BACKGROUND Ameloblastomas are common benign epithelial odontogenic neoplasms that present an aggressive and unpredictable behavior that may modify treatment strategies.Different signaling pathways that participate in ...BACKGROUND Ameloblastomas are common benign epithelial odontogenic neoplasms that present an aggressive and unpredictable behavior that may modify treatment strategies.Different signaling pathways that participate in the progression of these tumors have been identified.B-raf proto-oncogene serine/threonine kinase(BRAF)is a protein involved in the behavior of ameloblastomas,and it is related to many cell mechanisms.BRAF gene mutations have been identified in ameloblastomas,of which the BRAF V600E(valine substituted by glutamic acid at amino acid 600)mutation has been the most common and can be present concomitantly with other mutations that may be involved in its behavior.Targeted therapies have been used as an alternative in the case of resistance or contraindications to conventional treatments.AIM To document the presence of BRAF V600E and additional mutations,their behavior,and targeted therapies in these tumors.METHODS An electronic literature search was conducted according to PRISMA guidelines in PubMed/MEDLINE,Cochrane,EMBASE,and SpringerLink using the terms“ameloblastomas”,“BRAF V600E”,“additional mutations”,and“targeted therapies”.Ameloblastomas were classified according to WHO guidelines.Inclusion criteria were articles in English,published not more than 10 years ago,and studies with laboratory works related to BRAF V600E.Articles were evaluated by two independent reviewers and retrieved for full-text evaluation.The EBLIP Critical Appraisal Checklist was used to evaluate the quality of the eligible studies.Descriptive statistical analysis was performed.RESULTS Two independent reviewers,with a substantial concordance indicated by a kappa coefficient of k=0.76,evaluated a total of 19 articles that were included in this study.The analysis registered 521 conventional ameloblastomas(AM),81 unicystic ameloblastomas(UA),13 ameloblastic carcinomas(AC),three metastatic ameloblastomas(MA),and six peripheral ameloblastomas(PA),of which the histopathological type,anatomic location,laboratory tests,expression of BRAF mutation,and additional mutations were registered.The BRAF V600E mutation was found in 297 AM(57%),63 UA(77.7%),3 AC(23%),1 MA(50%),and 5 PA(83.3%).Follicular type predominated with a total of 116 cases(40%),followed by plexiform type with 63 cases(22.1%).Furthermore,both types presented additional mutations,in which alterations in JAK3 P132T,SMARCB1,PIK3CA,CTNNB1,SMO,and BRAF G606E genes were found.Four case reports were found with targeted therapy to BRAF V600E.CONCLUSION The identification of BRAF V600E and additional mutations as an aid in targeted therapies has been a breakthrough in alternative treatments of ameloblastomas where surgical treatments are contraindicated.展开更多
AIM:To explore mutations in serine/threonine kinase 11(STK11) gene in Peutz-Jeghers syndrome(PJS) with gastrointestinal(GI) hamartomatous polyps.METHODS:Six Japanese PJS patients in 3 families were enrolled in this st...AIM:To explore mutations in serine/threonine kinase 11(STK11) gene in Peutz-Jeghers syndrome(PJS) with gastrointestinal(GI) hamartomatous polyps.METHODS:Six Japanese PJS patients in 3 families were enrolled in this study.Each of the cases had hamartomatous polyposis in the gastrointestinal tract,including the small intestine,along with mucocutaneous hyperpigmentation.Narrow-band imaging(NBI)-magnification endoscopy was employed to detect microvascular and microsurface irregularities in the GI lesions.NBI magnification findings could be classified into three groups(type A,type B,or type C).Endoscopic polypectomy was performed using double-balloon enteroscopy or colonoscopy.Genomic DNA was extracted from a whole blood sample from each subject.All of the coding exons of STK11 gene,its boundary regions,and the promoter region containing the polymorphic regions were amplified by polymerase chain reaction,and direct sequencing was performed to assess the germline mutations.RESULTS:NBI-magnification endoscopic observation could detect the abnormalities in microvessels and microsurface structures of GI polyps.Overall,we found 5 cases of type A and one case without the examination for the gastric polyps,while there were 4 cases of type B and 2 case of type A for the colorectal polyps.Seventy-nine small-bowel and 115 colorectal polyps over 27 sessions for each were resected endoscopically without significant complications.The only delayed complication included the occurrence of bleeding in a case,and this was successfully managed with hemoclips.Resected polyps contained no malignant components.Based on mutation analysis,all 3 cases in Family I exhibited the +658C>T nonsense mutation in exon 5,which resulted in the production of a truncated protein(Q220X).In Family II,a case had-252C>A and-193C>A in the promoter region.In Family III,a case was found to have the +1062C>G(F342L) mutation in exon 8.CONCLUSION:We found two novel mutations of STK11 in association with PJS.Endoscopic polypectomy of GI polyps in PJS patients appears to be useful to prevent emergency laparotomies and reduce the cancer risk.展开更多
Microtubule-associated serine/threonine kinase(MASTL)functions to regulate chromosome condensation and mitotic progression.Therefore,aberrant MASTL expression is commonly implicated in various human cancers.This study...Microtubule-associated serine/threonine kinase(MASTL)functions to regulate chromosome condensation and mitotic progression.Therefore,aberrant MASTL expression is commonly implicated in various human cancers.This study analyzed MASTL expression in gastric cancer vs.adjacent normal tissue for elucidating the association with clinicopathological data from patients.This work was then extended to investigate the effects of MASTL knockdown on tumor cells in vitro.The level of MASTL expression in gastric cancer tissue was assessed from the UALCAN,GEPIA,and Oncomine online databases.Lentivirus carrying MASTL or negative control shRNA was infected into gastric cancer cells.RT-qPCR,Western blotting,cell viability,cell counting,flow cytometric apoptosis and cell cycle,and colony formation assays were performed.MASTL was upregulated in gastric cancer tissue compared to the adjacent normal tissue,and the MASTL expression was associated with advanced tumor stage,Helicobacter pylori infection and histological subtypes.On the other hand,knockdown of MASTL expression significantly reduced tumor cell viability and proliferation,and arrested cell cycle at G2/M stage but promoted tumor cells to undergo apoptosis.At protein level,knockdown of MASTL expression enhanced levels of cleaved PARP1,cleaved caspase-3,Bax and p-ERK1/2 expression,but downregulated expression levels of BCL-2 and p-NF-κB-p65 protein in AGS and MGC-803 cells.MASTL overexpression in gastric cancer tissue may be associated with gastric cancer development and progression,whereas knockdown of MASTL expression reduces tumor cell proliferation and induces apoptosis.Further study will evaluate MASTL as a potential target of gastric cancer therapeutic strategy.展开更多
