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1.
Microb Pathog ; 189: 106598, 2024 Apr.
Article in English | MEDLINE | ID: mdl-38423403

ABSTRACT

Propionibacterium acnes (P. acnes) is an anaerobic and gram-positive bacterium involved in the pathogenesis and inflammation of acne vulgaris. This study particularly focuses on the antimicrobial effect of Lacticaseibacillus paracasei LPH01 against P. acnes, a bacterium that causes acne vulgaris. Fifty-seven Lactobacillus strains were tested for their ability to inhibit P. acnes growth employing the Oxford Cup and double dilution methods. The cell-free supernatant (CFS) of L. paracasei LPH01 demonstrated a strong inhibitory effect, with an inhibition zone diameter of 24.65 ± 0.27 mm and a minimum inhibitory concentration of 12.5 mg/mL. Among the CFS, the fraction over 10 kDa (CFS-10) revealed the best antibacterial effect. Confocal laser scanning microscopes and flow cytometry showed that CFS-10 could reduce cell metabolic activity and cell viability and destroy the integrity and permeability of the cell membrane. A scanning electron microscope revealed that bacterial cells exhibited obvious morphological and ultrastructural changes, which further confirmed the damage of CFS-10 to the cell membrane and cell wall. Findings demonstrated that CFS-10 inhibited the conversion of triglycerides, decreased the production of free fatty acids, and down-regulated the extracellular expression of the lipase gene. This study provides a theoretical basis for the metabolite of L. paracasei LPH01 as a potential antibiotic alternative in cosmeceutical skincare products.


Subject(s)
Acne Vulgaris , Lacticaseibacillus paracasei , Humans , Propionibacterium acnes , Anti-Bacterial Agents/pharmacology , Anti-Bacterial Agents/therapeutic use , Acne Vulgaris/drug therapy , Acne Vulgaris/microbiology , Inflammation/drug therapy , Microbial Sensitivity Tests
2.
J Gastroenterol Hepatol ; 39(10): 2228-2238, 2024 Oct.
Article in English | MEDLINE | ID: mdl-38972728

ABSTRACT

BACKGROUND AND AIM: There is a pressing need for non-invasive preoperative prediction of microvascular invasion (MVI) in hepatocellular carcinoma (HCC). This study investigates the potential of exosome-derived mRNA in plasma as a biomarker for diagnosing MVI. METHODS: Patients with suspected HCC undergoing hepatectomy were prospectively recruited for preoperative peripheral blood collection. Exosomal RNA profiling was conducted using RNA sequencing in the discovery cohort, followed by differential expression analysis to identify candidate targets. We employed multiplexed droplet digital PCR technology to efficiently validate them in a larger sample size cohort. RESULTS: A total of 131 HCC patients were ultimately enrolled, with 37 in the discovery cohort and 94 in the validation cohort. In the validation cohort, the expression levels of RSAD2, PRPSAP1, and HOXA2 were slightly elevated while CHMP4A showed a slight decrease in patients with MVI compared with those without MVI. These trends were consistent with the findings in the discovery cohort, although they did not reach statistical significance (P > 0.05). Notably, the expression level of exosomal PRPSAP1 in plasma was significantly higher in patients with more than 5 MVI than in those without MVI (0.147 vs 0.070, P = 0.035). CONCLUSION: This study unveils the potential of exosome-derived PRPSAP1 in plasma as a promising indicator for predicting MVI status preoperatively.


Subject(s)
Biomarkers, Tumor , Carcinoma, Hepatocellular , Exosomes , Liver Neoplasms , Neoplasm Invasiveness , RNA, Messenger , Humans , Carcinoma, Hepatocellular/blood , Carcinoma, Hepatocellular/genetics , Carcinoma, Hepatocellular/pathology , Carcinoma, Hepatocellular/surgery , Liver Neoplasms/blood , Liver Neoplasms/genetics , Liver Neoplasms/pathology , Liver Neoplasms/surgery , Exosomes/genetics , Male , Female , Middle Aged , Biomarkers, Tumor/blood , RNA, Messenger/blood , Microvessels/pathology , Aged , Predictive Value of Tests , Prospective Studies , Hepatectomy
3.
J Sci Food Agric ; 104(10): 6233-6241, 2024 Aug 15.
Article in English | MEDLINE | ID: mdl-38451122

