Extraction, purification, characteristics, bioactivities, prospects, and toxicity of Lilium spp. polysaccharides.

The genus Lilium has been widely used worldwide as a food and medicinal ingredient in East Asia for over 2000 years due to its higher nutritional and medicinal value. Polysaccharide is the most important bioactive ingredient in Lilium spp. and has various health benefits. Recently, Lilium spp. polysaccharides (LSPs) have attracted significant attention from industries and researchers due to their various biological properties, such as antioxidant, immunomodulatory, antitumor, antibacterial, hypoglycaemic, and anti-radiation. However, the development and utilization of LSP-based functional biomaterials and medicines are limited by a lack of comprehensive understanding regarding the structure-activity relationships (SARs), industrial applications, and safety of LSPs. This review provides an inclusive overview of the extraction, purification, structural features, bioactivities, and mechanisms of LSPs. SARs, applications, toxicities, and influences of structural modifications on bioactivities are also highlighted, and the potential development and future study direction are scrutinized. This article aims to offer a complete understanding of LSPs and provide a foundation for further research and application of LSPs as therapeutic agents and multifunctional biomaterials.

Work-related experiences of prostate cancer survivors in Australia: a qualitative study.

BACKGROUND: Prostate cancer (PCa) is the most diagnosed cancer in Australian men, and the number of survivors is growing with advances in diagnosis and treatment. Work participation following PCa diagnosis and treatment becomes a significant aspect of quality of life and survivorship. Using a qualitative phenomenological approach, we explored the work-related experiences of PCa survivors in Australia. METHODS: Semi-structured telephone interviews were conducted with 16 men (6 salaried employees, 10 self-employed; 8 diagnosed ≥ 5 years) purposively sampled from a community setting. Interviews were inductively analysed. RESULTS: Five main themes emerged: motivations to work; treatment decisions and work; the effects of PCa and its treatment on ability to participate in work; being an employee versus being self-employed; and personal agency. PCa and its treatment side-effects were detrimental to men's work capacity and ability, and could persist over an extended period. Most men expressed a strong desire to retain work or return to work. Discussions with healthcare professionals about work-related consequences were largely missing when treatment decisions were made. Self-employed men faced greater challenges than their salaried counterparts due to high financial burden and limited social and business support. Family, workplace and wider community support, and self-care, enhanced men's work participation experiences. CONCLUSIONS: PCa and its treatment substantially and persistently impacted men's working lives, and their experiences were diverse and multifaceted. Self-employed and long-term PCa survivors face greater challenges and are at high risk of poor work outcomes. A systematic approach and involvement of stakeholders at all levels is required to support ongoing work participation.

Danhong Injection Up-regulates miR-125b in Endothelial Exosomes and Attenuates Apoptosis in Post-Infarction Myocardium.

OBJECTIVE: To investigate the involvement of endothelial cells (ECs)-derived exosomes in the anti-apoptotic effect of Danhong Injection (DHI) and the mechanism of DHI-induced exosomal protection against postinfarction myocardial apoptosis. METHODS: A mouse permanent myocardial infarction (MI) model was established, followed by a 14-day daily treatment with DHI, DHI plus GW4869 (an exosomal inhibitor), or saline. Phosphate-buffered saline (PBS)-induced ECs-derived exosomes were isolated, analyzed by miRNA microarray and validated by droplet digital polymerase chain reaction (ddPCR). The exosomes induced by DHI (DHI-exo), PBS (PBS-exo), or DHI+GW4869 (GW-exo) were isolated and injected into the peri-infarct zone following MI. The protective effects of DHI and DHI-exo on MI hearts were measured by echocardiography, Masson's trichrome staining, and TUNEL apoptosis assay. The Western blotting and quantitative reverse transcription PCR (qRT-PCR) were used to evaluate the expression levels of miR-125b/p53-mediated pathway components, including miR-125b, p53, Bak, Bax, and caspase-3 activities. RESULTS: DHI significantly improved cardiac function and reduced infarct size in MI mice (P<0.01), which was abolished by the GW4869 intervention. DHI promoted the exosomal secretion in ECs (P<0.01). According to the results of exosomal miRNA microarray assay, 30 differentially expressed miRNAs in the DHI-exo were identified (28 up-regulated miRNAs and 2 down-regulated miRNAs). Among them, DHI significantly elevated miR-125b level in DHI-exo and DHI-treated ECs, a recognized apoptotic inhibitor impeding p53 signaling (P<0.05). Remarkably, treatment with DHI and DHI-exo attenuated apoptosis, elevated miR-125b expression level, inhibited capsase-3 activity, and down-regulated the expression levels of proapoptotic effectors (p53, Bak, and Bax) in post-MI hearts, whereas these effects were blocked by GW4869 (P<0.05 or P<0.01). CONCLUSION: DHI and DHI-induced exosomes inhibited apoptosis, promoted the miR-125b expression level, and regulated the p53 apoptotic pathway in post-infarction myocardium.