Testis specific serine/threonine protein kinase 4(TSSK4) belongs to the TSSK family, and its members play an important role in spermatogenesis and/or spermiogenesis. Mouse TSSK4 has been reported to be expressed exc...Testis specific serine/threonine protein kinase 4(TSSK4) belongs to the TSSK family, and its members play an important role in spermatogenesis and/or spermiogenesis. Mouse TSSK4 has been reported to be expressed exclusively in the testis and can maintain its kinase activity through autophosphorylation at Thr-197. However, its biological function remains poorly understood. Here we found that GFP-TSSK4-overexpressed He La cells showed apoptotic bodies, indicating TSSK4 can lead to apoptosis in vitro. Furthermore, TSSK4 induced apoptosis in different cell lines including He La, Cos-7 and H1299 tested by flow cytometry but not its kinase-dead mutant TSSK4-K54 M. TSSK4 knockout mice showed increased testes weight and decreased apoptotic spermatogonia and spermatocytes at 21 st day after birth tested by TUNEL technology. So TSSK4 was able to induce cell apoptosis in vitro depending on its kinase activity, which leads to abnormal testes weight and apoptosis, shedding light on its function in the process of spermatogenesis and/or spermiogenesis.展开更多
A thorough understanding of the genetic basis of rice grain traits is critical for the improvement of rice (Oryza sativa L.) varieties. In this study, we generated an F2 population by crossing the large-grain japoni...A thorough understanding of the genetic basis of rice grain traits is critical for the improvement of rice (Oryza sativa L.) varieties. In this study, we generated an F2 population by crossing the large-grain japonica cultivar CW23 with Peiai 64 (PA64), an elite indica small-grain cultivar. Using QTL analysis, 17 QTLs for five grain traits were detected on four different chromosomes. Eight of the QTLs were newly-identified in this study. In particular, qGL3-1, a newly-identified grain length QTL with the highest LOD value and largest phenotypic variation, was fine-mapped to the 17 kb region of chromosome 3. A serine/threonine protein phosphatase gene encoding a repeat domain containing two Kelch motifs was identified as the unique candidate gene corresponding to this QTL. A comparison of PA64 and CW23 sequences revealed a single nucleotide substitution (C→A) at position 1092 in exon 10, resulting in replacement of Asp (D) in PA64 with Glu (E) in CW23 for the 364th amino acid. This variation is located at the D position of the conserved sequence motif AVLDT of the Kelch repeat. Genetic analysis of a near-isogenic line (NIL) for qGL3-1 revealed that the allele qGL3-1 from CW23 has an additive or partly dominant effect, and is suitable for use in molecular marker-assisted selection.展开更多
Based on a mechanism analogous to the serine/threonine ligation, the aspartic acid ligation, which is facilitated by the γ-amino alcohol based ligation and oxidation, is developed and applied to the synthesis of cycl...Based on a mechanism analogous to the serine/threonine ligation, the aspartic acid ligation, which is facilitated by the γ-amino alcohol based ligation and oxidation, is developed and applied to the synthesis of cyclic peptides. The γ-hydroxyl group triggers the ring-chain tautomerization via a 6-endo-trig process,while the δ-hydroxyl group facilitates the oxidative cleavage of the vicinal diol to give carboxylic acid.展开更多
Examining the plants in any forest or meadow reveals a remarkable diversity of leaf shape,suggesting the importance of this trait for adaptation to various environmental conditions(reviewed in Nicotra et al.2011).Inde...Examining the plants in any forest or meadow reveals a remarkable diversity of leaf shape,suggesting the importance of this trait for adaptation to various environmental conditions(reviewed in Nicotra et al.2011).Indeed,leaf shape may be constrained by biomechanical factors and affects thermoregulation,susceptibility to herbivory,the available light for photosynthesis,and water balance.展开更多
The nomenclature for compounds that are modified with isotopes is growing every day. Compounds can be modified with isotopes either individually, in a functional group or groups, or completely with all atomic centers ...The nomenclature for compounds that are modified with isotopes is growing every day. Compounds can be modified with isotopes either individually, in a functional group or groups, or completely with all atomic centers of the element. This diversity of isotope-modified compounds increases the range of researches that can be studied using them. Compounds modified with isotopes of carbon-13 or nitrogen-15 can be converted into carbon monoxide, carbon dioxide and molecular nitrogen. Currently, only the average value of carbon-13 or nitrogen-15 isotopes can be determined. However, by directly determining the atomic share of these isotopes in organic compounds modified with isotopes, information about the isotopic centers of the element can be obtained. The atomic fraction of an element is defined as a single carbon or nitrogen isotope-modified center or centers, or all centers that are isotope-modified with that element at the same time. Carbon-13 or nitrogen-15 isotopes’ atomic fraction can be determined molecularly or with fragment ions of different elemental content, or both. This makes the method self-verifying, increasing the accuracy and reliability of the results obtained. Amino acids, such as asparagine, aspartic acid, methionine, and threonine, are essential for the human body. This proposed method of isotopic analysis will increase the possibilities for scientific research using these compounds.展开更多
The effects of tacrolimus postconditioning on protein-serine-threonine kinases (Akt) phos- phorylation and apoptotic cell death in rats after spinal cord ischemia-reperfusion injury were investi- gated. Ninety male ...The effects of tacrolimus postconditioning on protein-serine-threonine kinases (Akt) phos- phorylation and apoptotic cell death in rats after spinal cord ischemia-reperfusion injury were investi- gated. Ninety male SD rats were randomly divided into sham operation group, ischemia-reperfusion group and tacrolimus postconditioning group. The model of spinal cord ischemia was established by means of catheterization through femoral artery and balloon dilatation. The spinal cord was reperfused 20 min after ischemia via removing saline out of balloon. The corresponding spinal cord segments were excised and determined for Akt activity in spinal cord tissue by using Western blotting at 5, 15, and 60 min after reperfusion respectively. Spinal cord tissue sections were stained immunohistochemically for detection of the phosphorylated Akt expression at 15 min after reperfusion. Flow cytometry was applied to assess apoptosis of neural cells, and dry-wet weights method was employed to measure water content in spinal cord tissue at 24 h after reperfusion. The results showed that the activities of Akt in tarcolimus postconditioning group were significantly higher than those in ischemia-reperfusion group at 5, 15, and 60 min after reperfusion (P〈0.05, P〈0.01). The Akt activities reached the peak at 15 min after reperfu- sion in ischemia-reperfusion group and tacrolimus postconditioning group. The percentage of apoptotic cells and water content in spinal cord tissue were significantly reduced (P〈0.01) in tacrolimus postcon- ditioning group as compared with those in ischemia-reperfusion group at 24 h after reperfusion. It is concluded that tacrolimus postconditioning can increase Akt activity in spinal cord tissue of rats, inhibit apoptosis of neural cells as well as tissue edema, and thereby alleviate spinal cord ischemia-reperfusion injury.展开更多
