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Fox04-DRI injection - Medswala pharmacy
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Fox04-DRI injection, Packaging Type: Box
₹ 6, 500/Box
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Box
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Packaging Type
Box
Packaging Size
1*1
Purity
99%
Usage
To support overall health and well-being by providing the body with the necessary nutrients
Prescription/Non prescription
Prescription
Country of Origin
Made in India
Senolytic Peptide FOXO4-DRI Selectively Removes Senescent Cells From in vitro Expanded Human Chondrocytes
In a recent study, FOXO4-DRI decreased levels of p53, p21, and p16 in the testes of aged mice, when compared to young mice (Zhang et al., 2020). Therefore, our study and published work collectively showed that FOXO4-DRI was able to remove senescent cells created by different methods.
FOXO4-DRI alleviates age-related testosterone secretion insufficiency by targeting senescent Leydig cells in aged mice
FOXO4-DRI is a peptide antagonist designed to block the interaction of forkhead box O 4 (FOXO4) and p53 [24]. Using ionizing radiation-induced senescent IMR90 cells, it was observed that FOXO4 maintains senescent cell viability by targeting p53 to the nucleus and preventing it from inducing apoptosis. Disrupting the p53-FOXO4 interaction using FOXO4-DRI caused p53 to be excluded from nucleus and directed to mitochondria for induction of apoptosis, ultimately eliminating the senescent cells. Therefore, the present study was designed to determine the pattern of FOXO4 expression in human testes and its role in Leydig cell senescence. We further sought to use an aged mice model to assess the ability of FOXO4-DRI to eliminate senescent Leydig cells and alleviate testosterone secretion insufficiency.
Autologous chondrocyte implantation (ACI) is a procedure used to treat articular cartilage injuries and prevent the onset of post-traumatic osteoarthritis. In vitro expansion of chondrocytes, a necessary step in ACI, results in the generation of senescent cells that adversely affect the quality and quantity of newly formed cartilage. Recently, a senolytic peptide, fork head box O transcription factor 4-D-Retro-Inverso (FOXO4-DRI), was reported to selectively kill the senescent fibroblasts. In this study, we hypothesized that FOXO4-DRI treatment could remove the senescent cells in the expanded chondrocytes, thus enhancing their potential in generating high-quality cartilage. To simulate the in vitro expansion for ACI, chondrocytes isolated from healthy donors were expanded to population doubling level (PDL) 9, representing chondrocytes ready for implantation. Cells at PDL3 were also used to serve as the minimally expanded control. Results showed that the treatment of FOXO4-DRI removed more than half of the cells in PDL9 but did not significantly affect the cell number of PDL3 chondrocytes. Compared to the untreated control, the senescence level in FOXO4-DRI treated PDL9 chondrocytes was significantly reduced. Based on the result from standard pellet culture, FOXO4-DRI pre-treatment did not enhance the chondrogenic potential of PDL9 chondrocytes. However, the cartilage tissue generated from FOXO4-DRI pretreated PDL9 cells displayed lower expression of senescence-relevant secretory factors than that from the untreated control group. Taken together, FOXO4-DRI is able to remove the senescent cells in PDL9 chondrocytes, but its utility in promoting cartilage formation from the in vitro expanded chondrocytes needs further investigation.
Keywords
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