Identification of a novel ferroptosis-related gene signature associated with retinal degeneration induced by light damage in mice.

Background: Neurodegenerative retinal diseases such as retinitis pigmentosa are serious disorders that may cause irreversible visual impairment. Ferroptosis is a novel type of programmed cell death, and the involvement of ferroptosis in retinal degeneration is still unclear. This study aimed to investigate the related ferroptosis genes in a mice model of retinal degeneration induced by light damage. Methods: A public dataset of GSE10528 deriving from the Gene Expression Omnibus database was analyzed to identify the differentially expressed genes (DEGs). Gene set enrichment analysis between light damage and control group was conducted. The differentially expressed ferroptosis-related genes (DE-FRGs) were subsequently identified by intersecting the DEGs with a ferroptosis genes dataset retrieved from the FerrDb database. The Gene Ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) were further performed using the DE-FRGs. A protein-protein interaction (PPI) network was constructed to identify hub ferroptosis-related genes (HFRGs). The microRNAs (miRNAs)-HFRGs, transcription factors (TFs)-HFRGs networks as well as target drugs potentially interacting with HFRGs were analyzed utilizing bioinformatics algorithms. Results: A total of 932 DEGs were identified between the light damage and control group. Among these, 25 genes were associated with ferroptosis. GO and KEGG analyses revealed that these DE-FRGs were mainly enriched in apoptotic signaling pathway, response to oxidative stress and autophagy, ferroptosis, necroptosis and cytosolic DNA-sensing pathway. Through PPI network analysis, six hub ferroptosis-related genes (Jun, Stat3, Hmox1, Atf3, Hspa5 and Ripk1) were ultimately identified. All of them were upregulated in light damage retinas, as verified by the GSE146176 dataset. Bioinformatics analyses predicated that 116 miRNAs, 23 TFs and several potential therapeutic compounds might interact with the identified HFRGs. Conclusion: Our study may provide novel potential biomarkers, therapeutic targets and new insights into the ferroptosis landscape in retinal neurodegenerative diseases.

A Novel Modulator of the Renin-Angiotensin System, Benzoylaconitine, Attenuates Hypertension by Targeting ACE/ACE2 in Enhancing Vasodilation and Alleviating Vascular Inflammation.

The monoester alkaloids in Aconitum carmichaelii, including benzoylaconitine (BAC), benzoylmesaconine, and benzoylhypaconitine, were found to have anti-hypertensive effects in spontaneously hypertension rats (SHRs), of which BAC is the strongest. However, its antihypertensive target and underlying molecular mechanisms remain unclear. In this study, first, we screened the antihypertensive targets of BAC by using the CVDPlatform (www.cbligand.org/CVD) and found that ACE/ACE2 are the most possible targets. Then, we verified the effect of BAC on ACE/ACE2 by virtual docking, SPR, enzyme activity assay, and HUVECs cell experiment. We found that BAC could bind with ACE/ACE2, inhibit ACE activity and protein expression, and activate ACE2 enzyme activity. Using vascular function test in vitro, we found that BAC could target ACE/ACE2 to enhance endothelium-dependent vasorelaxation. In BAC-treated SHRs, the levels of ACE and AngII in serum were reduced while Ang (1-7) was increased significantly, and the expression of ACE was reduced, which suggested that BAC can inhibit ACE and activate ACE2 to inhibit AngI to AngII and promote AngII to Ang (1-7) to inhibit vasoconstriction and finally attenuate hypertension. Furthermore, the signaling pathways with regard to vasorelaxation and vascular inflammation were investigated. The results showed that BAC could significantly activate Akt/eNOS, increase NO production, and promote endothelial-related vasodilation; BAC could also reduce inflammatory factors TNF-α and IL6, inhibition of COX-2 expression, and IKB-α phosphorylation to reduce vascular inflammation in SHRs. In brief, BAC targets ACE/ACE2 to enhance endothelium-dependent vasorelaxation and reduce vascular inflammation to attenuate hypertension as a potential modulator of the renin-angiotensin system.

