Fabrication of amino- and hydroxyl dual-functionalized magnetic microporous organic network for extraction of zearalenone from traditional Chinese medicine prior to the HPLC determination.

Efficient enrichment of trace zearalenone (ZEN) from the complex traditional Chinese medicine (TCM) samples is quite difficult, but of great significance for TCM quality control. Herein, we reported a novel magnetic solid phase extraction (MSPE) strategy for ZEN enrichment using the amino- and hydroxyl dual-functionalized magnetic microporous organic network (Fe3O4@MON-NH2-OH) as an advanced adsorbent combined with the high-performance liquid chromatography (HPLC) determination. Efficient extraction of ZEN was achieved via the possible hydrogen bonding, hydrophobic, and π-π interactions between Fe3O4@MON-NH2-OH and ZEN. The adsorption capacity of Fe3O4@MON-NH2-OH for ZEN was 215.0 mg g-1 at the room temperature, which was much higher than most of the reported adsorbents. Under the optimal condition, the developed Fe3O4@MON-NH2-OH-MSPE-HPLC method exhibited wide linear range (5-2500 µg L-1), low limits of detection (1.4-35 µg L-1), less adsorbent consumption (5 mg), and large enhancement factor (95) for ZEN. The proposed method was successfully applied to detect trace ZEN from 10 kinds of real TCM samples. Conclusively, this work demonstrates the Fe3O4@MON-NH2-OH can effectively extract trace ZEN from the complex TCM matrices, which may open up a new way for the application of MONs in the enrichment and extraction of trace contaminants or active constituents from the complex TCM samples.

First Detection of Atractylodes Mild Mottle Virus in Atractylodes lancea (Thunb.) DC. in Hubei Province of China.

The cultivated aromatic medicinal herb Atractylodes lancea (Thunb.) DC. is widely used in the pharmaceuticals, nutraceuticals, and cosmetics industries (Na-Bangchang et al. 2014; Zhan et al. 2023). Huanggang in Hubei Province is a major production area for A. lancea (Huang et al. 2022; Wang et al. 2023). In April 2023, more than two-thirds of the surveyed plant leaves in this region exhibited virus-like symptoms, such as curling and mosaic patterns. To identify the underlying cause, 80 symptomatic plant leaf samples were collected from four fields (20 leaves per field) in this region and pooled for virome analysis. Total RNA, including ribosomal RNA, was extracted from the pooled samples using the Plant RNA Extraction Mini Kit (Onrew Biotech, Guangdong, China), for sequencing library construction. The Illumina NovaSeq 6000 platform was used to sequence the library and generate 150 bp paired-end reads. After processing the raw data with Trimmomatic software, a total of 44,354,650 high-quality clean reads were obtained. The clean reads were aligned against ribosomal RNA using BWA software (v0.7.17) to avoid interference and eliminate corresponding sequences. After removing potential contamination, contig assembly of the clean reads was performed using Megahit software (v1.2.9). The resulting contigs were compared with the virus NT database using the BLASTn program. Sequence pairwise comparison revealed 8 contigs (574 nt to 2243 nt) with identities ranging from 81.88% to 90.77% with Atractylodes mild mottle virus (AMMV, NC_027924.1, Lim et al., 2015). Additionally, contigs mapped to Carlavirus, Pelarspovirus, and other plant viruses in our virome dataset had low coverage and pairwise identity (less than 70%), which need to be further investigated. The presence of AMMV was confirmed by aligning the clean reads to the reference sequence (NC_027924.1) using BWA and SAMtools software, resulting in a consensus sequence (8024 nt) with gaps. DNA extraction from the pooled samples was performed using the Rapid Universal Genomic DNA Extraction Kit (Simgen, Zhejiang, China). Two pairs of specific primers, 3399F (5'-AAAGAAGAACCTCCTGATACGG-3')/5924R (5'-TGAACCTGATTCTCTTGGC-3') and 1830F (5'- CTCAGGAAATCCCAATGC -3')/3640R(5'-TTTCCCAATGTTCTTCGGG-3'), were designed to amplify the complete gene sequences of polymerase and coat protein (CP), based on the consensus sequence. The PCR products with the lengths of 2521 bp and 1814 bp were cloned into the pMD18-T vector (Takara Biotech, Dalian, China) for sequencing. The BLASTn analysis showed that the polymerase and CP gene sequences shared an identity of 94.51% (1929/2041 nt) and 88.41% (1419/1605 nt) with the AMMV isolate (NC_027924.1), respectively. The sequences have been deposited in GenBank under the accession numbers OR544810 and OR544811. We collected leaves from 32 A. lancea plants (16 symptomatic and 16 asymptomatic) in the fields. RT-PCR was conducted using CPF (5'-CTGCGAATATGAAAGTGC-3') and CPR (5'-GGTGAGCTTGTCTGTTAGG-3') primers, which were designed targeting a 527bp fragment of the CP gene (OR544811). Amplicons of the expected size (527bp) were detected in 24 plants (11 symptomatic and 13 asymptomatic), three of which were sequenced by Sanger sequencing, showing a 100% match to OR544811. These findings indicate that AMMV is prevalent in the major production area of A. lancea. Further research is needed to better characterize the potential risks of AMMV to A. lancea cultivation in China as well as other countries.

