Investigating the therapeutic effects and mechanisms of Carthamus tinctorius L.-derived nanovesicles in atherosclerosis treatment.

BACKGROUND: Carthamus tinctorius L., a traditional herbal medicine used for atherosclerosis (AS), lacks a clear understanding of its therapeutic mechanisms. This study aimed to investigate the therapeutic effects and mechanisms of Carthamus tinctorius L.-derived nanovesicles (CDNVs) in AS treatment. METHODS: CDNVs were isolated and characterized using improved isolation methods. Transmission electron microscopy, nanoparticle tracking analysis, and protein analysis confirmed their morphology, size, and protein composition. Small RNA sequencing was performed to identify the miRNA profile of CDNVs, and bioinformatics analysis was used to determine their potential biological roles. In vivo biodistribution and toxicity studies were conducted in mice to assess the stability and safety of orally administered CDNVs. The anti-atherosclerotic effects of CDNVs were evaluated in ApoE-/- mice through plaque burden analysis. The protective effects of CDNVs on ox-LDL-treated endothelial cells were assessed through proliferation, apoptosis, reactive oxygen species activation, and monocyte adhesion assays. miRNA and mRNA sequencing of CDNV-treated endothelial cells were performed to explore their regulatory effects and potential target genes. RESULTS: CDNVs were successfully isolated and purified from Carthamus tinctorius L. tissue lysates. They exhibited a saucer-shaped or cup-shaped morphology, with an average particle size of 142.6 ± 0.7 nm, and expressed EV markers CD63 and TSG101. CDNVs contained proteins, small RNAs, and metabolites, including the therapeutic compound HSYA. Small RNA sequencing identified 95 miRNAs, with 10 common miRNAs accounting for 72.63% of the total miRNAs. These miRNAs targeted genes involved in cell adhesion, apoptosis, and cell proliferation, suggesting their relevance in cardiovascular disease. Orally administered CDNVs were stable in the gastrointestinal tract, absorbed into the bloodstream, and accumulated in the liver, lungs, heart, and aorta. They significantly reduced the burden of atherosclerotic plaques in ApoE-/- mice and exhibited superior effects compared to HSYA. In vitro studies demonstrated that CDNVs were taken up by HUVECs, promoted proliferation, attenuated ox-LDL-induced apoptosis and ROS activation, and reduced monocyte adhesion. CDNV treatment resulted in significant changes in miRNA and mRNA expression profiles of HUVECs, with enrichment in inflammation-related genes. CXCL12 was identified as a potential direct target of miR166a-3p. CONCLUSION: CDNVs isolated from Carthamus tinctorius L. tissue lysates represent a promising oral therapeutic option for cardiovascular diseases. The delivery of miRNAs by CDNVs regulates inflammation-related genes, including CXCL12, in HUVECs, suggesting their potential role in modulating endothelial inflammation. These findings provide valuable insights into the therapeutic potential of CDNVs and their miRNAs in cardiovascular disease.

Anticipation and Verification of Dendrobium-Derived Nanovesicles for Skin Wound Healing Targets, Predicated Upon Immune Infiltration and Senescence.

Background: Dendrobium, with profound botanical importance, reveals a rich composition of bioactive compounds, including polysaccharides, flavonoids, alkaloids, and diverse amino acids, holding promise for skin regeneration. However, the precise mechanism remains elusive. Seeking a potent natural remedy for wound healing, exocyst vesicles were successfully isolated from Dendrobium. Aims of the Study: This investigation aimed to employ bioinformatics and in vivo experiments to elucidate target genes of Dendrobium-derived nanovesicles in skin wound healing, focusing on immune infiltration and senescence characteristics. Materials and Methods: C57 mice experienced facilitated wound healing through Dendrobium-derived nanovesicles (DDNVs). Bioinformatics analysis and GEO database mining identified crucial genes by intersecting immune-related, senescence-related, and PANoptosis-associated genes. The identified genes underwent in vivo validation. Results: DDNVs remarkably accelerated skin wound healing in C57 mice. Bioinformatics analysis revealed abnormal expression patterns of immune-related, senescence-related, and pan-apoptosis-related genes, highlighting an overexpressed IL-1ß and downregulated IL-18 in the model group, Exploration of signaling pathways included IL-17, NF-kappa B, NOD-like receptor, and Toll-like receptor pathways. In vivo experiments confirmed DDNVs' efficacy in suppressing IL-1ß expression, enhancing wound healing. Conclusion: Plant-derived nanovesicles (PDNV) emerged as a natural, reliable, and productive approach to wound healing. DDNVs uptake by mouse skin tissues, labeled with a fluorescent dye, led to enhanced wound healing in C57 mice. Notably, IL-1ß overexpression in immune cells and genes played a key role. DDNVs intervention effectively suppressed IL-1ß expression, accelerating skin wound tissue repair.

