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•A general strategy for prepared multifunction double-ions agarose hydrogel dressing with interconnected pores is provided.•A new multifunctional double-ions macro-porous agarose ...hydrogel dressing was proposed.•It shows effectively antibacterial, and promoted tissue regeneration, accelerated wound healing.
In this study, a new multifunctional double-ions macro-porous agarose hydrogel dressing is proposed, which successfully loaded Ag+ and Li+ simultaneously through the interaction of hydrogen bonds on carboxymethyl agarose (CMA) molecular chains and the interaction of carboxymethyl with metal ions. The macro-porous double-ions hydrogel dressing shows excellent biocompatibility, water-absorbing and water retention capabilities, as well as pH and temperature response characteristics. Moreover, Ag+ ions can be released in the early stage of treatment and Li+ ions can be released steadily and controlled for a long time throughout the treatment, which contributed to effectively antibacterial, and promote tissue regeneration, accelerate wound healing. Significantly, this work provides a general strategy for prepared multifunction double-ions hydrogel dressing with interconnected pores, not limited only to Ag+ and Li+ double-ions, but also Ag+ and Cu2+ double-ions, and Li+ and Cu2+ double-ions, and so on. Thus, the multifunction double-ions hydrogel exhibits a great potential in becoming an effective, efficient and economical wound management dressing. Moreover, this work presents a promising strategy in providing the agarose hydrogel wound dressing to achieve personalized customization ideas.
Bone marrow mesenchymal stem cells (BMSCs) are widely used for therapeutic applications in tissue engineering and regenerative medicine. Nevertheless, the function of BMSCs is adversely affected by ...senescence. Thus, understanding the molecular mechanisms that contribute to BMSC senescence is critical for the development of BMSC-based tissue engineering and regenerative medicine. In this study, senescent BMSCs were characterized with >80 % of BMSCs stained positive for SA-β-gal, increased expressions of senescence-related genes (p16INK4a and p21Waf1). These senescent characters were accompanied by elevated autophagic activity, up-regulation of interleukin 6 (IL-6), IL-8, and FoxO3a. Autophagic activity inhibition alleviated the senescent state with reduced levels of IL-6 and IL-8 during BMSC senescence. The enhanced autophagic activity upregulated the levels of IL-6 and IL-8 which is associated with up-regulation of FoxO3a, and knockdown of FoxO3a reduced IL-6 and IL-8 expression in senescent BMSCs. Therefore, this study indicated the pivotal role of autophagic activity in the expressions of IL-6 and IL-8 during BMSC senescence, which is regulated by FoxO3a.
•Autophagy affects the progression of BMSC senescence.•Autophagic activity modulates the levels of IL-6 and IL-8 during BMSC senescence.•FoxO3a plays a critical role in the expression of IL6 and IL8 that allows autophagy to enhance senescent phenotype of BMSCs.
Maternal obesity induces placental dysfunction and intestinal microbial dysbiosis. However, the associations between intestinal microbiota and placental dysfunction are still unclear. In the present ...study, a gilt model was used to investigate the role of maternal obesity on placental oxidative stress, mitochondrial function, and fecal microbiota composition, meanwhile identifying microbiota markers associated with placental oxidative stress. Twenty gilts were divided into two groups based on their backfat thickness on parturition day: namely Con group (average backfat thickness = 33 mm), and Obese group (average backfat thickness = 39 mm). The results showed that Obese group was lower than Con group in the birth weight of piglets. Compared with the Con group, the Obesity group exhibited an increased oxidative damage and inflammatory response in placenta, as evidenced by the increased concentrations of placental reactive oxygen species (ROS), protein carboxyl, and interleukin-6 (IL-6). Obesity group was lower than Con group in the concentrations of placental adenosine triphosphate, citrate synthase, and complex I activity. In addition, lower propionate level and Bacteroidetes abundance in feces were seen in the Obese Group. Furthermore, the concentrations of placental ROS, protein carboxyl, and IL-6 were positively correlated with the abundance of
Christensenellaceae_
R-7_group and negatively correlated with that of
norank_f_Bacteroidales
_S24-7_group. In conclusion, these findings suggest that maternal obesity might impair oxidative and inflammatory response in placenta through modulating intestinal microbiota composition.
Aberrant placental angiogenesis is associated with fetal intrauterine growth restriction (IUGR), but the mechanism underlying abnormal placental angiogenesis remains largely unknown. Here, lower ...vessel density and higher expression of NADPH oxidases 2 (Nox2) were observed in the placentae for low birth weight (LBW) fetuses versus normal birth weight (NBW) fetuses, with a negative correlation between Nox2 and placental vessel density. Moreover, it was revealed for the first time that Nox2 deficiency facilitates angiogenesis in vitro and in vivo, and vascular endothelial growth factor-A (VEGF-A) has an essential role in Nox2-controlled inhibition of angiogenesis in porcine vascular endothelial cells (PVECs). Mechanistically, Nox2 inhibited phospho-signal transducer and activator of transcription 3 (p-STAT3) in the nucleus by inducing the production of mitochondrial reactive oxygen species (ROS). Dual-luciferase assay confirmed that knockdown of Nox2 reduces the expression of VEGF-A in an STAT3 dependent manner. Our results indicate that Nox2 is a potential target for therapy by increasing VEGF-A expression to promote angiogenesis and serves as a prognostic indicator for fetus with IUGR.
