The autophagy inhibitor 3-methyladenine restores sevoflurane anesthesiainduced cognitive dysfunction and neurons apoptosis.

This study was designed to explore the effect of 3-methyladenine (3-MA) on sevoflurane anesthesia-induced cognitive dysfunction. A total of 60 C57BL/6 (5-8 months old) mice were randomly arranged into 3 groups: Control, sevoflurane (Sev) and Sev+3-MA group with 3-MA administration was performed during Sev administration. Morris water maze and Y-maze test were performed to examine the behavioral disorders. Moreover, hippocampal neuronal cell apoptosis and expression of autophagy related genes were detected. Sevoflurane induced cognitive dysfunction in mice showing significant longer escape latency, lower number of correct response, higher apoptotic neurons, and higher expression of autophagy related genes. However, additional 3-MA administration inhibited the effect of sevoflurane on cognitive dysfunction by shorting escape latency, reducing correct response number, inhibiting neurons apoptosis and autophagy genes expression. 3-MA additional administration inhibited sevoflurane anesthesia-induced cognitive dysfunction on mice. 3-MA might be usefull as an inhibitor for sevoflurane anesthesia-induced cognitive dysfunction in clinical trials.

Equity in maternal and child health care utilization in Guangdong province of China 2009-2019: A retrospective analysis.

Background: Equity is the principal challenge of maternal and child health care (MCH) across the world, especially in China. Existing researches focused on equity in MCH resources and outcomes. There is an evidence gap regarding equity of MCH services utilization, revealing the black box between equity in MCH resources and MCH outcomes. In the study, we evaluate the changes of equity in integrated MCH service utilization in Guangdong province of China during 2009-2019. Methods: Data used in this study are from the Guangdong Maternal and Child Health Routine Reporting System and the Guangdong Health Statistical Yearbook (2009-2019). The Gini coefficient (G) and Theil index (T) were employed to assess equity and source of inequity in four geographic regions of Guangdong province. Results: Generally, among the integrated MCH care, coverage of pre-pregnancy care (<50%) is lower than in other stages. In the past decade, inequity of MCH care in the Equalization of Essential Public Health Service (EEPHS) program has gradually reduced to G < 0.1. Screening of genetic metabolic disease and of hearing showed largest reductions of inequity (G reducing from 0.3-0.4 to 0.03-0.04). Inequity in reproductive health tests for brides-to-be, psychological assessment and consultation, education classes for mother-to-be and health management of children under 3 were mainly contributed by intra-region disparities in 2019. Conclusion: Equity has gradually improved in the last decade in Guangdong. The national EEPHS program and the Integrated Prevention of Mother-to-Child Transmission of HIV, Syphilis and HBV of Guangdong have played important roles in reducing inequity in MCH service utilization. Further strategies, targeting pre-pregnancy reproductive healthcare, psychological assessments and consultations for the pregnant and education classes for mothers-to-be, should be taken to promote coverage and equity.

Association of Interpregnancy Interval With Adverse Birth Outcomes.

