Glaucatotones A-I: Guaiane-type sesquiterpenoids from the roots of Lindera glauca with anti-inflammatory activity.

Glaucatotones A - I, nine new guaiane-type sesquiterpenoids, along with two reported compounds, namely (1ß,5ß)-1-hydroxyguaia-4(15),11(13)-dieno-12,5-lactone (10) and pseudoguaianelactone C (11), were isolated from the roots of Lindera glauca. The structures and absolute configurations of these compounds were elucidated by extensive spectroscopic analyses, single-crystal X-ray diffraction, and comparison of experimental and calculated electronic circular dichroism (ECD) data. Structurally, glaucatotone A (1) is characterized as a dihomosesquiterpenoid with an unprecedented 5/5/7/6 ring system. A pair of enantiomers, (±)-glaucatotone B (2a/2b), represent the first rearranged norsesquiterpenoid with a (cyclopentylmethyl)cyclohexane skeleton. 3 is defined as a dinorsesquiterpenoid possessing a 5/7/5 ring system. 4-6 are three guaiane-type norsesquiterpenoids. In vitro bioactivity, 2a selectively inhibited Bcap-37 with IC50 value of 5.60 µM, and 9 selectively inhibited Du-145 with IC50 value of 5.52 µM. The anti-inflammatory activity of 1-9 were tested, and of these compounds, 1, 2a, 2b and 7 exhibited potent inhibitory effects.

Sesquiterpenoids from the roots of Lindera glauca and their cytotoxicity activities.

The chemical investigation of the roots of Lindera glauca guided the isolation and identification of 3 new sesquiterpenoids, namely glaucatotones J-L (1-3), and one known congener, (1ß,5ß)-1-hydroxyguaia-4(15),11(13)-dieno-12,5-lactone (4). The structures of new compounds were established based on comprehensive spectrographic methods, mainly including 1D & 2D NMR and HRESIMS analyses, and the absolute configurations were further confirmed by the comparison of experimental and calculated electronic circular dichroism. The cytotoxicity activities of isolates were evaluated, and the results showed that they have moderate cytotoxic activities.

Circular RNA circANKS1B acts as a sponge for miR-152-3p and promotes prostate cancer progression by upregulating TGF-α expression.

BACKGROUND: A growing number of studies indicate that circular RNAs (circRNAs) play critical roles in human diseases, and show great potential as biomarkers and therapeutic targets. This study aimed to investigate the expression and function of circANKS1B in prostate cancer (PC). METHODS: The expression of circANKS1B and miR-152-3p was analyzed by real-time quantitative reverse-transcription polymerase chain reaction (qRT-PCR). Cell migration and invasion were measured using a transwell assay. The interaction between circANKS1B and miR-152-3p was confirmed by a dual-luciferase reporter gene assay. Rescue experiments were conducted to determine whether circANKS1B regulated the invasion of PC cells via the circANKS1B-miR-152-3p-TGF-α pathway. RESULTS: The expression of circANKS1B was markedly upregulated in both PC cells and tissues. Moreover, high circANKS1B expression was associated with poor prognosis in PC patients. Dual-luciferase reporter assay indicated that circANKS1B directly bound to miR-152-3p. Furthermore, circANKS1B negatively regulated miR-152-3p expression. Knockdown of circANKS1B markedly suppressed cell migration and invasion and TGF-α expression in PC cells, whereas the effects of circANKS1B silencing were reversed by miR-152-3p deficiency. In addition, the impact of miR-152-3p silencing on invasion of circANKS1B-deficient PC cells was also abrogated by TGF-α deficiency. Overall, circANKS1B acts as a sponge for miR-152-3p to promote PC progression by upregulating TGF-α expression. CONCLUSION: Our findings reveal that circANKS1B may be a potential prognostic biomarker and therapeutic target for PC.

Positive abundance-elevational range size relationship weakened from temperate to subtropical ecosystems.

