Effects of sodium hyaluronate combined with rhEGF eye drops in patients with dry eye.

To analyze the effects of sodium hyaluronate combined with recombinant human epidermal growth factor (rhEGF) eye drops in patients with dry eye. Totally 97 patients who suffered dry eye after cataract surgery in our hospital from March 2018 to June 2020 were selected and randomly assigned into control group (n=57, sodium hyaluronate eye drops) and intervention group (n=63, sodium hyaluronate combined with rhEGF eye drops). The clinical efficacy, Break Up Time (BUT), schirmer I test (SLt), fluorescent test (FL) and ocular surface disease index (OSDI), the scale of quality of life for disease with visual impairment (SQOL-DVI), interleukin-6 (IL-6), tumor necrosis factor (TNF-a) level of the two groups were compared. The intervention group yielded remarkably higher effective rate than the control group (p<0.05). Markedly higher BUT, SLt, SQOL-DVI scores and lower OSDI scores were witnessed among patients in the intervention group than the control group (p<0.05). The clinical effect of sodium hyaluronate combined with rhEGF eye drops in the treatment of dry eye is superior to sodium hyaluronate alone, in terms of enhancing the stability of tear film, accelerating corneal healing, inhibiting the level of inflammatory factors and improving patients' quality of life.

WWP2 ameliorates acute kidney injury by mediating p53 ubiquitylation and degradation.

E3 ubiquitin ligase gene, WWP2, is associated with acute kidney injury (AKI). This research was conducted to explore the role of WWP2 in AKI. AKI cell model was produced in human renal proximal tubular epithelial cell line (HK-2) by ischemia-reperfusion (IR) injury. CCK8 and flow cytometry assay were performed to explore the influence of WWP2 overexpression on cell proliferation and apoptosis of IR-induced HK-2 cells. Quantitative real-time PCR and immunoblotting (IB) were performed to assess the gene and protein expression. Then, the influence of WWP2 on p53 ubiquitylation and degradation was estimated by immunoprecipitation assay. Our data indicated that WWP2 was down-regulated and p53 was up-regulated in IR-induced HK-2 cells. WWP2 overexpression promoted proliferation and inhibited apoptosis of IR-induced HK-2 cells. And WWP2 interacted with p53 and regulated p53 ubiquitylation and degradation. Furthermore, the influence of WWP2 on cell proliferation and apoptosis was rescued by MG132 (proteasome inhibitor) treatment. In conclusion, our work described for the first time the role of WWP2 in AKI, showing that WWP2 ameliorated AKI by mediating p53 ubiquitylation and degradation. Moreover, the study offers some important insights into the occurrence of AKI and WWP2 may be a novel target of AKI treatment. SIGNIFICANCE OF THE STUDY: Our data elaborates that WWP2 has protective effect against AKI by mediating p53 ubiquitylation and degradation. Thus, WWP2 might be a therapeutic target for AKI.

Tetrandrine prevents monocrotaline-induced pulmonary arterial hypertension in rats through regulation of the protein expression of inducible nitric oxide synthase and cyclic guanosine monophosphate-dependent protein kinase type 1.

