ANGPTL3 accelerates atherosclerotic progression via direct regulation of M1 macrophage activation in plaque.

INTRODUCTION: The N-terminal domain of angiopoietin-like protein 3 (ANGPTL3) inhibits lipoprotein lipase activity. Its C-terminal fibrinogen-like (FBN) domain is a ligand of macrophage integrin αvß3. OBJECTIVES: ANGPTL3 might home to plaque where it directly regulates macrophage function via integrin αvß3 for atherosclerosis progression. METHODS: Ldlr-/- mice on a high-fat diet and ApoE-/- mice on a chow diet were received adeno-associated virus (AAV)-mediated Angptl3 gene transfer and followed up for 12 weeks. ApoE-/- mice were injected AAV containing FLAG-tagged Angptl3 cDNA for tracing. Atherosclerotic features were compared between Angptl3-/-ApoE-/- mice and ApoE-/- littermates. THP-1 cells were exposed to 0 or 50 µg/ml ANGPTL3 FBN domain for 24 h to evaluate Toll-like receptor (TLR)4 expression using western blot analysis and circulating cytokine and chemokine profiles by the MILLIPLEX MAP assay. Phospho-proteomic profile was established in ANGPTL3-treated macrophages. Integrin ß3 deficient THP-1 cells were obtained by sgRNAs targeting RGD sequence using Lentivirus-Cas9 system. RESULTS: Angptl3 overexpression increased atherosclerotic progression and CD68+ macrophages in plaque (p < 0.05 for all). By immunostaining, FLAG+ cells were identified in plaque of gene transferred ApoE-/- mice. Fluorescent immunostaining detected co-localisation of Angptl3 and CD68 in plaque macrophages. Phospho-proteomic analysis revealed that Angptl3 induced phosphorylation of proteins that were involved in the IL-17 signalling pathway in THP-1 cells. In vitro, ANGPTL3 treatment increased the production of interleukin (IL)-1ß and tumour necrosis factor-α in THP-1 cells (p < 0.05 for both). Exposure of ANGPTL3 to THP-1 cells induced Akt phosphorylation which was weakened in integrin ß3 deficient ones. ANGPTL3 elevated TLR4 expression via Akt phosphorylation. In response to lipopolysaccharide, nuclear factor-κB activity was 2.2-fold higher in THP-1 cells pre-treated with ANGPTL3 than in untreated cells (p < 0.05). CONCLUSIONS: Targeting ANGPTL3 could yield a dual benefit of lowering lipid levels in the blood and suppressing macrophage activation in plaque.

Cellular Uptake of Cell-Penetrating Peptides Activated by Amphiphilic p-Sulfonatocalix[4]arenes.

We report the synthesis of a series of amphiphilic p-sulfonatocalix[4]arenes with varying alkyl chain lengths (CX4-Cn) and their application as efficient counterion activators for membrane transport of cell-penetrating peptides (CPPs). The enhanced membrane activity is confirmed with the carboxyfluorescein (CF) assay in vesicles and by the direct cytosolic delivery of CPPs into CHO-K1, HCT 116, and KTC-1 cells enabling excellent cellular uptake of the CPPs into two cancer cell lines. Intracellular delivery was confirmed by fluorescence microscopy after CPP entry into live cells mediated by CX4-Cn, which was also quantified after cell lysis by fluorescence spectroscopy. The results present the first systematic exploration of structure-activity relationships for calixarene-based counterion activators and show that CX4-Cn are exceptionally effective in cellular delivery of CPPs. The dodecyl derivative, CX4-C12, serves as best activator. A first mechanistic insight is provided by efficient CPP uptake at 4 °C and in the presence of the endocytosis inhibitor dynasore, which indicates a direct translocation of the CPP-counterion complexes into the cytosol and highlights the potential benefits of CX4-Cn for efficient and direct translocation of CPPs and CPP-conjugated cargo molecules into the cytosol of live cells.

Green growth strategies in Asia: unleashing the heterogeneous asymmetry of ICT capital, financial fragility, environmental policy stringency, and education.

