[Ginsenoside Re regulates mitochondrial biogenesis through Nrf2/HO-1/PGC-1α pathway to reduce hypoxia/reoxygenation injury in H9c2 cells].

This article explored the mechanism by which ginsenoside Re reduces hypoxia/reoxygenation(H/R) injury in H9c2 cells by regulating mitochondrial biogenesis through nuclear factor E2-related factor 2(Nrf2)/heme oxygenase-1(HO-1)/peroxisome prolife-rator-activated receptor gamma coactivator-1α(PGC-1α) pathway. In this study, H9c2 cells were cultured in hypoxia for 4 hours and then reoxygenated for 2 hours to construct a cardiomyocyte H/R injury model. After ginsenoside Re pre-administration intervention, cell activity, superoxide dismutase(SOD) activity, malondialdehyde(MDA) content, intracellular reactive oxygen species(Cyto-ROS), and intramitochondrial reactive oxygen species(Mito-ROS) levels were detected to evaluate the protective effect of ginsenoside Re on H/R injury of H9c2 cells by resisting oxidative stress. Secondly, fluorescent probes were used to detect changes in mitochondrial membrane potential(ΔΨ_m) and mitochondrial membrane permeability open pore(mPTP), and immunofluorescence was used to detect the expression level of TOM20 to study the protective effect of ginsenoside Re on mitochondria. Western blot was further used to detect the protein expression levels of caspase-3, cleaved caspase-3, Cyto C, Nrf2, HO-1, and PGC-1α to explore the specific mechanism by which ginsenoside Re protected mitochondria against oxidative stress and reduced H/R injury. Compared with the model group, ginse-noside Re effectively reduced the H/R injury oxidative stress response of H9c2 cells, increased SOD activity, reduced MDA content, and decreased Cyto-ROS and Mito-ROS levels in cells. Ginsenoside Re showed a good protective effect on mitochondria by increasing ΔΨ_m, reducing mPTP, and increasing TOM20 expression. Further studies showed that ginsenoside Re promoted the expression of Nrf2, HO-1, and PGC-1α proteins, and reduced the activation of the apoptosis-related regulatory factor caspase-3 to cleaved caspase-3 and the expression of Cyto C protein. In summary, ginsenoside Re can significantly reduce I/R injury in H9c2 cells. The specific mechanism is related to the promotion of mitochondrial biogenesis through the Nrf2/HO-1/PGC-1α pathway, thereby increasing the number of mitochondria, improving mitochondrial function, enhancing the ability of cells to resist oxidative stress, and alleviating cell apoptosis.

[Tetrahydropalmatine inhibiting mitophagy through ULK1/FUNDC1 pathway to alleviate hypoxia/reoxygenation injury in H9c2 cells].

This study explored the specific mechanism by which tetrahydropalmatine(THP) inhibited mitophagy through the UNC-51-like kinase 1(ULK1)/FUN14 domain containing 1(FUNDC1) pathway to reduce hypoxia/reoxygenation(H/R) injury in H9c2 cells. This study used H9c2 cells as the research object to construct a cardiomyocyte H/R injury model. First, a cell viability detection kit was used to detect cell viability, and a micro-method was used to detect lactate dehydrogenase(LDH) leakage to evaluate the protective effect of THP on H/R injury of H9c2 cells. In order to evaluate the protective effect of THP on mitochondria, the chemical fluorescence method was used to detect intracellular reactive oxygen species, intramitochondrial reactive oxygen species, mitochondrial membrane potential, and autophagosomes, and the luciferin method was used to detect intracellular adenosine 5'-triphosphate(ATP) content. Western blot was further used to detect the ratio of microtubule-associated protein 1 light chain 3(LC3) membrane type(LC3-Ⅱ) and slurry type(LC3-Ⅰ) and activated cleaved caspase-3 expression level. In addition, ULK1 expression level and its phosphorylation degree at Ser555 site, as well as the FUNDC1 expression level and its phosphorylation degree of Ser17 site were detected to explore its specific mechanism. The results showed that THP effectively reduced mitochondrial damage in H9c2 cells after H/R. THP protected mitochondria by reducing the level of reactive oxygen species in cells and mitochondria, increasing mitochondrial membrane potential, thereby increasing cellular ATP production, enhancing cellular activity, reducing cellular LDH leakage, and finally alleviating H/R damage in H9c2 cells. Further studies have found that THP could reduce the production of autophagosomes, reduce the LC3-Ⅱ/LC3-Ⅰ ratio, and lower the expression of the apoptosis-related protein, namely cleaved caspase-3, indicating that THP could reduce apoptosis by inhibiting autophagy. In-depth studies have found that THP could inhibit the activation of the ULK1/FUNDC1 pathway of mitophagy and the occurrence of mitophagy by reducing the phosphorylation degree of ULK1 at Ser555 and FUNDC1 at Ser17. The application of ULK1 agonist BL-918 reversely verified the effect of THP on reducing the phosphorylation of ULK1 and FUNDC1. In summary, THP inhibited mitophagy through the ULK1/FUNDC1 pathway to reduce H/R injury in H9c2 cells.