The signaling mechanisms underlying ischemia-induced nerve cell apoptosis are poorly understood. We investigated the effects of apoptosis-related signal transduction pathways following ischemic spinal cord injury, inc...The signaling mechanisms underlying ischemia-induced nerve cell apoptosis are poorly understood. We investigated the effects of apoptosis-related signal transduction pathways following ischemic spinal cord injury, including extracellular signal-regulated kinase(ERK), serine-threonine protein kinase(Akt) and c-Jun N-terminal kinase(JNK) signaling pathways. We established a rat model of acute spinal cord injury by inserting a catheter balloon in the left subclavian artery for 25 minutes. Rat models exhibited notable hindlimb dysfunction. Apoptotic cells were abundant in the anterior horn and central canal of the spinal cord. The number of apoptotic neurons was highest 48 hours post injury. The expression of phosphorylated Akt(pAkt) and phosphorylated ERK(p-ERK) increased immediately after reperfusion, peaked at 4 hours(p-Akt) or 2 hours(p-ERK), decreased at 12 hours, and then increased at 24 hours. Phosphorylated JNK expression reduced after reperfusion, increased at 12 hours to near normal levels, and then showed a downward trend at 24 hours. Pearson linear correlation analysis also demonstrated that the number of apoptotic cells negatively correlated with p-Akt expression. These findings suggest that activation of Akt may be a key contributing factor in the delay of neuronal apoptosis after spinal cord ischemia, particularly at the stage of reperfusion, and thus may be a target for neuronal protection and reduction of neuronal apoptosis after spinal cord injury.展开更多
The serine proteases of Mycobacteria tuberculosis(Mtb)are important contributors to the process of bacterial invasion and its pathogenesis.In the present study,we systematically characterized the role of the Rv1043c p...The serine proteases of Mycobacteria tuberculosis(Mtb)are important contributors to the process of bacterial invasion and its pathogenesis.In the present study,we systematically characterized the role of the Rv1043c protein in Mycobacterium infection by purifying the Rv1043c protein in Escherichia coli and constructing a Mycobacterium smegmatis(Msg)strain overexpressing Rv1043c(Msg_Rv1043c).We found that Rv1043c had serine protease activity and localized to the surface of Mtb.We determined that the optimal pH and temperature for the Rv1043c serine protease were 9.0 and 45°C,respectively.Moreover,the serine protease activity of Rv1043c was enhanced by divalent metal ions of Ca^(2+)and Mg^(2+).Site-directed mutagenesis studies demonstrated that the serine 279 residue in Rv1043c plays a catalytic role.Additionally,mouse model studies confirmed that Rv1043c significantly enhanced the survival of Msg in vivo,induced pulmonary injury and lung cell apoptosis,and promoted the release of pro-inflammatory cytokines interleukin-1βand interleukin-6 in mice.This study presents novel insights into the relationship between mycobacterial serine protease and the pathogenesis of the disease.展开更多
Female adults of the migratory locust,Locusta migratoria manilensis(Meyen),can sense seasonal photoperiod changes,which induces embryonic diapause as a key strategy to overwinter.Serine protease inhibitor genes(SPNs)w...Female adults of the migratory locust,Locusta migratoria manilensis(Meyen),can sense seasonal photoperiod changes,which induces embryonic diapause as a key strategy to overwinter.Serine protease inhibitor genes(SPNs)were thought to play key roles during diapause,while few SPNs were functionally characterized.LmSPN2 was one of those genes differentially expressed between diapause and non-diapause eggs;however,its biological function remained to be explored.So,we conducted RNAi knockdown of LmSPN2,resulting in a significant decrease of the egg diapause rate by 29.7%.Using yeast two-hybrid assays,co-immunoprecipitation,and pull-down methods,we found an interaction between LmSPN2 and LmSPN3,which was proved to be mediated by a glutamate(E331)binding site of LmSPN2.RNAi knockdown of LmSPN3 resulted in a significant increase in diapause rate by 14.6%,indicating an inverse function of LmSPN2 and LmSPN3 on diapause regulation.Double knockdown of two SPN genes resulted in a 26.4%reduction in diapause rate,indicating that LmSPN2 was the dominant regulatory signal.Moreover,we found four Toll pathway genes(easter,spätzle,pelle,and dorsal)upregulated significantly after the knockdown of LmSPN2 while downregulated after the knockdown of LmSPN3.Therefore,we speculate that two SPNs regulate diapause through the Toll pathway.Our results indicated that LmSPN2 positively regulates locust egg entry into diapause,while LmSPN3 is a negative regulator of embryonic commitment to diapause.Their interaction is mediated by the binding site of E331 and influences egg diapause through the Toll pathway.This mechanistic understanding of diapause regulation expands our understanding of insect developmental regulation and provides functional targets for developing locust management strategies.展开更多
Objective:To isolate,partially purify and evaluate the cytotoxic and antitumor activity of a serine protease from the chosen Indian earthworm Pheretima posthuma.Methods:Whole animal extract was prepared and purified i...Objective:To isolate,partially purify and evaluate the cytotoxic and antitumor activity of a serine protease from the chosen Indian earthworm Pheretima posthuma.Methods:Whole animal extract was prepared and purified its protein constituents by size and charge based chromatographic separation techniques using Sephadex G-50 and DEAE-Cellulose resin respectively.Average molecular weight of the protein isolate was determined and analyzed for its cytotoxic property against Vero cells in different dilutions(1:20 and 1:40)and anti-tumor activity by MTT assay(a colorimetric assay)using breast cancer cell line MCF-7,with tamoxifen as standard.Results:One of the protein constituents after purification was characterized as serine protease by Caseinolytic plate diffusion assay.Average molecular weight of this purified isolate was determined,by SDS-PAGE analysis with standard protein ladder,as of 15 kDa.The performed tests suggested that the 15kDa fraction has potent cytotoxic activity and satisfactory antitumor activity as well in vitro.Conclusions:Exact molecular mechanism of the cytotoxic and antitumor activities is yet to be explored and currently we are working on ultra-purification and biophysical characterization of this fraction.Further investigation into the mechanism(s)of cytotoxic and antitumor activities at molecular level would be useful in treatment of various classes of cancer and viral infections in future.展开更多