Financial fragility, ICT capital, environmental policy stringency, and education are the main factors that have also gained popularity regarding their impact on green growth. This study examines the impact of financial fragility, ICT capital, environmental policy stringency, and education on green growth. For analyzing the short- and long-run estimates, we have applied the panel QARDL model. The results of the panel QARDL model highlight that the estimates of non-performing bank loans and bank costs are negatively significant in both the short and long run, implying that financial fragility hurts green growth in the short and long run. Similarly, the estimated coefficients of the internet (mobile) and education estimates are positively significant in the short and long run, confirming that ICT capital and education are causing green growth, while environmental policy stringency promotes green growth only in the long run. Regarding the asymmetric effects of all the factors on green growth, the Wald test only confirms asymmetric effects in the long run. The study offers several significant recommendations for sustainable green development policies.

Using lanthanide ions as magnetic and sensing probes for the detection of tetracycline from complex samples.

Tetracycline (TC) is a broad-spectrum antibiotic and has been added to animal feeds to grow livestock under healthy conditions, making it important to have effective methods for rapidly detecting TC in complex samples. In this study, a novel method that uses lanthanide ions (i.e. Eu3+ and Gd3+) as magnetic and sensing probes for the detection of TC from aqueous samples is explored. When dissolving Gd3+ in tris(hydroxymethyl)aminomethane (Tris) buffer at pH 9, magnetic Gd3+-Tris conjugates can be readily generated. The magnetic Gd3+-Tris conjugates possess trapping capacity toward TC from sample solutions via the chelation of Gd3+ and TC. Eu3+ is used as the fluorescence sensing probe against TC on the Gd3+-TC conjugates via the antenna effect. The fluorescence response derived from Eu3+ is increased with the increase of TC trapped on the Gd3+-based probes. The linear dynamic range against TC ranges from 20 to 320 nM, whereas the limit of detection toward TC is ~2 nM. Furthermore, the developed sensing method can be employed for the visual assay of TC with a concentration above ~0.16 µM under UV light illumination in the dark. Furthermore, we have demonstrated the applicability of the developed method to quantify TC in a chicken broth sample with complex matrix. Our developed method offers several advantages, including high sensitivity and good selectivity, for the detection of TC in complex samples.

Exendin-4 attenuates atherosclerosis progression via controlling hematopoietic stem/progenitor cell proliferation.

Beyond glycemic control, applications of glucagon-like peptide-1 receptor (GLP-1r) agonists (GLP-1 RAs) inhibit inflammation and plaque development in murine atherosclerotic models. However, whether they modulate hematopoietic stem/progenitor cells (HSPCs) to prohibit skewed myelopoiesis in hypercholesteremia remains unknown. In this study, GLP-1r expression in fluorescence-activated cell sorting (FACS)-sorted wild-type HSPCs was determined by capillary western blotting. Bone marrow cells (BMCs) of wild-type or GLP-1r-/- mice were transplanted into lethally irradiated low-density lipoprotein receptor deficient (LDLr-/-) recipients followed by high-fat diet (HFD) for chimerism analysis by FACS. In parallel, LDLr-/- mice were placed on HFD for 6 weeks and then treated with saline or Exendin-4 (Ex-4) for another 6 weeks. HSPC frequency and cell cycle were analyzed by FACS, and intracellular metabolite levels were assessed by targeted metabolomics. The results demonstrated that HSPCs expressed GLP-1r and transplantation of GLP-1r-/- BMCs resulted in skewed myelopoiesis in hypercholesterolemic LDLr-/- recipients. In vitro, Ex-4 treatment of FACS-purified HSPCs suppressed cell expansion and granulocyte production induced by LDL. In vivo, Ex-4 treatment inhibited plaque progression, suppressed HSPC proliferation, and modified glycolytic and lipid metabolism in HSPCs of hypercholesteremic LDLr-/- mice. In conclusion, Ex-4 could directly inhibit HSPC proliferation induced by hypercholesteremia.

Atopomonas sediminilitoris sp. nov., isolated from beach sediment of Zhairuo Island, China.