Polyethyleneimine in designed nanocomposite based magnetic halloysite nanotubes for extraction and determination of gallic acid in green tea.

An innovative and simple nanocomposite denoted as MHNTs@PEI was synthesized for gallic acid (GA) analytical sample pretreatment. Polyethyleneimine (PEI) functionalized was binded onto magnetic halloysite nanotubes (MHNTs) to inhence adsorption capacity. MHNTs@PEI was obtained only through two steps modification (amination and PEI modification). Characterizations showed that there are layers of synthetic PEI on the tubular structure of the material and magnetic spheres on its surface, both indicating successful synthesis of the nanocomposite. Furthermore, the adsorption isotherms and kinetic modeling showed that the Langmuir model and pseudo-first-order model fit the adsorption data, respectively. MHNTs@PEI achieved an adsorption capacity of 158 mg·g-1. Overall, the abundant adsorption sites significantly improved the adsorption performance of the MHNTs@PEI. Regeneration tests demonstrated that the MHNTs@PEI exhibits effective adsorption, even after undergoing five consecutive cycles. Optimization of key parameters (ratio, volume of elution, elution time and frequency) in the process of adsorption and desorption was also conducted. The limit of detection (LOD) and that of the quantification (LOQ) were 0.19 and 0.63 µg·mL-1, respectively, and the recoveries were 95.67-99.43 %. Finally, the excellent magnetism (43.5 emu·g-1) and the adsorption feature of MHNTs@PEI enabled its successful utilization in analytical sample pretreatment through the extraction of GA from green tea.

Traditional Herb (Moxa) Modified Zinc Oxide Nanosheets for Quick, Efficient and High Tissue Penetration Therapy of Fungal Infection.

Fungal infection possesses the characteristics of high invasion depth and easy formation of a biofilm under the skin, which greatly hinders the treatment process. Here, traditional Chinese medicine moxa is carbonized and modified with zinc oxide (ZnO) nanosheets to synthesize carbonized moxa@ZnO (CMZ) with the dual response properties of yellow light (YL) and ultrasound (US) for synergistic antifungal therapy. CMZ with narrow bandgap can respond to long-wavelength YL that is highly safe and helpful for skin repair. Simultaneously, CMZ with a piezoelectric effect can further enhance the photocatalytic efficiency under the stimulation of US with high tissue penetration. Gene mechanism investigation indicates that when exposed to US and YL irradiation, CMZ-based therapy can adjust the expression of genes associated with fungal virulence, metabolic activity, mycelial growth and biofilm development, thus efficaciously eradicating planktonic Candida albicans (C. albicans) and mature biofilm. Importantly, despite the 1.00 cm thick tissue barrier, CMZ can rapidly eliminate 99.9% of C. albicans within 4 min, showing a satisfactory deep fungicidal efficacy. The in vivo therapeutic effect of this strategy is demonstrated in both open wound and deep cutaneous infection tests, speaking of dramatically better efficacy than the traditional fungicide ketoconazole (KTZ).

[DNA barcode screening, identification of germplasm resources, and analysis of genetic diversity of Anemarrhena asphodeloides].