Describing the patterns and revealing the underlying mechanisms responsible for variations in community structure remain a central focus in ecology. However, important gaps remain, including our understanding of species abundance. Most studies on abundance-based relationships are from either temperate ecosystems or tropical ecosystems, and few have explicitly tested abundance-based relationships across a temperate to tropical ecotone. Here, we use a comprehensive dataset of breeding birds across elevation spanning a temperate to subtropical gradient in the Himalayas-Hengduan Mountains of China to examine the relationship between species abundance and (a) elevational range size, (b) body size, (c) elevational range centre and (d) endemicity. We tested a priori predictions for abundance-elevational range size relationship, abundance-body size relationship and abundance-elevational range centre relationship, and explored how these relationships change along this temperate to subtropical mountain ecosystem. We found that species abundance was significantly positively correlated with elevational range size across the study sites, demonstrating the key importance of elevational range size towards species abundance. Body size and elevational range centre are weakly correlated with abundance. A novel finding of our study is that the abundance-elevational range size relationship gradually weakened from temperate to subtropical ecosystems, adding to a growing body of evidence suggesting that abundance-elevational range size tracks a temperate to tropical ecotone. Our study demonstrates that abundance range-size relationship can transition across ecotones where faunas of different evolutionary origins converge. Furthermore, measuring abundance relationships across different environmental variables at the same spatial scale with comparable biogeography is a key strategy that can reveal the underlying mechanisms behind abundance patterns.

RNA sequence analysis of dermal papilla cells' regeneration in 3D culture.

It is well known that dermal papilla cells (DPCs) are crucial for hair follicle growth and regeneration. However, dermal papilla cells in 2D culture could lose their ability of regeneration after several passage intervals. As opposed to DPCs in 2D culture, the DPCs in 3D culture could passage extensively. However, the molecular mechanisms of DPCs' regeneration in 3D culture remain unclear. Accordingly, gene sequencing is recommended for the investigation of hair regeneration between 2D and 3D culture, the three groups were established including DPCs in passage 2 in 2D culture, DPCs in passage 8 in 2D culture and DPCs in passage 8 in 3D culture. The differentially expressed genes (DEGs) were identified using the Venn diagram of these three groups, which included 1642 known and 359 novel genes, respectively. A total of 1642 known genes were used for Gene Ontology (GO), Kyoto Gene, Genomic Encyclopedia (KEGG) pathway enrichment and protein-protein interaction (PPI) analyses, respectively. The functions and pathways of DEGs were enriched in biological regulation, signal transduction and immune system, etc. The key module and the top 10 hub genes (IL1B, CXCL12, HGF, EGFR, APP, CCL2, PTGS2, MMP9, NGF and SPP1) were also identified using the Cytoscape application. Furthermore, the qRT-PCR results of the three groups validated that the hub genes were crucial for hair growth. In conclusion, the ten identified hub genes and related pathways in the current study can be used to understand the molecular mechanism of hair growth, and those provided a possibility for hair regeneration.

Isolated Bilateral Macrostomia.

Macrostomia (Tessier's 7 cleft) is a rare congenital lip deformity. Macrostomia can occur unilateral or bilateral, isolated or associated with other syndromes. Isolated bilateral macrostomia is exceedingly rare with only a few cases reported to date. The authors report 6 cases of isolated bilateral macrostomia surgically repaired in 4-layered approaches. The traditional method was improved and the result obtained was satisfactory after longest follow-up of 3 years. The technique is easy to imitate, simple in design, aesthetically and functionally corrects the deformity.

GUCA1A mutation causes maculopathy in a five-generation family with a wide spectrum of severity.

PURPOSE: The aim of this study was to investigate the genetic basis and pathogenic mechanism of variable maculopathies, ranging from mild photoreceptor degeneration to central areolar choroidal dystrophy, in a five-generation family. METHODS: Clinical characterizations, whole-exome sequencing, and genome-wide linkage analysis were carried out on the family. Zebrafish models were used to investigate the pathogenesis of GUCA1A mutations. RESULTS: A novel mutation, GUCA1A p.R120L, was identified in the family and predicted to alter the tertiary structure of guanylyl cyclase-activating protein 1, a photoreceptor-expressed protein encoded by the GUCA1A gene. The mutation was shown in zebrafish to cause significant disruptions in photoreceptors and retinal pigment epithelium, together with atrophies of retinal vessels and choriocapillaris. Those phenotypes could not be fully rescued by exogenous wild-type GUCA1A, suggesting a likely gain-of-function mechanism for p.R120L. GUCA1A p.D100E, another mutation previously implicated in cone dystrophy, also impaired the retinal pigment epithelium and photoreceptors in zebrafish, but probably via a dominant negative effect. CONCLUSION: We conclude that GUCA1A mutations could cause significant variability in maculopathies, including central areolar choroidal dystrophy, which represents a severe pattern of maculopathy. The diverse pathogenic modes of GUCA1A mutations may explain the phenotypic diversities.Genet Med advance online publication 26 January 2017.

