In mammalian, the periodic growth and development of ovarian follicles constitutes the physiological basis of female estrus and ovulation. Concomitantly, follicular angiogenesis exerts a pivotal role ...in the growth of ovarian follicles. Melatonin (N-acetyl-5-methoxytryptamine, Mel), exists in follicle fluid, was suggested to affect the development of follicles and angiogenesis. This research was conducted to investigate the effects and mechanisms of Mel on the development of ovarian follicles and its angiogenesis. In total, 40 ICR mice at age of 3 weeks were allocated into four groups at liberty: control, Mel, FSH and FSH + Mel for a 12-day trial. Ovaries were collected at 8:00 a.m. on Day 13 for detecting the development of ovarian follicles and angiogenesis. Results indicated that Mel promoted the development of ovarian follicles of 50-250 μm (secondary follicles) and periphery angiogenesis, while FSH remarkably increased the number of antral follicles and periphery angiogenesis. Mechanically, Mel and FSH may regulate the expression of VEGF and antioxidant enzymes in different follicular stages. In conclusion, Mel primarily acted on the secondary follicles, while FSH mainly promoted the development of antral follicles. They both conduced to related periphery angiogenesis by increasing the expression of VEGF. These findings may provide new targets for the regulating of follicular development.
Fibroblast growth factor 5 (FGF5) is a famous dominant inhibitor of anagen phase of hair cycle. Mutations of FGF5 gene result in a longer wool in mice, donkeys, dogs, cats, and even in human ...eyelashes. Sheep is an important source of wool production. How to improve the production of wool quickly and effectively is an urgent problem to be solved. In this study, we generated five FGF5-knockout Dorper sheep by the CRISPR/Cas9 system. The expression level of FGF5 mRNA in knockout (KO) sheep decreased significantly, and all FGF5 proteins were dysfunctional. The KO sheep displayed a significant increase in fine-wool and active hair-follicle density. The crosstalk between androgen and Wnt/β-catenin signaling downstream of FGF5 gene plays a key role. We established downstream signaling cascades for the first time, including FGF5, FGFR1, androgen, AR, Wnt/β-catenin, Shh/Gli2, c-MYC, and KRTs. These findings further improved the function of FGF5 gene, and provided therapeutic ideas for androgen alopecia.
In this study, two experiments were performed to assess the effect and the role of melatonin on human
embryo quality.
Experiment I: A total of 42 repeated-poor-quality-embryo patients were enrolled, ...with a total of 181 oocytes retrieval cycles. After IVF, for the same patient, the MT cycles group (10
M melatonin added to the culture medium; n=48) were compared with the previous non-MT cycles group (n=133), following by
culture to blastocyst stage and embryo transfer. 31 patients were transplanted with 65 embryo transfer, including 24 MT embryo transfer, 41 non-MT embryo transfer. Cycle outcomes were compared between the two groups. Experiment II:A total of 143 supernumerary human cleavage-stage embryos (from non-repeated-poor-quality-embryo patients) vitrified on Day 3 after IVF were warmed and randomized into two groups: melatonin group (10
M melatonin added to the culture medium; n=71) and control group (n=72), and then cultured for 72 h. Rate of blastocyst and high-quality blastocyst, reactive oxygen species (ROS) levels of culture media as well as embryonic
,
,
,
,
,
gene expression levels were analyzed.
Experiment I: Results showed that the rate of Day 3 high-quality embryos (29.6%
19.5%) in the MT cycles group was significantly higher than that in the non-MT cycles group (
<0.05). The rate of available blastocysts (17.1%
12.7%) and clinical pregnancy rate (25.0%
17.1%) were in tendency higher in the group treated with melatonin (
>0.05). Experiment II:Results showed that the blastocyst rates in the melatonin administered group were significantly higher than in control group (42.25%
26.38%,
<0.05). There were no significant differences in high-quality blastocyst rates. In addition, quantitative PCR showed that the expression of
was significantly upregulated by melatonin treatment (
<0.05), while there were no significant differences in the expression of
,
,
,
and
gene as well as the levels of ROS.
