This study examined the effect of dietary serine(Ser)on egg white quality,ovomucin content of laying hens fed low-gossypol cottonseed meal(LCSM)-based diet and sought to explore the regulatory mechanism underlying the...This study examined the effect of dietary serine(Ser)on egg white quality,ovomucin content of laying hens fed low-gossypol cottonseed meal(LCSM)-based diet and sought to explore the regulatory mechanism underlying the effects.A total of 288 Hy-Line Brown layers were randomly assigned into 3 treatments and respectively offered soybean meal(SBM)-based diet,LCSM-based diet,and LCSM-based diet supplemented with 0.435%L-Ser.Dietary Ser supplementation reversed the decrease in quality indices of albumen,including the proportion of thick albumen(P<0.05),thick-to-thin ratio(P<0.05),albumen height(P<0.05),Haugh unit(P<0.05),and apparent viscosity that were caused by LCSM intake.Also,dietary Ser supplementation mitigated the LCSM-induced reduction in ovomucin content of the albumen(P<0.05).FT-IR analysis of ovomucin revealed differences in second derivative spectra at 1,200-800 cm^(-1) between birds received SBM-and LCSM-based diets,meanwhile,the α-helix of ovomucin was decreased by LCSM but increased by Ser addition(P<0.05).Furthermore,Ser addition up-regulated the mRNA expression of β-ovomucin in magnum mucosa at 2 and 7.5 h post-oviposition(P<0.05).Ser mitigated the LCSMinduced impairment of magnum epithelium,increased goblet cell counts(P<0.05),and up-regulated the expression of occludin,mucin 2,and the relevant glycosyltransferases for O-glycosylation in magnum mucosa(P<0.05).Conclusively,the alleviating effect of Ser on declining albumen quality due to dietary LCSM,could be explained by the efficacy of Ser in regulating ovomucin synthesis.This regulation occurred at the levels of transcription and posttranscriptional O-glycosylation modification ofβ-ovomucin,while positive effect on magnum morphology and barrier function could also in part account for the ovomucin content.This would provide a promising research direction on the adoption of nutritional interventions for manipulation of egg white quality from perspectives of albumen protein synthesis.展开更多
In nature,certain plants exhibit“sleep”behaviors,such as leaves opening during the day and closing at night[1],which is synchronized with the human circadian rhythm.Traditional Chinese medicine(TCM)describes this ph...In nature,certain plants exhibit“sleep”behaviors,such as leaves opening during the day and closing at night[1],which is synchronized with the human circadian rhythm.Traditional Chinese medicine(TCM)describes this phenomenon as the plant's“diurnal opening and nocturnal closing”trait.Peanut stems and leaves(PSL)refers to the stems and leaves of the leguminous plant Arachis hypogaea L.,which displays this characteristic.PSL has been used as a traditional herbal medicine in TCM for treating insomnia,it was recommended by the Chinese Sleep Research Society's Insomnia Diagnosis and Treatment Guidelines as a recommended monotherapy for treating insomnia in primary healthcare institutions in 2024[2].Based on this,our research group developed a TCM formulation from PSL,named Luo Hua An Shen Oral Liquid(LAOL),which has been clinically applied for over 40 years to treat insomnia.Numerous clinical studies have shown that taking PSL before bedtime promotes sleep[3],while daytime administration enhances daytime functioning.Moreover,our findings demonstrate that the therapeutic efficacy of PSL is independent of administration dosage,administration frequency,and moderate-to-vigorous intensity physical activity.展开更多
We present a theoretical study of interactions of anionic and neutral serine （Ser） on pure or metal-doped graphene surfaces using density functional theory calculations. Interactions of both types of Ser with the pu...We present a theoretical study of interactions of anionic and neutral serine （Ser） on pure or metal-doped graphene surfaces using density functional theory calculations. Interactions of both types of Ser with the pure graphene surface show weak non-covalent interactions due to the formation of-COOH…π, -COO^-…π, and -OH…π interactions. On metal- doped graphene, covalent interactions to the surface dominate, due to the formation of strong metal-O and O-metal-O