Causal association between lipoproteins and risk of coronary artery disease-a systematic review and meta-analysis of Mendelian randomization studies.

OBJECTIVE: To systematically evaluate the causal effect of lipoproteins to the risk of coronary artery disease (CAD) by systematic review and meta-analysis of the associated Mendelian randomization (MR) studies. METHODS: This systematic review was registered in PROSPERO (ID CRD42023465430). Searches from the databases (e.g., PubMed, Embase, Cochrane, Web of Science) and non-database sources to collect MR studies. The search time frame was from the database inception to August 2023. After data extraction, quality evaluation was performed, and the meta-analysis with bias evaluation was carried out with RevMan software. RESULTS: A total of 5,828,409 participants from 21 records were included. Quality and bias assessment was performed by evaluating the internal three assumptions of MR studies. Meta-analysis for the causal association between non-HDL lipoproteins and CAD showed a significantly positive association between LDL and CAD (OR 1.37, 95% CI 1.26-1.49; P < 0.001, I2 = 95%), apoB and CAD (OR 1.38, 95% CI 1.11-1.71; P = 0.003, I2 = 98%), and Lp(a) and CAD (OR 1.21, 95% CI 1.12-1.31; P < 0.001, I2 = 99%). Interestingly, although there was no statistical significance in the association between VLDL/apoA1 and CAD (both P > 0.05), the pooled non-HDL lipoproteins showed a significantly positive association with CAD (OR 1.28, 95% CI 1.22-1.34; P < 0.001, I2 = 99%). For the HDL lipoproteins, the pooled OR showed a significantly negative association with CAD (OR 0.84, 95% CI 0.72-0.98; P = 0.002, I2 = 72%). However, the protective effect of HDL on CAD diminished when analyzed together with apoA1 and/or apoB (both P > 0.05). The funnel plot did not show serious publication bias, and sensitivity analysis performed relatively well robustness of the causal association of LDL, apoB, Lp(a), and total cholesterol with CAD. CONCLUSION: The present meta-analysis suggests an overall effect of causal association between lipoproteins and CAD. Most of the non-HDL lipoproteins (LDL, apoB, Lp(a)) promote CAD, while the protective effect of HDL in CAD still needs to be verified in the future.

Quantitation of nuclear factor kappa B activation in pancreatic acinar cells during rat acute pancreatitis by flow cytometry.

This study aimed to develop a specific and sensitive method for the rapid detection of NF-κB activity in pancreatic tissue. Male Wistar rats were randomly divided into two groups: (1) 16 rats in the acute pancreatitis (AP) group received retrograde injection of 5% sodium taurocholate (STC) into the biliopancreatic duct, and (2) 16 rats in the Control group received saline. NF-κB activation in rat pancreatic acinar cells was assessed by flow cytometry (FCM). We found that the NF-κB activity in the AP group significantly increased at 1.5 h (29.80%±7.83), had a peak at 3 h (65.17%±13.22), and then decreased gradually to 12 h time point, close to the level after 1.5 h stimulation of STC. The NF-κB activity of the Control group did not significantly vary at different time points (P>0.05). FCM is a specific and sensitive assay for the rapid detection of NF-κB activity in pancreatic tissue.

Recognition for avian influenza virus proteins based on support vector machine and linear discriminant analysis.

Total 200 properties related to structural characteristics were employed to represent structures of 400 HA coded proteins of influenza virus as training samples. Some recognition models for HA proteins of avian influenza virus (AIV) were developed using support vector machine (SVM) and linear discriminant analysis (LDA). The results obtained from LDA are as follows: the identification accuracy (R ia) for training samples is 99.8% and R ia by leave one out cross validation is 99.5%. Both R ia of 99.8% for training samples and R ia of 99.3% by leave one out cross validation are obtained using SVM model, respectively. External 200 HA proteins of influenza virus were used to validate the external predictive power of the resulting model. The external R ia for them is 95.5% by LDA and 96.5% by SVM, respectively, which shows that HA proteins of AIVs are preferably recognized by SVM and LDA, and the performances by SVM are superior to those by LDA.

Structural parameterization and functional prediction of antigenic polypeptome sequences with biological activity through quantitative sequence-activity models (QSAM) by molecular electronegativity edge-distance vector (VMED).

Only from the primary structures of peptides, a new set of descriptors called the molecular electronegativity edge-distance vector (VMED) was proposed and applied to describing and characterizing the molecular structures of oligopeptides and polypeptides, based on the electronegativity of each atom or electronic charge index (ECI) of atomic clusters and the bonding distance between atom-pairs. Here, the molecular structures of antigenic polypeptides were well expressed in order to propose the automated technique for the computerized identification of helper T lymphocyte (Th) epitopes. Furthermore, a modified MED vector was proposed from the primary structures of polypeptides, based on the ECI and the relative bonding distance of the fundamental skeleton groups. The side-chains of each amino acid were here treated as a pseudo-atom. The developed VMED was easy to calculate and able to work. Some quantitative model was established for 28 immunogenic or antigenic polypeptides (AGPP) with 14 (1-14) A(d) and 14 other restricted activities assigned as "1"(+) and "0"(-), respectively. The latter comprised 6 A(b)(15-20), 3 A(k)(21-23), 2 E(k)(24-26), 2 H-2(k)(27 and 28) restricted sequences. Good results were obtained with 90% correct classification (only 2 wrong ones for 20 training samples) and 100% correct prediction (none wrong for 8 testing samples); while contrastively 100% correct classification (none wrong for 20 training samples) and 88% correct classification (1 wrong for 8 testing samples). Both stochastic samplings and cross validations were performed to demonstrate good performance. The described method may also be suitable for estimation and prediction of classes I and II for major histocompatibility antigen (MHC) epitope of human. It will be useful in immune identification and recognition of proteins and genes and in the design and development of subunit vaccines. Several quantitative structure activity relationship (QSAR) models were developed for various oligopeptides and polypeptides including 58 dipeptides and 31 pentapeptides with angiotensin converting enzyme (ACE) inhibition by multiple linear regression (MLR) method. In order to explain the ability to characterize molecular structure of polypeptides, a molecular modeling investigation on QSAR was performed for functional prediction of polypeptide sequences with antigenic activity and heptapeptide sequences with tachykinin activity through quantitative sequence-activity models (QSAMs) by the molecular electronegativity edge-distance vector (VMED). The results showed that VMED exhibited both excellent structural selectivity and good activity prediction. Moreover, the results showed that VMED behaved quite well for both QSAR and QSAM of poly-and oligopeptides, which exhibited both good estimation ability and prediction power, equal to or better than those reported in the previous references. Finally, a preliminary conclusion was drawn: both classical and modified MED vectors were very useful structural descriptors. Some suggestions were proposed for further studies on QSAR/QSAM of proteins in various fields.