Interactions between long interpregnancy interval and advanced maternal age on neonatal outcomes.

BACKGROUND: After the implementation of the universal two-child policy in China, it was more frequent to have long interpregnancy intervals (IPIs) and advanced maternal age. However, the interactions between long IPIs and advanced maternal age on neonatal outcomes are unknown. METHODS: The study subjects of this historical cohort study were multiparas with singleton live births between October 1st, 2015, and October 31st, 2020. IPI was defined as the interval between delivery and conception of the subsequent pregnancy. Logistic regression models were used to calculate adjusted odds ratios (aORs) and 95% confidence intervals (CIs) of the risks of preterm birth (PTB), low birth weight (LBW), small for gestation age, and 1-min Apgar score ≤ 7 in different IPI groups. Relative excess risk due to interaction (RERI) was used to evaluate the additive interaction between long IPIs and advanced maternal age. RESULTS: Compared with the 24 ≤ IPI ≤ 59 months group, the long IPI group (IPI ≥ 60 months) was associated with a higher risk of PTB (aOR, 1.27; 95% CI: 1.07-1.50), LBW (aOR, 1.32; 95% CI 1.08-1.61), and one-minute Apgar score ≤ 7 (aOR, 1.46; 95% CI 1.07-1.98). Negative additive interactions (all RERIs < 0) existed between long IPIs and advanced maternal age for these neonatal outcomes. Meanwhile, IPI < 12 months was also associated with PTB (aOR, 1.51; 95% CI 1.13-2.01), LBW (aOR, 1.50; 95% CI 1.09-2.07), and 1-min Apgar score ≤ 7 (aOR, 1.93; 95% CI 1.23-3.04). CONCLUSIONS: Both short and long IPIs are associated with an increased risk of adverse neonatal outcomes. Appropriate IPI should be recommended to women planning to become pregnant again. In addition, better antenatal care might be taken to balance the inferiority of advanced maternal age and to improve neonatal outcomes.

[Effect of oral motor intervention in improving brain function development in preterm infants: a randomized controlled trial].

OBJECTIVE: To study the effect of oral motor intervention (OMI) on brain function development in preterm infants. METHODS: A total of 112 preterm infants were stratified into small-gestational-age (30-31+6 weeks) and large-gestational-age (32-33+6 weeks) according to gestational age at birth. The preterm infants were randomly divided into a control group and an intervention group, with 56 infants in each group. The infants in the control group were given routine treatment and nursing, while those in the intervention group were given OMI in addition to the treatment and nursing in the control group. Amplitude-integrated EEG (aEEG) and Neonatal Behavioral Neurological Assessment (NBNA) were performed on days 1, 7, and 14 of enrollment, and the level of brain function development was compared before and after intervention. RESULTS: On day 7 of OMI, the small-gestational-age intervention group had lower upper bounds of voltage and bandwidth and a higher aEEG score than the small-gestational-age control group (P < 0.05). Compared with the small-gestational-age control group, the small-gestational-age intervention group had higher upper bound of voltage, percentage of mature sleep-wake cycle, aEEG score, and NBNA score and a lower narrow bandwidth on day 14 of OMI (P < 0.05). Compared with the large-gestational-age control group, the large-gestational-age intervention group had lower upper voltage and voltage difference and higher lower bound of voltage and aEEG score on days 7 and 14 of OMI (P < 0.05). On day 7 of OMI, the large-gestational-age intervention group had a higher NBNA score than the large-gestational-age control group (P < 0.05). CONCLUSIONS: OMI can promote the maturation of aEEG background activities, improve neurobehavioral manifestations, and accelerate brain function development in preterm infants.

A meta-analysis of fluconazole for the prevention of invasive fungal infection in preterm infants.

