Circular RNA circHIPK3 modulates prostate cancer progression via targeting miR-448/MTDH signaling.

PURPOSE: Prostate cancer (PCa) is one of the most diagnosed cancers in men worldwide. Several studies have identified that circular RNAs (circRNAs) have a crucial impact on the biological processes in PCa. Therefore, it is necessary to study the molecular mechanism of circRNAs in tumor progression and metastasis. METHODS: RNA interference was used to decrease circHIPK3 and MTDH expression. Overexpression vector was used to increase circHIPK3 and MTDH expression. Luciferase reporter assay were used to detect the relationship between circHIPK3 and miR-448 or between miR-448 and MTDH. MTT assay, colony formation assay and transwell assay were used to measure proliferation and migration of PCa cells. RESULTS: Circular RNA circHIPK3 was significantly increased in PCa tissues and cell lines. And overexpression of circHIPK3 promoted the migration, proliferation, and invasion of PC-3 and 22Rv1 cells, while knockdown of circHIPK3 markedly repressed the above-mentioned series of biological processes. Furthermore, circHIPK3 promoted metadherin (MTDH) expression by sponging miR-448. In vivo experiments, it was also found that overexpression of circHIPK3 significantly promoted tumor growth. CONCLUSIONS: Our research shows that circHIPK3 plays a carcinogenic effect in PCa by regulating the miR-448/MTDH axis, indicating that circHIPK3 may be a potential therapeutic target for PCa.

Paeonol inhibits proliferation and induces cell apoptosis of human T24 and 5637 bladder cancer cells in vitro and in vivo.

PURPOSE: Paeonol is a natural chemical medicine derived from the bark of peony root, which has been found to inhibit tumor activity in various tumor cell lines, and can play a synergistic anti-tumor effect with chemotherapy or radiotherapy. METHODS: We used paeonol to act on human bladder cancer T24 and 5637 cells, and established xenograft tumor in nude mice by subcutaneous injection of T24 cells. RESULTS: CCK-8 assay and plate cloning experiments showed that paeonol could inhibit the proliferation of T24 and 5637 cells in vitro. The results of flow cytometry and the detection of BAX, Bcl-2 and Caspase-3 proteins suggested that paeonol can induce apoptosis of T24 and 5637 cells in vitro. Tumor formation, TUNEL detection and immunohistochemical results of Ki67, BAX, Bcl-2 and Caspase-3 in nude mice showed that paeonol could inhibit T24 cell proliferation and induce apoptosis in vivo, thus inhibiting tumor growth. Further research revealed that paeonol could reduce phosphorylation expression of PI3K and AKT in T24 and 5637 cells. CONCLUSION: We confirmed that paeonol could inhibit proliferation and induce apoptosis of human bladder cancer T24 and 5637 cells in vitro and in vivo, inhibit the growth of T24 tumor-forming nude mice, and possibly play a role by inhibiting the PI3K/AKT signaling pathway, so as to provide a potential therapeutic drug for bladder cancer.

[Metastatic renal cell carcinoma: a clinicopathological analysis of 196 cases].