Exploring the Possibility of a Retrograde Embolism Pathway from the Facial Artery to the Ophthalmic Artery System In Vivo.

BACKGROUND: Blindness caused by soft tissue fillers is an extremely low-probability event, but it results in great concern because of its devastating consequences. Currently, the mechanism of an embolism is usually considered to be an accidental injection of fillers into the blood vessels of the face, such as a facial artery, and then retrograding into the ophthalmic artery system, which causes retinal ischemic necrosis. In addition, previous studies have shown that there are anastomoses between facial arteries and branches of the ophthalmic artery in cadavers. An in vivo study, however, has not yet been reported. METHODS: This study was approved by the institutional review board of Xijing Hospital, Fourth Military Medical University. Under general anesthesia, we dissected the same side of the face and eyeball in rabbits to manifest the facial artery and retina separately. Later, a needle (27 g) connected to a syringe (10 ml) full of methylene blue was inserted into a rabbit facial artery. Then, after poking a tiny hole in the central retinal artery, methylene blue was injected into the facial artery as quickly as possible (0.5 ml per second). At the same time, we carefully observed whether the central retinal artery had dye spillover or staining in the sclera. If blue dye was observed in the eye ground and/or the sclera, then it was thought to have entered the ophthalmic artery system (a positive result). In contrast, if none of the blue dye was observed, it was considered a negative result. A Chi-square (χ 2) test with a fourfold table was used to compare the differences in the frequencies of blue dye observed between living and dead rabbits. A value of p < 0.05 was considered significant. RESULTS: One of the 20 rabbits showed the appearance of blue dye in the ophthalmic artery system in vivo, and the remaining 19 living rabbits had negative results. All 20 of the dead rabbits showed dye appearance in the eye ground. A statistically significant difference existed between the living and dead rabbits (p < 0.05). CONCLUSION: In vivo, fillers can retrogradely enter the ophthalmic artery if the fillers entered the facial artery. Although the possibility is much lower in vivo than it is in corpses, adequate attention should be paid because of the catastrophic complications. LEVEL OF EVIDENCE V: This journal requires that authors assign a level of evidence to each article. 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 .

PRPF4 mutations cause autosomal dominant retinitis pigmentosa.

Retinitis pigmentosa (RP), a disease characterized by progressive loss of photoreceptors, exhibits significant genetic heterogeneity. Several genes associated with U4/U6-U5 triple small nuclear ribonucleoprotein (tri-snRNP) complex of the spliceosome have been implicated in autosomal dominant RP (adRP). HPrp4, encoded by PRPF4, regulates the stability of U4/U6 di-snRNP, which is essential for continuous splicing. Here, we identified two heterozygous variants in PRPF4, including c.-114_-97del in a simplex RP patient and c.C944T (p.Pro315Leu), which co-segregates with disease phenotype in a family with adRP. Both variants were absent in 400 unrelated controls. The c.-114_-97del, predicted to affect two transcription factor binding sites, was shown to down-regulate the promoter activity of PRPF4 by a luciferase assay, and was associated with a significant reduction of PRPF4 expression in the blood cells of the patient. In fibroblasts from an affected individual with the p.Pro315Leu variant, the expression levels of several tri-snRNP components, including PRPF4 itself, were up-regulated, with altered expression pattern of SC35, a spliceosome marker. The same alterations were also observed in cells over expressing hPrp4(Pro315Leu), suggesting that they arose as a compensatory response to a compromised splicing mechanism caused by hPrp4 dysfunction. Further, over expression of hPrp4(Pro315Leu), but not hPrp4(WT), triggered systemic deformities in wild-type zebrafish embryos with the retina primarily affected, and dramatically augmented death rates in morphant embryos, in which orthologous zebrafish prpf4 gene was silenced. We conclude that mutations of PRPF4 cause RP via haploinsufficiency and dominant-negative effects, and establish PRPF4 as a new U4/U6-U5 snRNP component associated with adRP.

