Combination Administration of Heparin and Nitroglycerin for the Treatment of Polycaprolactone-Induced Intravascular Embolism: A Preclinical Investigation.

BACKGROUND: As a new-generation collagen stimulator, polycaprolactone (PCL) containing filler has been extensively applied in facial dermal fillers and other medical aesthetic fields. However, inadvertent intravascular injection of PCL may result in complications such as tissue edema, flap necrosis, and even blindness. To date, there is no effective treatment for PCL-induced intravascular embolism. OBJECTIVES: The aim of this study was to identify a viable resolution for the embolism resulting from intravascular administration of PCL-containing fillers. METHODS: Two different animal experiments were performed: (1) PCL-induced rat inferior epigastric arteries embolism, followed by gross observation, histological evaluation, and cytokines analysis from serum; and (2) PCL-induced rabbit auricular artery embolism, immediately treated with heparin and nitroglycerin. The ears were then evaluated by gross observation, Laser speckle imaging, in vivo imaging system (IVIS) imaging, and histological evaluation. Saline and hyaluronic acids (HA) were used as controls, hyaluronidase was used as a positive drug. RESULTS: In a rat model of inferior epigastric arteries embolism, both intravascular injection of HA and PCL resulted in flap necrosis, indicating that the filler-induced intravascular embolism can lead to serious complications. In a rabbit model of auricular artery embolism, the combination treatment of heparin and nitroglycerin resulted in a relative blood reperfusion recovery of 80% in the ischemic area of the PCL group on day 7 post-operation, which was comparable to that of the HA group treated with hyaluronidase. Histological analysis revealed that the administration of heparin and nitroglycerin significantly attenuated intravascular thrombosis formation and inflammatory cell aggregation. CONCLUSIONS: The combination of heparin and nitroglycerin effectively restores blood flow reperfusion in the intravascular embolization caused by PCL filler injection, alleviates local tissue edema and flap necrosis. These findings offer a novel approach for future clinical management of intravascular embolization with PCL-containing filler injection. NO LEVEL ASSIGNED: This journal requires that authors assign a level of evidence to each submission to which Evidence-Based Medicine rankings are applicable. This excludes Review Articles, Book Reviews, and manuscripts that concern Basic Science, Animal Studies, Cadaver Studies, and Experimental Studies. For a full description of these Evidence-Based Medicine ratings, please refer to the Table of Contents or the online Instructions to Authors www.springer.com/00266 .

Chinese bayberry (Myrica rubra Sieb. et Zucc.) leaves proanthocyanidins inhibit intestinal glucose transport in human Caco-2 cells.

Background: The hypoglycemic effects of Chinese bayberry leaves proanthocyanidins (BLPs) have been demonstrated. It is unclear, nevertheless, whether BLPs reduced postprandial blood glucose levels by regulating glucose uptake and glucose transport. Method: This study investigated the effect of BLPs (25, 50, and 100 µg/mL) on glucose uptake and glucose transport in human intestinal epithelial cells (Caco-2 cells). The uptake of 2-Deoxy-2-[(7-nitro-2,1,3-benzoxadiazol-4-yl) amino]-D-glucose (2-NBDG) and disaccharidases activity in Caco-2 cells were measured. The glucose transport ability across the cell membrane was determined using the established Caco-2 monolayer model. The transcript and protein levels of key glucose transporters were analyzed using real-time quantitative polymerase chain reaction (RT-qPCR) and western blotting, respectively. Results: The results showed that BLPs significantly decreased glucose uptake and disaccharidases activity (p < 0.05). Otherwise, BLPs treatment obviously inhibited glucose transport across the Caco-2 monolayer in both simulated-fast (5 mM glucose) and simulated-fed (25 mM glucose) conditions. It was attributed to the suppression of glucose transporter2 (GLUT2) and sodium-dependent glucose cotransporter 1 (SGLT1) by BLPs. BLPs were found to significantly downregulated the transcript level and protein expression of glucose transporters (p < 0.05). Meanwhile, the mRNA expression of phospholipase C (PLC) and protein kinase C (PKC) involved in the signaling pathway associated with glucose transport were decreased by BLPs. Conclusion: These results suggested that BLPs inhibited intestinal glucose transport via inhibiting the expression of glucose transporters. It indicated that BLPs could be potentially used as a functional food in the diet to modulate postprandial hyperglycemia.