These data showed that melatonin supplement in the culture medium will improve Day 3 high-quality embryos rate of repeated-poor-quality-embryo patients and improve blastocyst rate of vitrified-warmed cleavage-stage embryos, suggesting that melatonin intervention may provide a potential rescue strategy for IVF failures.
identifier ChiCTR2200059773.
Dynamic metabolic reprogramming occurs at different stages of myogenesis and contributes to the fate determination of skeletal muscle satellite cells (MuSCs). Accumulating evidence suggests that ...mutations in myostatin (MSTN) have a vital role in regulating muscle energy metabolism. Here, we explored the metabolic reprogramming in MuSCs and myotube cells in MSTN and FGF5 dual-gene edited sheep models prepared previously, and also focused on the metabolic alterations during myogenic differentiation of MuSCs. Our study revealed that the pathways of nucleotide metabolism, pantothenate and CoA biosynthesis were weakened, while the unsaturated fatty acids biosynthesis were strengthened during myogenic differentiation of sheep MuSCs. The MSTN and FGF5 dual-gene editing mainly inhibited nucleotide metabolism and biosynthesis of unsaturated fatty acids in sheep MuSCs, reduced the number of lipid droplets in per satellite cell, and promoted the pentose phosphate pathway, and the interconversion of pentose and glucuronate. The MSTN and FGF5 dual-gene editing also resulted in the inhibition of nucleotide metabolism and TCA cycle pathway in differentiated myotube cells. The differential metabolites we identified can be characterized as biomarkers of different cellular states, and providing a new reference for MSTN and FGF5 dual-gene editing in regulation of muscle development. It may also provide a reference for the development of muscle regeneration drugs targeting biomarkers.
Skeletal muscle myogenesis and injury-induced muscle regeneration contribute to muscle formation and maintenance. As myogenic stem cells, skeletal muscle satellite cells have the ability to ...proliferate, differentiate and self-renew, and are involved in muscle formation and muscle injury repair. Accumulating evidence suggests that non-coding RNAs (ncRNAs), including microRNAs (miRNAs), long non-coding RNAs (lncRNAs) and circular RNAs (circRNAs), are widely involved in the regulation of gene expression during skeletal muscle myogenesis, and their abnormal expression is associated with a variety of muscle diseases. From the perspective of the molecular mechanism and mode of action of ncRNAs in myogenesis, this review aims to summarize the role of ncRNAs in skeletal muscle satellite cells' myogenic differentiation and in muscle disease, and systematically analyze the mechanism of ncRNAs in skeletal muscle development. This work will systematically summarize the role of ncRNAs in myogenesis and provide reference targets for the treatment of various muscle diseases, such as muscle dystrophy, atrophy and aberrant hypertrophy.
Numerous factors trigger male infertility, including lifestyle, the environment, health, medical resources and pathogenic microorganism infections. Bacterial infections of the male reproductive ...system can cause various reproductive diseases. Several male reproductive organs, such as the testicles, have unique immune functions that protect the germ cells from damage. In the reproductive system, immune cells can recognize the pathogen-associated molecular patterns carried by pathogenic microorganisms and activate the host’s innate immune response. Furthermore, bacterial infections can lead to oxidative stress through multiple signaling pathways. Many studies have revealed that oxidative stress serves dual functions: moderate oxidative stress can help clear the invaders and maintain sperm motility, but excessive oxidative stress will induce host damage. Additionally, oxidative stress is always accompanied by autophagy which can also help maintain host homeostasis. Male reproductive system homeostasis disequilibrium can cause inflammation of the genitourinary system, influence spermatogenesis, and even lead to infertility. Here, we focus on the effect of oxidative stress and autophagy on bacterial infection in the male reproductive system, and we also explore the crosslink between oxidative stress and autophagy during this process.