Biopharmaceutical and Pharmacokinetic Activities of Oxymatrine Determined by a Sensitive UHPLC-MS/MS Method.

BACKGROUND: Oxymatrine is known as one of the most promising alkaloids from Sophora flavescens for its excellent pharmacological effects. OBJECTIVE: The aim of this research is to assess the biopharmaceutical and pharmacokinetic activities of oxymatrine and clarify its mechanisms of absorption and metabolism. METHODS: The biological characteristics of oxymatrine were systematically investigated by UHPLC-MS/MS. The mechanisms of absorption and metabolism of oxymatrine were further clarified through incubation in rat liver microsomes and transport across the Caco-2 monolayer cell absorption model. RESULTS: It was found that the absolute oral bioavailability of oxymatrine was 26.43%, and the pharmacokinetic parameters Cmax, Tmax, and t1/2 were 605.5 ng/mL, 0.75 h, and 4.181 h after oral administration, indicating that oxymatrine can be absorbed quickly. The tissue distribution tests showed that oxymatrine distributed throughout all the organs, with the small intestine accumulating the highest level, followed by the kidney, stomach, and spleen. The Papp in Caco-2 cell line absorption model was over 1 × 10-5 and PDR 1.064, and t1/2 of oxymatrine in rat liver microsome in vitro was 1.042 h, indicating that oxymatrine can be absorbed easily through passive diffusion and CYP450 enzymes could be involved in its metabolism. The plasma protein binding rate of oxymatrine was 2.78 ± 0.85%. CONCLUSION: Oxymatrine can be absorbed into blood easily through passive diffusion, mainly distributed in the intestine, stomach, liver, and spleen in vivo, and CYP450 enzymes in the liver could be involved in its metabolism.

Establishing the lower limits of total serum testosterone among Chinese proven fertile men who received treatment of assisted reproductive technology.

Testosterone (T) plays a crucial role in spermatogenesis because extremely low levels of intratesticular T lead to correspondingly low serum levels of total T (tT), severe disorders of spermatogenesis, and male sterility. However, there is little consensus on the lower limits of serum tT in proven fertile men undergoing assisted reproductive technology treatments in Chinese or other Asian populations. We aimed to establish the reference range of serum tT based on a population of 868 fertile Chinese men undergoing in vitro fertilization or intracytoplasmic sperm injection and embryo transfer (IVF/ICSI-ET) treatments. We defined a fertile man as having had a live baby with his partner as recorded in our IVF registration system. The lower limits of serum tT were established using a Siemens IMMULITE 2000 chemiluminescent system. The 1st, 2.5th, and 5th percentiles and their 95% confidence intervals (CIs) were 3.6 (95% CI: 2.7-4.1) nmol l-1, 4.3 (95% CI: 4.1-5.0) nmol l-1, and 5.6 (95% CI: 4.8-5.8) nmol l-1, respectively. Using the linear correlation of serum tT between the Siemens platform and a liquid chromatography-tandem mass spectrometry platform, the calculated lower limits of serum tT were also established for fertile Chinese men undergoing IVF/ICSI-ET treatments, which will benefit the clinical diagnosis and treatment of male infertility during such procedures.

[Source Appointment of Heavy Metals in Agricultural Soils of the Jiulong River Basin Based on Positive Matrix Factorization].