Importance: Many studies have reported an association of interpregnancy interval (IPI) between 2 consecutive births with adverse birth outcomes in low- and middle-income countries. However, most of these studies ignore the implications of some unmeasured confounders. Objective: To explore the association of IPI with adverse perinatal outcomes. Design, Setting, and Participants: This large-scale cohort study used the Guangdong Provincial Women and Children Health Information System in Guangdong Province, China, to obtain birth data recorded between January 1, 2014, and December 31, 2020. Matched-sibling design was used. The final cohort included first-born and second-born sibling pairs delivered by mothers who were permanent residents of Guangdong Province. Exposures: The exposure variable was IPI, which was categorized as follows: less than 6, 6 to 11, 12 to 17, 18 to 23, 24 to 29, 30 to 35, and 36 or more months. Main Outcomes and Measures: The outcome variables were adverse birth outcomes: preterm birth (PTB, gestational age <37 weeks), low birth weight (LBW, <2500 g), and small for gestational age (SGA). Adjusted odds ratio (OR) and interaction odds ratio (IOR) associated with IPI were calculated. Results: The study consisted of 725 392 sibling pairs of multiparous mothers. Among these mothers, 718 111 (99.0%) were aged 20 to 34 years, and 715 583 (98.7%) were of Han Chinese ethnicity. Unmatched analysis showed that a short IPI of less than 6 months was associated with higher risks of PTB (adjusted OR, 1.96; 95% CI, 1.87-2.06), LBW (adjusted OR, 1.88; 95% CI, 1.79-1.98), and SGA (adjusted OR, 1.34; 95% CI, 1.30-1.38) compared with an IPI of 18 to 23 months. These associations were attenuated in the matched-sibling analysis. An association of short IPI (<6 months) with PTB (adjusted IOR, 1.40; 95% CI, 1.30-1.51), LBW (adjusted IOR, 1.30; 95% CI, 1.21-1.40), and SGA (adjusted IOR, 1.16; 95% CI, 1.11-1.22) remained in the matched analysis. For IPI of 36 months or more, the odds of PTB (adjusted OR, 1.08; 95% CI, 1.03-1.14) and LBW (adjusted OR, 1.13; 95% CI, 1.07-1.19) in the unmatched analysis were also greater than the reference interval (18-23 months), but not for SGA (adjusted OR, 0.96; 95% CI, 0.93-0.99). Associations between a long IPI (≥36 months) and PTB (adjusted IOR, 1.10; 95% CI, 1.02-1.19) and LBW (adjusted IOR, 1.16; 95% CI, 1.07-1.26) remained through the sibling comparisons. Conclusions and Relevance: Results of this study indicated that mothers with a short (<6 months) or long (≥36 months) IPI had greater odds of adverse birth outcomes. The findings may inform family planning policies and guide individuals and families who are planning for another pregnancy in China.

Associations between ambient heat exposure early in pregnancy and risk of congenital heart defects: a large population-based study.

Some epidemiological studies have confirmed the association between environmental factors and congenital heart defects (CHD). While the possibility that maternal ambient heat exposures are related to CHD has received little attention. Our study aims to investigate the association between maternal ambient extreme heat exposure early in pregnancy and the risk of CHD in offspring in China. We conducted a retrospective cohort study of 1,918,105 fetuses between 2 and 8 weeks after gestation from May to October in Guangdong, China, 2015-2019. The main heat exposure was defined as extreme heat events (EHE) by using the 90th (EHE90) or 95th (EHE95) percentile of the daily maximum temperature. For each EHE definition, we further defined four indicators: having EHE or not, frequency, duration, and cumulative days. We used the log-binomial regression models to calculate the prevalence ratios (PR) of CHD with 95% confidence intervals (CI) for the associations between CHD and EHE, adjusted for potentially confounding covariates. There are 1,918,105 infants included in the study, of which 9588 had CHD, with a prevalence rate of 499.9 per 100,000 (95% CI: 489.9, 509.8). We found that all EHE indicators were positively associated with the increased risks of overall CHD, some CHD classes (congenital malformations of cardiac septa, congenital malformations of great arteries, and congenital malformations of great arteries), and some CHD subtypes (atrial septal defect and patent ductus arteriosus). In addition, the PR yielded higher estimates when exposing to EHE95. For instance, the risk of suffering congenital malformations of great arteries was 1.548 (95% CI: 1.401, 1.712) for EHE90 exposure and 1.723 (95% CI: 1.565, 1.898) for EHE95 exposure, respectively. Our study demonstrated that EHE during 2-8 weeks postconception was associated with overall CHD in offspring, particularly atrial septal defects and patent ductus arteriosus. The associations strengthened with the extent and cumulative days of maternal exposure to EHE.

Spatio-Temporal Distribution and Demographic Characteristics of Congenital Heart Defects in Guangdong, China, 2016-2020.

