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Zhongguo Yi Xue Ke Xue Yuan Xue Bao.... Jun 2024With the continuous development of identification technologies such as mass spectrometry,omics,and antibody technology,post-translational modification (PTM) has... (Review)
Review
With the continuous development of identification technologies such as mass spectrometry,omics,and antibody technology,post-translational modification (PTM) has demonstrated increasing potential in medical research.PTM as a novel chemical modification method provides new perspectives for the research on diseases.Succinylation as a novel modification has aroused the interest of more and more researchers.The available studies about succinylation mainly focus on a desuccinylase named sirtuin 5.This enzyme plays a key role in modification and has been preliminarily explored in cardiovascular studies.This paper summarizes the influencing factors and regulatory roles of succinylation and the links between succinylation and other PTMs and reviews the research progress of PTMs in the cardiovascular field,aiming to deepen the understanding about the role of this modification and give new insights to the research in this field.
Topics: Cardiovascular Diseases; Humans; Lysine; Protein Processing, Post-Translational; Succinic Acid
PubMed: 38953268
DOI: 10.3881/j.issn.1000-503X.15944 -
The ISME Journal Jul 2024Microbial interactions impact the functioning of microbial communities. However, microbial interactions within host-associated communities remains poorly understood....
Microbial interactions impact the functioning of microbial communities. However, microbial interactions within host-associated communities remains poorly understood. Here, we report that the beneficiary rhizobacterium Niallia sp. RD1 requires the helper Pseudomonas putida H3 for bacterial growth and beneficial interactions with the plant host. In the absence of the helper H3 strain, the Niallia sp. RD1 strain exhibited weak respiration and elongated cell morphology without forming bacterial colonies. A transposon mutant of H3 in a gene encoding succinate-semialdehyde dehydrogenase displayed much attenuated support of RD1 colony formation. Through subsequent addition of succinate to the media, we found that succinate serves as a public good that supports RD1 growth. Comparative genome analysis highlighted that RD1 lacked the gene for sufficient succinate, suggesting its evolution as a beneficiary of succinate biosynthesis. The syntrophic interaction between RD1 and H3 efficiently protected tomato plants from bacterial wilt and promoted the tomato growth. The addition of succinate to the medium restored complex II-dependent respiration in RD1 and facilitated the cultivation of various bacterial isolates from the rhizosphere. Taken together, we delineate energy auxotrophic beneficiaries ubiquitous in the microbial community, and these beneficiaries could benefit host plants with the aid of helpers in the rhizosphere.
PubMed: 38952008
DOI: 10.1093/ismejo/wrae120 -
World Journal of Stem Cells Jun 2024Validation of the reference gene (RG) stability during experimental analyses is essential for correct quantitative real-time polymerase chain reaction (RT-qPCR) data...
BACKGROUND
Validation of the reference gene (RG) stability during experimental analyses is essential for correct quantitative real-time polymerase chain reaction (RT-qPCR) data normalisation. Commonly, in an unreliable way, several studies use genes involved in essential cellular functions [glyceraldehyde-3-phosphate dehydrogenase (GAPDH), 18S rRNA, and β-actin] without paying attention to whether they are suitable for such experimental conditions or the reason for choosing such genes. Furthermore, such studies use only one gene when Minimum Information for Publication of Quantitative Real-Time PCR Experiments guidelines recommend two or more genes. It impacts the credibility of these studies and causes distortions in the gene expression findings. For tissue engineering, the accuracy of gene expression drives the best experimental or therapeutical approaches.
AIM
To verify the most stable RG during osteogenic differentiation of human dental pulp stem cells (DPSCs) by RT-qPCR.
METHODS
We cultivated DPSCs under two conditions: Undifferentiated and osteogenic differentiation, both for 35 d. We evaluated the gene expression of 10 candidates for RGs [ribosomal protein, large, P0 (), TATA-binding protein (), , actin beta (), tubulin (), aminolevulinic acid synthase 1 (), tyrosine 3-monooxygenase/tryptophan 5-monooxygenase activation protein, zeta (), eukaryotic translational elongation factor 1 alpha (), succinate dehydrogenase complex, subunit A, flavoprotein (), and beta-2-microglobulin ()] every 7 d (1, 7, 14, 21, 28, and 35 d) by RT-qPCR. The data were analysed by the four main algorithms, ΔCt method, geNorm, NormFinder, and BestKeeper and ranked by the RefFinder method. We subdivided the samples into eight subgroups.
