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Research advancements in the maintenance mechanism of Sporidiobolus pararoseus enhancing the quality of soy sauce during fermentation.
Zhao, S, Guo, T, Yao, Y, Dong, B, Zhao, G
International journal of food microbiology. 2024;:110690
Abstract
Soy sauce is a traditional condiment that undergoes microbial fermentation of various ingredients to achieve its desired color, scent, and flavor. Sporidiobolus pararoseus, which is a type of Rhodocerevisiae, shows promising potential as a source of lipids, carotenoids, and enzymes that can enrich the taste and color of soy sauce. However, there is currently a lack of systematic and comprehensive studies on the functions and mechanisms of action of S. pararoseus during soy sauce fermentation. In this review, it is well established that S. pararoseus produces lipids that are abundant in unsaturated fatty acids, particularly oleic acid, as well as various carotenoids, such as β-carotene, torulene, and torularhodin. These pigments are synthesized through the mevalonic acid pathway and possess remarkable antioxidant properties, acting as natural colorants. The synthesis of carotenoids is stimulated by high salt concentrations, which induces oxidative stress caused by NaCl. This stress further activates crucial enzymes involved in carotenoid production, ultimately leading to pigment formation. Moreover, S. pararoseus can produce high-quality enzymes that aid in the efficient utilization of soy sauce substrates during fermentation. Furthermore, this review focused on the impact of S. pararoseus on the color and quality of soy sauce and comprehensively analyzed its characteristics and ingredients. Thus, this review serves as a basis for screening high-quality oleaginous red yeast strains and improving the quality of industrial soy sauce production through the wide application of S. pararoseus.
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Machine learning-based classification of deubiquitinase USP26 and its cell proliferation inhibition through stabilizing KLF6 in cervical cancer.
Ye, Y, Li, M, Pan, Q, Fang, X, Yang, H, Dong, B, Yang, J, Zheng, Y, Zhang, R, Liao, Z
Computers in biology and medicine. 2024;:107745
Abstract
OBJECTIVE We aim to accurately distinguish ubiquitin-specific proteases (USPs) from other members within the deubiquitinating enzyme families based on protein sequences. Additionally, we seek to elucidate the specific regulatory mechanisms through which USP26 modulates Krüppel-like factor 6 (KLF6) and assess the subsequent effects of this regulation on both the proliferation and migration of cervical cancer cells. METHODS All the deubiquitinase (DUB) sequences were classified into USPs and non-USPs. Feature vectors, including 188D, n-gram, and 400D dimensions, were extracted from these sequences and subjected to binary classification via the Weka software. Next, thirty human USPs were also analyzed to identify conserved motifs and ascertained evolutionary relationships. Experimentally, more than 90 unique DUB-encoding plasmids were transfected into HeLa cell lines to assess alterations in KLF6 protein levels and to isolate a specific DUB involved in KLF6 regulation. Subsequent experiments utilized both wild-type (WT) USP26 overexpression and shRNA-mediated USP26 knockdown to examine changes in KLF6 protein levels. The half-life experiment was performed to assess the influence of USP26 on KLF6 protein stability. Immunoprecipitation was applied to confirm the USP26-KLF6 interaction, and ubiquitination assays to explore the role of USP26 in KLF6 deubiquitination. Additional cellular assays were conducted to evaluate the effects of USP26 on HeLa cell proliferation and migration. RESULTS 1. Among the extracted feature vectors of 188D, 400D, and n-gram, all 12 classifiers demonstrated excellent performance. The RandomForest classifier demonstrated superior performance in this assessment. Phylogenetic analysis of 30 human USPs revealed the presence of nine unique motifs, comprising zinc finger and ubiquitin-specific protease domains. 2. Through a systematic screening of the deubiquitinase library, USP26 was identified as the sole DUB associated with KLF6. 3. USP26 positively regulated the protein level of KLF6, as evidenced by the decrease in KLF6 protein expression upon shUSP26 knockdown in both 293T and Hela cell lines. Additionally, half-life experiments demonstrated that USP26 prolonged the stability of KLF6. 4. Immunoprecipitation experiments revealed a strong interaction between USP26 and KLF6. Notably, the functional interaction domain was mapped to amino acids 285-913 of USP26, as opposed to the 1-295 region. 5. WT USP26 was found to attenuate the ubiquitination levels of KLF6. However, the mutant USP26 abrogated its deubiquitination activity. 6. Functional biological assays demonstrated that overexpression of USP26 inhibited both proliferation and migration of HeLa cells. Conversely, knockdown of USP26 was shown to promote these oncogenic properties. CONCLUSIONS 1. At the protein sequence level, members of the USP family can be effectively differentiated from non-USP proteins. Furthermore, specific functional motifs have been identified within the sequences of human USPs. 2. The deubiquitinating enzyme USP26 has been shown to target KLF6 for deubiquitination, thereby modulating its stability. Importantly, USP26 plays a pivotal role in the modulation of proliferation and migration in cervical cancer cells.