Dryopteris crassirhizoma Nakai.: A review of its botany, traditional use, phytochemistry, pharmacological activity, toxicology and pharmacokinetics.

ETHNOPHARMACOLOGICAL RELEVANCE: The Dryopteris crassirhizoma Nakai., a commonly used herb, is known as "Guan Zhong" in China, "Oshida" in Japan and "Gwanjung" in Korea. It has long been used for parasitic infestation, hemorrhages and epidemic influenza. AIM OF THE REVIEW: The present paper aims to provide an up-to-date review at the advancements of the investigations on the traditional use, phytochemistry, pharmacological activity, toxicology and pharmacokinetics of D. crassirhizoma. Besides, possible trends, therapeutic potentials, and perspectives for future research of this plant are also briefly discussed. MATERIALS AND METHODS: Relevant information on traditional use, phytochemistry, pharmacological activity, toxicology and pharmacokinetics of D. crassirhizoma was collected through published materials and electronic databases, including the Chinese Pharmacopoeia, Flora of China, Web of Science, PubMed, Baidu Scholar, Google Scholar, and China National Knowledge Infrastructure. 109 papers included in the article and we determined that no major information was missing after many checks. All authors participated in the review process for this article and all research paper are from authoritative published materials and electronic databases. RESULTS: 130 chemical components, among which phloroglucinols are the predominant groups, have been isolated and identified from D. crassirhizoma. D. crassirhizoma with its bioactive compounds is possessed of extensive biological activities, including anti-parasite, anti-microbial, anti-viral, anti-cancer, anti-inflammatory, anti-oxidant, anti-diabetic, bone protective, immunomodulatory, anti-platelet and anti-hyperuricemia activity. Besides, D. crassirhizoma has special toxicology and pharmacokinetics characterization. CONCLUSIONS: D. crassirhizoma is a traditional Chinese medicine having a long history of application. This review mainly summarized the different chemical components extract from D. crassirhizoma and various reported pharmacological effects. Besides, the toxicology and pharmacokinetics of D. crassirhizoma also be analysed in this review. However, the chemical components of D. crassirhizoma are understudied and require further research to expand its medicinal potential, and it is urgent to design a new extraction scheme, so that the active ingredients can be obtained at a lower cost.

Bithiophene-Functionalized Infrared Two-Photon Absorption Metal Complexes as Single-Molecule Platforms for Synergistic Photodynamic, Photothermal, and Chemotherapy.

A planar conjugated ligand functionalized with bithiophene and its Ru(II), Os(II), and Ir(III) complexes have been constructed as single-molecule platform for synergistic photodynamic, photothermal, and chemotherapy. The complexes have significant two-photon absorption at 808 nm and remarkable singlet oxygen and superoxide anion production in aqueous solution and cells when exposed to 808 nm infrared irradiation. The most potent Ru(II) complex Ru7 enters tumor cells via the rare macropinocytosis, locates in both nuclei and mitochondria, and regulates DNA-related chemotherapeutic mechanisms intranuclearly including DNA topoisomerase and RNA polymerase inhibition and their synergistic effects with photoactivated apoptosis, ferroptosis and DNA cleavage. Ru7 exhibits high efficacy in vivo for malignant melanoma and cisplatin-resistant non-small cell lung cancer tumors, with a 100% survival rate of mice, low toxicity to normal cells and low residual rate. Such an infrared two-photon activatable metal complex may contribute to a new generation of single-molecule-based integrated diagnosis and treatment platform to address drug resistance in clinical practice and phototherapy for large, deeply located solid tumors.

[Simultaneous determination of seven artemisinin-related compounds in Artemisia annua by UPLC-QQQ-MS/MS].

A variety of compounds in Artemisia annua were simultaneously determined to evaluate the quality of A. annua from multiple perspectives. A method based on ultra-high performance liquid chromatography-triple quadrupole tandem mass spectrometry(UPLC-QQQ-MS/MS) was established for the simultaneous determination of seven compounds: amorpha-4,11-diene, artemisinic aldehyde, dihydroartemisinic acid, artemisinic acid, artemisinin B, artemisitene, and artemisinin, in A. annua. The content of the seven compounds in different tissues(roots, stems, leaves, and lateral branches) of A. annua were compared. The roots, stems, leaves, and lateral branches of four-month-old A. annua were collected and the content of seven artemisinin-related compounds in different tissues was determined. A multi-reaction monitoring(MRM) acquisition mode of UPLC-QQQ-MS/MS was used, with a positive ion mode of atmospheric pressure chemical ion source(APCI). Chromatographic separation was achieved on an Eclipse Plus RRHD C_(18) column(2.1 mm×50 mm, 1.8 µm). The gradient elution was performed with the mobile phase consisted of formic acid(0.1%)-ammonium formate(5 mmol·L~(-1))(A) and the methanol(B) gradient program of 0-8 min, 55%-100% B, 8-11 min, 100% B, and equilibrium for 3 min, the flow rate of 0.6 mL·min~(-1), the column temperature of 40 ℃, the injection volume of 5 µL, and the detection time of 8 min. Through methodological investigation, a method based on UPLC-QQQ-MS/MS was established for the simultaneous quantitative determination of seven representative compounds involved in the biosynthesis of artemisinin. The content of artemisinin in A. annua was higher than that of artemisinin B, and the content of artemisinin and dihydroartemisinic acid were high in all the tissues of A. annua. The content of the seven compounds varied considerably in different tissues, with the highest levels in the leaves and neither artemisinene nor artemisinic aldehyde was detected in the roots. In this study, a quantitative method based on UPLC-QQQ-MS/MS for the simultaneous determination of seven representative compounds involved in the biosynthesis of artemisinin was established, which was accurate, sensitive, and highly efficient, and can be used for determining the content of artemisinin-related compounds in A. annua, breeding new varieties, and controlling the quality of Chinese medicinal materials.

