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1.
Stereocontrolled access to thioisosteres of nucleoside di- and triphosphates.
Zhang, HJ, Ociepa, M, Nassir, M, Zheng, B, Lewicki, SA, Salmaso, V, Baburi, H, Nagel, J, Mirza, S, Bueschbell, B, et al
Nature chemistry. 2024;(2):249-258
Abstract
Nucleoside diphosphates and triphosphates impact nearly every aspect of biochemistry; however, the use of such compounds as tools or medicinal leads for nucleotide-dependent enzymes and receptors is hampered by their rapid in vivo metabolism. Although a successful strategy to address the instability of the monophosphate moiety in oligonucleotide therapeutics has been accomplished by their isosteric replacement with phosphorothioates, no practical methods exist to rapidly and controllably access stereopure di- and triphosphate thioisosteres of both natural and unnatural nucleosides. Here we show how a modular, reagent-based platform can enable the stereocontrolled and scalable synthesis of a library of such molecules. This operationally simple approach provides access to pure stereoisomers of nucleoside α-thiodiphosphates and α-thiotriphosphates, as well as symmetrical or unsymmetrical dinucleoside thiodiphosphates and thiotriphosphates (including RNA cap reagents). We demonstrate that ligand-receptor interactions can be dramatically influenced by P-stereochemistry, showing that such thioisosteric replacements can have profound effects on the potency and stability of lead candidates.
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2.
The origin of vitamin B12 levels and risk of all-cause, cardiovascular and cancer specific mortality: A systematic review and dose-response meta-analysis.
Liu, K, Yang, Z, Lu, X, Zheng, B, Wu, S, Kang, J, Sun, S, Zhao, J
Archives of gerontology and geriatrics. 2024;:105230
Abstract
BACKGROUND Vitamin B12 is essential to human but the implications of serum vitamin B12 level for mortality in clinical practice remain unclear. We conducted a systematic review and dose-response meta-analysis to quantify the relationship between vitamin B12 levels and the risk of all-cause, cardiovascular, and cancer mortality. METHODS Electronic databases of PubMed, Embase, and the Cochrane Library Central Register of Controlled Trials were searched from inception through May 2023. Two reviewers independently extracted individual study data and evaluated the risk of bias among the studies using the Newcastle‒Ottawa Scale. To examine a potential nonlinear relationship between the vitamin B12 levels and all-cause mortality, we performed a two-stage random effects dose‒response meta-analysis. RESULTS Twenty-two cohort studies (92,346 individuals with 10,704 all-cause deaths) were included. A linear trend dose-response analysis showed that each 100 pmol/L increase in serum vitamin B12 concentration was associated with a 4 % higher risk of all-cause mortality in the general population (adjusted HR 1.04, 95 % confidence interval CI 1.01 to 1.08; n = 8; P non-linearity = 0.11) and a 6 % higher risk for all-cause mortality in older adults (adjusted HR 1.06, 95 % CI 1.01 to 1.13; n = 4; P non-linearity = 0.78). Current evidence was mixed for the association between serum vitamin B12 concentration and cardiovascular mortality and was limited for cancer mortality. The meta-analysis of cohort studies showed a positive association between a high serum vitamin B12 concentration (>600 pmol/L) and all-cause mortality (adjusted HR 1.50, 95 % CI 1.29 to 1.74; n = 10; p < 0.01), CVD mortality (adjusted HR 2.04, 95 % CI 0.99 to 4.19; n = 2; p = 0.02), except cancer mortality (adjusted HR 1.56, 95 % CI 0.82 to 2.95; n = 3). Similarly, serum vitamin B12 concentrations (400-600 pmol/L) were associated with increased all-cause mortality (adjusted HR 1.34, 95 % CI 1.10 to 1.64; n = 9; p < 0.01). CONCLUSIONS Serum vitamin B12 concentration was positively associated with the risk of all-cause mortality, especially among older adults, with a linear increasing trend. These findings suggested the primary cause of elevated level of serum vitamin B12 concentration should be timely identified and effectively managed in clinical practice.
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3.
Progress on the mechanism of natural products alleviating androgenetic alopecia.
