A novel Y-specific long non-coding RNA associated with cellular lipid accumulation in HepG2 cells and Atherosclerosis-related genes
- Molina, Elsa, Chew, Guat, Myers, Stephen, Clarence, Elyse, Eales, James, Tomaszewski, Maciej, Charchar, Fadi
- Authors: Molina, Elsa , Chew, Guat , Myers, Stephen , Clarence, Elyse , Eales, James , Tomaszewski, Maciej , Charchar, Fadi
- Date: 2017
- Type: Text , Journal article
- Relation: Scientific Reports Vol. 7, no. 1 (2017), p. 1-12
- Relation: http://purl.org/au-research/grants/nhmrc/1009490
- Full Text:
- Reviewed:
- Description: There is an increasing appreciation for the role of the human Y chromosome in phenotypic differences between the sexes in health and disease. Previous studies have shown that genetic variation within the Y chromosome is associated with cholesterol levels, which is an established risk factor for atherosclerosis, the underlying cause of coronary artery disease (CAD), a major cause of morbidity and mortality worldwide. However, the exact mechanism and potential genes implicated are still unidentified. To date, Y chromosome-linked long non-coding RNAs (lncRNAs) are poorly characterized and the potential link between these new regulatory RNA molecules and hepatic function in men has not been investigated. Advanced technologies of lncRNA subcellular localization and silencing were used to identify a novel intergenic Y-linked lncRNA, named lnc-KDM5D-4, and investigate its role in fatty liver-associated atherosclerosis. We found that lnc-KDM5D-4 is retained within the nucleus in hepatocytes. Its knockdown leads to changes in genes leading to increased lipid droplets formation in hepatocytes resulting in a downstream effect contributing to the chronic inflammatory process that underpin CAD. Our findings provide the first evidence for the implication of lnc-KDM5D-4 in key processes related to fatty liver and cellular inflammation associated with atherosclerosis and CAD in men.
- Authors: Molina, Elsa , Chew, Guat , Myers, Stephen , Clarence, Elyse , Eales, James , Tomaszewski, Maciej , Charchar, Fadi
- Date: 2017
- Type: Text , Journal article
- Relation: Scientific Reports Vol. 7, no. 1 (2017), p. 1-12
- Relation: http://purl.org/au-research/grants/nhmrc/1009490
- Full Text:
- Reviewed:
- Description: There is an increasing appreciation for the role of the human Y chromosome in phenotypic differences between the sexes in health and disease. Previous studies have shown that genetic variation within the Y chromosome is associated with cholesterol levels, which is an established risk factor for atherosclerosis, the underlying cause of coronary artery disease (CAD), a major cause of morbidity and mortality worldwide. However, the exact mechanism and potential genes implicated are still unidentified. To date, Y chromosome-linked long non-coding RNAs (lncRNAs) are poorly characterized and the potential link between these new regulatory RNA molecules and hepatic function in men has not been investigated. Advanced technologies of lncRNA subcellular localization and silencing were used to identify a novel intergenic Y-linked lncRNA, named lnc-KDM5D-4, and investigate its role in fatty liver-associated atherosclerosis. We found that lnc-KDM5D-4 is retained within the nucleus in hepatocytes. Its knockdown leads to changes in genes leading to increased lipid droplets formation in hepatocytes resulting in a downstream effect contributing to the chronic inflammatory process that underpin CAD. Our findings provide the first evidence for the implication of lnc-KDM5D-4 in key processes related to fatty liver and cellular inflammation associated with atherosclerosis and CAD in men.