Efficacy of traditional Chinese medicine versus angiotensin-converting enzyme inhibitors, angiotensin receptor blockers, and their combinations in the treatment of IgA nephropathy: a systematic review and network meta-analysis.

Background: IgA nephropathy (IgAN), a condition posing a significant threat to public health, currently lacks a specific treatment protocol. Research has underscored the potential benefits of traditional Chinese medicine (TCM) for treating IgAN. Nevertheless, the effectiveness of various intervention strategies, such as combining TCM with angiotensin-converting enzyme inhibitors (ACEIs) or angiotensin II receptor blockers (ARBs), lacks a comprehensive systematic comparison. Therefore, this study aimed to conduct a network meta-analysis to assess the clinical efficacy of ACEIs, ARBs, TCM, and their combinations in treating IgAN to offer novel insights and approaches for the clinical management of IgAN. Methods: A systematic review conducted until November 2023 included relevant literature from databases such as PubMed, Embase, Cochrane, Web of Science, Scopus, CNKI, and Wanfang. Two independent researchers screened and assessed the data for quality. Network and traditional meta-analyses were performed using Stata 18.0 and RevMan 5.3 software, respectively. Outcome measures included 24-h urinary protein quantification (24 hpro), estimated glomerular filtration rate (eGFR), serum creatinine (Scr), blood urea nitrogen (BUN), and adverse event incidence rates (ADRs). Forest plots, cumulative ranking probability curves (SUCRA), and funnel plots generated using Stata 18.0 facilitated a comprehensive analysis of intervention strategies' efficacy and safety. Results: This study included 72 randomized controlled trials, seven interventions, and 7,030 patients. Comparative analysis revealed that ACEI + TCM, ARB + TCM combination therapy, and TCM monotherapy significantly reduced the levels of 24 hpro, eGFR, Scr, and BUN compared to other treatment modalities (p < 0.05). TCM monotherapy demonstrated the most favorable efficacy in reducing eGFR levels (SUCRAs: 78%), whereas the combination of ARB + TCM reduced Scr, 24 hpro, and BUN levels (SUCRAs: 85.7%, 95.2%, and 87.6%, respectively), suggesting that ARB + TCM may represent the optimal intervention strategy. No statistically significant differences were observed among the various treatment strategies in terms of ADR (p > 0.05). Conclusion: The combination of ACEI or ARB with TCM demonstrated superior efficacy compared to ACEI/ARB monotherapy in the treatment of IgAN without any significant ADRs. Therefore, combination therapies can be used to enhance therapeutic outcomes based on individual patient circumstances, highlighting the use of TCM as a widely applicable approach in clinical practice. Systematic Review Registration: https://www.crd.york.ac.uk/PROSPERO/, identifier CRD42023476674.

Shikonin suppresses rheumatoid arthritis by inducing apoptosis and autophagy via modulation of the AMPK/mTOR/ULK-1 signaling pathway.

