摘要：
Double-stranded RNA dependent kinase R (PKR) is originally identified as an intracellular sensor of viral infection, but its role in bacterial infection remains largely unknown. Here we report that PKR was an important regulator of antibacterial immunity in sepsis. Genetic deletion of PKR or pharmacological inhibition of its kinase activity markedly increased bacterial loads, organ injury, and mortality in polymicrobial infection induced by cecal ligation and puncture (CLP). In contrast, PKR deficiency or inhibition did not affect bacterial loads, organ injury, or mortality when mice were systemically challenged with Escherichia coli, an abundant microbe in the gastrointestinal tract. PKR deficiency or inhibition markedly decreased the release of interleukin (IL)-1β after CLP. Defect in IL-1 signaling phenocopied PKR deficiency or inhibition in CLP-induced bacterial sepsis. Taken together, these findings identified a critical role of the PKR signaling pathway in antibacterial immunity.
通讯机构：
[Qiu, RH; Yin, SF; Chen, Yi] H;Hunan Univ, Coll Chem & Chem Engn, State Key Lab Chemo Biosensing & Chemometr, Changsha 410082, Hunan, Peoples R China.;Hunan Univ Chinese Med, Sch Med, Changsha 410208, Hunan, Peoples R China.
摘要：
A series of organoantimony(iii) halide complexes with a tetrahydrodibenzo[c,f][1,5]azastibocine framework were synthesized and employed as water tolerant Lewis acid catalysts. The results of a systematic structure-activity relationship study demonstrated that the strength of N -> Sb donor-acceptor interaction could be synergistically modulated by tuning the properties of the nitrogen substituents and halogen atoms adjacent to the central antimony atom, and consequently resulted in distinct catalytic performances towards organic reactions such as Mannich, cross-condensation, cyclization-aromatization and epoxide aminolysis reaction. The fluorinated organoantimony(iii) derivatives were found to be more active than those of the chlorinated, brominated and iodinated analogues, owing to the use of an Sb-F moiety as a hydrogen bond acceptor. By comparison, the compound 6-cyclohexyl-12-fluoro-5,6,7,12-tetrahydrodibenzo[c,f][1,5] azastibocine (1d) is found to exhibit the highest catalytic activity, together with facile reusability in scale enlarged synthesis.
期刊：
Journal of Venomous Animals and Toxins Including Tropical Diseases,2019年25 ISSN：1678-9199
通讯作者：
Deng, Meichun
作者机构：
[Wu, Wenfang; Wang, Meng; Deng, Meichun; Luo, Qianxuan; Wu, Ting] Cent S Univ, Sch Life Sci, Dept Biochem & Mol Biol, Changsha 410013, Hunan, Peoples R China.;[Wang, Meng; Wu, Ting] Cent S Univ, Xiangya Sch Med, Changsha 410013, Hunan, Peoples R China.;[Jiang, Liping] Cent S Univ, Xiangya Sch Med, Dept Parasitol, Changsha 410013, Hunan, Peoples R China.;[Tao, Huai] Hunan Univ Chinese Med, Dept Biochem & Mol Biol, Changsha 410208, Hunan, Peoples R China.
通讯机构：
[Deng, Meichun] C;Cent S Univ, Sch Life Sci, Dept Biochem & Mol Biol, Changsha 410013, Hunan, Peoples R China.