Wu, S, Kou, X, Niu, Y, Liu, Y, Zheng, B, Ma, J, Liu, M, Xue, Z
European journal of medicinal chemistry. 2024;:116022
Abstract
Androgenetic alopecia (AGA) has become a widespread problem that leads to considerable impairment of the psyche and daily life. The currently approved medications for the treatment of AGA are associated with significant adverse effects, high costs, and prolonged treatment duration. Therefore, natural products are being considered as possible complementary or alternative treatments. This review aims to enhance comprehension of the mechanisms by which natural products treat AGA. To achieve this, pertinent studies were gathered and subjected to analysis. In addition, the therapeutic mechanisms associated with these natural products were organized and summarized. These include the direct modulation of signaling pathways such as the Wnt/β-catenin pathway, the PI3K/AKT pathway, and the BMP pathway. Additionally, they exert effects on cytokine secretion, anti-inflammatory, and antioxidant capabilities, as well as apoptosis and autophagy. Furthermore, the review briefly discusses the relationship between signaling pathways and autophagy and apoptosis in the context of AGA, systematically presents the mechanisms of action of existing natural products, and analyzes the potential therapeutic targets based on the active components of these products. The aim is to provide a theoretical basis for the development of pharmaceuticals, nutraceuticals, or dietary supplements.
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4.
Roles of abscisic acid and auxin in plants during drought: A molecular point of view.
Sharma, A, Gupta, A, Ramakrishnan, M, Ha, CV, Zheng, B, Bhardwaj, M, Tran, LP
Plant physiology and biochemistry : PPB. 2023;:108129
Abstract
Plant responses to drought are mediated by hormones like ABA (abscisic acid) and auxin. These hormones regulate plant drought responses by modulating various physiological and biological processes via cell signaling. ABA accumulation and signaling are central to plant drought responses. Auxin also regulates plant adaptive responses to drought, especially via signal transduction mediated by the interaction between ABA and auxin. In this review, we explored the interactive roles of ABA and auxin in the modulation of stomatal movement, root traits and accumulation of reactive oxygen species associated with drought tolerance.
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5.
Efficacy of N-acetylcysteine plus pirfenidone in the treatment of idiopathic pulmonary fibrosis: a systematic review and meta-analysis.
Zhang, XL, Cao, Y, Zheng, B
BMC pulmonary medicine. 2023;(1):479
Abstract
BACKGROUND Numerous studies have demonstrated the potential of pirfenidone to enhance the prognosis of patients afflicted with idiopathic pulmonary fibrosis (IPF). Although N-acetylcysteine (NAC) is utilized as an antioxidant in IPF treatment, the combination of NAC and pirfenidone has produced inconsistent outcomes in certain studies. To assess the clinical effectiveness and safety of NAC plus pirfenidone (designated as the treatment group) versus pirfenidone monotherapy (designated as the control group), we conducted a systematic review and meta-analysis of randomized controlled trials (RCTs). METHODS RCTs of NAC plus pirfenidone were reviewed searching from databases and networks of unpublished and published studies in any language. Using pair-wise meta-analysis, changes in pulmonary function test (PFT) parameters and safety were evaluated. RESULTS Two independent reviewers selected and obtained data from 5 RCTs (n = 398), comprising 1 study from Japan, 1 from Europe, and 3 from China. NAS plus pirfenidone as compared to pirfenidone monotherapy for IPF may not reduce the incidence of skin effects(RR 1.26 [95%CI 0.64 to 2.45]) and mortality(RR 0.35 [95%CI 0.07 to 1.68])(both moderate certainty). NAS plus pirfenidone as compared to pirfenidone monotherapy for IPF may not reduce the incidence of at least one side effects(RR 1.00 [95%CI 0.84 to 1.19]; low certainty),severe side effects(RR 0.67 [95%CI 0.30 to 1.47]; low certainty) and gastrointestinal effects(RR 0.67 [95%CI 0.41 to 1.09]; low certainty) with possibly no effect in Δ%DLco(SMD -0.17 [95%CI -0.15 to 0.48]; low certainty). Meanwhile, the effect of NAS plus pirfenidone as compared to pirfenidone monotherapy on ΔFVC(SMD 0.18 [95%CI -0.68 to 1.05]), Δ%FVC(SMD -2.62 [95%CI -5.82 to 0.59]) and Δ6MWT(SMD -0.35 [95%CI -0.98 to 0.28]) is uncertain(extremely low certainty). CONCLUSION Moderate certainty evidence suggests that NAS plus pirfenidone, compared to pirfenidone monotherapy for IPF, does not reduce the incidence of skin effects and mortality.
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6.