ABSTRACT

BACKGROUND: Zha cai, a pickled vegetable with unique flavors, is produced by fermenting fresh mustard tubers. In this study, the main physicochemical indices and volatile flavor compounds were determined in three fermentation periods. The bacterial and fungal communities in the three fermentation periods of zha cai were also monitored using high-throughput sequencing. Key microbial communities were identified based on significant correlations with flavor substances. RESULTS: Firmicutes and Proteobacteria were the main bacterial phyla found within the three fermentation periods. Lactic acid bacteria, namely Lactobacillus, was the predominant bacteria found at the genus level. Ascomycetes and Stenotrophomonas were the major fungal phyla found in the three fermentation periods. Yeast, namely Debaryomyces, was the predominant fungus found at the genus level. A total of 42 bacterial genera were negatively correlated with volatile flavor substances of zha cai, and 37 bacterial genera were positively correlated. Meanwhile, a total of 47 genera of fungi were negatively correlated with the volatile flavor substances of zha cai, while 50 genera were positively correlated. Several microbial genera were significantly correlated with volatile flavor compounds, including Lactobacillus, Halomonas, Rhodococcus, and Debaryomyces. CONCLUSION: This study identified the microbial classes that positively regulate the flavor of zha cai which could provide valuable help for flavor modulation in zha cai production. © 2024 Society of Chemical Industry.


Subject(s)
Bacteria , Fermentation , Flavoring Agents , Fungi , Microbiota , Volatile Organic Compounds , Bacteria/classification , Bacteria/genetics , Bacteria/metabolism , Bacteria/isolation & purification , Flavoring Agents/metabolism , Flavoring Agents/chemistry , Volatile Organic Compounds/metabolism , Volatile Organic Compounds/chemistry , Volatile Organic Compounds/analysis , Fungi/metabolism , Fungi/classification , Fungi/genetics , Fungi/isolation & purification , Mustard Plant/microbiology , Mustard Plant/chemistry , Mustard Plant/metabolism , Taste
4.
Crit Rev Food Sci Nutr ; : 1-23, 2023 Jun 21.
Article in English | MEDLINE | ID: mdl-37341655

ABSTRACT

Edible insect products contain high-quality protein and other nutrients, including minerals and fatty acids. The consumption of insect food products is considered a future trend and a potential strategy that could greatly contribute to meeting food needs worldwide. However, insect proteins have the potential to be allergenic to insect consumers. In this review, the nutritional value and allergy risk of insect-derived foods, and the immune responses elicited by insect allergens are summarized and discussed. Tropomyosin and arginine kinase are the most important and widely known insect allergens, which induce Th2-biased immune responses and reduced the activity of CD4+T regulatory cells. Besides, food processing methods have been effectively improving the nutrients and characteristics of insect products. However, limited reviews systematically address the immune reactions to allergens present in edible insect proteins following treatment with food processing technologies. The conventional/novel food processing techniques and recent advances in reducing the allergenicity of insect proteins are discussed in this review, focusing on the structural changes of allergens and immune regulation.

5.
Crit Rev Food Sci Nutr ; 63(27): 8768-8780, 2023.
Article in English | MEDLINE | ID: mdl-35400262

ABSTRACT

Allergic diseases, derived from the dysregulation of immune tolerance mechanisms, have been rising in the last two decades. Recently, increasing evidence has shown that probiotic-derived polysaccharide capsules exhibit a protective effect against allergic diseases, involving regulation of Th1/Th2 balance, induction of differentiation of T regulatory cells and activation of dendritic cells (DCs). DCs have a central role in controlling the immune response through their interaction with gut microbiota via their pattern recognition receptors, including Toll-like receptors and C-type-lectin receptors. This review discusses the effects and critical mechanism of probiotic-derived polysaccharide capsules in regulating the immune system to alleviate allergic diseases. We first describe the development of immune response in allergic diseases and recent relevant findings. Particular emphasis is placed on the effects of probiotic-derived polysaccharide capsules on allergic immune response. Then, we discuss the underlying mechanism of the impact of probiotic-derived polysaccharide capsules on DCs-mediated immune tolerance induction.