A novel bacterium designated A3.4T was isolated from the beach sediment of Zhairuo Island, which is located in the East China Sea. Strain A3.4T was found to be Gram-stain negative, cream coloured, rod-shaped, aerobic and motile via a single monopolar flagellum. The isolate grows at 20-37 °C (optimum 25-30 °C), at pH 6.0-8.0 (optimum pH 7.0-8.0), and in the presence of 0-5.0% (w/v) NaCl (optimum 0.5-1%). A3.4T has catalase and oxidase activity. The predominant fatty acids (≥ 10%) of the strain were identified as C16:0, summed feature 3 (C16:1 ω7c /C16:1 ω6c) and summed feature 8 (C18:1 ω7c /C18:1 ω6c). Q-9 was identified as the major isoprenoid quinone, with trace levels of Q-8 present. The major polar lipids were identified as diphosphatidylglycerol, phosphatidylethanolamine and phosphatidylglycerol. The draft genome size is 3.55 Mb, with a DNA G + C content of 57.7 mol%. Analysis of the 16S rRNA gene sequence of strain A3.4T indicates that it belongs to the genus Atopomonas and shares high sequence similarity with Atopomonas hussainii JCM 19513T (97.60%). This classification was also supported by phylogenetic analysis using rpoB and several core genes. The genome of strain A3.4T shows an average nucleotide identity of 82.3%, an amino acid identity of 83.0%, and a digital DNA-DNA hybridization value of 22.1% with A. hussainii. In addition, 20 conserved signature indels (CSIs) were identified to be specific for A3.4T and A. hussainii, demonstrating that the strain A3.4T is closely related to A. hussainii rather than other species of family Pseudomonadaceae. Hundreds of unique genes were identified in the genomes of A3.4T and A. hussainii, which may underly multiple phenotypic differences between these strains. Based on phenotypic, chemotaxonomic, phylogenetic, and genomic investigations, strain A3.4T is concluded to represent a novel species of the genus Atopomonas, for which the name Atopomonas sediminilitoris sp. nov. is proposed. The type strain is A3.4T (= LMG 32563T = MCCC 1K07166T).

Do meniscal repairs with meniscus cyst do better than meniscectomy?-a systematic review of meniscal cyst treatment.

Background: This systematic review aims to determine the best modality for the management of meniscal cysts and its associated meniscus tear; whether the meniscal cyst treated via arthroscopy or open methods and whether meniscal debridement or repair achieves better results. Methods: This systematic review was performed using PRISMA guidelines. A literature search of PubMed, EMBASE and Cochrane was carried out in July 2020 using the search terms 'meniscal cyst' and 'treatment'. All clinic studies that included filters for papers in the last 20 years, English language, and meniscal cysts found in humans were included. Studies that contained case reports, were in any language other than English, and with subjects that were not humans were excluded. The methodology quality assessment was performed through the modified Coleman methodology score (CMS). Results: A total of 166 results were obtained from PubMed, Cochrane library and EMBASE. Of them, 12 duplicates were identified across the databases and removed from consideration. Six papers were found relevant from EMBASE in which 1 was eventually included in this paper. In total, 12 papers were used in this study. The weighted mean age of the patients was 35.1 years, with total of 523 meniscal cysts, of which 488 of these cysts are associated with meniscal tears (93.31%). The studies included performed cystectomies and/or decompression of meniscal cysts while some left the meniscal cyst alone and dealt with the meniscal lesion instead. All clinical scores showed significant improvement following surgical procedures. Conclusions: Both arthroscopic and open methods can be used for meniscal cysts treatment. Open cystectomy rather than decompression seemed to confer lower risk of cyst recurrences and complications. It is inconclusive to whether meniscal repair or meniscus debridement influenced recurrence and outcome scores. A recommendation for meniscus repair cannot be made due to insufficient high-quality level I or II trials.

Zinc Ion-Based Switch-on Fluorescence-Sensing Probes for the Detection of Tetracycline.

Tetracycline (TC) is an antibiotic that has been widely used in the animal husbandry. Thus, TC residues may be found in animal products. Developing simple and sensitive methods for rapid screening of TC in complex samples is of great importance. Herein, we demonstrate a fluorescence-sensing method using Zn2+ as sensing probes for the detection of TC. Although TC can emit fluorescence under the excitation of ultraviolet light, its fluorescence is weak because of dynamic intramolecular rotations, leading to the dissipation of excitation energy. With the addition of Zn2+ prepared in tris(hydroxymethyl)amino-methane (Tris), TC can coordinate with Zn2+ in the Zn2+-Tris conjugates to form Tris-Zn2+-TC complexes. Therefore, the intramolecular motions of TC are restricted to reduce nonradiative decay, resulting in the enhancement of TC fluorescence. Aggregation-induced emission effects also play a role in the enhancement of TC fluorescence. Our results show that the linear dynamic range for the detection of TC is 15-300 nM. Moreover, the limit of detection was ~7 nM. The feasibility of using the developed method for determination of the concentration of TC in a complex chicken broth sample is also demonstrated in this work.

