Exploring the mechanism of Tingli Pill in the treatment of HFpEF based on network pharmacology and molecular docking.

To explore the mechanism of action of Tingli Pill (TLP) in the treatment of heart failure with preserved ejection fraction (HFpEF) by using network pharmacology and molecular docking technology. The active components and targets of TLP were screened using the TCMSP and UniProt databases. HFpEF-related targets were identified using the OMIM and GeneCards databases. Drug-disease intersection targets were obtained via Venny 2.1.0, as well as establishing the "component-target" network and screening out the core active components. Construct a protein-protein interaction network of intersecting targets using the STRING database as well as Cytoscape software and filter the core targets. Gene ontology and Kyoto Encyclopedia of Genes and Genomes enrichment analysis of core targets were performed using the Metascape database. The core active components of TLP for HFpEF were quercetin, kaempferol, ß-sitosterol, isorhamnetin and hederagenin. The core targets of TLP for HFpEF were JUN, MAPK1, TP53, AKT1, RELA, TNF, MAPK14, and IL16. Gene ontology enrichment analysis obtained 1528 biological processes, 85 cell components, and 140 molecular functions. The Kyoto Encyclopedia of Genes and Genomes pathway enrichment analysis yielded 1940 signaling pathways, mainly involved in lipid and atherosclerosis, regulation of apoptotic signaling pathway, PI3K-Akt signaling pathway, HIF-1 signaling pathway, oxidative stress, TNF signaling pathway, and IL-17 signaling pathway. TLP has the characteristics of multi-component, multi-target, and multi-pathway in the treatment of HFpEF. This study lays the foundation for revealing the pharmacodynamic substances and mechanism of TLP in the treatment of HFpEF.

Mechanical Signaling in Dental Pulp Stem Cells.

Dental pulp stem cells (DPSCs) are a type of mesenchymal stem cells derived from dental pulp that serves as an important model for investigating biological regeneration. DPSCs have a multipotent differentiation capacity and can promote different biological processes, including osteogenesis, odontogenesis, chondrogenesis, and angiogenesis. These biological processes are regulated by an extensive range of intra- and extra-cellular factors. Further, biomechanical cues, such as substrate stiffness, physical stress, and cell spreading, have been highlighted as particularly important modulators of DPSC function. This review sought to discuss various related signaling components involved in biomechanical cues and their respective roles in cellular and tissue responses in DPSCs, summarize current findings, and provide an outlook on the potential applications of biomechanics in regenerative medicine and tissue engineering.

Rheumatoid arthritis-associated interstitial lung disease hotspots and future directions: A Web-of-Science based scientometric and visualization study.

OBJECTIVE: To identify new trends and potential hotspots in research on rheumatoid arthritis-associated interstitial lung disease (RA-ILD). MATERIALS AND METHODS: The Web of Science (WOS) database was used to search for RA-ILD-related literature published between August 31, 2002 and August 31, 2022. CiteSpace 6.1.R3, VOSviewer version 1.6.17, Scimago Graphica, and Pajek V2.0 visualization software were used to conduct a comprehensive analysis and network visualization mapping of the authors, countries, institutions, journals, cited references, and keywords. RESULTS: A total of 2412 articles were retrieved, and the number of articles published has grown annually since 2002. Eric L. Matteson was the most prolific author, and the Mayo Clinic and UNITED STATES have the highest publishing volume and influence. Clinical Rheumatology is the journal with the most papers published. Rheumatology was the most cited journal. The citation clusters and keywords concentrated on the mechanism, treatment, and predictive and prognostic factors. CONCLUSION: Pathogenesis, treatment, and predictive and prognostic factors were among the RA-ILD research directions and hotspots. Antirheumatoid drugs, especially biologics and small molecule inhibitors, were among the most actively researched treatment options. The results of this study provides an in-depth understanding of the development of RA-ILD publications, aids researchers in understanding hotspots and trends and provides a new perspective for future RA-ILD research.

Zinc and selenium status in coronavirus disease 2019.