Anemarrhena asphodeloides is a common medicinal material used in clinical prescriptions and Chinese patent medicine. In this study, the Illumina platform was used to obtain the chloroplast genome sequences of seven kinds of A. asphodeloides from different areas. The specific DNA barcodes were screened by comparative genomics analysis, and the DNA barcodes were used to identify the germplasm resources and analyze the genetic diversity of A. asphodeloides samples from different areas in China. All the seven chloroplast genomes had a ring structure. The total length was 156 801-156 930 bp, and 113 genes were annotated, including 79 protein-coding genes, 30 tRNA genes, and four rRNA genes. The comparative genomics analysis showed that rps16, trnG-GCC, atpF, rpoB, ycf3, rpl16, ndhF, trnS-GCU＿trnG-GCC, petN-psbM, and ndhF-rpl32 were potential candidates for specific DNA barcodes of A. asphodeloides. In this study, the second intron of ycf3 and atpF intron sequences with a sequence length of 700-800 bp and easy amplification were selected for polymerase chain reaction(PCR) amplification and sequencing of 594 samples from 26 areas. The sequence analysis showed that six and eight haplotypes of ycf3 and atpF sequences could be identified, respectively, and 17 haplotypes could be identified by combined analysis of the two sequences, which were named Hap1-Hap17. The haplotype diversity(H_d), nucleotide diversity(P_i), and genetic distance of A. asphodeloides in 26 populations were 0.68, 0.93×10~(-3), and 0-0.003 1, respectively, indicating that the genetic diversity within the species of A. asphodeloides is rich. The intermediary adjacent network analysis showed that Hap5 was the oldest haplotype, which was mainly distributed in Yixian county of Baoding, Hebei province, Hequ county of Xinzhou, Shanxi province, and Xiangfen county of Linfen, Shanxi province. This study has important guiding significance for the identification of A. asphodeloides species, the protection and development of germplasm resources, and the identification of production areas, and it provides a research basis for further revealing the genetic evolution law of A. asphodeloides.

Complete genome sequence of a novel mitovirus isolated from the fungus Fusarium oxysporum f. sp. ginseng causing ginseng root rot.

A novel mitovirus, tentatively designated as "Fusarium oxysporum mitovirus 2" (FoMV2), was isolated from the pathogenic Fusarium oxysporum f. sp. ginseng strain 0414 infecting Panax ginseng. The complete genome of FoMV2 is 2388 nt in length with a GC content of 30.57%. It contains a large open reading frame (ORF) encoding a putative RNA-dependent RNA polymerase (RdRp) of 713 amino acids with a molecular weight of 83.05 kDa. The sequence identity between FoMV2 and Botrytis cinerea mitovirus 8 and Fusarium verticillioides mitovirus 1 was 87.94% and 77.85%, respectively. Phylogenetic analysis showed that FoMV2 belongs to the genus Unuamitovirus in the family Mitoviridae. To the best of our knowledge, this is the first report of an unuamitovirus isolated from F. oxysporum f. sp. ginseng causing ginseng root rot.

Hydroxysafflor Yellow A Inhibits Pyroptosis and Protecting HUVECs from OGD/R via NLRP3/Caspase-1/GSDMD Pathway.

OBJECTIVE: To observe the protective effect and mechanism of hydroxyl safflower yellow A (HSYA) from myocardial ischemia-reperfusion injury on human umbilical vein endothelial cells (HUVECs). METHODS: HUVECs were treated with oxygen-glucose deprivation reperfusion (OGD/R) to simulate the ischemia reperfusion model, and cell counting kit-8 was used to detect the protective effect of different concentrations (1.25-160 µ mol/L) of HSYA on HUVECs after OGD/R. HSYA 80 µ mol/L was used for follow-up experiments. The contents of inflammatory cytokines interleukin (IL)-18, IL-1 ß, monocyte chemotactic protein 1 (MCP-1), tumor necrosis factor α (TNF-α) and IL-6 before and after administration were measured by enzyme-linked immunosorbent assay. The protein expressions of toll-like receptor, NOD-like receptor containing pyrin domain 3 (NLRP3), gasdermin D (GSDMD) and GSDMD-N-terminal domain (GSDMD-N) before and after administration were detected by Western blot. NLRP3 inflammasome inhibitor cytokine release inhibitory drug 3 sodium salt (CRID3 sodium salt, also known as MCC950) and agonist were added, and the changes of NLRP3, cysteine-aspartic acid protease 1 (Caspase-1), GSDMD and GSDMD-N protein expressions were detected by Western blot. RESULTS: HSYA inhibited OGD/R-induced inflammation and significantly decreased the contents of inflammatory cytokines IL-18, IL-1 ß, MCP-1, TNF-α and IL-6 (P<0.01 or P<0.05). At the same time, by inhibiting NLRP3/Caspase-1/GSDMD pathway, HSYA can reduce the occurrence of pyroptosis after OGD/R and reduce the expression of NLRP3, Caspase-1, GSDMD and GSDMD-N proteins (P<0.01). CONCLUSIONS: The protective effect of HSYA on HUVECs after OGD/R is related to down-regulating the expression of NLRP3 inflammasome and inhibiting pyroptosis.