BACKGROUND: The overproliferation of fibroblast-like synoviocytes (FLS) contributes to synovial hyperplasia, a pivotal pathological feature of rheumatoid arthritis (RA). Shikonin (SKN), the active compound from Lithospermum erythrorhizon, exerts anti-RA effects by diverse means. However, further research is needed to confirm SKN's in vitro and in vivo anti-proliferative functions and reveal the underlying specific molecular mechanisms. PURPOSE: This study revealed SKN's anti-proliferative effects by inducing both apoptosis and autophagic cell death in RA FLS and adjuvant-induced arthritis (AIA) rat synovium, with involvement of regulating the AMPK/mTOR/ULK-1 pathway. METHODS: SKN's influences on RA FLS were assessed for proliferation, apoptosis, and autophagy with immunofluorescence staining (Ki67, LC3B, P62), EdU incorporation assay, staining assays of Hoechst, Annexin V-FITC/PI, and JC-1, transmission electron microscopy, mCherry-GFP-LC3B puncta assay, and western blot. In AIA rats, SKN's anti-arthritic effects were assessed, and its impacts on synovial proliferation, apoptosis, and autophagy were studied using Ki67 immunohistochemistry, TUNEL, and western blot. The involvement of AMPK/mTOR/ULK-1 pathway was examined via western blot. RESULTS: SKN suppressed RA FLS proliferation with reduced cell viability and decreased Ki67-positive and EdU-positive cells. SKN promoted RA FLS apoptosis, as evidenced by apoptotic nuclear fragmentation, increased Annexin V-FITC/PI-stained cells, reduced mitochondrial potential, elevated Bax/Bcl-2 ratio, and increased cleaved-caspase 3 and cleaved-PARP protein levels. SKN also enhanced RA FLS autophagy, featuring increased LC3B, reduced P62, autophagosome formation, and activated autophagic flux. Autophagy inhibition by 3-MA attenuated SKN's anti-proliferative roles, implying that SKN-induced autophagy contributes to cell death. In vivo, SKN mitigated the severity of rat AIA while also reducing Ki67 expression, inducing apoptosis, and enhancing autophagy within AIA rat synovium. Mechanistically, SKN modulated the AMPK/mTOR/ULK-1 pathway in RA FLS and AIA rat synovium, as shown by elevated P-AMPK and P-ULK-1 expression and decreased P-mTOR expression. This regulation was supported by the reversal of SKN's in vitro and in vivo effects upon co-administration with the AMPK inhibitor compound C. CONCLUSION: SKN exerted in vitro and in vivo anti-proliferative properties by inducing apoptosis and autophagic cell death via modulating the AMPK/mTOR/ULK-1 pathway. Our study revealed novel molecular mechanisms underlying SKN's anti-RA effects.

Arenobufagin modulation of PCSK9-mediated cholesterol metabolism induces tumor-associated macrophages polarisation to inhibit hepatocellular carcinoma progression.

BACKGROUND: The tumor microenvironment (TME) of hepatocellular carcinoma is heterogeneous enough to be prone to drug resistance and multidrug resistance during treatment, and reprogramming of cholesterol metabolism in TME mediates tumor-associated macrophages (TAMs) polarization, which has an impact on the regulation of malignant tumor progression. Arenobufagin (ARBU) was extracted and isolated from toad venom (purity ≥98 %), which is the main active ingredient of the traditional Chinese medicine Chan'su with good anti-tumor effects. PURPOSE: To investigate the regulatory effect of ARBU on lipid metabolism in tumor microenvironment, interfere with macrophage polarization, and determine its mechanism of action on liver cancer progression. METHODS: In this study, the inhibitory effect of ARBU on the proliferation of Hepa1-6 in C57 mice and the safety of administration were evaluated by establishing a transplanted tumor model of Hepa1-6 hepatocellular carcinoma mice and using 5-FU as a positive control drug. In addition, we constructed a co-culture system of Hepa1-6 cells and primary mouse macrophages to study the effects of ARBU on the polarization phenotypic transformation of macrophages and the proliferation and migration of hepatoma cells. The influence of ARBU on the metabolism of lipids in the hepatocellular carcinoma mouse model was investigated by combining it with lipidomics technology. The influence of ARBU on the PCSK9/LDL-R signaling pathway and macrophage polarization, which regulate cholesterol metabolism, was tested by using qRT-PCR, gene editing, IF, and WB. CONCLUSION: ARBU significantly inhibited the proliferation of Hepa1-6 in vivo and in vitro, regulated cholesterol metabolism, and promoted the M1-type polarization of macrophages in the tumor microenvironment. ARBU inhibits cholesterol synthesis in the TME through the PCSK9/LDL-R signaling pathway, thereby blocking macrophage M2 polarization, promoting apoptosis of the tumor cells, and inhibiting their proliferation and migration.

A review on extraction, purification, structural characteristics, biological activities, applications of polysaccharides from Hovenia dulcis Thunb. (Guai Zao).

Hovenia dulcis Thunb. (H. dulcis) is a widely distributed plant with a long history of cultivation and consumption. As a common plant, it has economic, edible and medicinal value. H. dulcis polysaccharides are one of their main bioactive ingredients and have many health benefits, such as anti-diabetes, antioxidation, anti-glycosylation, anti-fatigue, immune regulation activities and alcoholic liver disease protection activity. In this paper, the research progress of H. dulcis polysaccharides in extraction, purification, structural characteristics, biological activities, existing and potential applications were reviewed, which could provide new valuable insights for future studies.

Serum Iron Levels, Dietary Iron Intake, and Supplement Use in Relation to Metabolic Syndrome in Adolescents: A Cross-Sectional Study.

