Single-cell sequencing reveals the new existence form of dermal papilla cells in the hair follicle regeneration of cashmere goats.

The problem of human hair loss has caused widespread concern, however, such research is difficult because the periodicity is not obvious and the deeper levels knowledge of dermal papilla (DP) stem cells' differentiation are limited. Here, cashmere goats which have obvious periodicity of hair follicles were used, based on unbiased scRNA sequencing, we constructed DP cell lineage differentiation trajectory and revealed the key genes, signals and functions involved in cell fate decisions. And then we revealed the molecular landscape of hair follicle on regeneration. Revealed that DP cells differentiate into four intermediate cell states at different periodicity: Intermediate-cell-10 showed important functions in the growth and maintenance of cashmere; intermediate-cell-1 acting on apoptosis and cashmere shedding; intermediate-cell-0 initiated new follicular cycles, the migration of hair follicles and the occurrence of cashmere; and intermediate-cell-15 are suggested to be DP progenitor cells. In general, we provide new insights for hair regrowth. At the same time, it provides a new research ideas, directions and molecular landscape for the mechanism of dermal papilla cells.

Role of bilirubin in the prognosis of coronary artery disease and its relationship with cardiovascular risk factors: a meta-analysis.

BACKGROUND: Bilirubin is a heme catabolism product with antioxidant, anti-inflammatory, and anti-apoptotic properties and is implicated in the prognosis of several diseases. This study evaluates the prognostic role of bilirubin in coronary artery disease (CAD) patients. METHODS: After identifying studies from the literature, meta-analyses were performed to achieve a) overall estimates of serum total bilirubin levels in patients with myocardial infarction (MI), non-MI CAD and healthy individuals; b) odds ratios (OR) of adverse outcomes between higher and lower total bilirubin levels; c) standardized mean difference (SMD) in total bilirubin levels in patients with high vs low CAD severity; and d) correlation between disease severity and total bilirubin. Metaregression analyses were performed to examine the relationship between cardiovascular risk factors and increasing quantiles of total bilirubin levels. RESULTS: Forty-three studies were identified. Pooled serum total bilirubin levels were 0.72 mg/dl [95% confidence interval (CI): 0.60, 0.83] in MI patients; 0.65 mg/dl [95% CI: 0.60, 0.69] in non-MI CAD patients; and 0.66 mg/dl [95% CI: 0.56, 0.75] in healthy individuals. Higher total bilirubin levels were associated with greater odds of adverse outcomes in MI patients (OR: 1.08 [95% CI: 0.99, 1.18]) but lower odds in non-MI CAD patients (OR: 0.80 [95%CI: 0.73, 0.88]). Compared to non-severe cases, total bilirubin levels were higher in patients with severe MI (SMD 0.96 [95% CI: - 0.10, 2.01]; p = 0.074) but were lower in severe non-MI CAD patients (SMD - 0.30 [95%CI: - 0.56, - 0.03]; p = 0.02). Total bilirubin levels correlated positively with MI severity (r = 0.41 [95% CI: 0.24, 0.59]; p < 0.01) but correlated negatively with non-MI CAD severity (r = - 0.17 [95% CI: - 0.48, 0.14]; p = 0.28). Female sex was inversely associated with increasing quantiles of bilirubin (meta-regression coefficient: - 8.164 [- 14.531, - 1.769]; p = 0.016) in MI patients. CONCLUSION: Prognostic role of bilirubin for CAD appears complicated, as different odds are observed for MI and non-MI CAD patients which weakens the case of causal involvement of bilirubin in CAD etiology or prognosis.

Ellipinema and ×Ellipisorus? Just Lepisorus (Polypodiaceae)!

