Ginseng total saponin improves red blood cell oxidative stress injury by regulating tyrosine phosphorylation and glycolysis in red blood cells.

BACKGROUND: Oxidative stress is the main cause of many diseases, but because of its complex pathogenic factors, there is no clear method for treating it. Ginseng total saponin (GTS) an important active ingredients in Panax ginseng C.A. Mey (PG) and has potential therapeutic ability for oxidative stress due to various causes. However, the molecular mechanism of GTS in the treating oxidative stress damage in red blood cells (RBCs) is still unclear. PURPOSE: This study aimed to examine the protective effect of GTS on RBCs under oxidative stress damage and to determine its potential mechanism. METHODS: The oxidative stress models of rat RBCs induced by hydrogen peroxide (H2O2) and exhaustive swimming in vivo and in vitro was used. We determined the cell morphology, oxygen carrying capacity, apoptosis, antioxidant capacity, and energy metabolism of RBCs. The effect of tyrosine phosphorylation (pTyr) of Band 3 protein on RBCs glycolysis was also examined. RESULTS: GTS reduced the hemolysis of RBCs induced by H2O2 at the lowest concentration. Moreover, GTS effectively improved the morphology, enhanced the oxygen carrying capacity, and increased antioxidant enzyme activity, adenosine triphosphate (ATP) levels, and adenosine triphosphatase (ATPase) activity in RBCs. GTS also promoted the expression of membrane proteins in RBCs, inhibited pTyr of Band 3 protein, and further improved glycolysis, restoring the morphological structure and physiological function of RBCs. CONCLUSIONS: This study shows, that GTS can protect RBCs from oxidative stress damage by improving RBCs morphology and physiological function. Changes in pTyr expression and its related pTyr regulatory enzymes before and after GTS treatment suggest that Band 3 protein is the main target of GTS in the treating endogenous and exogenous oxidative stress. Moreover, GTS can enhance the glycolytic ability of RBCs by inhibiting pTyr of Band 3 protein, thereby restoring the function of RBCs.

[High performance liquid chromatography combined with the 2,2'-dithiodipyridine derivatization reaction for determination of different types of free thiols in human serum and analysis of their relationship with coronary heart disease].

Oxidative stress, which is characterized by an imbalance between antioxidants and free radicals, plays a pivotal role in the pathogenesis of coronary heart disease, a common and serious cardiovascular condition, and contributes significantly to its development and progression. Serum free thiols are crucial components of the body's antioxidant defense system. The accurate determination of serum free thiol levels provides a reference basis for understanding the body's status and monitoring the risk factors associated with the occurrence and progression of coronary heart disease. In this study, a high performance liquid chromatographic (HPLC) method based on the derivatization reaction of 2,2'-dithiodipyridine was developed to simultaneously obtain the concentrations of total free thiols (Total-SH), low-molecular-mass free thiols (LMM-SH), and protein-free thiols (P-SH) in human serum. An Agilent Eclipse XDB-C18 column (150 mm×4.6 mm, 5 µm) was used for the analysis, and gradient elution was performed at a flow rate of 1 mL/min. A 0.1% formic acid aqueous solution was used as mobile phase A, and a 0.1% formic acid acetonitrile solution was used as mobile phase B. The gradient elution program was as follows: 0-0.1 min, 12%B-30%B; 0.1-2 min, 30%B; 2-2.1 min, 30%B-100%B; 2.1-6 min, 100%B; 6-6.1 min, 100%B-12%B; 6.1-7 min, 12%B. Well-separated peaks appeared after a run time of 5 min. The peak of 2-thiopyridone represented the Total-SH content of the samples, and the peak of the pyridyldithio derivative represented the LMM-SH content. The difference between these two peaks indicated the P-SH content. The derivatization reaction conditions were optimized, and the method was validated. The method demonstrated good linearity, with a correlation coefficient ≥0.9994, over the concentration range of 31.25-1000 µmol/L. The limits of detection for Total-SH and LMM-SH were 2.61 and 0.50 µmol/L, and the limits of quantification for Total-SH and LMM-SH were 8.71 and 1.67 µmol/L, respectively. The recoveries of Total-SH and LMM-SH were in the range of 91.1%-106.0%. The intra- and inter-day precisions ranged from 0.4% to 9.1%. The developed method was used to analyze serum samples from 714 volunteers. The Total-SH concentrations ranged from 376.60 to 781.12 µmol/L, with an average concentration of 555.62 µmol/L. The LMM-SH concentrations varied from 36.37 to 231.65 µmol/L,with an average of 82.34 µmol/L. The P-SH concentrations ranged from 288.36 to 687.74 µmol/L, with an average of 473.27 µmol/L. Spearman's correlation test showed that serum thiol levels were correlated with the severity of coronary artery disease and common clinical biochemical indicators. The proposed study provides a simple and reliable HPLC method for detecting serum free thiols and exploring their relationship with coronary heart disease, offering a new reference for the study of markers related to the risk of coronary heart disease.