Prediction of herbal medicines based on immune cell infiltration and immune- and ferroptosis-related gene expression levels to treat valvular atrial fibrillation.

Inflammatory immune response is apparently one of the determinants of progressive exacerbation of valvular atrial fibrillation(VAF). Ferroptosis, an iron-dependent modality of regulated cell death, is involved in the immune regulation of cardiovascular disease. However, the relevant regulatory mechanisms of immune infiltration and ferroptosis in VAF have been less studied. In the current study, a highly efficient system for screening immunity- and ferroptosis-related biomarkers and immunomodulatory ability of herbal ingredients has been developed with the integration of intelligent data acquisition, data mining, network pharmacology, and computer-assisted target fishing. VAF patients showed higher infiltration of neutrophils and resting stage dendritic cells, while VSR patients showed higher infiltration of follicular helper T cells. In addition, six (e.g., PCSK2) and 47 (e.g., TGFBR1) ImmDEGs and one (SLC38A1) and four (TGFBR1, HMGB1, CAV1, and CD44) FerDEGs were highly expressed in patients with valvular sinus rhythm (VSR) and VAF, respectively. We further identified a core subnetwork containing 34 hub genes, which were intersected with ImmDEGs and FerDEGs to obtain the key gene TGFBR1. Based on TGFBR1, 14 herbs (e.g., Fructus zizyphi jujubae, Semen Juglandis, and Polygonum cuspidatum) and six herbal ingredients (curcumin, curcumine, D-glucose, hexose, oleovitamin A, and resveratrol) were predicted. Finally, TGFBR1 was found to dock well with curcumin and resveratrol, and it was further verified that curcumin and resveratrol could significantly reduce myocardial fibrosis. We believe that herbs rich in curcumin and resveratrol such as Rhizoma curcumae longae and Curcuma kwangsiensis, mitigate myocardial fibrosis to improve VAF by modulating the TGFß/Smad signaling pathway. This strategy provides a prospective approach systemically characterizing phenotype-target-herbs relationships based on the tissue-specific biological functions in VAF and brings us new insights into the searching lead compounds from Chinese herbs.

Effects of a natural nutritional supplement on immune cell infiltration and immune gene expression in exercise-induced injury.

Inflammatory immune response plays a key role in exercise-induced injury and healing; however, the relevant regulatory mechanisms of immune infiltration in exercise-induced injuries remain less studied. In the present study, a highly efficient system for screening immunity-related biomarkers and immunomodulatory ability of natural nutritional supplements was developed by integrating intelligent data acquisition, data mining, network pharmacology, and computer-assisted target fishing. The findings demonstrated that resting natural killer cells showed a higher rate of infiltration after exercise, whereas naive B cells and activated dendritic cells showed higher rate of infiltration before exercise. Four key genes, namely PRF1, GZMB, CCL4, and FASLG, were associated with exercise-induced injuries and inflammatory immune response. In total, 26 natural compounds including echinacoside, eugenol, tocopherol, and casuariin were predicted by using the HERB databases. Molecular docking analysis showed that GZMB, FASLG, and CCL4 bound to echinacoside. In vivo experiments in mice showed that after 30 min swimming, natural killer (NK) cells showed high infiltration rates, and the key genes (GZMB, PRF1, FASLG, and CCL4) were highly expressed; however, echinocandin significantly reduced the level of NK cells and decreased the expression of the four key genes post exercise. This natural nutritional supplement may act to protect against inflammatory injury after exercise by suppressing specific immune infiltration.

Corrigendum: Effects of Rhodiola Rosea Supplementation on Exercise and Sport: A Systematic Review.

[This corrects the article DOI: 10.3389/fnut.2022.856287.].

Transcriptomic Analysis Uncovers Immunogenic Characteristics of Ferroptosis for Myocardial Infarction and Potential Therapeutic Prediction of Chinese Herbs.