OBJECTIVE: Pulmonary arterial hypertension (PAH) is a fatal disease characterized by a persistent elevation of pulmonary artery pressure and ventricular hypertrophy. Tetrandrine is a bisbenzylisoquinoline alkaloid that can decrease blood pressure, inhibit the proliferation of vascular smooth muscle cells, and block cardiac hypertrophy, but whether it has a therapeutic effect on PAH remains poorly defined. This study was undertaken to investigate the efficacy of tetrandrine on PAH. METHODS: Forty-eight male Sprague-Dawley rats were randomly and equally divided into four groups. The control group was injected with normal saline; the others were injected with monocrotaline (MCT) to induce PAH, then treated with saline, tetrandrine, and vardenafil, respectively, from day 21 to day 42. On day 43, we measured the mean pulmonary artery pressure under general anesthesia, dissected the rat, and calculated the right ventricular hypertrophy index [right ventricle/(left ventricle plus septum)]. Later we observed the changes in the pulmonary vascular wall; measured the expression of cyclic guanosine monophosphate-dependent protein kinase type 1 and inducible nitric oxide synthase; measured the levels of superoxide dismutase, glutathione, malondialdehyde, and catalase; and then compared the results among groups. RESULTS: Compared with the MCT group, rats treated with tetrandrine had attenuated mean pulmonary artery pressure (20.48 ± 1.49 vs 30.07 ± 1.51; P < .01) and right ventricular hypertrophy index (49.19 ± 2.45 vs 68.50 ± 1.95; P < .01), inhibited proliferation of pulmonary artery smooth muscle cells, and improved endothelial function. Tetrandrine also upregulated the expression of protein kinase type 1 (90.86 ± 1.95 vs 67.34 ± 1.50; P < .01); downregulated the expression of inducible nitric oxide synthase (74.76 ± 1.48 vs 80.19 ± 0.28; P < .01); increased levels of superoxide dismutase (245.54 ± 12.98 vs 166.16 ± 21.42; P < .01), glutathione (0.699 ± 0.032 vs 0.514 ± 0.056; P < .01), and catalase (32.13 ± 2.33 vs 27.19 ± 2.72; P < .01); and decreased malondialdehyde (1.027 ± 0.039 vs 1.462 ± 0.055; P < .01). CONCLUSIONS: Tetrandrine alleviated MCT-induced PAH through regulation of nitric oxide signaling pathway and antioxidant and antiproliferation effects.

Humid heat exposure induced oxidative stress and apoptosis in cardiomyocytes through the angiotensin II signaling pathway.

Exposure to humid heat stress leads to the initiation of serious physiological dysfunction that may result in heat-related diseases, including heat stroke, heat cramp, heat exhaustion, and even death. Increasing evidences have shown that the humid heat stress-induced dysfunction of the cardiovascular system was accompanied with severe cardiomyocyte injury; however, the precise mechanism of heat stress-induced injury of cardiomyocyte remains unknown. In the present study, we hypothesized that humid heat stress promoted oxidative stress through the activation of angiotensin II (Ang II) in cardiomyocytes. To test our hypothesis, we established mouse models of humid heat stress. Using the animal models, we found that Ang II levels in serum were significantly up-regulated and that the Ang II receptor AT1 was increased in cardiomyocytes. The antioxidant ability in plasma and heart tissues which was detected by the ferric reducing/antioxidant power assay was also decreased with the increased ROS production under humid heat stress, as was the expression of antioxidant genes (SOD2, HO-1, GPx). Furthermore, we demonstrated that the Ang II receptor antagonist, valsartan, effectively relieved oxidative stress, blocked Ang II signaling pathway and suppressed cardiomyocyte apoptosis induced by humid heat stress. In addition, overexpression of antioxidant genes reversed cardiomyocyte apoptosis induced by Ang II. Overall, these results implied that humid heat stress increased oxidative stress and caused apoptosis of cardiomyocytes through the Ang II signaling pathway. Thus, targeting the Ang II signaling pathway may provide a promising approach for the prevention and treatment of cardiovascular diseases caused by humid heat stress.

Down-regulated miR-15a mediates the epithelial-mesenchymal transition in renal tubular epithelial cells promoted by high glucose.

High glucose (HG) has been reported to be associated with renal dysfunction. And one potential mechanism underlining the dysfunction is the epithelial-mesenchymal transition (EMT) of renal tubular epithelial cells. Present study showed that EMT was induced in the HG-treated renal tubular epithelial cells by promoting the expression of mesenchymal phenotype molecules, such as α-SMA and collagen I, and down-regulating the expression of epithelial phenotype molecule E-cadherin. Moreover, we have identified the down-regulation of miR-15a which was accompanied with the HG-induced EMT. And the miR-15a overexpression inhibited the α-SMA, collagen I expression, and the promotion of E-cadherin expression by targeting and down-regulating AP4 which was also significantly promoted by the HG in the renal tubular epithelial cells. Thus, this study revealed that the weakening regulation on the AP4 expression by miR-15a might contribute to the HG-induced EMT in the renal tubular epithelial cells.

Surgical Management of Pulmonary Artery Sling in a Pediatric Patient.