关键词：
Abstract Spider venoms are known to contain proteins and polypeptides that perform various functions including antimicrobial, neurotoxic, analgesic, cytotoxic, necrotic, and hemagglutinic activities. Currently, several classes of natural molecules from spider venoms are potential sources of chemotherapeutics against tumor cells. Some of the spider peptide toxins produce lethal effects on tumor cells by regulating the cell cycle, activating caspase pathway or inactivating mitochondria. Some of them also target the various types of ion channels (including voltage-gated calcium channels, voltage-gated sodium channels, and acid-sensing ion channels) among other pain-related targets. Herein we review the structure and pharmacology of spider-venom peptides that are being used as leads for the development of therapeutics against the pathophysiological conditions including cancer and pain. Keywords spider venom peptides;antitumor;pain;drug candidates
摘要：
Spider venoms are known to contain proteins and polypeptides that perform various functions including antimicrobial, neurotoxic, analgesic, cytotoxic, necrotic, and hemagglutinic activities. Currently, several classes of natural molecules from spider venoms are potential sources of chemotherapeutics against tumor cells. Some of the spider peptide toxins produce lethal effects on tumor cells by regulating the cell cycle, activating caspase pathway or inactivating mitochondria. Some of them also target the various types of ion channels (including voltage-gated calcium channels, voltage-gated sodium channels, and acid-sensing ion channels) among other pain-related targets. Herein we review the structure and pharmacology of spider-venom peptides that are being used as leads for the development of therapeutics against the pathophysiological conditions including cancer and pain. Keywords spider venom peptides; antitumor; pain; drug candidates
期刊：
American Journal of Physiology - Gastrointestinal and Liver Physiology,2019年316(6):G774-G784 ISSN：0193-1857
通讯作者：
Li, Yan Chun
作者机构：
[Adhikari, Sarbani; Pekow, Joel; Rubin, David T.; Zhou, Min; He, Lei; Du, Jie; Chen, Yinyin; Liu, Chunyan; Li, Yan Chun] Univ Chicago, Dept Med, Div Biol Sci, Chicago, IL 60637 USA.;[Du, Jie] Shanxi Med Univ, Inst Biomed Res, Taiyuan, Shanxi, Peoples R China.;[Chen, Yinyin] Hunan Normal Univ, Hunan Prov Peoples Hosp, Dept Nephrol, Changsha, Hunan, Peoples R China.;[Liu, Chunyan] Hunan Univ Chinese Med, Dept Pathol, Changsha, Hunan, Peoples R China.;[Zhou, Min] Shanghai Jiao Tong Univ, Xinhua Hosp, Div Gastroenterol, Sch Med, Shanghai, Peoples R China.
通讯机构：
[Li, Yan Chun] U;Univ Chicago, Dept Med, 900 E 57th St,KCBD 9110, Chicago, IL 60637 USA.
关键词：
JAK;STAT;T17;colitis;mucosal inflammation;renin-angiotensin system
摘要：
Previous studies suggest that the renin-angiotensin system (RAS) is a pathogenic factor for colitis. The goal of this study was to elucidate the molecular mechanism whereby angiotensin II (ANG II) promotes colonic inflammation. We found that renin was highly induced in colonic biopsies from patients with ulcerative colitis or Crohn's disease, and colonic renin and ANG II levels were markedly increased in a 2,4,6-trinitrobenzene sulfonic acid (TNBS)-induced colitis model, indicating that the colonic RAS is activated in colitis. Renin transgenic (RenTg) mice exhibited increased phosphorylation in Janus kinase-2 (JAK2) and signal transducer and activator of transcription1/3 (STAT1/3) within colonic mucosa at baseline and following TNBS induction, suggesting that ANG II promotes colonic inflammation via the JAK2/STAT1/3 pathway. Treatment with pan-JAK inhibitor tofacitinib blocked JAK2 and STAT1/3 phosphorylation, attenuated T helper (TH)1 and TH17 responses, alleviated colitis, and prevented death of RenTg mice in TNBS model. ANG II stimulated JAK2/STAT1/3 phosphorylation in both Jurkat T lymphocytes and HCT116 epithelial cells. In vitro polarization assays demonstrated that ANG II directly promoted TH17 polarization, but not TH1 polarization, via JAK2/STAT1/3. ANG II stimulation of transforming growth factor-beta1 (TGFbeta1), IL-6, myosin light chain kinase, and p53 upregulated modulator of apoptosis in HCT116 cells was also mediated by JAK2/STAT1/3. These observations suggest that ANG II promotes TH17 polarization directly as well as indirectly by inducing production of TH17-polarizing cytokines (e.g., TGFbeta1 and IL-6) from colonic epithelial cells, both via the JAK2/STAT pathway. Therefore, colonic RAS promotes colonic inflammation, at least in part, by stimulating TH17 activation. NEW & NOTEWORTHY This study demonstrates that the local renin-angiotensin system in the colon is activated in colitis development, which promotes mucosal T helper cell activation through the JAK2/STAT pathway. These observations provide molecular evidence that the renin-angiotensin system is a pathogenic factor for the development of inflammatory bowel diseases.