Inverted Supernumerary Nostril Together with Tessier 3 Incomplete Cleft: A Rare Congenital Deformity Case Report.

Supernumerary nostril and oblique facial cleft are both rare congenital anomalies. Here, we present a 2-year-old patient with a supernumerary nostril and a Tessier 3 incomplete facial cleft, which have not been reported previously. It should also be mentioned that the nostril and ala of this supernumerary nostril were inverted, which differs from the previous cases. Surgery was undertaken to excise the supernumerary nostril and correct the facial cleft anomaly, and the outcomes were both functionally and aesthetically satisfactory.

Mutation analysis of pre-mRNA splicing genes in Chinese families with retinitis pigmentosa.

PURPOSE: Seven genes involved in precursor mRNA (pre-mRNA) splicing have been implicated in autosomal dominant retinitis pigmentosa (adRP). We sought to detect mutations in all seven genes in Chinese families with RP, to characterize the relevant phenotypes, and to evaluate the prevalence of mutations in splicing genes in patients with adRP. METHODS: Six unrelated families from our adRP cohort (42 families) and two additional families with RP with uncertain inheritance mode were clinically characterized in the present study. Targeted sequence capture with next-generation massively parallel sequencing (NGS) was performed to screen mutations in 189 genes including all seven pre-mRNA splicing genes associated with adRP. Variants detected with NGS were filtered with bioinformatics analyses, validated with Sanger sequencing, and prioritized with pathogenicity analysis. RESULTS: Mutations in pre-mRNA splicing genes were identified in three individual families including one novel frameshift mutation in PRPF31 (p.Leu366fs*1) and two known mutations in SNRNP200 (p.Arg681His and p.Ser1087Leu). The patients carrying SNRNP200 p.R681H showed rapid disease progression, and the family carrying p.S1087L presented earlier onset ages and more severe phenotypes compared to another previously reported family with p.S1087L. In five other families, we identified mutations in other RP-related genes, including RP1 p. Ser781* (novel), RP2 p.Gln65* (novel) and p.Ile137del (novel), IMPDH1 p.Asp311Asn (recurrent), and RHO p.Pro347Leu (recurrent). CONCLUSIONS: Mutations in splicing genes identified in the present and our previous study account for 9.5% in our adRP cohort, indicating the important role of pre-mRNA splicing deficiency in the etiology of adRP. Mutations in the same splicing gene, or even the same mutation, could correlate with different phenotypic severities, complicating the genotype-phenotype correlation and clinical prognosis.

Maternal germline mosaicism of kinesin family member 21A (KIF21A) mutation causes complex phenotypes in a Chinese family with congenital fibrosis of the extraocular muscles.

PURPOSE: To identify the causative mutation with its possible origin in a Chinese family with congenital fibrosis of extraocular muscles type 1 (CFEOM1) and to characterize the ocular phenotypes and lesions in the corresponding intracranial nerves. METHODS: Three affected siblings and their asymptomatic parents underwent comprehensive ophthalmic examinations and neuropathologic analysis involving magnetic resonance imaging (MRI). KIF21A, PHOX2A, and TUBB3 genes were sequenced on the leukocyte-derived DNA to detect variants. The disease-linked haplotype was analyzed using four microsatellite markers across the KIF21A locus. RESULTS: All three affected individuals displayed typical CFEOM1. MRI revealed complicated but consistent neuromuscular abnormalities in the two patients examined, including hypoplastic oculomotor nerves, complete absence of bilateral superior rectus muscles, and unilateral absence of the abducens nerve with marked atrophy of the corresponding lateral rectus muscle. A heterozygous hotspot mutation KIF21A c.2860C>T was identified in all patients, but it was absent in both parents. Haplotype analysis of the disease locus showed the likely maternal inheritance of the disease-associated haplotype to all three affected offspring, strongly suggesting maternal germline mosaicism of the mutation. CONCLUSIONS: Germline mosaicism of KIF21A c.2860C>T is likely to cause the high occurrence of this mutation in the population. This information may be useful for genetic counseling. KIF21A mutations can affect the abducens nerve and cause complete absence of the bilateral superior rectus muscles. MRI characterization of new CFEOM1 phenotypes would assist clinical management.