BACKGROUND Pulmonary artery sling (PAS) is an anatomical vascular anomaly due to the origin of the left pulmonary artery from the right pulmonary artery, which runs posteriorly between the esophagus and trachea, resulting in compression of adjacent structures. Accurate evaluation for malformation of the pulmonary artery and severity of airway obstruction is essential to surgical strategy. This report presents the diagnosis and surgical management of pulmonary artery sling in a 12-year-old boy. CASE REPORT A 12-year-old boy had chest tightness and wheezing after exercise for 6 years. He was diagnosed with PSA based on findings from imaging tests, demonstrating the left pulmonary artery originated from the middle of the right pulmonary artery and the tracheal carina was located at the site of the T6 thoracic vertebra. The main bronchus and esophagus were compressed by the left pulmonary artery due to its ectopic origin. Then, after comprehensive preoperative assessment, the patient underwent surgical repair of PAS. CONCLUSIONS This report highlights the importance of pulmonary artery sling diagnosis, imaging, and surgical planning, and the role of a multidisciplinary team in preoperative and postoperative patient management. An individualized strategy based on the preoperative assessment, intraoperative coordination among cardiologists, surgeons, and perfusionists, and careful postoperative management are the core elements for successful PAS repair.

Resveratrol ameliorates subacute intestinal ischemia-reperfusion injury.

BACKGROUND: Resveratrol has been shown to attenuate reactive oxygen species formation and protect against ischemia-reperfusion (I/R) injury. However, the effects of resveratrol against subacute intestinal I/R injury are not clearly elucidated. Therefore, this study was designed to investigate the effects and possible protective mechanisms of resveratrol on subacute intestinal I/R injury in mice. METHODS: BALB/c mice were subjected to 1 h ischemia by occluding the superior mesenteric artery and 24 h reperfusion. Histologic injury; myeloperoxidase, superoxide dismutase, and glutathione peroxidase activity; malondialdehyde level; inducible nitric oxide synthase (iNOS), Ac-NF-κBp65, and sirtuin 1 (SIRT1) expression; NF-κB translocation; and nitric oxide (NO) production were examined in treated with or without resveratrol in the absence or presence of pharmacologic inhibitors. RESULTS: Resveratrol significantly ameliorated subacute intestinal I/R injury accompanied with the decrease of NO production as well as iNOS expression. In addition, resveratrol obviously upregulated the expression of SIRT1 and inhibited the activity of NF-κB. After application of iNOS inhibitor S-methylisothiourea and NF-κB inhibitor pyrrolidine dithiocarbamate, the protective effect of resveratrol was significantly augmented by attenuating iNOS and NO production, indicating that resveratrol exerted its protective effect on intestinal I/R injury via NF-κB-mediated iNOS pathway. Furthermore, the protective effect of resveratrol was correlated with SIRT1, because application of SIRT1 inhibitor nicotinamide strikingly weakened the protective effect of resveratrol. CONCLUSIONS: Taken together, our findings showed that resveratrol protects intestinal subacute I/R injury via the SIRT1-NF-κB pathway in an iNOS-NO-dependent manner. Therefore, resveratrol has a potential clinical prospect for further development of anti-injury therapy.

Protective effects of mGluR5 positive modulators against traumatic neuronal injury through PKC-dependent activation of MEK/ERK pathway.

Several previous studies utilizing selective pharmacological antagonists have demonstrated that type 5 metabotropic glutamate receptors (mGluR5) are potential therapeutic targets for the treatment of numerous disorders of the central nervous system, but the role of mGluR5 activation in traumatic brain injury (TBI) is not fully understood. Here in an in vitro TBI model, the mGluR5 agonist (RS)-2-chloro-5- hydroxyphenylglycine (CHPG) and the positive allosteric modulators 3-cyano-N-(1,3- diphenyl-1H-pyrazol-5-yl) benzamide (CDPPB) were used to investigate the neuroprotective potency of mGluR5 activation. Data showed that CHPG and CDPPB suppressed the increase of LDH release and caspase-3 activation induced by traumatic neuronal injury in a dose-dependent manner, and the salutary effects were also present when these compounds were added 1 h after injury. Western blot was used to examine the activation of three members of mitogen-activated protein kinases: extracellular signal-regulated kinase (ERK), c-Jun N-terminal kinase (JNK), and p38 kinase (p38). CHPG and CDPPB enhanced the activation of ERK after traumatic neuronal injury, and PD98059 and U0126, two selective MEK/ERK inhibitors, partly revised the protective effects. Furthermore, we also investigated the role of protein kinase C (PKC) in CHPG and CDPPB-induced neuroprotection. With the pretreatment of chelerythrine chloride, a PKC inhibitor, the surpressing effects of CHPG and CDPPB on traumatic injury-evoked LDH release and caspase-3 activation were blocked. All of these findings extended the protective role of mGluR5 activation in an in vitro model of TBI and suggested that these protective effects might be mediated by the PKC-dependent activation of MEK/ERK pathway. These results may have important implications for the development of mGluR5 modulators to treat TBI.