Objective: To analyze the clinico pathological features, differential diagnosis and prognosis of metastatic renal cell carcinomas. Methods: The clinical data, histology, immunophenotype and follow-up data of 196 patients with metastatic renal cell carcinoma diagnosed from 1994 to 2017 at the Department of Pathology, Changhai Hospital, Naval Military Medical University, Shanghai, China were analyzed retrospectively. Results: There were 142 males and 54 females, with a median age of 61 years. The top three metastatic sites for the 196 cases of metastatic renal cell carcinoma were lung (31.1%, 61/196), bone (29.1%, 57/196) and digestive system (19.4%, 38/196). Among the pathological subtypes of metastasis, the proportion of clear cell renal cell carcinoma was 94.4% (185/196) and that of type II papillary renal cell carcinoma was 3.6% (7/196). The TFE3 translocated renal cell carcinoma and congestive tubular carcinoma were rare, with 3 cases and 1 case, respectively. CK, vimentin, CAⅨ and CD10 were expressed in all metastatic clear cell renal cell carcinomas. CK7, CD10 and P504s were expressed in papillary renal cell carcinomas. TFE3 was expressed in TFE3 translocated renal cell carcinoma. The collecting duct carcinoma was positive for HCK. Conclusions: Lung metastasis and bone metastasis are still the most frequent metastatic sites of renal cell carcinoma. Five years after primary lesion resection may be the high risk time for metastasis. Most of the metastases are solitary when they are first identified. To better diagnose and identify the renal origin of a metastatic renal cell carcinoma, one should consider morphological characteristics, clinical history information of the metastasis and the combined immunohistochemistry of CK, vimentin, CD10, CK7, TFE3, PAX2 and PAX8.

Long non-coding RNA LINC00173 serves as sponge for miR-338-3p to promote prostate cancer progression via regulating Rab25.

OBJECTIVE: Long non-coding RNA LINC00173 (LINC00173) has been shown to facilitate the progression of a number of malignancies. In this study, we aimed to investigate the function of LINC00173 on prostate cancer (PCa) and discover the potential regulatory mechanism. PATIENTS AND METHODS: RT-PCR was used to determine the levels of LINC00173, miR-338-3p and Rab25 in PCa patients and cell lines. The clinical significance of LINC00173 was statistically analyzed in 124 PCa patients. CCK-8, colony formation, transwell, scratch wound, Ethynyldeoxyuridine (EdU) assays and flow cytometry assays were used to detect the proliferation, apoptosis, invasion and migration of PCa cells. The mechanism of LINC00173 action was explored through bioinformatics, RNA pull-down assays and Luciferase reporter assays. RESULTS: We observed that the expression of LINC00173 and Rab25 was distinctly upregulated in both PCa specimens and cell lines, while miR-338-3p expression was significantly down-regulated. High LINC00173 expression was associated with Gleason score, preoperative PSA level and reduced patient survivals. Functional assays revealed that knockdown of LINC00173 suppressed the proliferation, migration and invasion of PCa cells, and promoted apoptosis. Mechanistically, LINC00173 acted as a competitive endogenous RNA in PCa and increased Rab25 expressions via sponging miR-338-3p. Moreover, LINC00173 promoted PCa progression by interacting with miR-338-3p and Rab25. CONCLUSIONS: Our findings, for the first time, identified a novel PCa-related lncRNA, LINC00173 which might serve as an oncogene in PCa. The discovery of the LINC00173/miR-338-3p/Rab25 pathways provided new thinking for the treatments of PCa.

Oxidative stress induced necroptosis activation is involved in the pathogenesis of hyperoxic acute lung injury.

Necroptosis has been found to be involved in the pathogenesis of some lung diseases, but its role in hyperoxic acute lung injury (HALI) is still unclear. This study aimed to investigate contribution of necroptosis to the pathogenesis of HALI induced by hyperbaric hyperoxia exposure in a rat model. Rats were divided into control group, HALI group, Nec-1 (necroptosis inhibitor) group and edaravone group. Rats were exposed to pure oxygen at 250 kPa for 6 h to induce HALI. At 30 min before hyperoxia exposure, rats were intraperitoneally injected with Nec-1 or edaravone, and sacrificed at 24 h after hyperoxia exposure. Lung injury was evaluated by histology, lung water to dry ratio (W/D) and bronchoalveolar lavage fluid (BALF) biochemistry; the serum and plasma oxidative stress, expression of RIP1, RIP3 and MLKL, and interaction between RIP1 and RIP3 were determined. Results showed hyperoxia exposure significantly caused damage to lung and increased necroptotic cells and the expression of RIP1, RIP3 and MLKL. Edaravone pre-treatment not only inhibited the oxidative stress in HALI, but also reduced necroptotic cells, decreased the expression of RIP1, RIP3 and MLKL and improved lung pathology. Nec-1 pretreatment inhibited necroptosis and improved lung pathology, but had little influence on oxidative stress. This study suggests hyperoxia exposure induces oxidative stress may activate necroptosis, involving in the pathology of HALI, and strategies targeting necroptosis may become promising treatments for HALI.