Background: Inflammation and immune response play a key role in myocardial injury and repair after myocardial infarction (MI), while the relevant regulatory mechanisms of immune infiltration in MI have been fully explored. Ferroptosis is an iron-dependent form of regulated cell death characterized by an excessive accumulation of iron and lipid peroxides and involves in the pathogenesis of myocardial infarction. In the present study, by integrating intelligent data acquisition, data mining, network pharmacology, and computer-assisted target fishing, we developed a highly efficient system for screening immunity- and ferroptosis-related biomarkers and immunomodulatory ability of herbal ingredients. Results: Immune infiltration analysis of GSE97320 showed significant neutrophil infiltration in the myocardial infarction group compared to the healthy group, and 807 differentially expressed genes (DEGs) were obtained (526 up-regulated and 281 downregulated). Among these DEGs, 73 immune-related and 8 ferroptosis-related DEGs were obtained. Further protein-protein interaction network analysis revealed 30 hub genes. The DEGs were enriched in a total of 107 biological processes, of which neutrophil-related biological processes were the most significant, enriched in 31 cellular components such as bead-binding hemoglobin complex, hemoglobin complex, and enriched in 36 functions such as bead-binding hemoglobin complex and hemoglobin complex. The DEGs were also enriched in 21 KEGG pathways such as lipid-atherosclerosis and formation of neutrophil extracellular traps. Further analysis identified Toll-like receptor-4 (TLR4) as the key gene, and based on TLR4, 17 herbal ingredients and 6 herbal medicines were predicted by using HERB and Coremine databases. Further molecular docking analysis showed that TLR4 could bind to salvianolic acid b and stigmasterol. The molecular dynamics analysis revealed that TLR4 could bind to salvianolic acid b, stigmasterol, and resveratrol in the stable phase with the binding between TLR4 and salvianolic acid b being the most stable. Conclusions: TLR4 is a key gene that is related to ferroptosis and immune cell infiltration. Further analysis revealed that 17 herbal ingredients and 6 herbal medicines were predicted to have potential interactions with TLR4. These predicted herbal ingredients/medicines may act synergistically to protect against myocardial injury after MI through suppressing neutrophil extracellular traps. The protective effects may be associated with immune cell infiltration and ferroptosis.

Effects of Rhodiola Rosea Supplementation on Exercise and Sport: A Systematic Review.

Rhodiola rosea (Golden Root Extract; RR) is an herbaceous perennial, which is native to high altitude areas, such as East Asia, Central Asia, Siberia, and North America. It has been studied for its positive pharmacological effects on health. However, only a handful of studies have evaluated the effects of RR as an exercise supplement for sport and physical activity. The aim of this study was to evaluate whether Rhodiola can be used as a supplement to improve human exercise ability. Studies were reviewed in accordance with the PRISMA guidelines and conducted between August and November, 2021. Databases searched included Cochrane, Embase, Web of Science, PubMed and East View Universal Database. Related terms were combined with keywords and MeSH subject headings using the corresponding Boolean operators: Rhodiola rosea, arctic root, roseroot, golden root, hongjingtian, and sports and exercise. A total of 10 papers were reviewed. Most of the studies reported that RR supplementation has a positive effect on athletic ability and sports performance, and no obvious adverse reactions were reported. Subjects taking RR showed a reduction in pain and muscle damage after exercise training, improved skeletal muscle damage, enhanced antioxidant capacity thereby reducing oxidative stress, reduced RPE scores, and improved athletic explosive power, but did not reduce the rating of perceived exertion (RPE) scores. RR appears to act as a safe and effective supplementation for sport and exercise.

Development of a multi-arm polyrotaxanes modified mesoporous silica-coated gold nanoplatform for protecting endothelial progenitor cells against high glucose environment.

Recent study reported that endothelial progenitor cells (EPCs) have potential to treat diabetic macroangiopathy. High glucose environment of diabetes can affect the adhesion of EPCs by decreasing the expression of CXC chemokine receptor 4 (CXCR4) and affect the proliferation of EPCs by decreasing the expression of miR-126. The results showed that the cytotoxicity of GNR@MSNs@PEI to EPCs was significantly lower than PEI; the temperature of GNR@MSNs@PEI solution can be controlled between 38-40°C under 808 nm laser irradiation. 25.67 µg of pcDNA3.1-GFP-CXCR4 and 5.36 µg of FITC-miR-126 could be loaded in 1 mg of GNR@MSNs@PEI; GNR@MSNs@PEI has gene transfection almost the same as Lipofectamine 3000. Subsequent in vitro studies showed that pcDNA3.1-GFP-CXCR4 and miR-126 loaded GNR@MSNs@PEI can significantly increase the adhesion and proliferation and decrease the apoptosis of EPCs treated with high glucose under 808 nm laser irradiation. In conclusion, nano-carriers (GNR@MSNs@PEI) with high pcDNA3.1-CXCR4 and miR-126 loading capacity, high biocompatibility, well cell internalization, and controllable release ability were constructed to transfer CXCR4 expression plasmid (pcDNA3.1-CXCR4) and miR-126 into EPCs efficiently. Further in vitro studies indicated that pcDNA3.1-CXCR4 and miR-126-loaded GNR@MSNs@PEI could protect EPCs against high glucose-induced injury.

Shuyu pills inhibit immune escape and enhance chemosensitization in hepatocellular carcinoma.