Pangenome analysis of the genus Herbiconiux and proposal of four new species associated with Chinese medicinal plants.

Five Gram-stain-positive, aerobic, non-motile actinobacterial strains designated as CPCC 205763T, CPCC 203386T, CPCC 205716T, CPCC 203406T, and CPCC 203407 were obtained from different ecosystems associated with four kinds of Chinese traditional medicinal plants. The 16S rRNA gene sequences of these five strains showed closely related to members of the genus Herbiconiux of the family Microbacteriaceae, with the highest similarities of 97.4-99.7% to the four validly named species of Herbiconiux. In the phylogenetic trees based on 16S rRNA gene sequences and the core genome, these isolates clustered into the clade of the genus Herbiconiux within the lineage of the family Microbacteriaceae. The overall genome relatedness indexes (values of ANI and dDDH) and the phenotypic properties (morphological, physiological and chemotaxonomic characteristics) of these isolates, readily supported to affiliate them to the genus Herbiconiux, representing four novel species, with the isolates CPCC 203406T and CPCC 203407 being classified in the same species. For which the names Herbiconiux aconitum sp. nov. (type strain CPCC 205763T = I19A-01430T = CGMCC 1.60067T), Herbiconiux daphne sp. nov. (type strain CPCC 203386T = I10A-01569T = DSM 24546T = KCTC 19839T), Herbiconiux gentiana sp. nov. (type strain CPCC 205716T = I21A-01427T = CGMCC 1.60064T), and Herbiconiux oxytropis sp. nov. (type strain CPCC 203406T = I10A-02268T = DSM 24549T = KCTC 19840T) were proposed, respectively. In the genomes of these five strains, the putative encoding genes for amidase, endoglucanase, phosphatase, and superoxidative dismutase were retrieved, which were classified as biosynthetic genes/gene-clusters regarding plant growth-promotion (PGP) functions. The positive results from IAA-producing, cellulose-degrading and anti-oxidation experiments further approved their potential PGP bio-functions. Pangenome analysis of the genus Herbiconiux supported the polyphasic taxonomy results and confirmed their bio-function potential.

Corrigendum: Pangenome analysis of the genus Herbiconiux and proposal of four new species associated with Chinese medicinal plants.

[This corrects the article DOI: 10.3389/fmicb.2023.1119226.].

A software program for automated compressive vertebral fracture detection on elderly women's lateral chest radiograph: Ofeye 1.0.

Background: Because osteoporotic vertebral fracture (OVF) on chest radiographs is commonly missed in radiological reports, we aimed to develop a software program which offers automated detection of compressive vertebral fracture (CVF) on lateral chest radiographs, and which emphasizes CVF detection specificity with a low false positivity rate. Methods: For model training, we retrieved 3,991 spine radiograph cases and 1,979 chest radiograph cases from 16 sources, with among them in total 1,404 cases had OVF. For model testing, we retrieved 542 chest radiograph cases and 162 spine radiograph cases from four independent clinics, with among them 215 cases had OVF. All cases were female subjects, and except for 31 training data cases which were spine trauma cases, all the remaining cases were post-menopausal women. Image data included DICOM (Digital Imaging and Communications in Medicine) format, hard film scanned PNG (Portable Network Graphics) format, DICOM exported PNG format, and PACS (Picture Archiving and Communication System) downloaded resolution reduced DICOM format. OVF classification included: minimal and mild grades with <20% or ≥20-25% vertebral height loss respectively, moderate grade with ≥25-40% vertebral height loss, severe grade with ≥40%-2/3 vertebral height loss, and collapsed grade with ≥2/3 vertebral height loss. The CVF detection base model was mainly composed of convolution layers that include convolution kernels of different sizes, pooling layers, up-sampling layers, feature merging layers, and residual modules. When the model loss function could not be further decreased with additional training, the model was considered to be optimal and termed 'base-model 1.0'. A user-friendly interface was also developed, with the synthesized software termed 'Ofeye 1.0'. Results: Counting cases and with minimal and mild OVFs included, base-model 1.0 demonstrated a specificity of 97.1%, a sensitivity of 86%, and an accuracy of 93.9% for the 704 testing cases. In total, 33 OVFs in 30 cases had a false negative reading, which constituted a false negative rate of 14.0% (30/215) by counting all OVF cases. Eighteen OVFs in 15 cases had OVFs of ≥ moderate grades missed, which constituted a false negative rate of 7.0% (15/215, i.e., sensitivity 93%) if only counting cases with ≥ moderate grade OVFs missed. False positive reading was recorded in 13 vertebrae in 13 cases (one vertebra in each case), which constituted a false positivity rate of 2.7% (13/489). These vertebrae with false positivity labeling could be readily differentiated from a true OVF by a human reader. The software Ofeye 1.0 allows 'batch processing', for example, 100 radiographs can be processed in a single operation. This software can be integrated into hospital PACS, or installed in a standalone personal computer. Conclusions: A user-friendly software program was developed for CVF detection on elderly women's lateral chest radiographs. It has an overall low false positivity rate, and for moderate and severe CVFs an acceptably low false negativity rate. The integration of this software into radiological practice is expected to improve osteoporosis management for elderly women.