Total ginsenosides extend healthspan of aging Drosophila by suppressing imbalances in intestinal stem cells and microbiota.

BACKGROUND: Disruption of stem cell and microbial homeostasis accelerates the aging process. Hence, maintaining these balances effectively delays aging and alleviates the symptoms of age-related diseases. Recent research indicates that targeting endoplasmic reticulum (ER) stress and immune deficiency (IMD) signalling may play a positive role in maintaining homeostasis in aging intestinal stem cells (ISC) and microbial equilibrium. Previous research has suggested that total ginsenosides (TG) derived from Panax ginseng C. A. Meyer may exhibit potential anti-aging properties by mitigating ER stress and mediating the IMD pathway. Nevertheless, it remains unclear whether TG improve ISC and microbial homeostasis by modulating ER stress and the IMD pathway to promote healthy aging. PURPOSE: To elucidate whether TG promotes healthspan in Drosophila and its underlying molecular mechanisms, focusing on its role in regulating ER stress and the IMD pathway to maintain ISC and intestinal microbiota homeostasis. METHODS: High performance liquid chromatography was performed to detect the main saponin monomer in TG. Survival rate, gut length, barrier function, and feeding/excretion behaviour assays were used to evaluate the effects of TG on the lifespan and gut health of Drosophila. At the stem cell level, "esg-luciferase" reporter system, esg-GFP/delta stem cell fluorescent labelling, and phospho-histone H3+ mitotic activity assays were employed to determine whether TG prevented natural aging or oxidative stress-associated ISC over-proliferation in Drosophila. Immunofluorescence staining was used to detect the effects of TG on ER stress during aging. Overexpression or interference of ER stress target genes and their related c-Jun N-terminal kinase (JNK) gene was manipulated using gene editing technology to verify the molecular mechanism by which TG maintains age-related ISC proliferation homeostasis. Molecular docking and isothermal titration calorimetry were used to verify the direct interactions between TG and ER stress target genes. In addition, at the intestinal flora level, 16S rDNA sequencing was used to analyse the effect of TG on the diversity and abundance of Drosophila intestinal flora and the possible functional pathways involved. RT-qPCR was performed to determine whether TG mediated the expression of target genes in the IMD pathway. A dominant bacterial species-specific mono-association analysis were performed to verify whether the effects of TG on IMD target genes and ISC proliferation depended on the direct control of the dominant bacterial species. RESULTS: Our results suggest that administration of TG delays the decline in gut morphology and function in aging Drosophila. TG prevents age-associated ISC hyperproliferation by inhibiting ER stress IRE1-mediated JNK signaling. Furthermore, oral TG prevented aging-associated ISC and gut microbiota dysbiosis by remodelling the gut microbiota and inhibiting Acetobacter-mediated activation of IMD target genes. CONCLUSION: TG promotes healthy aging by inhibiting the excessive proliferation of ISC and alleviating intestinal microbial imbalance, thereby providing new insights for the research and development of anti-aging TG products.

Serum immunoglobulin M is associated with the severity of coronary artery disease in adults.