Resveratrol prevents hepatic steatosis induced by hepatitis C virus core protein.

Hepatitis C virus (HCV) core protein plays an important role in the development of hepatic steatosis in patients with chronic HCV infection. Treatment of C57BL/6 mice infected with HCV core recombinant adenoviruses with resveratrol significantly decreased hepatic triacylglycerols (TAG) while the serum TAG level was unaffected. RT-PCR and Western blotting showed that HCV core protein attenuated the expression of Sirt1 and PPAR-α, which would be reversed by resveratrol. This was also confirmed in primary mouse hepatic cells infected with HCV core protein expressing adenovirus. Thus, resveratrol may prevent against hepatic steatosis by blocking the inhibited expression of Sirt1 and PPAR-α induced by HCV core protein.

A rare association of invasive infective endocarditis due to Abiotrophia defectiva with ventricular septal defect and recurrent Henoch-Schonlein purpura in a child.

BACKGROUND: Henoch-Schonlein purpura is the most common vasculitis in childhood, usually triggered by an upper respiratory tract infection and rarely observed in infective endocarditis patients. Abiotrophia defectiva is a rare causative agent of infective endocarditis associated with pre-existing heart disease, immunocompromised and prosthetic valves. Dental procedures are also a common predisposing factor. CASE PRESENTATION: We present the first pediatric congenital heart disease case of infective endocarditis caused by Abiotrophia defectiva combined with recurrent Henoch-Schonlein purpura. A 10-year-old girl with uncorrected congenital heart defects and Henoch-Schonlein purpura developed a purple petechial rash again. Transthoracic echocardiography evaluation revealed multiple irregular vegetations on the right ventricular side of the ventricular septal defect and on the tricuspid valve leaflets. Blood cultures grew Abiotrophia defectiva. The girl received cardiac surgery for vegetation resection as well as congenital heart defect correction and tricuspid valve replacement. Five months after the surgery, the patient was in satisfactory condition without any signs of endocarditis or valve insufficiency and her purpuric rash disappeared. CONCLUSIONS: The coexistence of recurrent Henoch-Schonlein purpura and infective endocarditis is possible. Abiotrophia defectiva belongs to the streptococcus with a high virulence. In addition, cardiovascular surgery is often required for pediatric infective endocarditis associated with Abiotrophia defectiva, and bioprosthetic valve replacement is considered feasible for irreparable tricuspid valve in children.

Tetramethylpyrazine Improves Monocrotaline-Induced Pulmonary Hypertension through the ROS/iNOS/PKG-1 Axis.

