The aging lung: microenvironment, mechanisms, and diseases.

With the development of global social economy and the deepening of the aging population, diseases related to aging have received increasing attention. The pathogenesis of many respiratory diseases remains unclear, and lung aging is an independent risk factor for respiratory diseases. The aging mechanism of the lung may be involved in the occurrence and development of respiratory diseases. Aging-induced immune, oxidative stress, inflammation, and telomere changes can directly induce and promote the occurrence and development of lung aging. Meanwhile, the occurrence of lung aging also further aggravates the immune stress and inflammatory response of respiratory diseases; the two mutually affect each other and promote the development of respiratory diseases. Explaining the mechanism and treatment direction of these respiratory diseases from the perspective of lung aging will be a new idea and research field. This review summarizes the changes in pulmonary microenvironment, metabolic mechanisms, and the progression of respiratory diseases associated with aging.

Modulators targeting protein-protein interactions in Mycobacterium tuberculosis.

Tuberculosis (TB) is a chronic infectious disease caused by Mycobacterium tuberculosis (M. tuberculosis), mainly transmitted through droplets to infect the lungs, and seriously affecting patients' health and quality of life. Clinically, anti-TB drugs often entail side effects and lack efficacy against resistant strains. Thus, the exploration and development of novel targeted anti-TB medications are imperative. Currently, protein-protein interactions (PPIs) offer novel avenues for anti-TB drug development, and the study of targeted modulators of PPIs in M. tuberculosis has become a prominent research focus. Furthermore, a comprehensive PPI network has been constructed using computational methods and bioinformatics tools. This network allows for a more in-depth analysis of the structural biology of PPIs and furnishes essential insights for the development of targeted small-molecule modulators. Furthermore, this article provides a detailed overview of the research progress and regulatory mechanisms of PPI modulators in M. tuberculosis, the causative agent of TB. Additionally, it summarizes potential targets for anti-TB drugs and discusses the prospects of existing PPI modulators.

[Research on promoter region methylation status of tumor repressor gene P16 in human hepatocellular carcinoma by using methylation sensitive restriction enzyme and semi-nested PCR assay].

OBJECTIVE: To construct a combination method of methylation sensitive restriction enzyme and semi-nested touch down PCR assay for studying the promoter region methylation status of P16 gene in human hepatocellular carcinoma. METHODS: According to the sequence of CpG rich promoter region of P16 gene, three primers were designed and synthesized for semi-nested touch down PCR assay to examine the promoter region methylation status of P16 gene. 340 bp segment of this region was cloned into vector pMD18-T; the plasmid was transformed into E. coli JM109 to harvest an extended quantity, then the plasmid was treated by CpG methylase M. Sss I, the methylated plasmid was named P16Pm+. This P16Pm+ is validated by digestion of Hpa II and is employed in studying the specificity and sensitivity of this constructed method. After construction, the method was used to examine the promoter region methylation status in P16 gene of 40 DNA samples from human HCCs and three DNA samples from normal human liver tissue. RESULTS: It was confirmed that the specificity and sensitivity of this method are solid and reliable (100 fg). It was found that 12/40 (30%) of hepatocellular carcinoma showed promoter region methylation in P16 gene whereas none (0/3) of the normal tissues was methylated in the promoter region in P16 gene. CONCLUSION: Promoter region methylation in P16 gene may take part in human hepatocellular carcinogenesis. The constructed method is simple, cost-effective and is of high specificity and sensitivity, thus suggesting its potential application to detecting promoter methylation in population-based studies.

Relationship between plasma HDL subclasses distribution and lipoprotein lipase gene HindIII polymorphism in hyperlipidemia.