Background: This study was carried out to investigate effects of threonine levels on growth, digestive and absorptive capacity and antioxidant status in intestine and hepatopancreas of sub-adult grass carp ( Ctenoph...Background: This study was carried out to investigate effects of threonine levels on growth, digestive and absorptive capacity and antioxidant status in intestine and hepatopancreas of sub-adult grass carp ( Ctenopharyngodonidella). Results: Weight gain, specific growth rate, feed intake and feed efficiency were significantly improved by dietary threonine (P 〈 0.05). Intestinal activities of trypsin, chymotrypsin, alpha-amylase, lipase, alkaline phosphatase, y-glutamyl transpeptidase and creatine kinase took the similar trends. Contents of malondialdehyde and protein carbonyl in intestine and hepatopancreas were significantly decreased by dietary optimal threonine supplementation (P 〈 0.05). Anti-superoxide anion capacity, anti-hydroxyl radical capacity, glutathione content and activities of superoxide dismutase, catalase and glutathione-S-transferase in intestine and hepatopancreas were enhanced by dietary threonine (P 〈 0.05). Conclusions: Dietary threonine could improve growth, enhance digestive and absorptive capacity and antioxidant status in intestine and hepatopancreas of sub-adult grass carp. The dietary threonine requirement of sub-adult grass carp (441.9-1,013.4 g) based on weight gain was 11.6 g/kg diet or 41.5 g/kg of dietary protein by quadratic regression analysis.展开更多
First-principles, all-electron, ab initio calculations have been performed to construct an equivalent water potential for the electronic structure of serine (Ser) in solution. The calculation is composed of three st...First-principles, all-electron, ab initio calculations have been performed to construct an equivalent water potential for the electronic structure of serine (Ser) in solution. The calculation is composed of three steps. The first step is to search for the configuration of the Ser _ nH2O system with a minimum energy. The second step is to calculate the electronic structure of Ser with the water molecule potential via the self-consistent cluster-embedding method (SCCE), based on the result obtained in the first step. The last step is to calculate the electronic structure of Set with the dipole potential after replacing the water molecules with dipoles. The results show that the occupied states of Ser are raised by about 0.017 Ry on average due to the effect of water. The water effect can be successfully simulated by using the dipole potential. The obtained equivalent potential can be applied directly to the electronic structure calculation of protein in solution by using the SCCE method.展开更多
The authors have isolated and characterized a novel serine palmitoyltransferase (SPT)-like gene in marine Emiliania huxleyi virus (EhV-99B1). The open-reading frame (ORF) of EhV99BI-SPT encoded a protein of 496 ...The authors have isolated and characterized a novel serine palmitoyltransferase (SPT)-like gene in marine Emiliania huxleyi virus (EhV-99B1). The open-reading frame (ORF) of EhV99BI-SPT encoded a protein of 496 amino acids with a calculated molecular mass of 96 kDa and Ip 6.01. The results of sequence analysis showed that there was about 31% 45% identity in amino acid sequence with other organisms. The maximum likelihood phylogenetic tree suggested that the EhV99B1-SPT gene possibly horizontally transferred from the eukaryote. Hydrophobic profiles of deduced amino acid sequences suggested a hydrophobic, globular and membrane-associated protein with five transmembrane domains (TMDs) motifs. Several potential N-linked glycosylation sites were presented in SPT. These results suggested that EhV99BI-SPT was an integral endoplasmic reticulum membrane protein. Despite lower sequence identity, the secondary and three-dimensional structures predicted showed that the “pocket” structure element composed of 2a-helices and 4β- sheets was the catalytic center of this enzyme, with a typical conserved “TFTKSFG” active site in the N-terminal region and was very close to those of prokaryotic organisms. However, the N-terminal domain of EhV99B1-SPT most closely resembled the LCB2 catalysis subunit and the C-terminal domain most closely resembled the LCBI regulatory subunit of other organisms which together formed a spherical molecule. This “chimera” was highly similar to the prokaryotic homologous SPT. For a functional identification, the EhV99B1-LCB2 subunit gene was expressed in Escherichia coli, which resulted in significant accumulation of new sphingolipid in E. coli cells.展开更多
BACKGROUND: HtrA1, a serine protease, is down-regulated in various human solid tumors. Overexpression of HtrA1 in human cancer cells inhibits cell growth and proliferation in vitro and in vivo, suggesting its possible...BACKGROUND: HtrA1, a serine protease, is down-regulated in various human solid tumors. Overexpression of HtrA1 in human cancer cells inhibits cell growth and proliferation in vitro and in vivo, suggesting its possible role as a tumor suppressor. METHODS: Immunohistochemistry was used to determine the expression of HtrA1 in 50 hepatocellular carcinoma specimens and adjacent liver tissues. The correlation between the expression of HtrA1 and the clinico-pathologic data were analyzed. RESULTS: The levels of HtrA1 were lower in tumor tissues than in their adjacent liver tissues. Moreover, an inverse relationship was found between HtrA1 expression and the differentiation of hepatocellular carcinoma. Loss of HtrA1 was more frequently found in tumors in Edmondson grade especially in those with venous invasion, compared to tumors in Edmondson grade I-II. Most importantly, patients with higher HtrA1 expression had a better survival rate. CONCLUSION: All these data suggest an important role of HtrA1 in hepatocellular carcinoma development and progression, which may be a new target for its treatment.展开更多
Background: There is large variation in amino acids requirements among pigs,hence feeding pigs individually with daily tailored diets or in groups with a single feed may require different levels of nutrients.Thus,the ...Background: There is large variation in amino acids requirements among pigs,hence feeding pigs individually with daily tailored diets or in groups with a single feed may require different levels of nutrients.Thus,the response to different threonine levels(70%,85%,100%,115%,and 130% of the ideal threonine:lysine protein ratio of 0.65) was studied in growing pigs raised in a conventional group phase-feeding(GPF) system or fed individually using individual precision-feeding(IPF) techniques.In a 21-day trial,110 barrows(25 ± 0.80 kg body weight) were housed in the same room and fed using electronic feeders.Five pigs per treatment were slaughtered at the end of the trial.Results: Threonine intake increased linearly for the IPF and GPF pigs(P < 0.05).Lysine intake was similar across the treatments.Average daily gain,gain:feed ratio,and protein deposition were affected linearly by threonine level(P < 0.05)in both feeding systems.Protein deposition in the GPF pigs was maximized at 150 g/d and a 0.65 threonine:lysine ratio,whereas protein deposition increased linearly in the IPF pigs.Plasma Met and serine levels were 11 and 7% higher,respectively,in the IPF pigs than in the GPF pigs(P < 0.05).Dietary threonine increased(P < 0.05)threonine concentration in the longissimus dorsi in a quadratic manner in the IPF pigs,whereas there was no effect in the GPF pigs.Longissimus dorsi collagen decreased as dietary threonine increased in the IPF and GPF pigs(P < 0.10).Carcass muscle crude protein was 2% higher in the GPF pigs than in the IPF pigs(P < 0.05).Conclusions: Individual pigs are able to modulate growth and the composition of growth according to threonine intake.The average amino acid ratio value that is currently used for GPF cannot be used for IPF.展开更多