摘要：
Objective: To investigate the three-dimensional lip vermilion changes after extraction and non-extraction orthodontic treatment in female adult patients and explore the correlation between lip vermilion changes and incisor changes. Methods: Forty-seven young female adult patients were enrolled in this study (skeletal Class III patients were excluded), including 34 lip-protruding patients treated by extraction of four first premolars (18 patients requiring mini-implants for maximum anchorage control and 16 patients without mini-implants) and 13 patients requiring non-extraction treatment. Nine angles, seven distances, and the surface area of the lip vermilion were measured by using pre- and post-treatment three-dimensional facial scans. Linear and angular measurements of incisors were performed on lateral cephalograms. Results: There were no significant changes in the vermilion measurements in the non-extraction group. The vermilion angle, vermilion height, central bow angle, height/width ratio, and vermilion surface area decreased significantly after the orthodontic treatment in the extraction groups, but the upper/lower vermilion proportion remained unchanged. Significant correlations were found between the changes in incisor position and those in vermilion angles, vermilion height, and surface area. Conclusions: Extraction of the four first premolars probably produced an aesthetic improvement in lip vermilion morphology. However, the upper/lower vermilion proportion remained unchanged. The variations in the vermilion were closely related to incisor changes, especially the upper incisor inclination changes.
摘要：
The relationship between chemical structure and in vitro cytotoxic activities of a series of azastibocine-framework organoantimony(III) halide complexes against cancerous (HepG2, MDA-MB-231, MCF-7 and HeLa) and nonmalignant (HEK-293) cell lines was studied for the first time. A positive correlation between cytotoxic activity and the length of N-->Sb coordinate bond on azastibocine framework of same nitrogen substituent was observed. By comparison, the organoantimony(III) complex 6-cyclohexyl-12-fluoro-5,6,7,12-tetrahydrodibenzo[c,f][1,5]azastibocine (C4) exhibited the highest selectivity index, giving a IC50(nonmalignant)/IC50(cancerous) ratio of up to 8.33. The results of cell cycle analysis indicated that the inhibitory effect of C4 on the cellular viability was caused by cell cycle arrest mainly at the S phase. The necrosis induced by C4 was confirmed by the Trypan blue dye exclusion test and the increase of lactic dehydrogenase (LDH) released in the culture medium. Furthermore, evaluation of the levels of intracellular reactive oxygen species (ROS) in MDA-MB-231cells, by quantifying the relative fluorescence units (RFU) using spectrofluorometer, indicated that cytotoxic activity of C4 is dependent on the production of ROS. This work established the correlation between cytotoxic activity and N-->Sb inter-coordination, a finding that provided theoretical and experimental basis for in-depth design of antimony-based organometallic complexes as potential anticancer agents.
通讯机构：
[Yin, Shuang-Feng; Chen, Yi] H;Hunan Univ, Coll Chem & Chem Engn, State Key Lab Chemo Biosensing & Chemometr, Changsha 410082, Hunan, Peoples R China.;Hunan Univ Chinese Med, Sch Med, Changsha 410208, Hunan, Peoples R China.
摘要：
An efficient metal-free method for the synthesis of organophosphorus compounds via oxidative cross dehydrogenative coupling of benzylic C(sp(3))-H bonds in methylarenes with P(O)-OH compounds catalysed by cetyltrimethyl ammonium bromide (CTAB) is reported. Various methylarenes and P(O)-OH compounds are tolerated in the reaction with moderate to good yields. Compared to previous studies, the present study extends the substrate scope and adopts a new reaction system of an ammonium salt catalyst (CTAB) and an oxidant (DTBP). The results of control and mechanistic experiments are generally in agreement with the overall proposed pathway. This method circumvents the use of toxic P-halogen reagents and P(O)-H compounds for the synthesis of organophosphorus compounds.
摘要：
Schizophrenia (SZ) is a debilitating and heterogeneous disease. We hypothesized that the oxytocin (OXT) system, inflammation and one-carbon metabolism would have a link with SZ. In this study, serum OXT, OXT receptor (OXTR), interleukin-6 (IL-6), high sensitivity CRP (hsCRP) and homocysteine (Hcy) levels were measured in 52 first-episode schizophrenia (FES) patients and 41 healthy controls (HC) from the Second Xiangya Hospital of Central South University. Meanwhile, the mRNA expressions of OXT and OXTR genes were determined by real-time quantitative PCR. Serum OXT and OXTR levels were significantly lower in FES patients (518.96 +/- 22.22 and 174.60 +/- 17.11 pg/ml) than the HC group (711.58 +/- 40.57 and 252.15 +/- 20.62 pg/ml). Serum IL-6 and hsCRP levels showed no difference between the two groups (1.82 +/- 0.30 vs. 1.69 +/- 0.36 pg/ml, 0.66 (0.22, 1.07) vs. 0.31 (0.13, 0.91) mg/L), but serum Hcy levels were significantly higher in FES patients (20.18 +/- 1.83 vs. 15.24 +/- 0.82 mumol/ml). The FES patients (0.27 +/- 0.02 and 0.20 +/- 0.02) have relatively higher mRNA expressions of OXT and OXTR genes than the HC group (0.16 +/- 0.01 and 0.14 +/- 0.01). In summary, our results suggested the possible function of the OXT system and Hcy in the pathogenesis of SZ.
