[Development and application of SSR markers of Saposhnikovia divaricata based on transcriptome].

Transcriptome sequencing was employed to mine the simple sequence repeat(SSR) locus information of Saposhnikovia divaricata and design specific primers, which aimed to provide a basis for the research on the genetic diversity of S. divaricata germplasm resources. The seed purity, 1 000-seed weight, germination rate, and seed vigor were determined. MISA was used to obtain the SSR locus information from 12 606 unigene longer than 1 kb in the transcriptome database. Forty-three pairs of SSR primers designed in Primer 3 were used to analyze the polymorphism of 28 S. divaricata samples of different sources. The results showed that there were differences in the seed purity, 1 000-seed weight, germination rate, vigor, and seed length and width among S. divaricata samples of different sources. Particularly, the germination rate and seed vigor had significant differences, and HB-ZJK1, NMG-CF4, NMG-BT, NMG-HLE1, and NMG-CF2 had significantly higher 1 000-seed weight, germination rate, and seed vigor than the samples of other sources. Among the 86 233 unigene, 12 606(14.62%) unigene contained 15 958 SSR loci, with one SSR locus every 5 009 bp on average. The SSR loci were mainly single nucleotide and dinucleotide repeats, which were dominated by G/C and TC/AG, respectively. All the primers were screened by using 28 S. divaricata sample from different habitats, and the primers corresponding to the amplification products with clear bands and stable polymorphism were obtained. The clustering results of the biological characteristics and genetic diversity of the 28 S. divaricata samples were basically consistent, and the samples of the same origin(HB-AG1, HB-AG2, HB-ZJK1, and HB-ZJK2) generally gathered together and had close genetic relationship. The SSRs in S. divaricata transcriptome has high frequency, rich types, and high polymorphism, which provides candidate molecular markers for the germplasm identification, genetic map construction, and molecular-assisted breeding.

Isolation and purification of polysaccharides from Bupleurum marginatum Wall.ex DC and their anti-liver fibrosis activities.

Bupleurum marginatum Wall.ex DC [Apiaceae] (BM)is widely grown in southwestern China, and the whole plant is used as Traditional Chinese Medicine (TCM). Polysaccharides are main natural products in lots of TCM and have been studied for their effects of reducing oxidative stress, anti-inflammation and immune regulation. Herein, we investigated the extraction techniques of Bupleurum marginatum Wall.ex DC polysaccharides (BMP), the identification of their key components, and their ability to inhibit liver fibrosis in both cellular and animal models. Component identification indicated that monosaccharides in BMP mainly consisted of glucose, galactose, mannose, rhamnose, arabinose, and xylose. In vivo analysis revealed that BMP provided significant protective effects on N-Nitroso dimethylamine (NDMA)-induced liver fibrosis rats through reducing hepatomegaly, reducing tissue inflammation, and reducing collagen deposition. BMP also improved the hepatobiliary system and liver metabolism in accord to reduce the serum levels of ALT, AST, ALP, r-GT, and TBIL. In addition, BMP could reduce the level of inflammation and fibrosis through inhibition of IL-1ß and TGF-ß1. Cellular studies showed that the BMP could provide therapeutic effects on lipopolysaccharide (LPS)-induced cellular fibrosis model, and could reduce the level of inflammation and fibrosis by decreasing the level of TGF-ß1, IL-1ß, and TNF-α. Our study demonstrated that BMP may provide a new therapy strategy of liver injury and liver fibrosis.

Bioinformatics and LC-QTOF-MS based discovery of pharmacodynamic and Q-markers of Pitongshu against functional dyspepsia.