Background: Tetramethylpyrazine (TMP), a potent anti-free radical and anti-inflammations substance, has been demonstrated to possess a direct vessel relaxation property. This study aimed to evaluate the effect of TMP treatment in pulmonary hypertension (PH) and test the hypothesis that TMP prevents or reverses the process of PH. Methods: Rats (n = 36) injected with 50 mg/kg of monocrotaline (MCT) subcutaneously 4 weeks to develop PH were then randomized to TMP (5 mg/kg per day) for another 4 weeks. Hemodynamics was evaluated via the right ventricle. Pulmonary vessels structural remodeling and inflammation were examined by histologic and transmission electron microscopy observation. The expression of inducible nitric oxide synthase (iNOS) and cGMP-dependent protein kinases 1 (PKG-1) was detected by immunohistochemical staining and Western blot. Generation of reactive oxygen species (ROS) and antioxidation species was measured by biochemical analyses. Results: MCT increased PH and right ventricle hypertrophy. TMP alleviated pulmonary arterial pressure elevation, leukocyte infiltration, and structural remodeling of pulmonary arterials induced by MCT successfully. TMP treatment significantly increased the PKG-1 expression and suppressed the iNOS expression. The activity of superoxide dismutase (SOD), glutathione peroxidase (GSH), and catalase (CAT) was significantly higher than control group, while malondialdehyde (MDA) levels were lower compared with MCT group. Conclusion: TMP can suppress established MCT-induced PH through the ROS/iNOS/PKG axis. The underlying mechanisms may be associated with its anti-inflammatory, antioxidant, and antiproliferative properties in pulmonary arterial.

Effect of aquaporin 1 on mouse peritoneal mesothelial cells after a long-term peritoneal dialysis.

Aquaporin 1 (AQP1) is one member of the aquaporin family, also the deeply studied one. It is widely located on the endothelial cells, but the effect of AQP1 on the peritoneal mesothelial cells (PMCs) after long-term peritoneal dialysis (PD) has not been reported before. We divided normal mice into two groups, control group and dialysis group, to confirm the fibrotic changes and expression of APQ1 on peritoneal mesothelial cells. Then we assigned normal mice and AQP1 knockout mice into four groups: Control group, normal dialysis group, AQP1 knockout control group and AQP1 knockout dialysis group. The two dialysis groups received 4.25% glucose dialysis for 28 days. We found that mice in both dialysis groups showed peritoneal fibrotic changes, which were most severe in the AQP1 knockout dialysis group; the peritoneal thickness in the AQP1 knockout dialysis group was also thicker than that in the dialysis group (P < .05). We used electron microscopy to detect ultrastructural changes and observed changes in microvilli and vacuolar degeneration in mesothelial cells from all groups except the control group. The basement membranes were damaged in the AQP1 knockout dialysis group, and peritoneal mesothelial cells were disrupted and detached in this group. Together our findings indicate that AQP1 plays an important role in maintaining the physiological functions of peritoneal mesothelial cells, and AQP1 can protect mesothelial cells during dialysis.

Corrigendum to "Cordyceps militaris Improves Chronic Kidney Disease by Affecting TLR4/NF-κB Redox Signaling Pathway".

[This corrects the article DOI: 10.1155/2019/7850863.].

Resveratrol inhibits MMP-9 expression by up-regulating PPAR alpha expression in an oxygen glucose deprivation-exposed neuron model.

Resveratrol (trans-3,4',5-trihydroxystilbene, Res) is a natural polyphenol. A recent experiment confirmed that Res can selectively activate both peroxisome proliferators-activated receptors (PPAR) alpha and gamma. In addition, Res can protect neurons by matrix metalloproteinase-9 (MMP-9) down-regulation. The relationship between Res, MMP-9 and PPAR alpha or gamma was studied in an oxygen glucose deprivation-exposed neuron model. It showed that Res can inhibit mRNA and protein expression of MMP-9, while it up-regulates the expression of PPAR alpha and gamma. The effect of Res on both PPAR alpha and MMP-9 can be offset partially by MK886. However, PPAR gamma antagonist GW9662 had little effect on MMP-9 expression. These results suggest that Res can inhibit MMP-9 expression by up-regulating PPAR alpha.

Cordyceps militaris Improves Chronic Kidney Disease by Affecting TLR4/NF-κB Redox Signaling Pathway.