Recent Insights into Neutrophil Extracellular Traps in Cardiovascular Diseases.

Neutrophils are primary effector cells of the innate immune system. Emerging evidence has consistently shown that activated neutrophils produce and release neutrophil extracellular traps (NETs) that play roles in immunity and non-infectious diseases. NETs are composed of DNA and proteins and serve as a structural platform for pathogen sequestration and degradation. In contrast to their protective role during pathogenic infection, NETs are pathologically involved in cardiovascular disease (CVD). In this review, we introduce the formation, release, and clearance of NETs and the regulatory mechanisms of NETs formation, followed by an overview of the clinical evidence for the involvement of NETs in CVD. Because atherosclerosis is a fundamental part of the pathogenesis of CVD, we chose to focus on the mechanisms by which NETs promote endothelial cell damage and collaborate with macrophages and platelets to accelerate plaque progression and thrombosis. Finally, we present options for clinical intervention to inhibit NETs production and release in the treatment of CVD. In conclusion, this review integrates the latest findings and provides new insights into NETs, which represent a novel biomarker and therapeutic target in clinical practice.

The purine metabolite inosine monophosphate accelerates myelopoiesis and acute pancreatitis progression.

Hyperglycemia-induced myelopoiesis and atherosclerotic progression occur in mice with type I diabetes. However, less is known about the effects of metabolites on myelopoesis in type 2 diabetes. Here, we use fluorescence-activated cell sorting to analyze the proliferation of granulocyte/monocyte progenitors (GMP) in db/db mice. Using targeted metabolomics, we identify an increase in inosine monophosphate (IMP) in GMP cells of 24-week-old mice. We show that IMP treatment stimulates cKit expression, ribosomal S6 activation, GMP proliferation, and Gr-1+ granulocyte production in vitro. IMP activates pAkt in non-GMP cells. In vivo, using an established murine acute pancreatitis (AP) model, administration of IMP-treated bone marrow cells enhances the severity of AP. This effect is abolished in the presence of a pAkt inhibitor. Targeted metabolomics show that plasma levels of guanosine monophosphate are significantly higher in diabetic patients with AP. These findings provid a potential therapeutic target for the control of vascular complications in diabetes.

A novel 16-gene alternative mRNA splicing signature predicts tumor relapse and indicates immune activity in stage I-III hepatocellular carcinoma.

Background: Hepatocellular carcinoma (HCC) is a lethal disease with high relapse and dismal survival rates. Alternative splicing (AS) plays a crucial role in tumor progression. Herein, we aim to integratedly analyze the relapse-associated AS events and construct a signature predicting tumor relapse in stage I-III HCC. Methods: AS events of stage I-III HCC with tumor relapse or long-term relapse-free survival were profiled to identify the relapse-associated AS events. A splicing network was set up to analyze the correlation between the relapse-associated AS events and splicing factors. Cox regression analysis and receiver operating characteristic curve were performed to develop and validate the relapse-predictive AS signature. Single-sample gene set enrichment analysis (ssGSEA) and the ESTIMATE algorithm were used to assess the immune infiltration status of the HCC microenvironment between different risk subgroups. Unsupervised cluster analysis was conducted to assess the relationship between molecular subtypes and local immune status and clinicopathological features. Results: In total, 2441 ASs derived from 1634 mRNA were identified as relapse-associated AS events. By analyzing the proteins involved in the relapse-associated AS events, 1573 proteins with 11590 interactions were included in the protein-protein interaction (PPI) network. In total, 16 splicing factors and 61 relapse-associated AS events with 85 interactions were involved in the splicing network. The relevant genes involved in the PPI network and splicing network were also analyzed by Gene Ontology enrichment analysis. Finally, we established a robust 16-gene AS signature for predicting tumor relapse in stage I-III HCC with considerable AUC values in all of the training cohort, testing cohort, and entire cohort. The ssGSEA and ESTIMATE analyses showed that the AS signature was significantly associated with the immune status of the HCC microenvironment. Moreover, four molecular subgroups with distinguishing tumor relapse modes and local immune status were also revealed. Conclusion: Our study built a novel 16-gene AS signature that robustly predicts tumor relapse and indicates immune activity in stage I-III HCC, which may facilitate the deep mining of the mechanisms associated with tumor relapse and tumor immunity and the development of novel individualized treatment targets for HCC.

