Gain deeper insights into traditional Chinese medicines using multidimensional chromatography combined with chemometric approaches.

Traditional Chinese medicines (TCMs) possess a rich historical background, unique theoretical framework, remarkable therapeutic efficacy, and abundant resources. However, the modernization and internationalization of TCMs have faced significant obstacles due to their diverse ingredients and unknown mechanisms. To gain deeper insights into the phytochemicals and ensure the quality control of TCMs, there is an urgent need to enhance analytical techniques. Currently, two-dimensional (2D) chromatography, which incorporates two independent separation mechanisms, demonstrates superior separation capabilities compared to the traditional one-dimensional (1D) separation system when analyzing TCMs samples. Over the past decade, new techniques have been continuously developed to gain actionable insights from complex samples. This review presents the recent advancements in the application of multidimensional chromatography for the quality evaluation of TCMs, encompassing 2D-gas chromatography (GC), 2D-liquid chromatography (LC), as well as emerging three-dimensional (3D)-GC, 3D-LC, and their associated data-processing approaches. These studies highlight the promising potential of multidimensional chromatographic separation for future phytochemical analysis. Nevertheless, the increased separation capability has resulted in higher-order data sets and greater demands for data-processing tools. Considering that multidimensional chromatography is still a relatively nascent research field, further hardware enhancements and the implementation of chemometric methods are necessary to foster its robust development.

Multi-Stimuli-Responsive and Cell Membrane Camouflaged Aggregation-Induced Emission Nanogels for Precise Chemo-photothermal Synergistic Therapy of Tumors.

Targeted and controllable drug release at lesion sites with the aid of visual navigation in real-time is of great significance for precise theranostics of cancers. Benefiting from the marvelous features (e.g., bright emission and phototheranostic effects in aggregates) of aggregation-induced emission (AIE) materials, constructing AIE-based multifunctional nanocarriers that act as all-arounders to integrate multimodalities for precise theranostics is highly desirable. Here, an intelligent nanoplatform (P-TN-Dox@CM) with homologous targeting, controllable drug release, and in vivo dual-modal imaging for precise chemo-photothermal synergistic therapy is proposed. AIE photothermic agent (TN) and anticancer drug (Dox) are encapsulated in thermo-/pH-responsive nanogels (PNA), and the tumor cell membranes are camouflaged onto the surface of nanogels. Active targeting can be realized through homologous effects derived from source tumor cell membranes, which advantageously elevates the specific drug delivery to tumor sites. After being engulfed into tumor cells, the nanogels exhibit a burst drug release at low pH. The near-infrared (NIR) photoinduced local hyperthermia can activate severe cytotoxicity and further accelerate drug release, thus generating enhanced synergistic chemo-photothermal therapy to thoroughly eradicate tumors. Moreover, P-TN-Dox@CM nanogels could achieve NIR-fluorescence/photothermal dual-modal imaging to monitor the dynamic distribution of therapeutics in real-time. This work highlights the great potential of smart P-TN-Dox@CM nanogels as a versatile nanoplatform to integrate multimodalities for precise chemo-photothermal synergistic therapy in combating cancers.

Perceived knowledge, attitudes and practices regarding the medical consortium among medical staff in Sichuan, China: a cross-sectional survey.