Cordyceps militaris may show good promise in protecting against chronic kidney disease (CKD) but the molecular mechanism remains unclear. CKD risk is associated with the Toll-like receptor 4/nuclear factor-kappa B (TLR4/NF-κB) signaling pathway. Cordycepin is the main component of Cordyceps militaris and may affect the TLR4/NF-κB pathway. Cordycepin was prepared by preparative HPLC. CKD patients were assigned into Cordyceps militaris (COG, 100 mg daily) and placebo (CG) groups. Cordycepin activity was measured using human embryo kidney cells (HEK293T). Biochemical indices, the levels of TLR4, NF-κB, cyclooxygenase-2 (COX2), tumor necrosis factor-alpha (TNF-α), and interleukin-1 beta (IL-1ß), were measured by real-time qRT-PCR, or ELISA kits and or Western blot. After 3-month treatment, cordycepin reduced the levels of urinal protein, blood urea nitrogen (BUN), and creatinine by 36.7%±8.6%, 12.5%±3.2%, and 18.3%±6.6%, respectively (P < 0.05). Cordyceps militaris improved lipid profile and redox capacity of CKD patients by reducing the serum levels of TG, TC, and LDL-C by 12.8%±3.6%, 15.7%±4.1%, and 16.5%±4.4% and increasing the HDL-C level by 10.1%±1.4% in the COG group when compared with the CG group, respectively (P < 0.05). The serum levels of cystatin-C (Cys-C), myeloperoxidase (MPO), and malondialdehyde (MDA) were reduced by 14.0%±3.8%, 26.9%±12.3%, and 19.7%±7.9% while nitric oxide (NO) and superoxide dismutase (SOD) were increased by 12.5%±2.9% and 25.3%±13.4% in the COG group when compared with the CG group, respectively (P < 0.05). Cordycepin reduced the levels of TLR4, NF-κB, COX2, TNF-α, and IL-1ß in HEK293T cells too (P < 0.05). However, cordycepin could not affect the levels anymore if TLR4 was silenced. Cordyceps militaris protected against CKD progression by affecting the TLR4/NF-κB lipid and redox signaling pathway via cordycepin.

Resveratrol attenuates ischemic brain damage in the delayed phase after stroke and induces messenger RNA and protein express for angiogenic factors.

BACKGROUND: It has been reported recently that resveratrol preconditioning can protect the brain from ischemia-reperfusion injury. However, it was unclear whether resveratrol administration after stroke was beneficial to the delayed phases after focal cerebral ischemia injury. This study investigated the effects and possible protective mechanism of resveratrol on the delayed phase after focal cerebral ischemia injury in mice. METHODS: Mice were randomly assigned to five groups according to the time of administration of resveratrol. Control group mice received a corresponding volume of saline solution (0.9% NaCl) containing 20% hydroxypropyl h-cyclodextrin by gavage and were exposed to middle cerebral artery (MCA) occlusion and reperfusion injury. The treatment groups received resveratrol (50 mg/kg/d, gavage) until day 7. Ischemia group mice received their first dose 5 minutes before MCA ischemia, reperfusion group mice received their first dose 5 minutes before MCA reperfusion, first-day, group mice received their first dose 24 hours after MCA reperfusion, and third-day group mice received their first dose at 72 hours after MCA reperfusion. Brain injury was evaluated by triphenyltetrazolium chloride staining and neurologic examination 7 days after reperfusion. The microvascular cell number was examined with immunohistochemistry staining. Effect of resveratrol on matrix metalloproteinase-2 (MMP-2) and vascular endothelial growth factor (VEGF) gene expression was investigated with reverse transcriptase-polymerase chain reaction and Western blot. RESULTS: The mean neurologic scores and infarct volumes of the ischemia and reperfusion groups were lower than that of the control group at 7 days after MCA reperfusion (P < .05). Immunohistochemistry staining showed significantly less reduction in the number of microvessels in the cortical area of mice of the ischemia and reperfusion groups compared with controls. The ischemic hemispheres of the ischemia and reperfusion groups showed significantly (P < .05) elevated levels of protein of MMP-2 and VEGF. CONCLUSIONS: Resveratrol administration by gavage provided an important neuroprotective effect on focal cerebral ischemic injury in the delayed phase. The elevated MMP-2 and VEGF levels might be important in the neuroprotective effect of resveratrol administration by inducing angiogenesis.

Identification of 14-3-3 protein isoforms in human astrocytoma by immunohistochemistry.

