Elevated lactate dehydrogenase predicts poor prognosis of acute ischemic stroke.

BACKGROUND: Lactate dehydrogenase (LDH) is associated with the prognosis of many diseases, but the relationship between LDH and the poor prognosis (recurrence and death) of acute ischemic stroke (AIS) has not been fully clarified. This study aimed to investigate the association between admission LDH level and poor prognosis in patients with AIS. METHODS: This retrospective study enrolled AIS patients treated in Taizhou Hospital of Zhejiang Province from July 2019 to December 2019. Poor prognosis included AIS recurrence and all-cause death at 3, 6, and 18 months. The correction between LDH and poor prognosis or all-cause death was assessed. Lasso Cox expression and multivariate Cox expression analyses were used to evaluate the association of LDH with the risk of poor prognosis and all-cause death, respectively. A nomogram was constructed to evaluate the predictive Values of LDH for the poor prognosis and all-cause death of AIS. RESULTS: 732 patients were included in the study. Multivariate analysis shows that admission LDH levels were significantly correlated with poor prognosis [odds ratio (OR),1.003; 95% confidence interval (95% CI), 1.001-1.005; P = 0.001] and all-cause death (OR, 1.005; 95% CI, 1.000-1.009; P = 0.031). The correlation analysis showed that admission LDH level was positively correlated with National Institutes of Health Stroke Scale (NIHSS) score and modified Rankin Scale (mRS) score. Time-dependent receiver operating characteristic (td-ROC) curves analysis showed that the AUC values of admission LDH level for predicting prognosis of AIS patients in 3-month, 6-month, 12-month and 18-month were 0.706 (95% CI, 0.604-0.810), 0.653 (95% CI, 0.583-0.723), 0.616 (95% CI, 0.556-60676) and 0.610 (95% CI, 0.552-0.680), respectively. And td-ROC also showed that the AUC values of admission LDH level for predicting all-cause death of AIS patients in 3-month, 6-month,12-month and 18-month were 0.861 (95% CI, 0.764-0.958), 0.824 (95% CI, 0.753-0.890), 0.726 (95% CI, 0.633-0.819) and 0.715 (95% CI, 0.622-0.807), respectively. The nomograms were constructed to create the predictive models of the poor prognosis and all-cause death of AIS. CONCLUSION: Higher LDH levels are independently associated with poor prognosis and all-cause death of AIS.

Effects of Lecithin Supplementation in Feed of Different fat Levels on Serum Indexes and Liver Health of Laying Hens.

The aim of this experiment was to investigate the effect of soy lecithin on serum-related indicators and liver health in laying hens under the influence of high-fat diets. 180 peak laying hens at 40 weeks of age were randomly assigned to one of the four diets using a 2 × 2 factorial and fed for 5 weeks. The results showed that compared to the low-fat group, the high-fat group had lower egg production (p < 0.05) and higher average daily feed intake and feed-to-egg ratio (p < 0.05). At the 21st day, the serum levels of triglyceride (TC) and superoxide dismutase (SOD) were higher (p < 0.05), high-density lipoproteins cholesterol (HDL-C) levels were lower (p < 0.01), catalase (CAT) activity was lower (p < 0.05), TC and malondialdehyde (MDA) levels in liver were higher (p < 0.01) and SOD activity in liver was lower (p < 0.05) in layers supplemented with soy lecithin. CAT activity in serum was increased (p < 0.01) and total antioxidant capacity (T-AOC) activity in the liver was decreased (p < 0.05) after increasing the dietary fat concentration. The addition of soy lecithin and the increase in dietary fat concentration had a highly significant interaction on serum CAT activity and liver TC content in layers (p < 0.01). At the 35th day, the serum alanine aminotransferase (ALT) activity was higher (p < 0.01), serum glutathione peroxidase (GSH-Px) and CAT activity were higher (p < 0.05), and serum triglyceride (TG) content and total T-AOC capacity activity were lower (p < 0.05) in layers supplemented with soy lecithin. Increasing dietary fat concentration decreased alanine aminotransferase (ALT), aspartate aminotransferase (AST) and GSH-Px activity in serum (p < 0.05). However, it increased TG and MDA content in liver (p < 0.05), and highly decreased SOD content in liver (p < 0.01) in layers. The addition of soy lecithin and increasing dietary fat concentration had a highly significant reciprocal effect on serum ALT viability and CAT viability (p < 0.01) and liver TG and MDA content and SOD viability (p < 0.05) in layers. In conclusion, feeding high-fat diets will adversely affect the laying performance of laying hens, while long-term addition of lecithin can improve the blood lipids and liver lipids of laying hens, enhance the antioxidant capacity of the liver, and maintain liver health.

ERK/MAPK signalling pathway and tumorigenesis.