Subject(s)
Hypersensitivity , Probiotics , Humans , Dendritic Cells , Immunity , Polysaccharides/pharmacology
6.
Crit Rev Food Sci Nutr ; : 1-16, 2023 Feb 19.
Article in English | MEDLINE | ID: mdl-36803092

ABSTRACT

Host health and disease are influenced by changes in the abundance and structure of intestinal flora. Current strategies are focused on regulating the structure of intestinal flora to ensure host health by alleviating disease. However, these strategies are limited by multiple factors, such as host genotype, physiology (microbiome, immunity, and gender), intervention, and diet. Accordingly, we reviewed the prospects and limitations of all strategies regulating the structure and abundance of microflora, including probiotics, prebiotics, diet, fecal microbiota transplantation, antibiotics, and phages. Some new technologies that can improve these strategies are also introduced. Compared with other strategies, diets and prebiotics are associated with reduced risk and high security. Besides, phages have the potential for application in the targeted regulation of intestinal microbiota due to their high specificity. Notably, the variability in individual microflora and their metabolic response to different interventions should be considered. Future studies should use artificial intelligence combined with multi-omics to investigate the host genome and physiology based on factors, such as blood type, dietary habits, and exercise, in order to develop individualized intervention strategies to improve host health.

7.
Crit Rev Food Sci Nutr ; : 1-15, 2023 Nov 30.
Article in English | MEDLINE | ID: mdl-38032232

ABSTRACT

The impacts of probiotics on maintaining the host's intestinal health have been extensively confirmed. Organoid technology revolutionizes intestinal health research by providing a unique platform to study the effects of probiotics. It overcomes challenges posed by animal models and 2D cell models in accurately simulating the in vivo environment. This review summarizes the development of intestinal organoid technology and its potential applications in intestinal health research as well as highlights the regulatory mechanisms of probiotics on intestinal health, which have been revealed using intestinal organoid technology. Furthermore, an overview of its potential applications in probiotic research has also been provided. This review aims to improve the understanding of intestinal organoid technology's applications in this field as well as to contribute to its further development.

8.
Phys Chem Chem Phys ; 25(45): 31003-31011, 2023 Nov 22.
Article in English | MEDLINE | ID: mdl-37938867

ABSTRACT

Aqueous zinc ion batteries (AZIBs) offer a promising approach for electrical energy storage, combining cost-effectiveness and enhanced thermal safety. However, the cathode material, vanadium oxide, while known for its excellent theoretical specific capacity, faces a challenge in terms of its poor electronic conductance. In this study, we present a novel strategy to address this limitation by constructing the V5O12·6H2O/V6O13/CNT (VOH/CNT) nanocomposite, resulting in significantly improved electrochemical performance. This nanocomposite was synthesized through a facile solvothermal method, yielding a unique floral spherical structure featuring a central cluster and multiple smaller groupings. The integration of CNTs into the composite significantly enhanced its electronic conductance, effectively mitigating the electronic conductance issue associated with vanadium oxide. Moreover, the composite retains crystalline water within its structure, playing a crucial role in providing a favorable ion-conductive pathway. Consequently, the VOH/CNT nanocomposite exhibits an impressive reversible capacity of 201 mA h g-1 at 50 mA g-1, surpassing that of VOH (116 mA h g-1). Remarkably, even at a high current density, the VOH/CNT nanocomposite demonstrates an exceptional capacity retention, maintaining a capacity of 150 mA h g-1 over 500 cycles at 1 A g-1. Its outstanding electrochemical performance can be attributed to its distinctive structural arrangement, the conductive network facilitated by CNTs, and the introduced crystalline water component.