Shenmai Injection Alleviates Acute Lung Injury in a Severe Acute Pancreatitis Rat Model via Heme Oxygenase-1 Upregulation.

BACKGROUND: One of the serious complications of severe acute pancreatitis (SAP) is acute lung injury (ALI). Suppressing inflammation is a feasible treatment strategy for SAP-induced ALI. Shenmai injection (SMI), which is a Traditional Chinese Medicine (TCM treatment, can suppress inflammation. Therefore, this study used an established SAP rat model to determine the effect of SMI on ALI induced by SAP. METHODS: A total of 40 male Sprague-Dawley (SD) rats were assigned to one of four groups: the SAP group, the sham surgery (SS) group, the SAP + SMI group and the SAP + SMI + zinc protoporphyrin (ZnPP) group. Rats in the SAP group were intravenously injected with 1.6 ml/kg saline 30 minutes after induction of SAP models, rats in the SAP + SMI group were intravenously injected with 1.6 ml/kg SMI, while rats in the SAP + SMI + ZnPP group were intravenously injected with 1.6 ml/kg SMI and 30 mg/kg ZnPP via intraperitoneal injection. The rates were sacrificed 24 hours after SAP induction. Excised lung tissues were histologically examined, protein concentration in bronchoalveolar lavage fluid (BALF) was measured and lung wet-to-dry (W/D) weight ratio was calculated. The protein and mRNA levels of tumor necrosis factor (TNF)-α, heme oxygenase (HO)-1 and interleukin (IL)-10 in blood and tissue samples were measured. RESULTS: SMI treatment attenuated SAP-induced ALI as evidenced by lower lung damage scores compared with the untreated SAP group (P < .05). SMI also abolished the SAP-induced rise in BALF and W/D ratio protein concentrations (P < .05). Moreover, SMI treatment increased HO-1 and IL-10 levels but decreased TNF-α levels in serum and tissue samples (P < .05). However, inhibition of HO-1 expression by ZnPP led to significant inhibition of all the changes. CONCLUSION: SMI can alleviate SAP-induced ALI through HO-1 upregulation.

Evaluating a multicomponent survivorship programme for men with prostate cancer in Australia: a single cohort study.

OBJECTIVE: To evaluate the implementation of a multicomponent survivorship programme for men with prostate cancer and their carers. DESIGN: A single cohort study, guided by the RE-AIM framework. SETTING: Multiple health services in Australia. PARTICIPANTS: Men with prostate cancer and their carers, and health professionals. INTERVENTION: A 12-month telehealth programme that provided centralised and coordinated decision and information support, exercise and nutrition management, specialised clinical support and practical support to men and their carers. DATA COLLECTION: Multiple sources of data including participant-reported health outcomes and experience of care, qualitative interviews, records of the programme were collected at different time points. RESULTS: Reach: Of 394 eligible men at various stages of survivorship, 142 consented (36% consent rate) and 136 (96%) completed the programme. Adoption: All men participated in general care coordination and more than half participated in exercise and/or nutrition management interventions. Participation in the specialised support component (ie, psychosocial and sexual health support, continence management) was low despite the high level of need reported by men. Effectiveness: Overall, the men reported improvements in their experience of care. Implementation: Factors such as addressing service gaps, provision of specialised services, care coordination, adoption of needs-based and telehealth-based approaches were identified as enablers to the successful implementation of the programme. Issues such as insufficient integration with existing services, lack of resources and high caseload of the intervention team, men's reluctance to discuss needs and lack of confidence with technology were barriers in implementing the programme. CONCLUSION: Survivorship interventions are relevant to men regardless of the stage of their disease and treatments undertaken. It is possible to provide access to a comprehensive model of survivorship care to promote the health and quality of life for men with prostate cancer. TRIAL REGISTRATION NUMBER: This study was registered with the Australian and New Zealand Clinical Trials Registry (ACTRN12617000174381).