Dynamic carboxymethyl chitosan prodrug hydrogel precisely mediates robust therapy on wound infection.

Dynamic antibacterial polysaccharide prodrug hydrogels are in great demand for treatment of wound infection owing to their unique advantages such as excellent biocompatibility, superior antimicrobial property as well as favorable wound healing capacity. Herein, this work highlights the successful development of a dynamic carboxymethyl chitosan (CMC) prodrug hydrogel, which is facilely constructed through Schiffer base reaction between antibacterial components (amikacin and CMC) and crosslinker (dialdehyde PEG). Moderate dynamic imine linkages endow the hydrogel with excellent injectable and self-healing capability as well as targeted on-demand drug release in slightly alkaline condition at infected wound. All ingredients and their strong intermolecular interactions endow the hydrogel with favorable swelling and moisture retention capability. Moreover, the covalent and non-covalent interactions also endow the hydrogel with superior adhesion and mechanical property. These attractive characteristics enable hydrogel to effectively kill pathogens, promote wound healing and reduce side effects of amikacin. Thereby, such a dynamic CMC prodrug hydrogel may open a new avenue for a robust therapy on wound infection, greatly advancing their use in clinics.

Two novel mutations of fibrillin-1 gene correlate with different phenotypes of Marfan syndrome in Chinese families.

PURPOSE: To identify the causative mutations in two Chinese families with autosomal dominant Marfan syndrome and to describe the associated phenotypes. METHODS: Complete physical, ophthalmic, and cardiovascular examinations were given to the patients and unaffected individuals in the two families. Exclusive linkage mapping was performed for transforming growth factor beta receptor II (TGFBR2) and fibrillin-1 (FBN1) loci in both families. The entire coding region and flanking splice sites of the FBN1 gene were screened for mutations in the two families with Sanger sequencing. The potential mutations of FBN1 were tested in 100 normal controls. RESULTS: Lens dislocation was observed in two out of ten patients in the MF1 family and all patients in the MF2 family. However, the MF1 family displayed more severe cardiovascular and skeletal system involvement compared with the MF2 family. The transforming growth factor beta receptor II locus was excluded in both families by linkage analysis. A maximum multipoint lod score score of 2.83 was obtained for marker D15S992 (located in the FBN1 gene) in the MF1 family and 1.51 for the same marker in the MF2 family. Two novel mutations of FBN1, p.C271* and p.C637Y, were identified in the MF1 and MF2 families, respectively. CONCLUSIONS: Genotype-phenotype correlations in this study indicate that nonsense mutations of FBN1 may correlate with relatively severe systemic phenotypes when compared with cysteine substitutions, the most common type of FBN1 mutations. Genetic diagnosis for patients with Marfan syndrome would help with genetic counseling, clinical intervention, and prognosis.

[Targeted sequencing identifies a hotspot mutation SNRNP200 p.S1087L correlates with novel phenotypes in retinitis pigmentosa].

