Lactotransferrin promotes intervertebral disc degeneration by regulating Fas and inhibiting human nucleus pulposus cell apoptosis.

BACKGROUND: In recent years, intervertebral disc (IVD) degeneration (IDD) has increased in age. There is still a lack of effective treatment in clinics, which cannot improve the condition of IDD at the level of etiology. OBJECTIVE: To explore IDD pathogenesis at the cellular and gene levels and investigate lactotransferrin (LTF) expression in IDD patients and its possible mechanism. METHODS: We downloaded the IDD data set from the Gene Expression Omnibus (GEO) database, screened the differentially expressed genes (DEGs) and hub genes and performed Kyoto Encyclopedia of Genes and Genomes (KEGG) analysis to construct a protein-protein interaction (PPI) network. Subsequently, we verified LTF's regulatory mechanism through cell experiments. IL-1ß was used to intervene in nucleus pulposus cells (NPCs) to construct the IDD cell model, and LTF and Fas expression was detected by qRT-PCR. LTF inhibitor, Fas inhibitor, LTF mimic, and Fas mimic were used to intervene in each group. Western blotting was used to detect Fas, Caspase-3, Bax, and Bcl-2 expression. RESULTS: A total of 131 DEGs and 10 hub genes were screened. LTF mRNA in the IDD model was significantly higher than that in the control group, while Fas' mRNA was significantly lower. When LTF was upregulated or downregulated in NPCs, apoptosis marker expression showed the opposite trend. The rescue test showed that LTF and Fas' overexpression greatly enhanced NPC apoptosis. CONCLUSION: LTF promotes IDD progression by regulating Fas in NPCs, and it may be an effective gene therapy target.

A robust test for X-chromosome genetic association accounting for X-chromosome inactivation and imprinting.

The X chromosome is known to play an important role in many sex-specific diseases. However, only a few single-nucleotide polymorphisms on the X chromosome have been found to be associated with diseases. Compared to the autosomes, conducting association tests on the X chromosome is more intractable due to the difference in the number of X chromosomes between females and males. On the other hand, X-chromosome inactivation takes place in female mammals, which is a phenomenon in which the expression of one copy of two X chromosomes in females is silenced in order to achieve the same gene expression level as that in males. In addition, imprinting effects may be related to certain diseases. Currently, there are some existing approaches taking X-chromosome inactivation into account when testing for associations on the X chromosome. However, none of them allows for imprinting effects. Therefore, in this paper, we propose a robust test, ZXCII, which accounts for both X-chromosome inactivation and imprinting effects without requiring specifying the genetic models in advance. Simulation studies are conducted in order to investigate the validity and performance of ZXCII under various scenarios of different parameter values. The simulation results show that ZXCII controls the type I error rate well when there is no association. Furthermore, with regards to power, ZXCII is robust in all of the situations considered and generally outperforms most of the existing methods in the presence of imprinting effects, especially under complete imprinting effects.

A robust and powerful test for case-control genetic association study on X chromosome.

Hundreds of genome-wide association studies were conducted to map the disease genes on autosomes in human beings. It is known that many complex diseases are sex-determined and X chromosome is expected to play an important role. However, only a few single-nucleotide polymorphisms on X chromosome were found to be significantly associated with the diseases under study. On the other hand, to balance the genetic effect between two sexes, X chromosome inactivation occurs in most of X-linked genes by silencing one copy of two X chromosomes in females and dosage compensation is achieved. A few association studies on X chromosome incorporated the information on dosage compensation. However, some of them require the assumption of Hardy-Weinberg equilibrium and some need to specify the underlying genetic model. Therefore, in this article, we propose a novel method for association by taking account of different dosage compensation patterns. The proposed test is a robust approach because it requires neither specifying the underlying genetic models nor the assumption of Hardy-Weinberg equilibrium. Further, the proposed method allows for different deviations from Hardy-Weinberg equilibrium between cases and controls. Simulation results demonstrate that our proposed method generally outperforms the existing methods in terms of controlling the size and the test power. Finally, we apply the proposed test to the meta-analysis of the Graves' disease data for its practical use.

A statistical measure for the skewness of X chromosome inactivation based on family trios.