BACKGROUND: Hepatocellular carcinoma (HCC) is characterized by dysregulation of the immune microenvironment and the development of chemoresistance. Specifically, expression of the programmed cell death protein 1 (PD-1)/programmed cell death 1 ligand 1 (PD-L1) axis, an immune checkpoint, may lead to tumour immune escape, resulting in disease progression. The latest research shows that tumour immune escape may be caused by the upregulation of PD-L1 mediated by hypoxia-inducible factor-1 alpha (HIF-1α), and simultaneous inhibition of HIF-1α and PD-L1 has the potential to enhance the host's antitumour immunity. Moreover, inhibition of the PD-1/PD-L1 axis may mitigate tumour chemoresistance. Shuyu pills (SYPs) contain immunity-enhancing and antitumour components, making them a potential HCC treatment. AIM: To investigate the efficacy of SYPs for HCC treatment via simultaneous HIF-1α and PD-L1 inhibition and the mechanism involved. METHODS: A subcutaneous xenograft tumour model was first established in BALB/c nude mice by the subcutaneous injection of 1 × 107 SMMC-7721 cells. Male mice (male, 5 weeks old; n = 24) were then randomly divided into the following four groups (n = 6): Control (0.9% normal saline), SYP (200 mg/kg), SYP + cisplatin (DDP) (200 mg/kg + 5 mg/kg DDP weekly via intraperitoneal injection), and DDP (5 mg/kg cisplatin weekly via intraperitoneal injection). The dose of saline or SYPs for the indicated mouse groups was 0.2 mL/d via intragastric administration. The tumour volumes and body weights of the mice were measured every 2 d. The mice were euthanized by cervical dislocation after 14 d of continuous treatment, and the xenograft tissues were excised and weighed. Western blot assays were used to measure the protein expression of HIF-1α, PD-1, PD-L1, CD4+ T cells, and CD8+ T cells in HCC tumours from mice. Quantitative reverse transcription polymerase chain reaction was used for real-time quantitative detection of PD-1, PD-L1, and HIF-1α mRNA expression. An immunofluorescence assay was conducted to examine the expression of CD4+ T cells and CD8+ T cells. RESULTS: Compared to mice in the control group, those in the SYP and SYP + DDP groups exhibited reduced tumour volumes and tumour weights. Moreover, the protein and mRNA expression levels of the oncogene HIF-1α and that of the negative immunomodulatory factors PD-1 and PD-L1 were decreased in both the SYP and SYP + DDP groups, with the decrease effects being more prominent in the SYP + DDP group than in the SYP group (HIF-1α protein: Control vs SYP, P = 0.0129; control vs SYP + DDP, P = 0.0004; control vs DDP, P = 0.0152, SYP + DDP vs DDP, P = 0.0448; HIF-1α mRNA: control vs SYP, P = 0.0009; control vs SYP + DDP, P < 0.0001; control vs DDP, P = 0.0003, SYP vs SYP + DDP, P = 0.0192. PD-1 protein: Control vs SYP, P = 0.0099; control vs SYP + DDP, P < 0.0001, SPY vs SYP + DDP, P = 0.0009; SYP + DDP vs DDP, P < 0.0001; PD-1 mRNA: control vs SYP, P = 0.0002; control vs SYP + DDP, P < 0.0001; control vs DDP, P = 0.0003, SPY vs SYP + DDP, P = 0.0003; SYP + DDP vs DDP, P = 0.0002. PD-L1 protein: control vs SYP, P < 0.0001; control vs SYP + DDP, P < 0.0001; control vs DDP, P < 0.0001, SPY vs SYP + DDP, P = 0.0040; SYP + DDP vs DDP, P = 0.0010; PD-L1 mRNA: Control vs SYP, P < 0.0001; control vs SYP + DDP, P < 0.0001; control vs DDP, P < 0.0001, SPY vs SYP + DDP, P < 0.0001; SYP + DDP vs DDP, P = 0.0014). Additionally, the quantitative and protein expression levels of CD4+ T cells and CD8+ T cells were simultaneously upregulated in the SYP + DDP group, whereas only the expression of CD4+ T cells was upregulated in the SYP group. (CD4+ T cell quantitative: Control vs SYP + DDP, P < 0.0001, SYP vs SYP + DDP, P = 0.0005; SYP + DDP vs DDP, P = 0.0002. CD4+ T cell protein: Control vs SYP, P = 0.0033; Control vs SYP + DDP, P < 0.0001; Control vs DDP, P = 0.0021, SYP vs SYP + DDP, P = 0.0004; SYP + DDP vs DDP, P = 0.0006. Quantitative CD8+ T cells: Control vs SYP + DDP, P = 0.0013; SYP vs SYP + DDP, P = 0.0347; SYP + DDP vs DDP, P = 0.0043. CD8+ T cell protein: Control vs SYP + DDP, P < 0.0001; SYP vs SYP + DDP, P < 0.0001; SYP + DDP vs DDP, P < 0.0001). Finally, expression of HIF-1α was positively correlated with that of PD-1/PD-L1 and negatively correlated with the expression of CD4+ T cells and CD8+ T cells. CONCLUSION: SYPs inhibit immune escape and enhance chemosensitization in HCC via simultaneous inhibition of HIF-1α and PD-L1, thus inhibiting the growth of subcutaneous xenograft HCC tumours.