Portable paper-based probe for on-site ratiometric fluorescence determination of total flavonol glycosides in plant extract using smartphone imaging.

A smartphone-assisted, paper-based ratio fluorescence probe is presented for the rapid, low-cost and on-site quantification of total flavonol glycosides in Ginkgo biloba extracts (GBE). The Al3+/Eu-MOF/paper-based probe utilizes lanthanide metal-organic framework (Ln-MOF) nanoparticles immobilized on Whatman filter paper along with Al3+ for detecting flavonols, which are the hydrolyzed products of flavonol glycosides. The color change of the paper-based fluorescence image from red to orange depends on the concentration of the target analyte in the sample solution. The smartphone equipped with a red, green, blue (RGB) color detector measured the fluorescence signal intensity on the paper substrate after adding flavonol. The analytical variables affecting the performance of the probe, including the addition sequence of the aluminum nitrate solution, its concentration, that of the Ln-MOF solution, the drying time of the paper probe, the reaction time and the sensitivity parameters of the mobile phone camera (ISO), were optimized. Under optimal conditions, the Al3+/Eu-MOF/paper-based probe has good linear response in the concentration range 7 ~ 80 µg mL- 1 and a lower detection limit of 2.07 µg mL- 1. The results obtained with the paper-based ratio fluorescence probe and smartphone combination were validated by comparing them with high-performance liquid chromatography (HPLC) measurements. This study provides a potential strategy for fabricating Al3+/Eu-MOF/paper-based probe used for total flavonol glycosides determination.

Traditional Scraping (Gua Sha) Combined with Copper-Curcumin Nanoparticle Oleogel for Accurate and Multi-Effective Therapy of Androgenic Alopecia.

Androgenetic alopecia (AGA) is a prevalent systemic disease caused by diverse factors, for which effective treatments are currently limited. Herein, the oleogel (OG) containing copper-curcumin (CuR) nanoparticles is developed, designated as CuRG, which is also combined with traditional naturopathic scraping (Gua Sha, SCR) as a multifunctional therapy for AGA. With the assistance of lipophilic OG and SCR, CuR can efficaciously penetrate the epidermal and dermal regions where most hair follicles (HFs) reside, thereby releasing curcumin (CR) and copper ions (Cu2+) subcutaneously to facilitate hair regeneration. Concomitantly, the mechanical stimulation induced by SCR promotes the formation of new blood vessels, which is conducive to reshaping the microenvironment of HFs. This study validates that the combination of CuRG and SCR is capable of systematically interfering with different pathological processes, ranging from improvement of perifollicular microenvironment (oxidative stress and insufficient vascularization), regulation of inflammatory responses to degradation of androgen receptor, thus potentiating hair growth. Compared with minoxidil, a widely used clinical drug for AGA therapy, the designed synergistic system displays augmented hair regeneration in the AGA mouse model.

Honokiol targeting ankyrin repeat domain of TRPV4 ameliorates endothelial permeability in mice inflammatory bowel disease induced by DSS.