BACKGROUND: In China, fragmented and inefficient health care systems are common while quality resources are limited. To promote an organized, efficient system, the government launched a medical consortium policy to vertically integrate health care through the collaboration of different levels of medical care. Logically, medical staff's knowledge, attitudes and practices (KAP) regarding the consortium are critical for its development. The objective of this study was to explore the KAP regarding the medical consortium among medical staff in a medical consortium in Sichuan Province, China. METHODS: A cross-sectional survey was conducted. In total, 690 medical staff members in 3 cities of Sichuan Province, China, were interviewed from November 2018 to December 2018. The questionnaire consisted of 18 items, including 4 items related to perceived knowledge, 4 items related to attitudes and 2 items related to practices, and was rated on a 5-point Likert scale (one = strongly disagree/do not know, five = strongly agree/know). RESULTS: The effective response sample was 640 copies of the questionnaire, and most medical staff members (92.50%) knew about the cooperation with other hospitals in the medical consortium. Medical staff scored differently on each item in the questionnaire, with the highest score being the item 'agreeing with the ward rounds and clinical teaching and training organized by the leading hospital' (4.54 ± 0.76), and the lowest score being the item 'frequency in participating in ward rounds and clinical teaching organized by the leading hospital' (2.83 ± 1.36). In addition, the effect of demographic characteristics on KAP was evaluated by stepwise multiple regression analysis, and a significant positive correlation was found between all the studied variables by Spearman's correlation (p < 0.05). CONCLUSIONS: This study showed that the attitudes toward and knowledge of the medical consortium significantly contribute to practices, satisfaction with the support work performed by the leading hospital and agreement of improvement after joining the medical consortium. Thus, to improve medical staff's KAP and satisfaction, publicity and educational programs in medical consortia are necessary, and the leading hospital should attach importance to the informatization construction and demand of different medical staff members. CLINICAL TRIAL REGISTRATION: There are no clinical trials in this study.

Efficacy and safety of caffeic acid tablets in the treatment of thrombocytopenia: A systematic review and meta-analysis.

BACKGROUND: Caffeic acid tablets (CFA) are a proprietary Chinese medicine in treating thrombocytopenia. The efficacy and safety of CFA compared with other platelet-raising drugs for the treatment of thrombocytopenia have been widely reported in the literature, but there is no systematic evaluation. Therefore, we designed this meta-analysis to further establish the efficacy and safety of CFA in treating thrombocytopenia. METHODS: A computerized search was conducted in the Chinese biomedical database (CBM), Chinese National Knowledge Infrastructure (CNKI), Wanfang database, Chinese Scientific Journal Database (VIP), PubMed, and Web of Science databases using the keywords "caffeic acid tablets" and "thrombocytopenia." All randomized controlled trials were selected for the timeframe of build to 02/2023 and then screened and analyzed using RevMan 5.4 and stata17.0 software. RESULTS: A total of 35 publications with an overall 2533 patients were included in the study. The results of the meta-analysis showed that CFA were effective in the treatment of thrombocytopenia with a statistically significant difference [relative risk ratio (RR) = 1.24, 95% CI (1.17, 1.31), P < .00001] and in increasing platelet counts [standardized mean difference (SMD) = 1.50, 95% CI (1.09, 1.91), P < .00001], white blood cell count [SMD = 1.08, 95% CI (0.77, 1.39), P < .00001], and neutrophil count [SMD = 0.73, 95% CI (0.19, 1.28), P = .009], and CFA reduced myelosuppression [RR = 0.19, 95% CI (0.1, 0.37), P < .00001] and adverse effects [RR = 0.75, 95% CI (0.58, 0.96), P = .02]. CONCLUSION: CFA can effectively improve the clinical outcome of patients with thrombocytopenia with a good safety profile and are worth promoting. However, due to the low quality and small sample size of the included literature, a larger sample size and more standardized, high-quality studies are needed to validate these results.

Curcuma Longa Induces the Transcription Factor FOXP3 to Downregulate Human Chemokine CCR5 Expression and Inhibit HIV-1 Infection.

