Simultaneous Screening of 172 Veterinary Drugs by Modified QuEChERS-LC-MS/MS in TCM Galli Gigerii Endothelium Corneum.

An analytical method was developed for the screening of 172 veterinary drugs in traditional Chinese medicine Galli Gigerii Endothelium Corneum by high-performance liquid chromatography tandem mass spectrometry. The samples were pretreated by a modified QuEChERS method. A Zorbax Eclipse plus C18 column (1.8 µm, 3.0 × 150 mm2, Agilent) was used for the separation of analytes by gradient elution. All analytes were detected by electrospray ionization mass spectrometry with multiple reaction monitoring mode. Good linearity with R ≥ 0.99 was exhibited for all analytes within the respective range. The recoveries of all monitored analytes ranged from 55.4 to 127.6% at three spiked levels (limit of quantitation-LOQ, 2-fold LOQ, 10-fold LOQ), with relative standard deviations <17.8%. The estimated LOQ levels were 0.2-20 µg/kg. The application of this method provides a reference for the safety control of traditional Chinese medicines.

Adsorption of phosphate over a novel magnesium-loaded sludge-based biochar.

The production of sludge-based biochar to recover phosphorus (P) from wastewater and reuse the recovered phosphorus as agricultural fertilizer is a preferred process. This article mainly studied the removal of phosphate (PO4-P) from aqueous solution by synthesizing sludge-based biochar (MgSBC-0.1) from anaerobic fermentation sludge treated with magnesium (Mg)-loading-modification, and compared it with unmodified sludge-based biochar (SBC). The physicochemical properties, adsorption efficiency, and adsorption mechanism of MgSBC-0.1 were studied. The results showed that the surface area of MgSBC-0.1 synthesized increased by 5.57 times. The material surface contained MgO, Mg(OH)2, and CaO nanoparticles. MgSBC-0.1 can effectively remove phosphate in the initial solution pH range of 3.00-7.00, with a fitted maximum phosphorus adsorption capacity of 379.52 mg·g-1. The adsorption conforms to the pseudo second-order kinetics model and Langmuir isotherm adsorption curve. The characterization of the adsorbed composite material revealed the contribution of phosphorus crystal deposition and electrostatic attraction to phosphorus absorption.

Advancements of Macrophages Involvement in Pathological Progression of Colitis-Associated Colorectal Cancer and Associated Pharmacological Interventions.

Intestinal macrophages play crucial roles in both intestinal inflammation and immune homeostasis. They can adopt two distinct phenotypes, primarily determined by environmental cues. These phenotypes encompass the classically activated pro-inflammatory M1 phenotype, as well as the alternatively activated anti-inflammatory M2 phenotype. In regular conditions, intestinal macrophages serve to shield the gut from inflammatory harm. However, when a combination of genetic and environmental elements influences the polarization of these macrophages, it can result in an M1/M2 macrophage activation imbalance, subsequently leading to a loss of control over intestinal inflammation. This shift transforms normal inflammatory responses into pathological damage within the intestines. In patients with ulcerative colitis-associated colorectal cancer (UC-CRC), disorders related to intestinal inflammation are closely correlated with an imbalance in the polarization of intestinal M1/M2 macrophages. Therefore, reinstating the equilibrium in M1/M2 macrophage polarization could potentially serve as an effective approach to the prevention and treatment of UC-CRC. This paper aims to scrutinize the clinical evidence regarding Chinese medicine (CM) in the treatment of UC-CRC, the pivotal role of macrophage polarization in UC-CRC pathogenesis, and the potential mechanisms through which CM regulates macrophage polarization to address UC-CRC. Our objective is to offer fresh perspectives for clinical application, fundamental research, and pharmaceutical advancement in UC-CRC.

Efficacy of Intravitreal Injections Anti-Vascular Endothelial Growth Factor Treatment for Radiation Retinopathy: A Systematic Review and Meta-analysis.