Advances in the role and mechanism of fibroblasts in fracture healing.

With the development of social population ageing, bone fracture has become a global public health problem due to its high morbidity, disability and mortality. Fracture healing is a complex phenomenon involving the coordinated participation of immigration, differentiation and proliferation of inflammatory cells, angioblasts, fibroblasts, chondroblasts and osteoblasts which synthesize and release bioactive substances of extracellular matrix components, Mortality caused by age-related bone fractures or osteoporosis is steadily increasing worldwide as the population ages. Fibroblasts play an important role in the process of fracture healing. However, it is not clear how the growth factors and extracellular matrix stiffness of the bone-regeneration microenvironment affects the function of osteoblasts and fibroblasts in healing process. Therefore, this article focuses on the role of fibroblasts in the process of fracture healing and mechanisms of research progress.

Identification of therapeutic targets and prognostic biomarkers in the Siglec family of genes in tumor immune microenvironment of sarcoma.

Sarcomas (SARC) are a highly heterogeneous cancer type that is prone to recurrence and metastasis. Numerous studies have confirmed that Siglecs are involved in immune signaling and play a key role in regulating immune responses in inflammatory diseases and various cancers. However, studies that systematically explore the therapeutic and prognostic value of Siglecs in SARC patients are very limited. The online databases GEPIA, UALCAN, TIMER, The Kaplan-Meier Plotter, GeneMANIA, cBioPortal, and STING were used in this study. IHC staining was performed on the collected patient tissues, and clinical data were statistically analyzed. The transcript levels of most Siglec family members showed a high expression pattern in SARC. Compared with normal tissues, Siglec-5, Siglec-10, and Siglec-12 were abnormally highly expressed in tumor tissues. Importantly, Siglec-15 was significantly associated with poor prognosis. Functional enrichment analysis showed that the Siglec family was mainly enriched in hematopoietic cell lineages. The genes associated with molecular mutations in the Siglec family were mainly TP53 and MUC16, among which Siglec-2 and Siglec-15 were significantly associated with the survival of patients. The expression levels of all Siglec family members were significantly correlated with various types of immune cells (B cells, CD8 + T cells, CD4 + T cells, macrophages, neutrophils and dendritic cells). Furthermore, a significant correlation was found between the somatic copy number changes of all Siglec molecules and the abundance of immune infiltrates. Our study paints a promising vision for the development of immunotherapy drugs and the construction of prognostic stratification models by investigating the therapeutic and prognostic potential of the Siglec family for SARC.

One-plasmid double-expression system for preparation of MS2 virus-like particles packaging SARS-CoV-2 RNA.

COVID-19 is a disease caused by a virus named SARS-CoV-2. SARS-CoV-2 is a single-stranded positive-sense RNA virus. Reverse transcription quantitative PCR (RT-qPCR) assays are the gold standard molecular test for detection of RNA viruses. The aim of this study was to construct an RNA-positive control based on MS2 phage-like particles (MS2 VLPs) to detect SARS-CoV-2 RNA. pCDFDuet-1 was used as a one-plasmid double-expression system to construct MS2 VLPs containing ssRNA of SARS-CoV-2. The sequence encoding one copy of maturase, His-tag and coat protein dimer was cloned and inserted into MCS1 of the plasmid; the fragment encoding protein N and ORF1ab from SARS-CoV-2 was cloned and inserted into MCS2. The prepared plasmid was transformed into Escherichia coli strain BL2 (DE3), and expression of the construct was induced by 1 mM isopropyl-L-thio-D-galactopyranoside (IPTG) at 30°C for 12 hours. MS2 VLPs were purified and collected with Ni-NTA affinity chromatography columns. The size and shape of the MS2 VLPs were verified by transmission electron microscopy, and the stability of MS2 VLP packaged RNA was evaluated by treatment with RNase A. Effects of storage temperature and buffer on MS2 VLP stability were also investigated. The results showed that SARS-CoV-2 MS2 VLPs could be successfully produced by this one-plasmid double-expression system. MS2 VLPs showed high stability and may be used as a positive control in molecular diagnosis of COVID-19.

