Involvement of NEAT1/PINK1-mediated mitophagy in chronic obstructive pulmonary disease induced by cigarette smoke or PM2.5.

Background: This study sought to explore the underlying mechanism of long non-coding ribonucleic acid nuclear enriched abundant transcript 1 (NEAT1) and PTEN-induced kinase 1 (PINK1)-mediated mitophagy in chronic obstructive pulmonary disease (COPD) induced by cigarette smoke (CS) or fine particular matter (PM2.5). Methods: In total, 30 male Wistar Rats were divided into the following 3 groups: (I) the COPD group exposed to CS (CSM); (II) the COPD group exposed to PM2.5 (PMM); and (III) the control (Ctrl) group. Pulmonary function, the enzyme-linked immunoassay analysis results, the histopathology results, and the ultrastructures of the lung tissues were examined in the 3 groups, and NEAT1 expression levels and the mitophagy-related protein PINK1, Parkin, LC3B, and p62 levels were assessed by quantitative reverse transcription PCR (RT-qPCR) and Western blotting. The A549 cells were transfected with small interfering ribonucleic acid (siRNA) targeting NEAT1, and subsequently stimulated with CS extract (CSE) and PM2.5 suspension (PMS). Mitochondrial dysfunction and enhanced mitophagy were observed, and the expression of the NEAT1/PINK1 pathway was assessed by RT-qPCR and Western blotting. Results: Both the CSM and PMM groups had a lower tidal volume (VT), minute ventilation (MV), and a higher respiratory rate (f) than the Ctrl group. The interleukin (IL)-6, IL-8, and tumor necrosis factor-alpha levels in the serum and bronchoalveolar lavage fluid of the CSM and PMM groups were significantly increased. The histological examination results revealed airway remodeling, the formation of pulmonary bullae, and emphysema in the CSM and PMM groups. Subsequently, the ultrastructures of the lung tissues in the CSM and PMM groups showed mitochondrial swelling and autophagosomes. Additionally, NEAT1 expression, the level of the mitophagy-related protein PINK1, Parkin, and the ratio of LC3-II/I increased synchronously. Further, NEAT1 siRNA blocked PINK1 expression, inhibited mitochondrial dysfunctions, and mitophagy activation in the A549 cells exposed to CSE or PMS. Conclusions: Our results suggest that CS and PM2.5 exposure induce mitochondrial dysfunction, and the NEAT1/PINK1 pathway plays a critical role in the occurrence and development of COPD by regulating mitophagy.

Ursolic acid promotes the apoptosis of cervical cancer cells by regulating endoplasmic reticulum stress.

AIM: Ursolic acid is a triterpenoid common in plants and exhibits anti-carcinogenic activity. This study aimed to reveal the role of endoplasmic reticulum stress in cervical cancer cell apoptosis promoted by ursolic acid. METHODS: HeLa cells were treated with ursolic acid or/and 4-phenylbutyric acid. The viability and apoptosis of HeLa cells were evaluated by MTT assay and flow cytometry, respectively. RESULTS: Ursolic acid decreased HeLa cell viability in a time- and dose- dependent manner, and induced HeLa cell apoptosis in a dose-dependent manner. Moreover, ursolic acid increased the expression of C/EBP homologous protein and glucose-regulated protein 78 at protein levels, while 4-phenylbutyric acid antagonized the apoptosis of HeLa cells induced by ursolic acid. CONCLUSION: Ursolic acid inhibits the viability and promotes the apoptosis of HeLa cells. Endoplasmic reticulum stress may mediate the apoptosis of cervical cancer cells stimulated by ursolic acid.

[The role of occlusal factors in the occurrence of vertical root fracture].

PURPOSE: To investigate the occlusal characteristics and the condition of tooth abrasion in patients with vertical root fracture and to discuss the etiology of the vertical root fracture and the relationships between occlusal disorder, tooth abrasion and vertical root fracture of molars. METHODS: Two hundred and seventy-seven cases of root fracture patients were included in the study, with 309 involved teeth. The periodontal status, occlusal wear, occlusal contact area, occlusal interference, occlusal trauma and the X-ray film were observed and evaluated. All statistical analyses were performed using SPSS13.0 software package. Date was expressed as n(%).Differences between groups were compared using X(2) test with SPSS 13.0 software package. RESULTS: Vertical root fracture occurred in patients aging 40 to 60 years, the first molar mesial root or buccal root was mostly involved. Periodontal tissue destruction was significantly greater than roots without vertical fracture, with formation of localized periodontal pocket. Severe occlusal surface wear, high and steep non-work tip, working tip abrasion, deep occlusal surface concave and lower distal edge were seen in the affected teeth.The degree of vertical root fracture was related to the site of deep occlusal surface concave. Occlusal interference or occlusal trauma was the predisposing factors of vertical root fracture. CONCLUSIONS: Vertical root fracture is associated with malocclusion and tooth abrasion. Changes of occlusion leads to over occlusal force and abnormal direction of occlusal force, which may be important factor of vertical root fracture.

Integration of newly isolated biocatalyst and resin-based in situ product removal technique for the asymmetric synthesis of (R)-methyl mandelate.

The enantioselective reduction of methyl benzoylformate to (R)-methyl mandelate, an important pharmaceutical intermediate and a versatile resolving agent, was investigated in this study. After minimizing the reaction-specific constraints (constraints dependent on the nature of the substrate and product) by preliminary selection of the reaction parameters, an effective whole cell biocatalyst (Saccharomyces cerevisiae AS2.1392) was obtained by simple screening procedures. Under further optimized conditions, a product concentration of 103 mmol L(-1) could be attained within 5 h with a yield of 85.8% and an enantiometric excess of 95.4%, indicating S. cerevisiae AS2.1392 an efficient biocatalyst for the asymmetric synthesis of (R)-methyl mandelate. Furthermore, resin-based in situ product removal (ISPR) technique was applied to alleviate the substrate and product inhibition or toxicity to the whole cells. The integration of newly isolated biocatalyst and proper ISPR technique provides a practical route for the preparation of optically active pharmaceutical intermediates.

[Study on the cost of preventing AIDS transmission from mothers to children: an effect analysis].

OBJECTIVE: To evaluate the costs of preventing AIDS transmission from mothers to children in a high-incidence area and to investigate relations between costs and effects, as well as to study the economical effects of this approach. METHODS: According to the number of patients and each strategy on prevention of AIDS transmission, following aspects were calculated as: the cost of preventing each patient with HIV infection, to avoid the cost of one disability adjusted life year (DALY), to evaluate the cost of each patient with either HIV infection or HIV-infected thereafter,and to calculate the HIV-positive rates in mothers at the same levels between costs and effects. RESULTS: The costs-effects for stopping pregnancy:it was 2264 Yuan for preventing one DALY, the costs of avoiding one case with HIV infection was 46 963 Yuan, but it was 211,000 Yuan from each patient after HIV infection, the ratio between effects and costs was 4.5:1. The costs-effects for comprehensive strategies showed that the cost was 60 853 Yuan for avoiding one case with HIV infection. It was 211,000 Yuan for each patient after HIV infection and the ratio between effects and costs was 3.5:1. CONCLUSION: The cost-effect of preventing HIV transmission from mothers to children was significant on the basis of economical level. It was more effective to evaluate the relation between costs and effects according to economical level in screening and preventing transmission from mothers to children under the situation that the HIV-positive rate in pregnant mothers was more than 0.03%.