OBJECTIVE: The present aimed to evaluate the efficacy and safety of fluconazole for prophylactic use in preterm infants with very low birth weight (VLBW) by using an evidence-based methodology. METHODS: A computerized literature search was conducted in PubMed, the Cochrane Database of Systematic Reviews, MEDLINE, EMBASE, the ISI Web of Knowledge databases, the Chinese Biomedical (CBM) database, China National Knowledge Infrastructure, the WanFang database, and the VIP Chinese science and technology journal database to find all the randomized controlled trials conducted between January 2000 and December 2019 that studied the prevention of invasive fungal infection (IFI) by fluconazole in preterm infants with VLBW. A meta-analysis was conducted using the RevMan 5.3 and GRADEprofiler 3.2.2 software. RESULTS: A total of 14 studies (including 1,930 preterm infants with VLBW) were included. The meta-analysis found that the prophylactic use of fluconazole significantly reduced the incidence of IFI (RR = 0.39; 95% CI: 0.24-0.64, P < 0.05), overall mortality (RR = 0.77; 95% CI: 0.61-0.97, P < 0.05), and fungal colonization rate (RR = 0.32; 95% CI: 0.25-0.41, P < 0.05) in preterm infants with VLBW. There was no significant effect on some common complications and neurological development in preterm infants. The application of fluconazole would not lead to the development of fungal resistance in the short term and would have no significant adverse effects. CONCLUSION: The prophylactic use of fluconazole significantly reduced the incidence of IFI, overall mortality, and fungal colonization in preterm infants; however, the impact of prophylactic use of fluconazole on preterm infants needs to be evaluated in a large number of clinical studies because of the limited data.

[Dynamic observation of pulmonary function by plethysmography in preterm infants with bronchopulmonary dysplasia].

OBJECTIVE: To study the effect of bronchopulmonary dysplasia (BPD) on lung function in preterm infants. METHODS: According to the presence/absence or the severity of BPD, 72 preterm infants were divided into non-BPD group (n=44), mild BPD group (n=15) and moderate BPD group (n=13). Lung function was assessed by plethysmography on days 7, 14 and 28 after birth. RESULTS: The preterm infants in the three groups had gradual increases in tidal volume per kilogram (TV/kg), functional residual capacity (FRC), ratio of time to peak tidal expiratory flow to total expiratory time (%T-PF) and ratio of volume to peak tidal expiratory flow to total expiratory volume (%V-PF) on days 7, 14 and 28 after birth, while there were gradual reductions in effective airway resistance per kilogram (Reff/kg) and respiratory rate (RR) (P<0.05). Compared with the non-BPD group on days 7, 14 and 28 after birth, the mild and moderate BPD groups had significantly lower TV/kg, FRC, %T-PF, and %V-PF and significantly higher Reff/kg and RR (P<0.05). On day 7 after birth, the moderate BPD group had significantly higher airway resistance, Reff/kg and FRC/kg than the mild BPD group (P<0.05). CONCLUSIONS: There is a certain degree of pulmonary function impairment in preterm infants with BPD. Dynamic monitoring of lung function by plethysmography is useful for assessing lung development in the neonatal period in these infants.

[Effect of red blood cell storage duration on the clinical effect of exchange transfusion and internal environment in neonates with hyperbilirubinemia].

OBJECTIVE: To study the effect of red blood cell (RBC) storage duration on the clinical effect of exchange transfusion (ET) and internal environment in neonates with hyperbilirubinemia. METHODS: A retrospective analysis was performed for the clinical data of 135 neonates with hyperbilirubinemia who received ET between January 2015 and August 2018. According to RBC storage duration, the neonates were divided into short-term storage group (RBCs were stored for ≤7 days) with 56 neonates and long-term storage group (RBCs were stored for >7 days) with 79 neonates. The two groups were compared in terms of serum total bilirubin (TBIL) level and the rate of TBIL reduction at 0 and 12 hours after ET, as well as the duration of continued phototherapy and rate of repeated ET. Routine blood test parameters, electrolytes, blood glucose, and blood gas parameters were measured before ET and at 0 hour after ET. RESULTS: At 0 hour after ET, there were no significant differences in the TBIL level and the rate of TBIL reduction between the two groups (P>0.05). At 12 hours after ET, the long-term storage group had a significantly higher TBIL level and a significantly lower rate of TBIL reduction than the short-term storage group (P<0.01). The long-term storage group had a significantly longer duration of continued phototherapy after ET than the short-term storage group (P<0.05). Compared with the short-term storage group, the long-term storage group had significantly higher incidence rates of ET-related complications, including hyponatremia, hyperkalemia, and metabolic acidosis (P<0.05). CONCLUSIONS: The use of RBCs with a storage duration of >7 days in ET for neonates with hyperbilirubinemia does not affect the immediate effect of ET, but these neonates tend to have a poor outcome after continued phototherapy and high risk of hyponatremia, hyperkalemia, and metabolic acidosis.

