The ocean is a huge resource of organisms and about 80% of the world species live in it. Marine organisms synthesize various structurally-unique and pharmacologically-active metabolites which differ from those derived from the land organisms and serve as lead compounds for drug development. More than 15 000 new compounds have been isolated and identified from marine animals, plants and microorganisms since decades ago, and drugs like cephalosporins, ziconotide (Prialt), cytarabine (AraC) and vidarabine (AraA) were developed using these compounds as precursors.

The nuclear transcription factor nuclear factor erythroid 2-related factor 2 (NRF2) plays a crucial role in maintaining cellular redox homeostasis. The aberrant NRF2 signaling confers enhanced antioxidant capacity, which is linked to tumor progression and therapeutic resistance. The current study investigates the biological effects and molecular mechanism of tribbles homolog 3 (TRIB3), a stress-induced protein, in regulating cell survival and apoptosis in lung cancer. This study first performed the RNA sequencing data analysis with 576 lung adenocarcinoma patients from the cancer genome atlas (TCGA) database. The NRF2- antioxidant response element (ARE) signature was enriched in patients with high TRIB3 expression. Dual-luciferase reporter assay and real-time quantitative polymerase chain reaction (PCR) were used to confirm the effect of TRIB3 on the kelch-like ECH-associated protein-1 (KEAP1)-NRF2 pathway. Abrogation of TRIB3 impaired NRF2 transcriptional activity and reduced the expression of its target genes. Moreover, TRIB3 enhanced NRF2 stability via blocking KEAP1-NRF2 interaction. TRIB3-depletion promoted reactive oxygen species (ROS) production, restrained cell proliferation, and enhanced carboplatin-induced apoptosis. In addition, NRF2 overexpression recovered the tumor inhibition effect of TRIB3-depletion. Consistently, TRIB3 failed to modulate apoptosis in NRF2 depletion cells. In summary, this study shows that TRIB3 inhibits the KEAP1-NRF2 interaction and upregulates the transcriptional activity of NRF2, thereby promoting lung cancer cell proliferation and reducing the sensitivity to chemotherapy. Targeting the TRIB3-NRF2 signal axis may become a new strategy for ROS homeostasis and lung cancer treatment.

Macrolactins are 24-membered macrolides produced by unidentified marine bacterium, Actinomadura sp. and Bacillus sp., which exhibit both antibacterial and antitumor activities in vitro. The environmental strain X-2 which was isolated from the sediment of the East China Sea produce Macrolatin A, B and O. In this study, a set of degenerate oligonucleotide primers, designed for amplification ketosynthase(KS) domains, had been employed to identify KS gene fragments of the X-2 DNA samples. One 645 bp KS fragment(GenBank accession no. EF486351)had been cloned and used as a probe to screen the genome DNA fosmid library of X-2. Three positive clones were selected and sequenced, Homologous analysis and the function prediction of the obtained PKS gene fragments suggested that macrolactin is the Polyketide Biosynthesis Product of the gene cluster obtained in the environmental strain X-2.

Objective:To express Tumstatin_(183-230)-TRAIL fusion protein and to observe its biological functions.Methods: SOE-ing PCR was employed to amplify the recombinant sequence of Tumstatin_(183-230)and TNF-related apoptosis-inducing ligand (TRAIL_(114-281)).An expression vector pMAL-Tu-T was constructed by inserting Tu-T sequence into pMAL-c_2;the vector was used to transfect E.coli BL21(DE3)and expression of MBP-Tu-T fusion protein was induced by IPTG.Amylose Resin columns were employed to purify the fusion protein.The biological functions of MBP-Tu-T protein was examined by inhibitory test of endothelial cell proliferation,standard tumor cell cytotoxic assay,in vitro tube formation inhibition,and electron microscopic observation(apoptosis).Results:The expression rate of MBP-Tu-T fusion protein in E.coli was about 20%. Purified recombinant protein obviously inhibited endothelial cell proliferation(IC_(50)12.5?g/ml),induced apoptosis of pancreatic cancer cells,and inhibited tube formation.Conclusion:Constructed MBP-Tu-T fusion protein is bifunctional,which lays a solid foundation for further investigation of antitumor effect of Tumstatin_(183-230)-TRAIL in vivo.

