Genetic studies are traditionally based on single-gene analysis. The use of these analyses can pose tremendous challenges for elucidating complicated genetic interplays involved in complex human diseases. Modern pathway-based analysis provides a technique, which allows a comprehensive understanding of the molecular mechanisms underlying complex diseases. Extensive studies utilizing the methods and applications for pathway-based analysis have significantly advanced our capacity to explore large-scale omics data, which has rapidly accumulated in biomedical fields. This article is a comprehensive review of the pathway-based analysis methods—the powerful methods with the potential to uncover the biological depths of the complex diseases. The general concepts and procedures for the pathway-based analysis methods are introduced and then, a comprehensive review of the major approaches for this analysis is presented. In addition, a list of available pathway-based analysis software and databases is provided. Finally, future directions and challenges for the methodological development and applications of pathway-based analysis techniques are discussed. This review will provide a useful guide to dissect complex diseases.
Purpose Idiopathic pulmonary fibrosis (IPF) is a chronic, progressive fibrotic lung disease of unknown cause with a variable course. Acute exacerbations of IPF (AE-IPF) is sudden accelerations of the disease or a superimposed idiopathic acute injury significantly reducing lung function. To examine the serum concentrations of Progranulin (PGRN) and activin A in patients with AE-IPF in a pilot study. Methods Twenty-one patients with AE-IPF were compared with 23 patients with stable IPF as a control group. Serum PGRN and activin A levels, arterial blood gas measurements, and lung function were determined in these two groups. Results Peripheral blood PGRN and activin A levels in patients with AE-IPF were 83.7 + 10.0 and 14.2 ± 1.7 ng/ml (mean + SD), respectively; higher than those in the control group 61.0 + 5.8 and 5.8 + 1.0 (p < 0.001). PGRN and activin A levels were significantly negatively correlated with carbon monoxide diffusion capacity r = − 0.857 (p < 0.001) and r = − 0.757 (p < 0.001). Conclusion Progranulin (PGRN) and activin A may be involved in the pathogenesis of AE-IPF. They may be possible markers of disease activity in AE-IPF.
Based on the complexity of cognitive-related influences and the specificity of Chinese liquor culture, this study aimed to explore the associations and potential interactions between demographic characteristics, alcohol consumption, life and atmospheric environment, and cognitive function in seniors through a comprehensive analysis, in order to provide evidence support and feasible recommendations. The study sample was selected from the Chinese Longitudinal Healthy Longevity Survey, which included 40,583 seniors aged 65-115 years. Data analysis and processing were performed by R 4.0.4. The relationship between the factors and cognition was modeled and analyzed by generalized additive model, and the interaction was explored by combining the ANOVA. The generalized additive model confirmed that alcohol consumption was detrimental to the cognitive status of older adults, especially for liquor (≥ 38°) and beer. The higher the average daily alcohol consumption, the greater the impairment. SO 2 and PM 2.5 showed the same negative effects. In contrast, life environment factors such as good education, balanced diet, and positive activity participation had a positive effect on cognition in seniors. In addition, interactions between alcohol consumption and average daily alcohol consumption, frequency of vegetable and meat intake, and between open-air activities, and air pollution were also confirmed. Poor lifestyle choices such as alcohol consumption, unbalanced diet, lower activity participation, and air pollution deteriorate cognitive function in seniors. It is recommended that the elderly population should avoid alcohol consumption, maintain a balanced diet, and be physically active. Attention should also be paid to the effects of air quality.
Background In the context of increasing global aging, the long-term effects of alcohol consumption on cognitive function in older adults were analyzed in order to provide rationalized health recommendations to the elderly population. Methods The study used the Chinese Longitudinal Healthy Longevity Survey (CLHLS) dataset, from which 5354 Chinese seniors aged 65–112 years were selected as the subjects, spanning the years 1998–2018. Data on alcohol, diet, activity, and cognition were collected by questionnaire and cognitive levels were judged by the Mini-Mental State Examination scale (also referenced to the Functional Assessment Staging Test). Data cleaning and preprocessing was implemented by R software. The dynamic Cox model was applied for model construction and data analysis. Results The results of the dynamic Cox model suggested that seniors who drank alcohol were at higher risk of cognitive decline compared to those who never drank (HR = 1.291, 95%CI: 1.175–1.419). The risk was similarly exacerbated by perennial drinking habits (i.e., longer drinking years, HR = 1.008, 95%CI: 1.004–1.013). Compared to non-alcoholic beverages, liquor (≥ 38°), liquor (< 38°), wine and rice wine all showed negative effects. Whereas, the risk of cognitive decline was relatively lower in seniors who consumed liquors (< 38°) and rice wine compared to the high-level liquor (HR: 0.672 (0.508, 0.887) and 0.732 (0.559, 0.957), respectively). Conclusions Alcohol consumption has a negative and long-term effects on cognitive function in seniors. For the elderly, we suggested that alcohol intake should be avoided as much as possible.
Wetlands are the most biologically diverse ecosystems on Earth. The isolation of Streptomyces strains from wetlands is helpful to study their diversity and functions in such habitats. In this study, six strains of Streptomyces were isolated from the rhizosphere soil of three plant species in Huaxi Wetland of Guiyang and were identified as Streptomyces galilaeus, S. avidinii, S. albogriseolus, S. hydrogenans, S. spororaveus, and S. cellulosae, respectively. The six strains all solubilized phosphate, fixed nitrogen, and produced ACC deaminase and siderophores, and four strains also secreted indole-3-acetic acid. The six strains grew well in the ranges of 0%–3% NaCl, 0%–25% PEG, and pH 5.0–10.0, which showed that the screened strains were tolerant to certain degrees of salinity, drought, and acidic/alkaline pH stress. In addition, the S. avidinii WL3 and S. cellulosae WL9 strains (especially the former) significantly promoted seed germination of mung bean, pepper, and cucumber. A pot experiment further showed that WL3 significantly promoted the growth of cucumber seedlings compared with that of the control, with plant height, root length, lateral root number, and fresh weight increased by 104.99%, 49.99%, 94.12%, and 82.86%, respectively. Thus, strains of six species of Streptomyces with multiple plant growth-promoting characteristics were isolated from the wetland. These results lay a foundation for their potential use as microbial agents and seed-coating treatments.
Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) has becoming globally public health threat. Recently studies were focus on SARS-CoV-2 RNA to design vaccine and drugs. It was demonstrated that virus RNA could play as sponge to host noncoding RNAs to regulate cellular processes. Bioinformatic research predicted a series of motif on SARS-CoV-2 genome where are targets of human miRNAs. In this study, we used dual-luciferase reporter assays to validate the interaction between 3’UTR of SARS-CoV-2 S (S-3’UTR) gene and bioinformatic predicted targeting miRNAs. The growth of 293T cells and HUVECs with overexpressed S-3’UTR was determined, while miRNAs and IL6, TNF-α levels were checked in this condition. Then, miR-296 and miR-602 mimic were introduced into 293T cells and HUVECs with overexpressed S-3’UTR, respectively, to reveal the underlying regulation mechanism. In results, we screened 19 miRNAs targeting the S-3’UTR, including miR-296 and miR-602. In 293T cell, S-3’UTR could inhibit 293T cell growth through down-regulation of miR-296. By reducing miR-602, S-3’UTR could induce HUVECs cell proliferation, alter the cell cycle, reduce apoptosis, and enhanced IL6 and TNF-αlevel. In conclusion, SARS-CoV-2 RNA could play as sponge of host miRNA to disturb cell growth and cytokine signaling. It suggests an important clue for designing COVID-19 drug and vaccine.
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