Objective: Mice are routinely utilized as animal models of drug-induced liver injury (DILI), however, there are significant differences in the pathogenesis between mice and humans. This study aimed to compare gene expression between humans and mice in acetaminophen (APAP)-induced liver injury (AILI), and investigate the similarities and differences in biological processes between the two species.
Methods: A pair of public datasets (GSE218879 and GSE120652) obtained from GEO were analyzed using "Limma" package in R language, and differentially expressed genes (DEGs) were identified, including co-expressed DEGs (co-DEGs) and specific-expressed DEGS (specific-DEGs).
Recent reports have demonstrated that Sox9HNF4α hepatocytes are involved in liver regeneration after chronic liver injury; however, little is known about the origin of Sox9HNF4α hepatocytes and the regulatory mechanism. Employing a combination of chimeric lineage tracing, immunofluorescence, and immunohistochemistry, we demonstrate that Sox9HNF4α hepatocytes, generated by transition from mature hepatocytes, play an important role in the initial phase after partial hepatectomy (PHx). Additionally, knocking down the expression of Sox9 suppresses hepatocyte proliferation and blocks the recovery of lost hepatic tissue.
View Article and Find Full Text PDFPrevious studies have shown that tumor necrosis factor (TNF)-α is a mediator of hepatotoxicity in liver injury. Moreover, TNF-α has also been reported to have a protective effect in liver regeneration, yet the function of TNF-α during liver injury remains controversial. Here, we report that the concentration of TNF-α determines its functions.
View Article and Find Full Text PDFBackground: Babaodan (BBD), a traditional Chinese medicine, has been shown to have protective effects during liver injury and ameliorate liver disease progression, but little is known about its effect on non-alcoholic fatty liver disease (NAFLD). The aim of this study was to investigate the effects of BBD on obesity-induced NAFLD.
Methods: C57BL/6 J mice were fed with normal diet, high fat diet (HFD) or HFD + BBD for 8 weeks.
Robust evidence suggested that gut-derived lipopolysaccharide (LPS) plays a significant role in various liver injury diseases; however, the role of gut-derived LPS in acetaminophen (APAP) overdose-induced acute liver injury remains unclear. The present study aimed to investigate the effect of gut-derived LPS on APAP-induced liver injury. Our results revealed that reduction of gut-derived LPS using multiple antibiotics could significantly exacerbate APAP-induced liver injury and increase mortality in mice.
View Article and Find Full Text PDFHepatocellular carcinoma (HCC) is an inflammation-related disease. Tumor necrosis factor alpha (TNF-α) is an important inflammatory factor and it has been confirmed to promote tumor growth and poor prognosis of HCC. Hepatic progenitor cells (HPCs) are thought to play an important role in liver injury and repair, as well as tumorigenesis.
View Article and Find Full Text PDFBackground/aims: Naked mole rats (NMRs) spend their lives in burrow systems containing very low levels of oxygen, indicating long-term hypoxic exposure, and suggesting that pathological changes caused by hypoxia are attenuated or absent in this hypoxia-tolerant species. The mechanisms underlying NMRs hypoxia tolerance remain poorly understood. In this study, we explored whether hypoxia inducible factor 1α (HIF-1α), and vascular endothelial growth factor A (VEGFA) play a role in NMRs adaption to hypoxia.
View Article and Find Full Text PDFFertility is abolished in nonbreeding males in colonies of natal naked mole-rats (NMRs). Although spermatogenesis occurs in both breeding and nonbreeding male NMRs, the mechanisms underlying the differences in fertility between breeders and nonbreeders remain unexplored. In this study, a significant decrease in autophagy was observed in Leydig cells of the testis from nonbreeding male NMRs.
View Article and Find Full Text PDFThe domestic and foreign scholars have studied naked mole rats more focused on the respect such as its long life, resistant to low oxygen, little spontaneous tumor, but the study of the immune system is little. In this study, we compared the anatomy and tissue morphology of NMR and ICR mouse spleens and found that the gross appearance of the NNMR spleen differed from ICR. There were more macrophages in NNMR spleens than in ICR spleens.
View Article and Find Full Text PDFThe naked mole rat (NMR; ) is a small rodent species found in regions of Kenya, Ethiopia and Somalia. It has a high tolerance for hypoxia and is thus considered one of the most important natural models for studying hypoxia tolerance mechanisms. The various mechanisms underlying the NMR's hypoxia tolerance are beginning to be understood at different levels of organization, and next-generation sequencing methods promise to expand this understanding to the level of gene expression.
