, desipramine. In conclusion, our study shows that resveratrol exerted antidepressant-like effects in CUMS rats, mediated in part by normalizing serum corticosterone levels while up-regulating pERK, pCREB and BDNF levels in the hippocampus and amygdala.
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GEOZS, IJS, IMTLJ, KILJ, KISLJ, NUK, OILJ, PNG, SAZU, SBCE, SBJE, UL, UM, UPCLJ, UPUK
Emerging evidence shows that microRNAs (miRNAs) play important roles in the regulation of various biological and pathologic processes in human cancers and the aberrant expression of miRNAs ...contributes to the tumor development. In this study, our findings indicate that miR-451 is significantly overexpressed in pancreatic cancer tissues and cell lines and elevated expression of miR-451 contributes to promoted cell viability (in vitro and in vivo). Moreover, overexpression of miR-451 is closely linked to poor prognosis and lymphatic metastasis. Inhibition of miR-451 dramatically suppresses cell viability and invasion, promotes cell apoptosis, and induces cell cycle arrest. Furthermore, miR-451 directly targets CAB39 and negatively regulates its expression and inhibition of CAB39 contributes to the promoted cell viability and invasion. Our findings improve our understanding of the function of miR-451 in the identification and therapy of pancreatic cancer.
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DOBA, FZAB, GIS, IJS, IZUM, KILJ, NLZOH, NUK, OILJ, PILJ, PNG, SAZU, SBCE, SBMB, SIK, UILJ, UKNU, UL, UM, UPUK, VSZLJ
Verbascoside (VB), as an active component of multiple medicinal plants, has been proved to exert anti-oxidative, anti-aging and neuroprotective effects. This study was designed to investigate whether ...VB could play a cardioprotective role in septic heart injury.
Mice were injected with lipopolysaccharide (LPS; 10 mg/kg) to induce sepsis. The treatment group received an intraperitoneally injection of VB (20 mg/kg) before LPS challenge. Transthoracic echocardiography, ELISA, immunofluorescence, and qPCR were performed to assess the effect of VB on heart function, oxidative stress, inflammation and apoptosis. Transmission electronic microscopy and immunoblotting were used to evaluate the mitochondrial morphology and biogenesis of the septic heart. In vitro experiments were also performed to repeat above-mentioned assays.
Compared with LPS group, the VB treatment group showed improved cardiac function in sepsis. VB alleviated oxidative stress and inflammatory cell infiltration, as well as cardiomyocyte apoptosis. Specifically, VB could restore sepsis-induced mitochondrial alterations via regulating mitochondrial biogenesis. These results were also confirmed in in vitro experiments.
Verbascoside could protected from sepsis-induced cardiomyopathy by inhibiting oxidative stress, inflammation, and apoptosis, as well as promoting mitochondrial biogenesis.
•Verbascoside improved cardiac function impaired by LPS challenge.•VB alleviated oxidative stress, cardiac inflammation and cell apoptosis.•VB increased cardiac mitophagy and inhibited the activation of NLRP3 inflammasome.
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GEOZS, IJS, IMTLJ, KILJ, KISLJ, NLZOH, NUK, OILJ, PNG, SAZU, SBCE, SBJE, UILJ, UL, UM, UPCLJ, UPUK, ZAGLJ, ZRSKP
Parkinson's disease (PD) is a progressive neurodegenerative motor system disorder. Early diagnosis of PD is important to control the symptoms appropriately. Recent voice and speech recognition ...techniques provide alternative solutions for PD screening. In this paper, an optimal support vector machine (SVM) based on bacterial foraging optimization (BFO) was established to predict PD effectively. The effectiveness of the proposed method, BFO-SVM, was validated on a PD data set based on vocal measurements. The proposed method was compared with two of the most frequently used parameter optimization methods, including an SVM based on the grid search method and an SVM based on particle swarm optimization. Additionally, to further boost the prediction accuracy, the relief feature selection was employed prior to the BFO-SVM method, consequently the RF-BFO-SVM was proposed. The experimental results have demonstrated that the proposed framework exhibited excellent classification performance with a superior classification accuracy of 97.42%.
...this study summarized indicative genera associated with ESCC progression in paired esophageal biopsy and swab specimens, and developed risk stratification models of high-risk populations based on ...microbial factors, epidemiological factors, and actual detection requirements. ...we developed risk stratification models of ESCC and precancerous lesions based on multinomial logistic regression and plotted the receiver operator characteristic (ROC) curve with the area under the curve (AUC). According to the results of the present study, significant differences were observed in age, education level, oral health (gingival bleeding), and dietary habits (drinking water, meat, fried food and scallion, ginger, or garlic) among the normal, esophagitis, LGIN, HGIN, and ESCC groups. ...the highest accuracy of the risk stratification models for each detection requirement were 68.09% (model_1-adding tooth
Detection of extracutaneous melanoma is still challenging and is of importance in improving survival rate. In this report, an ultrasensitive biosensor is constructed where a C‐reactive protein (CRP) ...aptamers based molecular recognition core and a conductive polypyrrole (PPy) nanowire mesh based signal amplifier are developed. The conductive PPy nanowire (less than 10 nm in diameter) mesh architecture is uniformly dispersed within polymeric matrix via template‐free in situ synthesis. Serum CRP levels are quantitatively analyzed through monitoring the conductance change caused by polymeric network shrinkage upon the aptamer‐CRP binding. The limit of detection (LOD) of the polymeric sensor for human CRP sample can reach 7.85 × 10−19m. This CRP‐specific biosensor and a commercial CRP enzyme‐linked immunosorbent assay (ELISA) kit are used to perform side‐by‐side measurement of serum CRP in melanoma patients. The results indicate that this conductive polymeric senor is highly sensitive and selective in accurately discriminating melanoma patients from healthy controls using serum CRP as a biomarker, which is further validated by a commercial human CRP ELISA kit. Collectively, this novel ultrasensitive nanowire‐based polymeric biosensor may hold promise in biomarker detection and diagnosis of cancer.