interactions. Furthermore, the doped Fe, Cr, Mn, A1, or Ti enhances the ability of graphene to attract both types of Ser by a combination of the adsorption energy, the density of states, the Mulliken atomic charges, and differences of electron density. At the same time, the interaction strengths of anionic Ser on various graphene surfaces are stronger than those of neutral Ser. These results provide useful insights for the rational design and development of graphene-based sensors for the two forms of Ser by introducing appropriate doped atoms. Ti and Fe are suggested to be the best choices among all doped atoms for the anionic Ser and neutral Ser, respectively.展开更多
Shape resonances of electron-molecule system formed in the low-energy electron attachment to four low-lying conformers of serine （serine 1, serine 2, serine 3, and serine 4） in gas phase are investigated using the q...Shape resonances of electron-molecule system formed in the low-energy electron attachment to four low-lying conformers of serine （serine 1, serine 2, serine 3, and serine 4） in gas phase are investigated using the quantum scattering method with the non-empirical model potentials in single-center expansion. In the attachment energy range of 0-10 eV, three shape resonances for serine 1, serine 2, and serine 4 and four shape resonances for serine 3 are predicted. The one-dimensional potential energy curves of the temporary negative ions of electron-serine are calculated to explore the correlations between the shape resonance and the bond cleavage. The bond-cleavage selectivity of the different resonant states for a certain conformer is demonstrated, and the recent experimental results about the dissociative electron attachment to serine are interpreted on the basis of present calculations.展开更多
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
[Objective] The aim of the study is to construct cDNA library of midgut tissue of wild silkworm and isolate the serine protease gene. [Method] The midgut tissue-specific cDNA library of wild silkworm was constructed v...[Objective] The aim of the study is to construct cDNA library of midgut tissue of wild silkworm and isolate the serine protease gene. [Method] The midgut tissue-specific cDNA library of wild silkworm was constructed via cDNA Library Construction Kit (TaKaRa), then the serine protease gene was cloned via sequencing of the yielded cDNA library. [Result] The titer of cDNA library reached 6.2×105 pfu/ml, average insert size was about 1.2 kb. The serine protease gene cDNA fragment was obtained from colony sequencing (Accession No: EU672968). The nucleotide sequence of the cloned 854 bp fragment encodes 284 amino acid residues. Homology analyses showed some homology between putative amino acid sequence of the cloned fragment and amino acid sequences of serine proteases from other ten insects. [Conclusion] The results may avail to reveal the resistance of silkworm and wild silkworm to exotic intrusion.展开更多
Clip domain serine proteases （cSPs） and their homologs （SPHs） play an important role in various biological processes that are essential components of extracellular signaling cascades, especially in the innate immu...Clip domain serine proteases （cSPs） and their homologs （SPHs） play an important role in various biological processes that are essential components of extracellular signaling cascades, especially in the innate immune responses of invertebrates. Here, polymorphisms of PtcSP and PtSPH from the swimming crab Portunus tritubereulatus were investigated to explore their association with resistance/ susceptibility to Vibrio alginolyticus. Polymorphic loci were identified using Clustal X, and characterized with SPSS 16.0 software, and then the significance of genotype and allele frequencies between resistant and susceptible stocks was determined by a Zz test. A total of 109 and 77 single nucleotide polymorphisms （SNPs） were identified in the genomic fragments of PtcSP and PtSPH, respectively. Notably, nearly half of PtSPH polymorphisms were found in the non-coding exon 1. Fourteen SNPs investigated were significantly associated with susceptibility/resistance to I1. alginolyticus （P〈0.05）. Among them, eight SNPs were observed in introns, and one synonymous, four non-synonymous SNPs and one ins-del were found in coding exons. In addition, five simple sequence repeats （SSRs） were detected in intron 3 of PtcSP. Although there was no statistically significant difference of allele frequencies, the SSRs showed different polymorphic alleles on the basis of the repeat number between resistant and susceptible stocks. After fiarther validation, polymorphisms investigated here might be applied to select potential molecular markers ofP. trituberculatus with resistance to I1. alginolyticus.展开更多
