ABSTRACT
@#Thioredoxin-interacting protein (TXNIP), which mainly regulates glucose homeostasis in pancreatic β cells, is a novel target in the treatment of diabetes.In this study, 4-hydroxybenzopyrimidine was used as the raw material, four nitrogen-containing rings (imidazole, methylpiperazine, pyrazole, morpholine) were introduced, benzopyrimidine skeleton with nitrogen-containing rings derivatives targeting TXNIP was designed and synthesized, and the protective effect of compounds on palmitic acid-stimulated islet β cells was investigated.A total of 20 benzopyrimidine derivatives were designed and synthesized, and the structures were confirmed by 1H NMR and ESI-MS.Pharmacological studies showed that most of the compounds exhibited protective effects on islet β cells, with better axtivity for compounds C-1, C-2, C-4 and D-2 (cell survival rate > 70%) compared with PA model group (38.3%), Among the four compounds, D-2 had the highest activity of 87.2%, so it could become a potential new anti-diabetic chemical entity.
ABSTRACT
In order to explore the mechanisms underlying the calcium alleviating fluorosis at protein level, we made an attempt to establish fluorosis and calcium supplementation rat models to isolate and identify bone differential proteins. The bone proteins of different groups were compared by two-dimensional electrophoresis (2-DE) and mass spectrometry (MALDI-TOF MS), and analyzed by gene ontology annotation, pathway enrichment and interaction networks. The 17 proteins were identified in the fluorosis group (F) and the fluorosis calcium supplement group (F+Ca), including type I collagen (Col1a1), actin (Actb), protein glutamine transferase 2 (Tgm2), compared with the control group (C). These differential proteins are enriched in 38 bone metabolic pathways such as focal adhesion, PI3K-Akt signaling pathway, and AMPK signaling pathway. And the functions of these proteins are mainly related to cytoskeleton, energy metabolism, substance transport, ion channel, and apoptosis. Therefore, it is speculated that calcium may alleviate the fluoride-induced bone damage by regulating the focal adhesion, PI3K-Akt, AMPK and other signaling pathway, but the specific mechanism needs further research.
Subject(s)
Animals , Rats , Calcium , Dietary Supplements , Fluoride Poisoning , Fluorosis, Dental , Phosphatidylinositol 3-KinasesABSTRACT
Objective To evaluate the efficacy of the new treatment regimen versus the standardized scheme for the initial treatment of smear-positive tuberculosis in the elderly.Methods A total of 302 elderly patients meeting the inclusion and exclusion criteria were selected from 14 tuberculosis-designated medical institutions in Beijing.The patients received the initial treatment of smear-positive tuberculosis from January 2014 to August 2016 in the combined prospective and retrospective study.All patients were divided into observation group(n=63)receiving treatment with 6L2 HELfx regimen from August 1,2015 to August 31,2016,and control group (n =239) receiving treatment with 6L2HELfx regimen from January 1,2014 to January 31,2015.The nation-unified standard chemotherapy regimen 2RHZE/4RH was used in tuberculosis medical service institutions for all patients.The differences between the two groups were analyzed and compared in the completion of treatment,negative conversion of sputum culture or smear,adverse drug reactions and treatment outcome.Results The completion rate of long-course therapy was significantly higher in the observation group than in control group [90.5% (57/63) vs.79.5% (190/239),x2 =4.034,P =0.045].The rate of negative conversion of sputum culture or smear at the end of the 2nd month was higher in the observation group than in control group,but had no significant difference[87.0% (47/54)vs.81.6%(155/190),x2 =0.879,P=0.349].The incidence of adverse reactions was much lower in observation group than in control group[46.0% (29/63) vs.65.3% (156/239),x2 =7.777,P =0.005].The success rate of treatment(cure or completion of long-course therapy)was higher in observation group than in control group [90.5% (57/63) vs.77.4% (185/239),x2 =5.350,P =0.021].ConclusioNS As compared with the standard chemotherapy regimen,the L and Lfxcontaining treatment regimen has better effects,higher success rate of treatment and less adverse reactions in elderly patients with the initial treatment of smear-positive tuberculosis.