PURPOSE: This study aims to appraise the therapeutic effectiveness of intravitreal injections anti-vascular endothelial growth factor (anti-VEGF) vs alternative therapies in managing radiation retinopathy (RR). DESIGN: Systematic review and meta-analysis. METHODS: We obtained comprehensive data retrieval using PubMed, Embase, Web of Science, Scopus, and the Cochrane Library from their inception until December 15, 2023. This review included randomized controlled trials (RCTs) and nonrandomized studies (NRSs) reporting on best-corrected visual acuity (BCVA) among RR patients treated with intravitreal anti-VEGF. Study selection and data extraction were meticulously performed by 2 independent reviewers. The Cochrane Risk of Bias Tool 2.0 (RoB 2.0) and Risk of Bias in Nonrandomized Studies of Interventions (ROBINS-I) scales were utilized for bias risk assessment. Quantification of heterogeneity was executed using Q, H, and I2 statistics. The primary endpoint was the BCVA at the final observation point of each study. Secondary endpoints included central retinal thickness (CRT), foveal avascular zone (FAZ) area, and capillary density (CD) at the level of superficial capillary plexus. Subgroup analyses were undertaken to explore potential heterogeneity sources possibly due to treatment duration and study design. Sensitivity analyses were conducted to ascertain result stability. RESULTS: This analysis incorporated 7 studies (including 3 RCTs) encompassing 922 patients afflicted with RR. Relative to other treatment modalities, intravitreal anti-VEGF therapy was associated with a statistically significant mean decrease in BCVA of -0.34 logMAR (95% CI, -0.39 to -0.30 logMAR; I2 = 87.70%; P < .001), and a substantial reduction in CRT of -34.65 µm (95% CI, -50.70 to -18.60 µm; I2 = 30.40%; P < .001). Additionally, a reduction in the FAZ area by -0.69 mm² (95% CI, -0.91 to -0.46 mm², I2 = 0%; P < .001) was observed. A positive tendency was noted in CD at the superficial capillary plexus between anti-VEGF and other therapeutic interventions. CONCLUSIONS: Intravitreal anti-VEGF injections, in comparison to other treatments, demonstrate superior efficacy in enhancing BCVA and reducing CRT, thereby underscoring the potential of anti-VEGF in ameliorating radiation retinopathy outcomes. However, the conclusions are constrained by the incorporation of data from some NRSs and the small sample sizes.

Macrod1 suppresses diabetic cardiomyopathy via regulating PARP1-NAD+-SIRT3 pathway.

Diabetic cardiomyopathy (DCM), one of the most serious long-term consequences of diabetes, is closely associated with oxidative stress, inflammation and apoptosis in the heart. MACRO domain containing 1 (Macrod1) is an ADP-ribosylhydrolase 1 that is highly enriched in mitochondria, participating in the pathogenesis of cardiovascular diseases. In this study, we investigated the role of Macrod1 in DCM. A mice model was established by feeding a high-fat diet (HFD) and intraperitoneal injection of streptozotocin (STZ). We showed that Macrod1 expression levels were significantly downregulated in cardiac tissue of DCM mice. Reduced expression of Macrod1 was also observed in neonatal rat cardiomyocytes (NRCMs) treated with palmitic acid (PA, 400 µM) in vitro. Knockout of Macrod1 in DCM mice not only worsened glycemic control, but also aggravated cardiac remodeling, mitochondrial dysfunction, NAD+ consumption and oxidative stress, whereas cardiac-specific overexpression of Macrod1 partially reversed these pathological processes. In PA-treated NRCMs, overexpression of Macrod1 significantly inhibited PARP1 expression and restored NAD+ levels, activating SIRT3 to resist oxidative stress. Supplementation with the NAD+ precursor Niacin (50 µM) alleviated oxidative stress in PA-stimulated cardiomyocytes. We revealed that Macrod1 reduced NAD+ consumption by inhibiting PARP1 expression, thereby activating SIRT3 and anti-oxidative stress signaling. This study identifies Macrod1 as a novel target for DCM treatment. Targeting the PARP1-NAD+-SIRT3 axis may open a novel avenue to development of new intervention strategies in DCM. Schematic illustration of macrod1 ameliorating diabetic cardiomyopathy oxidative stress via PARP1-NAD+-SIRT3 axis.

Species discrimination of multiple botanical origins of Fritillaria species based on infrared spectroscopy, thin layer chromatography-image analysis and untargeted metabolomics.