Aims More and more advances show that hydrogen sulfide （H2S） sulfhydrates functional proteins and regulates their actions. However, much less is known about the endogenous sulfhydration of key proteins under physiol...Aims More and more advances show that hydrogen sulfide （H2S） sulfhydrates functional proteins and regulates their actions. However, much less is known about the endogenous sulfhydration of key proteins under physiological conditions. Methods Biotin-switch assay, electrophysiological recording, RNA interference, full ESI-MS scan et al. Results Herein, we found that the protein sulfhydration was dynamically regulated by neuro- nal activity. H2S sulfhydrated and activated serine racemase （SR） in the hippocampus, resuhantly increased D- serine level. Notably, sulfhydration of SR was markedly promoted by neuronal stimulation and underlay activity-de- pendent changes of D-serine availability. Both genetic knockdown and pharmacological inhibition of cystathionine β-synthase （CBS）, the key H2S-producing enzyme in brain, attenuated hippoeampal long-term potentiation （LTP） , which can be reversed by exogenous supplement of H2S or D-serine. We also observed that the increase in LTP induced by H2S is dependent on D-serine and polysulfides. In aged rats, sulfhydration of SR was significantly decreased. Furthermore, exogenous supplement of H2S restored the level of sulfhydration and reversed the age-re- lated deficits in hippocampal LTP. Conclusion Our data provide direct evidence for the biological significance of endogenous sulfhydration in physiological conditions and demonstrate a pivotal role of activity-dependent sulfhydra- tion in synaptic plasticity.展开更多
AIM： To test the hypothesis that calcium sensing receptor （CASR） polymorphisms are associated with chronic pancreatitis （CP）, and to determine whether serine protease inhibitor Kazal 1type （SPINK1） N34S or alco...AIM： To test the hypothesis that calcium sensing receptor （CASR） polymorphisms are associated with chronic pancreatitis （CP）, and to determine whether serine protease inhibitor Kazal 1type （SPINK1） N34S or alcohol are necessary co-factors in its etiology. METHODS： Initially, 115 subjects with pancreatitis and 66 controls were evaluated, of whom 57 patients and 21 controls were predetermined to carry the high-risk SPINK1 N34S polymorphism. We sequenced CASR gene exons 2, 3, 4, 5 and 7, areas containing the majority of reported polymorphisms and novel mutations. Based on the initial results, we added 223 patients and 239 controls to analyze three common nonsynonymous single nucleotide polymorphisms （SNPs） in exon 7 （A986S, R990G, and Q1011E）. RESULTS： The CASR exon 7 R990G polyrnorphism was significantly associated with CP （OR, 2.01; 95% CI, 1.12-3.59; P = 0.015）. The association between CASR R990G and CP was stronger in subjects who reported moderate or heavy alcohol consumption （OR, 3.12; 95% CI, 1.14-9.13; P = 0.018）. There was no association between the various CASR genotypes and SPINK1 N34S in pancreatitis. None of the novel CASR polymorphisms reported from Germany and India was detected. CONCLUSION： Our United States-based study confirmed an association of CASR and CP and for the first time demonstrated that CASR R990G is a significant risk factor for CP. We also conclude that the risk of CP with CASR R990G is increased in subjects with moderate to heavy alcohol consumption.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
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
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