Background: Congenital heart defects are the most common type of birth defects and bring a heavy disease burden in China. Examining the temporal and spatial trends of congenital heart defects epidemics can give some elementary knowledge for succeeding studies. Objective: To characterize the spatial-temporal patterns of the prevalence of congenital heart defects based on a substantial cohort of the perinatal fetus in south China in 2016-2020. Methods: This study was a retrospective population-based cohort study conducted in Guangdong, China from 2016 to 2020. Pregnant women and their infants received birth defect surveillance during pregnancy and seven days after delivery in more than 1,900 midwifery hospitals in 21 cities. Perinatal infants with congenital heart defects were identified and enrolled. The prevalence of congenital heart defects was calculated according to cities, years, urban and rural areas, regions of Guangdong, categories of maternal age at delivery, seasons of delivery, and infant's gender. Results: A total of 8,653,206 perinatal infants and 53,912 total congenital heart defects were monitored in Guangdong, including 46,716 (86.65%) without other defects and 7,736 (13.35%) with other defects. The average prevalence of total congenital heart defects was 62.30/10,000 (95% CI, 61.78/10,000-62.83/10,000), congenital heart defects without other defects was 53.36/10,000 (95% CI, 52.88/10,000-53.85/10,000), and congenital heart defects with other defects was 8.94/10,000 (95%CI, 8.74/10,000-9.14/10,000). From 2016 to 2020, the prevalence of total congenital heart defects was 54.92/10,000, 54.23/10,000, 63.79/10,000, 73.11/10,000, 68.20/10,000, respectively. We observed geographical variations within the prevalence of congenital heart defects. The prevalence of congenital heart defects was much higher in the Pearl River Delta region than in the non-Pearl River Delta region, as well as higher in urban areas than in rural areas. Conclusion: The findings of this study are helpful to the understanding of the etiology and epidemiology characteristics of congenital heart defects in south China. Our data likely reflect a better estimate of the spatiotemporal trends in congenital heart defects prevalence than reported previously.

Congenital anomalies associated with ambient temperature variability during fetal organogenesis period of pregnancy: Evidence from 4.78 million births.

BACKGROUNDS: Evidence for the effects of temperature variability on risk of congenital anomalies is lacking. We aimed to examine the association of temperature variability during fetal organogenesis period (weeks 3-8 post-conception) with major congenital anomalies. METHODS: A retrospective cohort study comprising 4,787,356 singleton live-births and stillbirths in China was performed. We defined two temperature variability indices within gestational week i: the standard deviation (SD) of daily temperature (TVSDi) and the maximum day-to-day temperature difference (TVDi). At 6-week long timescales, we computed the SD of daily temperature (TVSD3-8) and the average value of TVDi (TVD3-8). We matched two temperature variability indices, pollutant exposure levels over entire exposure window and data of each mother-infant pairs. An extended generalized estimating equation log-binomial regression model was constructed to explore their associations after adjusting for individual characters, temperature extremes and air pollutants. Stratified and sensitivity analyses were also performed. RESULTS: 59,571 neonates were registered as major congenital anomalies besides genetic and chromosomal anomalies. At weekly levels, the highest risk estimates of two temperature variability indices occurred at the 5th week for most anomaly groups. All TVSD5, TVD5, and maximum weekly TVSD and TVD were significantly associated with all anomaly groups; with the increment of 1 °C, the estimated risk ratio (RR) and corresponding 95% confidence interval (CI) ranges from 1.03 (1.01-1.05) to 1.19 (1.08-1.31). At 6-week scales, TVSD3-8 and TVD3-8 were associated with most anomaly subgroups. Overall, the strongest associations were estimated for isolated defects among morphology subgroups and cardiac defects among type subgroups. CONCLUSIONS: Exposure to temperature variability during fetal organogenesis period of pregnancy is associated with increased risk of major congenital defects. Our findings provide a research foundation for public health policies, and further mechanism investigation.

Prevalence of cleft lip and/or cleft palate in Guangdong province, China, 2015-2018: a spatio-temporal descriptive analysis.