Data correction and verification of thermal simulation experiments under the influence of bulging belly.
Zheng, B, Xu, D, Zou, Z, Wang, Y, Guo, L, Zhao, H, Ju, D
Scientific reports. 2023;(1):16382
Abstract
During the thermal simulation compression test, the formation of an obvious bulge in the specimen leads to a certain deviation between the calculated and actual values of the true stress. The finite element method was used to simulate the single-pass compression of specimens of 34CrNi3MoV steel and obtain the actual nonuniform deformation of the bulging belly during the compression process, and the results were applied to correct experimental flow curves. The results showed that the deformation conditions had a significant influence on the nonuniformity of the specimen deformation during the compression process, and all the modified flow curves were lower than the original ones. The size of the bulge and the metal flow line in the finite element simulation were consistent with the test results. The load value obtained by using the modified flow curve was similar to the load value measured in the test, which indicated that the modified flow curve was very close to the real flow force curve of the material. The method used to modify the flow force curve is simple and practical.
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7.
Nrf2-mediated therapeutic effects of dietary flavones in different diseases.
Huang, W, Zhong, Y, Gao, B, Zheng, B, Liu, Y
Frontiers in pharmacology. 2023;:1240433
Abstract
Oxidative stress (OS) is a pathological status that occurs when the body's balance between oxidants and antioxidant defense systems is broken, which can promote the development of many diseases. Nrf2, a redox-sensitive transcription encoded by NFE2L2, is the master regulator of phase II antioxidant enzymes and cytoprotective genes. In this context, Nrf2/ARE signaling can be a compelling target against OS-induced diseases. Recently, natural Nrf2/ARE regulators like dietary flavones have shown therapeutic potential in various acute and chronic diseases such as diabetes, neurodegenerative diseases, ischemia-reperfusion injury, and cancer. In this review, we aim to summarize nrf2-mediated protective effects of flavones in different conditions. Firstly, we retrospected the mechanisms of how flavones regulate the Nrf2/ARE pathway and introduced the mediator role Nrf2 plays in inflammation and apoptosis. Then we review the evidence that flavones modulated Nrf2/ARE pathway to prevent diseases in experimental models. Based on these literature, we found that flavones could regulate Nrf2 expression by mechanisms below: 1) dissociating the binding between Nrf2 and Keap1 via PKC-mediated Nrf2 phosphorylation and P62-mediated Keap1 autophagic degradation; 2) regulating Nrf2 nuclear translocation by various kinases like AMPK, MAPKs, Fyn; 3) decreasing Nrf2 ubiquitination and degradation via activating sirt1 and PI3K/AKT-mediated GSK3 inhibition; and 4) epigenetic alternation of Nrf2 such as demethylation at the promoter region and histone acetylation. In conclusion, flavones targeting Nrf2 can be promising therapeutic agents for various OS-related disorders. However, there is a lack of investigations on human subjects, and new drug delivery systems to improve flavones' treatment efficiency still need to be developed.
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8.
Production and Anti-Inflammatory Performance of PVA Hydrogels Loaded with Curcumin Encapsulated in Octenyl Succinic Anhydride Modified Schizophyllan as Wound Dressings.
Tu, L, Fan, Y, Deng, Y, Hu, L, Sun, H, Zheng, B, Lu, D, Guo, C, Zhou, L
Molecules (Basel, Switzerland). 2023;(3)
Abstract
Amphiphilic polysaccharides can be used as wall materials and applied to encapsulate hydrophobic active chemicals; moreover, there is significant demand for novel medical high-molecular-weight materials with various functions. In order to prepare amphiphilic schizophyllan (SPG), octenyl succinic anhydride (OSA) was chosen to synthesize OSA-modified schizophyllan (OSSPG) using an esterified reaction. The modification of OSSPG was demonstrated through FT-IR and thermal analysis. Moreover, it was found that OSSPG has a better capacity for loading curcumin, and the loading amount was 20 μg/mg, which was 2.6 times higher than that of SPG. In addition, a hydrogel made up of PVA, borax, and C-OSSPG (OSSPG loaded with curcumin) was prepared by means of the one-pot method, based on the biological effects of curcumin and the immune-activating properties of SPG. The mechanical properties and biological activity of the hydrogel were investigated. The experimental results show that the dynamic cross-linking of PVA and borax provided the C-OSSPG/BP hydrogel dressing with exceptional self-healing properties, and it was discovered that the C-OSSPG content increased the hydrogel's swelling and moisturizing properties. In fibroblast cell tests, the cells treated with hydrogel had survival rates of 80% or above. Furthermore, a hydrogel containing C-OSSPG could effectively promote cell migration. Due to the excellent anti-inflammatory properties of curcumin, the hydrogel also significantly reduces the generation of inflammatory factors, such as TNF-α and IL-6, and thus has a potential application as a wound dressing medicinal material.
