• Title/Summary/Keyword: SLC7A11

Search Result 15, Processing Time 0.03 seconds

Ginsenoside Rg5 promotes wound healing in diabetes by reducing the negative regulation of SLC7A11 on the efferocytosis of dendritic cells

  • Wei Xia;Zongdong Zhu;Song Xiang;Yi Yang
    • Journal of Ginseng Research
    • /
    • v.47 no.6
    • /
    • pp.784-794
    • /
    • 2023
  • Background: ginsenoside Rg5 is a rare ginsenoside with known hypoglycemic effects in diabetic mice. This study aimed to explore the effects of ginsenoside Rg5 on skin wound-healing in the Leprdb/db mutant (db/db) mice (C57BL/KsJ background) model and the underlying mechanisms. Methods: Seven-week-old male C57BL/6J, SLC7A11-knockout (KO), the littermate wild-type (WT), and db/db mice were used for in vivo and ex vivo studies. Results: Ginsenoside Rg5 provided through oral gavage in db/db mice significantly alleviated the abundance of apoptotic cells in the wound areas and facilitated skin wound healing. 50 μM ginsenoside Rg5 treatment nearly doubled the efferocytotic capability of bone marrow-derived dendritic cells (BMDCs) from db/db mice. It also reduced NF-κB p65 and SLC7A11 expression in the wounded areas of db/db mice dose-dependently. Ginsenoside Rg5 physically interacted with SLC7A11 and suppressed the cystine uptake and glutamate secretion of BMDCs from db/db and SLC7A11-WT mice but not in BMDCs from SLC7A11-KO mice. In BMDCs and conventional type 1 dendritic cells (cDC1s), ginsenoside Rg5 reduced their glycose storage and enhanced anaerobic glycolysis. Glycogen phosphorylase inhibitor CP-91149 almost abolished the effect of ginsenoside Rg5 on promoting efferocytosis. Conclusion: ginsenoside Rg5 can suppress the expression of SLC7A11 and inhibit its activity via physical binding. These effects collectively alleviate the negative regulations of SLC7A11 on anaerobic glycolysis, which fuels the efferocytosis of dendritic cells. Therefore, ginsenoside Rg5 has a potential adjuvant therapeutic reagent to support patients with wound-healing problems, such as diabetic foot ulcers.

A Study on the Correlation between SLC25A26 Polymorphism and Gastritis and Gastric Ulcers in Koreans (한국인의 SLC25A26 유전자 다형성과 위염, 위궤양과의 상관성에 관한 연구)

  • Soyeun PARK;Dahyun HWANG
    • Korean Journal of Clinical Laboratory Science
    • /
    • v.55 no.4
    • /
    • pp.291-297
    • /
    • 2023
  • Gastritis is an inflammation of the gastric mucosa and gastric ulcers are a break in the mucosa of the stomach lining. Past research on gastritis and gastric ulcers has been mainly conducted from the perspective that environmental factors are the primary cause of these gastric diseases. However, recently the importance of genetic factors has been emphasized due to current developments in genetic research. The SLC25A26 gene is believed to be associated with the accumulation of reactive oxygen species. Oxidative stress promotes an inflammatory response, which increases the production of free radicals and causes cellular damage, and these lead to the development of gastric diseases. In this study, the correlation between SLC25A26 and gastric diseases was analyzed. Polymorphisms in SLC25A26 were analyzed in 1,369 domestic gastric disease patients and 7,471 healthy controls. As a result, 11 single nucleotide polymorphisms (SNPs) (in the genotype) and 13 SNPs (in the imputation) showed statistical significance (P<0.05), and high relative risk of gastric diseases. Among them, the rs13874 allele of SLC25A26 showed a highly significant association with gastric diseases. In the genotype-based mRNA expression analysis, the minor allele (C) group showed increased mRNA expression and this could increase oxidative stress. In conclusion, SLC25A26 polymorphisms are associated with gastric diseases. These results may provide a basis for new guidelines for gastric disease management in the Korean population.