Berberine Attenuates Arterial Plaque Formation in Atherosclerotic Rats with Damp-Heat Syndrome via Regulating Autophagy.

PURPOSE: Berberine (BBR) is an effective component of Huanglian and has shown to attenuate atherosclerosis (AS); however, the detailed mechanism of BBR-mediated protective actions against AS remains elusive. This study was undertaken to examine the effects of BBR on aortic atherosclerotic plaque stability and the expression of autophagy-related proteins in AS rats with damp-heat syndrome or yang deficiency. METHODS: Thirty SD rats were randomly divided into (1) control (CON); (2) damp-heat syndrome atherosclerosis (AS + DH); (3) yang deficiency syndrome atherosclerosis (AS + YX); (4) damp-heat syndrome atherosclerosis + BBR (AS + DH + BBR); (5) yang deficiency syndrome, atherosclerosis + BBR (AS + YX + BBR); and (6) damp-heat syndrome, atherosclerosis + BBR + 3-methyladenine (AS + DH + BBR + 3-MA) (n = 5/group) groups. Pathological morphology, macrophage plaque infiltration, inflammation, and LC3-II and P62 expression were assessed. RESULTS: Compared with the CON group, the AS + DH and AS + YX groups had an increased plaque area in the aortic tissue with substantial foam cell and macrophage infiltration, and increased levels of IL-1ß and TNF-α (P < 0.01). After four weeks of BBR intervention, the plaque area in the AS + DH + BBR group was reduced with decreased foam cells and macrophage infiltration, and decreased levels of TNF-α and IL-1ß, whereas LC3-II protein expression was increased and P62 protein expression was decreased in the AS + DH + BBR group when compared to AS + DH group. In addition, the AS + DH + BBR + 3-MA group exhibited a significantly enlarged plaque, substantial foam cell and macrophage infiltration, increased levels of IL-1ß and TNF-α, and decreased LC3-II and P62 (P < 0.01) expression when compared to the AS + DH + BBR group. CONCLUSION: Our results indicated that the BBR could inhibit arterial plaque formation and alleviate the inflammatory response in the aortic tissues in the AS rats with damp-heat syndrome possibly via promoting autophagy. The molecular mechanisms of BBR-mediated protective effects in this animal model still require further investigation.

Semen Brassicae reduces thoracic aortic remodeling, inflammation, and oxidative damage in spontaneously hypertensive rats.

BACKGROUND: This study aimed to evaluate the role of Semen Brassicae, a common Traditional Chinese Medicine, in the treatment of hypertension. METHODS: Spontaneously hypertensive rats (SHRs) were divided into five groups and were gavaged with either distilled water, water-decocted solution from Semen Brassicae (0.5, 1 or 2 g/kg), or nifedipine (2.7 mg/kg). Normal rats gavaged with distilled water were used as a control. Systolic (SBP) and diastolic blood pressure (DBP) were measured using a non-invasive method. After 8 weeks of administration, all animals were anesthetized. Abdominal aortic serum was collected to measure serum factors; the thoracic aorta was collected for hematoxylin and eosin staining and western blot analysis. RESULTS: Both SBP and DBP were significantly decreased after Semen Brassicae treatment. Endothelin-1 and angiotensin II levels in abdominal aortic serum, as well as the levels of inflammatory factors interleukin (IL)-1ß, IL-6, and tumor necrosis factor-alpha, were significantly decreased after Semen Brassicae treatment. The wall thickness of the thoracic aorta was significantly reduced after Semen Brassicae treatment. Nitric oxide level and the activity of superoxide dismutase and glutathione peroxidase were significantly increased, and malondialdehyde level was significantly decreased in the abdominal aortic serum after Semen Brassicae treatment. Semen Brassicae treatment increased the levels of peroxisome proliferator-activated receptor gamma and IκB-α and decreased the levels of intercellular adhesion molecule 1, monocyte chemoattractant protein-1, von Willebrand factor, p-IκB-α and p-p65 NF-κB. CONCLUSIONS: In conclusion, water-decocted solution from Semen Brassicae can decrease blood pressure, improve vascular remodeling, and attenuate oxidative stress and inflammation in SHRs.

ß-Sitosterol Protects against Myocardial Ischemia/Reperfusion Injury via Targeting PPARγ/NF-κB Signalling.