BACKGROUND: Different high-density lipoprotein (HDL) subclasses have distinct but interrelated metabolic functions. HDL directly influences the atherogenic process, and changes in HDL subclasses distribution may be related to the incidence and prevalence of atherosclerosis. Lipoprotein lipase (LPL) is an important enzyme for hydrolysis of triglyceride-rich lipoproteins, and its activity is positively correlated with the plasma HDL cholesterol level. LPL gene HindIII polymorphism has been found associated with variations in lipid levels, but the impact on HDL subclasses distribution is less clearly established. METHODS: The relative apolipoprotein (apo) A-I contents (% apoA-I) of plasma HDL subclasses were determined by two-dimensional gel electrophoresis coupled with immunodetection and LPL gene HindIII polymorphism was assayed by polymerase chain reaction-restriction fragment length polymorphism (PCR-RFLP) in 173 hyperlipidemic and 155 normolipidemic subjects. RESULTS: The frequencies of 495TT genotype and allele T were the highest both in the hyperlipidemic and control groups. Compared with the control group, the frequency of 495TT genotype was higher, while the frequencies of 495TG and 495GG genotypes were significantly lower (P<0.05) in the hyperlipidemic group. Two-dimensional gel electrophoresis and immunodetection showed that HDL subclasses distribution was altered in hyperlipidemia, and had a general shift toward smaller size. Compared with the control group, the hyperlipidemic group had significantly higher relative apoA-I contents of prebeta1-HDL, prebeta2-HDL, HDL3b and HDL3a (P<0.05) and lower HDL2a and HDL2b levels (P<0.001). In the hyperlipidemic group, allele T carriers' frequency was higher than that in the control group (P<0.05), and the genotype of 495TT showed higher levels of plasma TG, apoB100, TG/HDL-C ratio, relative apoA-I contents of prebeta1-HDL, HDL3b and lower HDL2a, HDL2b compared with that of the 495GG genotype subgroup (P<0.05). In the control group, the genotype of 495TT had higher plasma TG, HDL3c and lower HDL2a compared with that of 495GG subgroup (P<0.05). CONCLUSIONS: The 495TT genotype of LPL gene HindIII polymorphism was associated with changes of HDL subclasses distribution in Chinese population with hyperlipidemia. The particle size of HDL shifted toward smaller, which, in turn, indicated that RCT might be weakened and HDL maturation might be abnormal in hyperlipidemic subjects with 495TT genotype.

Alterations of high-density lipoprotein subclasses in endogenous hypertriglyceridemia.

BACKGROUND: To investigate the alterations of high-density lipoprotein (HDL) subclasses in endogenous hypertriglyceridemic subjects. METHODS: Apolipoprotein A-I contents of plasma HDL subclasses were quantitated by 2-dimensional gel electrophoresis in 236 normolipidemic subjects (including 146 males and 90 females) and 176 endogenous hypertriglyceridemic subjects (including 103 males and 73 females). RESULTS: Apolipoprotein A-I contents of small-sized pre-beta1-HDL and HDL3a were significantly higher (P < .01 and P < .01, respectively), but those of large-sized HDL2a and HDL2b were significantly lower (P < .01 and P < .01, respectively) in hypertriglyceridemic subjects versus normolipidemic subjects. Moreover, with the elevation of triglyceride levels, small-sized pre-beta1-HDL and HDL3a increased successively; however, large-sized HDL2a and HDL2b decreased successively. Males had significantly higher apolipoprotein A-I contents of small-sized pre-beta1-HDL and HDL3b (P < .05 and P < .05, respectively), but lower contents of large-sized HDL2b (P < .01) than females in both normolipidemic and hypertriglyceridemic subjects. CONCLUSIONS: The particle size of HDL shifted toward smaller size in hypertriglyceridemic subjects, especially in male subjects. Of note, the shift was more obvious with the elevation of triglyceride levels. The changes mentioned above indicate that HDL maturation might be abnormal and reverse cholesterol transport might be weakened.

[Relationship between the contents of serum HDL subclasses and the extent of coronary stenosis in coronary heart disease patients].

OBJECTIVE: To explore the relationship between the contents of serum HDL subclasses and the extent of coronary stenosis in coronary heart disease (CHD) patients. METHODS: The contents of serum HDL subclasses in CHD patients (n = 51) and healthy controls (n = 56) were determined by two dimensional gel electrophoresis associated with immunodetection method. CHD patients were divided into three groups by average coronary severity score (CSS). Data were analyzed using linear regression and correlation method and multiple stepwise regression method. RESULTS: It was found that as the extent of coronary stenosis increases, the levels of pre beta1-HDL, HDL3b increase, meanwhile the level of HDL2b decreases (P < 0.001). There were significant positive correlations between CSS and pre beta1-HDL (P < 0.01), HDL3a (P < 0.05), HDL3b (P < 0.01), and significant negative correlation was observed between CSS and HDL2b (P < 0.01). apoB100, HDL2b, TG, HDL-C, TC/HDL-C, apoAI are all independent risk factors of CHD. CONCLUSION: The extent of coronary stenosis is highly correlated with the subclasses of HDL.

[The interrelationships between serum triglyceride, total cholesterol and HDL subpopulations].