9.
J Dairy Sci ; 106(6): 3779-3790, 2023 Jun.
Article in English | MEDLINE | ID: mdl-37105875

ABSTRACT

Antibacterial peptides can be released from yak milk casein. To date, the amino acid sequences and mechanism of action of yak casein-derived antibacterial peptides remain unknown. The current study identified antibacterial peptides from yak casein and their molecular mechanism of action. Our results showed that yak α-casein, ß-casein, and κ-casein could be effectively hydrolyzed by Flavourzyme (Solarbio Science and Technology Co. Ltd.), and the 2-h hydrolysate showed the highest antibacterial rate of 43.07 ± 2.59% against Staphylococcus aureus. The 1,000 to 3,000 Da fraction accounted for 23.61% of the 2-h hydrolysate and had an antibacterial rate of 62.64 ± 4.40%. Three novel peptides with antibacterial activity were identified from this fraction, and the ß-casein-derived peptide APKHKEMPFPKYP showed the strongest antibacterial effect (half-maximal inhibitory concentration = 0.397 mg/mL). Molecular docking predicted that APKHKEMPFPKYP interacted with 2 important enzymes of Staph. aureus, dihydrofolate reductase and DNA gyrase, through hydrophobic, hydrogen bonding, salt bridge, and π-π stacking interactions. Our findings suggest that the yak casein-derived peptides may serve as a potential source of natural preservatives to inhibit Staph. aureus.


Subject(s)
Caseins , Staphylococcus aureus , Cattle , Animals , Caseins/chemistry , Staphylococcus aureus/metabolism , Molecular Docking Simulation , Peptides/pharmacology , Anti-Bacterial Agents/pharmacology
10.
Molecules ; 28(24)2023 Dec 05.
Article in English | MEDLINE | ID: mdl-38138437

ABSTRACT

To explore the feasibility of the mechanochemical-assisted extraction (MCAE) of phenolic compounds from lotus seedpod (Receptaculum Nelumbinis), a single-factor experiment combined with response-surface methodology (RSM) was used to optimize the extraction process. The results showed the optimal extraction conditions as follows: Li2CO3 as a solid reagent (25%), an extraction time of 80 min, liquid/solid ratio of 42.8 mL/g, and extraction temperature of 80.7 °C; and the maximum value of total phenolic content (TPC) was 106.15 ± 1.44 gallic acid equivalents (GAE)/g dry weight (DW). Additionally, the 2,2-Diphenyl-1-picrylhydrazyl (DPPH), 2,2'-azinobis (3-ethylbenzothiazoline-6-sulfonic acid) (ABTS), and ferric reducing antioxidant power (FRAP) were 279.75 ± 18.71, 618.60 ± 2.70, and 634.14 ± 7.17 µmol TE/g, respectively. Ultra-high pressure liquid chromatography combined with triple-time-of-flight mass spectrophotometry (UPLC-Triple-TOF/MS) analysis identified eight phenolic compounds mainly consisting of polyphenols and flavonoids. Moreover, the phenolic compounds showed potent inhibitory effects on both α-amylase and α-glucosidase, with inhibition rates of over 80%. Furthermore, the results showed different degrees of inhibition activity against Bacillus subtilis, Staphylococcus aureus, and Escherichia coli, among which the inhibitory effect on the growth of B. subtilis was the best. This paper shows that the phenolic compounds have good biological activities, which provides a reference for the further exploitation of LSP.


Subject(s)
Phenols , Plant Extracts , Plant Extracts/chemistry , Phenols/chemistry , Antioxidants/chemistry , Seeds/chemistry
11.
J Sci Food Agric ; 103(13): 6406-6415, 2023 Oct.
Article in English | MEDLINE | ID: mdl-37209399

ABSTRACT

BACKGROUND: Among type 2 diabetes (T2D) patients, the incidence rate of liver metabolic disorders is much higher than that in healthy subjects. It was observed in our previous research that diabetic symptoms were improved by Lactobacillus plantarum SHY130 (LPSHY130) isolated from yak yogurt in a murine model of T2D. This study sought to investigate the LPSHY130-mediated hepatic metabolic regulation in a murine model of T2D. RESULTS: Treatment with LPSHY130 improved liver function and pathological damage in diabetic mice. Untargeted metabolome analysis revealed that T2D-induced changes in 11 metabolites were regulated after LPSHY130 treatment, mainly involving purine metabolism, amino acid metabolism, and choline metabolism and pantothenate and coenzyme A biosynthesis pathways. In addition, correlation analysis indicated that hepatic metabolic changes can be adjusted by the intestinal microbiota. CONCLUSION: Overall, this study suggests that treatment with LPSHY130 relieves liver injury and regulates liver metabolism in a murine model of T2D, thus providing a theoretical basis for the use of probiotics as dietary supplements to regulate hepatic metabolic disorders associated with T2D. © 2023 Society of Chemical Industry.