文摘BACKGROUND Ameloblastomas are common benign epithelial odontogenic neoplasms that present an aggressive and unpredictable behavior that may modify treatment strategies.Different signaling pathways that participate in the progression of these tumors have been identified.B-raf proto-oncogene serine/threonine kinase(BRAF)is a protein involved in the behavior of ameloblastomas,and it is related to many cell mechanisms.BRAF gene mutations have been identified in ameloblastomas,of which the BRAF V600E(valine substituted by glutamic acid at amino acid 600)mutation has been the most common and can be present concomitantly with other mutations that may be involved in its behavior.Targeted therapies have been used as an alternative in the case of resistance or contraindications to conventional treatments.AIM To document the presence of BRAF V600E and additional mutations,their behavior,and targeted therapies in these tumors.METHODS An electronic literature search was conducted according to PRISMA guidelines in PubMed/MEDLINE,Cochrane,EMBASE,and SpringerLink using the terms“ameloblastomas”,“BRAF V600E”,“additional mutations”,and“targeted therapies”.Ameloblastomas were classified according to WHO guidelines.Inclusion criteria were articles in English,published not more than 10 years ago,and studies with laboratory works related to BRAF V600E.Articles were evaluated by two independent reviewers and retrieved for full-text evaluation.The EBLIP Critical Appraisal Checklist was used to evaluate the quality of the eligible studies.Descriptive statistical analysis was performed.RESULTS Two independent reviewers,with a substantial concordance indicated by a kappa coefficient of k=0.76,evaluated a total of 19 articles that were included in this study.The analysis registered 521 conventional ameloblastomas(AM),81 unicystic ameloblastomas(UA),13 ameloblastic carcinomas(AC),three metastatic ameloblastomas(MA),and six peripheral ameloblastomas(PA),of which the histopathological type,anatomic location,laboratory tests,expression of BRAF mutation,and additional mutations were registered.The BRAF V600E mutation was found in 297 AM(57%),63 UA(77.7%),3 AC(23%),1 MA(50%),and 5 PA(83.3%).Follicular type predominated with a total of 116 cases(40%),followed by plexiform type with 63 cases(22.1%).Furthermore,both types presented additional mutations,in which alterations in JAK3 P132T,SMARCB1,PIK3CA,CTNNB1,SMO,and BRAF G606E genes were found.Four case reports were found with targeted therapy to BRAF V600E.CONCLUSION The identification of BRAF V600E and additional mutations as an aid in targeted therapies has been a breakthrough in alternative treatments of ameloblastomas where surgical treatments are contraindicated.
文摘AIM:To explore mutations in serine/threonine kinase 11(STK11) gene in Peutz-Jeghers syndrome(PJS) with gastrointestinal(GI) hamartomatous polyps.METHODS:Six Japanese PJS patients in 3 families were enrolled in this study.Each of the cases had hamartomatous polyposis in the gastrointestinal tract,including the small intestine,along with mucocutaneous hyperpigmentation.Narrow-band imaging(NBI)-magnification endoscopy was employed to detect microvascular and microsurface irregularities in the GI lesions.NBI magnification findings could be classified into three groups(type A,type B,or type C).Endoscopic polypectomy was performed using double-balloon enteroscopy or colonoscopy.Genomic DNA was extracted from a whole blood sample from each subject.All of the coding exons of STK11 gene,its boundary regions,and the promoter region containing the polymorphic regions were amplified by polymerase chain reaction,and direct sequencing was performed to assess the germline mutations.RESULTS:NBI-magnification endoscopic observation could detect the abnormalities in microvessels and microsurface structures of GI polyps.Overall,we found 5 cases of type A and one case without the examination for the gastric polyps,while there were 4 cases of type B and 2 case of type A for the colorectal polyps.Seventy-nine small-bowel and 115 colorectal polyps over 27 sessions for each were resected endoscopically without significant complications.The only delayed complication included the occurrence of bleeding in a case,and this was successfully managed with hemoclips.Resected polyps contained no malignant components.Based on mutation analysis,all 3 cases in Family I exhibited the +658C>T nonsense mutation in exon 5,which resulted in the production of a truncated protein(Q220X).In Family II,a case had-252C>A and-193C>A in the promoter region.In Family III,a case was found to have the +1062C>G(F342L) mutation in exon 8.CONCLUSION:We found two novel mutations of STK11 in association with PJS.Endoscopic polypectomy of GI polyps in PJS patients appears to be useful to prevent emergency laparotomies and reduce the cancer risk.
基金grants from Lanzhou Science and Technology Planning Project(No.2016-3-113)University Research Project of Gansu Province(No.2018A049)+2 种基金the Foundation of the Fundamental Scientific Research Funds for Colleges and Universities in Gansu Province[No.(2014)63-15]the China’s National Science and Technology Program for Public Wellbeing(No.2012GS620101)National Key Research and Development Planning(No.2017YFC0908302).
文摘Microtubule-associated serine/threonine kinase(MASTL)functions to regulate chromosome condensation and mitotic progression.Therefore,aberrant MASTL expression is commonly implicated in various human cancers.This study analyzed MASTL expression in gastric cancer vs.adjacent normal tissue for elucidating the association with clinicopathological data from patients.This work was then extended to investigate the effects of MASTL knockdown on tumor cells in vitro.The level of MASTL expression in gastric cancer tissue was assessed from the UALCAN,GEPIA,and Oncomine online databases.Lentivirus carrying MASTL or negative control shRNA was infected into gastric cancer cells.RT-qPCR,Western blotting,cell viability,cell counting,flow cytometric apoptosis and cell cycle,and colony formation assays were performed.MASTL was upregulated in gastric cancer tissue compared to the adjacent normal tissue,and the MASTL expression was associated with advanced tumor stage,Helicobacter pylori infection and histological subtypes.On the other hand,knockdown of MASTL expression significantly reduced tumor cell viability and proliferation,and arrested cell cycle at G2/M stage but promoted tumor cells to undergo apoptosis.At protein level,knockdown of MASTL expression enhanced levels of cleaved PARP1,cleaved caspase-3,Bax and p-ERK1/2 expression,but downregulated expression levels of BCL-2 and p-NF-κB-p65 protein in AGS and MGC-803 cells.MASTL overexpression in gastric cancer tissue may be associated with gastric cancer development and progression,whereas knockdown of MASTL expression reduces tumor cell proliferation and induces apoptosis.Further study will evaluate MASTL as a potential target of gastric cancer therapeutic strategy.