ABSTRACT
Metabolism and deposition of exogenous gene and protein from transgenic glyphosate herbicide-tolerant soybean meal in SD rats were studied in the experiment. The transgenic soybean GTS40-3-2 meal and its non-transgenic counterpart (parent A5403) were fed to the generation and the second generation Sprague-Dawley (SD) rats (Rattus norvegicus). The study added the genetically modified (GM) soybean meal and its non-transgenic control soybean meal (parent A5403) in a ratio of 20% respectively to the feeds. By using qualitative, quantitative PCR and ELISA methods to detect transgenic soybean residues of metabolism ingredients in rats, the safety and influence of GM soybean were evaluated. The results showed that the intestinal fecal and cecum contents of rats were detected with residues of GM ingredients, intestinal flora and organs were not found related genes and protein. These results indicated that transgenic glyphosate herbicide-tolerant soybean GTS40-3-2 meal was as safe as its non-GM soybean meal in long-term feeding study.
Subject(s)
Animals , Rats , Animal Feed , Animal Nutritional Physiological Phenomena , Digestion , Glycine , Herbicide Resistance , Herbicides , Plants, Genetically Modified , Proteolysis , Rats, Sprague-Dawley , Soybean Proteins , Glycine maxABSTRACT
To assess the presence of genetically modified (GM) maize and soybean in a range of commercialized feed in Shanxi province of China in 2015, improved hexadecyltrimethy ammonium bromide (CTAB) method was used to extract DNA. The screening of packed feeds was carried out by qualitative PCR. Then positive feeds were unpacked and detected by the CaMV 35S promoter, NOS terminator, zSSIIb, Lectin and CryIA (b) genes. The identified maize and soybean events were confirmed by event-specific MON810 and GTS40-3-2. Results showed that 83.3% of the feeds was tested positive for GMOs, in which positive rates of maize, soybean, pig and layer feeds were 6.67%, 100%, 93.3% and 73.3%, respectively. The results of real-time PCR were consistent with qualitative PCR. These results indicated that commercialized GM feed had a wide positive product scope in Shanxi province of China. Further studies are necessary to study effects of feeding livestock and poultry with feed containing GM ingredients on animals and their products.
ABSTRACT
Bacterial cell division is strictly regulated in the formation of equal daughter cells. This process is governed by a series of spatial and temporal regulators, and several new factors of interest to the field have recently been identified. Here, we report the requirement of gluconate 5-dehydrogenase (Ga5DH) in cell division of the zoonotic pathogen Streptococcus suis. Ga5DH catalyzes the reversible reduction of 5-ketogluconate to D-gluconate and was localized to the site of cell division. The deletion of Ga5DH in S. suis resulted in a plump morphology with aberrant septa joining the progeny. A significant increase was also observed in cell length. These defects were determined to be the consequence of Ga5DH deprivation in S. suis causing FtsZ delocalization. In addition, the interaction of FtsZ with Ga5DH in vitro was confirmed by protein interaction assays. These results indicate that Ga5DH may function to prevent the formation of ectopic Z rings during S. suis cell division.
Subject(s)
Bacterial Proteins , Chemistry , Genetics , Metabolism , Cell Division , Cell Shape , Cytoskeletal Proteins , Chemistry , Genetics , Metabolism , Mutation , Oxidoreductases , Genetics , Metabolism , Protein Binding , Streptococcus suisABSTRACT
Objective To explore the clinical value of high frequency ultrasound combined with serum tumor specific growth factor in diagnosis of thyroid cancer.Methods 155 patients with thyroid tumor received preoperative high frequency ultrasound and the detection of TSGF content,the histopathologic examination was given after operation.The clinical value of high frequency ultrasound and TSGF detection in diagnosis of thyroid cancer was analyzed.Results The sensitivity of high frequency ultrasound in diagnosis of thyroid carcinoma was 82.54%,the specificity was 81.52%.The sensitivity of TSGF in diagnosis of thyroid cancer was 79.37%,the specificity was 78.26%.The sensitivity of high frequency ultrasound combined with TSGF in diagnosis of thyroid cancer was 92.06%,the specificity was 93.48%.And the coincidence rate of combined detection was significantly higher than the two methods used alone,the difference was statistically significant (P < 0.05).Conclusion High frequency ultrasound combined with TSGF detection can make up the shortage of the two methods,which has important value in improving the diagnosis of thyroid carcinoma.