Risk factors for necrotizing enterocolitis in very preterm infants: a case-control study in southwest China.

OBJECTIVE: The objective of this study is to investigate perinatal risk factors for necrotizing enterocolitis (NEC) in very preterm infants. METHODS: This retrospective study included all preterm infants with a gestational age <32 weeks attending our institution from 2013 to 2016. The NEC group comprised patients with NEC enrolled according to the inclusion criteria. Controls were selected from the database and were matched for gender, gestational age, and birth weight. Enumeration data are expressed as percentages (%) and were compared using the χ2 test. Quantitative data are expressed as the mean (standard deviation) and were compared using Student's t-test. Conditional logistic regression analyses were performed to identify the factors significantly associated with NEC. RESULTS: During the study period, 945 very preterm infants were admitted to the neonatal intensive care unit, of whom 46 (4.87%) acquired NEC. A total of 33 cases were enrolled in the NEC group, and 33 controls were selected from the database. Univariate analyses revealed significant differences between groups in the incidence of maternal placenta previa, neonatal infection symptoms, septicemia, and intravenous aminophylline administration (p < .05). Conditional logistic regression analysis demonstrated statistically significant associations of neonatal septicemia (odds ratio [OR] = 4.000, p = .043) and intravenous aminophylline (OR = 4.922, p = .035) with NEC. CONCLUSION: Neonatal septicemia and intravenous aminophylline use are risk factors associated with NEC development in very preterm infants.

Asiaticoside attenuates hyperoxia-induced lung injury in vitro and in vivo.

OBJECTIVES: Asiaticoside (AS) displays anti-inflammation, and anti-apoptosis effect, but the role of AS in hyperoxia-induced lung injury (HILI) treatment is undefined. Therefore, the aim of this study was to investigate the effects of AS on HILI on premature rats and alveolar type II (AEC II) cells. MATERIALS AND METHODS: Sprague-Dawley premature rats (n=25/group) were exposed to 80% O2 with or without AS. Then, we detected 80% O2-induced lung injury and survival rate of premature rat. We tested the concentration of malondialdehyde (MDA), myeloperoxidase (MPO), total antioxidant capacity (TAOC), tumor necrosis factor α (TNF-α), interleukin 6 (IL-6), and interleukin 1ß (IL-1ß) in premature rats' blood. Then, the AEC II cell apoptosis was observed by Hoechst 33258 staining and flow cytometry. Simultaneously, nuclear factor (erythroid-derived 2)-like 2 (Nrf2) signaling pathway was measured by Western blot. RESULTS: Our results found that AS-treated group rats had significantly higher survival rates than 80% O2 group at day 14 (P<0.05). AS protected HILI, decreased the MPO and MDA concentration, and reversed TAOC level (P<0.05). AS also downregulated the levels of TNF-α, IL-1ß, and IL-6 in the premature rat's blood (P<0.01). Moreover, AS markedly attenuated AEC II cell apoptosis and increased Nrf2 and Heme oxygenase 1 (HO-1) expression in the nucleus (P<0.05). CONCLUSION: AS showed protective effects on premature rats of HILI in vitro and in vivo. AS can potentially be developed as a novel agent for the treatment of HILI diseases.

[Preventive effect of caffeine on bronchopulmonary dysplasia in preterm infants].

With the increase in the rescue success rate of critically ill preterm infants and extremely preterm infants, the incidence rate of bronchopulmonary dysplasia (BPD) is increasing year by year. BPD has a high mortality rate and high possibility of sequelae, which greatly affects the quality of life of preterm infants and brings a heavy burden to their families, and so the treatment of BPD is of vital importance. At present, no consensus has been reached on the treatment measures for BPD. However, recent studies have shown that early application of caffeine can prevent BPD. With reference to the latest studies on the effect of caffeine in the prevention of BPD, this article reviews the mechanism of action of caffeine in reducing pulmonary inflammation, improving morphological abnormalities of lung injury, reducing oxidative stress injury, and improving pulmonary function.