基金supported by National Natural Science Foundation of China(No.31301202)
文摘Testis specific serine/threonine protein kinase 4(TSSK4) belongs to the TSSK family, and its members play an important role in spermatogenesis and/or spermiogenesis. Mouse TSSK4 has been reported to be expressed exclusively in the testis and can maintain its kinase activity through autophosphorylation at Thr-197. However, its biological function remains poorly understood. Here we found that GFP-TSSK4-overexpressed He La cells showed apoptotic bodies, indicating TSSK4 can lead to apoptosis in vitro. Furthermore, TSSK4 induced apoptosis in different cell lines including He La, Cos-7 and H1299 tested by flow cytometry but not its kinase-dead mutant TSSK4-K54 M. TSSK4 knockout mice showed increased testes weight and decreased apoptotic spermatogonia and spermatocytes at 21 st day after birth tested by TUNEL technology. So TSSK4 was able to induce cell apoptosis in vitro depending on its kinase activity, which leads to abnormal testes weight and apoptosis, shedding light on its function in the process of spermatogenesis and/or spermiogenesis.
基金supported by grants from the Geneti-cally Modified Organisms Breeding Major Projects of China(2011ZX08001-004-009)the National Natural Science Foun-dation of China(30900881)+2 种基金the Jiangxi Province Major Science and Technology Projects and Super Hybrid Rice BreedingDemonstration and Dissemination Projects(20114ABF03105)the Natural Science Foundation of Shandong Province(Y2006D22)
文摘A thorough understanding of the genetic basis of rice grain traits is critical for the improvement of rice (Oryza sativa L.) varieties. In this study, we generated an F2 population by crossing the large-grain japonica cultivar CW23 with Peiai 64 (PA64), an elite indica small-grain cultivar. Using QTL analysis, 17 QTLs for five grain traits were detected on four different chromosomes. Eight of the QTLs were newly-identified in this study. In particular, qGL3-1, a newly-identified grain length QTL with the highest LOD value and largest phenotypic variation, was fine-mapped to the 17 kb region of chromosome 3. A serine/threonine protein phosphatase gene encoding a repeat domain containing two Kelch motifs was identified as the unique candidate gene corresponding to this QTL. A comparison of PA64 and CW23 sequences revealed a single nucleotide substitution (C→A) at position 1092 in exon 10, resulting in replacement of Asp (D) in PA64 with Glu (E) in CW23 for the 364th amino acid. This variation is located at the D position of the conserved sequence motif AVLDT of the Kelch repeat. Genetic analysis of a near-isogenic line (NIL) for qGL3-1 revealed that the allele qGL3-1 from CW23 has an additive or partly dominant effect, and is suitable for use in molecular marker-assisted selection.
基金supported by the Research Grants Council (Nos. 17309616, C6009-15G) of Hong KongThe National Science Foundation of China (Nos. 21672180, 91753101)the Area of Excellence Scheme of the University of Grants Committee of Hong Kong (No. AoE/P-705/16)
文摘Based on a mechanism analogous to the serine/threonine ligation, the aspartic acid ligation, which is facilitated by the γ-amino alcohol based ligation and oxidation, is developed and applied to the synthesis of cyclic peptides. The γ-hydroxyl group triggers the ring-chain tautomerization via a 6-endo-trig process,while the δ-hydroxyl group facilitates the oxidative cleavage of the vicinal diol to give carboxylic acid.
文摘Examining the plants in any forest or meadow reveals a remarkable diversity of leaf shape,suggesting the importance of this trait for adaptation to various environmental conditions(reviewed in Nicotra et al.2011).Indeed,leaf shape may be constrained by biomechanical factors and affects thermoregulation,susceptibility to herbivory,the available light for photosynthesis,and water balance.
文摘The nomenclature for compounds that are modified with isotopes is growing every day. Compounds can be modified with isotopes either individually, in a functional group or groups, or completely with all atomic centers of the element. This diversity of isotope-modified compounds increases the range of researches that can be studied using them. Compounds modified with isotopes of carbon-13 or nitrogen-15 can be converted into carbon monoxide, carbon dioxide and molecular nitrogen. Currently, only the average value of carbon-13 or nitrogen-15 isotopes can be determined. However, by directly determining the atomic share of these isotopes in organic compounds modified with isotopes, information about the isotopic centers of the element can be obtained. The atomic fraction of an element is defined as a single carbon or nitrogen isotope-modified center or centers, or all centers that are isotope-modified with that element at the same time. Carbon-13 or nitrogen-15 isotopes’ atomic fraction can be determined molecularly or with fragment ions of different elemental content, or both. This makes the method self-verifying, increasing the accuracy and reliability of the results obtained. Amino acids, such as asparagine, aspartic acid, methionine, and threonine, are essential for the human body. This proposed method of isotopic analysis will increase the possibilities for scientific research using these compounds.
基金supported by the Hubei Provincial Natural Science Foundation of China(No.2012FFB04406)
文摘The effects of tacrolimus postconditioning on protein-serine-threonine kinases (Akt) phos- phorylation and apoptotic cell death in rats after spinal cord ischemia-reperfusion injury were investi- gated. Ninety male SD rats were randomly divided into sham operation group, ischemia-reperfusion group and tacrolimus postconditioning group. The model of spinal cord ischemia was established by means of catheterization through femoral artery and balloon dilatation. The spinal cord was reperfused 20 min after ischemia via removing saline out of balloon. The corresponding spinal cord segments were excised and determined for Akt activity in spinal cord tissue by using Western blotting at 5, 15, and 60 min after reperfusion respectively. Spinal cord tissue sections were stained immunohistochemically for detection of the phosphorylated Akt expression at 15 min after reperfusion. Flow cytometry was applied to assess apoptosis of neural cells, and dry-wet weights method was employed to measure water content in spinal cord tissue at 24 h after reperfusion. The results showed that the activities of Akt in tarcolimus postconditioning group were significantly higher than those in ischemia-reperfusion group at 5, 15, and 60 min after reperfusion (P〈0.05, P〈0.01). The Akt activities reached the peak at 15 min after reperfu- sion in ischemia-reperfusion group and tacrolimus postconditioning group. The percentage of apoptotic cells and water content in spinal cord tissue were significantly reduced (P〈0.01) in tacrolimus postcon- ditioning group as compared with those in ischemia-reperfusion group at 24 h after reperfusion. It is concluded that tacrolimus postconditioning can increase Akt activity in spinal cord tissue of rats, inhibit apoptosis of neural cells as well as tissue edema, and thereby alleviate spinal cord ischemia-reperfusion injury.