摘要：
Cytokines activation and low complement levels are common in systemic lupus erythematosus (SLE) patients. This study is aimed to explore the relationship and clinical significance of cytokines and complements with SLE activity. Serum samples of 140 SLE patients and 36 age- and gender-matched healthy controls (HC) were collected. Serum interleukin (IL)-6, IL-17, high-sensitivity C-reactive proteins (hsCRP), and complements (C3, C4) were measured in all samples. These patients were divided into 3 subgroups based on clinical disease activity with SLE Disease Activity Index 2000 (SLEDAI-2K): stationary status subgroup, mild activity subgroup, and moderate/severe activity subgroup. The serum IL-6, IL-17, and hsCRP levels in SLE patients (4.72 +/- 0.28 pg/mL, 23.34 +/- 1.32 pg/mL, and 4.78 +/- 0.34 mg/mL) were significantly higher than those in the HC group (1.51 +/- 0.05 pg/mL, 18.28 +/- 1.93 pg/mL, and 1.32 +/- 0.29 mg/mL), whereas C3 and C4 levels in SLE patients (0.80 +/- 0.28 and 0.21 +/- 0.08 g/L) were significantly lower than those in the HC group (1.49 +/- 0.08 and 0.36 +/- 0.02 g/L). A positive correlation was noted between the SLEDAI-2K scores and serum IL-6, IL-17, and hsCRP levels. These results support the proinflammatory cytokines and complements in the pathogenesis of SLE. The serum IL-6, IL-17, and hsCRP levels were correlated with the disease activity.
摘要：
A highly sensitive and selective fluorometric method is described for determination of mercury(II). It is based on (a) the use of graphene oxide (GO) acting as a quencher of the fluoresence of the carboxy-fluorescein (FAM), and (b) of Hg(II)-triggered cleavage of the newly formed nucleic acid sequences harbored blunt 3'-hydroxyl termini by exonuclease III (Exo III) that leads to signal amplification. Two DNA probes are used, viz. a capture probe (CP) and a help probe; HP) that is partially complementary. In the absence of Hg(II), the FAM-labeled hairpin (signal probe, SP) is adsorbed onto the surface of GO via pi-stacking interactions. CP blocks the release of the HP for binding to SP. This results in quenching of the green fluorescence of the label. Upon addition of Hg(II), the linear structure of CP is converted to a hairpin structure due to the formation of thymidine-Hg(II)-thymidine duplexes. HP is released from the CP/HP hybrids, and this causes SP to be released from from GO and fluorescence to be recovered. The signal is strongly amplified by using Exo III-assisted targeting and recycling of HP. Hence, Hg(II) can be detected via the strong increase in fluorescence. The method has a linear response in the 0.1 to 30 nM Hg(II) concentration range and a 10 pM detection limit. It was applied to the determination of Hg(II) in three (spiked) Chinese medicines. Graphical abstract Schematic representation of fluorescence sensing strategy for Hg(2+) by using graphene oxide as a quencher and exonuclease III-assisted signal amplification.
作者机构：
[Zhang, Mengxia] Hunan Univ Chinese Med, Dept Histol & Embryol, Changsha 410208, Hunan, Peoples R China.;[Tang, Shengsong] Hunan Univ Med, Hunan Prov Key Lab Antibody Based Drug & Intellig, Huaihua 418000, Hunan, Peoples R China.;[Zhang, Mengxia; Liu, Qi; Mo, Zhongcheng] Univ South China, Clin Anat & Reprod Med Applicat Inst, Dept Histol & Embryol, Hengyang 421001, Hunan, Peoples R China.;[Tang, Shengsong; Lei, Xiaoyong; Tu, Jian; Li, Lijun] Univ South China, Insitute Pharm & Pharmacol, Hengyang 421001, Hunan, Peoples R China.;[Ning, Jing; Tang, Shengsong] Hunan Univ Med, Dept Pharmacol, Huaihua 418000, Hunan, Peoples R China.
通讯机构：
[Tang, Shengsong] H;Hunan Univ Med, Hunan Prov Key Lab Antibody Based Drug & Intellig, Huaihua 418000, Hunan, Peoples R China.