Purpose: The purpose of this study was to investigate the relationship between serum immunoglobulin M (IgM) and the severity of coronary artery disease in Chinese patients who underwent coronary angiography. Methods: A total of 2,045 patients who underwent coronary angiography (CAG) from March 2017 to March 2020 at Beijing Hospital were included in this study. Serum IgM concentration and biochemical indicators were measured before coronary angiography (CAG). The triquartile IgM levels at baseline in the population were analysed. Spearman rank correlation was used to analyse the association between IgM and traditional risk factors for coronary artery disease (CAD). CAD patients were divided into subgroups by affected area, number of affected vessels, and Gensini score to analyse the relationship between IgM and CAD severity. Multivariable logistic regression analysis was used to evaluate the association between IgM and CAD severity. Results: Serum IgM levels were significantly lower in the CAD group (63.5 mg/dL) than in the non-coronary artery disease (NCAD) group (72.3 mg/dL) (P < 0.001). Serum IgM levels were significantly associated with sex. Serum IgM levels were positively correlated with traditional CAD risk factors such as TG, TC and LDL-C (P < 0.05), and negatively associated with the number of obstructed vessels, the number of affected areas, and Gensini scores. After adjusting for age, sex, smoking status, hypertension, dyslipidaemia, diabetes, stroke, and statin use history, a high IgM level was independently negatively associated with the severity of CAD expressed by the Gensini score. Conclusion: We determined that serum IgM was independently negatively associated with the severity of CAD diagnosed by angiography in Chinese adults.

Preparation of hepatocellular carcinoma mRNA vaccines based on potential tumor targets and immunophenotypes.

Background: With the development of messenger RNA (mRNA)-based therapeutics for malignant tumor, mRNA vaccines have shown considerable promise for tumor immunotherapy. Immunophenotypes can reflect the tumor microenvironment, which might have a significant influence on the effect of immunotherapy. This study seeks to discover and validate effective antigens that can be employed to develop mRNA vaccines for hepatocellular carcinoma (HCC) and to construct immunophenotypes and immune landscapes to identify potential beneficiaries. Methods: RNA sequencing (RNASeq) data, mutation information, and clinical information were obtained from HCC patients and control cases from The Cancer Genome Atlas - Liver Hepatocellular Carcinoma (TCGA-LIHC), International Cancer Genome Consortium - Liver Cancer (ICGC-LIRI) and Gene Expression Omnibus (GEO) cohorts. Gene Expression Profiling Interactive Analysis (GEPIA2.0), cBioPortal for Cancer Genomics (cBioPortal), Tumor IMmune Estimation Resource (TIMER2.0), and immunohistochemistry (IHC) were employed to discover tumor antigens. ConsensusClusterPlus was employed to perform consistency matrix building and immunophenotypic clustering. Single sample gene set enrichment analysis (ssGSEA), ESTIMATE and monocle2 were employed to map immune cell distribution. Weighted correlation network analysis (WGCNA) was employed to identify potential gene modules that influence the efficacy of mRNA vaccines. Results: Six antigen targets were discovered in the TCGA cohort, including AURKA, CDC25C, KPNA2, MCM3, NEK2 and TUBG1, which were associated with antigen-presenting cell infiltration and poor prognosis. IHC scores of AURKA, CDC25C and MCM3 were higher in tumor tissues, and high scores of AURKA and CDC25C indicated poor prognosis in the validation cohort. Five immunophenotypes derived from TCGA-LIHC and ICGC-LIRI cohorts were consistent. Furthermore, increased expression of blue and black modules may reduce vaccine responsiveness. Conclusions: AURKA, CDC25C, KPNA2, MCM3, NEK2 and TUBG1 may be potential targets for mRNA vaccine development for HCC, especially AURKA and CDC25C. HCC patients with IS1 and IS5 subtypes perhaps present an autoimmunosuppressed state, then IS2 and IS3 subtypes perhaps the potential beneficiaries.

Exploration of the causal effects of leukocyte telomere length and four gastrointestinal diseases: a two-sample bidirectional Mendelian randomization study.

BACKGROUND: To explore the underlying causality between leukocyte telomere length (LTL) and four gastrointestinal diseases, we designed a two-sample bidirectional Mendelian randomization study. METHODS: Two-sample Mendelian randomization (MR) was used to explore genetic causality between LTL and four gastrointestinal diseases, including irritable bowel syndrome (IBS), gastroesophageal reflux disease (GERD), gastrointestinal ulcers disease (GUD), and nonalcoholic fatty liver disease (NAFLD). We utilized inverse-variance weighted (IVW) as the primary method for MR analysis. Supplementary analyses were conducted using methods such as MR-Egger regression, weighted-median, Maximum Likelihood (MaxLik), Robust adjusted profile score (MR-RAPS), Contamination mixture (ConMix), and MR-mix. Cochran's Q was calculated to check for heterogeneity. The MR-Egger regression and MR pleiotropy residual sum and outlier (MR-PRESSO) were detected for pleiotropy. RESULTS: The IVW analysis suggests that there may be a potential causal relationship between LTL and two diseases (odds ratio (OR): 1.062; 95% confidence interval (CI): 1.003, 1.124; p = 0.038 for IBS and OR: 0.889; 95% CI: 0.798, 0.990; p = 0.032 for GERD). However, other methods do not entirely align with the results of the IVW analysis. In the reverse MR analysis, we did not find statistically significant associations between LTL and these four diseases. CONCLUSION: The current evidence does not definitively rule out a causal relationship between LTL and these four gastrointestinal diseases but suggests a potential association between LTL and IBS, or LTL and GERD. Exploring the relationship between gastrointestinal diseases and LTL may offer new insights into the onset, progression, and treatment of these diseases.