A novel polymeric biosensor with a C‐reactive protein (CRP) aptamers based molecular recognition core and a conductive polypyrrole (PPy) nanowire‐mesh based signal amplifier is developed. The PPy nanowire (<10 nm in diameter) mesh is dispersed within polymeric matrix via template‐free in situ synthesis. Serum CRP is quantified via monitoring the conductance change induced by polymeric network shrinkage upon CRP binding.
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BFBNIB, FZAB, GIS, IJS, KILJ, NLZOH, NUK, OILJ, SAZU, SBCE, SBMB, UL, UM, UPUK
Family clustering of esophageal cancer (EC) has been found in high-risk areas of China. However, the relationships between cancer family history and esophageal cancer and precancerous lesions (ECPL) ...have not been comprehensively reported in recent years. This study aimed to provide evidence for identification of high-risk populations.
This study was conducted in five high-risk areas in China from 2017 to 2019, based on the National Cohort of Esophageal Cancer. The permanent residents aged 40 to 69 years were examined by endoscopy, and pathological examination was performed for suspicious lesions. Information on demographic characteristics, environmental factors, and cancer family history was collected. Unconditional logistic regression was applied to evaluate odds ratios between family history related factors and ECPL.
Among 33,008 participants, 6143 (18.61%) reported positive family history of EC. The proportion of positive family history varied significantly among high-risk areas. After adjusting for risk factors, participants with a family history of positive cancer, gastric and esophageal cancer or EC had 1.49-fold (95% confidence interval CI: 1.36-1.62), 1.52-fold (95% CI: 1.38-1.67), or 1.66-fold (95% CI: 1.50-1.84) higher risks of ECPL, respectively. Participants with single or multiple first-degree relatives (FDR) of positive EC history had 1.65-fold (95% CI: 1.47-1.84) or 1.93-fold (95% CI: 1.46-2.54) higher risks of ECPL. Participants with FDRs who developed EC before 35, 45, and 50 years of age had 4.05-fold (95% CI: 1.30-12.65), 2.11-fold (95% CI: 1.37-3.25), and 1.91-fold (95% CI: 1.44-2.54) higher risks of ECPL, respectively.
Participants with positive family history of EC had significantly higher risk of ECPL. This risk increased with the number of EC positive FDRs and EC family history of early onset. Distinctive genetic risk factors of the population in high-risk areas of China require further investigation.
ChiCTR-EOC-17010553.
Hutchinson–Gilford progeria syndrome (HGPS) is caused by the accumulation of mutant prelamin A (progerin) in the nuclear lamina, resulting in increased nuclear stiffness and abnormal nuclear ...architecture. Nuclear mechanics are tightly coupled to cytoskeletal mechanics via lamin A/C. However, the role of cytoskeletal/nuclear mechanical properties in mediating cellular senescence and the relationship between cytoskeletal stiffness, nuclear abnormalities, and senescent phenotypes remain largely unknown. Here, using muscle‐derived mesenchymal stromal/stem cells (MSCs) from the Zmpste24−/− (Z24−/−) mouse (a model for HGPS) and human HGPS fibroblasts, we investigated the mechanical mechanism of progerin‐induced cellular senescence, involving the role and interaction of mechanical sensors RhoA and Sun1/2 in regulating F‐actin cytoskeleton stiffness, nuclear blebbing, micronuclei formation, and the innate immune response. We observed that increased cytoskeletal stiffness and RhoA activation in progeria cells were directly coupled with increased nuclear blebbing, Sun2 expression, and micronuclei‐induced cGAS‐Sting activation, part of the innate immune response. Expression of constitutively active RhoA promoted, while the inhibition of RhoA/ROCK reduced cytoskeletal stiffness, Sun2 expression, the innate immune response, and cellular senescence. Silencing of Sun2 expression by siRNA also repressed RhoA activation, cytoskeletal stiffness and cellular senescence. Treatment of Zmpste24−/− mice with a RhoA inhibitor repressed cellular senescence and improved muscle regeneration. These results reveal novel mechanical roles and correlation of cytoskeletal/nuclear stiffness, RhoA, Sun2, and the innate immune response in promoting aging and cellular senescence in HGPS progeria.
There is increased RhoA activation and cytoskeleton stiffness in progeria cells, which mediates increased nuclear blebbing, micronuclei formation, innate immune response, and cellular senescence. RhoA activation is coupled with elevated Sun2 expression, but not Sun1, especially in nucleus with blebbing and micronuclei. Repression of RhoA and Sun2 activation was able to reduce cytoskeleton stiffness, nuclear blebbing, and micronuclei formation and delay the progression of cellular senescence.
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DOBA, FZAB, GIS, IJS, IZUM, KILJ, NLZOH, NUK, OILJ, PILJ, PNG, SAZU, SBCE, SBMB, UILJ, UKNU, UL, UM, UPUK
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