We systematically analyzed and attempted to discuss the possibility that deficiencies of zinc or selenium were associated with the incidence and severity of COVID-19. We searched for published and unpublished articles in PubMed, Embase, Web of Science and Cochrane up to 9 February 2023. And we selected healthy individuals, mild/severe, and even deceased COVID-19 patients to analyze their serum data. Data related to 2319 patients from 20 studies were analyzed. In the mild/severe group, zinc deficiency was associated with the degree of severe disease (SMD = 0.50, 95% CI 0.32-0.68, I2 = 50.5%) and we got an Egger's test of p = 0.784; but selenium deficiency was not associated with the degree of severe disease (SMD = - 0.03, 95% CI - 0.98-0.93, I2 = 96.7%). In the surviving/death group, zinc deficiency was not associated with mortality of COVID-19 (SMD = 1.66, 95%CI - 1.42-4.47), nor was selenium (SMD = - 0.16, 95%CI - 1.33-1.01). In the risk group, zinc deficiency was positively associated with the prevalence of COVID-19 (SMD = 1.21, 95% CI 0.96-1.46, I2 = 54.3%) and selenium deficiency was also positively associated with the prevalence of it (SMD = 1.16, 95% CI 0.71-1.61, I2 = 58.3%). Currently, serum zinc and selenium deficiencies increase the incidence of COVID-19 and zinc deficiency exacerbates the disease; however, neither zinc nor selenium was associated with mortality in patients with COVID-19. Nevertheless, our conclusions may change when new clinical studies are published.

Research on Liver Damage Caused by the Treatment of Rheumatoid Arthritis with Novel Biological Agents or Targeted Agents.

Rheumatoid arthritis (RA) is a chronic autoimmune disease characterized by polyarticular, symmetric, and aggressive inflammation of the small joints in the hands and feet, resulting in dysfunction. With progress and development in medicine, treatment of RA is constantly evolving, making several drugs available for the treatment of RA. From the nonsteroidal anti-inflammatory drugs (NSAIDs) at the start of illness to glucocorticoids and then to conventional synthetic DMARDs (csDMARDs), biologic DMARDs (bDMARDs), and targeted synthetic DMARDs (tsDMARDs), therapeutic-use drugs for RA have been keeping pace with scientific research. However, various types of drugs have additional side effects when used over the long-term. New and emerging biological and targeted agents have been widely applied in recent years; however, the side effects have not been thoroughly investigated. In this paper, we review the research progress on liver damage caused by novel biological and targeted agents available for RA treatment. The aim is to provide a reference for rational clinical administration of such drugs.

Association between passive smoking and the risk of rheumatoid arthritis: a systematic review and meta-analysis.

In order to provide a basis for the prevention of RA, this systematic review and meta-analysis evaluated the association between passive smoking and the risk of developing RA. We searched electronic databases, including PubMed, Cochrane Central Register of Controlled Trials, Web of Science, and Embase, for published literature from the establishment to March 2022. Then we included subject-related cohort studies and case-control studies, and two researchers independently screened and extracted relevant data. Finally, we performed a meta-analysis, cumulative meta-analysis, and dose-response meta-analysis using the Stata software and evaluated the included literature for the level of evidence. This meta-analysis included three case-control and three cohort studies. There was only a small amount of statistical heterogeneity among the studies (I2 = 34.9%). According to the study results, the risk of RA was 12% higher in passive smokers than in unexposed individuals. In subgroup analysis, a 12% increase in the prevalence of RA was observed in those exposed to passive smoking in adulthood. The developing RA rate was 34% higher in individuals exposed to passive smoking during childhood than in unexposed individuals. As time progressed and with the inclusion of extensive sample studies in the cumulative meta-analysis, the precision of the overall incidence effect values gradually increased. A dose-response meta-analysis showed no statistical significance that the risk of RA increased with the number of passive smoking years. Passive smoking may relate to the risk of RA, especially in childhood exposures.

Sulforaphane Ameliorates Hepatic Lipid Metabolism via Modulating Lipophagy In Vivo and In Vitro.

Although sulforaphane (SFN) is reported to ameliorate the excessive accumulation of lipid droplets (LDs) in hepatocytes, its underlying mechanism remains unclear. This paper aims to investigate how SFN induces hepatic LD degradation via activating macroautophagy. High-fat diet and free fatty acids (FFAs) were used to induce excessive LD formation in hepatocytes in vivo and in vitro, respectively. SFN-induced macroautophagy was shown by the increased LC3 protein expression both (1.32 ± 0.18) in vivo and (2.43 ± 0.22) in vitro. The mRNA levels of Lc3 (1.99 ± 0.16), Atg4 (2.12 ± 0.23), Ulk1 (1.19 ± 0.12), Atg7 (1.25 ± 0.11), and Atg5 (0.81 ± 0.1) genes were elevated by SFN. SFN individually enhanced the localization of LC3 (0.41 ± 0.15), LAMP1 (0.66 ± 0.14), ATG7 (0.26 ± 0.08), and ATG5 (0.38 ± 0.09) with LDs, indicating the occurrence of lipophagy. In the components of LDs isolated from SFN treatment, the expressions of LC3, ATG7, and ATG5 protein were largely increased both in vivo and in vitro. LDs were visualized in autophagosomes which confirmed that the lipophagy was triggered by SFN. Moreover, SFN treatment improved the profile of FFAs which was characterized by increasing the FFAs in liver (total FFA: 261.51 ± 39.58 µM/g) and serum (total FFA: 967.59 ± 239.18 nM/mL). After silencing the nrf2 gene, ATG7 and ATG5 protein expressions were decreased and attenuated this induction by SFN. Nrf2 gene silencing inversely increased TG contents. In summary, SFN enhanced the LD degradation via stimulating lipophagy in a Nrf2-dependent manner.