Genetic analysis of basal stalk rot resistance introgressed from wild Helianthus petiolaris into cultivated sunflower (Helianthus annuus L.) using an advanced backcross population.

Introduction: Sclerotinia sclerotiorum is a serious pathogen causing severe basal stalk rot (BSR) disease on cultivated sunflower (Helianthus annuus L.) that leads to significant yield losses due to insufficient resistance. The wild annual sunflower species H. petiolaris, commonly known as prairie sunflower is known for its resistance against this pathogen. Sunflower resistance to BSR is quantitative and determined by many genes with small effects on the resistance phenotype. The objective of this study was to identify loci governing BSR resistance derived from H. petiolaris using a quantitative trait loci (QTL) mapping approach. Methods: BSR resistance among lines of an advanced backcross population (AB-QTL) with 174 lines developed from a cross of inbred line HA 89 with H. petiolaris PI 435843 was determined in the field during 2017-2019, and in the greenhouse in 2019. AB-QTL lines and the HA 89 parent were genotyped using genotyping-by-sequencing and a genetic linkage map was developed spanning 997.51 cM and using 1,150 SNP markers mapped on 17 sunflower chromosomes. Results and discussion: Highly significant differences (p<0.001) for BSR response among AB-QTL lines were observed disease incidence (DI) in all field seasons, as well as disease rating (DR) and area under the disease progress curve (AUDPC) in the greenhouse with a moderately high broad-sense heritability (H 2) of 0.61 for the tested resistance parameters. A total of 14 QTL associated with BSR resistance were identified on nine chromosomes, each explaining a proportion of the phenotypic variation ranging from 3.5% to 28.1%. Of the 14 QTL, eight were detected for BSR resistance in the field and six were detected under greenhouse conditions. Alleles conferring increased BSR resistance were contributed by the H. petiolaris parent at 11 of the 14 QTL.

Comparative Transcriptome Profiling of mRNA and lncRNA of Mouse Spleens Inoculated with the Group ACYW135 Meningococcal Polysaccharide Vaccine.

The Group ACYW135 meningococcal polysaccharide vaccine (MPV-ACYW135) is a classical common vaccine used to prevent Neisseria meningitidis serogroups A, C, Y, and W135, but studies on the vaccine at the transcriptional level are still limited. In the present study, mRNAs and lncRNAs related to immunity were screened from the spleens of mice inoculated with MPV-ACYW135 and compared with the control group to identify differentially expressed mRNAs and lncRNAs in the immune response. The result revealed 34375 lncRNAs and 41321 mRNAs, including 405 differentially expressed (DE) lncRNAs and 52 DE mRNAs between the MPV group and the control group. Results of GO and KEGG enrichment analysis turned out that the main pathways related to the immunity of target genes of those DE mRNAs and DE lncRNAs were largely associated with positive regulation of T cell activation, CD8-positive immunoglobulin production in mucosal tissue, alpha-beta T cell proliferation, negative regulation of CD4-positive, and negative regulation of interleukin-17 production, suggesting that the antigens of MPV-ACYW135 capsular polysaccharide might activate T cell related immune reaction in the vaccine inoculation. In addition, it was noted that Bach2 (BTB and CNC homolog 2), the target gene of lncRNA MSTRG.17645, was involved in the regulation of immune response in MPV-ACYW135 vaccination. This study provided a preliminary catalog of both mRNAs and lncRNAs associated with the proliferation and differentiation of body immune cells, which was worthy of further research to enhance the understanding of the biological immune process regulated by MPV-ACYW135.

Effect of proanthocyanidins from different sources on the digestibility, physicochemical properties and structure of gelatinized maize starch.