Cumulus cells of pre-pubertal domestic animals are dysfunctional, perhaps due to age-specific epigenetic events. This study was designed to determine effects of melatonin treatment of donors on ...methylation modification of pre-pubertal cumulus cells. Cumulus cells from germinal vesicle stage cumulus oocyte complexes (COCs) were collected from eighteen lambs which were randomly divided into control group (C) and melatonin group given an 18 mg melatonin implant subcutaneous (M). Compared to the C group, the M group had higher concentrations of melatonin in plasma and follicular fluid (
< 0.05), greater superovulation, a higher proportion of fully expanded COCs, and a lower proportion of apoptotic cumulus cells (
< 0.05). Real-time PCR results showed that melatonin up-regulated expression of genes
,
,
,
and
, but down-regulated expression of genes
,
and
(
< 0.05). Furthermore, melatonin increased FI of FITC (global methylation level) on cumulus cells (
< 0.05). To understand the regulation mechanism, the
promoter methylation sequence were analyzed. Compared to the C group, although there was less methylation at two CpG sites of
(
< 0.05) and higher methylation at two CpG sites of
(
< 0.05), there were no significant differences in methylation of the detected
and
promoter regions. However, there were lower methylation levels at five CpG sites of
, which decreased methylation of detected
promoter region on M group (
< 0.05). In conclusion, alterations of methylation regulated by melatonin may mediate development of cumulus cells in lambs.
Cardiovascular disease is the result of complicated pathophysiological processes in the tissues that make up the blood vessels and heart. Heat shock protein 90 (HSP90) can interact with 10% of the ...proteome and is the most widely studied molecular chaperone in recent years. HSP90 is extensively involved in the regulation of protein folding and intracellular protein stability, making HSP90 a hopeful target for the treatment of multiple cardiovascular diseases. Numerous client proteins of HSP90 have been identified in known cardiac disease pathways, including MAPK signaling, PI3K/AKT (PKB)/mTOR, and TNF-α signaling. Therefore, these pathways can be controlled by regulating HSP90. Among them, the activity of HSP90 can be regulated via numerous inhibitors. In this review, first, we will discuss the function of HSP90 and its role in pathological pathways. In addition, HSP90 plays a significant role in most cardiovascular diseases, including hypertension, pulmonary venous hypertension, atherosclerosis, and heart failure; next we will focus on this part. Finally, we will summarize the currently known HSP90 inhibitors and their potential in the treatment of heart disease.
Patients with colon adenocarcinoma (COAD) are at a higher probability of infection with COVID-19 than healthy individuals. However, there is no globally accepted treatment protocol for patients with ...COAD/COVID-19. Quercetin has been found to have significant antitumor, antiviral and anti-inflammatory effects in several studies. Therefore, this study sought to evaluate the potential of quercetin as the agent for COAD/COVID-19 and to explore its mechanisms. We used bioinformatics algorithms to obtain COAD/COVID-19-related genes (CCRG) from COAD-related transcriptome data and COVID-related transcriptome sequencing data, and used these genes to construct a COAD prognostic model. We intersected the CCRG with the therapeutic target genes of quercetin and obtained a total of 105 genes (potential target genes of quercetin for the treatment of COAD/COVID-19). By constructing a protein-protein interaction (PPI) network, we ascertained FOS, NFKB1, NFKB1A, JUNB, and JUN as possible core target genes of quercetin for the treatment of COAD/COVID-19. Bioinformatic analysis of these 105 genes revealed that the mechanisms for quercetin the treatment of COAD/COVID-19 may be associated with oxidative stress, apoptosis, anti-inflammatory, immune, anti-viral and multiple pathways containing IL-17, TNF, HIF-1. In this study, we constructed a prognostic model of COAD/COVID19 patients by using CCRG and elucidated for the first time the potential target genes and molecular mechanisms of quercetin for the treatment of COAD/COVID-19, which may benefit the clinical treatment of COAD/COVID-19 patients. However, no clinical trials have yet been conducted to further validate the findings, but this will be the future direction of our research.
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