OBJECTIVES: This study aimed to investigate the temporal and spatial characteristics of cleft lip and/or palate based on a large-scale birth defect monitoring database. METHODS: Data on perinatal infants and children with cleft lip and/or palate defects from 1 January 2015 to 31 December 2018 in Guangdong province of China were collected. The variables including the demographic data, basic family information (address, education level, etc.), the infant's birth weight, gender and other basic parameters were collected and analysed. RESULTS: During the study period, the prevalence of cleft lip and/or palate was 7.55 per 10 000 perinatal infants. The prevalence of cleft lip, cleft palate and cleft lip and palate were 2.34/10 000, 2.22/10 000 and 2.98/10 000, respectively. The prevalence of cleft lip and/or palate showed a pronounced downward trend, reducing from 8.47/10 000 in 2015 to 6.51/10 000 in 2018. We observed spatial heterogeneity of prevalence of cleft lip and/or palate across the study period in Guangdong. In the Pearl River Delta region, the overall prevalence of cleft lip and/or palate was 7.31/10 000, while the figure (7.86/10 000) was slightly higher in the non-Pearl River Delta region (p<0.05). Concerning infant gender, the prevalence was in general higher in boys than girls (p<0.05). In addition, the higher prevalence was more common in mothers older than 35 years old. For the birth season, infants born in spring tended to have a higher prevalence than those born in other seasons, regardless of the prevalence of cleft lip and palate calculated separately or jointly (p<0.05). The majority of newborns with cleft lip and palate were accompanied by other birth defects. CONCLUSION: This study contributes a better understanding of the characteristics of spatio-temporal trends for birth defects of cleft lip and/or palate in south China.

Ambient air pollution and markers of fetal growth: A retrospective population-based cohort study of 2.57 million term singleton births in China.

BACKGROUNDS: Evidence is scarce on the relation between maternal exposure to ambient air pollution during pregnancy and fetal growth in developing countries. Moreover, the current evidence is inconsistent. We aimed to investigate the association of trimester-specific exposure to air pollution with risk of being born small for gestational age (SGA) and birth weight-markers of fetal growth-among Chinese term births. METHODS: This retrospective population-based cohort study consisted of 2,567,457 singleton term live-births from January 1, 2014 to December 31, 2017 across 123 Chinese districts and counties. Personal exposure to ambient air pollutants including carbon monoxide (CO), sulfur dioxide (SO2), nitrogen dioxide (NO2), ozone (O3), particulate matter with aerodynamic diameter < 2.5 µm (PM2.5), and PM10 was assigned using the inverse distance weighting spatial interpolation algorithm. Generalized estimating equations (GEE) logistic regression models were performed to estimate the associations between trimester-specific exposure to air pollution and risk of SGA or low birth weight (LBW), and GEE linear regression to examine the associations between the exposure and term birth weight, adjusting for maternal demographics, maternal cigarette smoking status during pregnancy, mode of delivery, gravidity, gestational age, year and month of conception, neonate's sex, and meteorological factors. Stratified and sensitivity analyses were also performed. RESULTS: When mother exposed to ambient air pollutants over the entire pregnancy, per IQR increment (0.122 mg/m3) in ambient CO concentrations was associated with higher risk of SGA (odds ratio (OR) = 1.04, 95% confidence interval (CI): 1.02, 1.05) and reduced birth weight among term births (-5.95 g, 95% CI: -8.01, -3.89). This association was also pronounced in the second and third trimesters. Term birth weight was negatively associated with per IQR increase of O3 (-3.52 g, 95% CI: -6.23, -0.81), PM2.5 (-5.93 g, 95% CI: -8.36, -3.49) and PM10 (-7.78 g, 95% CI: -10.41, -5.16) during the entire pregnancy, respectively. No significant association was detected between maternal exposure to air pollutants and term LBW. Effect estimates of heterogeneity suggested that maternal age and infant sex modified the impact of air pollution on birth weight. CONCLUSIONS: The findings suggest that maternal exposure to air pollution during pregnancy is adversely affecting fetal growth. Further studies are warranted to integrate these findings and take clinical or public health interventions in pregnancy.

Erratum: microRNA-34a overexpression inhibits cell migration and invasion via regulating SIRT1 in hepatocellular carcinoma.