The effect of proanthocyanidins (PAs) from Chinese bayberry leaves (BLPs), grape seeds (GSPs), peanut skins (PSPs) and pine barks (PBPs) on physicochemical properties, structure and in-vitro digestibility of gelatinized maize starch was investigated. The results showed that all PAs remarkably retarded starch digestibility, meanwhile, BLPs highlighted superiority in increasing resistant starch content from 31.29 ± 1.12 % to 68.61 ± 1.15 %. The iodine-binding affinity analysis confirmed the interaction between PAs and starch, especially the stronger binding of BLPs to amylose, which was driven by non-covalent bonds supported by XRD and FT-IR analysis. Further, we found that PAs altered the rheological properties, thermal properties and morphology structure of starch. In brief, PAs induced larger consistency, poorer flow ability, lower gelatinization temperatures and melting enthalpy change (ΔH) of starch paste. SEM and CLSM observation demonstrated that PAs facilitated starch aggregation. Our results indicated that PAs especially BLPs could be considered as potential additives to modify starch in food industry.

Association of variants and expression levels of MYOD1 gene with carcass and muscle characteristic traits in domestic pigeons.

This study was to investigate the correlations of myogenic differentiation 1 (MYOD1) gene polymorphisms with carcass traits and its expression with breast muscle development in pigeons. Four SNPs were found in the pigeon MYOD1 gene. Correlation analysis showed that individuals with AA genotype at both SNPs g.2967A > G (p < .01) and g.3044G > A (p < .05) have significantly higher live weight (LW), carcass weight (CW), semi-eviscerated weight (SEW), eviscerated weight (EW) and breast muscle weight (BMW). Moreover, the two SNPs also had the same significant effects on MYOD1 mRNA expression levels in breast muscle of pigeons, ie, the AA genotype showed higher MYOD1 mRNA expression levels. The diameter and cross-section area of muscle fibers continuously increased from 0w to 4w (p < .05), accompanied with the increasing expression of MYOD1 gene, while the density decreased (p < .05) dramatically from 0w to 1w and continuously fell over in the next few weeks (p > .05). What's more, the expression level of MYOD1 gene was positively correlated with a diameter (r = 0.937, p < .05) and cross-sectional area (r = 0.956, p < .01) of myofiber, and negatively correlated with density (r = -0.769, p < .01). The results showed that individuals with AA genotype at both SNPs g.2967A > G and g.3044G > A have showed higher carcass traits (LW, CW, SEW, EW, and BMW) and higher MYOD1 mRNA expression level in breast muscle than AB and BB genotypes. Moreover, the expression level of MYOD1 gene was closely correlated with muscle characteristic traits, indicating variants of MYOD1 gene was closely related to muscle development and could be a potential candidate gene in marker-assisted selection of pigeons.

" " Codes: A Hyaluronic Acid Injection Procedure of Facial Aesthetics and Rejuvenation for Chinese Patients.

ABSTRACT: We have summarized a simple and effective method of filler injection for facial rejuvenation in Chinese patients and named it " " Codes. It is simple and easy to operate, which worth clinical promotion and application.

Mutation and sequencing-based cloning and functional studies of a rust resistance gene in sunflower (Helianthus annuus).

Rust, caused by the fungus Puccinia helianthi Schwein., is one of the most devastating diseases of sunflower (Helianthus annuus L.), affecting global production. The rust R gene R11 in sunflower line HA-R9 shows broad-spectrum resistance to P. helianthi virulent races and was previously mapped to an interval on sunflower chromosome 13 encompassing three candidate genes annotated in the XRQr1.0 reference genome assembly. In the current study, we combined ethyl methane sulfonate (EMS) mutagenesis with targeted region capture and PacBio long-read sequencing to clone the R11 gene. Sequencing of a 60-kb region spanning the R11 locus from the R11 -HA-R9 rust-resistant line and three EMS-induced susceptible mutants facilitated the identification of R11 and definition of induced mutations. The R11 gene is predicted to have a single 3996-bp open reading frame and encodes a protein of 1331 amino acids with CC-NBS-LRR domains typical of genes conferring plant resistance to biotrophic pathogens. Point mutations identified in the R11 rust-susceptible mutants resulted in premature stop codons, consistent with loss of function leading to rust susceptibility. Additional functional studies using comparative RNA sequencing of the resistant line R11 -HA-R9 and R11 -susceptible mutants revealed substantial differences in gene expression patterns associated with R11 -mediated resistance at 7 days post-inoculation with rust, and uncovered the potential roles of terpenoid biosynthesis and metabolism in sunflower rust resistance.