ETHNOPHARMACOLOGICAL RELEVANCE: As a classic traditional Chinese medicine, Magnolia officinalis (M. officinalis) is widely used in digestive diseases. It has rich gastrointestinal activity including inflammatory bowel disease (IBD) treatment, but the mechanism is not clear. AIM OF THE STUDY: In recent years, there has been a growing interest in investigating the regulatory effects of herbal compounds on transient receptor potential (TRP) channel proteins. Transient receptor potential vanilloid 4 (TRPV4), a subtype involved in endothelial permeability regulation, was discussed as the target of M. officinalis in the treatment of IBD in the study. Based on the targeting effect of TRPV4, this study investigated the active ingredients and mechanism of M. officinalis extract in treating IBD. MATERIALS AND METHODS: To reveal the connection between the active ingredients in M. officinalis and TRPV4, a bioactivity-guided high performance liquid chromatography system coupled with mass spectrometry identification was utilized to screen for TRPV4 antagonists. TRPV4 siRNA knockdown experiment was employed to validate the significance of TRPV4 as a crucial target in regulating endothelial permeability by honokiol (HON). The interaction of the active ingredient representing HON with TRPV4 was confirmed by molecular docking, fluorescence-based thermal shift and live cell calcium imaging experiments. The potential binding sites and inhibitory mechanisms of HON in TRPV4 were analyzed by molecular dynamics simulation and microscale thermophoresis. The therapeutic effect of HON based on TRPV4 was discussed in DSS-IBD mice. RESULTS: Our finding elucidated that the inhibitory activity of M. officinalis against TRPV4 is primarily attributed to HON analogues. The knockdown of TRPV4 expression significantly impaired the calcium regulation and permeability protection in endothelial cells. The mechanism study revealed that HON specifically targets the Q239 residue located in the ankyrin repeat domain of TRPV4, and competitively inhibits channel opening with adenosine triphosphate (ATP) binding. The immunofluorescence assay demonstrated that the administration of HON enhances the expression and location of VE-Cadherin to protect the endothelial barrier and attenuates immune cell infiltration. CONCLUSIONS: The finding suggested that HON alleviates IBD by improving endothelial permeability through TRPV4. The discovery provides valuable insights into the potential therapeutic strategy of active natural products for alleviating IBD.

Catalpolaglycone disrupts mitochondrial thermogenesis by specifically binding to a conserved lysine residue of UCP2 on the proton leak tunnel.

BACKGROUND: Catalpol (CAT), a naturally occurring iridoid glycoside sourced from the root of Rehmannia glutinosa, affects mitochondrial metabolic functions. However, the mechanism of action of CAT against pyrexia and its plausible targets remain to be fully elucidated. PURPOSE: This study aimed to identify the specific targets of CAT for blocking mitochondrial thermogenesis and to unveil the unique biological mechanism of action of the orthogonal binding mode between the hemiacetal group and lysine residue on the target protein in vivo. METHODS: Lipopolysaccharide (LPS)/ carbonyl cyanide 3-chlorophenylhydrazone (CCCP)-induced fever models were established to evaluate the potential antipyretic effects of CAT. An alkenyl-modified CAT probe was designed to identify and capture potential targets. Binding capacity was tested using in-gel imaging and a cellular thermal shift assay. The underlying antipyretic mechanisms were explored using biochemical and molecular biological methods. Catalpolaglycone (CA) was coupled with protein profile identification and molecular docking analysis to evaluate and identify its binding mode to UCP2. RESULTS: After deglycation of CAT in vivo, the hemiacetal group in CA covalently binds to Lys239 of UCP2 in the mitochondria of the liver via an ɛ-amine nucleophilic addition. This irreversible binding affects proton leakage and improves mitochondrial membrane potential and ADP/ATP transformation efficiency, leading to an antipyretic effect. CONCLUSION: Our findings highlight the potential role of CA in modulating UCP2 activity or function within the mitochondria and open new avenues for investigating the therapeutic effects of CA on mitochondrial homeostasis.

D-A-D organic fluorescent probes for NIR-II fluorescence imaging and efficient photothermal therapy of breast cancer.

Near-infrared second region (NIR-II) fluorescent probes are used in the diagnosis of early cancer due to their high tissue penetration. However, there are still few reports on organic small molecule fluorescent probes with NIR-II fluorescence imaging (NIR-II FI) combined with efficient photothermal therapy (PTT). In this study, planar cyclopentadithiophene (CPDT) was incorporated into the twisted structural skeleton (D-A-D), and the strong acceptor TTQ molecule (A) and the donor triphenylamine (D) were introduced to synthesize an organic small molecule (TCT) with enhanced NIR-II fluorescence emission performance. To improve the hydrophilicity of TCT molecules, we used the nanoprecipitation method to coat DSPE-mPEG2000 on the TCT molecules and obtained nanoparticles (TCT-NPs) with a strong absorption band, good water dispersibility, and NIR-II FI ability, which realized NIR-II FI-guided PTT for breast cancer tumors. Due to their effective near-infrared absorption, TCT-NPs exhibit high photothermal conversion efficiency (η = 40.1%) under 660 nm laser irradiation, making them a photothermal therapeutic agent with good performance. Therefore, TCT-NPs have the potential to diagnose, eliminate, and monitor the diffusion of cancer.