Mitogen-activated protein kinase (MAPK) cascades are key signalling pathways that regulate a wide variety of cellular processes, including proliferation, differentiation, apoptosis and stress responses. The MAPK pathway includes three main kinases, MAPK kinase kinase, MAPK kinase and MAPK, which activate and phosphorylate downstream proteins. The extracellular signal-regulated kinases ERK1 and ERK2 are evolutionarily conserved, ubiquitous serine-threonine kinases that regulate cellular signalling under both normal and pathological conditions. ERK expression is critical for development and their hyperactivation plays a major role in cancer development and progression. The Ras/Raf/MAPK (MEK)/ERK pathway is the most important signalling cascade among all MAPK signal transduction pathways, and plays a crucial role in the survival and development of tumour cells. The present review discusses recent studies on Ras and ERK pathway members. With respect to processes downstream of ERK activation, the role of ERK in tumour proliferation, invasion and metastasis is highlighted, and the role of the ERK/MAPK signalling pathway in tumour extracellular matrix degradation and tumour angiogenesis is emphasised.

Resveratrol-loaded folic acid-grafted dextran stearate submicron particles exhibits enhanced antitumor efficacy in non-small cell lung cancers.

In this study, we have aimed to prepare folic acid-conjugated dextran stearate (DF) polymeric micelles to target resveratrol in lung cancers. The polymeric micelle was nanosized and exhibited a controlled drug release pattern. The resveratrol (RSV)-loaded dextran stearate (RSV-DF) micelles exhibited an enhanced cellular uptake in A549 cells due to the folic acid-based receptor interactions. We have demonstrated that RSV-DF polymeric micelles retain the cytotoxic and metabolic effects of RSV on A549 cancer cells with potencies similar to that of the free compound. Furthermore, RSV-DF showed an enhanced cellular apoptosis of cancer cells compared to that of free RSV. We have found that apoptosis induced by RSV-DF was associated with the higher expression of p53, caspase-3, and BAX than the free RSV. The higher level of BAX and caspase-3 further indicates the involvement of mitochondria-dependent apoptosis in the anticancer efficacy of formulations. Based on these results, it can be concluded that natural compound like RSV could be an interesting prospect to treat lung cancers and the fact that folic acid-conjugated dextran stearate could be a potential carrier to deliver the drug in the cancer cells.

The prevalence and correlates of syphilis and HIV among homosexual and bisexual men in Shijiazhuang, China.

Bisexual men (men who have sex with men and women) are potential epidemiological bridges responsible for the spread of HIV and other sexually transmitted infections from men who have sex with men only to the heterosexual population. We aimed to estimate the prevalence of syphilis and HIV and the factors associated with syphilis infection among men who have sex with men and women and men who have sex with men only from Shijiazhuang, China. In 2011-2013, a cross-sectional cohort of 427 men who have sex with men was recruited by a snowball sampling method and tested for syphilis and HIV. Chi square and logistic regression were performed to identify syphilis risk factors. Among the 427 men who have sex with men, 71 (16.6%) cases were syphilis-positive and 16 cases (3.7%) were HIV-positive. The proportions of men who have sex with men and women and men who have sex with men only in the total sample were 31.4% and 68.6%, respectively. Men who have sex with men and women exhibited double the syphilis prevalence of men who have sex with men only and were more likely to practice insertive anal sex. Higher education level, being married, having more male partners, and both receptive and insertive anal sex roles were associated with syphilis among men who have sex with men and women. Residing in suburban areas, being married, being HIV positive, and an absence of desire to change sexual orientation were associated with syphilis among men who have sex with men only. Therefore, men who have sex with men and women represent an important sub-group in the syphilis epidemic and further interventions should be developed to reduce risk among different sub-sets of men who have sex with men.

A novel small deletion mutation in RUNX2 gene in one Chinese family with cleidocranial dysplasia.

Cleidocranial dysplasia (CCD) is a skeletal dysplasia with autosomal-dominant inheritance. The runt related transcription factor 2 (RUNX2) gene is the only gene in which mutations are known to cause CCD. We report identification of a novel small deletions mutation in the RUNX2 gene in a Chinese family with CCD. A 29-year-old female was diagnosed as proband of CCD based on the clinical findings, which show delayed closure of the fontanels, hypoplastic or aplastic clavicles and dental anomalies. Similar dental and skeletal symptoms were also observed in the other three affected individuals. We prepared genomic DNA from all four affected individuals, unaffected individual from her family members, as well as 100 unrelated healthy controls. PCR was conducted using the above genomic DNA as template and the RUNX2 gene-specific primers. The PCR product was subjected to direct sequencing and the sequence was compared to that of RUNX2 gene within the NCBI database. We detected a small deletion CCTA from nucleotide 635 to nucleotide 638 in exon 3 of RUNX2 gene of the proband. This will lead to the introduction of a translational stop codon at codon 220, resulting in a truncated RUNX2 protein, and therefore within the runt domain of the RUNX2 protein. We detected the same mutation in the the other three affected individuals, and did not detect any mutation in the unaffected family members or the 100 unrelated healthy controls, demonstrating that this is a novel missense mutation in RUNX2 gene and therefore, contributes to the molecular diagnosis of CCD.

Smallest bitter taste receptor (T2Rs) gene repertoire in carnivores.