Mechanism of synergistic remediation of soil phenanthrene contamination in paddy fields by rice-crab coculture and bioaugmentation with Pseudomonas sp.

Polycyclic aromatic hydrocarbons (PAHs) are persistent and harmful pollutants with high priority concern in agricultural fields. This work constructed a rice-crab coculture and bioaugmentation (RCM) system to remediate phenanthrene (a model PAH) contamination in rice fields. The results showed that RCM had a higher remediation performance of phenanthrene in rice paddy compared with rice cultivation alone, microbial addition alone, and crab-rice coculture, reaching a remediation efficiency of 88.92 % in 42 d. The concentration of phenanthrene in the rice plants decreased to 6.58 mg/kg, and its bioconcentration effect was efficiently inhibited in the RCM system. In addition, some low molecular weight organic acids of rice root increased by 12.87 %∼73.87 %, and some amino acids increased by 140 %∼1150 % in RCM. Bioturbation of crabs improves soil aeration structure and microbial migration, and adding Pseudomonas promoted the proliferation of some plant growth-promoting rhizobacteria (PGPRs), which facilitated the degradation of phenanthrene. This coupling rice-crab coculture with bioaugmentation had favorable effects on soil enzyme activity, microbial community structure, and PAH degradation genes in paddy fields, enhancing the removal of and resistance to PAH contamination in paddy fields and providing new strategies for achieving a balance between production and remediation in contaminated paddy fields.

Treg cells-derived exosomes promote blood-spinal cord barrier repair and motor function recovery after spinal cord injury by delivering miR-2861.

The blood-spinal cord barrier (BSCB) is a physical barrier between the blood and the spinal cord parenchyma. Current evidence suggests that the disruption of BSCB integrity after spinal cord injury can lead to secondary injuries such as spinal cord edema and excessive inflammatory response. Regulatory T (Treg) cells are effective anti-inflammatory cells that can inhibit neuroinflammation after spinal cord injury, and their infiltration after spinal cord injury exhibits the same temporal and spatial characteristics as the automatic repair of BSCB. However, few studies have assessed the relationship between Treg cells and spinal cord injury, emphasizing BSCB integrity. This study explored whether Treg affects the recovery of BSCB after SCI and the underlying mechanism. We confirmed that spinal cord angiogenesis and Treg cell infiltration occurred simultaneously after SCI. Furthermore, we observed significant effects on BSCB repair and motor function in mice by Treg cell knockout and overexpression. Subsequently, we demonstrated the presence and function of exosomes in vitro. In addition, we found that Treg cell-derived exosomes encapsulated miR-2861, and miR-2861 regulated the expression of vascular tight junction (TJs) proteins. The luciferase reporter assay confirmed the negative regulation of IRAK1 by miR-2861, and a series of rescue experiments validated the biological function of IRAKI in regulating BSCB. In summary, we demonstrated that Treg cell-derived exosomes could package and deliver miR-2861 and regulate the expression of IRAK1 to affect BSCB integrity and motor function after SCI in mice, which provides novel insights for functional repair and limiting inflammation after SCI.

Sex difference in cardiac performance in individuals with irregular shift work.