Subject(s)
Diabetes Mellitus, Experimental , Diabetes Mellitus, Type 2 , Lactobacillus plantarum , Probiotics , Mice , Animals , Diabetes Mellitus, Type 2/metabolism , Disease Models, Animal , Diabetes Mellitus, Experimental/metabolism , Metabolomics , Liver/metabolism
12.
Anal Chem ; 94(16): 6261-6270, 2022 04 26.
Article in English | MEDLINE | ID: mdl-35404585

ABSTRACT

DNA methylation analysis holds great promise in the whole process management of cancer early screening, diagnosis, and prognosis monitoring. Nevertheless, accurate detection of target methylated DNA, especially its methylation ratio in the genome, remains challenging. Herein, we report for the first time an integrated strategy of target-induced nanoparticle-coupling and site-specific base oxidation damage for DNA methylation analysis with the assistance of well-designed nanosensors. The ultrahigh sensitivity for detecting target methylated DNA as low as 32 × 10-17 M and high specificity for distinguishing 0.001% methylation ratio are achieved by this proposed strategy without amplification operations. Notably, the precise quantification of target DNA methylation ratio has been achieved for the first time. Through quantitative detection of target methylated DNA and methylation ratio, this proposed strategy could reliably diagnose and monitor cancer progression and treatment responses for colorectal cancer, which is superior to the clinical Septin 9 kit. It is anticipated that the proposed strategy has attractive application prospects in early diagnosis and monitoring for colorectal cancer and other various diseases.


Subject(s)
Colorectal Neoplasms , Nanoparticles , Colorectal Neoplasms/diagnosis , Colorectal Neoplasms/genetics , DNA , DNA Methylation , Humans , Oxidative Stress
13.
Crit Rev Food Sci Nutr ; : 1-21, 2022 Nov 15.
Article in English | MEDLINE | ID: mdl-36377678

ABSTRACT

Milk is an essential source of protein for infants and young children. At the same time, cow's milk is also one of the most common allergenic foods causing food allergies in children. Recently, cow's milk allergy (CMA) has become a common public health issue worldwide. Modern food processing technologies have been developed to reduce the allergenicity of milk proteins and improve the quality of life of patients with CMA. In this review, we summarize the main allergens in cow's milk, and introduce the recent findings on CMA responses. Moreover, the reduced effects and underlying mechanisms of different food processing techniques (such as heating, high pressure, γ-ray irradiation, ultrasound irradiation, hydrolysis, glycosylation, etc.) on the allergenicity of cow's milk proteins, and the application of processed cow's milk in clinical studies, are discussed. In addition, we describe the changes of nutritional value in cow's milk treated by different food processing technologies. This review provides an in-depth understanding of the allergenicity reduction of cow's milk proteins by various food processing techniques.

14.
Anal Chem ; 93(49): 16683-16689, 2021 12 14.
Article in English | MEDLINE | ID: mdl-34860503

ABSTRACT

We report a self-terminated electroless deposition method to prepare surfactant-free and monodispersed Pt nanoparticle (NP)-modified carbon fiber microelectrodes (Pt NP/CFEs) for electrochemical detection of hydrogen peroxide (H2O2) released from living cells. The surfactant-free and monodispersed Pt NPs with a uniform size of 65 nm are spontaneously deposited on a CFE surface by immersing an exposed carbon fiber (CF) of CFE in the PtCl42- solution, in which an exposed CF can be used as the reducing agent and stabilizer. A self-terminated electroless deposition method is demonstrated, in which the density and size of Pt NPs on a CFE surface do not increase when the reaction time increases from 20 to 60 min. The self-terminated electroless deposition process not only can effectively avoid any manual electrode modification and thus largely minimize person-to-person and electrode-to-electrode deviations but also can avoid the use of any extra reductant or surfactant in the fabrication process. Therefore, Pt NPs/CFEs, with good reproducibility and sensitivity, not only exhibit high electrocatalytic activity toward the oxidation of H2O2 but also maintain the spatial resolution of CFEs. Moreover, Pt NPs/CFEs can detect H2O2 with a wide linear range of 0.5-80 µM and a low detection limit of 0.17 µM and then can be successfully applied in the monitoring of H2O2 released from RAW 264.7 cells. The self-terminated electroless deposition method can also be extended to selectively prepare other metal NP-modified CFEs, such as Au NPs/CFEs or Ag NPs/CFEs, by choosing the metal ions with higher reduction potential as precursors. This work provides a simple, straightforward, and general method for the preparation of small, surfactant-free, and monodispersed metal NP-modified CFEs with high sensitivity, reproducibility, and spatial resolution.