BACKGROUND: Fritillaria Bulbus (FB), a precious medicinal herb renowned for its heat-clearing, lung-moistening, cough-relieving and phlegm-eliminating effects. In pursuit of profits, unscrupulous merchants have engaged in the substitution or adulteration of valuable varieties with cheaper alternatives. It is, therefore, urgent to develop effective technical approaches to identify FBs from adulterants. METHODS: This paper employed infrared spectroscopy (IR), thin layer chromatography-image analysis (TLC-IA), and untargeted metabolomics techniques to discriminate ten species of FBs. RESULTS: Five species of FBs were successfully differentiated using mid-infrared spectroscopy. Furthermore, the power of TLC-IA technology allowed the differentiation of five species of FBs and two origins of FCBs (Fritillariae Cirrhosae Bulbus). Remarkably, through the application of untargeted metabolomics technique, the precise discrimination of five species of FBs, as well as three origins of FCBs were accomplished. Moreover, a comprehensive identification of 101 markers that reliably distinguished diverse FBs was achieved through the employment of untargeted metabolomics technique. CONCLUSION: The investigation presented powerful means of detection for assuring the quality control of Fritillaria herbs.

Low-Temperature Cleanup Followed by Dispersive Solid-Phase Extraction for Determination of Nine Polar Plant Growth Regulators in Herbal Matrices Using Liquid Chromatography-Tandem Mass Spectrometry.

Polar plant growth regulators, used alone or doped in fertilizers, are most effective and widely utilized plant growth regulators (PGRs) in agriculture, which play important roles in mediating the yield and quality of crops and foodstuffs. The application scope has been extended to herbal medicines in the past 2 decades and relevant study is inadequate. The aim of this study is to establish a QuPPe-based extraction method containing low-temperature and d-SPE cleanup procedure followed by the detection on a selective multiresidue ultrahigh-performance liquid chromatography - triple quadrupole tandem mass spectrometry (UHPLC-QqQ-MS/MS) in three herbal matrices. This simple, accurate, versatile and robust method was verified according to the validation criteria of the SANTE/12682/2019 guideline document. The analytical range was from 2.5 to 200 µg/L, and the average recoveries were in the range of 64.6-117.8% (n = 6). The optimized method was applied to 135 herbal medicines thereof. Result showed that the detection frequency of chlormequat was the highest in the investigated PGRs, with the positive rate of 15.6%. Improvement of the detection method for polar PGRs will enrich the coverage of PGRs, which is conducive to safeguard public health and ensure drug safety. Supplementary Information: The online version contains supplementary material available at 10.1007/s10337-023-04254-3.

The interplay between non-coding RNAs and alternative splicing: from regulatory mechanism to therapeutic implications in cancer.

Alternative splicing (AS) is a common and conserved process in eukaryotic gene regulation. It occurs in approximately 95% of multi-exon genes, greatly enriching the complexity and diversity of mRNAs and proteins. Recent studies have found that in addition to coding RNAs, non-coding RNAs (ncRNAs) are also inextricably linked with AS. Multiple different types of ncRNAs are generated by AS of precursor long non-coding (pre-lncRNAs) or precursor messenger RNAs (pre-mRNAs). Furthermore, ncRNAs, as a novel class of regulators, can participate in AS regulation by interacting with the cis-acting elements or trans-acting factors. Several studies have implicated abnormal expression of ncRNAs and ncRNA-related AS events in the initiation, progression, and therapy resistance in various types of cancers. Therefore, owing to their roles in mediating drug resistance, ncRNAs, AS-related factors and AS-related novel antigens may serve as promising therapeutic targets in cancer treatment. In this review, we summarize the interaction between ncRNAs and AS processes, emphasizing their great influences on cancer, especially on chemoresistance, and highlighting their potential values in clinical treatment.

MRTCM: A comprehensive dataset for probabilistic risk assessment of metals and metalloids in traditional Chinese medicine.