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Cardiovascular-renal protective effect and molecular mechanism of finerenone in type 2 diabetic mellitus.
Lv, R, Xu, L, Che, L, Liu, S, Wang, Y, Dong, B
Frontiers in endocrinology. 2023;:1125693
Abstract
Chronic kidney diseases (CKD) and cardiovascular diseases (CVD) are the main complications in type 2 diabetic mellitus (T2DM), increasing the risk of cardiovascular and all-cause mortality. Current therapeutic strategies that delay the progression of CKD and the development of CVD include angiotensin-converting enzyme inhibitors (ACEI), angiotensin II receptor blockers (ARB), sodium-glucose co-transporter 2 inhibitors (SGLT-2i) and GLP-1 receptor agonists (GLP-1RA). In the progression of CKD and CVD, mineralocorticoid receptor (MR) overactivation leads to inflammation and fibrosis in the heart, kidney and vascular system, making mineralocorticoid receptor antagonists (MRAs) as a promising therapeutic option in T2DM with CKD and CVD. Finerenone is the third generation highly selective non-steroidal MRAs. It significantly reduces the risk of cardiovascular and renal complications. Finerenone also improves the cardiovascular-renal outcomes in T2DM patients with CKD and/or chronic heart failure (CHF). It is safer and more effective than the first- and second-generation MRAs due to its higher selectivity and specificity, resulting in a lower incidence of adverse effects including hyperkalemia, renal insufficiency and androgen-like effects. Finerenone shows potent effect on improving the outcomes of CHF, refractory hypertension, and diabetic nephropathy. Recently studies have shown that finerenone may have potential therapeutic effect on diabetic retinopathy, primary aldosteronism, atrial fibrillation, pulmonary hypertension and so on. In this review, we discuss the characteristics of finerenone, the new third-generation MRA, and compared with the first- and second-generation steroidal MRAs and other nonsteroidal MRAs. We also focus on its safety and efficacy of clinical application on CKD with T2DM patients. We hope to provide new insights for the clinical application and therapeutic prospect.
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Exercise for sarcopenia in older people: A systematic review and network meta-analysis.
Shen, Y, Shi, Q, Nong, K, Li, S, Yue, J, Huang, J, Dong, B, Beauchamp, M, Hao, Q
Journal of cachexia, sarcopenia and muscle. 2023;(3):1199-1211
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Abstract
BACKGROUND Sarcopenia is a serious public health concern among older adults worldwide. Exercise is the most common intervention for sarcopenia. This study aimed to compare the effectiveness of different exercise types for older adults with sarcopenia. METHODS Randomized controlled trials (RCTs) that examined the effectiveness of exercise interventions on patient-important outcomes for older adults with sarcopenia were eligible. We systematically searched MEDLINE, Embase and Cochrane Central Register of Controlled Trials via Ovid until 3 June 2022. We used frequentist random-effects network meta-analyses to summarize the evidence and applied the Grading of Recommendations, Assessment, Development, and Evaluations framework to rate the certainty of evidence. RESULTS Our search identified 5988 citations, of which 42 RCTs proved eligible with 3728 participants with sarcopenia (median age: 72.9 years, female: 73.3%) with a median follow-up of 12 weeks. We are interested in patient-important outcomes that include mortality, quality of life, muscle strength and physical function measures. High or moderate certainty evidence suggested that resistance exercise with or without nutrition and the combination of resistance exercise with aerobic and balance training were the most effective interventions for improving quality of life compared to usual care (standardized mean difference from 0.68 to 1.11). Moderate certainty evidence showed that resistance and balance exercise plus nutrition (mean difference [MD]: 4.19 kg) was the most effective for improving handgrip strength (minimally important difference [MID]: 5 kg). Resistance and balance exercise with or without nutrition (MD: 0.16 m/s, moderate) were the most effective for improving physical function measured by usual gait speed (MID: 0.1 m/s). Moderate certainty evidence showed that resistance and balance exercise (MD: 1.85 s) was intermediately effective for improving physical function measured by timed up and go test (MID: 2.1 s). High certainty evidence showed that resistance and aerobic, or resistance and balance, or resistance and aerobic exercise plus nutrition (MD from 1.72 to 2.28 s) were intermediately effective for improving physical function measured by the five-repetition chair stand test (MID: 2.3 s). CONCLUSIONS In older adults with sarcopenia, high or moderate certainty evidence showed that resistance exercise with or without nutrition and the combination of resistance exercise with aerobic and balance training were the most effective interventions for improving quality of life. Adding nutritional interventions to exercise had a larger effect on handgrip strength than exercise alone while showing a similar effect on other physical function measures.