[Monitoring of kidney injury in preterm infants].

Acute kidney injury (AKI) is a common complication in the neonatal intensive care unit that causes a high mortality of preterm infants and various chronic kidney diseases in adulthood. Preterm infants have immature development of the kidneys at birth. The kidneys continue to develop within a specific time window after birth. However, due to various factors during pregnancy and after birth, preterm infants tend to develop AKI. At present, serum creatinine and urine volume are used for the assessment of kidney injury, and their early sensitivity and specificity have attracted increasing attention. In recent years, various new biomarkers have been identified for early recognition of AKI. This article reviews the features, risk factors, renal function assessment, and prevention/treatment of AKI of preterm infants, in order to provide a reference for improving early diagnosis and treatment of AKI in preterm infants and long-term quality of life.

Resveratrol suppresses hyperoxia-induced nucleocytoplasmic shuttling of SIRT1 and ROS production in PBMC from preterm infants in vitro.

OBJECTIVE: By assessing silent mating-type information regulation 2 homolog 1 (SIRT1) nucleocytoplasmic shuttling and reactive oxygen species (ROS) levels in peripheral blood mononuclear cells (PBMCs), this study aimed to explore the role of SIRT1 in premature infants after exposure to hyperoxia and assess the protective effects of resveratrol (Res). METHODS: Firstly, ROS levels as well as SIRT1 translocation and expression in PBMCs samples were evaluated from 40 premature infants with different oxygen amounts received at birth. Then, PBMCs, from additional 40 premature infants administered no oxygen at birth, were used to establish an in vitro model of hyperoxia. RESULTS: In infants that received O2 at birth, ROS and MDA levels, and SIRT1 translocation rates gradually increased in a concentration-dependent manner, while SIRT1 gradually decreased. In agreement, PBMCs cultured in vitro showed increased ROS levels after exposed to hyperoxia, SIRT1 translocation increased as well. However, treatment with Res resulted in opposite effects. CONCLUSION: Res inhibits ROS release in PBMCs from preterm infants exposed to hyperoxia, likely by preventing SIRT1 nucleocytoplasmic shuttling and increasing SIRT1 expression.

Comparison of twelve single-drug regimens for the treatment of type 2 diabetes mellitus.

We performed a network meta-analysis to compare the efficacy of 12 single-drug regimens (Glibenclamide, Glimepiride, Pioglitazone, Rosiglitazone, Repaglinide, Metformin, Sitaglitin, Exenatide, Liraglutide, Acarbose, Benfluorex, and Glipizide) in the treatment of type 2 diabetes mellitus (T2DM). Fifteen relevant randomized controlled trials (RCTs) were included; direct and indirect evidence from these studies was combined, and weighted mean difference (WMD) and surface under the cumulative ranking curves (SUCRAs) were examined to evaluate the monotherapies. Liraglutide was more effective than Glimepiride, Pioglitazone, Sitaglitin, Exenatide, and Glipizide at reducing glycated hemoglobin (HbA1c) levels. In contrast, Acarbose was less effective than Glibenclamide, Glimepiride, Pioglitazone, Rosiglitazone, Repaglinide, Metformin, and Liraglutide at decreasing HbA1c levels. Reductions in fasting plasma glucose (FPG) levels were similar after all treatments. Rosiglitazone was less effective than Glibenclamide and Repaglinide at reducing total cholesterol (TC) levels. High density lipoprotein (HDL), low density lipoprotein (LDL), and triglyceride levels did not differ after treatment with any of the monotherapies. HbA1c and FPG SUCRA values were highest for Liraglutide, while HbA1c and FPG values were lowest for Acarbose, and TC and LDL values were lowest for Rosiglitazone. These results suggest that Liraglutide may be most effective, and Acarbose least effective, at reducing blood glucose levels, while Glibenclamide, Repaglinide, and Metformin may be most effective, and Rosiglitazone least effective, at reducing lipoidemia, in T2DM patients.

Identification of cow milk in goat milk by nonlinear chemical fingerprint technique.