OBJECTIVE: To identify the pathogenic mutation in a four-generation Chinese family with autosomal dominant retinitis pigmentosa (ADRP) and to analyze its associated clinical phenotypes. METHODS: Twelve participants from the index family were recruited, including 5 patients, 6 asymptomatic siblings, and one spouse. All participants underwent ophthalmic examinations, including best-corrected visual acuity (BCVA), visual field (VF) testing, fundus photography, and full-field flash electroretinography (ERG). Targeted sequence capture array technique with next-generation of high throughput sequencing(NGS) was performed to detect variants in 189 hereditary retinal disease (HRD) related genes, comprising 179 identified HRD-causing genes and 10 potential causative genes which were involved in pre-messenger RNA(pre-mRNA) splicing. Variants detected by targeted sequencing were filtered by bioinformatic analyses, validated by Sanger sequencing and intra-familiar analysis.Genotype-phenotype correlation was also analyzed. RESULTS: SNRNP200 p.S1087L was identified as the disease causative mutation for this family by targeted sequencing and optimized bioinformatic analyses. This family demonstrated early onset of the disease by presenting nyctalopia among 6 to 8 years old, performed rapid disease progression and severely impaired visual function by displaying loss of VF among 14 to 17 years old and decreased central vision among 21 to 28 years old. The fundus presentations and ERG results showed typical RP presentations. CONCLUSIONS: SNRNP200 p.S1087L is identified as a hotspot mutation but correlates with distinct phenotypes in the present family, including early onset of the disease, rapid disease progression, and severely impaired visual function. This study also give evidence to that molecular diagnostic platform for HRD can improve the detection rate of causative genes/mutations in HRD patients, thus providing important approaches for further investigation of the genetic causes for HRD.

Synthesis of a novel photochemical and thermoresponsive diblock biomaterial with end-functionalized zinc porphyrin.

Porphyrin compound-based photochemical molecules and biomaterials have been synthesized for photosensitivity and bioimaging experiments. However, most porphyrin photosensitizers have limited application in biological environments owing to severe aggregation in aqueous solutions. In the present study, we prepared amphipathic and photosensitive copolymers using zinc porphyrin via consecutive atom transfer-free radical polymerizations (ATRPs) comprising photoresponsive and thermosensitive chain segments. Furthermore, we evaluated the photocatalytic activity of the copolymer for methylene blue (MB) in water. Methods: First, we synthesized a photoresponsive ain segment of poly (6-[4-(4-methoxyphenylazo)phenoxy]hexyl methacrylate) (ZnPor-PAzo); then, ZnPor-PAzo was used as a macroinitiator and was polymerized with N-isopropylacrylamide (NIPAM) via ATRPs to obtain a novel photochemical and thermoresponsive diblock biomaterial with end-functionalized zinc porphyrin [(ZnPor-PAzo)-PNIPAMs]. Results: The polydispersity index (M w/M n) of (ZnPor-PAzo)-PNIPAMs was 1.19-1.32. Furthermore, its photoresponsive and thermosensitive characteristics were comprehensively studied. Discussion: The end-functionalized diblock copolymer (ZnPor-PAzo)-PNIPAM exhibits obvious fluorescence and efficient photocatalytic activity for aqueous MB under visible light.

Microbial Communities and Correlation between Microbiota and Volatile Compounds in Fermentation Starters of Chinese Sweet Rice Wine from Different Regions.

Chinese sweet rice wines (CSRW) are traditional, regionally distinct alcoholic beverages that are generally brewed with glutinous rice and fermentation starters. This study aimed to characterize microbial communities and volatile compounds of CSRW starters and explore correlations between them. The major volatiles in starters include 1-heptanol, 1-octanol, 2-nonanol, phenylethyl alcohol, 2-nonanone, acetophenone, and benzaldehyde. Microbiological analysis based on high-throughput sequencing (HTS) technology demonstrated that starter bacterial communities are dominated by Weissella, Pediococcus, and Lactobacillus, while Saccharomycopsis and Rhizopus predominate in fungal communities. Carbohydrate and amino acid metabolism are the most active metabolic pathways in starters. Spearman correlation analysis revealed that 15 important volatile compounds including alcohols, acids, aldehydes and esters were significantly positively correlated with nine microbial genera (|r| > 0.7, p < 0.05), including five bacterial genera (i.e., Weissella, Pediococcus, Lactobacillus, Bacillus, and Nocardiopsis) and four fungal genera (i.e., Saccharomycopsis, Rhizopus, Wickerhamomyces, and Cyberlindnera), spanning 19 distinct relationships and these microorganisms were considered the core functional microorganisms in CSRW starters. The most important positive correlations detected between phenylethyl alcohol and Weissella or Saccharomycopsis and between 2-nonanol and Pediococcus. This study can serve as a reference to guide the development of defined starter cultures for improving the aromatic quality of CSRW.

