Efficacy of Procyanidins against In Vivo Cellular Oxidative Damage: A Systematic Review and Meta-Analysis

Aims

In this study, the efficacy of proanthocyanidins (PCs) against oxidative damage was systematically reviewed to facilitate their use in various applications.

Methods

A meta-analysis was performed by two researchers. Each investigator independently searched electronic databases, including Cochrane, PubMed, Springer, Web of Science, China National Knowledge Infrastructure (CKNI), China Science and Technology Journal Database (CSTJ), and WanFang Data, and analyzed published data from 29 studies on the effects of PCs against oxidative damage. Oxidative stress indexes included superoxide dismutase (SOD), malondialdehyde (MDA), catalase (CAT), glutathione (GSH), glutathione peroxidase (GPx), and total antioxidative capacity (T-AOC).

Results

Compared with the oxidative damage model group, PCs effectively improved the T-AOC, SOD, GSH, GPx, and CAT levels, and reduced the MDA levels; these differences were statistically significant (P < 0.05). In studies that used the gavage method, SOD (95% CI, 2.33–4.00) and GPx (95% CI, 2.10–4.05) were 3.16-fold and 3.08-fold higher in the PC group than in the control group, respectively. In studies that used the feeding method, SOD (95% CI, 0.32–1.74) and GPx (95% CI, -0.31 to 1.65) were 1.03-fold and 0.67-fold higher in the PC group than in the control group, respectively. Statistically significant differences in the effects of PCs (P < 0.00001) were observed between these two methods. MDA estimated from tissue samples (95% CI, -5.82 to -2.60) was 4.32-fold lower in the PC group than in the control group. In contrast, MDA estimated using serum samples (95% CI, -4.07 to -2.06) was 3.06-fold lower in the PC group than in the control group. The effect of PCs on MDA was significantly greater in tissue samples than in serum samples (P = 0.02).

Conclusion

PCs effectively antagonize oxidative damage and enhance antioxidant capacity. The antagonistic effect may be related to intervention time, intervention method, and the source from which the indexes are estimated.     

Effects of Break Crops on Yield and Grain Protein Concentration of Barley in a Boreal Climate

Rotation with dicotyledonous crops to break cereal monoculture has proven to be beneficial to successive cereals. In two fields where the soil had been subjected to prolonged, continuous cereal production, two 3-year rotation trials were established. In the first year, faba bean, turnip rape and barley were grown, as first crops, in large blocks and their residues tilled into the soil after harvest. In the following year, barley, buckwheat, caraway, faba bean, hemp and white lupin were sown, as second crops, in each block and incorporated either at flowering stage (except barley) or after harvest. In the third year, barley was grown in all plots and its yield and grain protein concentration were determined. Mineral N in the plough layer was determined two months after incorporation of crops and again before sowing barley in the following year. The effect of faba bean and turnip rape on improving barley yields and grain protein concentration was still detectable two years after they were grown. The yield response of barley was not sensitive to the growth stage of second crops when they were incorporated, but was to different second crops, showing clear benefits averaging 6-7% after white lupin, faba bean and hemp but no benefit from caraway or buckwheat. The effect of increased N in the plough layer derived from rotation crops on barley yields was minor. Incorporation of plants at flowering stage slightly increased third-year barley grain protein concentration but posed a great potential for N loss compared with incorporation of crop residues after harvest, showing the value of either delayed incorporation or using catch crops.     

Land Use/Cover Change in the Middle Reaches of the Heihe River Basin over 2000-2011 and Its Implications for Sustainable Water Resource Management