The objective of this paper was to develop a nonlinear chemical fingerprint technique for identifying and detecting adulteration of goat milk with cow milk. In this study, by taking the Belousov-Zhabotinsky oscillatory chemical reaction using acetone and substrates in goat milk or cow milk as main dissipative substances, when the same dosage of goat milk and cow milk was introduced to the "H+ + Mn2+ + BrO3- + acetone" oscillating system respectively, nonlinear chemical fingerprints were obtained for goat milk and cow milk from the same origin. The results showed that inductive time value and the content of cow milk in goat milk had a linear relationship in the range of 0-100% and the corresponding regression coefficient was 0.9991. A detection limit of 0.0107 g/g was obtained, and the content of cow milk in mixed milk was calculated. The proposed method in this study was simple, economical and effective. In addition, the method did not need the pretreatment and separation of samples for identifying and evaluating cow milk adulteration in goat milk.

[Pathogen distribution, risk factors, and outcomes of nosocomial infection in very premature infants].

OBJECTIVE: To study the pathogen distribution and risk factors of nosocomial infection in very preterm infants, as well as the risk of adverse outcomes. METHODS: A retrospective analysis was performed for the clinical data of 111 very preterm infants who were born between January and December, 2016 and had a gestational age of <32 weeks and a birth weight of <1 500 g. According to the presence or absence of nosocomial infection after 72 hours of hospitalization, the infants were divided into infection group and non-infection group. The infection group was analyzed in terms of pathogenic bacteria which caused infection and their drug sensitivity. A multivariate logistic regression analysis was used to investigate the potential risk factors and risk of adverse outcomes of nosocomial infection in very preterm infants. RESULTS: Gram-negative bacteria were the main pathogens for nosocomial infection in very preterm infants and accounted for 54%, among which Pseudomonas aeruginosa was the most common one; the following pathogens were fungi (41%), among which Candida albicans was the most common one. The drug sensitivity test showed that Gram-negative bacteria were highly resistant to ß-lactam and carbapenems and highly sensitive to quinolones, while fungi had low sensitivity to itraconazole and high sensitivity to 5-fluorocytosine and amphotericin B. Early-onset sepsis, duration of peripherally inserted central catheter, steroid exposure, and duration of parenteral nutrition were risk factors for nosocomial infection in very preterm infants (P<0.05). Compared with the non-infection group, the infection group had significantly higher risks of pulmonary complications (P<0.05), as well as a significantly longer length of hospital stay and a significantly higher hospital cost (P<0.001). CONCLUSIONS: Nosocomial infection in very preterm infants is affected by various factors and may increase the risk of adverse outcomes. In clinical practice, reasonable preventive and treatment measures should be taken with reference to drug sensitivity, in order to improve the prognosis of very premature infants.

Resveratrol as a potential therapeutic drug for respiratory system diseases.

Respiratory system diseases are common and major ailments that seriously endanger human health. Resveratrol, a polyphenolic phytoalexin, is considered an anti-inflammatory, antioxidant, and anticancer agent. Thanks to its wide range of biological activities, resveratrol has become a hotspot in many fields, including respiratory system diseases. Indeed, research has demonstrated that resveratrol is helpful to relieve pulmonary function in the general population. Meanwhile, growing evidence indicates that resveratrol plays a protective role in respiratory system diseases. This review aimed to summarize the main protective effects of resveratrol in respiratory system diseases, including its anti-inflammatory, antiapoptotic, antioxidant, antifibrotic, antihypertensive, and anticancer activities. We found that resveratrol plays a protective role in the respiratory system through a variety of mechanisms, and so it may become a new drug for the treatment of respiratory system diseases.

Construction of p66Shc gene interfering lentivirus vectors and its effects on alveolar epithelial cells apoptosis induced by hyperoxia.

