Two untargeted metabolomics reveals yogurt-associated metabolic alterations in women with multiple metabolic disorders from a randomized controlled study.
Journal of proteomics. 2022;:104394
The beneficial role of yogurt on metabolic profile has been widely reported. Yet, few studies have intended to describe the integrated metabolic alterations in response to yogurt. Yogurt and milk (220 g/d) were given to 48 and 44 obese women with metabolic syndrome and nonalcoholic fatty liver disease for 24 weeks in a randomized controlled trial (registered at http://www.chictr.org.cn as ChiCTR-IPR-15006801). Fasting serum samples were collected before and after intervention for global, untargeted metabolomics based on 1H nuclear magnetic resonance (NMR) and ultra-high-performance liquid chromatography coupled with electrospray ionization time-of-flight mass spectrometry (UPLC-Q-TOF-MS) (in positive and negative ion modes). Multivariable statistical analysis and pathway analysis were conducted. In both 1H NMR and UPLC-Q-TOF-MS metabolomics, no clustering was observed between the two groups at baseline. While, a clear clustering was shown after intervention, and the yogurt group had significantly different metabolic status from the milk. The metabolites that contributed mostly to class separation were identified, and involved into pathway analysis. Pathways on amino acids metabolism, fatty acid oxidation, cholesterol catabolism and choline metabolism significantly changed after yogurt intervention. The study revealed the integrated metabolic alterations in response to yogurt via two metabolomics approaches, suggesting the potential mechanisms of yogurt against metabolic disorders. TRIAL REGISTRATION Chinese Clinical Trial Registry, ChiCTR-IPR-15006801. Registered 20 July 2015, http://www.chictr.org.cn/ ChiCTR-IPR-15006801. SIGNIFICANCE Both review from prospective studies and our randomized clinical trial showed the protective role of yogurt against multiple metabolic disorders. However, they were focus on targeted glucose, lipid, and other metabolic indicators, which were only part of human metabolism, failing to show an integrated metabolic feature on yogurt. Therefore, two global, untargeted metabolomics were applied in our current randomized clinical trial, trying to uncover the significant metabolic alterations characterizing the effects of yogurt on obese women with multiple metabolic disorders, and to explore the potential biological mechanisms of yogurt. The finding will shed light on a more comprehensive picture of how yogurt affects host metabolism, and provide theoretical foundation for dietary prevention of chronic diseases.
Different Phenotypes Represent Advancing Stages of ABCA4-Associated Retinopathy: A Longitudinal Study of 212 Chinese Families From a Tertiary Center.
Investigative ophthalmology & visual science. 2022;(5):28
Purpose: To evaluate the nature and association of different phenotypes associated with ABCA4 mutations in Chinese. Methods: All patients were recruited from our pediatric and genetic eye clinic. Detailed ocular phenotypes were characterized. The disease course was evaluated by long-term follow-up observation, with a focus on fundus changes. Cox regression was used to identify the factors associated with disease progression. Results: A systematic review of genetic and clinical data for 228 patients and follow-up data for 42 patients indicated specific features in patients with two ABCA4 variants. Of 185 patients with available fundus images, 107 (57.8%) showed focal lesions restricted to the central macula without flecks. Among these 107 patients, 30 patients (28.0%) initially presented with relatively preserved visual acuity and inconspicuous performance on routine fundus screening. A pigmentary change in the posterior pole was observed in 22 of 185 patients (11.9%), and this change mimicked retinitis pigmentosa in 10 cases (45.5%). Follow-up visits and sibling comparisons demonstrated disease progression from cone-rod dystrophy, Stargardt disease, to retinitis pigmentosa. An earlier age of onset was associated with a more rapid decrease in visual acuity (P = 0.03). Patients with two truncation variants had an earlier age of onset. Conclusion: Phenotypic variation in ABCA4-associated retinopathy may represent sequential changes in a single disease: early-stage Stargardt disease may resemble cone-rod dystrophy, whereas the presence of diffuse pigmentation in the late stage may mimic retinitis pigmentosa. Recognizing the natural progression of fundus changes, especially those visualized by wide-field fundus autofluorescence, is valuable for diagnostics and therapeutic decision-making.