HIV mutations occur frequently despite the substantial success of combination antiretroviral therapy, which significantly impairs HIV progression. Failure to develop specific vaccines, the occurrence of drug-resistant strains, and the high incidence of adverse effects due to combination antiviral therapy regimens call for novel and safer antivirals. Natural products are an important source of new anti-infective agents. For instance, curcumin inhibits HIV and inflammation in cell culture assays. Curcumin, the principal constituent of the dried rhizomes of Curcuma longa L. (turmeric), is known as a strong anti-oxidant and anti-inflammatory agent with different pharmacological effects. This work aims to assess curcumin's inhibitory effects on HIV in vitro and to explore the underpinning mechanism, focusing on CCR5 and the transcription factor forkhead box protein P3 (FOXP3). First, curcumin and the RT inhibitor zidovudine (AZT) were evaluated for their inhibitory properties. HIV-1 pseudovirus infectivity was determined by green fluorescence and luciferase activity measurements in HEK293T cells. AZT was used as a positive control that inhibited HIV-1 pseudoviruses dose-dependently, with IC50 values in the nanomolar range. Then, a molecular docking analysis was carried out to assess the binding affinities of curcumin for CCR5 and HIV-1 RNase H/RT. The anti-HIV activity assay showed that curcumin inhibited HIV-1 infection, and the molecular docking analysis revealed equilibrium dissociation constants of [Formula: see text]9.8[Formula: see text]kcal/mol and [Formula: see text]9.3[Formula: see text]kcal/mol between curcumin and CCR5 and HIV-1 RNase H/RT, respectively. To examine curcumin's anti-HIV effect and its mechanism in vitro, cell cytotoxicity, transcriptome sequencing, and CCR5 and FOXP3 amounts were assessed at different concentrations of curcumin. In addition, human CCR5 promoter deletion constructs and the FOXP3 expression plasmid pRP-FOXP3 (with an EGFP tag) were generated. Whether FOXP3 DNA binding to the CCR5 promoter was blunted by curcumin was examined using transfection assays employing truncated CCR5 gene promoter constructs, a luciferase reporter assay, and a chromatin immunoprecipitation (ChIP) assay. Furthermore, micromolar concentrations of curcumin inactivated the nuclear transcription factor FOXP3, which resulted in decreased expression of CCR5 in Jurkat cells. Moreover, curcumin inhibited PI3K-AKT activation and its downstream target FOXP3. These findings provide mechanistic evidence encouraging further assessment of curcumin as a dietary agent used to reduce the virulence of CCR5-tropic HIV-1. Curcumin-mediated FOXP3 degradation was also reflected in its functions, namely, CCR5 promoter transactivation and HIV-1 virion production. Furthermore, curcumin inhibition of CCR5 and HIV-1 might constitute a potential therapeutic strategy for reducing HIV progression.

Du Huo Ji Sheng Tang inhibits Notch1 signaling and subsequent NLRP3 activation to alleviate cartilage degradation in KOA mice.

BACKGROUND: Knee osteoarthritis (KOA) has a complex pathological mechanism and is difficult to cure. The traditional medicine Du Huo Ji Sheng Tang (DHJST) has been used for the treatment of KOA for more than one thousand years, but its mechanism for treating KOA has not been revealed. In our previous study, we confirmed that DHJST inhibited the activation of NLRP3 signaling in rats and humans. In the current study, we aimed to determine how DHJST inhibits NLRP3 to alleviate knee cartilage damage. METHODS: Mice were injected with NLRP3 shRNA or Notch1-overexpressing adenovirus into the tail vein to construct systemic NLRP3 low-expressing or Notch1 high-expressing mice. Mice were injected with papain into the knee joint to replicate the KOA model. DHJST was used to treat KOA model mice with different backgrounds. The thickness of the right paw was measured to evaluate toe swelling. The pathohistological changes and the levels of IL-1ß, MMP2, NLRP3, Notch1, collagen 2, collagen 4, HES1, HEY1, and Caspase3 were detected by HE staining, ELISA, immunohistochemical staining, western blotting, or real-time qPCR. RESULTS: DHJST reduced tissue swelling and serum and knee cartilage IL-1ß levels, inhibited cartilage MMP2 expression, increased collagen 2 and collagen 4 levels, decreased Notch1 and NLRP3 positive expression rates in cartilage, and decreased HES1 and HEY1 mRNA levels in KOA model mice. In addition, NLRP3 interference decreased cartilage MMP2 expression and increased collagen 2 and collagen 4 levels without affecting the expression levels of notch1, HES1 and HEY1 mRNA levels in the synovium of KOA mice. In KOA mice with NLRP interference, DHJST further reduced tissue swelling and knee cartilage damage in mice. Finally, Notch1-overexpressing mice not only showed more severe tissue swelling and knee cartilage degradation but also abolished the therapeutic effect of DHJST on KOA mice. Importantly, the inhibitory effects of DHJST on the mRNA expression of NLRP3, Caspase3 and IL-1ß in the knee joint of KOA mice were completely limited after Notch1 overexpression. CONCLUSION: DHJST significantly reduced inflammation and cartilage degradation in KOA mice by inhibiting Ntoch1 signaling and its subsequent NLRP3 activation in the knee joint.