BACKGROUND: The aim of this study is to observe the inhibitive effects of p66Shc gene interfering lentivirus vectors on the expression of p66Shc, and to explore its effects on alveolar epithelial cells apoptosis induced by hyperoxia. METHODS: The gene sequences were cloned into the pLenR-GPH-shRNA lentiviral vector, which was selected by Genebank searches. The pLenR-GPH-shRNA and lentiviral vector packaging plasmid mix were cotransfected into 293T cells to package lentiviral particles. Culture virus supernatant was harvested, and then the virus titer was determined by serial dilution assay. A549 cells were transduced with the constructed lentiviral vectors, and real-time polymerase chain reaction (RT-PCR) and Western blot were used to evaluate p66Shc expression. This study is divided into a control group, a hyperoxia group, an A549-p66ShcshRNA hyperoxia group, and a negative lentivirus group. Cell apoptosis was detected by flow cytometry after 24 hours; the expression of X-linked inhibitor of apoptosis protein (XIAP) and caspase-9 were detected by immunohistochemistry assay. The production of reactive oxygen species and cellular mitochondria membrane potential (ΔΨm) were determined by fluorescence microscopy. RESULTS: We successfully established the p66Shc gene interfering lentivirus vectors, A549-p66ShcshRNA. The A549-p66ShcshRNA was transfected into alveolar epithelial cells, and the inhibitive effects on the expression of p66Shc were observed. Both RT-PCR and Western blot demonstrated downregulation of p66Shc expression in A549 cells. In the A549-p66ShcshRNA hyperoxia group, we found dampened oxidative stress. A549-p66ShcshRNA can cause p66Shc gene silencing, reduce mitochondrial reactive oxygen species generation, reduce membrane potential decrease, reduce the apoptosis of A549 cells, and reduce alveolar epithelial cell injury, while the lentiviral empty vector group had no such changes. CONCLUSION: p66Shc gene interfering lentivirus vector can affect the alveolar epithelial cells apoptosis induced by hyperoxia.

[Resveratrol increases sirtuin 1 expression in peripheral blood mononuclear cells of premature infants and inhibits the oxidative stress induced by hyperoxia in vivo].

OBJECTIVE: To explore the effect of resveratrol on the levels of sirtuin 1 (SIRT1) and reactive oxygen species (ROS) in peripheral blood mononuclear cells (PBMCs) of premature infants exposed to hyperoxia. METHODS: Peripheral blood and isolated PBMCs from premature infants (gestational age<32 weeks) without oxygen supplement were collected and were randomly assigned into four groups: control, air+resveratrol, hyperoxia, and hyperoxia+resveratrol. The PBMCs were cultured in vitro for 48 hours, then the ROS content in PBMCs was measured by laser scanning confocal microscopy. Malondialdehyde (MDA) content in the medium was measured by the whole spectrum spectrophotometer. SIRT1 positioning was assessed by immunofluorescence. SIRT1 expression levels in PBMCs were measured by Western bolt. RESULTS: Compared with the control group, the level of SIRT1 in the air+resveratrol group increased significantly (P<0.05). The levels of ROS and MDA and the SIRT1 transposition rate in the hyperoxia group increased significantly, while the expression level of SIRT1 decreased significantly compared with the control group (P<0.05). The levels of ROS and MDA and the SIRT1 transposition rate decreased significantly (P<0.05), and the expression level of SIRT1 increased significantly in the hyperoxia+resveratrol group (P<0.05). CONCLUSIONS: Resveratrol can increase SIRT1 expression in PBMCs and inhibit SIRT1 shuttle from nucleus to cytoplasm in order to increase the ability of antioxidative stress in premature infants exposed to hyperoxia, thereby reducing the oxidative stress injury in premature infants.

[Silencing of Pin1 suppresses hyperoxia-induced apoptosis of A549 cells].