Overexpression of Annexin A1 is associated with the formation of capillaries in infantile hemangioma.

Infantile hemangioma is a common benign tumor in infants. However, the molecular mechanism that controls the proliferation and differentiation of hemangioma is not well understood. Annexin A1 (ANX A1) is a phospholipid-binding protein involved in a variety of biological processes, including inflammation, cell proliferation and apoptosis. To explore the significance of ANX A1 in the process of proliferation or differentiation of hemangioma, proliferating and involuting hemangioma tissues were collected to detect the expression of ANX A1 using immunohistochemistry and western blotting. Normal skin tissues were used as the negative control. The results revealed that ANX A1 was upregulated in the proliferative phase of hemangioma, and its expression was decreased when the hemangioma entered the involuting phase. Additionally, in the proliferative phase, the strongest staining of ANX A1 was observed in newly born capillaries, and the staining of ANX A1 became weaker in enlarged vessels, indicating that ANX A1 plays an important role in promoting the formation of capillaries. The expression of hypoxia-inducible factor (HIF)-1α was positively associated with the expression trend of ANX A1, suggesting that the overexpression of ANX A1 may be associated with the increase of HIF-1α. In summary, the results of the present study revealed that the expression of ANX A1 was increased in proliferating hemangioma tissue, and that high expression of ANX A1 may be closely associated with the formation of capillaries in infantile hemangioma.

Chestnuts in Fermented Rice Beverages Increase Metabolite Diversity and Antioxidant Activity While Reducing Cellular Oxidative Damage.

Foods containing chestnuts (Castanea mollissima Blume) are relatively uncommon, despite the high nutrient and starch contents and purported health benefits. In this study, we examine the flavor-related metabolites, volatile compounds, and amino acids in a traditional glutinous rice fermented beverage supplemented with chestnuts as a fermentation substrate for lactic acid bacteria (LAB). Changes in antioxidant activity towards free radicals and effects on cellular oxidative stress are compared between beverages with or without chestnuts. The fermented chestnut-rice beverage (FCRB) has higher sensory scores and a wider range of volatiles and flavor-related compounds (74 vs. 38 species compounds), but lower amino acid contents, than the traditional fermented glutinous rice beverage (TFRB). In free radical scavenging assays, the FCRB exhibits higher activity than the TFRB in vitro. Furthermore, while neither beverage induces cytotoxity in Caco-2 cells at concentrations up to 2 mg/mL, pretreatment with the FCRB results in lower rates of apoptosis and necrosis and higher overall viability in cells with H2O2-induced oxidative stress compared to pretreatment with the TFRB. The enhanced reactive oxygen species neutralization in vitro and protection against oxidative damage in cells, coupled with increased diversity of volatiles and flavor-related metabolites of LAB, support the addition of chestnuts to enhance flavor profile and antioxidant properties of fermented functional foods.

MOF(Fe)-derived composites as a unique nanoplatform for chemo-photodynamic tumor therapy.

Fe-based metal-organic frameworks (MOFs) can be used for chemodynamic therapy (CDT) for tumors due to their unique Fenton-like effects and porous and biodegradable nature. The adsorption and transport of small molecule drugs by their structure has attracted much attention. Herein, MnO2@NH2-MIL101(Fe)@Ce6-F127 nanoparticles (MNMCF NPs) were synthesized using a facile solvothermal strategy. The small molecule photosensitizer Ce6 was adsorbed by MOFs to improve the biocompatibility of Ce6 and give it high bioavailability when injected intravenously. When the MNMCF NPs reached the tumor site, Fe-based MOFs exhibited Fenton-like properties, producing ˙OH and showing CDT effects. MnO2 could specifically respond to produce O2 in a tumor microenvironment, thereby improving the tumor hypoxia state and enhancing the efficacy of photodynamic therapy (PDT) by Ce6. Both the in vitro and in vivo experiments showed that the MNMCF-guided CDT/PDT combination therapy could effectively ablate tumors without the drawbacks of poor tolerability and potential long-term side effects. Therefore, the prepared MNMCF NPs can be used as promising candidates for synergistic CDT/PDT tumor therapy.