In this study, one-dimensional copper oxide nanorods (CuO NRs) as new type anticancer particles were synthesized by hydrothermal method along with sonication. Afterward, the biological properties of ...synthesized CuO NRs against murine B16F10 melanoma with high metastatic potential and normal fibroblast cell line (3 T3)were evaluated. XRD pattern of synthesized CuO NRs revealed a crystalline structure and FT-IR study disclosed that bands at 438–607 cm−1 and 1010 cm−1 are typically associated with the stretching and bending vibrations of the Cu–O bond. DLS study indicated that prepared NRs have a size distribution in the range of 37–99 nm in solution, with a zeta potential value of −37.00 mV. Finally, TEM analysis demonstrated that CuO NRs have a nanorod-like morphology with an average particle size of 5 nm in width and 25–100 nm in length. Furthermore, we discovered that CuO NRs provided an apparent and selective antiproliferative effect on B16F10 melanoma cells at a minimum concentration of 10 µg/ml, associated with induction of membrane leakage and elevation of oxidative stress. Also, induction of apoptotic process was observed in melanoma cells following exposure to CuO NRs mediated by elevation of cytochrome c, AIF, caspase-3, caspase-9, Bax, and downregulation of Bcl-2 genes and proteins. Therefore, it was deduced that both caspase-dependent and caspase-independent pathways were associated with anticancer mechanisms of CuO NRs against B16F10 melanoma. In conclusion, CuO NRs could be appointed as potential nanostructures in the modulation or prevention of skin cancer and may be an indication of a new potential anticancer compound in the treatment of melanoma, which warrants further investigations in future studies.
Obesity was associated with change in gut microbiota composition and their metabolites. We investigated the effects of dietary supplementation with leucine (Leu) in combination with arginine (Arg) or ...glutamic acid (Glu) on body fat weight, composition of gut microbiota, and short-chain fatty acids (SCFAs) concentration in the colon. Forty-eight Duroc × Large White × Landrace pigs with an initial body weight of 77.08 ± 1.29 kg were randomly assigned to one of the four groups (12 pigs per group). The pigs in the control group were fed a basal diet supplemented with 2.05% alanine (isonitrogenous control, BD group), and those in the three experimental groups were fed a basal diet supplemented with 1.00% Leu + 1.37% alanine (Leu group), 1.00% Leu + 1.00% Arg (Leu_Arg group), or 1.00% Leu + 1.00% Glu (Leu_Glu group). We found that dietary supplementation with Leu alone or in combination with Arg decreased (
< 0.05) body fat weight, and increased (
< 0.05) colonic propionate and butyrate concentrations compared to the BD group. The mRNA expression levels of genes related to lipolysis increased (
< 0.05) in the Leu or Leu_Arg group compared to the BD group. Negative relationships (
< 0.05) were observed between body fat weight, colonic propionate, and butyrate concentrations. Compared to the BD group, the abundance of
was higher (
< 0.05) in the Leu group, and that of
_1,
, and
were higher in the Leu_Arg group. The abundance of
was negatively correlated (
< 0.05) with body fat weight, and was positively correlated (
< 0.05) with butyrate, isovalerate, propionate, and isobutyrate concentrations, and that of
was positively correlated (
< 0.05) with butyrate, propionate, and isobutyrate concentrations. In conclusion, these findings suggest that decreased body fat weight in pigs can be induced by Leu supplementation alone or in combination with Arg and is associated with increased colonic butyrate and propionate concentrations. This provides new insights for potential therapy for obesity.
ABSTRACT
Introduction
Diabetic wounds are difficult to heal, but the pathogenesis is unknown. MicroRNAs (miRNAs) are thought to play important roles in wound healing. The effect of miR‐488‐3p in ...wound healing was studied in this article.
Materials and Methods
The gene methylation was measured by methylation specific PCR (MSP) assay. A dual‐luciferase reporter assay was adopted to analyze the interaction between miR‐488‐3p and MeCP2.
Results
Cytochrome P450 1B1 (CYP1B1) is a monooxygenase belonging to the cytochrome P450 family that aids in wound healing. Our findings showed that the miR‐488‐3p and CYP1B1 expression levels were much lower in wound tissues of diabetics with skin defects, but the methyl‐CpG‐binding protein 2 (MeCP2) level was significantly higher than that in control skin tissues. MiR‐488‐3p overexpression increased cell proliferation and migration, as well as HUVEC angiogenesis, while inhibiting apoptosis, according to function experiments. In vitro, MeCP2 inhibited wound healing by acting as a target of miR‐488‐3p. We later discovered that MeCP2 inhibited CYP1B1 expression by enhancing its methylation state. In addition, CYP1B1 knockdown inhibited wound healing. Furthermore, MeCP2 overexpression abolished the promoting effect of miR‐488‐3p on wound healing. It also turned out that CYP1B1 promoted wound healing by activating the Wnt4/β‐catenin pathway. Animal experiments also showed that miR‐488‐3p overexpression could accelerate wound healing in diabetic male SD rats.