Mechanisms of Immune-Related Long Non-Coding RNAs in Spleens of Mice Vaccinated with 23-Valent Pneumococcal Polysaccharide Vaccine (PPV23).

The 23-valent pneumococcal vaccine (PPV23) is a classical common vaccine used to prevent pneumococcal disease. In past decades, it was thought that vaccination with this vaccine induces humoral immunity, thereby reducing the disease associated with infection with 23 common serotypes of Streptococcus pneumoniae (Sp). However, for this polysaccharide vaccine, the mechanism of immune response at the transcriptional level has not been fully studied. To identify the lncRNAs (long noncoding RNAs) and mRNAs in spleens related to immunity after PPV23 vaccination in mice, high-throughput RNA sequencing of spleens between a PPV23 treatment group and a control group were performed and evaluated in this study. The RNA-seq results identified a total of 41,321 mRNAs and 34,375 lncRNAs, including 55 significantly differentially expressed (DE) mRNAs and 389 DE lncRNAs (p < 0.05) between the two groups. GO and KEGG annotation analysis indicated that the target genes of DE lncRNAs and DE mRNAs were related to T-cell costimulation, positive regulation of alpha-beta T-cell differentiation, the CD86 biosynthetic process, and the PI3K-Akt signaling pathway, indicating that the polysaccharide component antigens of PPV23 might activate a cellular immune response during the PPV23 immunization process. Moreover, we found that Trim35 (tripartite motif containing 35), a target gene of lncRNA MSTRG.9127, was involved in regulating immunity. Our study provides a catalog of lncRNAs and mRNAs associated with immune cells' proliferation and differentiation, and they deserve further study to deepen the understanding of the biological processes in the regulation of PPV23 during humoral immunity and cellular immunity.

Radiosynthesis, optimization and pharmacokinetic study of the 99m Tc-labeled human epidermal growth factor receptor 2 affibody molecule probe 99m Tc-(HE) 3 Z HER2:V2.

OBJECTIVE: To prepare a single-photon molecular probe easily labeled with 99m Tc for evaluating the expression status of the human epidermal growth factor receptor 2 (HER2) receptor in ovarian cancer. MATERIALS AND METHODS: The HEHEHE tag was added to the amino terminus of the affibody Z HER2:V2 by the method of gene recombinant expression, and a new affibody was synthesized which was easy to be labeled with 99m Tc. The newly prepared affibody was labeled with 99m Tc, and pharmacokinetic studies were carried out. RESULTS: A new affibody (HE) 3 Z HER2:V2 was prepared by the method of gene recombination and expression, which is easy to be labeled with 99m Tc. The 99m Tc labeling of the affibody can reach about 95% at 90°C. The pharmacokinetic study has shown that the 99m Tc-labeled molecular probe has a fast clearance time in the blood and little side effect, which may be a promising single-photon emission computed tomography (SPECT) imaging agent. CONCLUSION: The affibody (HE) 3 Z HER2:V2 is easy to be labeled with 99m Tc, has a high yield and has a suitable half-life in vivo, which is suitable for the next step in ovarian cancer model imaging research.

Minimally Invasive 980 nm Laser-Assisted Lipolysis and Skin Tightening on Lower Eyelids of Asian Patients.

OBJECTIVE: The present study aimed to evaluate the effectiveness of minimally invasive 980 nm laser-assisted lipolysis and skin tightening in lower eyelid blepharoplasty of Asian patients. METHODS: Patients with mild and moderate degree of eyebags underwent 980 nm laser-assisted lipolysis via lower eyelid stab incision between December 2017 and December 2019. Evaluation criteria was reviewed by photographs taken preoperatively and 6 months postoperatively in accordance with guidelines of Global Aesthetic Improvement Scale, the patient's perspective from the questionnaire with the perception of reduction in eyebags size, the average perception of improvement in skin tightening, and the patient overall satisfaction, all with a score of 1 to 5 (5 being the most noticeable and very satisfied) and complications such as dyspigmentation, hematoma, prolonged edema, skin bump and thermal burn were documented as well. RESULTS: A total of 178 cases with 137 women and 41 men (age range from 23 to 50 years) were included. Total energy of 1200 J to 2000 J was delivered to both eyebags at 6 to 10 W. They were followed up for at least 6 months. A total of 166 patients (93.26%) revealed an improvement in Global Aesthetic Improvement Scale, with the 12 patients (6.74%) complaint no change 6 month postoperatively. Perception of improvement in eye bag protrusion scored 4.39 ± 0.59, improvement in skin tightening scored 4.42 ± 0.58 and the overall patient's satisfaction scored 4.59 ± 0.53. The patients' average recovered swelling from 4.35 ± 2.3 days. There were 5 patients (2.8%) with dyspigmentation, 3 patients (1.69%) with prolonged edema and 2 patients (1.12%) with skin bump and none of the patients had thermal burn. All of them resolve after 6 months of follow up. CONCLUSION: Patients with mild to moderate degree of eyebags who resist surgery are good candidates for laser-assisted lower eyelid blepharoplasty.