Construction of conditionally replicating adenovirus expressing staphylococcal enterotoxin A gene: potential usefulness for anti-tumor therapies.

OBJECTIVE: The aim of this study was to construct a conditionally replicating adenovirus pPE3-SEA expressing staphylococcal enterotoxin A (SEA) gene. MATERIALS AND METHODS: A full-length SEA gene fragment was cloned into pENTR12 plasmid to obtain a recombinant viral plasmid pENTR12-SEA. The pENTR12-SEA plasmid was co-transfected into HEK293 cells along with pPE3-ccdB, which encoded for the virus backbone, to generate recombinant adenovirus pPE3-SEA vector. Amplified pPE3-SEA vectors were purified, and viral titer was determined using the 50% tissue culture infective dose method. RESULTS: The PCR, restriction enzyme digestion, and sequence analyses proved successful construction of replicating oncolytic adenovirus pENTR12-SEA and recombinant SEA expressing oncolytic adenovirus pPE3-SEA. The viral titer was 2.5 × 1010 pfu/ml. CONCLUSIONS: We successfully constructed conditionally replicating adenovirus pPE3-SEA which can be utilized for experimental studies of tumor-targeted therapies.

Cbl-b gene silencing in splenic T lymphocytes as a therapeutic strategy to target the prostate cancer RM-1 cell tumors in immune competent mice.

OBJECTIVE: In recent years, the field of cancer immunotherapy has become a research hotspot and is currently faced with numerous challenges. The objective of this study was to assess the success of cbl-b gene silencing in splenic T lymphocytes as an immune strategy to target the murine prostate cancer RM-1 cells in vitro and solid tumors in vivo. MATERIALS AND METHODS: For this purpose, cbl-b gene-specific siRNA was designed, synthesized, and was transfected into mouse splenic T lymphocytes, followed by assessment of T cell activation, TH1 cytokine production, and in vitro cytotoxicity against RM-1 cell targets. For in vivo cytotoxicity studies, first the RM-1 tumor model was established in immune competent mice that were later tumor-injected with splenic T lymphocytes transfected with specific shRNA for cbl-b gene silencing. RESULTS: The data show that the cbl-b gene silencing in T lymphocytes resulted in an enhanced surface expression of CD69 activation marker, elevated production of interleukin (IL)-2 and interferon (IFN)-γ, and their increased cytotoxicity as effectors against RM-1 prostate cancer cells. The tumor injection with cbl-b shRNA-transfected T lymphocytes also resulted in significant reduction of the tumor size as compared with controls. CONCLUSIONS: cbl-b gene silencing strategy enhanced the immune function of T lymphocytes, increased their cytotoxic potential against RM-1 prostate cancer cells, as well as caused significant suppression of the tumor growth in immune competent mice.

Experience with the treatment of testicular yolk sac tumor in children: a report of 14 cases.

OBJECTIVE: This paper discusses the optimal treatment for testicular yolk sac tumor at stage I in children. PATIENTS AND METHODS: Fourteen children with testicular yolk sac tumor (including 10 cases of stage I and 4 cases of stage II) underwent high ligation of internal spermatic cord vein and orchiectomy. Among these, seven cases of stage I were below 1 year of age. Retroperitoneal lymph node dissection without postoperative systemic chemotherapy was implemented in 9 cases (5 cases of stage I and 4 cases of stage II), and only one was positive. RESULTS: Among the 12 cases followed, 9 cases were alive (of these, 5 children < 1 year old, in stage I, underwent high ligation of internal spermatic cord vein and orchiectomy, with a survival time of 25 months to 10 years and 4 cases with radical retroperitoneal lymph node dissection). Three cases older than 1 year died of retroperitoneal lymph node and lung metastases. CONCLUSIONS: For the high ligation of internal spermatic cord vein, orchiectomy is a kind of simple and effective treatment for children younger than 1 year with stage I, without recurrence and metastases. However, attention to the accuracy of staging and close observation are important aspects of the treatment.