ETHNOPHARMACOLOGICAL RELEVANCE: Pitongshu (PTS) is a clinically effective empirical formula for the treatment of FD. The efficacy and safety of PTS have been demonstrated in randomized, controlled, double-blind trials, but there is a lack of understanding of the systematic evaluation of the efficacy of PTS and its material basis. OBJECTIVE: To investigate the efficacy of PTS in Functional dyspepsia (FD) mice and possible Q-markers. METHOD: In this study, we used "irregular feeding + chronic unpredictable chronic stimulation" to establish a mice model of FD with hepatogastric disharmony. The efficacy of PTS was assessed from hair condition, behavioral, pain, gastrointestinal function, and serum 5-HT, GAS, MTL levels in mice by instillation of different doses of PTS. In addition, the composition of drugs in blood was analyzed by LC-QTOF-MS and potential Q-markers were selected by combining network pharmacology, molecular docking and actual content. RESULT: Our study showed that different doses of PTS increased pain threshold and writhing latency, decreased the number of writhings, increased gastric emptying rate and small intestinal propulsion rate, decreased total acidity of gastric contents and gastric acid secretion, and increased serum levels of 5-HT, GAS, and MTL in mice to different degrees. Enrichment analysis showed that PTS may be anti-FD through multiple pathways such as Serotonergic synapse, thyroid hormone signaling pathway, cholinergic synapse, and dopaminergic synapse. In addition, potential active ingredient substances were explored by LC-QTOF-MS combined with bioinformatics. Combined with the actual contentselected six constituents, hesperidin, neohesperidin, naringin, paeoniflorin, magnolol and honokiol, possible as Q-markers. CONCLUSION: PTS may exert its anti-FD effects through multi-component, multi-target and multi-pathway". Constituents, hesperidin, neohesperidin, naringin, paeoniflorin, magnolol and honokiol may be the Q-markers of its anti-FD effects.

Nanoarchitectonics of Bimetallic Cu-/Co-Doped Nitrogen-Carbon Nanozyme-Functionalized Hydrogel with NIR-Responsive Phototherapy for Synergistic Mitigation of Drug-Resistant Bacterial Infections.

Superbug infections and transmission have become major challenges in the contemporary medical field. The development of novel antibacterial strategies to efficiently treat bacterial infections and conquer the problem of antimicrobial resistance (AMR) is extremely important. In this paper, a bimetallic CuCo-doped nitrogen-carbon nanozyme-functionalized hydrogel (CuCo/NC-HG) has been successfully constructed. It exhibits photoresponsive-enhanced enzymatic effects under near-infrared (NIR) irradiation (808 nm) with strong peroxidase (POD)-like and oxidase (OXD)-like activities. Upon NIR irradiation, CuCo/NC-HG possesses photodynamic activity for producing singlet oxygen(1O2), and it also has a high photothermal conversion effect, which not only facilitates the elimination of bacteria but also improves the efficiency of reactive oxygen species (ROS) production and accelerates the consumption of GSH. CuCo/NC-HG shows a lower hemolytic rate and better cytocompatibility than CuCo/NC and possesses a positive charge and macroporous skeleton for restricting negatively charged bacteria in the range of ROS destruction, strengthening the antibacterial efficiency. Comparatively, CuCo/NC and CuCo/NC-HG have stronger bactericidal ability against methicillin-resistant Staphylococcus aureus (MRSA) and ampicillin-resistant Escherichia coli (AmprE. coli) through destroying the cell membranes with a negligible occurrence of AMR. More importantly, CuCo/NC-HG plus NIR irradiation can exhibit satisfactory bactericidal performance in the absence of H2O2, avoiding the toxicity from high-concentration H2O2. In vivo evaluation has been conducted using a mouse wound infection model and histological analyses, and the results show that CuCo/NC-HG upon NIR irradiation can efficiently suppress bacterial infections and promote wound healing, without causing inflammation and tissue adhesions.

Chinese herbal medicine for post-viral fatigue: A systematic review of randomized controlled trials.

