Potential Mechanism
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2022 ◽  
Vol 8 ◽  
Guli Xu ◽  
Yexian Yuan ◽  
Pei Luo ◽  
Jinping Yang ◽  
Jingjing Zhou ◽  

Endurance training and explosive strength training, with different contraction protein and energy metabolism adaptation in skeletal muscle, are both beneficial for physical function and quality of life. Our previous study found that chronic succinate feeding enhanced the endurance exercise of mice by inducing skeletal muscle fiber-type transformation. The purpose of this study is to investigate the effect of acute succinate administration on skeletal muscle explosive strength and its potential mechanism. Succinate was injected to mature mice to explore the acute effect of succinate on skeletal muscle explosive strength. And C2C12 cells were used to verify the short-term effect of succinate on oxidative phosphorylation. Then the cells interfered with succinate receptor 1 (SUCNR1) siRNA, and the SUCNR1-GKO mouse model was used for verifying the role of SUCNR1 in succinate-induced muscle metabolism and expression and explosive strength. The results showed that acute injection of succinate remarkably improved the explosive strength in mice and also decreased the ratio of nicotinamide adenine dinucleotide (NADH) to NAD+ and increased the mitochondrial complex enzyme activity and creatine kinase (CK) activity in skeletal muscle tissue. Similarly, treatment of C2C12 cells with succinate revealed that succinate significantly enhanced oxidative phosphorylation with increased adenosine triphosphate (ATP) content, CK, and the activities of mitochondrial complex I and complex II, but with decreased lactate content, reactive oxygen species (ROS) content, and NADH/NAD+ ratio. Moreover, the succinate's effects on oxidative phosphorylation were blocked in SUCNR1-KD cells and SUCNR1-KO mice. In addition, succinate-induced explosive strength was also abolished by SUCNR1 knockout. All the results indicate that acute succinate administration increases oxidative phosphorylation and skeletal muscle explosive strength in a SUCNR1-dependent manner.

2022 ◽  
Vol 23 (2) ◽  
pp. 902
Magdalena Bryś ◽  
Karina Urbańska ◽  
Beata Olas

Genipin is an important monoterpene iridoid compound isolated from Gardenia jasminoides J.Ellis fruits and from Genipa americana fruits, or genipap. It is a precursor of a blue pigment which may be attractive alternative to existing food dyes and it possesses various potential therapeutic properties such as anti-cancer, anti-diabetic and hepatoprotective activity. Biomedical studies also show that genipin may act as a neuroprotective drug. This review describes new aspects of the bioactivity of genipin against various diseases, as well as its toxicity and industrial applications, and presents its potential mechanism of action.

2022 ◽  
Vol 12 ◽  
Xiaofei Shang ◽  
Xinghui Yuan ◽  
Lixia Dai ◽  
Yang Liu ◽  
Jian He ◽  

Ruangan granules (RGGs) have been used to treat liver fibrosis with good clinical efficacy for many years. However, the potential mechanism of action of RGGs against liver fibrosis is still unclear. In this study, we evaluated the quality and safety of this preparation and aimed to explore the anti-liver fibrosis activity and potential mode of action of RGGs using network pharmacology and metabolomics. The results showed that RGGs contained abundant ferulic acid, salvianolic acid B and paeoniflorin, and at the given contents and doses, RGGs were safe and presented anti-liver fibrosis activity. They presented anti-liver fibrosis activity by improving liver function (ALT and AST, p < 0.01) and pathology and decreasing fibrosis markers in the serum of rats caused by CCl4, including HA, LN, PC III, HYP, CoII-V, and α-SMA, and the oxidant stress and inflammatory response were also alleviated in a dose-dependent manner, especially for high-dose RGGs (p < 0.01). Further studies showed that RGGs inhibited the activation of the PI3K-Akt signaling pathway in rats induced by CCl4, regulated pyrimidine metabolism, improved oxidative stress and the inflammatory response by regulating mitochondrial morphology, and alleviated liver fibrosis. Luteolin, quercetin, morin and kaempferol were active compounds and presented the cytotoxicity toward to LX-02 cells. This study provides an overall view of the mechanism underlying the action of RGGs protecting against liver fibrosis.