Qing-Xue-Xiao-Zhi formula attenuates atherosclerosis by inhibiting macrophage lipid accumulation and inflammatory response via TLR4/MyD88/NF-κB pathway regulation.

BACKGROUND: Atherosclerosis is a progressive chronic disease characterised by aberrant lipid metabolism and a maladaptive inflammatory response. As atherosclerosis-driven cardiovascular disease remains the major cause of morbidity and mortality worldwide, more effective clinical therapies are urgently needed. Traditional Chinese Medicine (TCM) has demonstrated efficacy against atherosclerosis, with Qing-Xue-Xiao-Zhi formula (QXXZF) having been approved for clinical treatment of patients with atherosclerosis. However, the mechanisms underlying the anti-atherosclerotic activity of QXXZF remain unknown. PURPOSE: To investigate the anti-atherosclerotic effect of QXXZF and reveal its mechanisms using preclinical models. METHODS: In vivo, apolipoprotein E-deficient (ApoE-/-) mice were fed a high-fat and high-choline diet (HHD) to induce atherosclerosis. Serum metabolomic profiling was used to identify the concentration of trimethylamine N-oxide (TMAO) in mice. In vitro, RAW264.7 macrophages and bone marrow-derived macrophages (BMDMs) from WT and TLR4-/- C57BL/6 mice were used to explore the effects of QXXZF on macrophages. After confirming the therapeutic effects of QXXZF, mass spectrometry and network pharmacology analyses were used to predict and investigate the main components and the anti-atherogenic mechanisms of QXXZF in the context of atherosclerosis. RESULTS: Our results showed QXXZF significantly suppressed the development of atherosclerosis, as evidenced by the decreased atherosclerotic plaques in the aorta and aortic root, reduced plasma lipid levels and decreased serum TMAO content in HHD-fed ApoE-/- mice. Meanwhile, QXXZF effectively reduced foam cell formation in oxidized low-density lipoprotein (ox-LDL) and TMAO-stimulated RAW264.7 macrophages and BMDMs. Moreover, QXXZF facilitated reverse cholesterol transport (RCT) in macrophages by upregulating the expression of cholesterol efflux-related genes PPARγ/LXRα/ABCA1/ABCG1. Mechanistic studies revealed that QXXZF influenced cholesterol metabolism by inhibiting the TLR4-mediated nuclear factor kappa B (NF-κB) axis. Importantly, TLR4 knockout abolished the influence of QXXZF on macrophages. CONCLUSION: QXXZF promotes lipid efflux and inhibits macrophage-mediated inflammation, producing a therapeutic effect against atherosclerosis. Our study provides new insight into the mechanism of QXXZF against atherosclerosis.

The effect of low-dose IL-2 and Treg adoptive cell therapy in patients with type 1 diabetes.

BACKGROUNDA previous phase I study showed that the infusion of autologous Tregs expanded ex vivo into patients with recent-onset type 1 diabetes (T1D) had an excellent safety profile. However, the majority of the infused Tregs were undetectable in the peripheral blood 3 months postinfusion (Treg-T1D trial). Therefore, we conducted a phase I study (TILT trial) combining polyclonal Tregs and low-dose IL-2, shown to enhance Treg survival and expansion, and assessed the impact over time on Treg populations and other immune cells.METHODSPatients with T1D were treated with a single infusion of autologous polyclonal Tregs followed by one or two 5-day courses of recombinant human low-dose IL-2 (ld-IL-2). Flow cytometry, cytometry by time of flight, and 10x Genomics single-cell RNA-Seq were used to follow the distinct immune cell populations' phenotypes over time.RESULTSMultiparametric analysis revealed that the combination therapy led to an increase in the number of infused and endogenous Tregs but also resulted in a substantial increase from baseline in a subset of activated NK, mucosal associated invariant T, and clonal CD8+ T cell populations.CONCLUSIONThese data support the hypothesis that ld-IL-2 expands exogenously administered Tregs but also can expand cytotoxic cells. These results have important implications for the use of a combination of ld-IL-2 and Tregs for the treatment of autoimmune diseases with preexisting active immunity.TRIAL REGISTRATIONClinicalTrials.gov NCT01210664 (Treg-T1D trial), NCT02772679 (TILT trial).FUNDINGSean N. Parker Autoimmune Research Laboratory Fund, National Center for Research Resources.

An integrated multicomponent care model for men affected by prostate cancer: A feasibility study of TrueNTH Australia.