The establishment of a segregate lepisoroid fern genus Ellipinema was mainly to accommodate the isolated position of Lepisorus jakonensis (Polypodiaceae) recovered in plastid gene tree. Using newly obtained nuclear data, we recovered that Ellipinema and allied genera, such as Lepidomicrosorium, Lemmaphyllum, Neolepisorus, Paragramma, Tricholepidium and Weatherbya are deeply nested within Lepisorus. The nuclear phylogeny showing incongruent phylogenetic placement in comparison with plastid results perhaps indicated ancient hybridization events. The diagnostic morphology characterizing Ellipinema - elliptic scale-like paraphyses, which is shared by all the taxa of sect. Lepisorus and sect. Hymenophyton - falls within the range of continuous variation in the type species Ellipinema jakonense (=Lepisorus jakonensis). Our study, which integrated molecular and morphological data, demonstrates that the segregation of Ellipinema and ×Ellipisorus (= ×Lepinema Li Bing Zhang & Liang Zhang, nom. illeg.) from Lepisorus should be rejected.

Plastid phylogenomics provides novel insights into the infrafamilial relationship of Polypodiaceae.

The polygrammoids (Polypodiaceae) are the most species-rich and diversified epiphytic fern lineages, and hold an important role to understand the deep diverging events and rapid adaptation to changing environments in the plant tree of life. Despite progress in the phylogeny of this group of ferns in previous multilocus phylogenetic studies, uncertainty remains especially in backbone relationships among closely related clades, and the phylogenetic placement of recalcitrant species or lineages. Here, we investigated the deep phylogenetic relationships within Polypodiaceae by sampling all major lineages and using 81 plastid genomes (plastomes), of which 70 plastomes were newly sequenced with high-throughput sequencing technology. Based on parsimony, maximum-likelihood, Bayesian and multispecies coalescent analyses of genome skimming data, we achieved a better resolution of the backbone phylogeny of Polypodiaceae. Using simulated data matrices, we detected that potential phylogenetic artefacts, such as long-branch attraction and insufficient taxonomic sampling, may have a confounding impact on the incongruence of phylogenetic inferences. Furthermore, our phylogenetic analyses offer greater resolution than previous multilocus studies, providing a robust framework for future phylogenetic implications on the subfamilial taxonomy of Polypodiaceae. Our phylogenomic study not only demonstrates the advantage of a character-rich plastome dataset for resolving the recalcitrant lineages that have undergone rapid radiation, but also sheds new light on integrative explorations understanding the evolutionary history of large fern groups in the genomic era.

Backbone phylogeny of Lepisorus (Polypodiaceae) and a novel infrageneric classification based on the total evidence from plastid and morphological data.

The fern genus Lepisorus represents one of the most complicated and controversial lineages in Polypodiaceae, with about 80 species which have been classified into several separate genera, and is notorious for its taxonomic difficulty. Despite progress in recent phylogenetic studies of the family Polypodiaceae involving Lepisorus and its allies, the deep phylogenetic relationship within this group of ferns is still unresolved, and no formal infrageneric classification has been proposed. This contribution presents the most comprehensive phylogenetic analysis of the genus, with 72% species sampled, using a total-evidence approach based on eight plastid markers and ≤25 morphological characters for each species. The analyses resolve the backbone relationship and yield the most robust phylogenetic framework to date. Congruent with previous studies but with new findings, the results herein show that Lepisorus is monophyletic when Neolepisorus, Lemmaphyllum, Tricholepidium, Neocheiropteris and Lepidomicrosorium are included, as well as Lepisorus jakonensis and Paragramma. Furthermore, 17 well-resolved clades are found in the phylogenetic topology, which can be characterized by morphological synapomorphies from traits of rhizome scales, laminae, sori and paraphyses. Based on molecular and morphological evidence, a new infrageneric classification system of Lepisorus is proposed which subdivided Lepisorus into 17 sections.

Corrigendum of Zhao et al. (2020): a revised infrageneric classification of Lepisorus (Polypodiaceae).

Here, we publish Lepisorus sect. Paragramma (Blume) C.F. Zhao, R. Wei & X.C. Zhang as a combinatio nova to replace the section name in Zhao et al. (2020), which was published as a status nova and turned out to be an invalid name, because we cited an incorrect basionym. A revised infrageneric classification of Lepisorus also is proposed.

Effects of photoperiod on nutrient digestibility, hair follicle activity and cashmere quality in Inner Mongolia white cashmere goats.