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Inborn errors of OAS-RNase L in SARS-CoV-2-related multisystem inflammatory syndrome in children.
Lee, D, Le Pen, J, Yatim, A, Dong, B, Aquino, Y, Ogishi, M, Pescarmona, R, Talouarn, E, Rinchai, D, Zhang, P, et al
Science (New York, N.Y.). 2023;(6632):eabo3627
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Multisystem inflammatory syndrome in children (MIS-C) is a rare and severe condition that follows benign COVID-19. We report autosomal recessive deficiencies of OAS1, OAS2, or RNASEL in five unrelated children with MIS-C. The cytosolic double-stranded RNA (dsRNA)-sensing OAS1 and OAS2 generate 2'-5'-linked oligoadenylates (2-5A) that activate the single-stranded RNA-degrading ribonuclease L (RNase L). Monocytic cell lines and primary myeloid cells with OAS1, OAS2, or RNase L deficiencies produce excessive amounts of inflammatory cytokines upon dsRNA or severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) stimulation. Exogenous 2-5A suppresses cytokine production in OAS1-deficient but not RNase L-deficient cells. Cytokine production in RNase L-deficient cells is impaired by MDA5 or RIG-I deficiency and abolished by mitochondrial antiviral-signaling protein (MAVS) deficiency. Recessive OAS-RNase L deficiencies in these patients unleash the production of SARS-CoV-2-triggered, MAVS-mediated inflammatory cytokines by mononuclear phagocytes, thereby underlying MIS-C.
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Multidomain interventions for non-pharmacological enhancement (MINE) program in Chinese older adults with mild cognitive impairment: a multicenter randomized controlled trial protocol.
Wu, X, Zhang, T, Tu, Y, Deng, X, Sigen, A, Li, Y, Jing, X, Wei, L, Huang, N, Cheng, Y, et al
BMC neurology. 2023;(1):341
Abstract
BACKGROUND Dementia is characterized by progressive neurodegeneration and therefore early intervention could have the best chance of preserving brain health. There are significant differences in health awareness, living customs, and daily behaviors among Chinese older adults compared to Europeans and Americans. Because the synergistic benefits of multidomain non-pharmacological interventions are consistent with the multifactorial pathogenicity of MCI, such interventions are more appealing, easier to adhere to, and more relevant to daily life than single-mode interventions. One of the aims of this study is to verify the effect of multidomain intervention strategies for MCI patients based on Chinese population characteristics, and the other is to establish a biobank and image database to investigate the pathogenesis and pathways of cognitive impairment. METHODS Our study was designed as a national multicenter, community-based randomized controlled trial (RCT). Twelve medical institutions in ten Chinese cities will participate in our study from 2020 to 2024, and 1080 community residents aged 50 and above will be enrolled as participants. Each sub-center will be responsible for 90 participants (30 people per community) across three communities (non-contact control group, health education group, and multidomain intervention group). The community will be the basic unit of the present study, and all participants in each community will receive the same intervention/control measure. Three working groups are set up in each sub-center to manage the three communities independently to minimize interference at the implementation level between the groups. The multidomain intervention group will receive integrated interventions including exercise, nutrition, sleep, health education and mindfulness meditation. All data generated by the research will be analyzed and processed by statistical software (such as SPSS 21.0, Python 3.0, etc.), and part of the research data will be displayed in the form of graphs and tables. DISCUSSION In order to achieve a high-quality community intervention study, it is crucial to have a well-designed experimental protocol that follows rigorous scientific methodology. In addition, effective management of quality control measures and monitoring compliance throughout the study process are essential components. This study provides a detailed discussion of stakeholder compliance, research quality control, potential harm and mitigation, auditing, and future plans in order to better address research issues. TRIAL REGISTRATION ChiCTR2000035012 (July 27, 2020).