Preparation of pectin-chitosan hydrogels based on bioadhesive-design micelle to prompt bacterial infection wound healing.

The aim of this study was to design a pectin-chitosan (PEC-CS) hydrogel loaded with a bioadhesive-design micelle containing large amount of ciprofloxacin for antibacterial and healing wound applications. Pectin and chitosan are crosslinked in a safe and convenient way, and the PEC-CS hydrogel have high water content (>95 %), strong water absorption (15,000 %), good water retention (>10,000 % at 30 % RH for 12 h), and the PEC-CS hydrogels showed no cytotoxicity and hemolysis, thus providing a humid microenvironment suitable for wound. Additionally, the dopamine modified carrier can greatly improve the solubility and retention time in the wound of ciprofloxacin, effectively increase the efficiency of drug loading into the PEC-CS hydrogels and exert antibacterial activity in the wound for a long time. In vitro and in vivo pharmacodynamics experiments have shown that PEC-CS#CIP@DPDMCs hydrogels can resist bacteria and promote wound healing. Thus，The PEC-CS#CIP@DPDMCs hydrogels can be a potential anti-infective hydrogel excipient.

Research progress on metabolomics in the quality evaluation and clinical study of Panax ginseng.

Panax ginseng, an essential component of traditional medicine and often referred to as the king of herbs, has played a pivotal role in medicine globally for several millennia. Previously, traditional phytochemical methods were mainly used for quality evaluation and pharmacological mechanism studies of ginseng, resulting in the lack of systematicness and innovation and hindering the development and utilization of ginseng resources. Since the beginning of the new century, systems biology technology represented by metabolomics has shown unique advantages in the modernization and internationalization of herbal medicine, establishing a bridge for communication between traditional medicine and modern medicine. P. ginseng, a special herb used in medicine and food, is one of the main research objects for qualitative and quantitative analysis of metabolomics and has gradually become the focus of researchers globally. Here, we conducted a comprehensive summary and analysis of numerous studies published in ginseng metabolomics. This review aims to provide more novel ideas for the quality evaluation, development, and clinical application of ginseng in the future and offer more useful technical references for the modernization and internationalization of herbal medicine based on metabolomics.

Reactive Oxygen Species-Responsive Polypeptide Drug Delivery System Targeted Activated Hepatic Stellate Cells to Ameliorate Liver Fibrosis.

Hepatic fibrosis is a chronic liver disease that lacks effective pharmacotherapeutic treatments. As part of the disease's mechanism, hepatic stellate cells (HSCs) are activated by damage-related stimuli to secrete excessive extracellular matrix, leading to collagen deposition. Currently, the drug delivery system that targets HSCs in the treatment of liver fibrosis remains an urgent challenge due to the poor controllability of drug release. Since the level of reactive oxygen species (ROS) increases sharply in activated HSCs (aHSCs), we designed ROS-responsive micelles for the HSC-specific delivery of a traditional Chinese medicine, resveratrol (RES), for treatment of liver fibrosis. The micelles were prepared by the ROS-responsive amphiphilic block copolymer poly(l-methionine-block-Nε-trifluoro-acetyl-l-lysine) (PMK) and a PEG shell modified with a CRGD peptide insertion. The CRGD-targeted and ROS-responsive micelles (CRGD-PMK-MCs) could target aHSCs and control the release of RES under conditions of high intracellular ROS in aHSCs. The CRGD-PMK-MCs treatment specifically enhanced the targeted delivery of RES to aHSCs both in vitro and in vivo. In vitro experiments show that CRGD-PMK-MCs could significantly promote ROS consumption, reduce collagen accumulation, and avert activation of aHSCs. In vivo results demonstrate that CRGD-PMK-MCs could alleviate inflammatory infiltration, prevent fibrosis, and protect hepatocytes from damage in fibrotic mice. In conclusion, CRGD-PMK-MCs show great potential for targeted and ROS-responsive controlled drug release in the aHSCs of liver fibrosis.

Metabolism of Paeoniae Radix Rubra and its 14 constituents in mice.