Identification of all-against-all protein-protein interactions based on deep hash learning.
BMC bioinformatics. 2022;(1):266
BACKGROUND Protein-protein interaction (PPI) is vital for life processes, disease treatment, and drug discovery. The computational prediction of PPI is relatively inexpensive and efficient when compared to traditional wet-lab experiments. Given a new protein, one may wish to find whether the protein has any PPI relationship with other existing proteins. Current computational PPI prediction methods usually compare the new protein to existing proteins one by one in a pairwise manner. This is time consuming. RESULTS In this work, we propose a more efficient model, called deep hash learning protein-and-protein interaction (DHL-PPI), to predict all-against-all PPI relationships in a database of proteins. First, DHL-PPI encodes a protein sequence into a binary hash code based on deep features extracted from the protein sequences using deep learning techniques. This encoding scheme enables us to turn the PPI discrimination problem into a much simpler searching problem. The binary hash code for a protein sequence can be regarded as a number. Thus, in the pre-screening stage of DHL-PPI, the string matching problem of comparing a protein sequence against a database with M proteins can be transformed into a much more simpler problem: to find a number inside a sorted array of length M. This pre-screening process narrows down the search to a much smaller set of candidate proteins for further confirmation. As a final step, DHL-PPI uses the Hamming distance to verify the final PPI relationship. CONCLUSIONS The experimental results confirmed that DHL-PPI is feasible and effective. Using a dataset with strictly negative PPI examples of four species, DHL-PPI is shown to be superior or competitive when compared to the other state-of-the-art methods in terms of precision, recall or F1 score. Furthermore, in the prediction stage, the proposed DHL-PPI reduced the time complexity from [Formula: see text] to [Formula: see text] for performing an all-against-all PPI prediction for a database with M proteins. With the proposed approach, a protein database can be preprocessed and stored for later search using the proposed encoding scheme. This can provide a more efficient way to cope with the rapidly increasing volume of protein datasets.
Protective effect of Glutaredoxin 1 against oxidative stress in lens epithelial cells of age-related nuclear cataracts.
Molecular vision. 2022;:70-82
Purpose: Glutaredoxin 1 (Grx1) is a key antioxidant protein that catalyzes disulfide redox reactions. In this study, we investigated the expression and protective effect of Grx1 against oxidative stress in nuclear cataracts. Methods: Human anterior capsule membrane samples were obtained from the eyes of cataract patients (experimental group) and non-cataractous (control group) donors. The levels of Grx1 protein and mRNA expression were investigated. The human lens epithelial (HLE) cell line SRA 01/04 was transfected with Grx1-containing plasmid or Grx1 small interfering RNA, and cultured under H2O2 treatment, mimicking oxidative stress conditions. Cell counts, clone formation, cell apoptosis, cell cycle, and levels of oxidized glutathione disulfide and cellular reactive oxygen species (ROS) were evaluated and quantified. Results: Protein and mRNA transcript levels of Grx1 were significantly lower in the human anterior capsule membrane of the age-related nuclear (ARN) cataract group than in the control group. Grx1 overexpression protected HLE cells from H2O2-induced oxidative damage, including alleviating G1 phase arrest, promoting cell proliferation, reducing cell apoptosis, and decreasing intracellular ROS generation. Furthermore, extracellular-signal-regulated kinase (ERK) phosphorylation in the human anterior capsule membrane of ARN patients was higher in the experimental group than in the control group. Grx1 overexpression reduced the levels of oxidized glutathione disulfide and the phosphorylation of ERK. The administration of an ERK phosphorylation inhibitor, PD98059, induced antioxidant effects in Grx1-silenced cells. Conclusions: Grx1 expression is downregulated in the human anterior capsule membrane of ARN patients, accompanied by an increase in ERK phosphorylation. Thus, Grx1 can protect HLE cells against oxidative stress.