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Ligustri Lucidi Fructus, a traditional Chinese Medicine: Comprehensive review of botany, traditional uses, chemical composition, pharmacology, and toxicity.
Cao, M, Wu, J, Peng, Y, Dong, B, Jiang, Y, Hu, C, Yu, L, Chen, Z
Journal of ethnopharmacology. 2023;:115789
Abstract
ETHNOPHARMACOLOGICAL RELEVANCE Ligustri Lucidi Fructus (LLF) is one of the usual Chinese herbs that has long been used with high therapeutic and condition value. LLF is used for the treatment of dizziness and tinnitus, soreness and weakness of the waist and knees, premature greying of the hair, the darkness of the eyes, internal heat and thirst, bone steam and hot flashes and other symptoms. AIM OF THE STUDY This review reviews botany, traditional uses, processing, phytochemistry, quality control, pharmacology, toxicity and pharmacokinetics to better understand its therapeutic potential. MATERIALS AND METHODS The literature on LLF was obtained from Google Scholar and Baidu Scholar, PubMed, ScienceDirect, SciFinder, Web of Science, China National Knowledge Infrastructure (CNKI), WAN FANG DATA and libraries. Some local books, official websites, PhD or MS's dissertations were also included. Phytochemical constituents' structures were drawn by ChemDraw software. RESULTS So far, Multiple chemical components were isolated and identified from LLF, mainly including terpenoids and flavonoids. Modern studies have shown that LLF extracts and compounds have a wide range of pharmacological effects, including antitumor, liver protection, blood glucose, lipid-lowering, immune regulation, and other aspects. CONCLUSIONS LLF occupies an important position in the traditional medical system. It is cost-effective and is a significant plant with therapeutic applications in modern medicine. However, further in-depth studies are needed to determine the medical use of this plant and its chemical composition, pharmacological activity, quality control, toxicity and pharmacokinetics.
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The effect of probiotics on surgical outcomes in patients with gastric cancer: a meta-analysis of randomized controlled trials.
Ye, W, Dong, B, Li, G, Zhang, Y
Frontiers in surgery. 2023;:1254597
Abstract
The effect of probiotics on postoperative infectious complications and nutritional status in patients with gastric cancer is still controversial, and a comprehensive search and analysis of the current relevant evidence is necessary. Our study aimed to define the effects of probiotics on surgical outcomes in gastric cancer patients undergoing surgery. Up to June 20, 2023, Embase, PubMed, Web of Science, and Cochrane databases were searched for randomized controlled trials of probiotics in gastric cancer patients undergoing surgery. Relative risk (RR) or mean difference (MD) was used to calculate the effect sizes using RevMan 5.3. A total of nine studies reporting on 861 participants were included. Perioperative supplementation with probiotics did not improve weight loss (MD 0.73 kg; 95% CI: -0.56, 2.02) or serum prealbumin levels (MD 9.48 mg/L 95% CI: -3.43, 22.40), but did reduce the incidence of postoperative infectious complications (RR 0.46, 95% CI 0.28, 0.77), shorten the time to first exhaust (MD -11.27 h; 95% CI: -16.83, -5.70), the time to first defecation (MD -15.71 h; 95% CI: -25.62, -5.79), and the length of hospital stay (MD -0.94 days; 95% CI: -1.33, -0.55), and increase serum albumin levels (MD 0.73 g/L; 95% CI: 0.01, 1.46) in gastric cancer patients undergoing surgery. Probiotics are effective in preventing postoperative infectious complications, promoting postoperative recovery, and improving nutritional status in gastric cancer patients undergoing surgery. Our study highlights the importance of probiotics for healthcare systems and offers a potential strategy to improve the prognosis and reduce the medical burden of gastric cancer patients undergoing surgery.
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The impact of preoperative malnutrition on postoperative delirium: a systematic review and meta-analysis.