BACKGROUND: X chromosome inactivation (XCI) is an important gene regulation mechanism in females to equalize the expression levels of X chromosome between two sexes. Generally, one of two X chromosomes in females is randomly chosen to be inactivated. Nonrandom XCI (XCI skewing) is also observed in females, which has been reported to play an important role in many X-linked diseases. However, there is no statistical measure available for the degree of the XCI skewing based on family data in population genetics. RESULTS: In this article, we propose a statistical approach to measure the degree of the XCI skewing based on family trios, which is represented by a ratio of two genotypic relative risks in females. The point estimate of the ratio is obtained from the maximum likelihood estimates of two genotypic relative risks. When parental genotypes are missing in some family trios, the expectation-conditional-maximization algorithm is adopted to obtain the corresponding maximum likelihood estimates. Further, the confidence interval of the ratio is derived based on the likelihood ratio test. Simulation results show that the likelihood-based confidence interval has an accurate coverage probability under the situations considered. Also, we apply our proposed method to the rheumatoid arthritis data from USA for its practical use, and find out that a locus, rs2238907, may undergo the XCI skewing against the at-risk allele. But this needs to be further confirmed by molecular genetics. CONCLUSIONS: The proposed statistical measure for the skewness of XCI is applicable to complete family trio data or family trio data with some paternal genotypes missing. The likelihood-based confidence interval has an accurate coverage probability under the situations considered. Therefore, our proposed statistical measure is generally recommended in practice for discovering the potential loci which undergo the XCI skewing.

Effects of intravenous lidocaine, dexmedetomidine and their combination on postoperative pain and bowel function recovery after abdominal hysterectomy.

BACKGROUND: Intravenous (IV) lidocaine and dexmedetomidine have been shown to decrease postoperative pain, reduce analgesic consumption and facilitate return of bowel function. We investigated whether lidocaine combined with dexmedetomidine infusion was superior in controlling pain and recovery of bowel function. METHODS: A total of 240 women undergoing elective abdominal hysterectomy were randomly assigned into four groups: group CON received normal saline infusion, group LIDO received lidocaine infusion (1.5 mg/kg loading, 1.5 mg/kg/h infusion), group DEX received dexmedetomidine infusion (0.5 µg/kg loading, 0.4 µg/kg/h infusion) and group LIDO+DEX received lidocaine (1.5 mg/kg loading, 1.5 mg/kg/h infusion) and dexmedetomidine infusions (0.5 µg/kg loading, 0.4 µg/kg/h infusion). The primary outcome was visual analog pain scale (VAS) scores at 1, 4, 8, 12, 24, and 48 hours after surgery. The secondary outcomes included time to first bowel sounds and flatus, postoperative fentanyl requirement and perioperative propofol and remifentanil consumption. RESULTS: The VAS scores were significantly lower in groups LIDO and DEX at 4, 8, and 12 hours compared to group CON after surgery (P<0.01). The VAS scores were also significantly lower in group LIDO+DEX at 1, 4, 8, 12, and 24 hours compared to other three groups after surgery (P<0.01). Time to first bowel sounds and flatus was significantly shorter in groups LIDO and LIDO+DEX than groups CON and DEX (P<0.01). Postoperative fentanyl requirement was significantly lower in group LIDO at 1 and 4 hours and in group DEX at 1, 4, 8 hours compared to group CON after surgery (P<0.01). Postoperative fentanyl requirement was also significantly lower in group LIDO+DEX at 1, 4, 8, 12, 24 and 48 hours compared to other three groups after surgery (P<0.01). Propofol and remifentanil consumption was significantly lower in groups LIDO, DEX and LIDO+DEX compared to group CON (P<0.01). CONCLUSIONS: Lidocaine combined with dexmedetomidine infusion significantly improved postoperative pain and enhanced recovery of bowel function undergoing abdominal hysterectomy.

[Progress on propionibacterium acnes and degenerative intervertebral disc].