Bioinformatics for plant and agricultural discoveries in the age of multiomics: A review and case study of maize nodal root growth under water deficit.
Physiologia plantarum. 2022;(2):e13672
Advances in next-generation sequencing and other high-throughput technologies have facilitated multiomics research, such as genomics, epigenomics, transcriptomics, proteomics, metabolomics, and phenomics. The resultant emerging multiomics data have brought new challenges as well as opportunities, as seen in the plant and agriculture science domains. We reviewed several bioinformatic and computational methods, models, and platforms, and we have highlighted some of our in-house developed efforts aimed at multiomics data analysis, integration, and management issues faced by the research community. A case study using multiomics datasets generated from our studies of maize nodal root growth under water deficit stress demonstrates the power of these datasets and some other publicly available tools. This analysis also sheds light on the landscape of such applied bioinformatic tools currently available for plant and crop science studies and introduces emerging trends and how they may affect the future.
Effects of vitamin C stimulation on rehabilitation of dysphagia after stroke: a randomized trial.
European journal of physical and rehabilitation medicine. 2022;(4):558-564
BACKGROUND Stroke is a clinical syndrome of localized or global brain dysfunction caused by cerebrovascular disease. AIM: The aim of this study was to explore the effect of vitamin C acid stimulation on the rehabilitation process, Nourishment State Index and immune function indicators of stroke patients with dysphagia. DESIGN This is a prospective cohort study. SETTING This study was conducted at our hospital. POPULATION We analyzed stroke patients with dysphagia. METHODS A total of 120 stroke patients with dysphagia were randomly divided into a routine group and a test group, with 60 cases in each group. Routine swallowing training was performed in the routine group, and the test group was stimulated with vitamin C acid. The water swallow test (WST) and video fluoroscopic swallowing study (VFSS) were used to compare the rehabilitation of dysphagia in the two groups. Nourishment State Index was evaluated by BMI, serum albumin, total serum protein and hemoglobin. Immune Function Index was evaluated by IgA, IgM and IgG. RESULTS Compared with the control group, the WST level of patients treated with vitamin C acid stimulation intervention were significantly reduced, and the VFSS score were significantly increased. Serum levels of hemoglobin, albumin, total protein, IgA, IgM and IgG in the vitamin C acid stimulation group were remarkably increased than those in the control group. CONCLUSIONS Vitamin C acid stimulation exhibits a good application effect in patients with dysphagia after stroke. Moreover, vitamin C acid stimulation can further improve the nutritional status and immune function after stroke and promote postoperative recovery of patients. Therefore, we believe that vitamin C stimulation therapy can be widely used in stroke rehabilitation management. CLINICAL REHABILITATION IMPACT Vitamin C acid stimulation significantly improves rehabilitation of stroke patients with dysphagia and ameliorates the nutritional status and immune function of patients.
Amino Acids in Rice Grains and Their Regulation by Polyamines and Phytohormones.
Plants (Basel, Switzerland). 2022;(12)
Rice is one of the most important food crops in the world, and amino acids in rice grains are major nutrition sources for the people in countries where rice is the staple food. Phytohormones and plant growth regulators play vital roles in regulating the biosynthesis of amino acids in plants. This paper reviewed the content and compositions of amino acids and their distribution in different parts of ripe rice grains, and the biosynthesis and metabolism of amino acids and their regulation by polyamines (PAs) and phytohormones in filling grains, with a focus on the roles of higher PAs (spermidine and spermine), ethylene, and brassinosteroids (BRs) in this regulation. Recent studies have shown that higher PAs and BRs (24-epibrassinolide and 28-homobrassinolide) play positive roles in mediating the biosynthesis of amino acids in rice grains, mainly by enhancing the activities of the enzymes involved in amino acid biosynthesis and sucrose-to-starch conversion and maintaining redox homeostasis. In contrast, ethylene may impede amino acid biosynthesis by inhibiting the activities of the enzymes involved in amino acid biosynthesis and elevating reactive oxygen species. Further research is needed to unravel the temporal and spatial distribution characteristics of the content and compositions of amino acids in the filling grain and their relationship with the content and compositions of amino acids in different parts of a ripe grain, to elucidate the cross-talk between or among phytohormones in mediating the anabolism of amino acids, and to establish the regulation techniques for promoting the biosynthesis of amino acids in rice grains.