The objective of this study was to investigate the potential associations between serum iron levels, dietary iron intake, and iron supplementation, and the prevalence of metabolic syndrome (MetS) in adolescents A cross-sectional analysis was conducted, utilizing data from adolescents participating in the 2003-2018 cycle of the National Health and Nutrition Examination Survey (NHANES). Odds ratios (ORs) and their corresponding 95% confidence intervals (CIs) pertaining to serum iron, dietary iron, and iron supplementation were derived through multivariate logistic regression models. Additionally, a restricted cubic spline (RCS) regression model was applied to explore the nonlinear relationship between dietary iron and serum iron concerning MetS. The study encompassed 4858 American adolescents aged 12 to 19, among whom 413 (8.5%) manifested MetS. The study cohort exhibited an average age of 15.52 years, comprising 2551 males (52.51%) and 2307 females (47.49%). Relative to individuals in the lowest serum iron quartile, those in the highest quartile for serum iron (OR = 0.33, 95% CI 0.21-0.50), the highest quartile for dietary iron (OR = 0.53, 95% CI 0.32-0.89), and those utilizing iron supplements (OR = 0.61, 95% CI 0.37-0.99) evinced a diminished prevalence of MetS, even post adjustment for potential confounding variables. A non-linear relationship was discerned between serum iron and MetS, exhibiting a statistically significant negative correlation when serum iron concentrations exceeded the inflection point (serum iron = 8.66 µmol/L, P for nonlinear < 0.001). This investigation reveals that higher levels of serum iron, increased dietary iron intake, and the use of iron supplements are linked to a lower prevalence of MetS in US adolescents. These findings suggest that dietary modifications could play a role in promoting the health of adolescents.

Dichroa febrifuga Lour.: A review of its botany, traditional use, phytochemistry, pharmacological activities, toxicology, and progress in reducing toxicity.

ETHNOPHARMACOLOGICAL RELEVANCE: Dichroa febrifuga Lour., a toxic but extensively used traditional Chinese medicine with a remarkable effect, is commonly called "Changshan" in China. It has been used to treat malaria and many other parasitic diseases. AIM OF THE REVIEW: The study aims to provide a current overview of the progress in the research on traditional use, phytochemistry, pharmacological activities, toxicology, and methods of toxicity reduction of D. febrifuga. Additionally, further research directions and development prospects for the plant were put forward. MATERIALS AND METHODS: The article uses "Dichroa febrifuga Lour." "D. febrifuga" as the keyword and all relevant information on D. febrifuga was collected from electronic searches (Elsevier, PubMed, ACS, CNKI, Google Scholar, and Baidu Scholar), doctoral and master's dissertations and classic books about Chinese herbs. RESULTS: 30 chemical compounds, including alkaloids, terpenoids, flavonoids and other kinds, were isolated and identified from D. febrifuga. Modern pharmacological studies have shown that these components have a variety of pharmacological activities, including anti-malarial activities, anti-inflammatory activities, anti-tumor activities, anti-parasitic activities and anti-oomycete activities. Meanwhile, alkaloids, as the material basis of its efficacy, are also the source of its toxicity. It can cause multiple organ damage, including liver, kidney and heart, and cause adverse reactions such as nausea and vomiting, abdominal pain and diarrhea. In the current study, the toxicity can be reduced by modifying the structure of the compound, processing and changing the dosage forms. CONCLUSIONS: There are few studies on the chemical constituents of D. febrifuga, so the components and their structure characterization contained in it can become the focus of future research. In view of the toxicity of D. febrifuga, there are many methods to reduce it, but the safety and rationality of these methods need further study.

Acupuncture modulates the gut microbiota in Alzheimer's disease: current evidence, challenges, and future opportunities.

Alzheimer's disease, one of the most severe and common neurodegenerative diseases, has no effective cure. Therefore it is crucial to explore novel and effective therapeutic targets. The gut microbiota - brain axis has been found to play a role in Alzheimer's disease by regulating the neuro-immune and endocrine systems. At the same time, acupuncture can modulate the gut microbiota and may impact the course of Alzheimer's disease. In this Review, we discuss recent studies on the role of acupuncture on the gut microbiota as well current challenges and future opportunities of acupuncture as potential treatment for the prevention and treatment of Alzheimer's disease.

Validation of the IMPEDE VTE score for prediction of venous thromboembolism in Chinese patients with multiple myeloma: A single-center retrospective cohort study.

Multiple myeloma (MM) significantly increases the risk of venous thromboembolism (VTE) within 6 months of treatment initiation. The IMPEDE VTE score is a VTE risk prediction model which is recently incorporated into the National Comprehensive Cancer Network (NCCN) guidelines, but it lacks validation among Asians, including Chinese MM patients. We performed a retrospective chart review of 405 Chinese with newly diagnosed MM who started therapy at Beijing Jishuitan Hospital between April 2013 to October 2022. The 6-month cumulative incidence of VTE was 3.8 % (95 % CI:1.6-7.6), 8.6 % (95 % CI: 5.3-21.9) and 40.5 % (95 % CI: 24.9-55.7) in the low-, intermediate- and high-risk groups (P < 0.001), respectively. The C-statistic of the IMPEDE VTE scores for predicting VTE within 6 months of treatment initiation was 0.74 (95 % CI: 0.65-0.83). Of note, in this single-center cohort study, we propose that the anticoagulant LMWH may be more effective than the antiplatelet aspirin in potentially preventing VTE in newly diagnosed MM patients. Our findings suggest that the IMPEDE VTE score is a valid evidence-based risk stratification tool in Chinese patients with newly diagnosed MM.