Background: sex differences existed in animal behavioral adaption and activity rhythms when exposed to chronic disruption of the circadian rhythm. Whether these differences extend to cardiac performance has not been fully investigated by cardiac imaging technology. Methods: One hundred and thirty patients enrolled in this study. Patients were divided into the day shift (DS) group and the irregular shift (IRS) group based on whether involved in the night shift and the frequency of the night shift. Comparisons of clinical data and cardiac imaging parameters were performed to identify the sex difference in cardiac function in the participants with day shift work or irregular shifts. Results: The absolute value of GLS was significantly lower in male IRS group than in male DS group. In females, no significant difference was tested in left ventricular function between the two groups. In male participants, Weekly work hours (WWH) was positively correlated with HR (r = 0.51, p = 0.02) and QTc duration (r = 0.68, p < 0.00), and weakly negatively correlated with the GLS (r = -0.38, p = 0.05). Amongst patients, there was a 2.67-fold higher relative risk (RR) for impaired GLS in males than in females, with a 95 % confidence interval (CI) of 1.20-5.61. Moreover, there was an increased risk in the male IRS group compared to the female IRS group to develop impaired GLS (RR:3.14, 95 % CI 1.20-7.84). Conclusions: The present study suggests that chronic circadian disruption brings cardiac dysfunction in people with night-shift work. Gender differences exist in the impact of circadian rhythmicity on cardiac function and may help to guide the work schedule and breaks in shift workers and bring forward prevention strategies in response to chronic circadian disruption.

L. barbarum (Lycium barbarum L.) supplementation for lipid profiles in adults: A systematic review and meta-analysis of RCTs.

BACKGROUND: Dyslipidemia is a global health concern with an increasing prevalence worldwide. Lycium barbarum (L. barbarum) is widely used as a medicinal and functional food, and evidence suggests that it may be beneficial for lipid management. In this study, we performed a systematic review and meta-analysis of randomized controlled trials investigating the effects of L. barbarum supplementation on lipid profiles in adults. METHODS: PubMed, China National Knowledge Infrastructure, The Cochrane Library, Web of Science, and Wanfang Database were searched from inception until October 2022. The random-effect model was applied, and the pooled effect sizes were expressed as mean differences (MDs) and 95% confidence intervals (CIs). RESULTS: The meta-analysis of 5 randomized controlled trials involving 259 subjects indicated that L. barbarum supplementation significantly decreased the triglyceride (TG) concentration (MD: 0.14 mmol/L, 95% CI: 0.08-0.20) and increased the high-density lipoprotein cholesterol concentration (HDL-C) (MD: -0.07 mmol/L, 95% CI: -0.13 to -0.01). However, the reductions in total cholesterol (TC) concentration (MD: 0.11 mmol/L, 95% CI: -0.37 to 0.59) and low-density lipoprotein cholesterol (LDL-C) concentration (MD: 0.21 mmol/L, 95% CI: -0.46 to 0.89) were not statistically significant. CONCLUSION: The present study showed that L. barbarum supplementation might have some beneficial effects on TG and HDL-C concentrations in adults, and L. barbarum fruit has an even greater effect on TG and HDL-C concentrations. Considering the sensitivity analyses and limitations of the study included, further large-scale studies are needed to confirm these findings.

Ginsenosides on stem cells fate specification-a novel perspective.

Recent studies have demonstrated that stem cells have attracted much attention due to their special abilities of proliferation, differentiation and self-renewal, and are of great significance in regenerative medicine and anti-aging research. Hence, finding natural medicines that intervene the fate specification of stem cells has become a priority. Ginsenosides, the key components of natural botanical ginseng, have been extensively studied for versatile effects, such as regulating stem cells function and resisting aging. This review aims to summarize recent progression regarding the impact of ginsenosides on the behavior of adult stem cells, particularly from the perspective of proliferation, differentiation and self-renewal.

Isoalantolactone relieves depression-like behaviors in mice after chronic social defeat stress via the gut-brain axis.

RATIONALE: The management of depression continues to be challenging despite the variety of available antidepressants. Herbal medicines are used in many cultures but lack stringent testing to understand their efficacy and mechanism of action. Isoalantolactone (LAT) from Elecampane (Inula helenium) improved the chronic social defeat stress (CSDS)-induced anhedonia-like phenotype in mice comparable to fluoxetine, a selective serotonin reuptake inhibitor (SSRI). OBJECTIVES: Compare the effects of LAT and fluoxetine on depression-like behaviors in mice exposed to CSDS. RESULT: The CSDS-induced decrease in protein expression of postsynaptic density (PSD95), brain derived neurotrophic factor (BDNF), and glutamate receptor subunit-1 (GluA1) in the prefrontal cortex was restored by LAT. LAT showed robust anti-inflammatory activity and can lessen the increase in IL-6 and TNF-α caused by CSDS. CSDS altered the gut microbiota at the taxonomic level, resulting in significant changes in α- and ß-diversity. LAT treatment reestablished the bacterial abundance and diversity and increased the production of butyric acid in the gut that was inhibited by CSDS. The levels of butyric acid were negatively correlated with the abundance of Bacteroidetes, and positively correlated with those of Proteobacteria and Firmicutes across all treatment groups. CONCLUSIONS: The current data suggest that, similar to fluoxetine, LAT show antidepressant-like effects in mice exposed to CSDS through the modulation of the gut-brain axis.