Ancylobacter gelatini sp. nov., isolated from beach sediment of Zhairuo Island, China.

A Gram-negative, aerobic, non-motile, oxidase-positive, catalase-positive, methyl red-positive, and lipase-negative bacterium, designated A5.8T, was isolated from beach sediment of Zhairuo Island located in the East China Sea. Growth occurred at 10-40 °C (optimum, 30 °C), pH 5.5-9.5 (optimum, 7.5), and 0-2% NaCl (optimum, 1.5%). Based on 16S rRNA gene sequence analysis, strain A5.8T belongs to the genus Ancylobacter, sharing the highest similarity with Ancylobacter aquaticus JCM 20518T (98.0%). Its polar lipids mainly consist of phosphatidylethanolamine (PE) and phosphatidylcholine (PC). The predominant fatty acids are summed feature 8 (C18:1ω7c and/or C18:1ω6c, 91.0%), and the major respiratory quinone is Q-10. The DNA G + C content is 67.2 mol%. Based on above analysis, as well as digital DNA-DNA hybridization (22.5-22.9%) and average nucleotide identity (83.0-83.6%) of strain A5.8T with reference type strains of the genus Ancylobacter, strain A5.8T was suggested to represent a novel species of the genus Ancylobacter, for which the name Ancylobacter gelatini sp. nov. is proposed. The type strain is A5.8T (= MCCC 1K07167T = LMG 32566T).

Algoriphagus algorifonticola sp. nov., a marine bacterium isolated from cold spring area of South China Sea.

A Gram-stain-negative, aerobic, non-motile, short-rod-shaped bacterium, designated strain hg1T, was isolated from marine sediment within the cold spring area of South China Sea and subjected to a polyphasic taxonomic investigation. Colonies were circular and 1.0-2.0 mm in diameter, coral in colour, convex and smooth after growth on marine agar at 28 °C for 3 days. Strain hg1T was found to grow at 4-40 °C (optimum, 35-37 °C), at pH 6.5-9.0 (optimum, pH 7.5) and with 0-8 % (w/v) NaCl (optimum, 1.5-2 %). Chemotaxonomic analysis showed the sole respiratory quinone was MK-7, and the principal fatty acids are iso-C15 : 0, summed feature 3 (C16 : 1 ω7c and/or C16 : 1 ω6c), and iso-C16 : 0. The major polar lipids are phosphatidylethanolamine, an unidentified phospholipid and five unidentified glycolipids. The DNA G+C content of strain hg1T was 39.6 mol% based on the genome sequence. The comparison of 16S rRNA gene sequence similarities showed that hg1T was closely related to Algoriphagus ornithinivorans DSM 15282T (98.6 % sequence similarity), Algoriphagus zhangzhouensis MCCC 1F01099T (97.9 %) and Algoriphagus vanfongensis DSM 17529T (97.2 %); it exhibited 97.0 % or less sequence similarity to the type strains of other species of the genus Algoriphagus with validly published names. Phylogenetic trees reconstructed with the neighbour-joining, maximum-parsimony and maximum-likelihood methods based on 16S rRNA gene sequences showed that strain hg1T constituted a separate branch with A. ornithinivorans, A. zhangzhouensis, A. vanfongensis in a clade of the genus Algoriphagus. OrthoANI values between strain hg1T and A. ornithinivorans, A. zhangzhouensis and A. vanfongensis were 94.3, 74.1, 73.2 %, respectively, and in silico DNA-DNA hybridization values were 56.2, 18.5 and 18.3 %, respectively. Differential phenotypic properties, together with phylogenetic distinctiveness, demonstrated that strain hg1T is clearly distinct from recognized species of genus Algoriphagus. On the basis of these features, we propose that strain hg1T (=MCCC 1K03570T=KCTC 72111T) represents a novel species of the genus Algoriphagus with the name Algoriphagus algorifonticola sp. nov.

Adipocyte-derived PGE2 is required for intermittent fasting-induced Treg proliferation and improvement of insulin sensitivity.