Effects of Polycan, a ß-glucan, on experimental periodontitis and alveolar bone loss in Sprague-Dawley rats.

BACKGROUND AND OBJECTIVE: Polycan is a promising candidate for the treatment of periodontal disease. This study was undertaken to examine whether Polycan, a type of ß-glucan, has a protective effect on ligature-induced experimental periodontitis and related alveolar bone loss in Sprague-Dawley rats. MATERIAL AND METHODS: Polycan was orally administered, daily, for 10 d, at 21.25, 42.5 or 85 mg/kg, beginning 1 d after ligation. Changes in body weight and alveolar bone loss were monitored, and the anti-inflammatory effects of Polycan were determined by measuring the levels of myeloperoxidase (MPO), interleukin-1beta (IL-1ß) and tumor necrosis factor-alpha (TNF-α) in gingival tissue. We also evaluated inducible nitric oxide synthase (iNOS) activity and malondialdehyde (MDA) concentrations as a measure of the antioxidant effect. RESULTS: Ligature placement led to a marked decrease in body weight, increased alveolar bone loss and increased concentrations of MPO, IL-1ß, TNF-α and MDA, as well as increased iNOS activity and inflammatory cell infiltration and decreased collagen-fiber content. Histological examination revealed increases in the number and activity of osteoclast cells, decreases in alveolar bone volume and elevated percentages of osteclasts on the alveolar bone surface. Daily oral treatment with 42.5 or 85 mg/kg of Polycan for 10 d led to significant, dose-dependent inhibition of the effect of ligature placement. CONCLUSION: Taken together, these results suggest that 10 d of oral treatment with Polycan effectively inhibits ligature placement-induced periodontitis and related alveolar bone loss via an antioxidant effect.

Chemotherapy-induced reversible posterior leucoencephalopathy syndrome.

Reversible posterior leucoencephalopathy syndrome is a neurological condition seen in various areas of acute medicine, including the administration of antineoplastic therapies used in haemato-oncology patients. It is a rare complication that has been increasingly recognized. It is characterized by altered mental status, visual disturbance, headache and seizures. Magnetic resonance imaging typically shows vasogenic oedema in the posterior regions of the brain. Although its name suggests reversibility, it may result in an irreversible brain injury without prompt treatment. Therefore, it is vital for treating clinicians to recognize this syndrome. We describe the case of a 55-year-old woman with advanced pancreatic adenocarcinoma, who developed clinical and radiological manifestations consistent with this syndrome as a complication of gemcitabine monotherapy.

Vitellogenesis in both sexes of gonochoristic mud shrimp, Upogebia major (Crustacea): analyses of vitellogenin gene expression and vitellogenin processing.

The mud shrimp, Upogebia major is a gonochoristic species with distinct sexual dimorphism; however, the male has the "ovarian part of testis" in the gonad and mature-looking eggs appear in a similar reproductive cycle to the female. Vitellogenesis of U. major was investigated focusing on the characterization of vitellogenin (Vg) gene expression and Vg processing. Vg cDNA cloned by PCR-based methods was 7,799 bp-long, encoding 2,568 amino acids in a single open reading frame. The deduced amino acid sequence shared common characteristics conserved in other shrimp Vgs. The Vg gene was expressed in the hepatopancreas of females and males, the ovary, and the ovarian part of testis. Vitellins (Vns) were detected in the gonads of both females and males as three prominent polypeptides with apparent molecular masses of 82 kDa, 100 kDa, and 115 kDa. N-terminal amino acid sequences determined for the three polypeptides were present in the deduced amino acid sequence, demonstrating that they derived from a single long Vg polypeptide. Immunoblot analysis using polyclonal antibodies raised against two Vns (82 kDa and 100 kDa) confirmed Vg processing in the hepatopancreas, in the hemolymph and possibly in the oocytes, similarly in both sexes.