RESULTS
All of the data sets from clonogenic and osteogenic samples were analysed using the RefFinder algorithm. The final ranking showed RPLP0/TBP as the two most stable RGs and TUB/B2M as the two least stable RGs. Either the ΔCt method or NormFinder analysis showed TBP/RPLP0 as the two most stable genes. However, geNorm analysis showed RPLP0/EF1α in the first place. These algorithms' two least stable RGs were B2M/GAPDH. For BestKeeper, ALAS1 was ranked as the most stable RG, and SDHA as the least stable RG. The pair RPLP0/TBP was detected in most subgroups as the most stable RGs, following the RefFinfer ranking.
CONCLUSION
For the first time, we show that RPLP0/TBP are the most stable RGs, whereas TUB/B2M are unstable RGs for long-term osteogenic differentiation of human DPSCs in traditional monolayers.
PubMed: 38948092
DOI: 10.4252/wjsc.v16.i6.656 -
JCEM Case Reports Jul 2024The diagnosis of pheochromocytoma or paraganglioma (PGL) during pregnancy is extremely rare, with 2 large case series suggesting that the prevalence is between 0.0002%...
The diagnosis of pheochromocytoma or paraganglioma (PGL) during pregnancy is extremely rare, with 2 large case series suggesting that the prevalence is between 0.0002% and 0.007%. Here, we present a case of a 38-year-old woman who presented during pregnancy with clinical features suggestive of preeclampsia and was found to have a norepinephrine-secreting inferior laryngeal nerve PGL, which was diagnosed after pregnancy. She underwent uncomplicated surgical resection and genetic testing revealed a succinate dehydrogenase subunit B pathogenic variant. In conclusion, PGLs diagnosed during pregnancy and hypersecreting head and neck PGLs are both rare clinical entities. Hyperfunctioning PGLs may mimic pregnancy-induced hypertension or preeclampsia. Metanephrine testing should be considered in patients with atypical features and can be reliably assessed using nonpregnant reference ranges. Overall, maternal and fetal mortality has improved considerably with early diagnosis and treatment.
PubMed: 38947415
DOI: 10.1210/jcemcr/luae107 -
Diabetes & Metabolism Journal Jul 2024Although the prevalence of diabetic kidney disease (DKD) is increasing, reliable biomarkers for its early detection are scarce. This study aimed to evaluate the...
BACKGROUND
Although the prevalence of diabetic kidney disease (DKD) is increasing, reliable biomarkers for its early detection are scarce. This study aimed to evaluate the association of adenosine and succinate levels and their related pathways, including hyaluronic acid (HA) synthesis, with DKD.
METHODS
We examined 235 participants and categorized them into three groups: healthy controls; those with diabetes but without DKD; and those with DKD, which was defined as estimated glomerular filtration rate (eGFR) <60 mL/min/1.73 m2. We compared the concentrations of urinary adenosine, succinate, and HA and the serum levels of cluster of differentiation 39 (CD39) and CD73, which are involved in adenosine generation, among the groups with DKD or albuminuria. In addition, we performed multiple logistic regression analysis to evaluate the independent association of DKD or albuminuria with the metabolites after adjusting for risk factors. We also showed the association of these metabolites with eGFR measured several years before enrollment. This study was registered with the Clinical Research Information Service (https://cris.nih.go.kr; Registration number: KCT0003573).
RESULTS
Urinary succinate and serum CD39 levels were higher in the DKD group than in the control and non-DKD groups. Correlation analysis consistently linked urinary succinate and serum CD39 concentrations with eGFR, albuminuria, and ΔeGFR, which was calculated retrospectively. However, among the various metabolites studied, only urinary succinate was identified as an independent indicator of DKD and albuminuria.
CONCLUSION
Among several potential metabolites, only urinary succinate was independently associated with DKD. These findings hold promise for clinical application in the management of DKD.