Myocardial ischemia/reperfusion (I/R) injury is a clinically severe complication, which can cause high rates of disability and mortality particularly in patients with myocardial infarction, yet the molecular mechanisms underlying this process remain unclear. This study aimed to explore the protective effects of ß-sitosterol against myocardial I/R injury and to elucidate the underlying molecular mechanisms. Our results showed that hypoxia/reoxygenation (H/R) treatment suppressed cell viability, induced cell apoptosis and reactive oxygen species production, increased caspase-3 and -9 activities, upregulated caspase-3 and -9 protein expressions, downregulated the Bcl-2 protein expression, and reduced the mitochondrial membrane potential. ß-Sitosterol treatment attenuated H/R-induced cardiomyocyte injury. Moreover, ß-sitosterol treatment counteracted the inhibitory effects of H/R treatment on the peroxisome proliferator-activated receptor gamma (PPARγ) expression and enhanced effects of H/R treatment on the NF-κB expression in cardiomyocytes. Furthermore, inhibition of PPARγ impaired the protective actions of ß-sitosterol against H/R-induced cardiomyocyte injury. In the I/R rats, ß-sitosterol treatment reduced the myocardial infarcted size and apoptosis, which was attenuated by the inhibition of PPARγ. In conclusion, our results demonstrate that ß-sitosterol protected against in vitro H/R-induced cardiomyocyte injury and in vivo myocardial I/R injury. The ß-sitosterol-mediated cardioprotective effects may involve the modulation of PPARγ/NF-κB signalling during myocardial I/R injury. Further studies are required to further explore the clinical application of ß-sitosterol in the myocardial I/R injury.

Hydrogen Sulfide Protects Against High Glucose-Induced Human Umbilical Vein Endothelial Cell Injury Through Activating PI3K/Akt/eNOS Pathway.

PURPOSE: Dysfunction of endothelial cells plays a key role in the pathogenesis of diabetic atherosclerosis. High glucose (HG) has been found as a key factor in the progression of diabetic complications, including atherosclerosis. PI3K/Akt/eNOS signaling pathway has been shown to involve in HG-induced vascular injuries. Hydrogen sulfide (H2S) has been found to exhibit protective effects on HG-induced vascular injuries. Moreover, H2S activates PI3K/Akt/eNOS pathway in endothelial cells. Thus, the present study aimed to determine if H2S exerts protective effects against HG-induced injuries of human umbilical vein endothelial cells (HUVECs) via activating PI3K/Akt/eNOS signaling. MATERIALS AND METHODS: The endothelial protective effects of H2S were evaluated and compared to the controlled groups. Cell viability, cell migration and tube formation were determined by in vitro functional assays; protein levels were evaluated by Western blot assay and ELISA; cell apoptosis was determined by Hoechst 33258 nuclear staining; Reactive oxygen species (ROS) production was evaluated by the ROS detection kit. RESULTS: HG treatment significantly inhibited PI3K/Akt/eNOS signaling in HUVECs, which was partially reversed by the H2S treatment. HG treatment inhibited cell viability of HUVECs, which were markedly prevented by H2S or PI3K agonist Y-P 740. HG treatment also induced HUVEC cell apoptosis by increasing the protein levels of cleaved caspase 3, Bax and Bcl-2, which were significantly attenuated by H2S or 740 Y-P. ROS production and gp91phox protein level were increased by HG treatment in HUVECs and this effect can be blocked by the treatment with H2S or Y-P 740. Moreover, HG treatment increased the protein levels of pro-inflammatory cytokines, caspase-1 and phosphorylated JNK, which was significantly attenuated by H2S or Y-P 740. Importantly, the cytoprotective effect of H2S against HG-induced injury was inhibited by LY294002 (an inhibitor of PI3K/Akt/eNOS signaling pathway). CONCLUSION: The present study demonstrated that exogenous H2S protects endothelial cells against HG-induced injuries by activating PI3K/Akt/eNOS pathway. Based on the above findings, we proposed that reduced endogenous H2S levels and the subsequent PI3K/Akt/eNOS signaling impairment may be the important pathophysiological mechanism underlying hyperglycemia-induced vascular injuries.

Myocardial hypertrophy is improved with berberine treatment via long non-coding RNA MIAT-mediated autophagy.

OBJECTIVES: This study aimed to evaluate berberine (BBR) effects on myocardial hypertrophy (MH) and associated mechanisms. METHODS: BBR effects on MH were evaluated in rats with constriction of abdominal aorta (CAA). qRT-PCR assay was used to measure MH-related genes, long non-coding RNAs (lncRNAs) and autophagy-related genes expressions. Western blot was performed to detect autophagy markers expression. Filamentous actin and phalloidin expressions were detected using immunofluorescence assay. KEY FINDINGS: BBR significantly attenuated CAA-induced MH and cardiomyocyte enlargement. CAA upregulated ß myosin heavy chain and atrial natriuretic peptide expressions in heart tissues, which was attenuated by BBR. BBR suppressed myocardial infarction associated transcript (MIAT) expression in rats with CAA. p62 mRNA expression was upregulated and beclin1 and autophagy related 5 were downregulated in CAA versus control groups. The effects were abolished by BBR. In vitro studies showed that BBR ameliorated angiotensin II-induced MH and attenuated Ang II-induced MIAT expression in H9C2 cells. Expressions of phosphorylated mTOR, phosphorylated AMPK and LC3 were upregulated in H9C2 cells after Ang II stimulation, and the effects were abolished by BBR. CONCLUSIONS: BBR exerted beneficial effects on MH induced by CCA, and the mechanisms were associated with decreased MIAT expression and enhanced autophagy.