Effect of humic acid-modified attapulgite on polycyclic aromatic hydrocarbon adsorption and release from paddy soil into the overlying water in a rice-crab coculture paddy ecosystem and the underlying process.

Phenanthrene (Phe), a typical polycyclic aromatic hydrocarbon (PAH) pollutant, poses an enormous safety risk to rice-crab coculture (RC) paddy ecosystems. In this study, humic acid-modified purified attapulgite (HA-ATP) with a composite structure was successfully fabricated to adsorb PAHs released from paddy soil to overlying water in RC paddy ecosystems in Northeast China. The maximum crab bioturbation intensities for dissolved Phe and particulate Phe were 64.83nullng/L·(cm2·d) and 214.29nullng/L·(cm2·d), respectively. The highest concentration of dissolved Phe released from paddy soil to overlying water due to crab bioturbation reached 80.89nullng/L, while the corresponding concentration of particulate Phe reached 267.36nullng/L. The dissolved organic carbon (DOC) and total suspended solid (TSS) concentrations in overlying water increased correspondingly and were strongly correlated with dissolved Phe and particulate Phe concentrations, respectively (P < 0.05). When 6% HA-ATP was added to the surface layer of paddy soil, the efficiency of the adsorption of Phe release was 24.00%-36.38% for particulate Phe and 89.99%-91.91% for dissolved Phe. Because HA-ATP has a large adsorption pore size (11.33 nm) and surface area (82.41nullm2/g) as well as many HA functional groups, it provided multiple hydrophobic adsorption sites for dissolved Phe, which was conducive to competitive adsorption with DOC in the overlying water. In contrast to that adsorbed by DOC, the average proportion of dissolved Phe adsorbed by HA-ATP reached 90.55%, which reduced the dissolved Phe concentration in the overlying water. Furthermore, even though the particulate Phe was resuspended by crab bioturbation, HA-ATP immobilized particulate Phe due to its capacity to inhibit desorption, which achieved the goal of reducing the Phe concentration in the overlying water. This result was confirmed by research on the adsorption-desorption characteristics of HA-ATP. This research provides an environmentally friendly in situ remediation method for reducing agricultural environmental risks and improving rice crop quality.

Choline and trimethylamine N-oxide supplementation in normal chow diet and western diet promotes the development of atherosclerosis in Apoe -/- mice through different mechanisms.

Trimethylamine N-oxide (TMAO), a gut microbiota-dependent metabolite, has been shown to aggravate cardiovascular disease. However, the mechanisms of TMAO in the setting of cardiovascular disease progress remain unclear. Here, we aim to investigate the effects of TMAO on atherosclerosis (AS) development and the underlying mechanisms. Apoe -/- mice received choline or TMAO supplementation in a normal diet and a western diet for 12 weeks. Choline or TMAO supplementation in both normal diet and western diet significantly promoted plaque progression in Apoe-/- mice. Besides, serum lipids levels and inflammation response in the aortic root were enhanced by choline or TMAO supplementation. In particular, choline or TMAO supplementation in the western diet changed intestinal microbiota composition and bile acid metabolism. Therefore, choline or TMAO supplementation may promote AS by modulating gut microbiota in mice fed with a western diet and by other mechanisms in mice given a normal diet, even choline or TMAO supplementation in a normal diet can promote AS.

Research progress on pharmacological effects of isoalantolactone.

OBJECTIVES: To review the pharmacokinetics, pharmacological action and mechanism of isoalantolactone (IAL). Explore the therapeutic potential of isoalantolactone.Keywords including isoalantolactone, pharmacological effects, pharmacokinetic and toxicity were used for literature search in PubMed, Excerpta Medica Database (EMBASE) and Web of Science, to identify articles published from 1992 to 2022. KEY FINDINGS: IAL has a great many obiological activities such as anti-inflammatory, antioxidant, antitumour, neuroprotection, with no obvious toxicity. This review suggests that IAL exerts different pharmacological effects with different mechanisms of action at different doses, and may be a potential drug candidate to treat inflammatory diseases, neurodegenerative diseases and cancer, with medicinal value. SUMMARY: IAL has various pharmacological activities and medicinal values. However, further research is needed to determine its specific intracellular action sites and targets, so as to fully understand its therapeutic mechanism and provide a reference for the treatment of related diseases.