Conclusions
MiR‐488‐3p is a potential therapeutic target for diabetic wound healing since it improved wound healing by activating the CYP1B1‐mediated Wnt4/‐catenin signaling cascade via MeCP2.
The expressions of miR‐488 and CYP1B1 were markedly reduced in wound tissues of diabetic with skin defect, while MeCP2 was significantly upregulated. MeCP2 was the downstream target of miR‐488, and MeCP2 overexpression suppressed wound healing in vitro.
Because number of matured muscle fibers in poultry does not increase after birth, the meat yield is mainly determined during embryogenesis. We previously indicated breast muscle grew rapidly from ...18th day after hatching (E18) to E27, and almost stopped from E27 to E34 of Jiaji ducks, while the mechanism is unclear. This study utilized RNA-seq to explore the related genes of muscle development and their relationship with small molecule metabolites at E18, E27 and E34 of Jiaji ducks. Several thousand differentially expressed genes (DEGs) were detected among E18, E27 and E34. DEGs expression profiles included 8 trend maps, among which trend 1 was opposite to and trend 6 was consistent with breast muscle development trend of Jiaji ducks. Through joint analysis between trend 1 of DEGs and trend 1 of differential metabolites (DEMs), protein digestion and absorption pathway stood out. The decrease of COL8A2 gene expression will lead to the decrease of arginine content, which will inhibit the development of breast muscle in embryonic Jiaji duck. Similarly, joint analysis between trend 6 of DEGs and trend 6 of DEMs indicated the increase of GAMT gene expression will cause the increase of proline content, and then promote the development of breast muscle of Jiaji duck in embryonic period. These results will be helpful for further understanding the mechanism of muscle yields of Jiaji ducks.
Purpose
In our previous study, the maternal high-fat/low-fiber (HF-LF) diet was suggested to induce metabolic disorders and placental dysfunction of the dam, but the effects of this diet on glucose ...metabolism of neonatal offspring remain largely unknown. Here, a neonatal pig model was used to evaluate the effects of maternal HF-LF diet during pregnancy on glucose tolerance, transition of skeletal muscle fiber types, and mitochondrial function in offspring.
Methods
A total of 66 pregnant gilts (Guangdong Small-ear Spotted pig) at day 60 of gestation were randomly divided into two groups: control group (CON group; 2.86% crude fat, 9.37% crude fiber), and high-fat/low-fiber diet group (HF-LF group; 5.99% crude fat, 4.13% crude fiber).
Results
The maternal HF-LF diet was shown to impair the glucose tolerance of neonatal offspring, downregulate the protein level of slow-twitch fiber myosin heavy chain I (MyHC I), and upregulate the protein levels of fast-twitch fiber myosin heavy chain IIb (MyHC IIb) and IIx (MyHC IIx) in soleus muscle. Additionally, compared with the CON group, the HF-LF offspring showed inhibition of insulin signaling pathway and decrease in mitochondrial function in liver and soleus muscle.
Conclusion
Maternal HF-LF diet during pregnancy impairs glucose tolerance, induces the formation of glycolytic muscle fibers, and decreases the hepatic and muscular mitochondrial function in neonatal piglets.
For deep-buried thick top-coal roadways under high stress, there exists great difficulty in controlling the stability of the surrounding rock as well as in the necessity for low driving speeds. ...Taking the return air roadway 20201 (RAR 20201) of the Dahaize Coal Mine as the background, this paper presents a typical engineering case of a deep-buried thick top-coal roadway in a western mine. Through methods such as in situ investigation, theoretical analysis, numerical simulation and engineering practice, we studied the deformation and failure mechanisms of the surrounding rock in a deep-buried high-stress thick top-coal roadway, and revealed the driving speed effect. Results show that compared with shallow buried roadways, the deep-buried thick-roof coal roadway suffers a greater range of damage and failure. The roof damage is so deep that it exceeds the action range of bolts, resulting in the stress transferring to both sides, which affects the stability of the roadway surroundings. The curve of unloading disturbance stress produced by roadway head-on driving is in accordance with the “power exponential” composite function; that is, the faster the driving speed, the less unloading disturbance intensity that is exerted on the roof strata. This paper puts forward targeted cooperative control countermeasures of efficient driving and support in a deep-buried thick top-coal roadway. On one hand, the support efficiency of a single bolt is improved so as to reduce the overall support density; on the other hand, under low support density, the driving-supporting circulation efficiency is also accelerated so as to weaken the unloading disturbance and improve roadway formation speed. Engineering practice shows great control effect of the roadway surrounding rock, and the roadway formation speed is also greatly improved. This research can provide reference for efficient driving and support design in similar deep-buried thick top-coal roadways.
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