OBJECTIVE: To evaluate the feasibility of implementing an integrated multicomponent survivorship care model for men affected by prostate cancer. METHODS: Using a single arm prospective cohort study design, men with prostate cancer were recruited from two regional public hospitals in Australia for a 6-months program that provided information and decision support, exercise and nutrition management, specialised clinical support, and practical support through localised and central care coordination. Carers of the men were also invited to the program. Data were collected from multiple sources to evaluate: (1) recruitment capability and participant characteristics; (2) appropriateness and feasibility of delivering the specific intervention components using an electronic care management tool; and (3) suitability of data collection procedures and proposed outcome measures. RESULTS: Of the 105 eligible men, 51 (consent rate 49%) participated in the program. Of the 31 carers nominated by the men, 13 consented (consent rate 42%). All carers and 50 (98%) men completed the program. Most (92%) men were newly diagnosed with localised prostate cancer. All men attended initial screening and assessment for supportive care needs; a total of 838 episodes of contact/consultation were made by the intervention team either in person (9%) or remotely (91%). The intervention was implemented as proposed with no adverse events. The proposed outcome measures and evaluation procedures were found to be appropriate. CONCLUSIONS: Our results support the feasibility of implementing this integrated multicomponent care model for men affected by prostate cancer.

Pinin acts as a poor prognostic indicator for renal cell carcinoma by reducing apoptosis and promoting cell migration and invasion.

Pinin (PNN) was originally characterized as a desmosome-associated molecule. Its function and the mechanism of its regulation in renal cell carcinoma (RCC) are still undefined. Data on PNN expression, clinicopathological features, and prognosis of patients with RCC were obtained from The Cancer Genome Atlas (TCGA) database. Immunohistochemistry revealed high PNN expression in tumour cells. PNN expression showed negative correlation with survival in patients with RCC, acting as an independent prognostic factor in RCC. PNN up-regulation might be attributed to epigenetic alterations in RCC. Immunofluorescence revealed PNN expression mainly in the nucleus of RCC cells. The transfection of siRNA targeting the PNN gene resulted in enhanced apoptosis, which was detected by flow cytometry, and reduced cell migration and invasion, which were assessed using wound healing and transwell migration assay. Gene set enrichment analysis revealed associations between PNN expression and several signalling pathways involved in cancer progression, as a potential mechanism underlying the carcinogenicity of PNN. The analyses of the Tumor Immune Estimation Resource platform showed significant positive associations between high PNN expression and tumour immune infiltrating cells. PNN may function as an oncogenic factor by reducing apoptosis and promoting cell migration and invasion in RCC.

LncRNA NEAT1 Regulates the Development of Parkinson's Disease by Targeting AXIN1 Via Sponging miR-212-3p.

Long non-coding RNA (lncRNA) nuclear-enriched assembly transcript 1 (NEAT1) has been reported to be highly expressed in Parkinson's disease (PD). However, the mechanism of NEAT1 in PD progression has not been fully elucidated. 1-methyl-4-phenyl-1, 2, 3, 6-tetrahydropyridine injection (MPTP) was used to construct PD mouse models in vivo, and 1-methyl-4-phenyl pyridine (MPP+) was used to build PD cell models in vitro. Quantitative real-time polymerase chain reaction (qRT-PCR) was employed to test the expression of NEAT1, microRNA (miR)-212-3p and axis inhibition protein 1 (AXIN1). The viability, apoptosis and inflammation of cells were determined using cell counting kit 8 (CCK8) assay, flow cytometry and enzyme-linked immunosorbent assay (ELISA), respectively. Then, the protein levels of apoptosis-related markers and AXIN1 were measured by western blot (WB) analysis. Furthermore, dual-luciferase reporter assay and RNA immunoprecipitation (RIP) assay were performed to verify the interaction between miR-212-3p and NEAT1 or AXIN1. NEAT1 was upregulated in PD mouse models and cell models. Function experiments confirmed that NEAT1 knockdown could promote the viability, suppress the apoptosis and inflammation of MPP+-stimulated SK-N-SH cells to restrain PD progression. MiR-212-3p was downregulated in PD, and its inhibitor could reverse the suppression effect of NEAT1 knockdown on PD progression. Additionally, AXIN1 was a target of miR-212-3p, and its overexpression could invert the inhibition effect of miR-212-3p mimic on PD progression. Furthermore, AXIN1 expression was inhibited by NEAT1 silencing and promoted by NEAT1 overexpression, while these effect could be recovered by miR-212-3p inhibitor and mimic, respectively. Our results demonstrated that NEAT1 knockdown suppressed PD progression through regulating the miR-212-3p/AXIN1 pathway, indicating that NEAT1 might be a therapeutic target for neuroprotection in PD.