[This corrects the article DOI: 10.3892/ol.2017.7090.].

MiR-103 alleviates autophagy and apoptosis by regulating SOX2 in LPS-injured PC12 cells and SCI rats.

OBJECTIVES: Recent studies revealed that microRNAs (miRNAs) may play crucial roles in the responses and pathologic processes of spinal cord injury (SCI). This study aimed to investigate the effect and the molecular basis of miR-103 on LPS-induced injuries in PC12 cells in vitro and SCI rats in vivo. MATERIALS AND METHODS: PC12 cells were exposed to LPS to induce cell injuries to mimic the in vitro model of SCI. The expression of miR-103 and SOX2 in PC12 cells were altered by transient transfections. Cell viability and apoptotic cell rate were measured by CCK-8 assay and flow cytometry assay. Furthermore, Western blot analysis was performed to detect the expression levels of apoptosis- and autophagy- related proteins, MAPK/ERK pathway- and JAK/STAT pathway-related proteins. In addition, we also assessed the effect of miR-103 agomir on SCI rats. RESULTS: LPS exposure induced cell injuries in PC12 cells. miR-103 overexpression significantly increased cell viability, reduced cell apoptosis and autophagy, and opposite results were observed in miR-103 inhibition. miR-103 attenuated LPS-induced injuries by indirect upregulation of SOX2. SOX2 overexpression protected PC12 cells against LPS-induced injuries, while SOX2 inhibition expedited LPS-induced cell injuries. Furthermore, miR-103 overexpression inhibited MAPK/ERK pathway and JAK/STAT pathway through upregulation of SOX2. We also found that miR-103 agomir inhibited cell apoptosis and autophagy in SCI rats. CONCLUSION: This study demonstrates that miR-103 may represent a protective effect against cell apoptosis and autophagy in LPS-injured PC12 cells and SCI rats by upregulation of SOX2 expression.

Decreased hospital charges and postoperative pain in septoplasty by application of enhanced recovery after surgery.

OBJECTIVE: Septoplasty has been the definitive treatment for nasal septum deviation, but its postoperative procedure may affect patients' quality of life. While new procedures in general surgery, such as enhanced recovery after surgery (ERAS), can speed up postoperative rehabilitations to improve quality of life, it is rarely applied in the ear-nose-throat field. This study therefore aims to evaluate the application of ERAS in patients with nasal septum deviation as a means of improving perioperative outcomes. MATERIALS AND METHODS: Fifty patients with nasal septum deviation undergoing septoplasty were randomized as ERAS or control group (25 patients in both groups). Patients were investigated for outcomes including length of stay, operating time, bleeding volume, total cost, complications, and Self-Rating Anxiety Scale (SAS) and visual analog symptom score of nasal obstruction, sleep disturbance, and head facial pain. RESULTS: The preoperative anxiety in ERAS group (SAS 35.4±6.2) was lower than the control group (SAS 43.6±8.6). The anxiety levels in ERAS group (SAS 31.6±5.4) was also reduced compared to the control group (SAS 38.1±10.4) in the 3 days postsurgery, but showed no significant difference thereafter at 7 days postsurgery. In addition, the length of stay and total cost were significantly lower for the ERAS group as well. The visual analog symptom score of nasal obstruction, sleep disturbance, and head facial pain in ERAS group were all also found to be lower than the control group. The only outcomes with no significant differences were the operation time, blood volume, and complications between the groups. CONCLUSION: Our study indicated ERAS application can reduce hospital charges and postoperative pain in septoplasty, thereby improving patient quality of life and hospital expenses at the same time.

microRNA-34a overexpression inhibits cell migration and invasion via regulating SIRT1 in hepatocellular carcinoma.