Intercropped Flemingia macrophylla successfully traps tea aphid (Toxoptera aurantia) and alters associated networks to enhance tea quality.

BACKGROUND: The tea aphid, Toxoptera aurantia is a destructive pest causing severe damage to the quality and yield of tea, Camellia sinensis. Relying on chemical insecticides to control this pest causes adverse ecological and economic consequences. Trap plants are an eco-friendly alternative strategy to mitigate pest damage on focal plants by attracting target insects and natural enemies. Yet, the utilization of trap plants in tea plantations remains limited. Besides, the effects of the trap plant on the tea aphid-ant-predator community and tea quality and yield are unknown. RESULTS: Intercropped Flemingia macrophylla successfully trapped tea aphids and enhanced the complexity of aphid-ant-predator networks over three consecutive years compared to monoculture management. Moreover, F. macrophylla significantly increased the abundance of natural predators by 3100% and species richness by 57%. The increasing predators suppressed the aphid population and hampered its spillover to neighbouring tea plants. Consequently, F. macrophylla improved tea quality by an 8% increase in soluble sugar and a 26% reduction in polyphenols to amino acids ratio. CONCLUSION: The study illustrated that F. macrophylla is a suitable trap crop for tea aphid control in tea plantations. This legume increases species nodes and strengthens multiple connections in aphid-associated communities through its cascade effects, improving tea quality. These findings shed light on the potential application of trap plants in tea plantations as an efficient integrated pest management (IPM) strategy. © 2023 Society of Chemical Industry.

Chromosome-scale genome assembly of sweet tea (Lithocarpus polystachyus Rehder).

Lithocarpus, with >320 species, is the second largest genus of Fagaceae. However, the lack of a reference genome limits the molecular biology and functional study of Lithocarpus species. Here, we report the chromosome-scale genome assembly of sweet tea (Lithocarpus polystachyus Rehder), the first Lithocarpus species to be sequenced to date. Sweet tea has a 952-Mb genome, with a 21.4-Mb contig N50 value and 98.6% complete BUSCO score. In addition, the per-base consensus accuracy and completeness of the genome were estimated at 60.6 and 81.4, respectively. Genome annotation predicted 37,396 protein-coding genes, with repetitive sequences accounting for 64.2% of the genome. The genome did not undergo whole-genome duplication after the gamma (γ) hexaploidy event. Phylogenetic analysis showed that sweet tea diverged from the genus Quercus approximately at 59 million years ago. The high-quality genome assembly and gene annotation resources enrich the genomics of sweet tea, and will facilitate functional genomic studies in sweet tea and other Fagaceae species.

[Mechanism of Buyang Huanwu Decoction in protecting ischemic myocardium by regulating platelet autophagy in rats with acute myocardial infarction].

This study explored the effects of Buyang Huanwu Decoction(BYHWD) on platelet activation and differential gene expression after acute myocardial infarction(AMI). SD rats were randomly divided into a sham-operated group, a model group, a positive drug(aspirin) group, and a BYHWD group. Pre-treatment was conducted for 14 days with a daily oral dose of 1.6 g·kg~(-1) BYHWD and 0.1 g·kg~(-1) aspirin. The AMI model was established using the high ligation of the left anterior descending coronary artery method. The detection indicators included myocardial infarct size, heart function, myocardial tissue pathology, peripheral blood flow perfusion, platelet aggregation rate, platelet membrane glycoprotein CD62p expression, platelet transcriptomics, and differential gene expression. The results showed that compared with the sham-operated group, the model group showed reduced ejection fraction and cardiac output, decreased peripheral blood flow, and increased platelet aggregation rate and CD62p expression, and activated platelets. At the same time, TXB_2 content increased and 6-keto-PGF1α content decreased in serum. Compared with the model group, BYHWD increased ejection fraction and cardiac output, improved blood circulation in the foot and tail regions and cardiomyocytes arrangement, reduced myocardial infarct size and inflammatory infiltration, down-regulated platelet aggregation rate and CD62p expression, reduced serum TXB_2 content, and increased 6-keto-PGF1α content. Platelet transcriptome sequencing results revealed that BYHWD regulated mTOR-autophagy pathway-related genes in platelets. The differential gene expression levels were detected using real-time quantitative PCR. BYHWD up-regulated mTOR, down-regulated autophagy-related FUNDC1 and PINK genes, and up-regulated p62 gene expression. The results demonstrated that BYHWD could regulate platelet activation, improve blood circulation, and protect ischemic myocardium in AMI rats, and its mechanism is related to the regulation of the mTOR-autophagy pathway in platelets.