OBJECTIVE: To explore the effect of silence of Pin1 expression on hyperoxia-induced apoptosis in alveolar epithelial cells A549. METHODS: A549 cells were divided into four groups: control, hyperoxia, negative lentivirus and Pin1-shRNA hyperoxia. The hyperoxia group was exposed to a mixture of 95%O2 and 5%CO2 for 10 minutes. Then cells were cultured in a closed environment. After 24 hours, the changes of morphology were observed under an inverted microscope. Cell apoptosis was detected by flow cytometry (FCM). The expression of X-linked inhibitor of apoptosis protein (XIAP) and Caspase-9 were detected by immunohistochemistry. The production of reactive oxygen species (ROS) and cellular mitochondria membrane potential (△Ψm) were determined by fluorescence microscopy. RESULTS: Under the inverted microscope, the A549 cells grew slowly and the changes in morphology of the cells were most obvious in the hyperoxia and negative lentivirus groups. The changes in morphology of A549 cells were obviously improved in the Pin1-shRNA hyperoxia group. The FCM results showed that the apoptosis rate of A549 cells increased, Caspase-9 expression increased, XIAP expression decreased, mitochondrial ROS production increased and mitochondrial membrane potential decreased in the hyperoxia and negative lentivirus groups compared with the control group (P<0.05). Compared with the hyperoxia and negative lentivirus groups, the apoptosis rate of A549 cells decreased, Caspase-9 expression decreased, XIAP expression increased, mitochondrial ROS production decreased and mitochondrial membrane potential increased in the Pin1-shRNA hyperoxia group (P<0.05), although the levels of the indexes did not reach to those of the control group. CONCLUSIONS: Silencing of Pin1 could suppress hyperoxia-induced apoptosis of A549 cells.

[Roles of PKCß/P66Shc oxidative stress signal pathway in mediating hyperoxia-induced ROS production in alveolar epithelial cells].

OBJECTIVE: To explore the roles of PKCß/P66Shc oxidative stress signal pathway in mediating hyperoxia-induced reactive oxgen species (ROS) production in alveolar epithelial cells (A549) and the protective effects of PKCß inhibitor on hyperoxia-induced injuries of alveolar epithelial cells. METHODS: A549 cells were cultured in vitro and randomly divided into three groups: control, hyperoxia and PKCß inhibitor LY333531 treatment. The hyperoxia group was exposed to a mixture of O2 (950 mL/L) and CO2 (50 mL/L) for 10 minutes and then cultured in a closed environment. The LY333531 group was treated with PKCß inhibitor LY333531 of 10 µmol/L for 24 hours before hyperoxia induction. Cells were collected 24 hours after culture and the levels of PKCß, Pin1, P66Shc and P66Shc-Ser36 were detected by Western blot. The intracellular translocation of P66Shc, the production of ROS and cellular mitochondria membrane potential were measured using the confocal microscopy. RESULTS: Compared with the control group, the levels of PKCß, Pin1, P66Shc and P-P66Shc-Ser36 in A549 cells 24 hours after culture increased significantly in the hyperoxia group. These changes in the hyperoxia group were accompanied with an increased translocation rate of P66Shc from cytoplasm into mitochondria, an increased production of mitochondrial ROS, and a reduced mitochondrial membrane potential. Compared with the hyperoxia group, the levels of Pin1, P66Shc and P66Shc-Ser36 in A549 cells, the translocation rate of P66Shc from cytoplasm into mitochondria and the production of mitochondrial ROS decreased significantly, while the mitochondrial membrane potential increased significantly in the LY333531 treatment group. However, there were significant differences in the above mentioned measurements between the LY333531 treatment and control groups. CONCLUSIONS: Hyperoxia can increase the expression of PKCß in alveolar epithelial cells and production of mitochondrial ROS and decrease mitochondrial membrane potential. PKCß inhibitor LY333531 can partially disrupt these changes and thus alleviate the hyperoxia-induced alveolar epithelial cell injury.

Four new sesquiterpenoids from fruiting bodies of the fungus Inonotus rickii.

Three new bisabolane sesquiterpenoids, inonotic acid A (1), 3-O-formyl inonotic acid A (2), inonotic acid B (3), and one new drimane sesquiterpenoid 3α,6ß-dihydroxycinnamolide (4), were isolated from the fruiting bodies of mushroom Inonotus rickii. Their structures were elucidated by means of extensive spectroscopic methods. Compound 4 had moderate inhibitory activity on human colon cancer SW480 (IC50 = 20.4 µmol).

New chlamydosporol derivatives from the endophytic fungus Fusarium sp. #001.

Two new chlamydosporol derivatives, fusarilactone A (1) and fusarilactone B (2), together with nine known compounds (3-11), have been isolated from the crude extract of endophytic fungus Fusarium sp. #001. The structures of new compounds 1 and 2 were elucidated on the basis of extensive spectroscopic methods. Compound 1 showed mild cytotoxicities against three tumor cell lines (SMMC-7721, A-549, and MCF-7).