Subject(s)
Hydrogen Peroxide , Metal Nanoparticles , Carbon Fiber , Humans , Microelectrodes , Reproducibility of Results , Surface-Active Agents
15.
J Bioenerg Biomembr ; 53(5): 597-608, 2021 10.
Article in English | MEDLINE | ID: mdl-34309767

ABSTRACT

Cervical cancer (CC) is one of the most common malignancy and is the second leading cause of death in gynecologic malignancies worldwide. The homeobox transcription factor homeobox C13 (HOXC13) has been demonstrated to play crucial roles in various cancers. However, its function in CC remains to be addressed. In the present study, upregulation of HOXC13 expression in human CC tissues was found in The Cancer Genome Atlas (TCGA) dataset and clinical samples and was associated with tumor size, FIGO stage and lymph node metastasis. Quantitative real-time polymerase chain reaction (qRT-PCR) and western blot assays suggested that the expression of HOXC13 was up-regulated in CC cells. Cell Counting Kit (CCK)-8, colony formation and cell cycle analysis assays indicated that HOXC13 promoted the proliferation and cycle progression of CC cells in vitro. Of note, knockdown of HOXC13 hinders tumor growth of xenograft tumor mice in vivo. Moreover, transwell and glycolysis measurement assays demonstrated that HOXC13 enhanced the migration, invasion and glycolysis of CC cells in vitro. Further mechanism analysis suggested that HOXC13 participated in CC progression through regulation of the ß-catenin/c-Myc signaling pathway. Collectively, HOXC13 facilitated cell proliferation, migration, invasion and glycolysis through modulating ß-catenin/c-Myc signaling pathway in CC, indicating that HOXC13 may provide a promising therapeutic target for the therapy of CC.


Subject(s)
Homeodomain Proteins/metabolism , Proto-Oncogene Proteins c-myc/metabolism , Uterine Cervical Neoplasms/metabolism , beta Catenin/metabolism , Animals , Cell Line, Tumor , Disease Progression , Female , HeLa Cells , Heterografts , Humans , Mice , Mice, Inbred BALB C , Mice, Nude , Neoplasm Invasiveness , Up-Regulation , Uterine Cervical Neoplasms/pathology , Warburg Effect, Oncologic
16.
Microb Pathog ; 152: 104567, 2021 Mar.
Article in English | MEDLINE | ID: mdl-33129950

ABSTRACT

BACKGROUND: Tuberculosis (TB) remains a major public health problem. SH3RF1 and SH3RF2 are candidate genes with multiple single-nucleotide polymorphisms (SNPs) that have the potential to participate in Mycobacterium infection via activation of the JNK signaling pathway. In this case-control study, we aimed to investigate the association of five SH3RF1 and SH3RF2 SNPs with susceptibility to TB in the Western Chinese population. METHODS: A total of 900 TB patients and 1534 healthy control subjects were enrolled in our study. All samples used were obtained from the Bio-Bank of resources of Tuberculosis Research in the Department of Laboratory Medicine, West China Hospital, Sichuan University, China. SNP genotyping was conducted using a commercial custom-by-design 2 × 48-Plex SNPscan Kit. RESULTS: The rs758037 variant of the SH3RF2 gene was found to be associated with decreased TB risk based on allelic effects (p = 0.00001, OR = 0.731, 95% CI = 0.641-0.833) and three genetic models (padd = 0.00001, pdom = 0.0003, prec = 0.0007) after the data were controlled for age and gender and underwent Bonferroni correction. The rs4913057 variant of the SH3RF2 gene was found to be associated with increased TB risk in a dominant model (p = 0.021, OR: 1.260, 95% CI: 1.065-1.490). No significant association was observed between other SNPs and TB risk. CONCLUSION: These findings indicate that polymorphisms in the SH3RF2 gene are involved in susceptibility to TB in the Western Chinese population.