We studied the responses of the activities of adenosine-triphosphate (ATP) sulfurylase (ATPS) and serine acetyltransferase (SAT) to cadmium (Cd) levels and treatment time in hyperaccumulating ecotype (HE) Sedum alfred...We studied the responses of the activities of adenosine-triphosphate (ATP) sulfurylase (ATPS) and serine acetyltransferase (SAT) to cadmium (Cd) levels and treatment time in hyperaccumulating ecotype (HE) Sedum alfredii Hance, as compared with its non-hyperaccumulating ecotype (NHE). The results show that plant growth was inhibited in NHE but promoted in HE when exposed to high Cd level. Cd concentrations in leaves and shoots rapidly increased in HE rather than in NHE, and they became much higher in HE than in NHE along with increasing treatment time and Cd supply levels. ATPS activity was higher in HE than in NHE in all Cd treatments, and increased with increasing Cd supply levels in both HE and NHE when exposed to Cd treatment within 8 h. However, a marked difference of ATPS activity between HE and NHE was found with Cd treatment for 168 h, where ATPS activity increased in HE but decreased in NHE. Similarly, SAT activity was higher in HE than in NHE at all Cd treatments, but was more sensitive in NHE than in HE. Both ATPS and SAT activities in NHE leaves tended to decrease with increasing treatment time after 8 h at all Cd levels. The results reveal the different responses in sulfur assimilation enzymes and Cd accumulation between HE and NHE. With increasing Cd stress, the activities of sulfur assimilation enzymes (ATPS and SAT) were induced in HE, which may contribute to Cd accumulation in the hyperaccumulator Sedum alfredii Hance.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
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
Soybean stachyose (SBS) and phytic acid (PA) are anti-nutritional factors (ANF) which have deleterious effects on the growth and digestibility in fish. The present research studied the effects of dietary SBS and PA on...Soybean stachyose (SBS) and phytic acid (PA) are anti-nutritional factors (ANF) which have deleterious effects on the growth and digestibility in fish. The present research studied the effects of dietary SBS and PA on the expression of three serine protease genes in the liver of Japanese flounder (Paralichthys olivaceus). These genes are trypsinogen 1 (poTRY), elastase 1 (poEL) and chymotrypsinogen 1 (poCTRY). Eight artificial diets with graded levels of supplemented ANFs were formulated to 4 levels of SBS (0.00, 0.40, 0.80 and 1.50%), 4 levels of PA (0.00, 0.20, 0.40 and 0.80), respectively.Japanese flounder (initial weight 2.45 g ± 0.01 g) were fed with these diets for 10 weeks with three replications per treatment. At the end of 10 weeks, supplementation of 0.40% of dietary SBS or PA significantly increased the gene expression of poTRY and poCTRY (P<0.05). The same level of dietary SBS significantly decreased the gene expression of poEL. In comparison with the control group (ANF-free),dietary PA (0.2% and 0.8%) significantly decreased the gene expression of poTRY, poCTRY and poEL (P<0.05). However, excessive supplement of dietary SBS (1.5%) has no significant effects on these gene expressions (P>0.05). These results suggested that dietary SBS and dietary PA could directly affect the serine protease genes at the transcriptional level in Japanese flounder, and these genes'expression was more sensitive to dietary PA than to SBS under the current experimental conditions.展开更多
Serine, one of the nonessential amino acids, is of principal interest because of its capability to form magic-number ionic clusters, which provide a remarkable preference for homochirality. With L-aspartic acid as the...Serine, one of the nonessential amino acids, is of principal interest because of its capability to form magic-number ionic clusters, which provide a remarkable preference for homochirality. With L-aspartic acid as the precursor, this study provides experimental evidence for serine formation in weak acidified aqueous solutions in the presence of iron, with exposure to sunlight, which simulates the natural conditions of the prebiotic aqueous environment. The resultant mixture is directly analyzed via desorption electrospray ionization mass spectrometry（ DESI-MS）, without any sample preseparation. The serine monomer is successfully detected as protonated molecules, giving a peak at m/z 106, which is confirmed by the MS/MS fragments. Protonated serine octamer（ m/z 841 ） is also observed with significant abundance in the MS spectra and is confirmed by the MS/MS data, which shows the formation of the serine octamer by a synthesized serine in the resultant mixture. It is also found that the serine octamer yielded equivalent abundance in the DESI mass spectra in a wide pH range（pH = 1-5 ）, and that existence of ferrous salt and sunshine are essential for the conversion of aspartic acid to serine in the acidic water solution.展开更多