Complement factor H levels are decreased and correlated with serum C-reactive protein in late-onset Alzheimer's disease / Os níveis de fator H do complemento estão diminuídos e correlacionados com a proteína C-reativa sérica na doença de Alzheimer de início tardio

Abstract Alzheimer's disease (AD) is the most common cause of dementia. Despite numerous studies on the subject, the pathologies for AD are still unclear and there is still no ideal biomarker for diagnosis. The present study aimed to investigate clinical significance of human complement factor H (CFH) in patients with late-onset AD. Methods: The present prospective study included 187 late-onset AD patients who went to our hospital from January 2015 to December 2017. One hundred patients with mild cognitive impairment (MCI) and 80 healthy individuals who were age and gender matched to AD patients were enrolled as controls. Demographic data such as age, gender, and education duration were recorded. Blood samples were collected and serum levels of C-reactive protein (CRP), CFH, and brain-derived neurotrophic factor (BDNF) were determined by Enzyme-linked immunosorbent assay (ELISA). The mini-mental state examination (MMSE) score was measured for all patients. Results: No significant difference was found in age, gender, and education duration for all participants. The MMSE scores showed AD patients had lower MMES scores than the other two groups. All factors of CFH, CRP, and BDNF were dramatically decreased in AD patients compared with the MCI and the ealthy control. Levels of CFH were found to be positively correlated with levels of CRP; however, no significant correlation was found between CFH and BDNF, nor CFH and MMSE. Conclusion: CFH was decreased in late-onset AD patients, and serum levels of CFH was correlated with serum levels of CRP, but not MMSE and BDNF. These results may provide more clinical evidences for the role of CFH in AD patients.

Resumo A doença de Alzheimer (DA) é a causa mais comum de demência. Apesar de inúmeros estudos sobre DA, suas patologias ainda não são claras e ainda não existe um biomarcador ideal para o diagnóstico da condição. O presente estudo teve como objetivo investigar a significância clínica do fator H do complemento humano (CFH) em pacientes com DA de início tardio. Métodos: O presente estudo prospectivo incluiu um total de 187 pacientes com DA de início tardio que foram ao nosso hospital entre janeiro de 2015 e dezembro de 2017. Cem pacientes com comprometimento cognitivo leve (CCL) e 80 indivíduos saudáveis com idade e sexo pareados com pacientes com DA foram incluídos como controle. Dados demográficos como idade, sexo e duração da educação foram registrados. As amostras de sangue foram coletadas e os níveis séricos de proteína C-reativa (PCR), CFH e fator neurotrófico derivado do cérebro (BDNF) foram determinados pelo ensaio imunoabsorvente ligado à enzima (ELISA). O escore do miniexame do estado mental (MEEM) foi medido para todos os pacientes. Resultados: Não foram encontradas diferenças significativas em idade, sexo e duração da educação para todos os participantes. Pacientes com DA tinham os menores escores de MEEM em relação aos outros dois grupos. Todos os fatores de CFH, PCR e BDNF diminuíram drasticamente em pacientes com DA em comparação com o CCL e o controle saudável. Os níveis de CFH mostraram correlação positiva com os níveis de PCR; no entanto, não foi encontrada correlação significativa entre CFH e BDNF, nem CFH e MEEM. Conclusão: A CFH diminuiu nos pacientes com DA de início tardio e os níveis séricos de CFH foram correlacionados com os níveis séricos de PCR, mas não o MEEM e o BDNF. Esses resultados podem fornecer mais evidências clínicas do papel da CFH em pacientes com DA.

Danhong Injection Alleviates Cardiac Fibrosis via Preventing the Hypermethylation of Rasal1 and Rassf1 in TAC Mice.