The intermittent fasting (IF) diet has profound benefits for diabetes prevention. However, the precise mechanisms underlying IF's beneficial effects remain poorly defined. Here, we show that the expression levels of cyclooxygenase-2 (COX-2), an enzyme that produces prostaglandins, are suppressed in white adipose tissue (WAT) of obese humans. In addition, the expression of COX-2 in WAT is markedly upregulated by IF in obese mice. Adipocyte-specific depletion of COX-2 led to reduced fractions of CD4+Foxp3+ Tregs and a substantial decrease in the frequency of CD206+ macrophages, an increase in the abundance of γδT cells in WAT under normal chow diet conditions, and attenuation of IF-induced antiinflammatory and insulin-sensitizing effects, despite a similar antiobesity effect in obese mice. Mechanistically, adipocyte-derived prostaglandin E2 (PGE2) promoted Treg proliferation through the CaMKII pathway in vitro and rescued Treg populations in adipose tissue in COX-2-deficient mice. Ultimately, inactivation of Tregs by neutralizing anti-CD25 diminished IF-elicited antiinflammatory and insulin-sensitizing effects, and PGE2 restored the beneficial effects of IF in COX-2-KO mice. Collectively, our study reveals that adipocyte COX-2 is a key regulator of Treg proliferation and that adipocyte-derived PGE2 is essential for IF-elicited type 2 immune response and metabolic benefits.

Acinetobacter sedimenti sp. nov., isolated from beach sediment.

A Gram-stain-negative, aerobic, non-motile, non-haemolytic, oxidase-negative, catalase-positive bacillus strain (A3.8T) was isolated from beach sediment from Zhairuo Island, PR China. The strain grew at pH 6.0-9.0 (optimum, 7.0), with 0-4.5 % NaCl (optimum, 2 %) and at 10-35 °C (optimum, 30 °C). Its whole-genome sequence was 2.5 Mb in size, with a DNA G+C content of 41.6 mol%. On the basis of the results of core genome phylogenetic analysis, A3.8T represents a separate branch within the clade formed by five species of the genus Acinetobacter with 'Acinetobacter marinus' as the most closely related species. The average nucleotide identity compared with the closely related species of the genus Acinetobacter was below 83.66 % and digital DNA-DNA hybridization values were less than 28.80 %. The predominant fatty acids included C18 : 1ω9c, C16 : 0 and summed feature 3 (C16 : 1ω7c and/or C16 : 1ω6c). Q-9 was the major respiratory quinone. The polar lipids are mainly composed of diphosphatidylglycerol, phosphatidylglycerol, phosphatidylethanolamine, two phospholipids, an aminolipid and four unknown lipids. A3.8T cannot assimilate dl-lactate and weakly utilizes l-glutamate, l-leucine, l-phenylalanine and l-tartrate, which distinguishes it from other species of the genus Acinetobacter. On the basis of the genotype, phenotype and biochemical data, strain A3.8T represents a novel species of the genus Acinetobacter, for which the name Acinetobacter sedimenti sp. nov. is proposed. The type strain is A3.8T (=MCCC 1K07161T=LMG 32568T).

Diabetic Bone Marrow Cell Injection Accelerated Acute Pancreatitis Progression.

Acute pancreatitis (AP) is one of the leading causes of hospital admission, 20% of which could progress to the severe type with extensive acinar cell necrosis. Clinical studies have reported that diabetes is an independent risk factor of the incidence of AP and is associated with higher severity than nondiabetic subjects. However, how diabetes participates in AP progression is not well defined. To investigate this question, wild-type (wt) and diabetic db/db mice at the age of 16 weeks were used in the study. AP was induced in wt recipients by 10 injections of 50 µg/kg caerulein with a 1 h interval. One hour after the last caerulein injection, bone marrow cells (BMC) isolated from wt and db/db mice were injected intraperitoneally into the recipients (1 × 107cells/recipient). The recipients with no BMC injection served as controls. Thirteen hours after BMC injection, serum lipase activity was 1.8- and 1.3-folds higher in mice that received db/db BMC, compared with those with no injection and wt BMC injection, respectively (p ≤ 0.02 for both). By H&E staining, the overall severity score was 14.7 for no cell injection and 16.6 for wt BMC injection and increased to 22.6 for db/db BMC injection (p ≤ 0.002 for both). In particular, mice with db/db BMC injection developed more acinar cell necrosis and vacuolization than the other groups (p ≤ 0.03 for both). When sections were stained with an antibody against myeloperoxidase (MPO), the density of MPO+ cells in pancreatitis was 1.9- and 1.6-folds higher than wt BMC and no BMC injection groups, separately (p ≤ 0.02 for both). Quantified by ELISA, db/db BMC produced more IL-6, GM-CSF, and IL-10 compared with wt BMC (p ≤ 0.04 for all). In conclusion, BMC of db/db mice produced more inflammatory cytokines. In response to acinar cell injury, diabetic BMC aggravated the inflammation cascade and acinar cell injury, leading to the progression of acute pancreatitis.