Traditional Chinese medicine (TCM) is still considered a global complementary or alternative medical system, but exogenous hazardous contaminants remain in TCM even after decocting. Besides, it is time-consuming to conduct a risk assessment of trace elements in TCMs with a non-automatic approach due to the wide variety of TCMs. Here, we present MRTCM, a cloud-computing infrastructure for automating the probabilistic risk assessment of metals and metalloids in TCM. MRTCM includes a consumption database and a pollutant database involving forty million rows of consumption data and fourteen types of TCM potentially toxic elements concentrations. The algorithm of probabilistic risk assessment was also packaged in MRTCM to assess the risks of eight elements with Monte Carlo simulation. The results demonstrated that 96.64% and 99.46% had no non-carcinogenic risk (hazard indices (HI) were < 1.0) for animal and herbal medicines consumers, respectively. After twenty years of exposure, less than 1% of the total carcinogenic risk (CRt) was > 10-4 for TCM consumers, indicating that they are at potential risk for carcinogenicity. Sensitivity analysis revealed that annual consumption and concentration were the main variables affecting the assessment results. Ultimately, a priority management list of TCMs was also generated, indicating that more attention should be paid to the non-carcinogenic risks of As, Mn, and Hg and the carcinogenic risks of As and Cr in Pheretima and Cr in Arcae Conch. In general, MRTCM could significantly enhance the efficiency of risk assessment in TCM and provide reasonable guidance for policymakers to optimize risk management.

Effects of hyperbaric oxygen on Notch signaling pathway after severe carbon monoxide poisoning in mice.

Demyelination of the cerebral white matter is the most common pathological change after carbon monoxide (CO) poisoning. Notch signaling, the mechanism underlying the differentiation of astrocytes and oligodendrocytes, is critical to remyelination of the white matter after brain lesion. The purpose of this work was to determine the effects of hyperbaric oxygen (HBO) on Notch signaling pathway after CO poisoning for the explanation of the protective effects of HBO on CO-poisoning-related cerebral white matter demyelination. The male C57 BL/6 mice with severe CO poisoning were treated by HBO. And HBO therapy shortened the escape latency and improved the body mass after CO poisoning. HBO therapy also significantly suppressed protein and mRNA levels of Notch1 and Hes5 after CO poisoning. Our findings suggested that HBO could suppress the activation of Notch signaling pathway after CO poisoning, which is the mechanism underlying the neuroprotection of HBO on demyelination after severe CO poisoning.

Integrated Metabolome and Lipidome Strategy to Reveal the Action Pattern of Paclobutrazol, a Plant Growth Retardant, in Varying the Chemical Constituents of Platycodon Root.

Platycodon root, a medicinal food homology species which has been used in Asian countries for hundreds of years, is now widely cultivated in China. Treatment with paclobutrazol, a typical plant growth retardant, has raised uncertainties regarding the quality of Platycodon root, which have been rarely investigated. In the present study, metabolomic and lipidomic differences were revealed by ultra-high performance liquid chromatography coupled to ion mobility-quadrupole time of flight mass spectrometry (UPLC-IM-QTOF-MS). A significant decrease of platycodigenin-type saponins was observed in the paclobutrazol-treated sample. Carrying out a comprehensive quantitative analysis, the contents of total saponins and saccharides were determined to illustrate the mode of action of paclobutrazol on Platycodon root. This study demonstrated an exemplary research model in explaining how the exogenous matter influences the chemical properties of medicinal plants, and therefore might provide insights into the reasonable application of plant growth regulators.

Potential molecular mechanism of Guiqi Baizhu Decoction in radiation-induced intestinal edema by regulating HIF-1a, AQP4 and Na+/K+-ATPase.

BACKGROUND: Guiqi Baizhu Decoction (GQBZD) has a good protective effect on radiation-induced intestinal edema (RIIE). However, the underlying molecular mechanisms need further elucidation. PURPOSE: To reveal the potential mechanism of RIIE and GQBZD treatment. METHODS: SD rats were irradiated with 6Gy X-ray to establish RIIE model. The general condition of the rats was observed; the dry/wet weight ratio of colon tissue was detected; the morphological changes of colon tissue were observed by HE staining; the expressions of ROS, HIF-1α and AQP4 in colon tissue were detected by confocal laser scanning; the expression of edema-related proteins was detected by Western blot. In addition, human colon epithelial cells (NCM460) was irradiated with 2Gy X-ray, and HIF-1α expression in NCM460 was knocked down by small interfering RNA (siRNA) transfection, and the activity of Na+/K+-ATPase was detected by enzyme activity kit; the ROS expression was detected by flow cytometer; the AQP4 expression was detected by laser confocal microscopy; and the expression of edema-related proteins were detected by Western blot. RESULTS: We found that after irradiation, the colon tissue of rats was significantly edema, mainly manifested as mucosal and submucosal edema, and the ultrastructure was reflected in the structural damage of nucleus and mitochondria. ROS, HIF-1α and AQP4 were significantly expressed, and Na+/K+-ATPase expression/activity was decreased. After the intervention of GQBZD, the edema of the colon tissue of the rats was improved, the expressions of ROS, HIF-1α and AQP4 were decreased, and the expression/activity of Na+/K+-ATPase was increased. CONCLUSION: Ionizing radiation (IR) can cause significant intestinal edema. AQP4 and Na+/K+-ATPase are the key factors of RIIE, which are regulated by ROS and HIF-1α. GQBZD can improve hypoxia and oxidative stress, regulate the expression of AQP4 and Na+/K+-ATPase, and achieve a protective effect on RIIE. This study is the first to reveal the mechanism of RIIE.