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9.
Resistant starch from sweet potatoes: Recent advancements and applications in the food sector.
Bodjrenou, DM, Li, X, Lu, X, Lei, S, Zheng, B, Zeng, H
International journal of biological macromolecules. 2023;:13-26
Abstract
In tropical and subtropical areas, tuber and root crops are staple foods and a key source of energy. Sweet potato (SP) is currently regarded as one of the world's top ten foods because of its diverse sizes, shapes, color, and health benefits. The resistant starch (RS) content of SP is substantial. It is predicted to become the cheapest item in the food industry due to its extensive variety, food stability, emulsifier and fat substitution capabilities, and as filler. As a result, interest in SP-sourced RS has recently increased. Due to their unique nutritional and functional qualities, novelty has become a popular research focus in recent years. This review will summarize the current understanding of SP starch components and their impact on the technological and physicochemical properties of produced starch for commercial viability. The importance of sweet potato RS in addressing future RS demand sustainability is emphasized. SPs are a viable alternative to tubers as a sustainable raw material for RS production. It has an advantage over tubers because of its intrinsic nutritional value and climatic endurance. Thermal, chemical, and enzymatic treatments are effective RS manufacturing procedures. The adaptability of sweet potato RS allows for a wide range of food applications.
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10.
A new CCCH-type zinc finger-related lncRNA signature predicts the prognosis of clear cell renal cell carcinoma patients.
Shen, C, Chen, Z, Jiang, J, Zhang, Y, Xu, W, Peng, R, Zuo, W, Jiang, Q, Fan, Y, Fang, X, et al
Frontiers in genetics. 2022;:1034567
Abstract
Background: Clear cell renal cell carcinoma (ccRCC) is the main component of renal cell carcinoma (RCC), and advanced ccRCC frequently indicates a poor prognosis. The significance of the CCCH-type zinc finger (CTZF) gene in cancer has been increasingly demonstrated during the past few years. According to studies, targeted radical therapy for cancer treatment may be a revolutionary therapeutic approach. Both lncRNAs and CCCH-type zinc finger genes are essential in ccRCC. However, the predictive role of long non-coding RNA (lncRNA) associated with the CCCH-type zinc finger gene in ccRCC needs further elucidation. This study aims to predict patient prognosis and investigate the immunological profile of ccRCC patients using CCCH-type zinc finger-associated lncRNAs (CTZFLs). Methods: From the Cancer Genome Atlas database, RNA-seq and corresponding clinical and prognostic data of ccRCC patients were downloaded. Univariate and multivariate Cox regression analyses were conducted to acquire CTZFLs for constructing prediction models. The risk model was verified using receiver operating characteristic curve analysis. The Kaplan-Meier method was used to analyze the overall survival (OS) of high-risk and low-risk groups. Multivariate Cox and stratified analyses were used to assess the prognostic value of the predictive feature in the entire cohort and different subgroups. In addition, the relationship between risk scores, immunological status, and treatment response was studied. Results: We constructed a signature consisting of eight CTZFLs (LINC02100, AC002451.1, DBH-AS1, AC105105.3, AL357140.2, LINC00460, DLGAP1-AS2, AL162377.1). The results demonstrated that the prognosis of ccRCC patients was independently predicted by CTZFLs signature and that the prognosis of high-risk groups was poorer than that of the lower group. CTZFLs markers had the highest diagnostic adequacy compared to single clinicopathologic factors, and their AUC (area under the receiver operating characteristic curve) was 0.806. The overall survival of high-risk groups was shorter than that of low-risk groups when patients were divided into groups based on several clinicopathologic factors. There were substantial differences in immunological function, immune cell score, and immune checkpoint expression between high- and low-risk groups. Additionally, Four agents, including ABT737, WIKI4, afuresertib, and GNE 317, were more sensitive in the high-risk group. Conclusion: The Eight-CTZFLs prognostic signature may be a helpful prognostic indicator and may help with medication selection for clear cell renal cell carcinoma.