Corrigendum: Cinnamaldehyde promotes the intestinal barrier functions and reshapes gut microbiome in early weaned rats.

[This corrects the article DOI: 10.3389/fnut.2021.748503.].

Corrigendum: The therapeutic efficacy of adipose tissue-derived mesenchymal stem cell conditioned medium on experimental colitis was improved by the serum from colitis rats.

[This corrects the article DOI: 10.3389/fbioe.2021.694908.].

Corrigendum: Expression of DGAT2 gene and its associations with intramuscular fat content and breast muscle fiber characteristics in domestic pigeons (Columba livia).

[This corrects the article DOI: 10.3389/fvets.2022.847363.].

Ameliorative effect of bayberry leaves proanthocyanidins on high sugar diet induced Drosophila melanogaster.

Bayberry leaves proanthocyanidins (BLPs) were distributed in natural plant food, considered to have the potential for metabolic syndrome. In this study, we raised Drosophila melanogaster on high sugar diet (HSD) from the egg stage to induce hyperglycemia, and the ameliorative effect of BLPs was assessed based on this model. Phenotypical, biochemical, and molecular analyses related to diabetes mellitus pathogenesis were measured. Flies exposed to BLPs were found to suppress the HSD-induced high glucose and high triglycerides levels. Moreover, BLPs showed an inhibitory effect on carbohydrate digestive enzymes (α-amylase and α-glucosidase) activity and mRNA expression, exhibiting the potential for carbohydrate digestion retardation. Transcriptional levels of key genes associated with glycolipid metabolism were further evaluated, including dilp, InR, and downstream dAKT-dFOXO-PEPCK, together with E78, SREBP, FAS, and LSD genes, were all downregulated after BLPs-exposure, suggesting the ameliorative effect of BLPs on dysbiosis associated with the insulin signaling pathway. This study provided a new functional compound, which is beneficial to further antidiabetic therapy studies.

Genetic Insight into Disease Resistance Gene Clusters by Using Sequencing-Based Fine Mapping in Sunflower (Helianthus annuus L.).

Rust and downy mildew (DM) are two important sunflower diseases that lead to significant yield losses globally. The use of resistant hybrids to control rust and DM in sunflower has a long history. The rust resistance genes, R13a and R16, were previously mapped to a 3.4 Mb region at the lower end of sunflower chromosome 13, while the DM resistance gene, Pl33, was previously mapped to a 4.2 Mb region located at the upper end of chromosome 4. High-resolution fine mapping was conducted using whole genome sequencing of HA-R6 (R13a) and TX16R (R16 and Pl33) and large segregated populations. R13a and R16 were fine mapped to a 0.48 cM region in chromosome 13 corresponding to a 790 kb physical interval on the XRQr1.0 genome assembly. Four disease defense-related genes with nucleotide-binding leucine-rich repeat (NLR) motifs were found in this region from XRQr1.0 gene annotation as candidate genes for R13a and R16. Pl33 was fine mapped to a 0.04 cM region in chromosome 4 corresponding to a 63 kb physical interval. One NLR gene, HanXRQChr04g0095641, was predicted as the candidate gene for Pl33. The diagnostic SNP markers developed for each gene in the current study will facilitate marker-assisted selections of resistance genes in sunflower breeding programs.