Comprehensive profiling of Platycodonis radix in different growing regions using liquid chromatography coupled with mass spectrometry: from metabolome and lipidome aspects.

Platycodon grandiflorus (Jacq.) A. DC. is widely cultivated across the south and north of China. Its root, Platycodonis radix, is commonly used as a vegetable, functional food, and traditional herbal medicine with various biological benefits. It is critical to fully clarify the chemical composition of Platycodonis radix for the sake of the food industry and traditional herb markets. In this study, a strategy of metabolome and lipidome profiling based on ultra-high performance liquid chromatography coupled to ion mobility-quadrupole time of flight mass spectrometry (UPLC-IM-QTOF-MS) was developed to reveal the overall chemical composition of Platycodonis radix. IN particular, comprehensive lipidome profiling was first performed for Platycodonis radix, in which 170 lipid molecular species including 55.9% glycerophospholipids, 31.2% glycerolipids, and 12.9% sphingolipids were identified. Platycodonis radix from two major production regions in China, Inner Mongolia and Anhui province, were collected and analyzed by the MS based approach combined with multivariate statistical analysis from both the metabolome and lipidome aspects. This study threw focus on the profiling investigations of Platycodonis radix from different growing regions and provided new potential in the lipidome analysis of medicinal food.

Exposure assessment and risk-based limit levels evaluation of ochratoxin A in Astragali Radix in China.

Ochratoxin A (OTA) is a mycotoxin found in a variety of foods and herbal medicines, and several governmental bodies around the world have set maximum allowable levels of OTA in different foods and herbal medicines. This study aims to evaluate the health risk of OTA in Astragali Radix (AR) in China, and to evaluate the effects of different limit levels on the risk control of OTA in AR. The concentrations of OTA in 187 samples of AR were investigated, and 61 (32.6%) samples were positive. The mean, 50th and 95th percentile values of OTA in positive samples were 56.2, 5.1 and 304.5 µg/kg, respectively. A margin of exposure (MOE) approach was applied to assess the risk. Considering other food sources, long-term consumers have a relatively high risk of OTA exposure due to the ingestion of AR. Theoretical limit levels of OTA in AR were evaluated from two dimensions by weighing the costs and the benefits. The results indicated that the limit levels that might be applied to the management of OTA contamination in AR in China could be screened out through risk-based evaluation of limit levels.

[Ductal adenocarcinoma of the prostate: Report of 45 cases and review of the literature].

OBJECTIVE: To explore the clinical features, treatment and prognosis of ductal adenocarcinoma of the prostate (DAP) and get a deeper insight into the malignancy. METHODS: We retrospectively studied the clinical data on 45 cases of confirmed DAP, 26 in the high-risk group and 19 in the medium-risk group, treated from January 2013 to September 2020. We compared the time and rate of biochemical recurrence and the rate of imaging progression between the two groups of patients, and evaluated the effect of palliative transurethral bipolar plasma resection of the prostate (pTU-PKRP) on the lower urinary tract symptoms (LUTS). RESULTS: Of the 45 cases of DAP, 4 (8.9%) were of the simple type, and 41 (91.1%) complicated by prostatic acinar carcinoma (PAA). And of the latter 41 cases, 9 (21.9%) were complicated by neuroendocrine differentiation and another 4 (9.8%) by intraductal carcinoma. The time to biochemical recurrence was longer in the medium-risk than in the high-risk group (P < 0.05). No statistically significant differences were observed in the rates of biochemical recurrence and imaging progression between the two groups (P > 0.05). The maximum urinary flow rate (Qmax), postvoid residual urine volume (PVR), IPSS and QOL of the patients were significantly improved at 6 months after pTU-PKRP compared with the baseline (P < 0.05). CONCLUSION: Radical prostatectomy can improve the prognosis of early DAP, while for advanced DAP with serious LUTS, pTU-PKRP can improve the quality of life of the patients.