Australian ethnomedicinal plant extracts promote apoptosis-mediated cell death In human hepatocellular carcinoma in vitro
- Kiran, Sudha, Chew, Guat, Johnson, Joel, Mani, Janice Sandra, Wakeling, Lara, Portman, Andrew, Naiker, Mani
- Authors: Kiran, Sudha , Chew, Guat , Johnson, Joel , Mani, Janice Sandra , Wakeling, Lara , Portman, Andrew , Naiker, Mani
- Date: 2021
- Type: Text , Journal article
- Relation: Pharmacognosy communications Vol. 11, no. 4 (2021), p. 210-213
- Full Text:
- Reviewed:
- Description: Introduction: Hepatocellular carcinoma (HCC) Is the leading cause of primary liver cancer with Its prevalence continuing to rise. Although the number of cases continues to rise In both developing and developed countries, prognosis remains poor due to a lack of successful treatments. Inspired by the prospect of developing complementary medicines for this condition, we explore several native Australian plants for anti-carcinogenic activity, especially against HCC. Methods: Cytotoxicity assays against HCC cell lines were conducted using various plant extracts. Biochemical profiling of the plant species was conducted for total phenolics and antioxidant capacity, while reverse transcription-polymerase chain reaction (RT-PCR) was used to determine the active apoptotic pathways. Results: Westringia fruticosa and Prostanthera ovalifolia (small-leaved variety) had high antioxidant (410 and 227 mg/g, respectively) and phenolic contents (72.7 and 42.7 mg/g, respectively). P ovalifolia (small-leaved variety) demonstrated the greatest cytotoxic activity against HepG2 cells (IC50 4.61 ± 0.98 pg/mL) followed by Solanum laciniatum leaves (11.79 ± 0.43 pg/mL) and fruit extracts (ripe, unripe) (14.85 ± 1.80 and 19 ± 1.32 pg/mL, respectively). RT-PCR results confirmed apoptotic events in HepG2 cells, exposed to ripe and unripe S. laciniatum fruit extracts, via caspase-3 pathway. The highest apoptotic induction occurred after 8 hr. Compared to unripe fruits, ripe fruits induced a greater level of apoptosis, as evidenced by a 73 % higher level of caspase-3 mRNA expression and 22 % lower IC50 value. Conclusion: With further investigation, these fruits may provide a valuable source of anticarcinogenic compounds for use as chemotherapeutic or complementary therapies.
- Authors: Kiran, Sudha , Chew, Guat , Johnson, Joel , Mani, Janice Sandra , Wakeling, Lara , Portman, Andrew , Naiker, Mani
- Date: 2021
- Type: Text , Journal article
- Relation: Pharmacognosy communications Vol. 11, no. 4 (2021), p. 210-213
- Full Text:
- Reviewed:
- Description: Introduction: Hepatocellular carcinoma (HCC) Is the leading cause of primary liver cancer with Its prevalence continuing to rise. Although the number of cases continues to rise In both developing and developed countries, prognosis remains poor due to a lack of successful treatments. Inspired by the prospect of developing complementary medicines for this condition, we explore several native Australian plants for anti-carcinogenic activity, especially against HCC. Methods: Cytotoxicity assays against HCC cell lines were conducted using various plant extracts. Biochemical profiling of the plant species was conducted for total phenolics and antioxidant capacity, while reverse transcription-polymerase chain reaction (RT-PCR) was used to determine the active apoptotic pathways. Results: Westringia fruticosa and Prostanthera ovalifolia (small-leaved variety) had high antioxidant (410 and 227 mg/g, respectively) and phenolic contents (72.7 and 42.7 mg/g, respectively). P ovalifolia (small-leaved variety) demonstrated the greatest cytotoxic activity against HepG2 cells (IC50 4.61 ± 0.98 pg/mL) followed by Solanum laciniatum leaves (11.79 ± 0.43 pg/mL) and fruit extracts (ripe, unripe) (14.85 ± 1.80 and 19 ± 1.32 pg/mL, respectively). RT-PCR results confirmed apoptotic events in HepG2 cells, exposed to ripe and unripe S. laciniatum fruit extracts, via caspase-3 pathway. The highest apoptotic induction occurred after 8 hr. Compared to unripe fruits, ripe fruits induced a greater level of apoptosis, as evidenced by a 73 % higher level of caspase-3 mRNA expression and 22 % lower IC50 value. Conclusion: With further investigation, these fruits may provide a valuable source of anticarcinogenic compounds for use as chemotherapeutic or complementary therapies.
- «
- ‹
- 1
- ›
- »