基金financially supported by the National Natural Science Foundation of China(32072774)the China Postdoctoral Science Foundation(2023M733822)+2 种基金the Beijing Innovation Consortium of Agriculture Research System(BAIC04),Chinathe earmarked fund for CARS National System for Layer Production Technology,China(CARS-40)the Agricultural Science and Technology Innovation Program(ASTIP)of the Chinese Academy of Agricultural Sciences。
文摘This study examined the effect of dietary serine(Ser)on egg white quality,ovomucin content of laying hens fed low-gossypol cottonseed meal(LCSM)-based diet and sought to explore the regulatory mechanism underlying the effects.A total of 288 Hy-Line Brown layers were randomly assigned into 3 treatments and respectively offered soybean meal(SBM)-based diet,LCSM-based diet,and LCSM-based diet supplemented with 0.435%L-Ser.Dietary Ser supplementation reversed the decrease in quality indices of albumen,including the proportion of thick albumen(P<0.05),thick-to-thin ratio(P<0.05),albumen height(P<0.05),Haugh unit(P<0.05),and apparent viscosity that were caused by LCSM intake.Also,dietary Ser supplementation mitigated the LCSM-induced reduction in ovomucin content of the albumen(P<0.05).FT-IR analysis of ovomucin revealed differences in second derivative spectra at 1,200-800 cm^(-1) between birds received SBM-and LCSM-based diets,meanwhile,the α-helix of ovomucin was decreased by LCSM but increased by Ser addition(P<0.05).Furthermore,Ser addition up-regulated the mRNA expression of β-ovomucin in magnum mucosa at 2 and 7.5 h post-oviposition(P<0.05).Ser mitigated the LCSMinduced impairment of magnum epithelium,increased goblet cell counts(P<0.05),and up-regulated the expression of occludin,mucin 2,and the relevant glycosyltransferases for O-glycosylation in magnum mucosa(P<0.05).Conclusively,the alleviating effect of Ser on declining albumen quality due to dietary LCSM,could be explained by the efficacy of Ser in regulating ovomucin synthesis.This regulation occurred at the levels of transcription and posttranscriptional O-glycosylation modification ofβ-ovomucin,while positive effect on magnum morphology and barrier function could also in part account for the ovomucin content.This would provide a promising research direction on the adoption of nutritional interventions for manipulation of egg white quality from perspectives of albumen protein synthesis.
基金supported by the National Key R&D Program of China(Grant No.:2021YFC2501500)Shanghai Key Laboratory for Pharmaceutical Metabolite Research,China(Grant No.:SHZYDX2023-01)Shanghai Technical Superiority Project of"Preventive Treatment of Disease",Shanghai Municipal Health Commission,China(Grant No.:ZY(2021-2023)-0104-02-GF-04).
文摘In nature,certain plants exhibit“sleep”behaviors,such as leaves opening during the day and closing at night[1],which is synchronized with the human circadian rhythm.Traditional Chinese medicine(TCM)describes this phenomenon as the plant's“diurnal opening and nocturnal closing”trait.Peanut stems and leaves(PSL)refers to the stems and leaves of the leguminous plant Arachis hypogaea L.,which displays this characteristic.PSL has been used as a traditional herbal medicine in TCM for treating insomnia,it was recommended by the Chinese Sleep Research Society's Insomnia Diagnosis and Treatment Guidelines as a recommended monotherapy for treating insomnia in primary healthcare institutions in 2024[2].Based on this,our research group developed a TCM formulation from PSL,named Luo Hua An Shen Oral Liquid(LAOL),which has been clinically applied for over 40 years to treat insomnia.Numerous clinical studies have shown that taking PSL before bedtime promotes sleep[3],while daytime administration enhances daytime functioning.Moreover,our findings demonstrate that the therapeutic efficacy of PSL is independent of administration dosage,administration frequency,and moderate-to-vigorous intensity physical activity.