Exploring the mechanism of Buxue Yimu Pill on hemorrhagic anemia through molecular docking, network pharmacology and experimental validation.

Buxue Yimu Pill (BYP) is a classic gynecological medicine in China, which is composed of Angelica sinensis (Oliv.) Diels, Leonurus japonicus Houtt, Astragalus membranaceus (Fisch.) Bunge, Colla corii asini and Citrus reticulata Blanco. It has been widely used in clinical therapy with the function of enriching Blood, nourishing Qi, and removing blood stasis. The current study was designed to determine the bioactive molecules and therapeutic mechanism of BYP against hemorrhagic anemia. Herein, GC-MS and UPLC/Q-TOF-MS/MS were employed to identify the chemical compounds from BYP. The genecards database (https: //www.genecards.org/) was used to obtain the potential target proteins related to hemorrhagic anemia. Autodock/Vina was adopted to evaluate the binding ability of protein receptors and chemical ligands. Gene ontology and KEGG pathway enrichment analysis were conducted using the ClusterProfiler. As a result, a total of 62 candidate molecules were identified and 152 targets related to hemorrhagic anemia were obtained. Furthermore, 34 active molecules and 140 targets were obtained through the virtual screening experiment. The data of molecular-target (M-T), target-pathway (T-P), and molecular-target-pathway (M-T-P) network suggested that 32 active molecules enhanced hematopoiesis and activated the immune system by regulating 57 important targets. Pharmacological experiments showed that BYP significantly increased the counts of RBC, HGB, and HCT, and significantly down-regulated the expression of EPO, IL-6, CSF3, NOS2, VEGFA, PDGFRB, and TGFB1. The results also showed that leonurine, leonuriside B, leosibiricin, ononin, rutin, astragaloside I, riligustilide and levistolide A, were the active molecules closely related to enriching Blood. In conclusion, based on molecular docking, network pharmacology and validation experiment results, the enriching blood effect of BYP on hemorrhagic anemia may be associated with hematopoiesis, anti-inflammation, and immunity enhancement.

Ionizing radiation downregulates estradiol synthesis via endoplasmic reticulum stress and inhibits the proliferation of estrogen receptor-positive breast cancer cells.

Breast cancer is a major threat to women's health and estrogen receptor-positive (ER+) breast cancer exhibits the highest incidence among these cancers. As the primary estrogen, estradiol strongly promotes cellular proliferation and radiotherapy, as a standard treatment, exerts an excellent therapeutic effect on ER+ breast cancer. Therefore, we herein wished to explore the mechanism(s) underlying the inhibitory effects of radiation on the proliferation of ER+ breast cancer cells. We used the ER+ breast cancer cell lines MCF7 and T47D, and their complementary tamoxifen-resistant cell lines in our study. The aforementioned cells were irradiated at different doses of X-rays with or without exogenous estradiol. CCK8 and clone-formation assays were used to detect cellular proliferation, enzyme-linked immunosorbent assay (ELISA) to determine estradiol secretion, western immunoblotting analysis and quantitative real-time PCR to evaluate the expression of proteins, and immunofluorescence to track endoplasmic reticulum stress-related processes. Finally, BALB/C tumor-bearing nude mice were irradiated with X-rays to explore the protein expression in tumors using immunohistochemistry. We found that ionizing radiation significantly reduced the phosphorylation of estrogen receptors and the secretion of estradiol by ER+ breast cancer cells. CYP19A (aromatase) is an enzyme located in the endoplasmic reticulum, which plays a critical role in estradiol synthesis (aromatization), and we further demonstrated that ionizing radiation could induce endoplasmic reticulum stress with or without exogenous estradiol supplementation, and that it downregulated the expression of CYP19A through ER-phagy. In addition, ionizing radiation also promoted lysosomal degradation of CYP19A, reduced estradiol synthesis, and inhibited the proliferation of tamoxifen-resistant ER+ breast cancer cells. We concluded that ionizing radiation downregulated the expression of CYP19A and reduced estradiol synthesis by inducing endoplasmic reticulum stress in ER+ breast cancer cells, thereby ultimately inhibiting cellular proliferation.