BACKGROUND: Fatigue is a common symptom after viral infection. Chinese herbal medicine (CHM) is thought to be a potential effective intervention in relieving fatigue. PURPOSE: To assess the effectiveness and safety of CHM for the treatment of post-viral fatigue. STUDY DESIGN: Systematic review and meta-analysis of randomized controlled trials (RCTs). METHODS: The protocol of this systematic review was registered on PROSPERO (CRD42022380356). Trials reported changes of fatigue symptom, which compared CHM to no treatment, placebo or drugs, were included. Six electronic databases and three clinical trial registration platforms were searched from inception to November 2023. Literature screening, data extraction, and risk bias assessment were independently carried out by two reviewers. Quality of the included trials was evaluated using Cochrane risk of bias tool, and the certainty of the evidence was evaluated using GRADE. The meta-analysis was performed using Review Manager 5.4, mean difference (MD) and its 95% confidence interval (CI) was used for estimate effect of continuous data. Heterogeneity among trials was assessed through I2 value. RESULTS: Overall, nineteen studies with 1921 patients were included. Results of individual trial or meta-analysis showed that CHM was better than no treatment (MD = -0.80 scores, 95%CI -1.43 to -0.17 scores, P = 0.01, 60 participants, 1 trial), placebo (MD = -1.90 scores, 95%CI -2.38 to -1.42 scores, P<0.00001, 184 participants, 1 trial), placebo on basis of rehabilitation therapy (MD = -14.90 scores, 95%CI -24.53 to -5.27 scores, P = 0.02, 118 participants, 1 trial) or drugs (MD = -0.38 scores, 95%CI -0.48 to -0.27 scores, I2 = 0%, P<0.00001, 498 participants, 4 trials) on relieving fatigue symptoms assessing by Traditional Chinese Medicine fatigue scores. Trials compared CHM plus drugs to drugs alone also showed better effect of combination therapy (average MD = -0.56 scores). In addition, CHM may improve the percentage of CD4 T lymphocytes and reduce the level of serum IL-6 (MD = -14.64 scores, 95%CI 18.36 to -10.91 scores, I2 = 0%, P<0.00001, 146 participants, 2 trials). CONCLUSION: Current systematic review found that the participation of CHM can improve the symptoms of post-viral fatigue and some immune indicators. However, the safety of CHM remains unknown and large sample, high quality multicenter RCTs are still needed in the future.

Comprehensive evaluation of chemical constituents and antioxidant activity between crude and processed Polygalae radix based on UPLC-Q-TOF-MS/MS combined with multivariate statistical analysis.

Polygalae radix (PR) is a famous herbal medicine obtained by drying the root of Polygala tenuifolia Willd., one of the traditional Chinese medicines (TCM) that can be used for healthy food. There are three main processed methods of PR, including removing the xylem of roots (Polygalae Cortex, PC), frying PC with licorice (LP), and frying PC with honey (HP). While processing is believed to enhance efficacy and reduce toxicity, it is crucial to understand the differences in chemical composition and biological activities between crude and processed PR. This study used ultra-performance liquid chromatography with quadrupole time-of-flight mass spectrometry (UPLC-Q-TOF-MS/MS) combined with multivariate statistical analysis to analyze the chemical profiles and differences between the crude and processed products. Total polyphenol contents (TPC), total flavonoid contents (TFC), total saponin contents (TSC) and antioxidant activity of the processed and crude PR were also investigated. A total of 131 chemical compounds, including 42 saponins, 44 oligosaccharide esters, 25 xanthones, 2 organic acids, 3 Carbohydrates, and 15 components detected in auxiliary materials, were detected in all samples. Notably, PC exhibited significant changes among the three processed products, with the content of 62 compounds being higher. Processing of licorice (LP) and honey (HP) decreased the content of several compounds due to temperature and moisture influences. Comprehensive comparison of the antioxidant capacity of crude and processed PR showed that the antioxidant capacity of PC was higher than that of PR, HP, and LP. Our results can provide a scientific basis for further developing and applying P. tenuifolia resources.

Paeoniflorin attenuates cuproptosis and ameliorates left ventricular remodeling after AMI in hypobaric hypoxia environments.

This study investigates the cardioprotective effects of Paeoniflorin (PF) on left ventricular remodeling following acute myocardial infarction (AMI) under conditions of hypobaric hypoxia. Left ventricular remodeling post-AMI plays a pivotal role in exacerbating heart failure, especially at high altitudes. Using a rat model of AMI, the study aimed to evaluate the cardioprotective potential of PF under hypobaric hypoxia. Ninety male rats were divided into four groups: sham-operated controls under normoxia/hypobaria, an AMI model group, and a PF treatment group. PF was administered for 4 weeks after AMI induction. Left ventricular function was assessed using cardiac magnetic resonance imaging. Biochemical assays of cuproptosis, oxidative stress, apoptosis, inflammation, and fibrosis were performed. Results demonstrated PF significantly improved left ventricular function and remodeling after AMI under hypobaric hypoxia. Mechanistically, PF decreased FDX1/DLAT expression and serum copper while increasing pyruvate. It also attenuated apoptosis, inflammation, and fibrosis by modulating Bcl-2, Bax, NLRP3, and oxidative stress markers. Thus, PF exhibits therapeutic potential for left ventricular remodeling post-AMI at high altitude by inhibiting cuproptosis, inflammation, apoptosis and fibrosis. Further studies are warranted to optimize dosage and duration and elucidate PF's mechanisms of action.