The 14-3-3 proteins are highly conserved, ubiquitous molecules involved in a variety of biologic events, such as cell cycle control, and apoptosis. In our previous study, it has been proved that they are expressed in primary human nervous system tumors. However, the isoform-specific expression of 14-3-3 protein is still need to be identified. This study is the first detection of 14-3-3 isoforms' specific expression in human astrocytoma. In the normal brain tissues, all the seven 14-3-3 isoforms' immunoreactivity was localized mainly in the neurons, while only weak expression of epsilon, zeta and theta was found in some glial cells. However, beta, epsilon, zeta, eta and theta isoforms' immunoreactivity was seen in the majority of astrocytoma samples and its immunoreactivity score was increased markedly with an increase in the pathologic grade of human astrocytomas. These results indicate that the five isoforms may play an important role in tumorigenesis of human astrocytoma.

New insights into mechanism for the effect of resveratrol preconditioning against cerebral ischemic stroke: Possible role of matrix metalloprotease-9.

Resveratrol, a natural polyphenolic compound, is found in a few edible materials and is well known for its phytoestrogenic and antioxidant properties. A growing body of in vivo and in vitro evidence indicates that resveratrol has protective effect on cerebral ischemic stroke. Here, we review the effect of resveratrol on cerebral ischemic stroke, and propose a possible mechanism. During acute phases after stroke, resveratrol preconditioning suppresses matrix metalloprotease-9 activity to ameliorate blood-brain barrier disruption, edema formation and neuronal cell death caused by ischemia and reperfusion. But during delayed phases after stroke, resveratrol preconditioning conduces to cerebral angiogenesis and brain regeneration through increasing matrix metalloprotease-9 activity and expression. Resveratrol's effect on matrix metalloprotease-9 is distinguishing in different phases because of temporal and spatial redistribution of matrix metalloprotease-9 within the cells of the neurovascular unit after cerebral ischemia. This paper also hypothesizes that resveratrol treatment after cerebral ischemia might be beneficial for cerebral angiogenesis and brain regeneration during delayed phases after stroke.

Grouped Gene Selection of Cancer via Adaptive Sparse Group Lasso Based on Conditional Mutual Information.

This paper deals with the problems of cancer classification and grouped gene selection. The weighted gene co-expression network on cancer microarray data is employed to identify modules corresponding to biological pathways, based on which a strategy of dividing genes into groups is presented. Using the conditional mutual information within each divided group, an integrated criterion is proposed and the data-driven weights are constructed. They are shown with the ability to evaluate both the individual gene significance and the influence to improve correlation of all the other pairwise genes in each group. Furthermore, an adaptive sparse group lasso is proposed, by which an improved blockwise descent algorithm is developed. The results on four cancer data sets demonstrate that the proposed adaptive sparse group lasso can effectively perform classification and grouped gene selection.

Protective effects of IFN-γ on the kidney of type- 2 diabetic KKAy mice.

BACKGROUND: Development of novel therapeutic strategies that specifically target diabetic kidney disease (DKD) is urgently needed. METHODS: Male KKAy mice were divided randomly into three equal groups - KK, KI, and KF; Male C57BL/6 mice were the control group. All KKAy mice were fed a high-fat diet. From the 16th week, the KI group was given IFN-γ, and the KF group was assigned to be treated with fludarabine. C57BL/6 mice were always fed a normal mouse diet. Every 4 weeks, body weight, random blood sugar, urine albumin and urea of all mice were measured. At the 20th week, all mice were killed, renal tissue was obtained to observe the pathological manifestations and extract proteins, and transforming growth factor- beta1 (TGF-ß1), collagen IV and Janus kinase 2/signal transducers and activators of transcription 1 (JAK2/STAT1) pathway proteins were measured by western blot. RESULTS: The present study showed that all KKAy mice appeared obese and hyperglycaemic from 12 weeks old and exhibited an increased urine albumin-to-creatinine ratio (ACR) from 16 weeks old. At the 20th week, compared to the KK group, the KI group showed lower ACR, more overexpression of P-STAT1 and less expression of TGF-ß1 and collagen IV proteins in renal tissue. The KI group mice showed less accumulation of glomerular mesangial matrix than those in the KK group. CONCLUSIONS: Our results indicate that IFN-γ might activate STAT1 to suppress the overexpression of TGF-ß1 and collagen IV proteins and attenuate the excessive accumulation of mesangial matrix under DKD conditions in KKAy mice.