Pueraria protein extract inhibits melanogenesis and promotes melanoma cell apoptosis through the regulation of MITF and mitochondrial­related pathways.

Pueraria Lobata Radix (P. Lobata Radix) is an edible traditional Chinese medicine that contains various active compounds. Proteins from P. Lobata Radix have become the subject of increased interest in recent years. In evaluating the whitening effect on the skin, the present study found that the P. Lobata Radix water­soluble total protein extract (PLP) had the strongest inhibitory effect on tyrosinase activity. In the present study, the anti­melanogenic effect of PLP and the inhibitory effect on B16 melanoma cells were investigated. PLP significantly reduced the tyrosinase activity and melanin content in B16 melanoma cells. Mechanistically, PLP inhibited melanogenesis by decreasing the expression of tyrosinase, tyrosinase­related protein (TRP)­1 and TRP­2 through downregulation of the microphthalmia­associated transcription factor (MITF) gene, which was mediated by inhibition of p38 mitogen­activated protein kinase signaling. In addition, PLP inhibited cell viability and triggered apoptosis of B16 cells in a dose­dependent manner. Exposure to PLP reduced the mitochondrial membrane potential (MMP) and decreased ATP generation, leading to mitochondria­related apoptosis of B16 melanoma cells. The expression levels of succinate dehydrogenase (SDH) and its two related subunits (SDHA and SDHB) were downregulated significantly by PLP, which may be associated with the regulation of mitochondrial energy metabolism by PLP. These results may explain why MMP collapse and reduced ATP generation were observed in B16 melanoma cells treated with PLP. Finally, the present study demonstrated that the inhibition of melanin synthesis by PLP was correlated with the regulation of antioxidant enzymes to reduce reactive oxygen species levels. These results suggested that PLP inhibits melanogenesis by downregulating the expression of MITF­related melanogenic enzymes and triggering apoptosis through mitochondria­related pathways.

Ginsenoside Rg1 Delays Chronological Aging in a Yeast Model via CDC19- and SDH2-Mediated Cellular Metabolism.

Ginsenosides, active substances in Panax ginseng C. A. Meyer (ginseng), extend lifespan in multiple species, ameliorate age-associated damage, and limit functional decline in multiple tissues. However, their active components and their molecular mechanisms are largely unknown. Here, ginsenoside Rg1 (Rg1) promoted longevity in Saccharomyces cerevisiae. Treatment with Rg1 decreased aging-mediated surface wrinkling, enhanced stress resistance, decreased reactive oxygen species' production and apoptosis, improved antioxidant enzyme activity, and decreased the aging rate. Proteomic analysis indicated that Rg1 delays S. cerevisiae senescence by regulating metabolic homeostasis. Protein-protein interaction networks based on differential protein expression indicated that CDC19, a homologue of pyruvate kinase, and SDH2, the succinate dehydrogenase iron-sulfur protein subunit, might be the effector proteins involved in the regulation by Rg1. Further experiments confirmed that Rg1 improved specific parameters of mitochondrial bioenergetics and core enzymes in the glycolytic pathway. Mutant strains were constructed that demonstrated the relationships between metabolic homeostasis and the predicted target proteins of Rg1. Rg1 could be used in new treatments for slowing the aging process. Our results also provide a useful dataset for further investigations of the mechanisms of ginseng in aging.

[Determination of phosphatidylethanol in whole-blood by liquid chromatography-tandem mass spectrometry based on intelligent scheduled time-zone acquisition technology and the application to population level survey].