Structural and expression analyses of two vitellogenin genes in the carp, Cyprinus carpio.

We cloned and sequenced two vitellogenin (vg) cDNAs of the carp, Cyprinus carpio, using a cDNA library constructed from estradiol-17 beta (E2)-treated livers. One was a novel, longer 5000 bp-long cDNA termed vg-B2 encoding 1624 amino acids in a single open reading frame. The other was a shorter cDNA (vg-B1), identical to that registered previously as carp vg cDNA in the international nucleotide sequence database. The deduced amino acid sequences of these two molecules were well-aligned with known vertebrate Vgs sharing common characteristics such as N-terminal lipovitellin I (LVI), phosvitin (PV) and C-terminal lipovitellin II (LVII). The novel Vg-B2 bore a highly conserved GL/ICG motif within the LVII region, in contrast to the shorter Vg-B1 that has a truncated C-terminal and lacks the beta-component within the LVII region including the GL/ICG motif. Both vg-B2 and vg-B1 genes were expressed in the livers of females and E2-injected males. Western blot analysis using anti-Vg and anti-vitellin (Vn) antisera demonstrated that both Vg-B2 and Vg-B1 were detected as polypeptides with an estimated molecular mass of 180 kDa and 160 kDa, respectively, in the blood of females and E2-injected males. The results suggest the potential utilization of these genes as sensitive xenoestrogenic markers.

Methanolic extract of Pterocarpus santalinus induces apoptosis in HeLa cells.

Ptercarpus santalinus (Fabaceae) has been used as a folk remedy in Korea, and it has been shown to exhibit antiinflammations, antiulcers and anticancer effects. In this study, therefore, we report the cytotoxic activity and the mechanism of cell death exhibited by the methanol extract of Ptercarpus santalinus (MEPS) against human cervical adenocarcinoma cell line, HeLa. Treatment of HeLa cells with various concentrations of MEPS resulted in growth inhibition and induction of apoptosis in a dose-dependent manner as determined by cell viability, chromatin condensation, DNA fragmentation and sub-G1 phase accumulation. In Western blot analysis, apoptosis in the HeLa cells was associated with the release of cytochrome C from mitochondria into the cytosol, activation of caspases-3, -8, -9 and proteolytic cleavage of PARP. These results suggest that MEPS exhibits antiproliferative effect on HeLa cells via apoptosis, and it may be a potential candidate in field of anticancer drug discovery.

A novel homodimeric lactose-binding lectin from the edible split gill medicinal mushroom Schizophyllum commune.

A homodimeric lactose-binding lectin with a molecular mass of 64kDa was isolated from fresh fruiting bodies of the split gill mushroom Schizophyllum commune. The N-terminal sequence of the lectin is similar to a part of the sequence of the cell division protein from Gleobacter violaceus. The lectin was isolated by using a procedure which involved ion exchange chromatography on DEAE-cellulose, CM-cellulose, and Q-Sepharose, and gel filtration by fast protein liquid chromatography on Superdex 75. The hemagglutinating activity of the lectin was stable at temperatures up to 40 degrees C, and in concentrations of NaOH and HCl solution up to 125 and 25mM, respectively. The lectin exhibited potent mitogenic activity toward mouse splenocytes, antiproliferative activity toward tumor cell lines, and inhibitory activity toward HIV-1 reverse transcriptase. It was devoid of antifungal activity.

Antioxidant activities of dioscorin, the storage protein of yam (Dioscorea batatas Decne) tuber.