Genome Sequence Resource for Colletotrichum viniferum, the Cause of Grapevine Ripe Rot in China.

Grape ripe rot is an important disease that has seriously damaged the yield and quality of grape worldwide. The disease is caused by Colletotrichum viniferum, a hemibiotrophic fungus that belongs to the Glomerellaceae family of Sordariomycetes class. Here, we present the genome of C. viniferum CvYL2a from grape, based on Illumina HiSeq 2500 and PacBio RS II. The high-quality genome consists of 70 contigs with a 73.41 Mb genome size and encodes 14,668 protein-coding genes. These genes were annotated using Gene Ontology, Kyoto Encyclopedia of Genes and Genomes, EuKaryotic Orthologous Groups, Nonredundant Protein, and Swiss-Prot databases. In addition, we identified a series of genes involved in pathogenicity, including 909 carbohydrate-active enzymes, 67 secondary metabolite gene clusters, and 307 cytochrome P450 enzymes. This genome sequence provides a valuable reference for research on grape-C. viniferum interactions, the pathogenesis of C. viniferum, and comparative genome analyses.[Formula: see text] Copyright © 2021 The Author(s). This is an open access article distributed under the CC BY-NC-ND 4.0 International license.

Sulforaphane inhibits the production of Aß partially through the activation of Nrf2-regulated oxidative stress.

Sulforaphane (SFN), a potent nuclear factor erythroid 2-related factor 2 (Nrf2) activator, presents a potential role in improving Alzheimer's disease (AD)-specific symptoms. However, the regulation mechanism of SFN in AD is poorly understood. Here, we established AD models both in vitro and in vivo. Animal behaviors were tested by the Morris water maze test. The pathology of the hippocampus and the content of Aß were detected. SFN (40 mg kg-1) decreased the escape latency (24.96 ± 7.43 s) and increased the target-zone frequency (3.19 ± 1.19) in rats. SFN improved the pathological morphology and the number of neurons in the hippocampus. Additionally, SFN significantly upregulated the contents of thioredoxin and glutathione as well as the activities of antioxidant enzymes, along with the expression of the Nrf2 protein. Conversely, SFN lowered the Aß content and ROS level in N2a/APP cells. After silencing the Nrf2 by SiRNA, the inhibitory effects of SFN on ROS and Aß production were partially weakened. In conclusion, the improvement of AD by SFN was closely related with Nrf2 activation.

Melamine-based Covalent Organic Polymers (MCOPs) as Lipase Nanocarrier for Recyclable Esters Hydrolysis and Transesterification.

Present study has successfully synthesized melamine-based covalent organic polymers (MCOPs) and applied it as lipase carrier for recyclable esters hydrolysis and transesterification. The synthesized MCOPs are composed of dense nanosheet structures having a thickness of 3.5 nm. Three immobilization methods namely physical adsorption, cross-linking and carrier activation were employed to prepare the MCOPs-immobilized CRL. Cross-linked MCOPs-immobilized CRL (41.30 mg protein/g MCOPs) and carrier activated MCOPs-immobilized CRL (33.20 mg protein/g MCOPs) had higher enzyme loading as compared to physical absorb MCOPs-immobilized CRL (29.30 mg protein/g MCOPs). Nevertheless, physical absorb MCOPs-immobilized CRL demonstrated the highest esters hydrolysis (49.85 U) and transesterification (1.04 U) activities. Despite having the highest enzymatic activity, physical absorb MCOPs-immobilized CRL were not able to maintain its catalytic stability with more than 30% decreased in enzymatic activity during consecutive hydrolysis and transesterification activities. Meanwhile, cross-linked MCOPs-immobilized CRL demonstrated highest catalytic stability with highest enzymatic activities at the end of consecutive reactions. All the MCOPs-immobilized CRL can be easily recovered and reused through centrifugation with more than 85% of recovery rate.