Objective: Paeoniae Radix Rubra (PRR) is a commonly used traditional Chinese medicine with the effects of clearing away heat, cooling the blood, and relieving blood stasis. To 1) elucidate the metabolites and metabolic pathways of PRR and its 14 main constituents in mice and 2) reveal the possible origins of the known effective forms of PRR and their isomers, the metabolism of PRR in mice was systematically studied for the first time. Methods: PRR and its 14 constituents were administered to mice by gavage once a day for seven consecutive days, respectively. All urine and feces were collected during the 7 days of dosing, and blood was collected at 1 h after the last dose. Metabolites were detected and identified using high performance liquid chromatography with diode array detector and combined with electrospray ionization ion trap time-of-flight multistage mass spectrometry (HPLC-DAD-ESI-IT-TOF-MSn). Results: In total, 23, 16, 24, 17, 18, 30, 27, 17, 22, 17, 33, 3, 8, 24, and 31 metabolites of paeoniflorin, albiflorin, oxypaeoniflorin, benzoylpaeoniflorin, hydroxybenzoylpaeoniflorin, benzoyloxypaeoniflorin, galloylpaeoniflorin, lactiflorin, epicatechin gallate, catechin gallate, catechin, ellagic acid, 3,3'-di-O-methylellagic acid, methylgallate, and PRR were respectively identified in mice; after eliminating identical metabolites, a total of 195 metabolites remained, including 8, 11, 25, 17, 18, 30, 27, 17, 21, 17, 1, 2, 8, 20, and 20 newly identified metabolites, respectively. The metabolic reactions of PRR and its 14 main constituents in mice were primarily methylation, hydrogenation, hydrolysis, hydroxylation, glucuronidation, and sulfation. Conclusion: We elucidated the metabolites and metabolic pathways of PRR and its 14 constituents (e.g., paeoniflorin, catechin, ellagic acid, and gallic acid) in mice and revealed the possible origins of the 10 known effective forms of PRR and their isomers. The findings are of great significance to studying the mechanism of action and quality control of PRR.

Arterial blood gas analysis aids early differential diagnosis and treatment of primary and secondary hypokalaemic periodic paralysis.

This study aimed to examine changes in electrolytes and acid-base status in primary and secondary hypokalaemic periodic paralysis (HypoPP), which will help early differential diagnosis of HypoPP. A total of 64 HypoPP patients were enrolled and relevant data from clinical records was collected. Overall, 64 patients (mean age 28.2±7.3 years) of which 58(91%) were males, with 39, 11 and 14 patients, respectively, diagnosed as primary HypoPP, thyrotoxic HypoPP, and other secondary HypoPPs at discharge, were assessed. Those with HypoPP secondary to conditions other than hyperthyroidism were more likely to develop acid-base imbalance (p<0.001); they had higher pH (p=0.046) and HCO3 levels (p=0.014) at baseline, and needed a higher dose of potassium supplement before the serum potassium level returned to normal (p=0.007) and a longer time to regain full muscle strength (p=0.004), compared with those with primary or thyrotoxic HypoPP. Emergent arterial blood gas analysis may aid early differential diagnosis of patients with primary and secondary HypoPP.

[Comparison of transcriptome of Atractylodes lancea rhizome and exploration of genes for sesquiterpenoid biosynthesis].

This study compared the transcriptome of Atractylodes lancea rhizome at different development stages and explored genes encoding the key enzymes of the sesquiterpenoid biosynthesis pathway. Specifically, Illumina NovaSeq 6000 was employed for sequencing the cDNA libraries of A. lancea rhizome samples at the growth stage(SZ), flowering stage(KH), and harvesting stage(CS), respectively. Finally, a total of 388 201 748 clean reads were obtained, and 16 925, 8 616, and 13 702 differentially expressed genes(DEGs) were identified between SZ and KH, KH and CS, and SZ and CS, separately. Among them, 53 genes were involved in the sesquiterpenoid biosynthesis pathways: 9 encoding 6 enzymes of the mevalonic acid(MVA) pathway, 15 encoding 7 enzymes of the 2-C-methyl-D-erythritol-4-phosphate(MEP) pathway, and 29 of sesquiterpenoid and triterpenoid biosynthesis pathway. Weighted gene co-expression network analysis(WGCNA) yielded 12 genes related to sesquiterpenoid biosynthesis for the SZ, 1 gene for the KH, and 1 gene for CS, and several candidate genes for sesquiterpenoid biosynthesis were discovered based on the co-expression network. This study laid a solid foundation for further research on the sesquiterpenoid biosynthesis pathway, analysis of the regulation mechanism, and mechanism for the accumulation of sesquiterpenoids in A. lancea.