Dioscorin, the storage protein of yam (Dioscorea batatas Decne) tuber (which is different from dioscorine found in tubers of Dioscorea hirsuta), was purified to homogeneity after DE-52 ion exchange column according to the methods of Hou et al. (J. Agric. Food Chem. 1999, 47, 2168-2172). A single band of 32 kDa dioscorin was obtained on a sodium dodecyl sulfate-polyacrylamide gel electrophoresis gel with 2-mercaptoethanol treatment. This purified dioscorin was shown by spectrophotometric method to have scavenging activity against 1,1-diphenyl-2-picrylhydrazyl (DPPH) radical in a pH-dependent manner. There is a positive correlation between scavenging effects against DPPH (8-46%) and amounts of 32 kDa dioscorin (5.97-47.80 nmol) added in Tris-HCl buffer (pH 7.9), which are comparable to those of glutathione at the same concentrations. Using electron paramagnetic resonance (EPR) spectrometry for DPPH radical detection, it was found that the intensities of the EPR signal were decreased by 28.6 and 57 nmol of 32 kDa dioscorin in Tris-HCl buffer (pH 7.9) more than in distilled water compared to controls. EPR spectrometry was also used for hydroxyl radical detection. It was found that 32 kDa dioscorin could capture hydroxyl radical, and the intensities of the EPR signal were significantly decreased dose-dependently by 1.79-14.32 nmol of 32 kDa dioscorin (r = 0.975) compared to the control. It is suggested that 32 kDa dioscorin, the storage protein of yam tuber, may play a role as antioxidant in tubers and may be beneficial for health when people take it as a food additive or consume yam tubers.

Role of scavenger receptors SR-BI and CD36 in selective sterol uptake in the small intestine.

The serum lipoprotein high-density lipoprotein (HDL), which is a ligand of scavenger receptors such as scavenger receptor class B type I (SR-BI) and cluster determinant 36 (CD36), can act as a donor particle for intestinal lipid uptake into the brush border membrane (BBM). Both cholesterol and phospholipids are taken up by the plasma membrane of BBM vesicles (BBMV) and Caco-2 cells in a facilitated (protein-mediated) process. The protein-mediated transfer of cholesterol from reconstituted HDL to BBMV depends on the lipid composition of the HDL. In the presence of sphingomyelin, the transfer of cholesterol is slowed by a factor of about 3 probably due to complex formation between cholesterol and the sphingolipid. It is shown that the mechanism of lipid transfer from reconstituted HDL to either BBMV or Caco-2 cells as the acceptor is consistent with selective lipid uptake: the lipid donor docks at the membrane-resident scavenger receptors which mediate the transfer of lipids between donor and acceptor. Selective lipid uptake implies that lipid, but no apoprotein is transferred from the donor to the BBM, thus excluding endocytotic processes. The two BBM models used here clearly indicate that fusion of donor particles with the BBM can be ruled out as a major mechanism contributing to intestinal lipid uptake. Here we demonstrate that CD36, another member of the family of scavenger receptors, is present in rabbit and human BBM vesicles. This receptor mediates the uptake of free cholesterol, but not of esterified cholesterol, the uptake of which is mediated exclusively by SR-BI. More than one scavenger receptor appears to be involved in the uptake of free cholesterol with SR-BI contributing about 25% and CD36 about 35%. There is another yet unidentified protein accounting for the remaining 30 to 40%.

Calcified subcutaneous fat necrosis induced by prolonged exposure to cold weather: a case report.

We present a 22-day-old infant with extensive subcutaneous calcifications due to subcutaneous fat necrosis caused by prolonged exposure to cold.

Characterization of the flavoprotein domain of gp91phox which has NADPH diaphorase activity.