Ultrasonographic Features and Pregnancy Outcomes of Complications in Monochorionic Twin Pregnancy During Various Pregnancy Periods.

Objective: It was to explore the ultrasonic characteristics of complications of twin pregnancies with monochorionic diamniotic (MCDA) during various pregnancy periods and the differences in pregnancy outcomes. Methods: One hundred pregnant women with MCDA were included in the study. They were rolled into a complication group (44 cases) and a non-complication group (56 cases) according to whether they had complications. The pulsatility index (PI), resistance index (RI), and systolic/diastolic (S/D) values of ultrasound in pregnant women and the final neonatal situation at each time period were compared and analyzed. Results: In pregnant women with twin-twin transfusion syndrome (TTTS), there was no significant difference in RI and S/D values between the larger and smaller twin during pregnancy (P > .05). Compared to the group without complications, the incidence of neonatal death was significantly increased in the complication group, and the newborn's weight, length, head circumference, and Apgar score were significantly lower (P < .05). In pregnant women with selective intrauterine growth restriction (sIUGR), the RI and PI values of the larger twin were significantly higher than those of the smaller twin during pregnancy, and S/D values were significantly lower (P < .05). The newborns in the group without complications had significantly higher body weight, length, and head circumference (P < .05). In pregnant women with gestational diabetes mellitus (GDM), there was no significant difference in RI and S/D values between the larger and smaller twin during pregnancy (P > .05), and there were no significant differences in other indicators compared to the group without complications. In pregnant women with premature rupture of membrane (PROM), there was no significant difference in RI and S/D values between the larger and smaller twin during pregnancy (P > .05), but the newborns in the group without complications had significantly higher weight, length, Apgar score, and lower incidence of neonatal death (P < .05). In pregnant women with preeclampsia (PE), there was no significant difference in RI and S/D values between the larger and smaller twin during pregnancy (P > .05), and there were no significant differences in other indicators compared to the group without complications (P > .05). Conclusion: Pregnant women with sIUGR had significantly higher RI and PI values in the larger twin and significantly lower S/D values compared to the smaller twin during pregnancy, while no significant differences were observed for other complications. The combination of TTTS and PROM decreased the birth weight, body length, head circumference, and Apgar score of twins and increased the mortality rate.

Consensus statement on research and application of Chinese herbal medicine derived extracellular vesicles-like particles (2023 edition).

To promote the development of extracellular vesicles of herbal medicine especially the establishment of standardization, led by the National Expert Committee on Research and Application of Chinese Herbal Vesicles, research experts in the field of herbal medicine and extracellular vesicles were invited nationwide with the support of the Expert Committee on Research and Application of Chinese Herbal Vesicles, Professional Committee on Extracellular Vesicle Research and Application, Chinese Society of Research Hospitals and the Guangdong Engineering Research Center of Chinese Herbal Vesicles. Based on the collation of relevant literature, we have adopted the Delphi method, the consensus meeting method combined with the nominal group method to form a discussion draft of "Consensus statement on research and application of Chinese herbal medicine derived extracellular vesicles-like particles (2023)". The first draft was discussed in online and offline meetings on October 12, 14, November 2, 2022 and April and May 2023 on the current status of research, nomenclature, isolation methods, quality standards and research applications of extracellular vesicles of Chinese herbal medicines, and 13 consensus opinions were finally formed. At the Third Academic Conference on Research and Application of Chinese Herbal Vesicles, held on May 26, 2023, Kewei Zhao, convenor of the consensus, presented and read the consensus to the experts of the Expert Committee on Research and Application of Chinese Herbal Vesicles. The consensus highlights the characteristics and advantages of Chinese medicine, inherits the essence, and keeps the righteousness and innovation, aiming to provide a reference for colleagues engaged in research and application of Chinese herbal vesicles at home and abroad, decode the mystery behind Chinese herbal vesicles together, establish a safe, effective and controllable accurate Chinese herbal vesicle prevention and treatment system, and build a bridge for Chinese medicine to the world.