A dual-responsive "Yin-Yang" photothermal delivery system to accelerate Parthenolide anti-tumor efficacy.

Parthenolide (PTL), a germacrane sesquiterpene lactone extracted from the "Yin" Chinese traditional herb feverfew, has gained interest due to its lethal effects on tumor cells and its pharmacological effects within traditional Chinese medicine theory. To overcome low, non-targeted accumulation and uncontrolled release of PTL administration, a dual-responsive PTL-liposomes@chitosan@gold nanoshells (PTL-Lips@CS@GNS) system was fabricated. Hyperthermia generated under light irradiation in the near-infrared region via local surface plasmon resonance of gold nanoshells induced photothermal therapy, which also stimulated PTL release due to the liposomes gel-to-liquid crystalline phase transition. Additionally, PTL-Lips@CS@GNS exhibited a pH-responsive release in the acidic tumor microenvironment. Collectively, this study provides a realistic strategy for an effective combination of traditional Chinese medicine and current nanotechnology for tumor therapy.

[Construction status and development strategy of GAP bases for Chinese herbal medicine].

Good agricultural practices(GAP) for Chinese herbal medicine(CHM) is the source of quality control in the production of CHM. To ensure the safety, efficacy, and quality of Chinese herbal and natural medicine, the international community has been exploring the implementation of GAP for CHM. The implementation of GAP for CHM has a far-reaching impact, and the scale planting of CHM has been expanding. However, the medicinal materials produced by the GAP bases for CHM still cannot fully meet the market demand, and the output and quality of CHM remain to be improved. This paper summarizes construction status of GAP bases for CHM.The 129 companies that passed the certification during the implementation of GAP for CHM included 196 GAP bases, forming the scale CHM production zone with Sichuan province, Yunnan province, Jilin province, Henan province, and Shandong province as the core.The total area of GAP bases for CHM in China is about 250 000-500 000 Mu(1 Mu≈667 m2), which is still less than 1% of the total production area of CHM. The international agricultural production quality management strategies are all market-oriented behaviors.Drawing on the international good agricultural and collection practice(GACP) and hazard analysis critical control point(HACCP) as well as the relevant policies of Chinese quality management of CHM, we put forward feasible suggestions for the further implementation of GAP for CHM:(1)The market rules and international experience should be followed and employed to promote GAP management of CHM and third-party implementation of GAP certification;(2)The sound development of GAP for CHM should be boosted with the HACCP management system and the revision of GAP for CHM;(3)The implementation of policies and standards should be stepped up to facilitate the building of a whole-course traceability system for the production of CHM with high quality and reasonable prices.

[Construction of pharmacophore model and its application in identification of effective components of Chinese medicine].

The effective material basis of Chinese medicine is the key and difficult point in the quality control and modernization research of Chinese medicine. With the increasing application of pharmacophore-based virtual screening in computer-aided drug design, it is possible to employ this technology in the modernization of Chinese medicine. Based on the systematic research method of the pharmacophore model, the present study systematically reviewed the pharmacophore-based technologies and strategies in the identification of active components in Chinese medicine.

[Current status and prospects of implementing GAP in Chinese medicine injection materials].

Chinese medicine injections(CMIs) have higher requirements for quality consistency and controllability than other traditional Chinese medicine products. The implementation of Good Agricultural Practice of Medicinal Plants and Animals(GAP) is an important factor that guarantees the quality stability of raw Chinese medicinal materials and affects the quality of CMIs. Through literature review, data research, expert consultation, and statistical analysis, this paper analyzes the current status of GAP management of key CMIs and the impact of GAP management of raw medicinal materials on the quality consistency and controllability of CMIs. Furthermore, it demonstrates the rationality, necessity, and feasibility of the full implementation of GAP on the basis of CMIs safety re-evaluation.