文摘We present a theoretical study of interactions of anionic and neutral serine （Ser） on pure or metal-doped graphene surfaces using density functional theory calculations. Interactions of both types of Ser with the pure graphene surface show weak non-covalent interactions due to the formation of-COOH…π, -COO^-…π, and -OH…π interactions. On metal- doped graphene, covalent interactions to the surface dominate, due to the formation of strong metal-O and O-metal-O interactions. Furthermore, the doped Fe, Cr, Mn, A1, or Ti enhances the ability of graphene to attract both types of Ser by a combination of the adsorption energy, the density of states, the Mulliken atomic charges, and differences of electron density. At the same time, the interaction strengths of anionic Ser on various graphene surfaces are stronger than those of neutral Ser. These results provide useful insights for the rational design and development of graphene-based sensors for the two forms of Ser by introducing appropriate doped atoms. Ti and Fe are suggested to be the best choices among all doped atoms for the anionic Ser and neutral Ser, respectively.
基金This work is supported by the National Natural Science Foundation of China （No.21303212 and No.21573209）, the Ministry of Science and Technology of China （No.2013CB834602）.
文摘Shape resonances of electron-molecule system formed in the low-energy electron attachment to four low-lying conformers of serine （serine 1, serine 2, serine 3, and serine 4） in gas phase are investigated using the quantum scattering method with the non-empirical model potentials in single-center expansion. In the attachment energy range of 0-10 eV, three shape resonances for serine 1, serine 2, and serine 4 and four shape resonances for serine 3 are predicted. The one-dimensional potential energy curves of the temporary negative ions of electron-serine are calculated to explore the correlations between the shape resonance and the bond cleavage. The bond-cleavage selectivity of the different resonant states for a certain conformer is demonstrated, and the recent experimental results about the dissociative electron attachment to serine are interpreted on the basis of present calculations.
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[Objective] The aim of the study is to construct cDNA library of midgut tissue of wild silkworm and isolate the serine protease gene. [Method] The midgut tissue-specific cDNA library of wild silkworm was constructed via cDNA Library Construction Kit (TaKaRa), then the serine protease gene was cloned via sequencing of the yielded cDNA library. [Result] The titer of cDNA library reached 6.2×105 pfu/ml, average insert size was about 1.2 kb. The serine protease gene cDNA fragment was obtained from colony sequencing (Accession No: EU672968). The nucleotide sequence of the cloned 854 bp fragment encodes 284 amino acid residues. Homology analyses showed some homology between putative amino acid sequence of the cloned fragment and amino acid sequences of serine proteases from other ten insects. [Conclusion] The results may avail to reveal the resistance of silkworm and wild silkworm to exotic intrusion.
基金Supported by the National Natural Science Foundation of China(Nos.41206147,31302187)the Scientific and Technological Innovation Project Financially Supported by Qingdao National Laboratory for Marine Science and Technology(No.2015ASKJ02)
文摘Clip domain serine proteases （cSPs） and their homologs （SPHs） play an important role in various biological processes that are essential components of extracellular signaling cascades, especially in the innate immune responses of invertebrates. Here, polymorphisms of PtcSP and PtSPH from the swimming crab Portunus tritubereulatus were investigated to explore their association with resistance/ susceptibility to Vibrio alginolyticus. Polymorphic loci were identified using Clustal X, and characterized with SPSS 16.0 software, and then the significance of genotype and allele frequencies between resistant and susceptible stocks was determined by a Zz test. A total of 109 and 77 single nucleotide polymorphisms （SNPs） were identified in the genomic fragments of PtcSP and PtSPH, respectively. Notably, nearly half of PtSPH polymorphisms were found in the non-coding exon 1. Fourteen SNPs investigated were significantly associated with susceptibility/resistance to I1. alginolyticus （P〈0.05）. Among them, eight SNPs were observed in introns, and one synonymous, four non-synonymous SNPs and one ins-del were found in coding exons. In addition, five simple sequence repeats （SSRs） were detected in intron 3 of PtcSP. Although there was no statistically significant difference of allele frequencies, the SSRs showed different polymorphic alleles on the basis of the repeat number between resistant and susceptible stocks. After fiarther validation, polymorphisms investigated here might be applied to select potential molecular markers ofP. trituberculatus with resistance to I1. alginolyticus.