基金supported by the National Natural Science Foundation of ChinaNo.81271387+3 种基金the Research Special Fund of Public Welfare and Health Department of ChinaNo.201402009the National Key Technology R&D Program in ChinaNo.Z141107002514031
文摘The signaling mechanisms underlying ischemia-induced nerve cell apoptosis are poorly understood. We investigated the effects of apoptosis-related signal transduction pathways following ischemic spinal cord injury, including extracellular signal-regulated kinase(ERK), serine-threonine protein kinase(Akt) and c-Jun N-terminal kinase(JNK) signaling pathways. We established a rat model of acute spinal cord injury by inserting a catheter balloon in the left subclavian artery for 25 minutes. Rat models exhibited notable hindlimb dysfunction. Apoptotic cells were abundant in the anterior horn and central canal of the spinal cord. The number of apoptotic neurons was highest 48 hours post injury. The expression of phosphorylated Akt(pAkt) and phosphorylated ERK(p-ERK) increased immediately after reperfusion, peaked at 4 hours(p-Akt) or 2 hours(p-ERK), decreased at 12 hours, and then increased at 24 hours. Phosphorylated JNK expression reduced after reperfusion, increased at 12 hours to near normal levels, and then showed a downward trend at 24 hours. Pearson linear correlation analysis also demonstrated that the number of apoptotic cells negatively correlated with p-Akt expression. These findings suggest that activation of Akt may be a key contributing factor in the delay of neuronal apoptosis after spinal cord ischemia, particularly at the stage of reperfusion, and thus may be a target for neuronal protection and reduction of neuronal apoptosis after spinal cord injury.
基金This research was supported by the National Key Research and Development Program of China(2021YFD1800403)the National Natural Science Foundation of China(32273005 and 32002256).
文摘The serine proteases of Mycobacteria tuberculosis(Mtb)are important contributors to the process of bacterial invasion and its pathogenesis.In the present study,we systematically characterized the role of the Rv1043c protein in Mycobacterium infection by purifying the Rv1043c protein in Escherichia coli and constructing a Mycobacterium smegmatis(Msg)strain overexpressing Rv1043c(Msg_Rv1043c).We found that Rv1043c had serine protease activity and localized to the surface of Mtb.We determined that the optimal pH and temperature for the Rv1043c serine protease were 9.0 and 45°C,respectively.Moreover,the serine protease activity of Rv1043c was enhanced by divalent metal ions of Ca^(2+)and Mg^(2+).Site-directed mutagenesis studies demonstrated that the serine 279 residue in Rv1043c plays a catalytic role.Additionally,mouse model studies confirmed that Rv1043c significantly enhanced the survival of Msg in vivo,induced pulmonary injury and lung cell apoptosis,and promoted the release of pro-inflammatory cytokines interleukin-1βand interleukin-6 in mice.This study presents novel insights into the relationship between mycobacterial serine protease and the pathogenesis of the disease.
基金This work was supported by the National Key R&D Program of China(2022YFD1400500)the China Agriculture Research System of MOF and MARA(CARS-34-07)+1 种基金the Publicinterest Scientific Institution Basal Research Fund,China(Y2022GH12)the Central Public-interest Scientific Institution Basal Research Fund,China(S2021XM22 and S2022XM21)。
文摘Female adults of the migratory locust,Locusta migratoria manilensis(Meyen),can sense seasonal photoperiod changes,which induces embryonic diapause as a key strategy to overwinter.Serine protease inhibitor genes(SPNs)were thought to play key roles during diapause,while few SPNs were functionally characterized.LmSPN2 was one of those genes differentially expressed between diapause and non-diapause eggs;however,its biological function remained to be explored.So,we conducted RNAi knockdown of LmSPN2,resulting in a significant decrease of the egg diapause rate by 29.7%.Using yeast two-hybrid assays,co-immunoprecipitation,and pull-down methods,we found an interaction between LmSPN2 and LmSPN3,which was proved to be mediated by a glutamate(E331)binding site of LmSPN2.RNAi knockdown of LmSPN3 resulted in a significant increase in diapause rate by 14.6%,indicating an inverse function of LmSPN2 and LmSPN3 on diapause regulation.Double knockdown of two SPN genes resulted in a 26.4%reduction in diapause rate,indicating that LmSPN2 was the dominant regulatory signal.Moreover,we found four Toll pathway genes(easter,spätzle,pelle,and dorsal)upregulated significantly after the knockdown of LmSPN2 while downregulated after the knockdown of LmSPN3.Therefore,we speculate that two SPNs regulate diapause through the Toll pathway.Our results indicated that LmSPN2 positively regulates locust egg entry into diapause,while LmSPN3 is a negative regulator of embryonic commitment to diapause.Their interaction is mediated by the binding site of E331 and influences egg diapause through the Toll pathway.This mechanistic understanding of diapause regulation expands our understanding of insect developmental regulation and provides functional targets for developing locust management strategies.
基金supported by the Research Grant for Faculty(Grant No.R&J/Budget/2011-12/251)
文摘Objective:To isolate,partially purify and evaluate the cytotoxic and antitumor activity of a serine protease from the chosen Indian earthworm Pheretima posthuma.Methods:Whole animal extract was prepared and purified its protein constituents by size and charge based chromatographic separation techniques using Sephadex G-50 and DEAE-Cellulose resin respectively.Average molecular weight of the protein isolate was determined and analyzed for its cytotoxic property against Vero cells in different dilutions(1:20 and 1:40)and anti-tumor activity by MTT assay(a colorimetric assay)using breast cancer cell line MCF-7,with tamoxifen as standard.Results:One of the protein constituents after purification was characterized as serine protease by Caseinolytic plate diffusion assay.Average molecular weight of this purified isolate was determined,by SDS-PAGE analysis with standard protein ladder,as of 15 kDa.The performed tests suggested that the 15kDa fraction has potent cytotoxic activity and satisfactory antitumor activity as well in vitro.Conclusions:Exact molecular mechanism of the cytotoxic and antitumor activities is yet to be explored and currently we are working on ultra-purification and biophysical characterization of this fraction.Further investigation into the mechanism(s)of cytotoxic and antitumor activities at molecular level would be useful in treatment of various classes of cancer and viral infections in future.
基金National 973 Project of China(2014CB138600)National Department Public Benefit Research Foundation(Agriculture) of China (201003020)+1 种基金Science and Technology Support Programme of Sichuan Province of China(2014NZ0003)Major Scientific and Technological Achievement Transformation Project of Sichuan Province of China(2012NC0007 and 2013NC0045) for their financial support
文摘Background: This study was carried out to investigate effects of threonine levels on growth, digestive and absorptive capacity and antioxidant status in intestine and hepatopancreas of sub-adult grass carp ( Ctenopharyngodonidella). Results: Weight gain, specific growth rate, feed intake and feed efficiency were significantly improved by dietary threonine (P 〈 0.05). Intestinal activities of trypsin, chymotrypsin, alpha-amylase, lipase, alkaline phosphatase, y-glutamyl transpeptidase and creatine kinase took the similar trends. Contents of malondialdehyde and protein carbonyl in intestine and hepatopancreas were significantly decreased by dietary optimal threonine supplementation (P 〈 0.05). Anti-superoxide anion capacity, anti-hydroxyl radical capacity, glutathione content and activities of superoxide dismutase, catalase and glutathione-S-transferase in intestine and hepatopancreas were enhanced by dietary threonine (P 〈 0.05). Conclusions: Dietary threonine could improve growth, enhance digestive and absorptive capacity and antioxidant status in intestine and hepatopancreas of sub-adult grass carp. The dietary threonine requirement of sub-adult grass carp (441.9-1,013.4 g) based on weight gain was 11.6 g/kg diet or 41.5 g/kg of dietary protein by quadratic regression analysis.