关键词：
macrophage colony-stimulating factor;breast cancer;apoptosis;HIF-1 and BINP3
摘要：
Macrophage colony-stimulating factor (M-CSF), a tumour marker, is related to tumour cell anti-apoptosis and drug resistance. However, the role of M-CSF in MCF-7 cells is unknown. In the present study, the effect and mechanism of M-CSF on hypoxia-inducible factor-1 (HIF-1)/BCL2/adenovirus E1B 19 kDa-interacting protein 3 (BNIP3)/Apoptosis Regulator BAX signalling in human breast cancer MCF-7 cells were investigated. Western blotting revealed that the expression of HIF-1, BNIP3, Bax, caspase-3 and caspase-9 was lower in MCF-7-M cells compared to MCF-7 and MCF-7-C cells treated with adriamycin (ADM). Immunoprecipitation combined with western blotting was used to detect the interaction between Bcl-2 and BNIP3 or Bax protein. MCF-7-M cells had a higher amount of Bax binding to Bcl-2 compared to MCF-7 cells or MCF-7-C cells, while the amount of BNIP3 binding to Bcl-2 was decreased in MCF-7-M cells. Hoechst 33342 staining and flow cytometry were utilized to evaluate the effect of M-CSF on apoptosis in MCF-7 cells treated with ADM. Compared to ADM-treated MCF-7 cells, the apoptotic rate of MCF-7-M cells was significantly decreased. These effects were dependent on the concentration of ADM. In conclusion, cytoplasmic M-CSF suppressed apoptosis by inhibiting the HIF-1/BNIP3/Bax signalling pathway, which potentiated the dissociation of Bcl-2 from Bcl-2-BNIP3 compounds and the formation of Bcl-2-Bax compounds.
摘要：
Combination with genomic DNA is one of the important ways for microRNAs (miRNAs) to perform biological processes. However, because of lack of an experimental method, the identified genomic sites targeted by microRNA were only located in the promoter and enhancer regions. In this study, based on affinity purification of labeled biotin at the 3'-end of miRNAs, we established an efficiently experimental method to screen miRNA binding sequences in the whole genomic regions in vivo. Biotinylated miR-373 was used to test our approach in MCF-7 cells, and then Sanger and next-generation sequencing were used to screen miR-373 binding sequences. Our results demonstrated that the genomic fragments precipitated by miR-373 were located not only in promoter but also in intron, exon, and intergenic. Eleven potentially miR-373 targeting genes were selected for further study, and all of these genes were significantly regulated by miR-373. Furthermore, the targeting sequences located in E-cadherin, cold-shock domain-containing protein C2 (CSDC2), and PDE4D genes could interact with miR-373 in MCF-7 cells rather than HeLa cells, which is consistent with our data that these three genes can be regulated by miR-373 in MCF-7 cells while not in HeLa cells. On the whole, this is an efficient method to identify miRNA targeting sequences in the whole genome.
关键词：
Inflammation;Systemic lupus erythematosus;Vitamin D receptor
摘要：
OBJECTIVE: Systemic lupus erythematosus (SLE) is characterized by uncontrolled production of pro-inflammatory cytokines. Vitamin D receptor (VDR) has potent anti-inflammatory activities. The aim of this study was to examine the correlation between VDR expression and inflammation and disease activity in patients with SLE. METHODS: Ninety-five SLE patients were recruited and divided into two groups, active and inactive, according to their SLE disease activity index (SLEDAI)-2 K, and 40 healthy individuals served as controls. The expression of VDR and NF-kappaB p65 in peripheral blood mononuclear cells (PBMCs) was determined by quantitative RT-PCR and Western blotting. VDR expression was correlated with inflammatory and diseases parameters in SLE patients. VDR regulation was also studied in THP-1 and Jurkat cell lines. RESULTS: PBMC VDR expression was downregulated in SLE patients, especially in the active SLE group. VDR mRNA levels were negatively correlated with SLEDAI-2 K (r = - 0.348, P = 0.001), Systemic Lupus International Collaborating Clinics (SLICC) renal activity scores (r = - 0.346, P = 0.014), and proteinuria (r = - 0.309, P = 0.002) and positively associated with serum complement C3 levels (r = 0.316, P = 0.002). Multiple stepwise regression analysis indicated that PBMC VDR downregulation was an independent risk factor for SLEDAI-2 K. VDR levels were also negatively correlated with NF-kappaB p65 (r = - 0.339, P = 0.001), TNF-alpha (r = - 0.268, P = 0.009), and IL-6 (r = - 0.313, P = 0.002) levels. In monocyte and T lymphocyte cell lines, TNF-alpha suppressed VDR expression, whereas 1,25-dihydroxyvitamin D blocked TNF-alpha-induced VDR downregulation. CONCLUSION: PBMC VDR expression is inversely associated with disease activity and inflammation in SLE patients, and VDR downregulation is likely driven by inflammation.