Biomembrane nanostructures: Multifunctional platform to enhance tumor chemoimmunotherapy via effective drug delivery.

Chemotherapeutic drugs have been found to activate the immune response against tumors by inducing immunogenic cell death, in addition to their direct cytotoxic effects toward tumors, therefore broadening the application of chemotherapy in tumor immunotherapy. The combination of other therapeutic strategies, such as phototherapy or radiotherapy, could further strengthen the therapeutic effects of immunotherapy. Nanostructures can facilitate multimodal tumor therapy by integrating various active agents and combining multiple types of therapeutics in a single nanostructure. Biomembrane nanostructures (e.g., exosomes and cell membrane-derived nanostructures), characterized by superior biocompatibility, intrinsic targeting ability, intelligent responsiveness and immune-modulating properties, could realize superior chemoimmunotherapy and represent next-generation nanostructures for tumor immunotherapy. This review summarizes recent advances in biomembrane nanostructures in tumor chemoimmunotherapy and highlights different types of engineering approaches and therapeutic mechanisms. A series of engineering strategies for combining different biomembrane nanostructures, including liposomes, exosomes, cell membranes and bacterial membranes, are summarized. The combination strategy can greatly enhance the targeting, intelligence and functionality of biomembrane nanostructures for chemoimmunotherapy, thereby serving as a stronger tumor therapeutic method. The challenges associated with the clinical translation of biomembrane nanostructures for chemoimmunotherapy and their future perspectives are also discussed.

Marine Chitosan-Oligosaccharide Ameliorated Plasma Cholesterol in Hypercholesterolemic Hamsters by Modifying the Gut Microflora, Bile Acids, and Short-Chain Fatty Acids.

This study evaluated the cholesterol-alleviating effect and underlying mechanisms of chitosan-oligosaccharide (COS) in hypercholesterolemic hamsters. Male hamsters (n = 24) were divided into three groups in a random fashion, and each group was fed one particular diet, namely a non-cholesterol diet (NCD), a high-cholesterol diet (HCD), and an HCD diet substituting 5% of the COS diet for six weeks. Subsequently, alterations in fecal bile acids (BAs), short-chain fatty acids (SCFAs), and gut microflora (GM) were investigated. COS intervention significantly reduced and increased the plasma total cholesterol (TC) and high-density lipoprotein-cholesterol (HDL-C) levels in hypercholesteremic hamsters. Furthermore, Non-HDL-C and total triacylglycerols (TG) levels were also reduced by COS supplementation. Additionally, COS could reduce and increase food intake and fecal SCFAs (acetate), respectively. Moreover, COS had beneficial effects on levels of BAs and GM related to cholesterol metabolism. This study provides novel evidence for the cholesterol-lowering activity of COS.

Factors Associated with Lesion Recurrence Following Cervical Conization.