The mechanism of degenerative intervertebral disc is very complex, which may be associated with multiple factors such as the mechanical stress force injury of intervertebral disc, nutritional deficiency, inflammatory stimulation, etc. Recently, many studies detected propionibacterium acnes(P. acnes) in degenerative intervertebral disc and supposed P. acnes was associated with degenerative intervertebral disc. Here, the papers related to P. acnes and degenerative intervertebral disc were reviewed. Further, we deduced the approach of P. acnes enterring into the intervertebral disc as well as the mechanism of P. acnes aggravating the disc degeneration. These may provide suggestions for treating degenerative intervertebral disc.

Protective Effects of Peroxisome Proliferator-Activated Receptor-α Agonist, Wy14643, on Hypoxia/Reoxygenation Injury in Primary Rat Hepatocytes.

This study investigates the effects and possible mechanism of an agonist of PPARα, Wy14643, on primary hepatocytes subjected to H/R injury in rats. H/R induced a significant increase ALT, AST, MDA in the culture medium and ROS in the hepatocytes. These effects were reversed by pretreatment with Wy14643 in the dose-dependent manner. The activity of SOD and the level of GSH in the hepatocytes were decreased after H/R, which were increased by Wy14643 pretreatment. Moreover, the mRNA expressions of PPARα significantly increased in H/R+Wy14643 groups when compared with that in H/R group. A PPARα agonist, Wy14643, exerts significant protective effect against H/R injury in primary hepatocytes via PPARα activation and attenuating oxidative stress.

[Research progress of atmospheric iodine speciation in aerosol].

Iodine in the atmosphere directly influences on many kinds of photochemical reactions in troposphere, and indirectly poses impact on global climate change. It is thus that the research on the mechanism of atmospheric chemistry of iodine has attracted more and more attention. Iodine compounds in the aerosol are the final product of atmospheric chemistry reactions of iodine, which can be inferred and known via investigating the iodine speciation in aerosol. IO3- is often considered to be the dominant form of iodine precipitation. But field measurement in recent years showed that soluble organic iodine or I- were mostly the dominant forms in atmospheric aerosol. This implies that atmospheric chemistry mechanism of iodine still remain to perfect further. Here we focus on the research progress of atmospheric chemistry of iodine and its speciation in aerosols up to date.

Effects of Wy14643 on hepatic ischemia reperfusion injury in rats.

AIM: To investigate the effects and possible mechanisms of Wy14643 on hepatic ischemia-reperfusion (I/R) injury in rats. METHODS: Thirty male Sprague-Dawley rats weighing 220-280 g were randomly divided into five experimental groups: sham group (G1, n=6): a sham operation was performed (except for liver I/R); I/R-untreated group (G2, n=6): rats underwent liver ischemia for 90 min followed by reperfusion for 4 h; and I/R+Wy14643 groups (G3, G4, G5; n=6): after the same surgical procedure as in group 2, animals were pretreated with Wy14643 at the dose of 1, 5 and 10 mg/kg 1 h before ischemia, respectively. Hepatic ischemia-reperfusion (I/R) was induced by clamping blood supply to the left lateral and median lobes of the liver for 90 min, and atraumatic clamp was removed for 4 h reperfusion. Blood samples and liver tissues were obtained at the end of reperfusion to assess serum and hepatic tissue homogenate aminotransferase (ALT), aspartate aminotransferase (AST), myeloperoxidase (MPO), serum interleukin-1beta (IL-1beta) and tumor necrosis factor alpha (TNF-alpha), as well as activity of superoxide dismutase (SOD) and content of malondialdehyde (MDA) in the hepatic tissue homogenate. RESULTS: Hepatic I/R induced a significant increase in the serum levels of ALT, AST, TNF-alpha, IL-1beta and MPO, as well as the levels of ALT, AST and MDA in the liver tissue homogenate, which were reduced by pretreatment with Wy14643 at the dose of 1, 5 and 10 mg/kg, respectively. The activity of SOD in the liver tissue homogenate was decreased after hepatic I/R, which was enhanced by Wy14643 pretreatment. In addition, serum and liver tissue homogenate ALT and AST in the Wy14643 10 mg/kg group were lower than in the Wy14643 1 mg/kg and 5 mg/kg groups, respectively. CONCLUSION: Wy14643 pretreatment exerts significant protection against hepatic I/R injury in rats. The protective effects are possibly associated with enhancement of anti-oxidant and inhibition inflammation response.