OBJECTIVE: This study investigated the effects of photoperiod on nutrient digestibility, hair follicle (HF) activity and cashmere quality in Inner Mongolia white cashmere goats. METHODS: Twenty-four female (non-pregnant) Inner Mongolia white cashmere goats aged 1 to 1.5 years old with similar live weights (mean, 20.36±2.63 kg) were randomly allocated into two groups: a natural daily photoperiod group (NDPP group:10 to 16 h light, n = 12) and a short daily photoperiod group (SDPP group: 7 h light:17 h dark, n = 12). All the goats were housed in individual pens and fed the same diets from May 15 to October 15, 2015. The digestibility of crude protein (CP), dry matter (DM), and neutral detergent fiber (NDF) were measured in different months, along with secondary hair follicle (SHF) activity, concentration of melatonin (MEL), and cashmere quality. RESULTS: Although there was no significant difference in the live weights of goats between the SDPP and NDPP groups (p>0.05), the CP digestibility of goats in the SDPP group was significantly increased compared to the NDPP group in July, September, and October (p<0.05). For the DM and NDF digestibility of goats, a significant increase (p<0.05) was found during in September in the SDPP group. Furthermore, compared to the NDPP group, the SHF activity in July, the MEL concentration in July, and the cashmere fiber length and fiber weight in October were significantly increased in the SDPP group (p<0.05). CONCLUSION: The cashmere production of Inner Mongolia white cashmere goats was increased without obvious deleterious effects on the cashmere fibers in the SDPP group (metabolizable energy, 8.34 MJ/kg; CP, 11.16%; short daily photoperiod, 7 h light:17 h dark).

[Schizophrenia-associated single nucleotide polymorphisms affecting microRNA function].

MicroRNAs (miRNAs) compose a class of non-coding transcripts with a mean length of 22 nucleotides, and play critical roles in regulating gene expression in the process of development, proliferation and differentiation of neurons. Recent genome-wide association studies (GWAS) find most of schizophrenia-associated single nucleotide polymorphisms (SNPs) locating in the non-coding regions, providing functional implications of miRNAs in the development of schizophrenia. In this review, we highlight the interplays between GWAS-SNPs and miRNAs in four perspectives: SNP in miRNA gene; miRNA located in the host gene; SNP located in the miRNA's seed sequence; SNP located in the miRNA's binding site. We also speculate on the future research on the role of miRNA in the development of schizophrenia.

A total-evidence phylogeny of the lady fern genus Athyrium Roth (Athyriaceae) with a new infrageneric classification.

The lady fern genus Athyrium represents one of the most diversified lineages in Athyriaceae with about 160-220 known species, and is notorious for its taxonomic difficulty. Despite progress in recent phylogenetic studies involving this genus, it still lacks a modern systematic and taxonomic update using integrative analyses of molecular and morphological evidence based on a broad species sampling. Here, we present, to our knowledge, the most comprehensive phylogenetic analysis of the genus to date based on a total-evidence approach, covering all formerly accepted segregates within the athyrioid ferns. We sampled up to eight plastid markers and 20 morphological characters for each species. Our analyses, including maximum parsimony, maximum likelihood and Bayesian inference, yield a robust phylogenetic framework. We find that Athyrium is not monophyletic by recovering Athyrium skinneri and A. alpestre nested with Anisocampium and Cornopteris respectively while Pseudocystopteris is included in Athyrium. Furthermore, eight well-resolved clades and two isolated species within Athyrium are found in the phylogenetic topology, which can be also characterized by morphological synapomorphies from traits of petioles, leaves, sori and spores. In the interest of recognizing monophyletic taxa with morphological synapomorphies, we agree with the inclusion of Pseudocystopteris in Athyrium as proposed in previous studies, but treat Anisocampium and Cornopteris as separate genera. We further propose to resurrect a monotypic Pseudathyrium to accommodate A. alpestre. Based on morphological characters and molecular phylogeny, a new infrageneric classification system of Athyrium is proposed which subdivided it into ten sections, and one New-World species A. skinneri is transferred into Anisocampium.

Interleukin-6 as a Predictor of the Risk of Cardiovascular Disease: A Meta-Analysis of Prospective Epidemiological Studies.