Comprehensive characterization of the chemical constituents in Platycodon grandiflorum by an integrated liquid chromatography-mass spectrometry strategy.

Platycodon grandiflorum (PG), as a well-known medicine food homology species, possess various pharmacological effects and health benefits. Aiming to facilitate in-depth and global characterization of the chemical compositions of PG, a profiling method based on ultra-high performance liquid chromatography coupled with ion mobility quadrupole time-of-flight mass spectrometry (UPLC/IM-QTOF-MS) was conducted. Consequently, as many as 187 compounds were plausibly or unambiguously identified. Most importantly, phospholipids (PLs) were first observed and identified in PG. Due to their widely confirmed bioactivities, an analysis scheme was developed by hydrophilic interaction liquid chromatography and electrospray ionization tandem mass spectrometry combined with the online Paternò-Büchi reaction (HILIC-PB-MS/MS). The fatty acyl chains and C=C locations of 180 PLs molecular species, which fell into four classes, were unprecedently characterized. This exposure strategy of multi-type constituents greatly enriches the chemical profiling of PG, and helps promoting the further development of therapeutic agents and nutraceutical products from PG.

Proteomics analysis in the kidney of mice following oral feeding Realgar.

ETHNOPHARMACOLOGICAL RELEVANCE: Realgar, a famous traditional Chinese mineral medicine, has been toxic to the renal system. However, the underlying mechanism of Realgar nephrotoxicity is still unclear. AIM OF THE STUDY: This study aimed to investigate the potential mechanism of Realgar-induced nephrotoxicity by using a label-free quantitative proteomic method. MATERIALS AND METHODS: 36 mice were randomly divided into four groups: Control group, 0.5-, 1.0, and 2.0 g/kg Realgar group. After one week, serum biochemical parameters and renal histopathological examination were performed. Label-free quantitative proteomics was used to identify differentially expressed proteins which were subsequently analyzed with bioinformatics methods. Western blot was utilized to verify the six representative protein expressions. RESULTS: The results showed that 2.0 g/kg Realgar significantly increased blood urea nitrogen and induced the formation of tube cast of renal tubules, while the lower-dose of 0.5 g/kg and 1.0 g/kg Realgar showed no changes. Label-free proteomic analysis identified 3138 proteins, and 272 of those proteins were screened for significant changes in a dose-dependent manner. Functional enrichment analysis suggested that these proteins could affect the apoptotic process and oxidative stress. Representative proteins in the 2.0 g/kg Realgar group, including Cat, Bad, Cycs, Nqo1, Podxl, and Hmox1, were verified by western blot. CONCLUSIONS: The results in this study suggest that apoptosis and oxidative stress might be related to the Realgar-induced nephrotoxicity in mice. Moreover, the strategy of proteomics could contribute to the understanding of the mechanisms of nephrotoxicity in mice exposed to Realgar.

Plant metabolomics for studying the effect of two insecticides on comprehensive constituents of Lonicerae Japonicae Flos.

Pesticides' overuse and misuse have been reported to induce ingredient variations in herbal medicine, which is now gaining attention in the medicinal field as a form of alternative medicine. To date, available studies on pesticide-induced ingredient variations of herbal medicine are limited only on a few compounds and remain most others unexamined. In this study, a plant metabolomics-based strategy was performed to systematically explore the effects of two frequently used insecticides on the comprehensive constituents of Lonicerae Japonicae Flos (LJF), the flower buds of Lonicera japonica Thunb. Field trials were designed on a cultivating plot of L. japonica with controls and treatments of imidacloprid (IMI) and compound flonicamid and acetamiprid (CFA). Unbiased metabolite profiling was conducted by ultra-high performance liquid chromatography/quadrupole-Orbitrap mass spectrometer. After data pretreatment by automatic extraction and screening, a data matrix of metabolite features was submitted for statistical analyses. Consequently, 29 metabolic markers, including chlorogenic acids, iridoids and organic acid-glucosides were obtained and characterized. The relative quantitative assay was subsequently performed to monitor their variations across flowering developments. This is the first study that systematically explored the insecticide-induced metabolite variations of LJF while taking into account the inherent variability of flowering development. The results were beneficial for holistic quality assessment of LJF and significant for guiding scientific use of pesticides in the large-scale cultivation.