Dendrobium officinale flowers' topical extracts improve skin oxidative stress and aging.

BACKGROUND: Dendrobium officinale flowers (DOF) have the effects of antiaging and nourishing yin, but it lacks pharmacological research on skin aging. OBJECTIVE: Confirming the role of DOF in delaying skin aging based on the "in vitro animal-human" model. METHODS: In this experiment, three kinds of free radical scavenging experiments in vitro, D-galactose-induced aging mouse model, and human antiaging efficacy test were used to test whether DOF can improve skin aging through anti-oxidation. RESULTS: In vitro experiment shows that DOF has certain scavenging effect on 2,2-diphenyl-1-picrylhydrazyl (DPPH) free radical, hydroxyl free radical, and superoxide free radical, and its IC50 is 0.2090 µg/mL, 15.020, and 1.217 mg/mL respectively. DOF can enhance the activities of T-AOC, SOD, CAT, and GSH Px in the serum of aging mice, increase the content of GSH, and reduce the content of MDA when administered with DOF of 1.0, 2.0, and 4.0 g/kg for 6 weeks. In addition, it can enhance the activity of SOD in the skin of aging mice, increase the content of Hyp, and decrease the content of MDA, activated Keap1/Nrf2 pathway in the skin of aging mice. Applying DOF with a concentration of 0.2 g/mL on the face for 8 weeks can significantly improve the skin water score and elasticity value, reduce facial wrinkles, pores, acne, and UV spots, and improve the facial brown spots and roughness. CONCLUSION: DOF can significantly improve skin aging caused by oxidative stress, and its mechanism may be related to scavenging free radicals in the body and improving skin quality.

Alumina inhibits pyrite oxidative dissolution by regulating solid film passivation layer and S, Fe, and Al speciation transformation.

The oxidation of pyrite results in the formation of a solid film passivation layer on its surface. This layer effectively hinders the direct interaction between H2O, O2, and the pyrite surface, thereby impeding the oxidation dissolution of pyrite. There are few studies on whether alumina (Al2O3), a common aluminum-containing oxide, affects the formation of a solid film passivation layer on the surface of pyrite and inhibits the oxidation dissolution of pyrite. This research investigates the impact of Al2O3 incorporation on the speciation transformation of S, Fe, and Al on the surface of pyrite during oxygen pyrite process. The oxidation of pyrite followed the "polysulfide-thiosulfate" complex oxidation pathway. When <1.5 g/L Al2O3 was introduced, it increase pyrite oxidation, whereas ≥1.5 g/L Al2O3 prevented pyrite oxidation. The process of Al2O3 dissolution results in the consumption of H+ and the subsequent release of Al3+. This, in turn, facilitates the hydrolysis of Fe3+ and Al3+ to generate a secondary mineral layer on the pyrite surface. As a result of the accumulation of S promotes the formation of polysulfide chemical (FeSn) or iron deficiency sulfide (Fe1-xS), resulting in the formation of a solid film passivation layer composed of sulfur film and secondary mineral layer. The results demonstrated that Al2O3 can promote the formation of a solid film passivation layer on the surface of pyrite, which has significant implications for controlling the oxidation dissolution process of pyrite and offers a new perspective for the source control of acid mine drainage.

Biocompatible N-carbazoleacetic acid decorated CuxO nanoparticles as self-cascading platforms for synergistic single near-infrared triggered phototherapy treating microbial infections.