OBJECTIVE: The etiology of cardiovascular disease (CVD) is complex owing to the interactions of genetic variance with environmental factors. Inflammatory processes are now being increasingly implicated in the pathogenesis of CVD. This meta-analysis investigated the potential role of interleukin-6 (IL-6) as a risk factor for CVD development in healthy individuals. METHODS: Literature search was carried out in multiple electronic databases, and study selection followed a priori eligibility criteria. Meta-analyses of standardized mean differences were carried out to determine an overall effect size of the difference in IL-6 levels between CVD cases and non-CVD matched controls. Meta-regression analyses were performed to examine the relationship between the IL-6 levels in CVD cases and several explanatory variables. RESULTS: Seventeen studies enrolling 288738 healthy individuals with an average follow-up duration of 7.4 ± 4.1 years were found eligible. Overall, data of 5400 CVD cases and 14607 matched non-CVD controls are used in the present meta-analysis. Baseline IL-6 levels were significantly higher in CVD cases than in non-CVD controls (standardized mean difference [95% confidence interval]) of 0.14 [0.09, 0.20]/mean difference of 0.36 [0.28, 0.44] picogram per milliliter). Total cholesterol, LDL-cholesterol, and triglyceride levels were also significantly higher, and HDL-cholesterol levels were significantly lower in CVD cases in comparison with the controls. Systolic blood pressure and total cholesterol levels had a significantly positive relationship, whereas triglyceride levels had a significantly inverse relationship with the levels of IL-6. CONCLUSION: Higher IL-6 levels in healthy individuals are associated with CVD risk, which is co-associated with hypertension and hypercholesterolemia.

Knockdown of CTRP6 inhibits adipogenesis via lipogenic marker genes and Erk1/2 signalling pathway.

C1q/tumor necrosis factor-related protein 6 (CTRP6), an adipose-tissue secretory factor, plays an important role in inflammatory reaction and carcinogenesis. However, the biological function of CTRP6 in adipogenesis remains unclear. In this study, we examined the effects of CTRP6 knockdown on lipogenesis of 3T3-L1 adipocytes. The results showed that after 3T3-L1 adipocytes transfected with anti-CTRP6 small interfering RNA (siRNA), not only levels of secreted CTRP6 protein in the culture medium but also the expression level of the CTRP6 protein in the 3T3-L1 adipocytes was significantly reduced (P < 0.01). In addition, the number of lipid droplets in the adipocytes was reduced, as well as the OD values reflecting the fat content being significantly decreased (P < 0.01). Meanwhile the levels of adipogenic markers, including peroxisome proliferator activated receptor γ (PPARγ), CCAAT/enhancer-binding protein α (C/EBPα), CCAAT/enhancer-binding protein ß (C/EBPß) and adipocyte fatty acid-binding protein 4 (aP2), were decreased after treatment with anti-CTRP6 siRNA, whereas the expression of adipose triglyceride lipase (ATGL) and triacylglycerol hydrolase (TGH) were increased. Furthermore, after transfection, activity of phosphorylated Erk1/2 (p-Erk1/2) was inhibited in the early stage of differentiation, but in terminal differentiation of adipocytes, its activity was activated. Taken together, the results indicate that knockdown of CTRP6 can inhibit adipogenesis of 3T3-L1 adipocytes through lipogenic marker genes and Erk1/2 signaling pathway.

DNA hypermethylation and X chromosome inactivation are major determinants of phenotypic variation in women heterozygous for G6PD mutations.

Glucose-6-phosphate dehydrogenase (G6PD) deficiency is an X-linked incompletely dominant enzyme deficiency that results from G6PD gene mutations. Women heterozygous for G6PD mutations exhibit variation in the loss of enzyme activity but the cause of this phenotypic variation is unclear. We determined DNA methylation and X-inactivation patterns in 71 G6PD-deficient female heterozygotes and 68 G6PD non-deficient controls with the same missense mutations (G6PD Canton c.1376G>T or Kaiping c.1388G>A) to correlate determinants with variable phenotypes. Specific CpG methylations within the G6PD promoter were significantly higher in G6PD-deficient heterozygotes than in controls. Preferential X-inactivation of the G6PD wild-type allele was determined in heterozygotes. The incidence of preferential X-inactivation was 86.2% in the deficient heterozygote group and 31.7% in the non-deficient heterozygote group. A significant negative correlation was observed between X-inactivation ratios of the wild-type allele and G6PD/6-phosphogluconate dehydrogenase (6PGD) ratios in heterozygous G6PD Canton (r=-0.657, p<0.001) or Kaiping (r=-0.668, p<0.001). Multivariate logistic regression indicated that heterozygotes with hypermethylation of specific CpG sites in the G6PD promoter and preferential X-inactivation of the wild-type allele were at risk of enzyme deficiency.