Hepatocellular carcinoma (HCC) remains one of the most common types of malignancy with high mortality and morbidity rates. Previous studies have suggested that microRNAs (miRs) serve pivotal functions in various types of tumor. The aim of the present study was to assess the association between miR-34a expression and HCC cell migration and invasion, and the potential underlying mechanisms. The miR-34a overexpression vector or scramble control was transfected into human Hep3B and Huh7 cell lines. Transwell assays, and Matrigel and wound healing assays were used to detect the effects of miR-34a expression on HCC cell invasion and migration, respectively. The expression of miR-34a and the mRNA expression of other associated proteins were detected using quantitative reverse transcription polymerase chain reaction, and protein levels were measured using western blot analysis. Compared with the control, miR-34a expression was significantly downregulated in Hep3B and Huh7 cells, but this was reversed by the transfection with exogenous miR-34a (P<0.01). The number of migrated or invaded cells was significantly reduced by the overexpression of miR-34a in Hep3B or Huh7 cells (P<0.01). The expression of sirtuin 1 was upregulated, while the level of acetylate-p53 was downregulated by overexpression of miR-34a. Taken together, the results of the present study suggested that the overexpression of miR-34a may have suppressed HCC metastasis via inhibited cell migration and invasion.

Isoflurane anesthesia induces liver injury by regulating the expression of insulin-like growth factor 1.

It has been suggested that isoflurane may cause perioperative liver injury. However, the mechanism of its action remains unknown. The purpose of the present study was to determine this possible mechanism. Sprague-Dawley rats were randomly assigned into one of three groups (all n=12): Control group (exposed to mock anesthesia), isoflurane group (exposed to 2% isoflurane for 90 min), and isoflurane + insulin-like growth factor 1 (IGF-1) group (exposed to 2% isoflurane for 90 min and then treated with IGF-1). Reverse transcription-quantitative polymerase chain reaction (RT-qPCR) and western blotting were conducted to determine the levels of expression of IGF-1 and its receptor IGF-R. Liver necrosis was assessed by histological examination. TUNEL assay was performed to determine the apoptosis of hepatic cells. In addition, the levels of the proteins caspase-3 and B-cell lymphoma-extra large (Bcl-xL) were measured. Compared with the control group, levels of IGF-1 and IGF-1R mRNA and protein were significantly decreased following exposure to isoflurane (all P<0.05). The necrosis rate and liver apoptosis were significantly increased in the group treated with isoflurane alone compared with the control group (P<0.05), but were significantly decreased compared with the isoflurane group following application of IGF-1 (P<0.05). Additionally, isoflurane exposure significantly increased levels of caspase-3 compared with the control group (P<0.05), but decreased levels of Bcl-xL (P<0.05). By contrast, application of IGF-1 reversed these changes. The present study therefore suggests that isoflurane induces liver injury in part by regulating the expression of IGF-1 and that application of IGF-1 may protect against liver injury induced by isoflurane exposure.

Evaluation of Neuroprotective Effect of Thymoquinone Nanoformulation in the Rodent Cerebral Ischemia-Reperfusion Model.

The purpose of the present study was to evaluate the neuroprotective efficacy of optimized thymoquinone loaded PLGA-chitosan nanoparticles delivered via nose to brain route in the rodent cerebral ischemia-reperfusion model. The neuroprotective efficacy of the optimized thymoquinone loaded PLGA-chitosan nanoparticles was evaluated in middle cerebral artery occluded rats by various pharmacodynamic and biochemical studies. The pharmacokinetics of thymoquinone loaded PLGA-chitosan nanoparticles in the brain and blood plasma together with qualitative localization of florescent labelled PLGA-chitosan nanoparticles in brain tissues were also determined. Intranasal delivery of optimized thymoquinone loaded PLGA-chitosan nanoparticles (183.5 ± 8.2 nm, 33.63 ± 2.25 mV) to brain significantly reduced the ischemia infarct volume and enhanced the locomotor activity and grip strength in the middle cerebral artery occluded rats. Biochemical studies showed that intranasal delivery of thymoquinone loaded PLGA-chitosan nanoparticles significantly reduced the lipid peroxidation but elevated the glutathione, catalase, and superoxide dismutase in the brain of middle cerebral artery occluded rats. The pharmacokinetic and localization studies showed that thymoquinone loaded PLGA-chitosan nanoparticles facilitated the delivery of thymoquinone to brain by intranasal nose to brain transport pathways and enhanced their pharmacokinetic profile in brain tissues. Thus, intranasal delivery of thymoquinone loaded PLGA-chitosan nanoparticles to brain could be potentially used for the neuroprotection and treatment of cerebral ischemia.