Copper-induced tumor cell death mechanisms and antitumor theragnostic applications of copper complexes.
Nanomedicine (London, England). 2022;(5):303-324
Recent studies found that unbalanced copper homeostasis affect tumor growth, causing irreversible damage. Copper can induce multiple forms of cell death, including apoptosis and autophagy, through various mechanisms, including reactive oxygen species accumulation, proteasome inhibition, and antiangiogenesis. Hence, copper in vivo has attracted tremendous attention and is in the research spotlight in the field of tumor treatment. This review first highlights three typical forms of copper's antitumor mechanisms. Then, the development of diverse biomaterials and nanotechnology allowing copper to be fabricated into diverse structures to realize its theragnostic action is discussed. Novel copper complexes and their clinical applications are subsequently described.
Accumulation and Enrichment of Trace Elements by Yeast Cells and Their Applications: A Critical Review.
Maintaining the homeostasis balance of trace elements is crucial for the health of organisms. Human health is threatened by diseases caused by a lack of trace elements. Saccharomyces cerevisiae has a wide and close relationship with human daily life and industrial applications. It can not only be used as fermentation products and single-cell proteins, but also as a trace elements supplement that is widely used in food, feed, and medicine. Trace-element-enriched yeast, viz., chromium-, iron-, zinc-, and selenium-enriched yeast, as an impactful microelements supplement, is more efficient, more environmentally friendly, and safer than its inorganic and organic counterparts. Over the last few decades, genetic engineering has been developing large-scaled genetic re-design and reconstruction in yeast. It is hoped that engineered yeast will include a higher concentration of trace elements. In this review, we compare the common supplement forms of several key trace elements. The mechanisms of detoxification and transport of trace elements in yeast are also reviewed thoroughly. Moreover, genes involved in the transport and detoxification of trace elements are summarized. A feasible way of metabolic engineering transformation of S. cerevisiae to produce trace-element-enriched yeast is examined. In addition, the economy, safety, and environmental protection of the engineered yeast are explored, and the future research direction of yeast enriched in trace elements is discussed.
Tumor microenvironment-responsive fenton nanocatalysts for intensified anticancer treatment.
Journal of nanobiotechnology. 2022;(1):69
Chemodynamic therapy (CDT) based on Fenton or Fenton-like reactions is an emerging cancer treatment that can both effectively fight cancer and reduce side effects on normal cells and tissues, and it has made important progress in cancer treatment. The catalytic efficiency of Fenton nanocatalysts(F-NCs) directly determines the anticancer effect of CDT. To learn more about this new type of therapy, this review summarizes the recent development of F-NCs that are responsive to tumor microenvironment (TME), and detailedly introduces their material design and action mechanism. Based on the deficiencies of them, some effective strategies to significantly improve the anticancer efficacy of F-NCs are highlighted, which mainly includes increasing the temperature and hydrogen peroxide concentration, reducing the pH, glutathione (GSH) content, and the dependence of F-NCs on acidic environment in the TME. It also discusses the differences between the effect of multi-mode therapy with external energy (light and ultrasound) and the single-mode therapy of CDT. Finally, the challenges encountered in the treatment process, the future development direction of F-NCs, and some suggestions are analyzed to promote CDT to enter the clinical stage in the near future.