Alcohol intake is an important risk factor for cardiovascular disease， liver disease， and diabetes. The accurate and objective evaluation of alcohol intake is important for disease prevention and intervention， as well as alcohol intake monitoring. Phosphatidylethanol （PEth） is a potential clinical biomarker of alcohol consumption. Monitoring PEth levels can provide an objective and quantitative basis for alcohol intake studies. Unlike other current alcohol biomarkers， PEth can only be produced in the presence of alcohol. Therefore， PEth is highly specific for alcohol intake and not affected by confounding factors， such as age， gender， hypertension， kidney disease， liver disease， and other comorbidities. Because of its long half-life and high specificity for alcohol intake， PEth may be used as a tool for monitoring drinking behavior in the clinical， transportation， and other fields. Given rapid developments in mass spectrometry technology over the past decade， liquid chromatography-tandem mass spectrometry （LC-MS/MS） has become the preferred method for PEth detection. However， most current LC-MS/MS methods focus on the determination of one or several PEth homologs， and the number of PEth homologs that can be determined simultaneously is relatively limited. Moreover， the detection capacity of the available methods remains insufficient， and their analytical sensitivity for some PEth homologs must be further improved. In this study， a novel LC-MS/MS method based on an intelligent scheduled time-zone negative multiple reaction monitoring acquisition technology （Scheduled-MRM） was developed. The technology monitors two ion channels in each PEth to ensure reliable results and can quantify 18 PEth homologs in human whole blood simultaneously. Methanol-methyl tert-butyl ether-water was used as the extraction system. An XBridge C18 column （100 mm×2.1 mm， 3.5 µm） was selected for gradient elution with 2.5 mmol/L ammonium acetate isopropanol solution and 2.5 mmol/L ammonium acetate aqueous solution-acetonitrile （50∶50， v/v） as the mobile phases. Negative electronic spray ionization in scheduled-MRM mode was applied for MS/MS detection. The method was validated to have a linear range of 10-2500 ng/mL with correlation coefficients greater than 0.9999. The limits of detection and quantification were 0.7-2.8 and 2.2-9.4 ng/mL， respectively， and the spiked recoveries ranged from 91.0% to 102.2%. The method was confirmed to be simple， rapid， and precise， and subsequently validated for the measurement of 18 PEth homologs in human blood. Scheduled-MRM can assign a suitable scan time to each ion channel and effectively reduce the number of concurrent ion pairs monitored per unit time. This technology overcomes the problem of insufficient dwell time caused by an excessive number of ion channels， thereby avoiding the redundant monitoring of non-retention times. Scheduled-MRM significantly improved the detection sensitivity， data acquisition quality， and signal response of the proposed method. Whole blood samples from 359 volunteers with regular drinking habits were analyzed using this method. The total PEth concentrations ranged from 51.13 ng/mL to 2.89 µg/mL， with a mean of 363.16 ng/mL. PEth 16∶0/18∶1 and 16∶0/18∶2 were the two most abundant homologs， with mean concentrations of 74.21 and 48.75 ng/mL， accounting for approximately 20.43% and 13.42%， respectively， of the total PEth. Spearman correlation analyses showed that the PEth homologs correlated well with each other， γ-glutamyltransferase， a clinically available biological marker of alcohol， and other clinical biochemical parameters related to liver and kidney function. Overall， the method was demonstrated to be sensitive， precise， and accurate； thus， it may be an effective tool for monitoring alcohol intake in the clinical and other fields.

Porous Organic Polymer with Hierarchical Structure and Limited Volume Expansion for Ultrafast and Highly Durable Sodium Storage.

Sustainable organic electrode materials, as promising alternatives to conventional inorganic electrode materials for sodium-ion batteries (SIBs), are still challenging to realize long-lifetime and high-rate batteries because of their poor conductivity, limited electroactivity, and severe dissolution. It is also urgent to deeply reveal their electrochemical mechanism and evolution processes. A porous organic polymer (POP) with a conjugated and hierarchical structure is designed and synthesized here. The unique molecule and structure endow the POP with electron delocalization, high ionic diffusivity, plentiful active sites, exceptional structure stability, and limited solubility in electrolytes. When evaluated as an anode for SIBs, the POP exhibits appealing electrochemical properties regarding reversible capacity, rate behaviors, and long-duration life. Importantly, using judiciously combined experiments and theoretical computation, including in situ transmission electron microscopy (TEM), and ex situ spectroscopy, we reveal the Na-storage mechanism and dynamic evolution processes of the POP, including 12-electron reaction process with Na, low volume expansion (125-106% vs the initial 100%), and stable composition and structure evolution during repeating sodiation/de-sodiation processes. This quantitative design for ultrafast and highly durable sodium storage in the POP could be of immediate benefit for the rational design of organic electrode materials with ideal electrochemical properties.