Objective: To chine and express the recombinant human endothelial monocyte-activating polypeptide-Ⅱ(EMAP-Ⅱ)and identify its anti-tumor biological activities.Methods: EMAP-Ⅱ_(147-312)was expressed by the expression vector pMAL-p2x and E.coli BL-21 and the product was purified.The production of tissue factor(TF)in human umbili- cal vein endothelial cell ECV-304 mediated by the recombinant EMAP-Ⅱwas determined by chemiluminescence sub- strate.The promoting effect of recombinant EMAP-Ⅱon TNF?-induced ECV-304 cell.Apoptosis was determined by flow cytometry.Its inhibitory effect on human pancreaic cancer cell SW1990 proliferation was determined by MTT method. Results:DNA sequencing verified that EMAP-Ⅱwas correctly cloned.The molecular mass of the protein identified by SDS-PAGE was consistent with the theoretic value.The productivity of recombinant EMAP-Ⅱwas 500?g per 1 g bacteria (wet mass).The purified product induced expression of tissue factor(TF)in ECV-304 cells;it also enhanced the sensi- tivity of ECV-304 cells to the apoptotic effect of TNF?([16.6?2.5]% vs[25.6?2.3]%,P

The strain F12-11-1-2 was isolated from the East China Sea,which had antimitosis activity using Pyricularia oryzae mode.Ac- cording to phenotypical study,salt-aggregation test and 16S rDNA sequence analysis,the strain F12-11-1-2 has been identified to be Bacillus subtilis.

OBJECTIVETo investigate the dentoalveolar characteristics in skeletal class I patients with excessive overjet.

METHODSTen cephalometric measurements of 60 skeletal class I patients with excessive overjet were analyzed.

RESULTSCompared with patients with normal overjet, 1-SN, 1-NA and MxAAH were significantly increased in excessive overjet group I (overjet: 3 - 5 mm) and 1-SN, 1-NA and MxAAH were significantly increased in excessive overjet group II (overjet: 5 - 7 mm).

CONCLUSIONSThe protrusion and tipping of maxillary incisor, and absence of compensatory proclination of mandibular incisor may be the factors, caused skeletal class I excessive overjet. Increased height of anterior maxillary anterior alveolar process was the compensatory change in skeletal class I patients with excessive overjet.

Adolescent ; Alveolar Process ; diagnostic imaging ; pathology ; Cephalometry ; Child ; Female ; Humans ; Incisor ; diagnostic imaging ; pathology ; Male ; Malocclusion, Angle Class I ; diagnostic imaging ; pathology ; Radiography

This study is to investigate the influence and mechanism of action of asymmetrical dimethylarginine (ADMA) and the induced oxidative stress level on Alzheimer's disease (AD) incidence. ADMA concentration, nitric oxide, Abeta(40)/Abeta(42) ratio, inducible NO synthase (iNOS) activity and the concentrations of the induced free radicals including malondialdehyde (MDA), 3-nitrotyrosine (3-NT) and peroxynitrite (ONOO-) in the cerebrospinal fluid (CSF) from 34 neurologically normal controls and 37 AD patients were quantitatively determined and statistically compared. The results showed that the ADMA concentration significantly decreased in AD patients, and it showed negative correlation with the NO, iNOS activity, and showed positive correlation with MMSE score. ADMA concentration was negatively correlated with Abeta(40)/Abeta(42) ratio (P<0.01) with the observation that Abeta(40)/Abeta(42) ratio increased while ADMA level decreased in CSF in AD patients. The concentration levels of MDA, 3-NT and ROS significantly increased compared with the control with all the P values less than 0.05. These findings suggested that the ADMA disorder and the oxidative damage effect of the induced free radicals in CSF of AD patients are an important mechanism of AD incidence, and their joint regulation may provide new idea for the prevention and clinical treatment of AD.
Aged ; Alzheimer Disease ; cerebrospinal fluid ; Amyloid beta-Peptides ; cerebrospinal fluid ; Arginine ; analogs & derivatives ; cerebrospinal fluid ; Female ; Humans ; Male ; Malondialdehyde ; cerebrospinal fluid ; Middle Aged ; Nitric Oxide ; cerebrospinal fluid ; Nitric Oxide Synthase Type II ; cerebrospinal fluid ; Oxidative Stress ; Peptide Fragments ; cerebrospinal fluid ; Peroxynitrous Acid ; cerebrospinal fluid ; Reactive Oxygen Species ; cerebrospinal fluid ; Tyrosine ; analogs & derivatives ; cerebrospinal fluid