2022 ◽  
Vol 12 ◽  
Chen Liu ◽  
Yuhan Huang ◽  
Yaoyuan Cui ◽  
Jun Zhou ◽  
Xu Qin ◽  

BackgroundOvarian cancer (OC) is one of the most lethal gynecologic cancers. Growing evidence has proven that CDK4/6 plays a key role in tumor immunity and the prognosis of many cancers. However, the expression and function of CDK4/6 in OC remain unclear. Therefore, we aimed to explore the influence of CDK4/6 in OC, especially on immunity.MethodsWe analyzed CDK4/6 expression and prognosis using The Cancer Genome Atlas (TCGA), Gene Expression Omnibus (GEO) and Genotype Tissue Expression (GTEx) data. Subsequently, we used the cytoHubba plug-in of Cytoscape software and starBase to identify the noncoding RNAs (ncRNAs) regulating CDK4/6. Finally, we verified the effect of CDK4/6 on immunity in OC cell lines and animal models.ResultsCDK4/6 expression was higher in OC tissues than in normal ovarian tissues, and the high expression levels of CDK4/6 contributed to the immunosuppressive state of OC and were thus related to the poor prognosis of OC patients. This was also in general agreement with the results of OC cell line and animal experiments. Mechanistically, the CDK4/6 inhibitor palbociclib increased the secretion of interferon (IFN)-γ and the interferon-stimulated gene (ISG) response, thereby upregulating the expression of antigen-presenting molecules; this effect was partly dependent on the STING pathway and thus activated immunity in OC. Additionally, according to public data, the LRRC75A-AS1-hsa-miR-330-5p axis could inhibit the immune response of OC patients by upregulating CDK4/6, leading to a poor prognosis.ConclusionCDK4/6 affects the immune microenvironment of OC and correlates with the prognosis of OC patients.

2022 ◽  
Grace C George ◽  
Sara A Heyn ◽  
Shuka Konishi ◽  
Marie-France Marin ◽  
Mohammed R Milad ◽  

Children must learn basic functional processes directly from their caregivers and child psychopathology may disrupt this transmission. This transmission may be seen through biological measures like peripheral nervous system outputs like skin conductance (SCR). Fear learning deficits have been seen in affective disorders like PTSD and are useful for studying parent-child learning transmission. Our study uses a vicarious fear extinction paradigm to study if biological synchrony (SCR and heart rate variability (HRV)) are potential mechanisms in which children learn safety cues from their parents. There were 16 dyads (PTSD n=11, TD n=5) undergoing a vicarious fear extinction paradigm. We used cross-recurrence quantification analysis (CRQA) to assess SCR and HRV synchrony between parent-child dyads. We then used a linear model looking at group differences between PTSD dyads and typically developing (TD) dyads. For SCR, we saw a significant group difference (p=.037) indicating that TD dyads had higher SCR synchrony compared to PTSD dyads. For HRV, there were no group differences between PTSD and TD dyads (p=.325). These results suggest that SCR synchrony, but not HRV, may be a potential mechanism that allows for fear and safety learning in youth. While this is preliminary, it may give the first insights on how therapies such as Trauma-Focused Cognitive Behavioral Therapy critically rely on parental coaching to model appropriate fear responses to help their child to recover from trauma.

Joshua D. Landvatter ◽  
Bert N. Uchino ◽  
Timothy W. Smith ◽  
Jos A. Bosch

Social support has been linked to lower cardiovascular morbidity and mortality. However, most studies have examined perceived support as an intrapersonal construct. A dyadic approach to social support highlights how interdependence between individuals within relationships, including partner perceptions and interactions, can influence one’s health. This study’s overall purpose was to test actor–partner models linking perceived social support to inflammation. Ninety-four cisgender married couples completed perceived support measures and had their blood drawn for CRP and IL-6 to produce an overall inflammatory index. The primary results indicate that only a partner’s level of perceived support was related to lower inflammation in their spouse. Our sample size, although moderate for inflammatory studies, was probably not large enough to detect actor influences. These data highlight the importance of taking a dyadic perspective on modeling perceived support and its potential mechanism.