Maximization of The Number of Follicular Oocytes Recovered from The Bovine Ovaries (소 난소로부터 회수난포란수의 극대화 방법)

  • 유형진;최승철;이상호
    • Korean Journal of Animal Reproduction
    • /
    • v.17 no.2
    • /
    • pp.149-157
    • /
    • 1993
  • A new technique was established to maximize the numbers of follicular oocytes recovered from the ovaries obtained at the slaughter house. And their further developmental capacity was demonstrated. There recovery techniques were used; aspiration (ASP, control), slicing (SLC) and slicing combining aspiration (ASP+SLC). Recovered oocytes were cultured in TCM 199+15% FCS+gonadotrophins in an atmosphere of 5% CO$_2$ in air at 39$^{\circ}C$ for 24 h. The nuclear maturation was detemined with chromo-some configuration by rapid staining. And cytoplasmic maturation was examined by the formation of female pronuclei with parthenogenetic activation of the matured oocyte after 18 h of co-culture with granulosa cell monolayer. Total 1,641 bovine follicular oocytes recovered from 245 ovaries. The number of oocytcs per ovary was 1.87 in ASP, 11.05 in SLC and 7.88 in ASP+SLC, respectively. SLC would yield 5.9 folds increase, compared with ASP. The rate of maturation were 92.9% in ASP, 79.1% in SLC and 71.7% in ASP+SLC, respectively. Although the maturation rate in ASP was the highest, metaphase II oocytes per ovary in SLC was 5 times higher than that of ASP. The rates of pronuclei formation upon ethanol activation were 75% in ASP, 67% in SLC and 62.5% in ASP+SLC, respectively. The results demonstrate that it should be possible to maximize the number of the follicular oocyte from the ovary for mass production of bovine embryos. Thus the established technique may provide efficient supply of bovine embryos for biochemical and molecular study of early bovine embryos.

  • PDF

circRNA circSnx12 confers Cisplatin chemoresistance to ovarian cancer by inhibiting ferroptosis through a miR-194-5p/SLC7A11 axis

  • Kaiyun Qin;Fenghua Zhang;Hongxia Wang;Na Wang;Hongbing Qiu;Xinzhuan Jia;Shan Gong;Zhengmao Zhang
    • BMB Reports
    • /
    • v.56 no.3
    • /
    • pp.184-189
    • /
    • 2023
  • Ovarian cancer (OC) is the most common gynecological malignancy worldwide, and chemoresistance occurs in most patients, resulting in treatment failure. A better understanding of the molecular processes underlying drug resistance is crucial for development of efficient therapies to improve OC patient outcomes. Circular RNAs (circRNAs) and ferroptosis play crucial roles in tumorigenesis and resistance to chemotherapy. However, little is known about the role(s) of circRNAs in regulating ferroptosis in OC. To gain insights into cisplatin resistance in OC, we studied the ferroptosis-associated circRNA circSnx12. We evaluated circSnx12 expression in OC cell lines and tissues that were susceptible or resistant to cisplatin using quantitative real-time PCR. We also conducted in vitro and in vivo assays examining the function and mechanism of lnc-LBCSs. Knockdown of circSnx12 rendered cisplatin-resistant OC cells more sensitive to cisplatin in vitro and in vivo by activating ferroptosis, which was at least partially abolished by downregulation of miR-194-5p. Molecular mechanics studies indicate that circSnx12 can be a molecular sponge of miR-194-5p, which targets SLC7A11. According to our findings, circSnx12 ameliorates cisplatin resistance by blocking ferroptosis via a miR-194-5p/SLC7A11 pathway. CircARNT2 may thus serve as an effective therapeutic target for overcoming cisplatin resistance in OC.

DNA Polymorphism in SLC11A1 Gene and its Association with Brucellosis Resistance in Indian Zebu (Bos indicus) and Crossbred (Bos indicus×Bos taurus) Cattle

  • Kumar, Nishant;Ganguly, Indrajit;Singh, Rajendra;Deb, Sitangsu M.;Kumar, Subodh;Sharma, Arjava;Mitra, Abhijit
    • Asian-Australasian Journal of Animal Sciences
    • /
    • v.24 no.7
    • /
    • pp.898-904
    • /
    • 2011
  • The PCR- restriction fragment length polymorphism (RFLP) in and around TM4 of SLC11A1 gene and its association with the incidences of brucellosis in Hariana breed (Bos indicus) and Holstein Friesian crossbred (Bos indicus${\times}$Bos taurus) cattle was examined. A fragment of 954 bp encoding the TM4 was amplified, and RFLP was identified by digestion of the amplicon independently with AluI and TaqI. The amplicon (GenBank Acc. No. AY338470 and AY338471) comprised of a part of exon V (<59 bp) and VII (62>), and entire intron 5 (423 bp), exon VI (71 bp) and intron 6 (339 bp). Digestion with AluI revealed the presence of two alleles viz, A (281, 255, 79 and 51 bp) and B (541, 255, 79 and 51 bp). The frequency of A allele was estimated as 0.80 and 0.73 in Hariana and crossbred cattle, respectively. Due to presence of a polymorphic TaqI site at intron 5, two alleles: T (552 and 402 bp) and Q (231, 321 and 402 bp) were identified. The frequency of T allele was estimated as 0.96 and 0.97, respectively. For association study, on the basis of serological tests and history of abortion, the animals were grouped into "affected" and "non-affected". However, no association could be established with the observed RFLPs.