In this work, positively charged N-carbazoleacetic acid decorated CuxO nanoparticles (CuxO-CAA NPs) as novel biocompatible nanozymes have been successfully prepared through a one-step hydrothermal method. CuxO-CAA can serve as a self-cascading platform through effective GSH-OXD-like and POD-like activities, and the former can induce continuous generation of H2O2 through the catalytic oxidation of overexpressed GSH in the bacterial infection microenvironment, which in turn acts as a substrate for the latter to yield ˙OH via Fenton-like reaction, without introducing exogenous H2O2. Upon NIR irradiation, CuxO-CAA NPs possess a high photothermal conversion effect, which can further improve the enzymatic activity for increasing the production rate of H2O2 and ˙OH. Besides, the photodynamic performance of CuxO-CAA NPs can produce 1O2. The generated ROS and hyperthermia have synergetic effects on bacterial mortality. More importantly, CuxO-CAA NPs are more stable and biosafe than Cu2O, and can generate electrostatic adsorption with negatively charged bacterial cell membranes and accelerate bacterial death. Antibacterial results demonstrate that CuxO-CAA NPs are lethal against methicillin-resistant Staphylococcus aureus (MRSA) and ampicillin-resistant Escherichia coli (AREC) through destroying the bacterial membrane and disrupting the bacterial biofilm formation. MRSA-infected animal wound models show that CuxO-CAA NPs can efficiently promote wound healing without causing toxicity to the organism.

Effect of l-Carnitine Supplementation on Osteoarthritis: A Systematic Review.

SCOPE: Comprehensive assessment of l-carnitine's safety and effectiveness in reducing inflammatory markers in osteoarthritis (OA) patients. METHODS AND RESULTS: Journal articles on l-carnitine for OA are gathered using computer searches of PubMed, Embase, the Cochrane Library, and Web of Science. The kind of literature that is found is restricted to clinical randomized controlled trials (RCTs). The Cochrane Handbook risk of bias assessment tool RevMan 5.4 software is used to conduct a meta-analysis. The systematic assessment comprises eight trials totaling 619 patients; the included studies' quality is mediocre. The study's findings demonstrate that OA patients' Western Ontario and McMaster University (WOMAC) function improves and that treatment efficacy outperforms that of the control group (mean difference [MD] = -7.75, 95% CI [-14.63, -0.86]; Z = 2.21; p = 0.03), WOMAC total (MD = -10.24, 95% CI [-18.97, -1.51]; Z = 2.30; p = 0.02), and visual analogue scale (VAS) pain (MD = -14.01, 95% CI [-16.16, -11.85]; Z = 12.74; p < 0.00001). The studies that are methodically reviewed also discover heterogeneity, which may have resulted from the created pooled data and requires more analysis. CONCLUSION: In patients with OA, l-carnitine effectively decreases clinical signs and symptoms, inflammatory markers, pain, and stiffness indicators, and significantly improves WOMAC and VAS scores.

Advances in the study of endocannabinoid receptors in experimental acupuncture analgesia. / å† æºæ€§å¤§éº»ç´ å—ä½“åœ¨é’ˆåˆºé•‡ç—›æœºåˆ¶ä¸­çš„ç ”ç©¶è¿›å±•.

The endocannabinoid system, an important biological network for maintaining and balancing various functions of the human body, is involved in many physiological functions such as pain, emotion, learning and memory, etc. Among which the endocannabinoid receptors ï¼»including type I (CB1) and type II (CB2) receptorsï¼½ play an important role in the regulation of pain and have become an important target in the mechanism research of acupuncture analgesia. CB1 is mainly distributed in the central nervous system, including the spinal cord, cerebral cortex, amygdala, insular cortex, and basal ganglia, etc. CB2 is mainly distributed in peripheral immune tissues, such as spleen, bone, skin, etc. In the central and peripheral nervous systems, acupuncture can activate CB1 and CB2 receptors respectively, which is involved in the transmission of central nociceptive signals and related transmitters as well as the peri-pheral pro-nociceptive inflammatory response, thereby alleviating the nociceptive hypersensitivity in animal models. In this paper, we systematically summarize the roles of the above mechanisms in different types of animal models (inflammatory pain, neuropathological pain, visceral pain, etc.), so as to provide new ideas for the study of the underlying mechanisms of acupuncture analgesia.

Antihypertensive effect and mechanism of the traditional recipe of medicine food homology (Buyang Huanwu Decoction) in China: Meta analysis and network pharmacological exploration.