View Article and Find Full Text PDFJ Am Assoc Lab Anim Sci
January 2017
The unique biologic characteristics of naked mole-rats (NMR, Heterocephalus glaber) include longevity, cancer resistance, hypoxia tolerance, and pain insensitivity, making NMR an attractive model for biomedical research on aging, cancer, and neurobiology. However, breeding and rearing NMR in captivity is challenging. Here, we report a method for breeding NMR by using a closed-colony mating system.
View Article and Find Full Text PDFNaked mole-rats (NMR; Heterocephalus glaber) display extreme longevity and resistance to cancer. Here, we examined whether autophagy contributes to the longevity of NMRs by assessing the effects of the PI3K/Akt pathway inhibitor LY294002 and the autophagy inhibitor chloroquine (CQ) on autophagy and apoptosis in NMR skin fibroblasts. Serum starvation, H2O2 treatment, and LY294002 treatment all increased the LC3-II/LC3-I ratio and numbers of double-membraned autophagosomes and autophagic vacuoles, and decreased levels of p70S6K, p-AktSer473, and p-AktThr308.
View Article and Find Full Text PDFDiacylglycerol kinases ζ (DGKζ) is a critical lipid kinase which is involved in phosphatidic acid (PA) generation via diacylglycerol (DAG) phosphorylation. DGKζ is highly expressed in central nervous system and essential for brain development. Studies have indicated that DGKζ is associated with colon cancer invasion and metastasis.
View Article and Find Full Text PDFThe resuscitation-promoting factor (Rpf), a secretory protein first reported in Micrococcus luteus, plays a critical role in mycobacterial survival and infection. There are five functionally redundant Rpf-like proteins identified in M. tuberculosis (Mtb).
View Article and Find Full Text PDFBackground: The detection of Mycobacterium tuberculosis (Mtb) specific human antibodies has been an important diagnostic aid in the diagnosis of tuberculosis (TB) cases with smear-negative sputum samples, especially for the screening of high-risk population. This study focused on the analysis and comparison of the four potential Mtb-secreted proteins (ESAT6, CFP10, Ag85B, Hsp16.3) and the fusion protein Ag85B-Hsp16.
View Article and Find Full Text PDFBackground/aims: Naked mole rats (NMRs) survive and thrive in dark, dank environments with low levels of oxygen and poor quality nutrition. Their long lifespan is attributed to sustained good health and pronounced resistance to cancer. Physiological and biochemical processes, such as autophagy, may contribute to the successful aging of this exceptionally long-lived species.
View Article and Find Full Text PDFCell Physiol Biochem
October 2014
Background/aims: The maximum lifespan of the naked mole rat is over 28.3 years, which exceeds that of any other rodent species, suggesting that age-related changes in its body composition and functionality are either attenuated or delayed in this extraordinarily long-lived species. However, the mechanisms underlying the aging process in this species are poorly understood.
View Article and Find Full Text PDFBackground/aims: It has been demonstrated that KRAS mutations represent about 90% of cancer-associated mutations, and that KRAS mutations play an essential role in neoplastic transformation. Cancer-associated RAS mutations occur frequently in acute myeloid leukemia (AML), suggesting a functional role for Ras in leukemogenesis.
Methods: We successfully established a mouse model of human leukemia by transplanting bone marrow cells co-transfected with the K-ras (G12D) mutation and AML1/ETO fusion protein.
Tuberculosis (TB) remains a major worldwide health problem. The only vaccine against TB, Mycobacterium bovis Bacille Calmette-Guerin (BCG), has demonstrated relatively low efficacy and does not provide satisfactory protection against the disease. More efficient vaccines and improved therapies are urgently needed to decrease the worldwide spread and burden of TB, and use of a viable, metabolizing mycobacteria vaccine may be a promising strategy against the disease.
View Article and Find Full Text PDFHybridoma (Larchmt)
October 2011
The secreted Mycobacterium tuberculosis (MTB) proteins, Ag85B and Hsp16.3, have been the focus of intensive research in recent years. These proteins have high sensitivity in bacterium-negative tuberculosis (TB) patients, and are valuable for the rapid diagnosis of bacterium-negative TB.
View Article and Find Full Text PDFCurrent tuberculosis control measures are focused on the prompt detection and treatment of active tuberculosis. Despite the measured success of this strategy, tuberculosis continues to be a public health issue of major significance around the world. This unwanted situation suggests the need to expand our control efforts by exploring specific markers for the disease.
View Article and Find Full Text PDFZhongguo Ying Yong Sheng Li Xue Za Zhi
February 2004
Zhongguo Ying Yong Sheng Li Xue Za Zhi
November 2003
Aim: To study the effects of different acute hypoxia on blood pressure, heart rate and microvessels and free radical in rabbits.
Methods: The experiment model was carried out with acute hypoxia on two groups of rabbits, using artificial inspiration 12.5% O2 and 87.