PubMed: 38945526
DOI: 10.4093/dmj.2023.0377 -
ACS Sustainable Chemistry & Engineering Jun 2024Understanding the properties of polymers, such as their crystallinity, is crucial for their material performance and predicting their behavior during and after use,...
Understanding the properties of polymers, such as their crystallinity, is crucial for their material performance and predicting their behavior during and after use, especially in the case of environmentally friendly (bio)degradable polymers, enabling optimized design. In this work, for the first time, a pressure-induced condis crystal-like mesophase of poly(butylene succinate--butylene adipate) (PBSA) is presented. The phase behavior of pressed films obtained from commercial PBSA with 25% butylene adipate units is investigated at various processing temperatures from room temperature to 100 °C, pressed at a pressure of the press jaws and at 2-5 t for 1-5 min. The characterization and quantification evaluation of the condis crystal-like mesophase of pressed PBSA formed at temperatures above the glass transition is investigated by X-ray diffraction, polarized optical microscopy (POM), and differential scanning calorimetry (DSC) methods. Our results demonstrate that pressed PBSA films at 60 °C show a condis crystal-like mesophase, characterized by the presence of reflections at wide angles, birefringence by POM, as well as a higher melting point (endotherm) by DSC. The resulting oriented mesomorphic green polymer can, in a sustainable manner, expand further technological applications of (bio)degradable polymers, especially in the medical field, and open up opportunities for further research that could provide such polymers with tailored persistence and degradation, thus changing the shelf life.
PubMed: 38939870
DOI: 10.1021/acssuschemeng.4c03285 -
Advances in Pharmacological and... 2024Nutritional supplements are gaining traction for their effects in mitigating the impacts of various health conditions. In particular, many supplements are being proposed...
Nutritional supplements are gaining traction for their effects in mitigating the impacts of various health conditions. In particular, many supplements are being proposed to reduce the impacts of type 2 diabetes (T2D), a metabolic condition that has reached global epidemic proportions. Recently, a supplement of oleic acid (OA) and succinic acid (SA; 1 : 1, w/w) was reported to improve glycaemic control in type 2 diabetic (T2D) Sprague-Dawley (S-D) rats through ameliorating insulin release and sensitivity. Here, we investigate the effects of the supplement (OA and SA) on hepatic and pancreatic function in T2D S-D rats. Eighteen (18) S-D rats were rendered diabetic and were divided into three equal groups: diabetic control, diabetic treatment, and diabetic glibenclamide. Another 12 S-D rats were obtained and served as the normal groups. The animals were treated daily with the vehicle, OA and SA (800 mg/kg body weight (bw); 1 : 1), or glibenclamide (10 mg/kg bw) which served as the positive control. The findings indicated that treatment with the supplement resulted in a 35.69 ± 4.22% reduction (=0.006) in blood glucose levels (BGL). Analysis of hepatic enzymes depicted that the nutritional supplement reduced the activity of the gluconeogenesis enzyme, glucose-6-phosphatase (G6P) while improved the activity of catabolic enzymes such as glucose-6-phosphate dehydrogenase (G6PD) and pyruvate kinase (PK). Furthermore, the supplement attenuated oxidative stress through restoration of catalase (CAT) and superoxide dismutase (SOD), while reducing malondialdehyde (MDA) levels. Finally, the supplement showed no liver or kidney toxicity and improved the size and number of pancreatic islets of Langerhans, indicating its potential application in treating T2D. The study highlighted that a supplement of the two organic acids may be beneficial in reducing the rate of pathogenesis of type 2 diabetes. Therefore, it may offer therapeutic value as a dietary or nutritional supplement in the approach against diabetes and its complications.