Background: Hypertension has become a part of the lives of many people worldwide. With the development, an increasing number of people have begun to control their hypertension through products of medicine food homology, such as Buyang Huanwu Decoction (BYHWD). However, there has been no objective review of the regulation of hypertension by BYHWD. Methods: As of 9 October 2023, this review made a detailed search of nine databases to look for random controlled trials (RCTs) focused on the use of BYHWD for treating hypertension. This was followed by network pharmacological analysis, and molecular docking assessment using AutoDockTools to explore the mode of action. Results: BYHWD was effective in reducing SBP (MD: 0.767; 95 % CI: 0.629, 0.905; p = 0.000), DBP (MD: 0.427; 95 % CI: 0.292, 0.561; p = 0.000), 24h SBP (MD: 0.665; 95 % CI: 0.368, 0.962; p = 0.000), 24h DBP (MD: 0.547; 95 % CI: 0.318, 0.777; p = 0.000), dSBP (MD: 0.625; 95 % CI: 0.395, 0.855; p = 0.000), dDBP (MD: 0.632; 95 % CI: 0.401, 0.862; p = 0.000), nSBP (MD: 0.859; 95 % CI: 0.340, 1.377; p = 0.001), nDBP (MD: 0.704; 95 % CI: 0.297, 1.112; p = 0.001), pv (MD: 1.311; 95 % CI: 0.363, 2.259; p = 0.007) and NIHSS (MD: 1.149; 95 % CI: 0.100, 2.199; p = 0.032), and elevating CER (OR = 2.848; 95 % CI: 1.388, 5.843; p = 0.004). However, BYHWD did not significantly reduce HCY, and there was no significant difference in the incidence of AE. In terms of the mechanism of action, the main active ingredient of BYHWD is quercetin, and the core targets are AKT1, MMP9, and others. Molecular docking also showed that quercetin mainly interacts with the amino acid residue CYS-28 of MMP2. Second, the KEGG analysis showed that BYHWD mainly act on HIF-1, Apelin, and cGMP-PKG signalling pathways, and GO analysis showed that it related to the apical part of the cell, circulatory system processes, and nuclear receptor activity. Conclusion: BYHWD can lowered blood pressure, reduced plasma viscosity, and restored neurological function with good tolerability, and had no significant effect on HCY levels. This study further demonstrated that quercetin is the main active ingredient of BYHWD that acts via the AKT1 and HIF-1 signalling pathways. These results provide new guidance for people's dietary choices by the general public.

Loureirin A Promotes Cell Differentiation and Suppresses Migration and Invasion of Melanoma Cells via WNT and AKT/mTOR Signaling Pathways.

Resina Draconis is a traditional Chinese medicine, with the in-depth research, its medicinal value in anti-tumor has been revealed. Loureirin A is extracted from Resina Draconis, however, research on the anti-tumor efficacy of Loureirin A is rare. Herein, we investigated the function of Loureirin A in melanoma. Our research demonstrated that Loureirin A inhibited the proliferation of and caused G0/G1 cell cycle arrest in melanoma cells in a concentration-dependent manner. Further study showed that the melanin content and tyrosinase activity was enhanced after Loureirin A treatment, demonstrated that Loureirin A promoted melanoma cell differentiation, which was accompanied with the reduce of WNT signaling pathway. Meanwhile, we found that Loureirin A suppressed the migration and invasion of melanoma cells through the protein kinase B (AKT)/mammalian target of rapamycin (mTOR) signaling pathway. Taken together, this study demonstrated for the first time the anti-tumor effects of Loureirin A in melanoma cells, which provided a novel therapeutic strategy against melanoma.

Targeting the PHF8/YY1 axis suppresses cancer cell growth through modulation of ROS.

High levels of mitochondrial reactive oxygen species (mROS) are linked to cancer development, which is tightly controlled by the electron transport chain (ETC). However, the epigenetic mechanisms governing ETC gene transcription to drive mROS production and cancer cell growth remain to be fully characterized. Here, we report that protein demethylase PHF8 is overexpressed in many types of cancers, including colon and lung cancer, and is negatively correlated with ETC gene expression. While it is well known to demethylate histones to activate transcription, PHF8 demethylates transcription factor YY1, functioning as a co-repressor for a large set of nuclear-coded ETC genes to drive mROS production and cancer development. In addition to genetically ablating PHF8, pharmacologically targeting PHF8 with a specific chemical inhibitor, iPHF8, is potent in regulating YY1 methylation, ETC gene transcription, mROS production, and cell growth in colon and lung cancer cells. iPHF8 exhibits potency and safety in suppressing tumor growth in cell-line- and patient-derived xenografts in vivo. Our data uncover a key epigenetic mechanism underlying ETC gene transcriptional regulation, demonstrating that targeting the PHF8/YY1 axis has great potential to treat cancers.