Identification and Characterization of Single Nucleotide Polymorphisms of SLC22A11 (hOAT4) in Korean Women Osteoporosis Patients

  • Lee, Woon Kyu;Kwak, Jin Oh;Hwang, Ji-Sun;Suh, Chang Kook;Cha, Seok Ho
    • Molecules and Cells
    • /
    • v.25 no.2
    • /
    • pp.265-271
    • /
    • 2008
  • Single nucleotide polymorphisms (SNPs) are the most common form of human genetic variation. Non-synonymous SNPs (nsSNPs) change an amino acid. Organic anion transporters (OATs) play an important role in eliminating or reabsorbing endogenous and exogenous organic anionic compounds. Among OATs, hOAT4 mediates high affinity transport of estrone sulfate and dehydroepiandrosterone sulfate. The rapid bone loss that occurs in post-menopausal women is mainly due to a net decrease of estrogen. In the present study we searched for SNPs within the exon regions of hOAT4 in Korean women osteoporosis patients. Fifty healthy subjects and 50 subjects with osteoporosis were screened for genetic polymorphism in the coding region of SLC22A11 (hOAT4) using GC-clamp PCR and denaturing gradient gel electrophoresis (DGGE). We found three SNPs in the hOAT4 gene. Two were in the osteoporosis group (C483A and G832A) and one in the normal group (C847T). One of the SNPs, G832A, is an nsSNP that changes the $278^{th}$ amino acid from glutamic acid to lysine (E278K). Uptake of [$3^H$] estrone sulfate by oocytes injected with the hOAT4 E278K mutant was reduced compared with wild-type hOAT4. Km values for wild type and E278K were $0.7{\mu}M$ and $1.2{\mu}M$, and Vmax values were 1.8 and 0.47 pmol/oocyte/h, respectively. The present study demonstrates that hOAT4 variants can causing inter-individual variation in anionic drug uptake and, therefore, could be used as markers for certain diseases including osteoporosis.

Gene Expression Signatures for Compound Response in Cancers

  • He, Ningning;Yoon, Suk-Joon
    • Genomics & Informatics
    • /
    • v.9 no.4
    • /
    • pp.173-180
    • /
    • 2011
  • Recent trends in generating multiple, large-scale datasets provide new challenges to manipulating the relationship of different types of components, such as gene expression and drug response data. Integrative analysis of compound response and gene expression datasets generates an opportunity to capture the possible mechanism of compounds by using signature genes on diverse types of cancer cell lines. Here, we integrated datasets of compound response and gene expression profiles on NCI60 cell lines and constructed a network, revealing the relationship for 801 compounds and 341 gene probes. As examples, obtusol, which shows an exclusive sensitivity on a small number of colon cell lines, is related to a set of gene probes that have unique overexpression in colon cell lines. We also found that the SLC7A11 gene, a direct target of miR-26b, might be a key element in understanding the action of many diverse classes of anticancer compounds. We demonstrated that this network might be useful for studying the mechanisms of varied compound response on diverse cancer cell lines.

Dataline Redundancy Circuit Using Simple Shift Logic Circuit for Dual-Port 1T-SRAM Embedded in Display ICs (디스플레이 IC 내장형 Dual-Port 1T-SRAM를 위한 간단한 시프트 로직 회로를 이용한 데이터라인 리던던시 회로)

  • Kwon, O-Sam;Min, Kyeong-Sik
    • Journal of IKEEE
    • /
    • v.11 no.4
    • /
    • pp.129-136
    • /
    • 2007
  • In this paper, a simple but effective Dataline Redundancy Circuit (DRC) is proposed for a dual-port 1T-SRAM embedded in Display ICs. The DRC designed in the dual-port $320{\times}120{\times}18$-bit 1T-SRAM is verified in a 0.18-um CMOS 1T-SRAM process. In the DRC, because its control logic circuit can be implemented by a simple Shift Logic Circuit (SLC) with only an inverter and a NAND that is much simpler than the conventional, it can be placed in a pitch as narrow as a bit line pair. Moreover, an improved version of the SLC is also proposed to reduce its worst-case delay from 12.3ns to 5.9ns by 52%. By doing so, the timing overhead of the DRC can be hidden under the row cycle time because switching of the datalines can be done between the times of the word line setup and the sense amplifier setup. The area overhead of the DRC is estimated about 7.6% in this paper.

  • PDF