Effects of UV/H2O2 degradation on Moringa oleifera Lam. leaves polysaccharides: Composition, in vitro fermentation and prebiotic properties on gut microorganisms.

Moringa oleifera Lam. leaves are a new raw food material rich in polysaccharides. These polysaccharides exhibit various biological properties, including antioxidant, hypoglycemic and immunoregulatory effects. However, the use of Moringa oleifera Lam. leaves polysaccharides (MOLP) may be limited by their large molecular weight (MW) and presence of numerous impurities, such as pigments. Research has indicated that degraded polysaccharides usually exhibit high biological activity because of changes in physical structure and chemical properties. In this study, we focused on the extraction of a degraded-modified fraction from MOLP using the Ultraviolet/ Hydrogen peroxide (UV/H2O2) method. Specifically, the physicochemical properties and glycosidic bond composition of a particular fraction (UV/H2O2 degraded Moringa oleifera Lam. leaves polysaccharides in 3 h called DMOLP-3) were investigated. In addition, in vitro simulated digestion experiments showed that DMOLP-3 was only partially degraded during gastrointestinal digestion, indicating that DMOLP-3 can be utilised by gut microorganisms. Furthermore, the prebiotic properties of MOLP and DMOLP-3 was studied using an in vitro faecal fermentation model. The results indicated that compared with MOLP, DMOLP-3 led to a decrease in both the colour and MW of the polysaccharides. In addition, this model exhibited enhanced solubility and antioxidant capabilities while also influencing the surface morphology. Moreover, DMOLP-3 can facilitate the proliferation of advantageous microorganisms and enhance the synthesis of short-chain fatty acids (SCFAs). These results provide valuable insights into the utilization of bioactive components in Moringa oleifera Lam. leaves for the intestinal health.

Tripartite motif-containing 9 promoted proliferation and migration of bladder cancer cells through CEACAM6-Smad2/3 axis.

Studies have shown that tripartite motif-containing (TRIM) family proteins function as E3 ubiquitin ligases and play essential roles in cancer biology. In the present study, we validated a contribution of TRIM9 to bladder cancer progression. 296 patients derived from The Cancer Genome Atlas (TCGA) database and 22 clinical specimens were included, in which accumulated TRIM9 correlated with the poor prognosis and higher relapse in bladder patients. In vitro, TRIM9 promoted bladder cancer cells Biu-87 and T24 cell proliferation and migration. Meanwhile, overexpression of TRIM9 reduced the chemosensitivity in Biu-87 and T24 to mitomycin C (MMC) and gemcitabine (GEM). As an underlying mechanism, we found that TRIM9 stimulated carcinoembryonic antigen 6 (CEACAM6) upregulation, which further facilitated Smad2/3-matrix metalloproteinase 2 (MMP2) signaling activation both in vitro and in vivo. Those results indicated that TRIM9 facilitated bladder cancer development and chemoresistance by CEACAM6-Smad2/3 axis. TRIM9 and its associated molecules could be a potential diagnostic indicator and therapeutic target in bladder cancer.

Recent developments in Moringa oleifera Lam. polysaccharides: A review of the relationship between extraction methods, structural characteristics and functional activities.