摘要：
Polycystic ovary syndrome (PCOS) is widely accepted as the most common endocrine abnormality in women of childbearing age and may be accompanied by dyslipidemia, hyperandrogenism, hyperinsulinemia, oxidative stress and infertility. Dyslipidemia is now known to play an important role in the development of PCOS. Lipid abnormalities, including elevated low-density lipoprotein and triglyceride levels and reduced high-density lipoprotein levels, are often found in women with PCOS and play an important role in PCOS; therefore, we summarize the effect of lipid abnormalities on hyperandrogenism, insulin resistance, oxidative stress and infertility in PCOS and review the effects of common lipid-lowering drugs on patients with PCOS. The purpose of this article is to elucidate the mechanisms of lipid metabolism abnormalities in the development of PCOS. (C) 2019 Taiwan Association of Obstetrics & Gynecology. Publishing services by Elsevier B.V.
期刊：
International Journal of Molecular Medicine,2019年43(5):2055-2063 ISSN：1107-3756
通讯作者：
Liu, Lu-Shan;Wang, Mei-Mei
作者机构：
[Jiang, Zhi-Sheng; Ren, Zhong; Xiao, Jun; Liao, Ling; Tang, Zhi-Han; Zhou, Min; Xiang, Qiong; Peng, Juan; Bai, Xue-Qin; Liu, Lu-Shan] Univ South China, Inst Cardiovasc Dis, Key Lab Arteriosclerol Hunan Prov, 28 West Changsheng Rd, Hengyang 421001, Hunan, Peoples R China.;[Wen, Hong-Yan] Hunan Univ Chinese Med, Med Coll, Changsha 410208, Hunan, Peoples R China.;[Wang, Mei-Mei] Univ South China, Affiliated Nanhua Hosp, Dept Pediat, 28 West Changsheng Rd, Hengyang 421001, Hunan, Peoples R China.
通讯机构：
[Liu, Lu-Shan; Wang, Mei-Mei] U;Univ South China, Inst Cardiovasc Dis, Key Lab Arteriosclerol Hunan Prov, 28 West Changsheng Rd, Hengyang 421001, Hunan, Peoples R China.;Univ South China, Affiliated Nanhua Hosp, Dept Pediat, 28 West Changsheng Rd, Hengyang 421001, Hunan, Peoples R China.
关键词：
HepG2 cells;Hydrogen sulfide;Lipid metabolism;Low-density lipoprotein receptor;Phosphoinositide 3-kinase/protein kinase B;Proprotein convertase subtilisin/kexin type 9;Sterol regulatory element-binding protein 2
摘要：
Hydrogen sulfide (H2S) is an endogenous gaseous signaling molecule that plays important roles in the cardiovascular system. In our previous studies, we demonstrated that H2S regulates lipid metabolism. In the present study, we aimed to explore the mechanisms through which H2S regulates lipid metabolism in HepG2 cells in vitro. Treatment of the HepG2 cells with H2S inhibited the expression of proprotein convertase subtilisin/kexin type 9 (PCSK9) and increased the level of lowdensity lipoprotein receptor (LDLR) in a time and dosedependent manner. The knockdown of PCSK9 by siRNA effectively increased the levels of LDLR and 1,1'dioctadecyl3,3,3',3'tetramethylindocarbocyanine perchloratelabeled LDL (DiILDL) uptake in the H2Streated HepG2 cells. Furthermore, the phosphoinositide 3kinase (PI3K)/protein kinase B (Akt)sterol regulatory element binding proteins 2 (SREBP2) signaling pathway was confirmed to be involved in H2Sregulated PCSK9 expression. Notably, the HepG2 cells were incubated with 30% serum and DiILDL for 24 h, and the results revealed that H2S increased lipid uptake, but caused no increase in lipid accumulation. On the whole, the findings of this study demonstrate that H2S is involved in the regulation of lipid metabolism in HepG2 cells through the regulation of the expression of PCSK9 via the PI3K/AktSREBP2 signaling pathway. To the very best of our knowledge, this study is the first to report that H2S can regulate the expression of PCSK9.