Sesamin Protects against and Ameliorates Rat Intestinal Ischemia/Reperfusion Injury with Involvement of Activating Nrf2/HO-1/NQO1 Signaling Pathway.

Intestinal ischemia-reperfusion (I/R) may induce cell/tissue injuries, leading to multiple organ failure. Based on our preexperiments, we proposed that sesamin could protect against and ameliorate intestinal I/R injuries and related disorders with involvement of activating Nrf2 signaling pathway. This proposal was evaluated using SD intestinal I/R injury rats in vivo and hypoxia/reoxygenation- (H/R-) injured rat small intestinal crypt epithelial cell line (IEC-6 cells) in vitro. Sesamin significantly alleviated I/R-induced intestinal histopathological injuries and significantly reduced serum biochemical indicators ALT and AST, alleviating I/R-induced intestinal injury in rats. Sesamin also significantly reversed I/R-increased TNF-α, IL-6, IL-1ß, and MPO activity in serum and MDA in tissues and I/R-decreased GSH in tissues and SOD in both tissues and IEC-6 cells, indicating its anti-inflammatory and antioxidative stress effects. Further, sesamin significantly decreased TUNEL-positive cells, downregulated the increased Bax and caspase-3 protein expression, upregulated the decreased protein expression of Bcl-2 in I/R-injured intestinal tissues, and significantly reversed H/R-reduced IEC-6 cell viability as well as reduced the number of apoptotic cells among H/R-injured IEC-6 cell, showing antiapoptotic effects. Activation of Nrf2 is known to ameliorate tissue/cell injuries. Consistent with sesamin-induced ameliorations of both intestinal I/R injuries and H/R injuries, transfection of Nrf2 cDNA significantly upregulated the expression of Nrf2, HO-1, and NQO1, respectively. On the contrary, either Nrf2 inhibitor (ML385) or Nrf2 siRNA transfection significantly decreased the expression of these proteins. Our results suggest that activation of the Nrf2/HO-1/NQO1 signaling pathway is involved in sesamin-induced anti-inflammatory, antioxidative, and antiapoptotic effects in protection against and amelioration of intestinal I/R injuries.

Wheat embryo globulin nutrients ameliorate d-galactose and aluminum chloride-induced cognitive impairment in rats.

Wheat embryo globulin nutrient (WEGN), with wheat embryo globulin (WEG) as the main functional component, is a nutritional combination that specifically targets memory impairment. In this study, we explored the protective role of WEGN on Alzheimer's disease (AD)-triggered cognitive impairment, neuronal injury, oxidative stress, and acetylcholine system disorder. Specifically, we established an AD model via administration of d-galactose (d-gal) and Aluminum chloride (AlCl3) for 70 days, then on the 36th day, administered animals in the donepezil and WEGN (300, 600, and 900 mg/kg) groups with drugs by gavage for 35 days. Learning and memory ability of the treated rats was tested using the Morris water maze (MWM) and novel object recognition (NOR) test, while pathological changes and neuronal death in their hippocampus CA1 were detected via HE staining and Nissl staining. Moreover, we determined antioxidant enzymes by measuring levels of superoxide dismutase (SOD), malondialdehyde (MDA), and glutathione peroxidase (GSH-Px) in serum, cortex, and hippocampus, whereas changes in the acetylcholine system were determined by evaluating choline acetyltransferase (ChAT), and acetylcholinesterase (AChE) activities, as well as choline acetylcholine (Ach) content. Results revealed that rats in the WEGN group exhibited significantly lower escape latency, as well as a significantly higher number of targeted crossings and longer residence times in the target quadrant, relative to those in the model group. Notably, rats in the WEGN group spent more time exploring new objects and exhibited lower damage to their hippocampus neuron, had improved learning and memory activity, as well as reversed histological alterations, relative to those in the model group. Meanwhile, biochemical examinations revealed that rats in the WEGN group had significantly lower MDA levels and AChE activities, but significantly higher GSH, SOD, and ChAT activities, as well as Ach content, relative to those in the model group. Overall, these findings indicate that WEGN exerts protective effects on cognitive impairment, neuronal damage, oxidative stress, and choline function in AD rats treated by d-gal/AlCl3.