Subject(s)
Genetic Predisposition to Disease , Tuberculosis , Asian People/genetics , Carrier Proteins , Case-Control Studies , China/epidemiology , Humans , Oncogene Proteins , Polymorphism, Single Nucleotide , Tuberculosis/genetics , Ubiquitin-Protein Ligases
17.
Crit Rev Food Sci Nutr ; 61(22): 3857-3875, 2021.
Article in English | MEDLINE | ID: mdl-32815398

ABSTRACT

Mitochondria control various processes in cellular metabolic homeostasis, such as adenosine triphosphate production, generation and clearance of reactive oxygen species, control of intracellular Ca2+ and apoptosis, and are thus a critical therapeutic target for metabolic syndrome (MetS). The mitochondrial targeted antioxidant mitoquinone (MitoQ) reduces mitochondrial oxidative stress, prevents impaired mitochondrial dynamics, and increases mitochondrial turnover by promoting autophagy (mitophagy) and mitochondrial biogenesis, which ultimately contribute to the attenuation of MetS conditions, including obesity, insulin resistance, hypertension and cardiovascular disease. The regulatory effect of MitoQ on mitochondrial homeostasis is mediated through AMPK and its downstream signaling pathways, including MTOR, SIRT1, Nrf2 and NF-κB. However, there are few reviews focusing on the critical role of MitoQ as a therapeutic agent in the treatment of MetS. The purpose of this review is to summarize the mitochondrial role in the pathogenesis of MetS, especially in obesity and type 2 diabetes, and discuss the effect and underlying mechanism of MitoQ on mitochondrial homeostasis in MetS.


Subject(s)
Diabetes Mellitus, Type 2 , Metabolic Syndrome , Diabetes Mellitus, Type 2/drug therapy , Homeostasis , Humans , Metabolic Syndrome/drug therapy , Mitochondria , Organophosphorus Compounds , Ubiquinone/analogs & derivatives
18.
Microbiol Immunol ; 65(4): 143-153, 2021 Apr.
Article in English | MEDLINE | ID: mdl-33527427

ABSTRACT

Antituberculosis drug-induced liver injury (ATDILI) has received increasing attention globally, which may limit the effectiveness of antituberculosis (anti-TB) treatment. Many host genetic determinants of ATDILI have been identified recently. As little knowledge is currently available about the association between aldehyde dehydrogenase 1 family member A1 (ALDH1A1) polymorphisms and ATDILI, the association between their variants and the susceptibility to ATDILI was investigated. A total of 747 patients with TB treated by first-line anti-TB drugs were prospectively enrolled at West China Hospital. Genomic DNA was extracted from the peripheral blood sample of each patient and seven single-nucleotide polymorphisms (SNPs) of ALDH1A1 gene were screened and genotyped with a custom-designed 2×48-plex SNP Scan TM kit. The patients were followed up monthly to monitor the development of ATDILI. The C allele and the CA genotype of rs7852860 were significantly associated with an elevated risk for ATDILI (p = .006 and 0.005, respectively), which was consistent with the results in the dominant and additive models. No allele, genotype, or genetic model of the other six SNPs (rs3764435, rs348471, rs63319, rs610529, rs7027604, rs8187876) were found to be associated with susceptibility to ATDILI. The findings first demonstrate that rs7852860 variants in ALDH1A1 gene is associated with susceptibility to ATDILI in the Chinese Han population. Validation studies with larger sample sizes and other ethnic groups are needed to confirm the findings.