Improving liming mode for remediation of Cd-contaminated acidic paddy soils: Identifying the optimal soil pH, model and efficacies.

Liming has been widely taken to remediate Cd-contaminated acidic paddy soils, whereas liming mode involving in the relevant optimal soil pH, model and efficacies remain unclear. Both soil and field liming experiments were conducted to improve liming mode for precise remediation of Cd-contaminated acidic paddy soils. Soil batch liming experiments indicated soil DTPA-Cd and CaCl2-Cd were piecewise linearly correlated to soil pH with nodes of 6.8-8.0, and decreased respectively by 15.3%37.7% and 80.7%93.8% (P < 0.05) when soil pH raised over the nodes, indicating an appropriate target soil pH 7.0 for liming. Stepwise linear regression revealed that liming ratio (LR, kg ha-1) could be estimated from soil basal pH (pH0) and the interval to the target soil pH (ΔpH), as [LR=exp(1.10 ×ΔpH+0.61 ×pH0-4.98), R2 = 0.97, n = 42, P < 0.01]. The model exhibited high prediction accuracy (95.2%), low mean estimation error (-0.02) and root mean square error (0.20). Field liming experiment indicated liming to target pH decreased respectively soil CaCl2-Cd by 95.2-98.0% and rice grain Cd by 59.8-80.6% (P < 0.01), whereas uninfluenced rice grain yield. Correlation analysis and structural equation models (SEM) demonstrated that great reduction in Cd phytoavailability was mainly attributed to the transformation of soil water-soluble and exchangeable Cd to carbonate-bound Cd and Fe/Mn oxides-bound Cd and reduced Cd in iron plaque as increasing soil pH. However, rice grain Cd of 50% samples met national food safety standards limit of China (0.2 mg kg-1) due to the high soil Cd level (0.8 mg kg-1). In conclusion, liming to target soil pH 7.0 could be considered as a precise and effective remediation mode for Cd-contaminated acidic paddy soils and complementary practices should be implemented for severe pollution. Our results could provide novel insights on precise liming remediation of Cd-contaminated acidic paddy soils.

Study on network pharmacology of Ginkgo biloba extract against ischaemic stroke mechanism and establishment of UPLC-MS/MS methods for simultaneous determination of 19 main active components.

INTRODUCTION: Ginkgo biloba extract (GBE) is an effective substance from traditional Chinese medicine (TCM) G. biloba for treating ischaemic stroke (IS). However, its active ingredients and mechanism of action remain unclear. OBJECTIVES: This study aimed to reveal the potential active component group and possible anti-IS mechanism of GBE. MATERIALS AND METHODS: The network pharmacology method was used to reveal the possible anti-IS mechanism of these active ingredients in GBE. An ultra-high-performance liquid chromatography triple quadrupole electrospray tandem mass spectrometry (UPLC-MS/MS) method was established for the simultaneous detection of the active ingredients of GBE. RESULTS: The active components of GBE anti-IS were screened by literature integration. Network pharmacology results showed that the anti-IS effect of GBE is achieved through key active components such as protocatechuic acid, bilobalide, ginkgolide A, and so on. Gene Ontology (GO) function and Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway analysis showed that the possible anti-IS mechanism of GBE is regulating the PI3K-Akt signalling pathway and other signal pathways closely related to inflammatory response and apoptosis regulation combined with AKT1, MAPK, TNF, ALB, CASP3, and other protein targets. Nineteen main constituents in seven batches of GBE were successfully analysed using the established UPLC-MS/MS method, and the results showed that the content of protocatechuic acid, gallic acid, ginkgolide A, and so forth was relatively high, which was consistent with network pharmacology results, indicating that these ingredients may be the key active anti-IS ingredients of GBE. CONCLUSION: This study revealed the key active components and the anti-IS mechanism of GBE. It also provided a simple and sensitive method for the quality control of related preparations.