文摘Aims More and more advances show that hydrogen sulfide （H2S） sulfhydrates functional proteins and regulates their actions. However, much less is known about the endogenous sulfhydration of key proteins under physiological conditions. Methods Biotin-switch assay, electrophysiological recording, RNA interference, full ESI-MS scan et al. Results Herein, we found that the protein sulfhydration was dynamically regulated by neuro- nal activity. H2S sulfhydrated and activated serine racemase （SR） in the hippocampus, resuhantly increased D- serine level. Notably, sulfhydration of SR was markedly promoted by neuronal stimulation and underlay activity-de- pendent changes of D-serine availability. Both genetic knockdown and pharmacological inhibition of cystathionine β-synthase （CBS）, the key H2S-producing enzyme in brain, attenuated hippoeampal long-term potentiation （LTP） , which can be reversed by exogenous supplement of H2S or D-serine. We also observed that the increase in LTP induced by H2S is dependent on D-serine and polysulfides. In aged rats, sulfhydration of SR was significantly decreased. Furthermore, exogenous supplement of H2S restored the level of sulfhydration and reversed the age-re- lated deficits in hippocampal LTP. Conclusion Our data provide direct evidence for the biological significance of endogenous sulfhydration in physiological conditions and demonstrate a pivotal role of activity-dependent sulfhydra- tion in synaptic plasticity.
基金NIH R01 DK061451 (DCW) and Andrew and Michelle Aloe
文摘AIM： To test the hypothesis that calcium sensing receptor （CASR） polymorphisms are associated with chronic pancreatitis （CP）, and to determine whether serine protease inhibitor Kazal 1type （SPINK1） N34S or alcohol are necessary co-factors in its etiology. METHODS： Initially, 115 subjects with pancreatitis and 66 controls were evaluated, of whom 57 patients and 21 controls were predetermined to carry the high-risk SPINK1 N34S polymorphism. We sequenced CASR gene exons 2, 3, 4, 5 and 7, areas containing the majority of reported polymorphisms and novel mutations. Based on the initial results, we added 223 patients and 239 controls to analyze three common nonsynonymous single nucleotide polymorphisms （SNPs） in exon 7 （A986S, R990G, and Q1011E）. RESULTS： The CASR exon 7 R990G polyrnorphism was significantly associated with CP （OR, 2.01; 95% CI, 1.12-3.59; P = 0.015）. The association between CASR R990G and CP was stronger in subjects who reported moderate or heavy alcohol consumption （OR, 3.12; 95% CI, 1.14-9.13; P = 0.018）. There was no association between the various CASR genotypes and SPINK1 N34S in pancreatitis. None of the novel CASR polymorphisms reported from Germany and India was detected. CONCLUSION： Our United States-based study confirmed an association of CASR and CP and for the first time demonstrated that CASR R990G is a significant risk factor for CP. We also conclude that the risk of CP with CASR R990G is increased in subjects with moderate to heavy alcohol consumption.