Therapeutic potential of natural flavonoids in pulmonary arterial hypertension: A review.

BACKGROUND: Pulmonary arterial hypertension (PAH) is a fatal disease caused by pulmonary vascular remodeling, with a high incidence and mortality. At present, many clinical drugs for treating PAH mainly exert effects by relaxing the pulmonary artery, with limited therapeutic effects, so the search for viable therapeutic agents continues uninterrupted. In recent years, natural flavonoids have shown promising potential in the treatment of cardiovascular diseases. It is necessary to comprehensively elucidate the potential of natural flavonoids to combat PAH. PURPOSE: To evaluate the potential of natural flavonoids to hinder or slow down the occurrence and development of PAH, and to identify promising drug discovery candidates. METHODS: Literature was collected from PubMed, Science Direct, Web of science, CNKI databases and Google scholar. The search terms used included "pulmonary arterial hypertension", "pulmonary hypertension", "natural products", "natural flavonoids", "traditional chinese medicine", etc., and several combinations of these keywords. RESULTS: The resources, structural characteristics, mechanisms, potential and prospect strategies of natural flavonoids for treating PAH were summarized. Natural flavonoids offer different solutions as possible treatments for PAH. These mechanisms may involve various pathways and molecular targets related to the pathogenesis of PAH, such as inflammation, oxidative stress, vascular remodeling, genetic, ion channels, cell proliferation and autophagy. In addition, prospect strategies of natural flavonoids for anti-PAH including structural modification and nanomaterial delivery systems have been explored. This review suggests that the potential of natural flavonoids as alternative therapeutic agents in the prevention and treatment of PAH holds promise for future research and clinical applications. CONCLUSION: Despite displaying the enormous potential of flavonoids in PAH, some limitations need to be further explored. Firstly, using advanced drug discovery tools, including computer-aided design and high-throughput screening, to further investigate the safety, biological activity, and precise mechanism of action of flavonoids. Secondly, exploring the structural modifications of these compounds is expected to optimize their efficacy. Lastly, it is necessary to conduct well controlled clinical trials and a comprehensive evaluation of potential side effects to determine their effectiveness and safety.

The function of chemical folic acid in calibration methods and neurodevelopmental disorders.

Functional molecules have been attracting increasing attention in environmental and physiological studies. In particular, folic acid (FA) could be considered a key factor in estimating, adjusting, and making decisions in the treatment of neurodevelopmental disorders. It promotes the general significance and conceptual for considering FA molecular scientific research detections, which implies related advancement in both of biological structure and detection methods. Among these applications, the FA molecule acts as a coenzyme that incorporates carbon atoms and synthesizes purines and pyrimidines. Therefore, the calibration method has real applications and can be used as a sensing platform and for detection approaches, which conveys the internal relationship between the FA molecule and physiological characterization. This mini review briefly discusses multiple FA application fields and detection pathways and could supplement their utilization in anticipation of the onset of disease.

Efficacy and safety of neoadjuvant sintilimab in combination with FLOT chemotherapy in patients with HER2-negative locally advanced gastric or gastroesophageal junction adenocarcinoma: an investigator-initiated, single-arm, open-label, phase II study.

BACKGROUND: The addition of immune checkpoint inhibitors to neoadjuvant chemotherapy in operable advanced gastric or gastroesophageal junction (G/GEJ) cancer aroused wide interest. This study was designed to assess the efficacy and safety of neoadjuvant sintilimab, a programmed cell death protein-1 (PD-1) inhibitor, in combination with fluorouracil, leucovorin, oxaliplatin, and docetaxel (FLOT) chemotherapy for HER2-negative locally advanced G/GEJ cancer. METHODS: Eligible patients with clinical stage cT4 and/or cN+M0 G/GEJ cancer were enroled in this phase II study. Patients received neoadjuvant sintilimab (200 mg every 3 weeks) for three cycles plus FLOT (50 mg/m 2 docetaxel, 80 mg/m 2 oxaliplatin, 200 mg/m 2 calcium levofolinate, 2600 mg/m 2 5-fluorouracil every 2 weeks) for four cycles before surgery, followed by four cycles of adjuvant FLOT with same dosages after resection. The primary endpoint was the pathological complete response (pCR) rate. RESULTS: Thirty-two patients were enroled between August 2019 and September 2021, with a median follow-up of 34.8 (95% CI, 32.8-42.9) months. Thirty-two (100%) patients received neoadjuvant therapy, and 29 underwent surgery with an R0 resection rate of 93.1%. The pCR (TRG0) was achieved in 5 (17.2%; 95% CI, 5.8-35.8%) patients, and the major pathological response was 55.2%. Twenty-three (79.3%) patients had T downstaging, 21 (72.4%) had N downstaging, and 19 (65.5%) had overall TNM downstaging. Six (20.7%) patients experienced recurrence. Patients achieving pCR showed better event-free survival (EFS), disease-free survival (DFS), and overall survival (OS) than non-pCR. The estimated 3-year EFS rate, 3-year DFS rate, and 3-year OS rate were 71.4% (95% CI, 57.2-89.2%), 78.8% (95% CI, 65.1-95.5%), and 70.9% (95% CI, 54.8-91.6%), respectively. The objective response rate and disease control rate were 84.4% (95% CI, 68.3-93.1%) and 96.9% (95% CI, 84.3-99.5%), respectively. Twenty-five (86.2%) received adjuvant therapy. The main grade ≥3 treatment-related adverse events (TRAEs) were lymphopenia (34.4%), neutropenia (28.1%), and leukopenia (15.6%). no patients died from TRAE. The LDH level exhibited a better predictive value to pathological responses than PD-L1 and MSI status. CONCLUSIONS: The study demonstrated an encouraging efficacy and manageable safety profile of neoadjuvant sintilimab plus FLOT in HER2-negative locally advanced G/GEJ cancer, which suggested a potential therapeutic option for this population.