Bitter taste reception is presumably associated with dietary selection, preventing animals from ingesting potentially harmful compounds. Accordingly, carnivores, who encounter these toxic substances less often, should have fewer genes associated with bitter taste reception compared with herbivores and omnivores. To investigate the genetic basis of bitter taste reception, we confirmed bitter taste receptor (T2R) genes previously found in the genome sequences of two herbivores (cow and horse), two omnivores (mouse and rat) and one carnivore (dog). We also identified, for the first time, the T2R repertoire from the genome of other four carnivore species (ferret, giant panda, polar bear and cat) and detected 17-20 bitter receptor genes from the five carnivore genomes, including 12-16 intact genes, 0-1 partial but putatively functional genes, and 3-8 pseudogenes. Both the intact T2R genes and the total T2R gene number among carnivores were the smallest among the tested species, supporting earlier speculations that carnivores have fewer T2R genes, herbivores an intermediate number, and omnivores the largest T2R gene repertoire. To further explain the genetic basis for this disparity, we constructed a phylogenetic tree, which showed most of the T2R genes from the five carnivores were one-to-one orthologs across the tree, suggesting that carnivore T2Rs were conserved among mammals. Similarly, the small carnivore T2R family size was likely due to rare duplication events. Collectively, these results strengthen arguments for the connection between T2R gene family size, diet and habit.

Involvement of cytoskeleton-associated proteins in the commitment of C3H10T1/2 pluripotent stem cells to adipocyte lineage induced by BMP2/4.

The developmental pathway that gives rise to mature adipocytes involves two distinct stages: commitment and terminal differentiation. Although the important proteins/factors contributing to terminal adipocyte differentiation have been well defined, the proteins/factors in the commitment of mesenchymal stem cells to the adipocyte lineage cells have not. In this study, we applied proteomics analysis profiling to characterize differences between uncommitted C3H10T1/2 pluripotent stem cells and those that have been committed to the adipocyte lineage by BMP4 or BMP2 with the goal to identify such proteins/factors and to understand the molecular mechanisms that govern the earliest stages of adipocyte lineage commitment. Eight proteins were found to be up-regulated by BMP2, and 27 proteins were up-regulated by BMP4, whereas five unique proteins were up-regulated at least 10-fold by both BMP2/4, including three cytoskeleton-associated proteins (i.e. lysyl oxidase (LOX), translationally controlled tumor protein 1 (TPT1), and αB-crystallin). Western blotting further confirmed the induction of the expression of these cytoskeleton-associated proteins in the committed C3H10T1/2 induced by BMP2/4. Importantly, knockdown of LOX expression totally prevented the commitment, whereas knockdown of TPT1 and αB-crystallin expression partially inhibited the commitment. Several published reports suggest that cell shape can influence the differentiation of partially committed precursors of adipocytes, osteoblasts, and chondrocytes. We observed a dramatic change of cell shape during the commitment process, and we showed that knockdown of these cytoskeleton-associated proteins prevented the cell shape change and restored F-actin organization into stress fibers and inhibited the commitment to the adipocyte lineage. Our studies indicate that these differentially expressed cytoskeleton-associate proteins might determine the fate of mesenchymal stem cells to commit to the adipocyte lineage through cell shape regulation.

[Construction of murine CXCR3 gene transfected cell line, identifiction and study of its biological function].

AIM: To construct recombinant murine CXCR3 gene retroviral vector and obtain L929-mCXCR3 gene transfected cell line for stably expressing murine CXCR3. We further study on L929-mCXCR3 migration effect resulted from interaction by CXCR3 and its ligand IP-10. METHODS: One female BALB/c mouse (7 weeks) was injected with 0.5 mg Con A intravenously (i.v.) via a tail vein. Twelve hours later the mouse was sacrificed and the spleen was removed.The spleen was pressed through a 150 microm stainless steel mesh. The isolated splenocytes were cultured in RPMI1640 supplemented with 50 U/mL human IL-2 for 3 days.Total RNA was extracted with TRIzol. Murine CXCR3 gene of full length was amplified by RT-PCR, then, it was inserted into retrovirus vector pEGZ-term. The recombinant vector together with its helper virus vector were co-transfected into package cell 293T with Lipofectamine(TM); 2000.The supernatant of 293T was collected for infecting L929 cells (repeated three times), and cell clones stably expressing murine CXCR3 molecule were screened by zeocin(500 mg/L). We used FCM and RT-PCR to verify expression of CXCR3 from protein level and gene level, respectively. Studied migration ability of L929-mCXCR3 interacted with its ligand IP-10 by transwell system. RESULTS: We have constructed recombinant murine CXCR3 gene retroviral vector and obtained L929-mCXCR3 gene transfected cell line which can stably expressing murine CXCR3 molecule. Positive expression rate of membrane is 97.0%, and it can directly migrate induced by IP-10, the chemotatic index is 4.356%. CONCLUSION: Construction of L929-mCXCR3 cell line has laid a good foundation on research of biologic characteristics of CXCR3 signal path , establishment of tumor metastasis model and preparation of anti-murineCXCR3 monoclonal antibody.