The Heihe River Basin (HRB) is a typical arid inland river basin in northwestern China. From the 1960s to the 1990s, the downstream flow in the HRB declined as a result of large, artificial changes in the distribution of water and land and a lack of effective water resource management. Consequently, the ecosystems of the lower reaches of the basin substantially deteriorated. To restore these degraded ecosystems, the Ecological Water Diversion Project (EWDP) was initiated by the Chinese government in 2000. The project led to agricultural and ecological changes in the middle reaches of the basin. In this study, we present three datasets of land use/cover in the middle reaches of the HRB derived from Landsat TM/ETM+ images in 2000, 2007 and 2011. We used these data to investigate changes in land use/cover between 2000 and 2011 and the implications for sustainable water resource management. The results show that the most significant land use/cover change in the middle reaches of the HRB was the continuous expansion of farmland for economic interests. From 2000 to 2011, the farmland area increased by 12.01%. The farmland expansion increased the water resource stress; thus, groundwater was over-extracted and the ecosystem was degraded in particular areas. Both consequences are negative and potentially threaten the sustainability of the middle reaches of the HRB and the entire river basin. Local governments should therefore improve the management of water resources, particularly groundwater management, and should strictly control farmland reclamation. Then, water resources could be ecologically and socioeconomically sustained, and the balance between upstream and downstream water demands could be ensured. The results of this study can also serve as a reference for the sustainable management of water resources in other arid inland river basins.     

miR-326 Targets Antiapoptotic Bcl-xL and Mediates Apoptosis in Human Platelets

Platelets play crucial roles in hemostasis, thrombosis, wound healing, inflammation, angiogenesis, and tumor metastases. Because they are anucleated blood cells, platelets lack nuclear DNA, but they do contain mitochondrial DNA, which plays a key role in regulating apoptosis. Recent evidence has suggested that miRNAs are also involved in regulating gene expression and apoptosis in platelets. Our previous study showed that the expression of miR-326 increased visibly when apheresis platelets were stored in vitro. The antiapoptotic Bcl-2 family regulator Bcl-xL has been identified as a putative target of miR-326. In the present study, dual reporter luciferase assays were used to characterize the function of miR-326 in the regulation of the apoptosis of platelet cells. These assays demonstrated that miR-326 bound to the 3′-translated region of Bcl-xL. To directly assess the functional effects of miR-326 expression, levels of Bcl-xL and the apoptotic status of stored apheresis platelets were measured after transfection of miR-326 mimic or inhibitor. Results indicated that miR-326 inhibited Bcl-xL expression and induced apoptosis in stored platelets. Additionally, miR-326 inhibited Bcl-2 protein expression and enhanced Bak expression, possibly through an indirect mechanism, though there was no effect on the expression of Bax. The effect of miR-326 appeared to be limited to apoptosis, with no significant effect on platelet activation. These results provide new insight into the molecular mechanisms affecting differential platelet gene regulation, which may increase understanding of the role of platelet apoptosis in multiple diseases.     

Anti-Inflammatory Effects of Ang-(1-7) in Ameliorating HFD-Induced Renal Injury through LDLr-SREBP2-SCAP Pathway

The angiotensin converting enzyme 2-angiotensin-(1–7)-Mas axis (ACE2-Ang-(1–7)-Mas axis) is reported to participate in lipid metabolism in kidney, but its precise effects and underlying mechanisms remain unknown. We hypothesized that Ang-(1–7) reduces lipid accumulation and improves renal injury through the low density lipoprotein receptor–sterol regulatory element binding proteins 2–SREBP cleavage activating protein (LDLr-SREBP2-SCAP) system by suppressing inflammation in high fat diet (HFD)-fed mice. In this study, male C57BL/6 mice were randomized into four groups: STD (standard diet)+saline, HFD+saline, HFD+Ang-(1–7) and STD+Ang-(1–7). After 10 weeks of feeding, mice were administered Ang-(1–7) or saline for two weeks. We found that high inflammation status induced by HFD disrupted the LDLr-SREBP2-SCAP feedback system. Treatment of mice fed a high-fat diet with Ang-(1–7) induced significant improvement in inflammatory status, following the downregulation of LDLr, SREBP2 and SCAP, and then, decreased lipid deposition in kidney and improved renal injury. In conclusion, the anti-inflammatory effect of Ang-(1–7) alleviates renal injury triggered by lipid metabolic disorders through a LDLr- SREBP2-SCAP pathway.     

Ultrasound-Assisted Thoracic Paravertebral Block Reduces Intraoperative Opioid Requirement and Improves Analgesia after Breast Cancer Surgery: A Randomized,Controlled, Single-Center Trial

Objectives

The contribution of ultrasound-assisted thoracic paravertebral block to postoperative analgesia remains unclear. We compared the effect of a combination of ultrasound assisted-thoracic paravertebral block and propofol general anesthesia with opioid and sevoflurane general anesthesia on volatile anesthetic, propofol and opioid consumption, and postoperative pain in patients having breast cancer surgery.