Diabetes Worsens Ischemia-Reperfusion Brain Injury in Rats Through GSK-3ß.

BACKGROUND: Diabetes aggravates brain injury after cerebral ischemia/reperfusion (I/R). OBJECTIVE: To investigate whether limb I/R causes cerebral injury in a rat diabetes model and whether glycogen synthase kinase-3ß (GSK-3ß) is involved. METHODS: Male adult Sprague-Dawley rats were assigned into streptozotocin-induced diabetes (n = 30; blood glucose ≥16.7 mmol/L) or control (n = 20) groups, further subdivided into diabetes I/R (3-hour femoral artery/vein clamping), diabetes-I/R + TDZD-8 (I/R plus GSK-3ß inhibitor), diabetes-sham, control-sham and control-I/R groups (n = 10 each). Cortical and hippocampal morphology (hematoxylin/eosin); hippocampal CA1 apoptosis (TUNEL assay); cleaved caspase-3 (apoptosis), and Iba1 (microglial activation) protein expression (immunohistochemistry); phosphorylated/total GSK-3ß and nuclear factor-κB (NF-κB) protein levels (Western blotting); and serum and brain tissue tumor necrosis factor (TNF)-α levels (enzyme-linked immunosorbent assay) were analyzed. RESULTS: The diabetes-I/R group showed greater cortical and hippocampal injury, apoptosis, cleaved caspase-3 expression and Iba1 expression than the control-I/R group; TDZD-8 reduced injury/apoptosis and cleaved caspase-3/Iba1 expressions. The diabetes-I/R group had lower p-GSK-3ß and p-NF-κBp65 expression than the control-I/R group (P < 0.05); TDZD-8 increased p-GSK-3ß expression but decreased p-NF-κBp65 expression (P < 0.05). The diabetes-I/R group showed higher elevation of serum and brain tissue TNF-α than the control-I/R group (P < 0.05); TDZD-8 reduced TNF-α production. CONCLUSIONS: Diabetes exacerbates limb I/R-induced cerebral damage and activates NF-κB and GSK-3ß.

Curcumin improves bone microarchitecture in glucocorticoid-induced secondary osteoporosis mice through the activation of microRNA-365 via regulating MMP-9.

The present study aimed to investigate bone microarchitecture of the proximal tibia in glucocorticoid-induced osteoporosis (GIOP) mice, and the underlying molecular mechanisms of curcumin in DXM-induced osteoporosis were performed. DXM-treated facilitated to induce hypercalciuria in mice, and curcumin-treated showed a decrease in urine calcium. Curcumin reversed DXM-induced bone resorption, including an increase in serum OCN and a decrease in bone resorption markers CTX and TRAP-5b. H&E staining showed the increased disconnections and separation in trabecular bone network as well as the reduction of trabecular thickness throughout the proximal metaphysis of tibia in GIOP group. Importantly, curcumin reversed DXM-induced trabecular deleterious effects and stimulated bone remodeling. The further evidence showed that curcumin supplement significantly decreased the TRAP-positive stained area and inhibited the activity of OPG/RANKL/RANK signaling in the GIOP mice. Moreover, bioinformatics analysis suggested that miR-365 was a regulator of MMP9. The levels of miR-365 were markedly suppressed; however, curcumin treatment could reverse the downregulation of miR-365 in the tibia of GIOP mice. Simultaneously, the results demonstrated that the mRNA and protein expression of MMP-9 were significantly increased in GIOP mice compared with that of the control group. Curcumin treatment could suppress the expression of MMP-9 in the tibia of GIOP mice. The present study demonstrated the protective effects of curcumin against bone deteriorations in the experimentally DIOP mice, and the underlying mechanism was mediated, at least partially, through the activation of microRNA-365 via suppressing MMP9.