Lipase-catalyzed selective enrichment of omega-3 polyunsaturated fatty acids in acylglycerols of cod liver and linseed oils: Modeling the binding affinity of lipases and fatty acids.

Present study employed molecular modeling method to elucidate the binding affinity of lipases with fatty acids of different chain lengths; and investigated the effects of lipases positional and fatty acids specificity on omega-3 polyunsaturated fatty acids (ω-3 PUFAs) enrichment in cod liver and linseed oils. Among the lipases studied, molecular modeling showed the active sites of Candida rugosa lipase (CRL) had a low C-Docker interactive energy for saturated (SFA) and monounsaturated (MUFA) fatty acids which predicted CRL to have highest preferences to selectively hydrolyze resulting in efficient enrichment of ω-3 PUFAs. Verification experiments showed the SFA and MUFA in the acylglycerol fraction includes monoacylglcyerols (MAG), diacyglycerols (DAG), and triacylglycerols (TAG) of CRL-hydrolyzed cod liver oil decreased from the initial 25.21 to 16.88% and 45.25 to 32.17%, respectively. In addition, CRL-hydrolyzed cod liver oil demonstrated 88.36% of ω-3 PUFAs enrichment. The regio-distribution of fatty acids in CRL-hydrolyzed cod liver oil were not significantly different than that of cod liver oil indicating the ω-3 PUFAs enrichment was due to fatty acids selectivity and not positional selectivity of CRL.

Characterization of Diastereo- and Enantioselectivity in Degradation of Synthetic Pyrethroids in Soils.

Permethrin (PM), cypermethrin (CP), and cyfluthrin (CF) are three important synthetic pyrethroids, which contain two, four, and four enantiomeric pairs (diastereomers) and thus have four, eight, and eight stereoisomers, respectively. In this study, the stereo- and enantioselective degradation of PM, CP, and CF in a Shijiazhuang alkaline yellow soil and a Wuhan acidic red soil were studied in detail by a combination of achiral and chiral high-performance liquid chromatography (HPLC). The results showed that PM, CP, and CF degraded faster in Shijiazhuang soil than in Wuhan soil, and the dissipation rate followed an order of PM > CF > CP in both soils. The three pyrethroids exhibited similar diastereomer selectivity, while CP and CF showed higher enantioselectivity than PM. Moreover, the trans-diastereomers degraded faster, and showed higher enantioselectivity than the corresponding cis-diastereomers. For PM, the enantiomer 1S-trans-PM degraded most rapidly in both soils. As for CP and CF, the highest enantioselectivity was observed for diastereomer trans-3, and the insecticidally active enantiomer 1R-trans-αS degraded fastest among the 8 CP or CF stereoisomers in both soils. In addition, the Wuhan acidic soil displayed higher diastereomer and enantiomer selectivity than the Shijiazhuang alkaline soil for the three pyrethroids. Further incubation of CF in an alkaline-treated Wuhan soil showed that the dissipation rate greatly increased and the diastereo- and enantioselectivity significantly decreased after the alkaline treatment process.

Stereoselective degradation and microbial epimerization of triadimenol in soils.

Triadimenol is a widely used triazole fungicide and consists of four stereoisomers with 1R,2S, 1S,2R, 1R,2R, and 1S,2S configurations. The trans-enantiomeric pair (1R,2S-isomer and 1S,2R-isomer) is also called triadimenol-A and the cis-enantiomeric pair (1R,2R-isomer and 1S,2S-isomer) triadimenol-B. In this study, the stereoselective degradation and chiral stability of triadimenol in two soils were investigated in details. The dissipation of technical triadimenol, a 6:1 mixture of triadimenol-A and triadimenol-B, showed significant epimerization from triadimenol-A to triadimenol-B occurred along with the dissipation process. The degradation exhibited some stereoselectivity, resulting in a concentration order of 1S,2S > 1R,2R > 1R,2S > 1S,2R or 1S,2S > 1R,2R > 1S,2R > 1R,2S at the end of the 100 days incubation for Baoding soil or Wuhan soil, respectively. Further incubation of triadimenol-B revealed no epimerization, i.e. triadimenol-B was configurationally stable in soil, and 1R,2R-triadimenol degraded slightly slower in the former part and slightly faster in the later part of the incubation than 1S,2S-triadimenol. Moreover, by incubation of enantiopure 1S,2R-triadimenol and 1R,2S-triadimenol, the results documented the epimerization for each enantiomer occurred at both C-1 and C-2 positions. Finally, the present work also documented that the enantiomerization reaction for all the four stereoisomers was nearly negligible in the soils.