A series of truncated forms of gp91phox were expressed in Escherichia coli in which the N-terminal hydrophobic transmembrane region was replaced with a portion of the highly soluble bacterial protein thioredoxin. TRX-gp91phox (306-569), which contains the putative FAD and NADPH binding sites, showed weak NADPH-dependent NBT (nitroblue tetrazolium) reductase activity, whereas TRX-gp91phox (304-423) and TRX-gp91phox (424-569) were inactive. Activity saturated at about a 1:1 molar ratio of FAD to TRX-gp91phox (306-569), and showed the same K(m) for NADPH as that for superoxide generating activity by the intact enzyme. Activity was not inhibited by superoxide dismutase, indicating that it was not mediated by superoxide, but was blocked by an inhibitor of the respiratory burst oxidase, diphenylene iodonium. In the presence of Rac1, the cytosolic regulatory protein p67phox stimulated the NBT reductase activity, but p47phox had no effect. Truncated p67phox containing the activation domain (residues 199-210) [C.-H. Han, J.R. Freeman, T. Lee, S.A. Motalebi, and J.D. Lambeth (1998) J. Biol. Chem. 273, 16663-16668] stimulated activity approximately 2-fold, whereas forms mutated or lacking this region failed to stimulate the activity. Our data indicate that: (i) TRX-gp91phox (306-569) contains binding sites for both pyridine and flavin nucleotides; (ii) this flavoprotein domain shows weak diaphorase activity; and (iii) the flavin-binding domain of gp91phox is the target of regulation by the activation domain of p67phox.

[Changes of the certain functions of mitochondria induced by acute exercise and the protective effect of bilirubin].

AIM: To study the mechanism of fatigue induced by acute exercise and the protective effect of bilirubin. METHODS: 41 Wistar male rats were divided into five groups: control group, exercise group, exercise recovery group, bilirubin-treated exercise group and bilirubin-treated exercise recovery group. The rats were administrated with 1 micromol/kg body weight of bilirubin or saline once every day for 4 weeks, after swimming with load for 2 h, all of the rats were killed and several index were determined. RESULTS: Acute exercise could induce the increase of Ca2+ content in cytoplasm and mitochondria of gastrocnemius, Ca2+ content increased continuously after 12 hours in mitochondria. The Ca2(+)-Mg2(+)-ATPase activity decreased obviously after acute exercise, and the activity increased again after 12 hours. Bilirubin could inhibit these changes. The change of Mg2(+)-ATPase activity in mitochondria had little difference between bilirubin-treated and untreated groups, both of which were lower than that of control group, but the recovery was faster in the bilirubin-treated group than that in untreated group. CONCLUSION: Bilirubin could protect muscle fibers from injury induced by acute exercise and delay the development of fatigue and promote the recovery through inhibiting the disturbance of the certain function of mitochondria.

Intestinal sterol absorption mediated by scavenger receptors is competitively inhibited by amphipathic peptides and proteins.

Exchangeable serum apolipoproteins and amphipathic alpha-helical peptides are effective inhibitors of sterol (free and esterified cholesterol) uptake at the small-intestinal brush border membrane. The minimal structural requirement of an inhibitor is an amphipathic alpha-helix of 18 amino acids. The inhibition is competitive, indicating that the inhibitor binds to scavenger receptor class B type I (SR-BI) present in the brush border membrane and responsible for sterol uptake. Binding of apolipoprotein A-I to SR-BI of rabbit brush border membrane is cooperative, characterized by a dissociation constant K(d) = 0.45 microM and a Hill coefficient of n = 2.8. The cooperativity of the interaction is due to binding of the inhibitor molecule to a dimeric or oligomeric form of SR-BI held together by disulfide bridges. Consistent with the competitive nature of the inhibition, the K(d) value agrees within experimental error with the IC(50) value of inhibition and with the inhibition constant K(I). After proteinase K treatment of brush border membrane vesicles, the affinity of the interaction of apolipoprotein A-I expressed as K(d) is reduced by a factor of 20, and the cooperativity is lost. The interaction of proteinase K-treated brush border membrane vesicles with apolipoprotein A-I is nonspecific partitioning of the apolipoprotein into the lipid bilayer of brush border membrane vesicles.