OBJECTIVE: To assess the influence of serum triglyceride (TG) level and total cholesterol (TC) level on the change of the contents of serum HDL subpopulations. METHODS: The apolipoprotein (apo) A-I contents of serum HDL subpopulations in 289 subjects were determined by two-dimensional gel electrophoresis associated with immunodetection method. RESULTS: Analysis of the data on the serum TG levels in subjects revealed that the apoA-I contents of pre beta 1-HDL, pre beta 2-HDL, HDL3b and HDL3a increased with the increase of TG level, whereas the apoA-I contents of HDL2a and HDL2b decreased. By comparison with the data of normal TG group, the apoA-I contents of pre beta 1-HDL and HDL3b in the high TG and very high TG groups were significantly higher, whereas those of HDL2b were significantly lower in the high TG and very high TG groups. Analysis of the data on the serum TC levels in subjects revealed that the apoA-I contents of pre beta 1-HDL, pre beta 2-HDL, HDL2c and HDL3b increased with the increase of TC level, while the apoA-I contents of HDL2b decreased. As compared with the data of TC desirable group, the apoA-I contents of pre beta 1-HDL, HDL3c and HDL3b were significantly higher in the high TC group. CONCLUSION: With the increase of serum TG or TC, there is a general shift toward small-sized HDL in subjects. Besides, the change of serum TG level is a more important factor influencing the components of HDL subpopulations, compared with the change of serum TC level.

[Effect of purified pre-beta 1 HDL on efflux of 3H-cholesterol loaded in human smooth muscle cells].

OBJECTIVE: To compare the effects of different HDL subclasses on the efflux of 3H-cholesterol loaded human smooth muscle cells (SMCS). METHODS: 3H-cholesterol loaded human SMCS were incubated with purified pre-beta 1 HDL, alpha-HDL and apoE-deficient HDL3 respectively. The cholesterol effluxing capacity and incubating time of different HDL subclasses were detected, and were analysed by double-reciprocal mapping. RESULTS: It was found that the value of Emax of pre-beta 1 HDL is higher than that of alpha-HDL and apoE-deficient HDL3 (P < 0.01), and the value of Ke of pre-beta 1 HDL is lower than that of alpha-HDL and apoE-deficient HDL3 (P < 0.01). CONCLUSION: The results showed the effluxing capacity and efficiency of pre-beta 1 HDL were greater than those of alpha-HDL and apoE-deficient HDL3, thus suggesting that pre-beta 1 HDL is a more efficient acceptor of cell-derived 3H-cholesterol.

[Study on lipoprotein lipase gene Hind III polymorphism in Chinese type IIb hyperlipoproteinemia].

OBJECTIVE: To investigate whether lipoprotein lipase (LPL) gene Hind III polymorphism is associated with Chinese type IIb hyperlipoproteinemia. METHODS: Lipoprotein lipase gene Hind III polymorphism was studied using polymerase chain reaction (PCR) and restriction fragment length polymorphisms (RFLP) in 103 type IIb hyperlipoproteinemia patients and 129 healthy subjects from a population of Chinese Hans in Chengdu area. RESULTS: Both in type IIb hyperlipoproteinemia group and control group, the H+H+ homozygote was the major allelotype. The H+ allelic frequency of type IIb hyperlipoproteinemia group was higher than that of control group (0.864 vs 0.705, P<0.01). But the H- allelic frequency of type IIb hyperlipoproteinemia group was significantly lower than that of control group (0.136 vs 0.295, P<0.01). The plasma triglycerides (TG) level of H+H+ genotype was significantly higher than that of H+H- and H-H- genotypes (P<0.05 and P<0.01); the plasma TC level and TG/HDL C ratio were higher than those of H+H- and H-H- genotypes (P<0.05); apoA II levels of H+H+ and H+H- genotypes were significantly lower than that of H-H- genotype (P<0.01 and P<0.05). CONCLUSION: The Hind III RFLP at intron 8 of LPL gene is associated with type II b hyperlipoproteinemia to some extent in Chinese population.

[Subclasses of serum HDL in 151 healthy adults in Chengdu].

OBJECTIVE: To investigate the components of subclasses of serum HDL in healthy adults and the impact of age and gender on these components. METHODS: The components of subclasses of serum HDL in 151 healthy adults were determined by two dimensional gel electrophoresis associated with immunodetection method. RESULTS: The average concentration of prebeta1-HDL, prebeta2-HDL, HDL(3c), HDL(3b), HDL(3a), HDL2a, and HDL(2b) were 6.11%, 4.74%, 5.97%, 11.70%, 20.27%, 21. 85%, and 29.19%, respectively. The prebeta1-HDL increased with age, whereas the HDL(2b) decreased. The components of prebeta1-HDL in men over 50 and women over 60 were significantly greater than those of the same gender who were younger than 40, while the components of HDL2b in both men and women over 50 decreased compared to those of the same gender who were younger than 40. The component of prebeta1-HDL was significantly greater in men than in women, but it was reversed for HDL(2b). The prebeta1-HDL increased with the body mass index, age, and the concentration of TG. The HDL2b decreased with age and the concentrations of TG and apoB100. CONCLUSION: With the increase of age, there is a general shift toward smaller sized HDL, which indicates that the reverse cholesterol transport might be weakened. Men has smaller particle size than women.