YBX-1 mediated sorting of miR-133 into hypoxia/reoxygenation-induced EPC-derived exosomes to increase fibroblast angiogenesis and MEndoT.

BACKGROUND: Myocardial fibrosis is a common pathophysiological change in cardiovascular disease, which can cause cardiac dysfunction and even sudden death. Excessively activated fibroblasts proliferate and secret excessive extracellular matrix (ECM) components, resulting in normal cardiac structural damage and cardiac fibrosis. We previously found that human endothelial progenitor cell (EPC)-derived exosomes, after hypoxia/reoxygenation (H/R) induction, could significantly increase the mesenchymal-endothelial transition (MEndoT) compared to normal culture EPC-derived exosomes. Exosomes have been shown to carry different nucleic acids, including microRNAs. However, the effects of microRNAs in EPC-derived exosomes on MEndoT and myocardial fibrosis remain unknown. METHODS: EPCs were isolated from human peripheral blood, and fibroblasts were isolated from rat hearts, then transfected with miR-133 inhibitor, si-YBX-1, and ov-YBX-1 into EPCs. After H/R induction for 48 h, isolation and characterization of exosomes derived from human EPCs were performed. Finally, fibroblasts were treated by exosome at 48 h. The expression of miR-133 was measured by qRT-PCR; YBX-1 expression was measured by qRT-PCR and western blot. Angiopoiesis was measured by tube formation assay. Endothelial markers and fibrosis markers were measured by western blot. RESULTS: H/R treatment promoted miR-133 expression in EPCs and EPC-derived exosomes. miR-133 could be incorporated into exosomes and transmitted to cardiac fibroblasts, increasing the angiogenesis and MEndoT of cardiac fibroblasts. miR-133 silencing in H/R-induced EPCs could inhibit miR-133 expression in EPCs and EPCs-derived exosomes. miR-133 silencing in H/R-induced EPCs could inhibit the angiogenesis and MEndoT of cardiac fibroblasts and reverse the effect of H/R treatment. Additionally, miR-133 was specially sorted into H/R-induced EPC-derived exosomes via YBX-1. YBX-1 silencing inhibited miR-133 transfer and reduced fibroblast angiogenesis and MEndoT. CONCLUSION: miR-133 was specially sorted into H/R-induced EPC-derived exosomes via YBX-1 to increase fibroblast angiogenesis and MEndoT.

Internal mammary artery injury during percutaneous coronary intervention: a case report.

BACKGROUND: Percutaneous coronary intervention (PCI) is widely used to treat coronary artery disease (CAD). However, complications of PCI are inevitable. Internal mammary artery (IMA) injury is an infrequent but potentially lethal complication of PCI. CASE PRESENTATION: A 78-year-old man was diagnosed with multivessel lesions by coronary angiography. The IMA was injured during PCI, then cured by early identification and active rescue. CONCLUSIONS: This is the first reported case, to our knowledge, of injury to the IMA during PCI. We we report this case to discuss how to treat this injury effectively and avoid this complication during clinical therapy.

Use of Jianpi Jiedu Herbs in Patients with Advanced Colorectal Cancer: A Systematic Review and Meta-Analysis.

OBJECTIVE: To systematically review the effect of invigorating Pi and detoxification (Jianpi Jiedu, (JPJD)) herbs in advanced colorectal cancer (CRC) patients receiving chemotherapy. METHODS: Three English and four Chinese databases were searched. Literature was screened by EndNote X7 and data were analyzed by RevMan 5.2. RESULTS: This review comprised 12 randomized clinical studies of 701 patients. The results showed that JPJD herbs improved the therapeutic effect on Chinese medicine symptoms [risk ratio (RR) = 1.59; 95% confidence interval (CI): 1.35~1.88] and Karnofsky performance score [RR = 2.07; 95% CI: 1.52~2.82] for advanced CRC patients receiving chemotherapy, lowered the Chinese medicine symptoms' score [weighted mean difference = -2.44; 95% CI: -3.23~-1.64], reduced the incidence of nausea and vomiting [RR = 0.23; 95% CI: 0.11~0.49], improved platelet at toxicity grades III-IV [odds ratio = 0.29; 95% CI: 0.12~0.74] and I-IV [RR = 0.65; 95% CI: 0.51~0.82], and improved white blood cell at toxicity grades III-IV [RR = 0.37; 95% CI: 0.23~0.58] and I-IV [RR = 0.69; 95% CI: 0.60~0.79]. However, the results showed no significant effect on tumor response. CONCLUSION: JPJD herbs can improve quality of life, relieve symptoms, and reduce adverse events of advanced CRC patients receiving chemotherapy.