ABSTRACT
Objective Sperm screening is an essential step in IVF procedures. The swim-up method, an assay on sperm motility, is used clinically to select the ideal sperm for subsequent manipulation. However, additional parameters, including acrosome reaction capability, chemotaxis, and thermotaxis are also important indicators of mammalian sperm health. To monitor both sperm motility and chemotaxis simultaneously during sperm screening, we designed and constructed a microdevice comprising a straight channel connected with a bi-branch channel that mimics the mammalian female reproductive tract. Methods The width and length of the straight channel were optimized to select the motile sperm. Cumulus cells were selectively cultured in the bi-branch channel to generate a chemoattractant-forming chemical gradient. Sperm chemotaxis was represented by the ratio of the sperm swimming towards different branches. Results The percentage of motile sperm was improved from ( 58. 5 ± 3. 8 ) % to ( 82. 6±2.9)% by a straight channel 7 mm in length and 1 mm in width. About 10% of sperm were found chemotactically responsive in our experiment, which is consistent with previous studies. Conclusion The combined evaluation of both sperm motility and chemotaxis was achieved for the first time, and the motile and chemotactically responsive sperm can be easily enriched on a lab-on-a-chip device to improve IVF outcome.
ABSTRACT
Objectiye To optimize the depth of the microchannel and the time point for sperm collection,and improve the efficiency of sperm screening on a microfluidic device. Methods Microchannels with four different depths of 25, 50, 100 and 200 μm were tested. Mice sperm were added to the inlet of the microchannel. The relative quantity and motility of sperm in the outlet were recorded at different collection times, i.e. ,5, 15, 30 and 60 min. Statistical method one-way ANOVA and appropriate post-hoc testing were applied to analyze differences between different groups, and further to select the best-fit depth of the microchannel and the time point for collection. Results In microchannels with depths of 25, 50, 100 and 200 μm, the sperm motilities measured in each outlet were (85.4 ± 2.3)%, (85.8 ± 5.8)%,( 87. 2 ± 2. 8 ) %, (76. 5 ± 2. 8 ) % respectively with statistical significance ( F = 5.8, P < 0. 05 ). No obvious differences were found among 25-100 μm channels, however the motility dramatically decreased in the 200 μm group. The relative sperm quantities were (5.2 ±2.0)%, (7.2 ±2.5)%,(12.3 ±2.0)%,(7. 7 ± 1.1 ) % respectively with statistical significance ( F = 6. 9, P < 0. 05), which increased with channel depth from 25 to 100 μm,while it decreased in the 200 μm channel Taking 2 indexes into account, 100 μmwas the most fit channel depth for sperm motility screening. The sperm motility in the outlet gradually decreased with time. At the time points of 5, 15, 30 and 60 min after adding sperm, the sperm motilities were (99. 6 ±0. 7)%, (87.2 ±2. 8)%, (79. 3 ±2. 2)% and (62. 6 ±8.0)% respectively with statistical significance ( F = 37. 3, P < 0. 01 ). Yet the relative quantities of sperm in the outlet increased almost three times in this process. At the time points mentioned above, the relative quantities of sperm were (5.8±1.1)%, (10.6 ± 0.9)%, (12.1 ± 1.7)%, (17.9 ± 3.4)% respectively with statistical significance ( F = 17.8, P < 0. 01 ). Thus 15-30 min was the ideal screening time. Conclusion An effective microdevice for sperm screening with optimized depth and collection time period is developed,which may contribute significantly for the screening of healthy sperm on microfluidic chips.