2022 ◽  
Yong-Zheng Zhang ◽  
ZHANG Yong-Zheng ◽  
LI Meng-Jia ◽  
WU Yang ◽  

Abstract Background At present, scholars believe that severe COVID-19 is related to a variety of basic diseases, and we also observe this point using multi-omics method. The latest sequencing data of severe COVID-19 patients were combined to analyze the pathological mechanism, and pharmacological experimental research on local drugs was conducted, and a compound ingredient was found to have potential medicinal value. Results Here, we observed, for patients with severe COVID-19 disease, the differential miRNA expression is mainly low but having higher expression of mRNA. These differential mRNA expressions are associated with the activation of inflammatory pathways and ultimately with hypoxia and coagulation. Using database analysis, we found that Yi Xin Tong Mai Granule(YXTMG) might regulate COVID-19 through Toll-like receptor signaling pathway by acting on different immune targets. We found a new molecular mechanism for COVID-19 to turn the crisis around, the down-regulated miR-181a-5p mediates the up-regulation of PLAU and SERPINE1 molecules to cause cardiovascular adverse events, and YXTMG may prevent it. At the same time, molecular docking indicated that the its various components have anti-inflammatory activity. In vitro studies, we confirmed that YXTMG had antioxidant and anti-inflammatory activities. Conclusions The study has supplemented the potential mechanism for the conversion of mild to critical COVID-19 disease and screened the Chinese medicines for improving these factors, providing methodological reference for disease pathology and drug development.

2022 ◽  
Vol 12 (1) ◽  
David E. Ausband

AbstractThe genetic composition of an individual can markedly affect its survival, reproduction, and ultimately fitness. As some wildlife populations become smaller, conserving genetic diversity will be a conservation challenge. Many imperiled species are already supported through population augmentation efforts and we often do not know if or how genetic diversity is maintained in translocated species. As a case study for understanding the maintenance of genetic diversity in augmented populations, I wanted to know if genetic diversity (i.e., observed heterozygosity) remained high in a population of gray wolves in the Rocky Mountains of the U.S. > 20 years after reintroduction. Additionally, I wanted to know if a potential mechanism for such diversity was individuals with below average genetic diversity choosing mates with above average diversity. I also asked whether there was a preference for mating with unrelated individuals. Finally, I hypothesized that mated pairs with above average heterozygosity would have increased survival of young. Ultimately, I found that females with below average heterozygosity did not choose mates with above average heterozygosity and wolves chose mates randomly with respect to genetic relatedness. Pup survival was not higher for mated pairs with above average heterozygosity in my models. The dominant variables predicting pup survival were harvest rate during their first year of life and years pairs were mated. Ultimately, genetic diversity was relatively unchanged > 20 years after reintroduction. The mechanism for maintaining such diversity does not appear related to individuals preferentially choosing more genetically diverse mates. Inbreeding avoidance, however, appears to be at least one mechanism maintaining genetic diversity in this population.

Yonggang Zhang ◽  
Hongling Yang ◽  
Yipeng Zhang ◽  
Junzhu Shi ◽  
Yan Long

eLife ◽  
2022 ◽  
Vol 11 ◽  
Tatsuya Sato ◽  
Jason Solomon Shapiro ◽  
Hsiang-Chun Chang ◽  
Richard A Miller ◽  
Hossein Ardehali

Iron is an essential molecule for biological processes, but its accumulation can lead to oxidative stress and cellular death. Due to its oxidative effects, iron accumulation is implicated in the process of aging and neurodegenerative diseases. However, the mechanism for this increase in iron with aging, and whether this increase is localized to specific cellular compartment(s), are not known. Here, we measured the levels of iron in different tissues of aged mice, and demonstrated that while cytosolic non-heme iron is increased in the liver and muscle tissue, only the aged brain cortex exhibits an increase in both the cytosolic and mitochondrial non-heme iron. This increase in brain iron is associated with elevated levels of local hepcidin mRNA and protein in the brain. We also demonstrate that the increase in hepcidin is associated with increased ubiquitination and reduced levels of the only iron exporter, ferroportin-1 (FPN1). Overall, our studies provide a potential mechanism for iron accumulation in the brain through increased local expression of hepcidin, and subsequent iron accumulation due to decreased iron export. Additionally, our data support that aging is associated with mitochondrial and cytosolic iron accumulation only in the brain and not in other tissues.

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