Shen-Shuai-II-Recipe inhibits tubular inflammation by PPARα-mediated fatty acid oxidation to attenuate fibroblast activation in fibrotic kidneys.

BACKGROUND: Shen Shuai Ⅱ Recipe (SSR) is clinically used to treat chronic kidney diseases (CKDs) with remarkable efficacy and safety. In earlier research, we found the anti-inflammatory, antioxidant, and mitochondrial protective properties of SSR in hypoxic kidney injury model, which is closely related to its renal protection. Further work is needed to understand the underlying molecular mechanisms. PURPOSE: Further investigation of the mechanisms of action of SSR against renal interstitial fibrosis (RIF) building on previous research leads. METHODS: Rats receiving CKD model surgery were given with Fenofibrate or SSR once a day for eight weeks. In vitro, the NRK-52E cells were treated with SSR in the presence or absence of 10 µM Sc75741, 0.5 µM PMA, or 1 µM fenofibrate under 1% O2. The effects of SSR on NF-κB/NLRP3 inflammatory cascade, secretion of pro-inflammatory cytokines, fatty acid oxidation (FAO), and renal tubular injury were determined by immunoblotting, luminex liquid suspension chip assay, transmission electron microscopy, and Oil red O staining. Next, we delivered PPARα-interfering sequences to kidney tissue and NRK-52E cells by adeno-associated virus (AAV) injection and siRNA transfection methods. Finally, we evaluated the effect of renal tubular cells on fibroblast activation by co-culture method. RESULTS: SSR attenuated the release of IL-18, VEGF, and MCP1 cytokines, inhibited the activation of NF-κB/NLRP3 cascade, increased the PPARα, CPT-1α, CPT-2, ACADL, and MCAD protein expression, and improved the lipid accumulation. Further studies have demonstrated that one of the ways in which SSR suppresses the inflammatory response to protect renal tubular cells is through the restoration of PPARα-mediated FAO. In addition, by means of co-culture ways, the results demonstrated that SSR attenuated secretion of inflammatory mediators in NRK-52E cells by PPARα/NF-κB/NLRP3 pathway, thereby inhibiting renal fibroblast activation. CONCLUSION: SSR inhibits RIF by suppressing inflammatory response of hypoxia-exposed RTECs through PPARα-mediated FAO.

[Buyang Huanwu Decoction promotes arteriogenesis after hindlimb ischemia in mice by activating PDGF signaling pathway].

This study aims to investigate the effect of Buyang Huanwu Decoction on blood flow recovery and arteriogenesis after hindlimb ischemia in mice via the platelet-derived growth factor(PDGF) signaling pathway. Forty C57BL/6 mice were randomized into model(clean water, 10 mL·kg~(-1)·d~(-1)), beraprost sodium(positive control, 18 µg·kg~(-1)·d~(-1)), and low-, medium-, and high-dose(10, 20, and 40 g·kg~(-1)·d~(-1), respectively) Buyang Huanwu Decoction groups(n=8). The hindlimb ischemia model was established by femoral artery ligation. The mice were administrated with corresponding agents by gavage daily for 14 days after ligation. For laser Doppler perfusion imaging, the mice were anesthetized and measured under a Periscan PSI imager. The density of capillary and arterio-le in the ischemic gastrocnemius was measured using immunofluorescence staining of the frozen tissue sections. Western blot was employed to determine the expression of PDGF subunit B(PDGFB), phosphorylated mitogen extracellular kinase(p-MEK), MEK, phosphorylated extracellular signal-regulated kinase(p-ERK), and ERK. Real-time PCR was employed to determine the mRNA level of PDGFB. The Buyang Huanwu Decoction-containing serum was used to treat the vascular smooth muscle cells(VSMCs) in hypoxia at doses of 10% and 20%. The proliferation and migration of VSMCs was assessed in vitro. The results showed that compared with the model group, beraprost sodium and Buyang Huanwu Decoction enhanced the blood flow recovery, increased the capillary and arteriole density, and up-regulated the protein levels of PDGFB, p-MEK, p-ERK, and mRNA levels of PDGFB, with the medium-dose Buyang Huanwu Decoction demonstrating the most significant effect. The 10% Buyang Huanwu Decoction-containing serum enhanced the proliferation and migration of VSMCs. Our findings demonstrate that Buyang Huanwu Decoction up-regulates PDGFB transcription and activates PDGF signaling pathway to promote arteriogenesis and blood flow recovery in ischemic gastrocnemius.