Development a multi-immunoaffinity column LC-MS-MS method for comprehensive investigation of mycotoxins contamination and co-occurrence in traditional Chinese medicinal materials.

Mycotoxins are poisonous secondary fungal toxic metabolites and harmful to human health. Traditional Chinese medicinal materials (TCMs), including more than two hundred functional foods, are vulnerably bred fungi, causing spoilage and multi-mycotoxins contamination. This study established a simultaneous analytical method by using multi-mycotoxins immunoaffinity column (multi-IAC) and HPLC-MS/MS to evaluate mycotoxins' contamination levels and natural incidence in TCMs. Aflatoxins (AFs, including AFB1, AFB2, AFG1 and AFG2), ochratoxin A (OTA), fumonisins (FB1 and FB2), zearalenone (ZEN), deoxynivalenol (DON) and T-2 toxins in three TCMs or functional foods of Polygalae Radix (PR), Coicis Semen (CS) and Eupolyphaga Steleophaga (ES) were detected. The systematically investigated results of 30 batch AFB1 positive samples revealed co-occurrence and correlation of multi-mycotoxins are significant differences in various matrices. All the samples in this study contain more than 5 mycotoxins. AFB1-AFs, AFB1-FBs, AFB1-DON, and AFB1-T-2 are the most observed co-occurrence, AFB1-OTA is also of concern due to its synergistic toxicity. This study's results can be used to establish guidelines for screening mycotoxin contaminants and limitations on acceptable levels in TCMs. Simultaneously, mycotoxin's correlation results in different matrices can also provide a reference for the standardization of TCM production and processing.

[Current situation of nitrogen application and its effects on yield and quality of Chinese materia medica].

Nitrogen fertilizer has been the long-lasting crucial component in cultivation of Chinese materia medica(CMM) and crops for its profound effects on enhancing the productivity. In consideration of its role in better production, intensive and excessive application of N fertilizer is often found in CMM cultivation. Therefore, firstly, this review summarized various concentrations of N application with regards to different CMM and districts from the literatures published in the last two decades. The recommended concentration of nitrogen application of forty seven CMM species were covered in this review. We found that the optimum rates of nitrogen fertili-zer for different medicinal plants species were varied in the range between 0-1 035.55 kg·hm~(-2). Most of the optimum rates of nitrogen fertilizer for CMM in published researches fell between 100-199 kg·hm~(-2). The optimum rate of nitrogen fertilizer is not only related to amount of nitrogen required for different medicinal plants but also to soil fertilities of different fields. In addition, we outlined the diffe-rent effects of proper and excessive nitrogen deposition on yield of CMM. Proper nitrogen deposition benefits the yield of CMM, howe-ver, excessive nitrogen use accounts for a decrease in CMM yield. We elucidated that nutritional content, water use efficiencies, and photosynthesis capacity were major influencing factors. Researches showed that proper nitrogen fertilizer could promote the water use efficiencies of plants and boost photosynthesis. Consequently, the yield of CMM can be enhanced after nitrogen deposition. However, negative effects of nitrogen fertilizer were also found on plant including producing toxic substances to the soil and causing severe pest damages. Lastly we analyzed the impact of N fertilizer application on secondary metabolites which accounts for a large part of active pharmaceutical ingredients of CMM. It usually caused an increase in nitrogen-containing secondary metabolites content and a decrease in non-nitrogen-containing secondary metabolites content respectively. The potential underlying mechanisms are the different synthetic pathways of these metabolites and the plant nutritional status. Synthesis of non-nitrogen-containing secondary metabolites like phenols can be inhibited after nitrogen application because of the competition of the same precursor substances between metabolites synthesis and plant growth. To sum up, impacts and mechanisms of nitrogen fertilizer on yield and quality enhancement of CMM were discussed in this review. Negative effects of excessive nitrogen application on CMM should be paid special attention in CMM cultivation and prescription fertilization based on the field soil quality is strongly recommended. Overall, this review aims to provides insights on improving the proper application of N fertilizer in the cultivation of CMM.