BACKGROUND/AIM: Danhong injection (DHI) is a Chinese patent drug used for relieving cardiovascular diseases. Recent studies have suggested that DNA methylation plays a pivotal role in the maintenance of cardiac fibrosis (CF) in cardiovascular diseases. This study was aimed at identifying the effect and the underlying mechanism of DHI on CF, especially the DNA methylation. METHODS: A CF murine model was established by thoracic aortic constriction (TAC). A 28-day daily treatment with or without DHI via intraperitoneal injection was carried out immediately following TAC surgery. The changes in cardiac function, pathology, and fibrosis following TAC were measured by echocardiography and immunostaining. We used methyl-seq analysis to assess the DNA methylation changes in whole genes and identified the methylation changes of two Ras signaling-related genes in TAC mice, including Ras protein activator like-1 (Rasal1) and Ras-association domain family 1 (Rassf1). Next, the methylation status and expression levels of Rasal1 and Rassf1 genes were consolidated by bisulfite sequencing, quantitative reverse transcription polymerase chain reaction (RT-qPCR), and Western blotting, respectively. To determine the underlying molecular mechanism, the expressions of DNA methyltransferases (DNMTs), Tet methylcytosine dioxygenase 3 (TET3), fibrosis-related genes, and the activity of Ras/ERK were measured by RT-qPCR and Western blotting. RESULTS: DHI treatment alleviated CF and significantly improved cardiac function on day 28 of TAC. The methyl-seq analysis identified 42,606 differential methylated sites (DMSs), including 19,618 hypermethylated DMSs and 22,988 hypomethylated DMSs between TAC and sham-operated mice. The enrichment analysis of these DMSs suggested that the methylated regulation of Ras signal transduction and focal adhesion-related genes would be involved in the TAC-induced CF development. The results of bisulfite sequencing revealed that the TAC-induced methylation affected the CpG site in both of Rasal1 and Rassf1 genes, and DHI treatment remarkably downregulated the promoter methylation of Rasal1 and Rassf1 in CF hearts. Furthermore, DHI treatment upregulated the expressions of Rasal1 and Rassf1, inhibited the hyperactivity of Ras/ERK, and decreased the expressions of fibrosis-related genes. Notably, we found that DHI treatment markedly downregulated the expression of DNMT3B in CF hearts, while it did not affect the expressions of DNMT1, DNMT3A, and TET3. CONCLUSION: Aberrant DNA methylation of Rasal1 and Rassf1 genes was involved in the CF development. DHI treatment alleviated CF, prevented the hypermethylation of Rasal1 and Rassf1, and downregulated DNMT3B expression in CF hearts.

Lampropedia aestuarii sp. nov., isolated from the estuary of a freshwater river.

A Gram-stain-negative, strictly aerobic, catalase-positive and oxidase-positive bacterium, designated strain YIM MLB12T, was isolated from estuary sediment sampled at Maliao River where it flows into a plateau lake (Dianchi) in Yunnan, south-west PR China. Cells were non-motile and rod-shaped. Growth was observed at 15-35 °C (optimum, 25-30 °C), pH 6.0-10.0 (optimum, pH 7.0-8.0) and in the presence of 0-7 % (w/v) NaCl (optimum, 0.5-2 %). Results of phylogenetic analysis based on 16S rRNA gene sequences showed that strain YIM MLB12T formed a tight phylogenic lineage with members of the genus Lampropedia and was closely related to 'Lampropedia puyangensis' 2-bin with 98.3 % sequence similarity and had low similarities to the type strains of Lampropediahyalina ATCC 11041T (96 %) and Lampropedia cohaerens CT6T (95.5 %). Average nucleotide identity and in silico DNA-DNA hybridization values between strain YIM MLB12T and 'L. puyangensis' KCTC 32235 were 76.5 and 22.6 %, respectively. Strain YIM MLB12T contained ubiquinone-8 as the major quinone. The predominant cellular fatty acids were summed feature 3 (C16 : 1 ω7c and/or C16 : 1 ω6c), C16 : 0, C10 : 0 3-OH, summed feature 8 (C18 : 1 ω6c and/or C18 : 1 ω7c), C12 : 0 3-OH and C14 : 0. The polar lipid profile of strain YIM MLB12T was composed predominantly of diphosphatidylglycerol, phosphatidylmonomethylethanolamine, phosphatidylethanolamine and phosphatidylglycerol. The major polyamine was spermidine. The genomic DNA G+C content of strain YIM MLB12T was 56.8 mol%. Based on its genotypic and chemotaxonomic features and results of phenotypic analyses, strain YIM MLB12T represents a novel species of the genus Lampropedia, for which the name Lampropediaaestuarii sp. nov. is proposed. The type strain is YIM MLB12T (=KCTC 42886T=CGMCC 1.17071T).

Danhong injection enhances angiogenesis after myocardial infarction by activating MiR-126/ERK/VEGF pathway.

BACKGROUND/AIM: Danhong injection (DHI) is a Chinese drug used for relieving cardiovascular diseases. This study aimed to identify the effect and mechanism of action of DHI on post-infarct angiogenesis, especially the epigenetic regulation of angiogenesis. METHODS: A myocardial infarction (MI) mouse model was induced by ligating the left anterior descending coronary artery. A 4-week daily treatment with or without DHI via intraperitoneal injection was started immediately following MI. The changes in cardiac function, pathology, and angiogenesis following MI were measured by echocardiography and immunostaining. Matrigel tube formation and scratch wound assays were used to evaluate the effect of DHI on the proliferation and migration of hypoxic human umbilical vein endothelial cells (HUVECs). The expression of miR-126, Spred-1, and angiogenesis-related mRNAs was measured by quantitative real-time polymerase chain reaction (qRT-PCR). The expression of related proteins and the phosphorylated levels of extracellular signal-regulated kinase (ERK) and protein kinase B were detected by Western blot analysis. The loss-of-function study was performed using antagomir-126. RESULTS: The DHI-treated mice had significantly reduced infarct area, improved ejection fraction, and increased capillary density 4 weeks after MI. Also, DHI promoted the proliferation and migration of hypoxic HUVECs. The qRT-PCR and Western blot analysis revealed that DHI intervention upregulated miR-126, suppressed Spred-1 expression, and activated the ERK pathway, but not the Akt pathway. The loss-of-function study showed the blockade of the pro-angiogenic effect of DHI by antagomir-126 involving the ERK/vascular endothelial growth factor (VEGF) pathway. CONCLUSION: DHI enhanced post-infarct angiogenesis after MI by activating the miR-126/ERK/VEGF pathway.