Objective: To investigate the efficacy of alternative donor (AD) in the treatment of aplastic anemia (AA) in children. Methods: The clinical data of AA children who received AD HSCT in our center from Apr. 2010 to Dec. 2016 were retrospectively analyzed. The overall survival (OS) rate, implant success rate, incidence of acute and chronic graft-versus-host disease (GVHD) were statistically analyzed. Results: A total of 109 children with acquired AA, including 64 severe AA (SAA) , 32 very severe AA (VSAA) and 13 transfusion dependent non-severe AA (NSAA) , were recruited in this retrospective AD HSCT study, the median age was 6 (0.8-18) years old. Of them, 44 patients with 10/10 matched unrelated donor (MUD) , 44 patients with mismatched unrelated donor (MMUD) and 21 patients with mismatched related donor (MMRD) . All patients did not receive ATG before HSCT and the active infection was excluded. Except 3 patients suffered from a second graft failure (2 of them rescued by second HSCT) , 106/109 (97.2%) were engrafted with neutrophil and platelet recovery occurring at a median of 13 days (range, 9-19) and 16 days (range, 10-81) post-transplant. Until day 100 post transplantation, the incidence was 74.3% (81/109) for acute GVHD (aGVHD) and 39.4% (43/109) for grade Ⅱ-Ⅳ aGVHD, 30.7% (31/101) and 9.9% (10/101) for overall chronic GVHD (cGVHD) and moderate cGVHD, respectively, and nobody developed an extend cGVHD. After median follow up of 39 (0.7-103) months for all patients, 13 of 109 patients died. The estimated 5-year overall survival (OS) of the entire cohort was 88.1% (95%CI 81.1%-91.4%) with no difference among the MUD, MMUD and MMRD cohort (93.2%, 84.1% and 85.7%, respectively, P=0.361) . Conclusion: These excellent outcomes suggest that unmanipulated AD PBSC is a good HSCT source for children with SAA. It's reasonable to consider AD HSCT as first line therapy for SAA children without matched sibling donor. Better strategies are required to prevent GVHD.
Adolescent ; Anemia, Aplastic ; Child ; Child, Preschool ; Graft vs Host Disease ; Hematopoietic Stem Cell Transplantation ; Humans ; Infant ; Retrospective Studies ; Tissue Donors ; Treatment Outcome

OBJECTIVETo assess the nasal airway changes after maxillary advancement following Le Fort I osteotomy.

METHODS13 cases with class III malocclusion, aged 18-35 years old, were studied prospectively. All the patients underwent Le Fort I osteotomy and maxillary advancement. Rhinological inspectrum, acoustic rhinometry (AR) were performed before operation, 3 and 6 months after operation. The Nasal Obstruction Symptom Evaluation (NOSE) scale was also completed by 13 patients before and after operation. SPSS was used for statistical assay.

RESULTSAR assessment showed that NAR was (1.189 +/- 0.38) cm H2O/L/mi, (1.081 +/- 0.43) cm H2O/L/mi and (1.111 +/- 0.40) cm H2O/L/mi before operation, 3 and 6 months after operation; NV was (14.920 +/- 1.95) ml, (16.380 +/- 4.32) ml and (15.660 +/- 4.25) ml; and MCA was (0.500 +/- 0.09) cm2, (0.570 +/- 0.15) cm2 and (0.560 +/- 0.14) cm2, respectively. However, no significant improvement was showed. For the whole cohort, significant improvement in nasal breathing was documented (by NOSE scores) at 6 months after surgery.

CONCLUSIONSLe Fort I osteotomy with maxillary advancement doesn't cause bad effect on nasal airways in patients with maxillary dysplasia. And the combination of objective (AR) and subjective (NOSE scale) assessment can better evaluate of the structure and function of the nose.

Adolescent ; Adult ; Female ; Humans ; Male ; Maxilla ; surgery ; Nose ; physiopathology ; Osteotomy, Le Fort ; methods ; Postoperative Period ; Respiration ; Young Adult