The curative efficacy of auricular comprehensive therapy on menstrual migraine and its effect on serum prostaglandin. / è€³ç©´ç»¼åˆç–—æ³•æ²»ç–—æœˆç»æ€§åå¤´ç—›æ‚£è€ ä¸´åºŠç–—æ•ˆåŠå¯¹è¡€æ¸ å‰åˆ—è ºç´ çš„å½±å“.

OBJECTIVES: To observe the curative efficacy of auricular comprehensive therapy on menstrual migraine(MM) and its effect on serum prostaglandin F2α(PGF2α), prostaglandin E2(PGE2) contents and ratio, so as to explore its possible mechanism. METHODS: A total of 66 patients with MM of liver-fire syndrome were randomly divided into observation group (33 cases, 2 cases dropped off) and control group (33 cases, 2 cases dropped off), and 20 healthy women were included in the normal group. Patients in the control group were given flunarizine hydrochloride capsules orally, twice a day, for 3 consecutive weeks. Patients in the observation group were treated with auricular comprehensive therapy, starting 2-5 days before menstrual cramps, once a week, for a total of 3 weeks. The visual analogue scale (VAS) and migraine score were evaluated before and after treatment, and follow-up for 1 and 2 menstrual cycles. Serum PGF2α and PGE2 contents were measured before and after treatment, and the PGF2α/PGE2 ratio was calculated. The clinical effective rates in the two groups were calculated. RESULTS: After treatment and follow-up for 1 and 2 menstrual cycles, the VAS scores, headache degree, the frequency and duration of headache attacks, as well as accompanying symptoms of the observation and control groups were lower than those before treatment(P<0.05), and those of the observation group was lower than those of the control group(P<0.05). Before treatment, the PGF2α contents in the observation and control group were significantly higher(P<0.05), while the PGE2 contents lower(P<0.05) and PGF2α/PGE2 ratio higher(P<0.05) than those in the normal group. After treatment, the serum PGF2α contents in the observation and control group were significantly reduced compared with which before treatment(P<0.05), and were lower in the observation group than that in the control group (P<0.05). The serum PGE2 contents in the observation and control groups were significantly increased after treatment compared with which before treatment(P<0.05), with the contents in the observation group higher than that in the control group(P<0.05). The serum PGF2α/PGE2 ratio in the observation and control group was significantly reduced after treatment compared with which before treatment(P<0.05), with the control group higher than the normal group(P<0.05), and the observation group lower than the control group(P<0.05). The clinical effective rate of the observation group was 93.5% (29/31), and that of the control group was 77.4% (24/31). The effective rate of the observation group was significantly higher than that of the control group(P<0.05). CONCLUSIONS: The curative efficacy of auricular comprehensive therapy on MM with liver-fire syndrome is significantly better than that of oral flunarizine hydrochloride capsules, especially in relieving hea-daches, reducing the frequency and duration of headache attacks, as well as accompanying symptoms. Its mechanism may be related to regulating the abnormal PGF2α and PGE2 contents of patients and reducing the ratio of PGF2α/PGE2.

Effectiveness and safety of Moluodan in the treatment of precancerous lesions of gastric cancer: A randomized clinical trial.

OBJECTIVE: To investigate the clinical potential and safety of Moluodan to reverse gastric precancerous lesions. METHODS: Patients aged 18-70 years diagnosed with moderate-to-severe atrophy and/or moderate-to-severe intestinal metaplasia, with or without low-grade dysplasia, and negative for Helicobacter pylori were recruited in this randomized, double-blind, parallel-controlled trial. The primary outcome was the improvement of global histological diagnosis at 1-year follow-up endoscopy using the operative link for gastritis assessment, the operative link for gastric intestinal metaplasia assessment, and the disappearance rate of dysplasia. RESULTS: Between November 3, 2017 and January 27, 2021, 166 subjects were randomly assigned to the Moluodan group, 168 to the folic acid group, 84 to the combination group, and 84 to the high-dose Moluodan group. The improvement in global histological diagnosis was achieved in 60 (39.5%) subjects receiving Moluodan, 59 (37.8%) receiving folic acid, 26 (32.1%) receiving the combined drugs, and 36 (47.4%) receiving high-dose Moluodan. Moluodan was non-inferior to folic acid (95% confidence interval: -9.2 to 12.5; P = 0.02). High-dose Moluodan had a trend for better protective efficacy, though there was no statistical significance. The disappearance rate of dysplasia was 82.8% in the Moluodan group, which was superior to folic acid (53.9%; P = 0.006). No drug-related serious adverse events were observed. CONCLUSIONS: One pack of Moluodan three times daily for 1 year was safe and effective in reversing gastric precancerous lesions, especially dysplasia. Doubling its dose showed a better efficacy trend.