Danhong Injection Attenuates High-Fat-Induced Atherosclerosis and Macrophage Lipid Accumulation by Regulating the PI3K/AKT Insulin Pathway.

BACKGROUND AND AIMS: High-fat diet (HFD) is reported to induce atherosclerosis and insulin resistance. Macrophage lipid accumulation has been implicated as key mediators during the development of HFD-induced atherosclerosis. Traditional Chinese formula, which has long been used to improve disorder of glucose and lipid metabolism of patients, is now gradually being used as complementary therapy. This study aimed to investigate the effect of Danhong injection (DHI), a Chinese medicine used for the treatment of coronary artery disease, on atherosclerosis and its underlying mechanisms. METHODS AND RESULTS: We observed the effects of DHI on HFD-induced atherosclerosis in a mice model, macrophage lipid accumulation in an ox-LDL-stimulated macrophage model, and the role of PI3K/AKT insulin pathway in the process of DHI ameliorating atherosclerosis. The data demonstrated that DHI attenuated atherosclerosis by ameliorating blood lipids, reducing the atherosclerotic index and atherosclerotic plaque area in HFD-induced atherosclerotic mice, and inhibiting TC levels in an ox-LDL-induced macrophage model. By estimating the levels of serum insulin resistance-related indexes and protein expression of GLUT-4, DHI treatment dramatically inhibited the levels of fasting serum NEFA and fasting serum insulin and promoted the protein expression of GLUT-4 in aortas of the HFD-induced atherosclerotic mice. Moreover, according to the hints provided by microarray-based transcriptional profiling, the results demonstrated that DHI treatment also promoted the activation of PI3K/AKT insulin signaling pathway induced by IRS-1 in aortas of HFD-induced atherosclerotic mice. Furthermore, in an ox-LDL-induced macrophage model, the activation of PI3k/AKT signaling pathway also effectively functioned in the process of DHI inhibiting macrophage lipid accumulation. CONCLUSIONS: These results highlight that DHI treatment attenuates atherosclerosis and macrophage lipid accumulation by promoting the activation of PI3K/AKT insulin signaling pathway. It provides new insights into the molecular mechanism of DHI and its therapeutic potential in the treatment of atherosclerosis.

Desertihabitans aurantiacus gen. nov., sp. nov., a novel member of the family Propionibacteriaceae.

The taxonomic position of an actinobacterium isolated from a desert soil sample collected from Badain Jaran Desert, designated as CPCC 204711T, was established using a polyphasic approach. Cells of the isolate were Gram-staining-positive, aerobic, non-motile cocci. Good growth was observed at 28 °C (range 20-40 °C), pH 7.0 (range pH 6.0-8.0) and 0-1 % NaCl concentration (range 0-5 %, w/v). Galactose, arabinose and ribose were detected as the sugar compositions in the whole cell hydrolysates. The peptidoglycan type was A3gamma (ll-Dpm-Gly). MK-9(H4) was detected as the predominant menaquinone, and diphosphatidylglycerol, phosphatidylglycerol, phosphatidylcholine, several unidentified glycolipids, and one unidentified amino-glycolipid were detected as the major polar lipids. The predominant fatty acid was anteiso-C15 : 0. The genomic DNA G+C content was 73.1 mol%. Phylogenetic analysis based on 16S rRNA gene sequences revealed that strain CPCC 204711T affiliated to the family Propionibacteriaceae, in which the strain formed a distinct phylogenetic lineage next to the genus Mariniluteicoccus, with the highest 16S rRNA gene sequence similarity of 96.0 % to Mariniluteicoccus endophyticus YIM 2617T. Both phylogenetic analysis and phenotypic characteristics supported that strain CPCC 204711T represents a novel species of a new genus in the family Propionibacteriaceae, for which the name Desertihabitans aurantiacus gen. nov., sp. nov. is proposed, with CPCC 204711T (=KCTC 39977T=DSM 105431T) as the type strain.