PubMed: 38938594
DOI: 10.1155/2024/5556722 -
Scientifica 2024is well known for its medicinal properties. It has exhibited various pharmacological activities, such as antidiabetic, anti-inflammatory, and antimicrobial activities....
is well known for its medicinal properties. It has exhibited various pharmacological activities, such as antidiabetic, anti-inflammatory, and antimicrobial activities. Although this plant is used worldwide as a vegetable and medicinal ingredient in herbal medicines, its toxicity studies have not been conducted to date. This study attempts to understand its toxicity. The present study examined the activity of two enzymes, acetylcholinesterase and succinate dehydrogenase, as well as histopathological variations in the liver, intestine, and gills of zebrafish. The results of the acetylcholinesterase assay showed that the concentrations of 40 mg/L and 60 mg/L of the four extracts (leaf and fruit extracts of both varieties) exhibited increased enzyme activity. Interestingly, the leaves of the green fruit variety at a concentration of 60 mg/L showed the highest activity, with a value of 2.824 ± 0.0682 micromoles/min compared to the control value of 1.8347 ± 0.0046 micromoles/min. On the other hand, the succinate dehydrogenase assay revealed that the concentrations of 40 mg/L and 60 mg/L of the extracts decreased the enzyme activity. The highest inhibition was observed in the concentration of 60 mg/L of the leaves of the white-fruited variety and the green-fruited variety, with values of 1.884 ± 0.0482 micromoles/min compared to the control value of 2.747 ± 0.0046 micromoles/min. The studies on histopathological changes also demonstrated abnormalities in the brain, liver, intestine, and gills of zebrafish after the exposure to the extracts of . The severity of the damage varied from low to high concentraions. In general, this study sheds light on the safety profile of and highlights its potential toxicity in animal models. The findings suggest that more research is needed to fully understand the toxicity of this plant and its implications for human use.
PubMed: 38938544
DOI: 10.1155/2024/4689625 -
Frontiers in Immunology 2024Succinate, traditionally viewed as a mere intermediate of the tricarboxylic acid (TCA) cycle, has emerged as a critical mediator in inflammation. Disruptions within the... (Review)
Review
Succinate, traditionally viewed as a mere intermediate of the tricarboxylic acid (TCA) cycle, has emerged as a critical mediator in inflammation. Disruptions within the TCA cycle lead to an accumulation of succinate in the mitochondrial matrix. This excess succinate subsequently diffuses into the cytosol and is released into the extracellular space. Elevated cytosolic succinate levels stabilize hypoxia-inducible factor-1α by inhibiting prolyl hydroxylases, which enhances inflammatory responses. Notably, succinate also acts extracellularly as a signaling molecule by engaging succinate receptor 1 on immune cells, thus modulating their pro-inflammatory or anti-inflammatory activities. Alterations in succinate levels have been associated with various inflammatory disorders, including rheumatoid arthritis, inflammatory bowel disease, obesity, and atherosclerosis. These associations are primarily due to exaggerated immune cell responses. Given its central role in inflammation, targeting succinate pathways offers promising therapeutic avenues for these diseases. This paper provides an extensive review of succinate's involvement in inflammatory processes and highlights potential targets for future research and therapeutic possibilities development.
Topics: Humans; Succinic Acid; Inflammation; Signal Transduction; Animals; Citric Acid Cycle; Receptors, G-Protein-Coupled
PubMed: 38933270
DOI: 10.3389/fimmu.2024.1404441 -
Polymers Jun 2024Biodegradable poly(butylene succinate--2-methyl succinate) (PBSMS)/cellulose nanocrystals (CNC) composites were successfully prepared at low CNC loadings with the aims...
Biodegradable poly(butylene succinate--2-methyl succinate) (PBSMS)/cellulose nanocrystals (CNC) composites were successfully prepared at low CNC loadings with the aims of improving crystallization and mechanical properties and extending the practical application of PBSMS. CNC is finely dispersed in the PBSMS matrix without obvious aggregations. The low content of CNC obviously promoted the crystallization behavior of PBSMS under different conditions. The spherulitic morphology study revealed that CNC, as an effective heterogeneous nucleating agent, provided more nucleation sites during the melt crystallization process. In addition, the nucleation effect of CNC was quantitatively evaluated by the following two parameters, i.e., nucleation activity and nucleation efficiency. The crystal structure and crystallization mechanism of PBSMS remained unchanged in the composites. In addition, as a reinforcing nanofiller, CNC significantly increased Young's modulus and the yield strength of PBSMS. The crystallization behavior and mechanical properties of PBSMS were significantly improved by the low content of CNC, which should be interesting and essential from the perspective of biodegradable polymer composites.
PubMed: 38932085
DOI: 10.3390/polym16121735