Moringa oleifera Lam. (M. oleifera Lam) is a perennial tropical deciduous tree that belongs to the Moringaceae family. Polysaccharides are one of the major bioactive compounds in M. oleifera Lam and show immunomodulatory, anticancer, antioxidant, intestinal health protection and antidiabetic activities. At present, the structure and functional activities of M. oleifera Lam polysaccharides (MOPs) have been widespread, but the research data are relatively scattered. Moreover, the relationship between the structure and biological activities of MOPs has not been summarized. In this review, the current research on the extraction, purification, structural characteristics and biological activities of polysaccharides from different sources of M. oleifera Lam were summarized, and the structural characteristics of purified polysaccharides were focused on this review. Meanwhile, the biological activities of MOPs were introduced, and some molecular mechanisms were listed. In addition, the relationship between the structure and biological activities of MOPs was discussed. Furthermore, new perspectives and some future research of M. oleifera Lam polysaccharides were proposed in this review.

Antifatigue Effect of Panax Notoginseng Leaves Fermented With Microorganisms: In-vitro and In-vivo Evaluation.

Fatigue is a common physiological phenomenon caused by many complicated factors. Excessive fatigue will lead to a series of uncomfortable reactions and damage body health. Panax notoginseng leaves (PNL) is a new resource food that good for soothing nerves, nourishing the heart, and strengthening the spleen. Microbial fermentation could increase the content of bio-ingredients and produce new active ingredients. However, the effect of fermented P. notoginseng leaves (FPNL) on antifatigue and the molecular mechanisms remain to be elucidated. Thus, in this study, we evaluated the antifatigue effect of co-fermented P. notoginseng leaves by Saccharomyces cerevisiae and Bacillus subtilis in-vitro and in-vivo, and its mechanism was further elucidated. The results showed that FPNL exhibited higher saponins, organic phenolic acids content, and antioxidant activity than PNL. FPNL improved ISO-induced H9c2 myocardial cell damage by alleviating apoptosis (modulating Bax and Bcl-2 protein expression) and reducing antioxidant activity in-vitro. Moreover, in-vivo experiment showed that FPNL significantly prolonged the weight-loading swimming time of mice. After gavaged FPNL, the levels of liver glycogen (LG) and serum lactate dehydrogenase (LDH) activity were increased in mice. In contrast, the levels of blood urea nitrogen (BUN), lactate acid, and malondialdehyde (MDA) were decreased. In summary, our results indicated that FPNL showed a good antifatigue effect in-vivo and in-vitro.

Identification of body size characteristic points based on the Mask R-CNN and correlation with body weight in Ujumqin sheep.

The measurements of body size data not only reflect the physical fitness, carcass structure, excellent growth condition, and developmental relationship among tissues and organs of animals but are also critical indicators to measure the growth and development of sheep. Computer vision-based body size identification is a non-contact and stress-free method. In this study, we analyzed different body size traits (height at wither, body slanting length, chest depth, chest circumference, shank circumference, hip height, shoulder width, and rump width) and the body weight of 332 Ujumqin sheep and significant correlations (P < 0.05) were obtained among all traits in Ujumqin sheep. Except for shoulder width, rump width, and shank circumference, all were positively correlated, and the effect of sex on Ujumqin sheep was highly significant. The main body size indexes affecting the body weight of rams and ewes were obtained through stepwise regression analysis of body size on body weight, in order of chest circumference, body slanting length, rump width, hip height, height at wither, and shoulder width for rams and body slanting length, chest circumference, rump width, hip height, height at wither and shoulder width for ewes. The body slanting length, chest circumference, and hip height of ewes were used to construct prediction equations for the body weight of Ujumqin sheep of different sexes. The model's prediction accuracy was 83.9% for the rams and 79.4% for ewes. Combined with a Mask R-CNN and machine vision methods, recognition models of important body size parameters of Ujumqin sheep were constructed. The prediction errors of body slanting length, height at wither, hip height, and chest circumference were ~5%, chest depth error was 9.63%, and shoulder width, rump width, and shank circumference errors were 14.95, 12.05, and 19.71%, respectively. The results show that the proposed method is effective and has great potential in precision management.

Identification of key pathways and genes that regulate cashmere development in cashmere goats mediated by exogenous melatonin.