Subject(s)
Aldehyde Dehydrogenase 1 Family/genetics , Antitubercular Agents , Chemical and Drug Induced Liver Injury , Retinal Dehydrogenase/genetics , Antitubercular Agents/adverse effects , Asian People , Case-Control Studies , Chemical and Drug Induced Liver Injury/drug therapy , Chemical and Drug Induced Liver Injury/genetics , China , Genetic Predisposition to Disease , Genotype , Humans , Polymorphism, Single Nucleotide , Prospective Studies
19.
BMC Infect Dis ; 21(1): 788, 2021 Aug 10.
Article in English | MEDLINE | ID: mdl-34376176

ABSTRACT

BACKGROUND: Tuberculosis (TB) is one of the leading causes of morbidity and mortality in Western China. Preclinical studies have suggested the protective effect of the C-type lectin receptor of family 4 member E (CLEC4E) from TB. Herein, we investigated the association between CLEC4E gene variants and TB susceptibility in a western Chinese Han population. METHODS: We genotyped four single nucleotide polymorphisms (SNPs) rs10841856, rs10770847, rs10770855 and rs4480590 in the CLEC4E gene using the improved multiplex ligation detection reaction (iMLDR) assay in 900 TB cases and 1534 healthy controls. RESULTS: After stratifying the whole data by sex, it was found that males exhibited mutant allele G of rs10841856 was more strongly associated with increased TB risk after Bonferroni correction (OR = 1.334, 95% CI: 1.142-1.560; P < 0.001 after adjusting for age; p = 0.001 after Bonferroni correction). The genetic model analysis found that rs10841856 was associated with the increased risk of TB among males under the dominant model (OR = 1.557, 95% CI = 1.228-1.984, P < 0.001 after adjusting for age, P < 0.001 after Bonferroni correction). Bioinformatics analysis suggested that rs10841856 might fall in putative functional regions and might be the expression quantitative trait loci (eQTL) for CLEC4E and long noncoding RNA RP11-561P12.5. CONCLUSIONS: Our study revealed that rs10841856 in the CLEC4E gene might be related to increased TB risk, especially the dominant genetic model among male Han individuals from Western China.


Subject(s)
Polymorphism, Single Nucleotide , Tuberculosis , Alleles , Asian People , Case-Control Studies , China/epidemiology , Genetic Predisposition to Disease , Genotype , Humans , Lectins, C-Type , Male , Receptors, Immunologic , Tuberculosis/epidemiology , Tuberculosis/genetics
20.
J Clin Pharm Ther ; 46(1): 66-73, 2021 Feb.
Article in English | MEDLINE | ID: mdl-32170986

ABSTRACT

WHAT IS KNOWN AND OBJECTIVE: Combination regimens of six-month duration may increase the incidence of anti-tuberculosis drug-induced liver injury (ATLI), which is clinically characterized by mild cholestasis and hepatocanalicular lesions. UGT2B4 is a predominant UDP-glucuronosyltransferase enzyme in the human liver that plays an important role in the detoxification of bile acids, which yields water-soluble inactive compounds that can easily be excreted in the bile or urine. This study aimed to investigate the potential association between UGT2B4 variants and the susceptibility to ATLI. METHODS: Genomic DNA was extracted from whole blood sample of each patient, and all SNPs were genotyped using an improved multiplex ligation detection reaction method. Clinical symptoms and laboratory results were recorded regularly. Five genetic variants at UGT2B4(rs1131878, rs1966151, rs28361541, rs4557343 and rs79407331) were identified in a prospective study of 118 ATLI cases and 628 non-ATLI controls. All participants were treated by first-line anti-TB drugs in Western China Hospital. The potential association between SNPs, ATLI risk and clinical phenotypes were determined based on the distribution of allelic frequencies and different genetic models. RESULTS AND DISCUSSION: Statistical comparisons of cases and controls after correction for multiple testing did not yield any significant association between genetic variants at UGT2B4 and risk of ATLI via the analyses of single locus and subgroup differences. WHAT IS NEW AND CONCLUSION: This is the first study aimed to investigate the association of UGT2B4 polymorphisms with ATLI risk. Our results revealed that UGT2B4 genetic variants are unlikely to confer susceptibility to ATLI in the Western Chinese Han population.


Subject(s)
Antitubercular Agents/therapeutic use , Chemical and Drug Induced Liver Injury/epidemiology , Genetic Predisposition to Disease , Glucuronosyltransferase/genetics , Tuberculosis, Pulmonary/drug therapy , Adult , Antitubercular Agents/adverse effects , Asian People , Chemical and Drug Induced Liver Injury/genetics , China/epidemiology , Female , Humans , Male
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