Dong, B, Wang, J, Li, P, Li, J, Liu, M, Zhang, H
Perioperative medicine (London, England). 2023;(1):55
Abstract
BACKGROUND Postoperative delirium (POD) is a common postoperative complication, characterized by disturbance of attention, perception, and consciousness within 1 week after surgery, and linked to cognitive decline, increased mortality, and other serious surgical outcomes. Early identification and treatment of risk factors for POD could reduce the occurrence of delirium and the related poor outcomes. Malnutrition as a possible precipitating factor, defined as the poor anthropometric, functional, and clinical outcomes of nutrient deficiency, has been investigated. However, the evidence is controversial. The goal of this systematic review and meta-analysis was to comprehensively assess the correlation between preoperative malnutrition and POD. METHODS PubMed, Embase, Cochrane Library, and Web of Science were used to search prospective cohort articles that explored the correlation between preoperative malnutrition and POD from inception until September 30, 2022. Two researchers independently conducted the literature selection and data extraction. The quality of the literature was evaluated according to the Newcastle-Ottawa scale (NOS). Odds ratios (ORs) and 95% confidence intervals (CIs) for POD associated with malnutrition relative to normal nutritional status were calculated. RESULTS Seven prospective cohort studies qualified for the meta-analysis, which included 2701 patients. The pooled prevalence of preoperative malnutrition was 15.1% (408/2701), and POD occurred in 428 patients (15.8%). The NOS score was above 7 points in all 7 studies. Our results demonstrated that the pooled OR for malnutrition and POD was 2.32 (95% CI 1.62-3.32) based on a random-effects model. Our subgroup analysis suggested that the relationship between malnutrition and POD was significant in adults following noncardiac surgery (OR = 3.04, 95% CI, 1.99-4.62, P < 0.001), while there was no statistical significance in adults following cardiac surgery (OR = 1.76, 95% CI, 0.96-3.22, P = 0.07). Additionally, in the subgroup analysis based on different malnutrition assessment tools (MNA-SF versus others), a significant association was found in the MNA-SF group (OR = 3.04, 95% CI, 1.99-4.62, P < 0.001), but not in the others group (OR = 1.76, 95% CI, 0.96-3.22, P = 0.07). Other subgroup analyses showed that this association was not significantly affected by evaluation instruments for POD, location of the study, or quality of the article (all P < 0.05). CONCLUSIONS Based on the currently available evidence, our results suggested that preoperative malnutrition was independently associated with POD in adult surgical patients.
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Identification of potential ferroptosis-associated biomarkers in rheumatoid arthritis.
He, X, Zhang, J, Gong, M, Gu, Y, Dong, B, Pang, X, Zhang, C, Cui, Y
Frontiers in immunology. 2023;:1197275
Abstract
BACKGROUND Rheumatoid arthritis (RA) is a chronic autoimmune disorder characterized by inflammation and gradual joint degeneration, resulting in function disability. Recently, ferroptosis, a novel form of regulated cell death that involves iron-dependent lipid peroxidation, has been implicated in the pathogenesis of RA. However, the underlying molecular mechanisms and key genes involved in ferroptosis in RA remain largely unknown. METHODS The GSE134420 and GSE77298 datasets were downloaded and DEGs were identified using R software. The DEGs were then mapped to the dataset of 619 ferroptosis-related genes obtained from the GeneCards database. Gene Ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway analyses were conducted to investigate the possible biological functions. Protein-protein interaction (PPI) networks were constructed to identify the hub genes. The relationship between hub genes and immune infiltration was estimated using the CIBERSORT algorithms. Gene Set Enrichment Analysis (GSEA) was used to explore the underlying signaling pathways of hub genes. Genome-wide association studies (GWAS) analysis was performed to confirm the pathogenic regions of the hub genes. RcisTarget and Gene-motif ranking databases were used to identify transcription factors (TFs) associated with the hub genes. The miRcode databases were utilized to construct the microRNA (miRNA)-messenger RNA (mRNA) network. Single-cell analysis was utilized to cluster cells and display the expression of hub genes in cell clusters. Finally, the expression and potential mechanism of hub genes were investigated in human and experimental samples. RESULTS Three hub genes PTGS2, ENO1, and GRN highly associated with ferroptosis were identified. Four pathogenic genes HLA-B, MIF, PSTPIP, TLR1 were identified that were significantly and positively correlated with the expression levels of hub genes. The results of the GSEA showed that the hub genes were significantly enriched in pathways related to immunity, lysosome, phagocytosis and infection. ENO1 and PTGS2 were enriched in the TF-binding motif of cisbp_M5493. The hub genes were validated in experimental and patient samples and highly level of ENO1 expression was found to inhibit ACO1, which reduces ferroptosis in proliferating fibroblast-like synoviocytes (FLS). CONCLUSION PTGS2, ENO1 and GRN were identified and validated as potential ferroptosis-related biomarkers. Our work first revealed that ENO1 is highly expressed in RA synovium and that ferroptosis may be regulated by the ENO1-ACO1 axis, advancing the understanding of the underlying ferroptosis-related mechanisms of synovial proliferation and providing potential diagnostic and therapeutic targets for RA.