Chinese medicine for outcomes in colorectal cancer patients: A retrospective clinical study.

OBJECTIVE: To investigate the effect of Chinese medicine (CM) on survival of patients with stage II and III colorectal cancer (CRC). METHODS: A total of 295 patients who received chemotherapy were assigned to Group 1. The other 171 patients received the same chemotherapy treatment combined with the usage of CM Jianpi Jiedu Formula (, JPJD) for more than 3 months (Group 2). Patients' survival time, relapse and metastasis, and cause of death were observed. Cox proportional hazard regression models were established for the analysis of the effect of independent factors on the survival prognosis of patients with CRC. RESULTS: The survival rate of patients in Group 2 was higher than that of Group 1 (P<0.05). Compared with Group 1, the mean survival time was prolonged by 5.594 months and the median survival time was prolonged by 6 months in Group 2 (P=0.004). Cox regression analysis indicated that CM combined with chemotherapy provided signifificant protective effect, as observed with the improvements in the survival rates of CRC patients (P<0.01). CONCLUSION: CM can improve the survival rate in patients with stage II and III CRC.

[Inhibitory effect of jianpi-jiedu prescription-contained serum on colorectal cancer SW48 cell proliferation by mTOR-P53-P21 signalling pathway].

OBJECTIVE: To investigate the effect of jianpi-jiedu (JPJD) prescription-contained serum on colorectal cancer SW48 cell proliferation and the underlying mechanisms.
 Methods: Crude extract from JPJD was made by water extract method and the main components of crude extract from JPJD were analyzed by ultra-performance liquid phase high resolution time of flight mass spectrometry (UPLC-Q-TOF/MS). The low, medium, and high-concentration of JPJD-contained serum were prepared by the serum pharmacological method. The effect of serum containing JPJD on SW48 cell proliferation was determined by MTT assay. The cell cycle was detected by flow cytometric method. The protein levels of mammalian target of rapamycin (mTOR), phospho-mTOR, P-P53, and -P21, and the mRNA level of mTOR were examined by Western blot and RT-PCR, respectively.
 Results: Seven compounds including calycosin-7-glucoside, astragaloside, ginsenoside-Re, ginsenoside-Rb1, glycyrrhizinic acid, apigenin, atractylenolide-II were identified. MTT assays demonstrated that the SW48 cell proliferation was inhibited by medium and high concentration of JPJD-contained serum and the percentages of cells at G1 phase in SW48 cell cultured in the medium and high concentration of JPJD serum group were significantly higher than those in the control group (P<0.05). Meanwhile, the levels of mTOR mRNA and phospho-mTOR protein in the medium and high concentration of JPJD serum groups were substantially lower than those in the control group (P<0.05). Conversely, the expressions of phospho-P53 and P21 protein were significantly increased in the medium and high concentration of JPJD serum group compared with those in the control group.
 Conclusion: JPJD prescription-contained serum can inhibit SW48 cell proliferation, which may be related to mTOR-P53-P21 signaling pathways.

Multiple myeloma-associated skin light chain amyloidosis: A case of misdiagnosis.

The present study reports the case of a 42-year-old male with multiple myeloma (MM)-associated skin light chain amyloidosis who presented with skin purpura as the initial symptom, which was misdiagnosis as Henoch-Schönlein purpura nephritis prior to admission to the Second Xiangya Hospital (Changsha, Hunan, China). The patient presented with purpura, papules petechiae and spontaneous ecchymosis, which was located scattered around the neck, chest and limbs, accompanied by a small amount of bleeding in the conjunctival and oral mucosa, and a swollen tongue. Upon laboratory examination, the serum immunological change showed increased serum immunoglobulin G and λ light chain levels, and a urine Bence Jones protein level of >1 g/24 h. This was accompanied with an abnormal result for immunofixation electrophoresis, and positive staining with Congo red showing apple-green birefringence in skin biopsy specimens. Thus, the patient was diagnosed with MM-associated skin amyloidosis with the initial symptom of skin purpura. Following treatment with chemotherapy consisting of prednisone and bortezomib, the skin lesions markedly improved. The present study indicates that the presentation of skin purpura in systemic amyloidosis associated with MM may be an important aid in the diagnosis and direct treatment of this disease in the clinic.