Objective: To investigate the factors influencing lesion recurrence during the follow-up after cervical conization and evaluate the clinical value of human papillomavirus (HPV) testing and thinprep cytology test (TCT) in postoperative follow-up patients undergoing cervical conization. Methods: A total of 289 patients with cervical lesions who underwent primary cervical conization at our hospital between January 1, 2018, and December 31, 2019, were included in this study. TCT, HPV testing, and colposcopy were performed every 6 months for a follow-up period of 3 years. Based on the follow-up results, the patients were divided into recurrence and non-recurrence groups. The basic and colposcopic data of the two groups were analyzed to identify factors influencing lesion recurrence. Additionally, the clinical value of HPV testing and TCT in postoperative follow-up and recurrence diagnosis of patients undergoing cervical conization was assessed. Results: The recurrence group showed significantly higher age of onset, concurrent rate of other chronic diseases, and parity, as well as a markedly lower barrier contraceptive rate compared to the non-recurrence group, with statistically significant differences (P < .05). In the recurrence group, the type III transformation zone (TZ) predominated (59.26%), which significantly differed from the non-recurrence group (P < .05). The detection rates of abnormal TCT findings and HPV infections in postoperative reexaminations were significantly higher in the recurrence group compared to the non-recurrence group (P < .05), whereas no significant differences were observed between the two groups before cervical conization (P > .05). Among the recurrence group (n = 54), 52 cases (96.3%) had HPV infections, and 29 cases (53.7%) had abnormal TCT findings, with a significantly higher detection rate for HPV infections (P < .05). The area under the receiver operating characteristic (ROC) curve (AUC) for HPV testing, TCT, and combined HPV testing with TCT after cervical conization were 0.861, 0.712, and 0.882, respectively. These results indicate that HPV testing alone performs similarly to combined HPV testing with TCT and significantly outperforms TCT alone in predicting lesion recurrence after cervical conization. Conclusions: Factors influencing lesion recurrence after cervical conization include patient age, barrier contraceptive rate, concurrent rate of other chronic diseases, parity, and type of transformation zone. HPV testing alone is more sensitive and accurate than TCT in predicting lesion recurrence during postoperative follow-up of patients undergoing cervical conization. This finding can reduce missed diagnoses and provide a significant theoretical basis for postoperative follow-up of patients undergoing cervical conization.

Magnolol alleviates pulmonary fibrosis inchronic obstructive pulmonary disease by targeting transient receptor potential vanilloid 4-ankyrin repeat domain.

Transient receptor potential vanilloid 4 (TRPV4) plays a role in regulating pulmonary fibrosis (PF). While several TRPV4 antagonists including magnolol (MAG), have been discovered, the mechanism of action is not fully understood. This study aimed to investigate the effect of MAG on alleviating fibrosis in chronic obstructive pulmonary disease (COPD) based on TRPV4, and to further analyze its mechanism of action on TRPV4. COPD was induced using cigarette smoke and LPS. The therapeutic effect of MAG on COPD-induced fibrosis was evaluated. TRPV4 was identified as the main target protein of MAG using target protein capture with MAG probe and drug affinity response target stability assay. The binding sites of MAG at TRPV4 were analyzed using molecular docking and small molecule interaction with TRPV4-ankyrin repeat domain (ARD). The effects of MAG on TRPV4 membrane distribution and channel activity were analyzed by co-immunoprecipitation, fluorescence co-localization, and living cell assay of calcium levels. By targeting TRPV4-ARD, MAG disrupted the binding between phosphatidylinositol 3 kinase γ and TRPV4, leading to hampered membrane distribution on fibroblasts. Additionally, MAG competitively impaired ATP binding to TRPV4-ARD, inhibiting TRPV4 channel opening activity. MAG effectively blocked the fibrotic process caused by mechanical or inflammatory signals, thus alleviating PF in COPD. Targeting TRPV4-ARD presents a novel treatment strategy for PF in COPD.

Cardiovascular disease treatment using traditional Chinese medicine：Mitochondria as the Achilles' heel.

Cardiovascular disease (CVD), involving the pathological alteration of the heart or blood vessels, is one of the main causes of disability and death worldwide, with an estimated 18.6 million deaths per year. CVDs are caused by a variety of risk factors, including inflammation, hyperglycemia, hyperlipidemia, and increased oxidative stress. Mitochondria, the hub of ATP production and the main generator of reactive oxygen species (ROS), are linked to multiple cellular signaling pathways that regulate the progression of CVD and therefore are recognized as an essential target for CVD management. Initial treatment of CVD generally focuses on diet and lifestyle interventions; proper drugs or surgery can prolong or save the patient's life. Traditional Chinese medicine (TCM), a holistic medical care system with an over 2500-year history, has been proven to be efficient in curing CVD and other illnesses, with a strengthening effect on the body. However, the mechanisms underlying TCM alleviation of CVD remain elusive. Recent studies have recognized that TCM can alleviate cardiovascular disease by manipulating the quality and function of mitochondria. This review systematically summarizes the association of mitochondria with cardiovascular risk factors, and the relationships between mitochondrial dysfunction and CVD progression. We will investigate the research progress of managing cardiovascular disease by TCM and cover widely used TCMs that target mitochondria for the treatment of cardiovascular disease.