Nocardioides malaquae sp. nov., a novel actinobacterium isolated from sewage sludge of a fisheries processing factory.

A Gram-stain-positive, rod-shaped, strictly aerobic bacterial strain (Y6T) was isolated from a sewage sludge sample collected from a fisheries processing factory in Zhoushan, Zhejiang Province, PR China. The growth range of NaCl concentration was 0-6.0 % (w/v), with an optimum at 3.0 % (w/v). The temperature range for growth was 10-42 °C, with an optimum at 37 °C. The pH range for growth was pH 7.0-10.0, with an optimum at pH 9.0. Phylogenetic analysis based on 16S rRNA gene sequences revealed that strain Y6T belonged to the genus Nocardioides and showed the highest sequence similarity of 97.8 % to Nocardioides jishulii dk3136T. The average nucleotide identity and in silico DNA-DNA hybridization values between strain Y6T and the reference strains were 76.9-81.2 % and 20.6-23.6 %, respectively. Chemotaxonomic analysis indicated that the sole respiratory quinone was MK-8(H4) and the predominant cellular fatty acids were iso-C16 : 0, 10-methyl-C17 : 0 and C18 : 1 ω9c. The polar lipid profile was composed of diphosphatidylglycerol, phosphatidylglycerol, phosphatidylethanolamine, phosphatidylcholine, four unidentified phospholipids, three unidentified aminolipids and five unidentified lipids. The peptidoglycan was ll-2,6-diaminopimelic acid. On the basis of the phenotypic, genotypic, phylogenetic and chemotaxonomic features, strain Y6T is considered to represent a novel species, for which the name Nocardioides malaquae sp. nov. is proposed. The type strain is Y6T (=KCTC 49504T=MCCC 1K04765T).

Nanomedicine for the treatment of diabetes-associated cardiovascular diseases and fibrosis.

Cardiomyopathy and fibrosis are the main causes of heart failure in diabetes patients. For therapeutic purposes, a delivery system is required to enhance antidiabetic drug efficacy and specifically target profibrotic pathways in cardiomyocytes. Nanoparticles (NPs) have distinct advantages, including biocompatibility, bioavailability, targeting efficiency, and minimal toxicity, which make them ideal for antidiabetic treatment. In this review, we overview the latest information on the pathogenesis of cardiomyopathy and fibrosis in diabetes patients. We summarize how NP applications improve insulin and liraglutide efficacy and their sustained release upon oral administration. We provide a comprehensive review of the results of NP clinical trials in diabetes patients and of animal studies investigating the effects of NP-mediated anti-fibrotic treatments. Collectively, the application of advanced NP delivery systems in the treatment of cardiomyopathy and fibrosis in diabetes patients is a promising and innovative therapeutic strategy.

Roles of Hematopoietic Stem and Progenitor Cells in Ischemic Cardiovascular Disease.

Macrophage proliferation and skewed myelopoiesis-induced monocytosis, as well as neutrophils, enhance the generation of atherogenic inflammatory cells in a lesion area, leading to plaque formation and Cardiovascular Disease (CVD). Among all risk factors, accumulated data have shown that hyperlipidemia activates Hematopoietic Stem/Progenitor Cells (HSPCs) in the Bone Marrow (BM) niche. Recently, proliferation of Granulocyte-Monocyte Progenitors (GMPs) has been demonstrated to drive skewed myelopoiesis, while HSPCs remain quiescent. In this review, we discuss how HSPCs and GMPs participate in atherosclerosis of mice in terms of proliferation and cell mobilization from BM to peripheral blood and the lesion area. We also describe how the spleen, an extramedullary organ, is involved in skewed myelopoiesis and inflammation in atherosclerosis. We further summarize the clinical evidence of the relationship of HSPCs with coronary stenoses in patients with CVD. Ultimately, this review facilitates understanding the pathological roles of HSPCs and GMPs in atherosclerosis for future treatments.