Methods

Patients undergoing breast cancer surgery were randomly assigned to ultrasound-assisted paravertebral block with propofol general anesthesia (PPA group, n = 121) or fentanyl with sevoflurane general anesthesia (GA group, n = 126). Volatile anesthetic, propofol and opioid consumption, and postoperative pain intensity were compared between the groups using noninferiority and superiority tests.

Results

Patients in the PPA group required less sevoflurane than those in the GA group (median [interquartile range] of 0 [0, 0] vs. 0.4 [0.3, 0.6] minimum alveolar concentration [MAC]-hours), less intraoperative fentanyl requirements (100 [50, 100] vs. 250 [200, 300]μg,), less intense postoperative pain (median visual analog scale score 2 [1, 3.5] vs. 3 [2, 4.5]), but more propofol (median 529 [424, 672] vs. 100 [100, 130] mg). Noninferiority was detected for all four outcomes; one-tailed superiority tests for each outcome were highly significant at P<0.001 in the expected directions.

Conclusions

The combination of propofol anesthesia with ultrasound-assisted paravertebral block reduces intraoperative volatile anesthetic and opioid requirements, and results in less post operative pain in patients undergoing breast cancer surgery.

Trial Registration

ClinicalTrial.gov NCT00418457     

Mutations in QARS,Encoding Glutaminyl-tRNA Synthetase,Cause Progressive Microcephaly,Cerebral-Cerebellar Atrophy,and Intractable Seizures

Progressive microcephaly is a heterogeneous condition with causes including mutations in genes encoding regulators of neuronal survival. Here, we report the identification of mutations in QARS (encoding glutaminyl-tRNA synthetase [QARS]) as the causative variants in two unrelated families affected by progressive microcephaly, severe seizures in infancy, atrophy of the cerebral cortex and cerebellar vermis, and mild atrophy of the cerebellar hemispheres. Whole-exome sequencing of individuals from each family independently identified compound-heterozygous mutations in QARS as the only candidate causative variants. QARS was highly expressed in the developing fetal human cerebral cortex in many cell types. The four QARS mutations altered highly conserved amino acids, and the aminoacylation activity of QARS was significantly impaired in mutant cell lines. Variants p.Gly45Val and p.Tyr57His were located in the N-terminal domain required for QARS interaction with proteins in the multisynthetase complex and potentially with glutamine tRNA, and recombinant QARS proteins bearing either substitution showed an over 10-fold reduction in aminoacylation activity. Conversely, variants p.Arg403Trp and p.Arg515Trp, each occurring in a different family, were located in the catalytic core and completely disrupted QARS aminoacylation activity in vitro. Furthermore, p.Arg403Trp and p.Arg515Trp rendered QARS less soluble, and p.Arg403Trp disrupted QARS-RARS (arginyl-tRNA synthetase 1) interaction. In zebrafish, homozygous qars loss of function caused decreased brain and eye size and extensive cell death in the brain. Our results highlight the importance of QARS during brain development and that epilepsy due to impairment of QARS activity is unusually severe in comparison to other aminoacyl-tRNA synthetase disorders.     

MicroRNA-141 promotes the proliferation of non-small cell lung cancer cells by regulating expression of PHLPP1 and PHLPP2

The dysregulation of microRNAs (miRNAs) is crucially implicated in the development of various cancers. In this study, we explored the biological role of miR-141 in non-small cell lung cancer (NSCLC). miR-141 expression was significantly up-regulated in NSCLC tissues, and its overexpression accelerated NSCLC cell proliferation in vitro and tumor growth in vivo. We subsequently identified the antagonists of PI3K/AKT signaling, PH domain leucine-rich-repeats protein phosphatase 1 (PHLPP1) and PHLPP2, as direct targets of miR-141. Re-introduction of PHLPP1 and PHLPP2 abrogated miR-141-induced proliferation of NSCLC cells. Together, the results of this study suggest that miR-141 and its targets PHLPP1 and PHLPP2 play critical roles in NSCLC tumorigenesis, and provide potential therapeutic targets for NSCLC treatment.