The growth of secondary hair follicles in cashmere goats follows a seasonal cycle. Melatonin can regulate the cycle of cashmere growth. In this study, melatonin was implanted into live cashmere goats. After skin samples were collected, transcriptome sequencing and histological section observation were performed, and weighted gene co-expression network analysis (WGCNA) was used to identify key genes and establish an interaction network. A total of 14 co-expression modules were defined by WGCNA, and combined with previous analysis results, it was found that the blue module was related to the cycle of cashmere growth after melatonin implantation. Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway enrichment analysis showed that the first initiation of exogenous melatonin-mediated cashmere development was related mainly to the signaling pathway regulating stem cell pluripotency and to the Hippo, TGF-beta and MAPK signaling pathways. Via combined differential gene expression analyses, 6 hub genes were identified: PDGFRA, WNT5A, PPP2R1A, BMPR2, BMPR1A, and SMAD1. This study provides a foundation for further research on the mechanism by which melatonin regulates cashmere growth.

Comparison of porcine milk microRNA expression in milk exosomes versus whole swine milk and prediction of target genes.

Milk exosomal microRNAs (miRNAs) are important for postnatal growth and immune system maturation in newborn mammals. The functional hypothesis of milk exosomal miRNAs and their potential bioavailability in milk to newborn mammals were investigated. Briefly, 37 exosomal miRNAs were upregulated compared to miRNAs found outside the exosomes. Among these miRNAs, ssc-miR-193a-3p expression was upregulated 1467.35 times, while ssc-miR-423-5p, ssc-miR-551a, ssc-miR-138, ssc-miR-1 and ssc-miR-124a were highly concentrated and upregulated 13.58-30.06 times. Moreover, these miRNAs appeared to be relevant for cell development and basic physiological processes of the immune system. Following the analysis of target gene prediction and related signalling pathways, 9262 target genes were mainly concentrated in three signalling pathways: metabolic pathways, pathways in cancer, and phosphatidylinositol 3-kinase/protein kinase B (PI3K/Akt) signalling pathways. Among 9262 target genes, more than 20 miRNAs were enriched in exosomes, such as methyl CpG binding protein 2 (MECP2) and glycogen synthase 1 (GYS1). After determining the miRNA localization-, distribution- and function-related metabolism, we found that these exosomes were specifically concentrated miRNA target genes and they were interrelated with cell development and basic cell functions, such as metabolism and immunity. It is speculated that miRNAs in milk can influence offspring via milk exosomes.

Astragalin Inhibits the Proliferation and Migration of Human Colon Cancer HCT116 Cells by Regulating the NF-κB Signaling Pathway.

Astragalin is a flavonoid found in a variety of natural plants. It has anti-inflammatory, anti-oxidant effects and has inhibited effects against several malignant tumor cell types. However, its effects on colon cancer and the molecular mechanisms have remained to be elucidated. In this study, we evaluated the inhibitory effect of astragalin on proliferation and migration of human colon cancer HCT116 cells in vitro and in vivo. Furthermore, we elucidated the mechanism of these effects. The results showed that astragalin significantly inhibited the proliferation and diffusion of HCT116 cells by induced apoptosis (by modulation of Bax, Bcl-2, P53, caspase-3, caspase 6, caspase 7, caspase 8, caspase 9 protein express) and cell cycle arrest (by modulation of Cyclin D1, Cyclin E, P21, P27, CDK2, CDK4 protein express). Moreover, astragalin suppressed HCT116 cell migration by inhibiting the expression of matrix metalloproteinases (MMP-2, MMP-9). In addition, astragalin significantly downregulated the expression of key proteins in the NF-κB signaling pathway and inhibited the transcriptional activity of NF-κB P65 stimulated with inflammatory cytokines TNF-α, thereby inhibiting the growth of colon cancer cells in vitro. Our further investigations unveiled astragalin gavage significantly reduced the proliferation of colon cancer xenograft in nude mice, in vivo experiments showed that tumor growth was related to decreased expression of apoptotic proteins in tumor tissues and decreased activity of the NF-κB signaling pathway. In summary, our results indicated that astragalin inhibits the proliferation and growth of colon cancer cells in vivo and in vitro via the NF-κB pathway. Therefore, astragalin maybe become a potential plant-derived antitumor drug for colon cancer.