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supported by the National Natural Science Foundation of China (No. 30630046)the Hi-Tech Research and Development Program (863) of China (No. 2006AA06Z386)the Program for Changjiang Scholars and Innovative Research Team in University, China (No. IRT0536)
文摘We studied the responses of the activities of adenosine-triphosphate (ATP) sulfurylase (ATPS) and serine acetyltransferase (SAT) to cadmium (Cd) levels and treatment time in hyperaccumulating ecotype (HE) Sedum alfredii Hance, as compared with its non-hyperaccumulating ecotype (NHE). The results show that plant growth was inhibited in NHE but promoted in HE when exposed to high Cd level. Cd concentrations in leaves and shoots rapidly increased in HE rather than in NHE, and they became much higher in HE than in NHE along with increasing treatment time and Cd supply levels. ATPS activity was higher in HE than in NHE in all Cd treatments, and increased with increasing Cd supply levels in both HE and NHE when exposed to Cd treatment within 8 h. However, a marked difference of ATPS activity between HE and NHE was found with Cd treatment for 168 h, where ATPS activity increased in HE but decreased in NHE. Similarly, SAT activity was higher in HE than in NHE at all Cd treatments, but was more sensitive in NHE than in HE. Both ATPS and SAT activities in NHE leaves tended to decrease with increasing treatment time after 8 h at all Cd levels. The results reveal the different responses in sulfur assimilation enzymes and Cd accumulation between HE and NHE. With increasing Cd stress, the activities of sulfur assimilation enzymes (ATPS and SAT) were induced in HE, which may contribute to Cd accumulation in the hyperaccumulator Sedum alfredii Hance.
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.
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financially supported by grant from the National Natural Science Foundation of China(No.31072219)
文摘Soybean stachyose (SBS) and phytic acid (PA) are anti-nutritional factors (ANF) which have deleterious effects on the growth and digestibility in fish. The present research studied the effects of dietary SBS and PA on the expression of three serine protease genes in the liver of Japanese flounder (Paralichthys olivaceus). These genes are trypsinogen 1 (poTRY), elastase 1 (poEL) and chymotrypsinogen 1 (poCTRY). Eight artificial diets with graded levels of supplemented ANFs were formulated to 4 levels of SBS (0.00, 0.40, 0.80 and 1.50%), 4 levels of PA (0.00, 0.20, 0.40 and 0.80), respectively.Japanese flounder (initial weight 2.45 g ± 0.01 g) were fed with these diets for 10 weeks with three replications per treatment. At the end of 10 weeks, supplementation of 0.40% of dietary SBS or PA significantly increased the gene expression of poTRY and poCTRY (P<0.05). The same level of dietary SBS significantly decreased the gene expression of poEL. In comparison with the control group (ANF-free),dietary PA (0.2% and 0.8%) significantly decreased the gene expression of poTRY, poCTRY and poEL (P<0.05). However, excessive supplement of dietary SBS (1.5%) has no significant effects on these gene expressions (P>0.05). These results suggested that dietary SBS and dietary PA could directly affect the serine protease genes at the transcriptional level in Japanese flounder, and these genes'expression was more sensitive to dietary PA than to SBS under the current experimental conditions.
基金Supported by the National Natural Science Foundation of China(No.20505003).
文摘Serine, one of the nonessential amino acids, is of principal interest because of its capability to form magic-number ionic clusters, which provide a remarkable preference for homochirality. With L-aspartic acid as the precursor, this study provides experimental evidence for serine formation in weak acidified aqueous solutions in the presence of iron, with exposure to sunlight, which simulates the natural conditions of the prebiotic aqueous environment. The resultant mixture is directly analyzed via desorption electrospray ionization mass spectrometry（ DESI-MS）, without any sample preseparation. The serine monomer is successfully detected as protonated molecules, giving a peak at m/z 106, which is confirmed by the MS/MS fragments. Protonated serine octamer（ m/z 841 ） is also observed with significant abundance in the MS spectra and is confirmed by the MS/MS data, which shows the formation of the serine octamer by a synthesized serine in the resultant mixture. It is also found that the serine octamer yielded equivalent abundance in the DESI mass spectra in a wide pH range（pH = 1-5 ）, and that existence of ferrous salt and sunshine are essential for the conversion of aspartic acid to serine in the acidic water solution.