基金supported by the National Natural Science Foundation of China(Grant No 30470410)the Science and Technology Development Foundation of Shanghai,China(Grant No 03JC14070)
文摘First-principles, all-electron, ab initio calculations have been performed to construct an equivalent water potential for the electronic structure of serine (Ser) in solution. The calculation is composed of three steps. The first step is to search for the configuration of the Ser _ nH2O system with a minimum energy. The second step is to calculate the electronic structure of Ser with the water molecule potential via the self-consistent cluster-embedding method (SCCE), based on the result obtained in the first step. The last step is to calculate the electronic structure of Set with the dipole potential after replacing the water molecules with dipoles. The results show that the occupied states of Ser are raised by about 0.017 Ry on average due to the effect of water. The water effect can be successfully simulated by using the dipole potential. The obtained equivalent potential can be applied directly to the electronic structure calculation of protein in solution by using the SCCE method.
基金The National High Technology Research and Development Program of China under contract No. 2008AA09Z408Fujian Province Nature Science Foundation,China under contract No. 2010J01261the Foundation for Innovative Research Team of Jimei University,China under contract No. 2010A007
文摘The authors have isolated and characterized a novel serine palmitoyltransferase (SPT)-like gene in marine Emiliania huxleyi virus (EhV-99B1). The open-reading frame (ORF) of EhV99BI-SPT encoded a protein of 496 amino acids with a calculated molecular mass of 96 kDa and Ip 6.01. The results of sequence analysis showed that there was about 31% 45% identity in amino acid sequence with other organisms. The maximum likelihood phylogenetic tree suggested that the EhV99B1-SPT gene possibly horizontally transferred from the eukaryote. Hydrophobic profiles of deduced amino acid sequences suggested a hydrophobic, globular and membrane-associated protein with five transmembrane domains (TMDs) motifs. Several potential N-linked glycosylation sites were presented in SPT. These results suggested that EhV99BI-SPT was an integral endoplasmic reticulum membrane protein. Despite lower sequence identity, the secondary and three-dimensional structures predicted showed that the “pocket” structure element composed of 2a-helices and 4β- sheets was the catalytic center of this enzyme, with a typical conserved “TFTKSFG” active site in the N-terminal region and was very close to those of prokaryotic organisms. However, the N-terminal domain of EhV99B1-SPT most closely resembled the LCB2 catalysis subunit and the C-terminal domain most closely resembled the LCBI regulatory subunit of other organisms which together formed a spherical molecule. This “chimera” was highly similar to the prokaryotic homologous SPT. For a functional identification, the EhV99B1-LCB2 subunit gene was expressed in Escherichia coli, which resulted in significant accumulation of new sphingolipid in E. coli cells.
文摘BACKGROUND: HtrA1, a serine protease, is down-regulated in various human solid tumors. Overexpression of HtrA1 in human cancer cells inhibits cell growth and proliferation in vitro and in vivo, suggesting its possible role as a tumor suppressor. METHODS: Immunohistochemistry was used to determine the expression of HtrA1 in 50 hepatocellular carcinoma specimens and adjacent liver tissues. The correlation between the expression of HtrA1 and the clinico-pathologic data were analyzed. RESULTS: The levels of HtrA1 were lower in tumor tissues than in their adjacent liver tissues. Moreover, an inverse relationship was found between HtrA1 expression and the differentiation of hepatocellular carcinoma. Loss of HtrA1 was more frequently found in tumors in Edmondson grade especially in those with venous invasion, compared to tumors in Edmondson grade I-II. Most importantly, patients with higher HtrA1 expression had a better survival rate. CONCLUSION: All these data suggest an important role of HtrA1 in hepatocellular carcinoma development and progression, which may be a new target for its treatment.
基金funded by Swine Innovation Porc under the Swine Cluster2:Driving Results through Innovation research programFunding was also provided by Agriculture and Agri-Food Canada(AAFC)through the AgriInnovation Program,by industry partners and provincial producer organizations,and by Aliments Breton Inc.and Ajinomoto Animal Nutrition Europe+4 种基金Financial support was also provided by the Sao Paulo Research Foundation(FAPESP)(grant no.2012/03781–0 fellowship grant no.2014/25075–6fellowship grant no.2016/09703–2)the Coordena??o de Aperfei?oamento de Pessoal de Nível Superior(CAPES)the Conselho Nacional de Desenvolvimento Científico e Tecnológico(CNPq)(fellowship grant no.132530/2013–9)for their financial support of this project
文摘Background: There is large variation in amino acids requirements among pigs,hence feeding pigs individually with daily tailored diets or in groups with a single feed may require different levels of nutrients.Thus,the response to different threonine levels(70%,85%,100%,115%,and 130% of the ideal threonine:lysine protein ratio of 0.65) was studied in growing pigs raised in a conventional group phase-feeding(GPF) system or fed individually using individual precision-feeding(IPF) techniques.In a 21-day trial,110 barrows(25 ± 0.80 kg body weight) were housed in the same room and fed using electronic feeders.Five pigs per treatment were slaughtered at the end of the trial.Results: Threonine intake increased linearly for the IPF and GPF pigs(P < 0.05).Lysine intake was similar across the treatments.Average daily gain,gain:feed ratio,and protein deposition were affected linearly by threonine level(P < 0.05)in both feeding systems.Protein deposition in the GPF pigs was maximized at 150 g/d and a 0.65 threonine:lysine ratio,whereas protein deposition increased linearly in the IPF pigs.Plasma Met and serine levels were 11 and 7% higher,respectively,in the IPF pigs than in the GPF pigs(P < 0.05).Dietary threonine increased(P < 0.05)threonine concentration in the longissimus dorsi in a quadratic manner in the IPF pigs,whereas there was no effect in the GPF pigs.Longissimus dorsi collagen decreased as dietary threonine increased in the IPF and GPF pigs(P < 0.10).Carcass muscle crude protein was 2% higher in the GPF pigs than in the IPF pigs(P < 0.05).Conclusions: Individual pigs are able to modulate growth and the composition of growth according to threonine intake.The average amino acid ratio value that is currently used for GPF cannot be used for IPF.