In order to study the source appointment of heavy metals in agricultural soils of the Jiulong River Basin, Fujian Province, China. 71 agricultural soil samples were collected in July 2017. The concentrations of heavy metals in agricultural soils were determined by inductively coupled plasma mass spectrometry (ICP-MS) and atomic fluorescence spectrometry (AFS). Here, we use a positive matrix factorization (PMF) model for the source appointment of heavy metals in the sampled soils. The results showed that most of the heavy metal concentrations in the sampled agricultural soils were higher than soil background concentrations for the Fujian Province. The concentrations of Cd, Zn, Pb, and Cu in some soil samples were greater than the screening value of the Chinese soil pollution risk levels for agricultural land (GB 15618-2018). The spatial distributions of heavy metals showed a moderate variation across three regions of the study area (i.e., the North River watershed, West River watershed, and the estuary area). The highest concentration of Cr, Ni, Cu, Zn, and Cd were found in Longyan City (North River watershed), the highest concentrations of Pb were found in the West River watershed, and the highest concentrations of Co, Hg, and As were found in the estuary area. The non-negative properties of the source component spectrum and source contribution rate (obtained by the PMF model), as well as the significant correlation between the measured and PMF predicted concentrations, indicated that the results of the PMF model were relatively reasonable and can meet research needs. The source apportionment results of the PMF model showed that natural sources, agricultural sources, coal combustion, and industrial sources were the four major potential sources for heavy metals in the sampled agricultural soils, contributing 37.0%, 26.7%, 17.6%, and 18.7%, respectively.

[Limited external fixation of plastic cardboard for the treatment of senile comminuted humeral fracture].

OBJECTIVE: To explore clinical efficacy of limited external fixation with plastic paperboard in treating senile proximal comminuted humeral fracture. METHODS: From June 2015 to December 2017, 32 senile patients with proximal comminuted fracture of humerus were treated with plasticized cardboard after manual external fixation. Among them, including 13 males and 19 females aged from 55 to 85 years old with an average of(68.22±8.36) years old; 18 patients on the left side and 14 patients on the right side; all patients were regularly review shoulder X-rays and performed appropriate functional exercises. Constant-Murley shoulder joint scoring was used to evaluate clinical effects. RESULTS: Thirty-two patients were followed up for 3 to 12 months with an average of (4.97±2.39) months. All patients were underwent functional exercise under guidance of physicians. Nine patients were treated with topical Chinese herbal moist heat compresses to promote shoulder function recovery. Thirty-one patients were obtained fracture healing, the time ranged from 5 to 12 weeks with an average of(7.44±1.72)weeks. One patient was not healed due to comminuted fracture of fracture end and the separation was large, the blood supply to humeral head was insufficient for necrosis absorption. Postoperative Constant-Murley shoulder score at 3 months was 87.56±6.93; 15 patients got excellent results, 14 good, 2 fair and 1 poor. CONCLUSIONS: Limited external fixation with plastic paperboard for the treatment of senile proximal comminuted humeral fracture could ensure biomechanical stability of fracture, promote early recovery of shoulder joint function and shorten recovery time.

MiR-212-5p exerts a protective effect in chronic obstructive pulmonary disease.

Chronic obstructive pulmonary disease (COPD) is a common respiratory tract disease with an incompletely understood pathogenesis. According to previous reports, miRNAs play a crucial pathophysiological role in COPD. MiR-212 was reported to be downregulated in COPD patients; however, the role of miR-212 in COPD remains unknown. In this study, the expression level of miR-212-5p and miR-223 decreased significantly in COPD patients compared to healthy controls. In vitro experiments showed that cigarette smoke extract (CSE) induced NCI-H292 cell apoptosis and inhibited cell proliferation. Inflammation and COPD related genes were also upregulated by CSE, while miR-212-5p inhibited the overexpression of these genes. Furthermore, miR-212-5p promoted cell proliferation and inhibited IGFBP3 expression which was induced by CSE. The expression of p-Akt was also inhibited by CSE, while miR-212-5p significantly promoted the phosphorylation of Akt. In summary, our data suggest that miR-212-5p exerts a protective effect in COPD, and may serve as a prognostic biomarker and potential therapeutic target for COPD.

Application of 3-Dimensional Computerized Tomography Angiography for Defining Cavernous Sinus Aneurysms and Intradural Aneurysms Involving the Internal Carotid Artery Around the Anterior Clinoid Process.

OBJECTIVE: This study aimed to investigate the application of 3-dimensional computed tomography angiography (3D-CTA) for defining cavernous sinus aneurysms and intradural aneurysms involving the internal carotid artery around the anterior clinoid process. METHODS: Results from 42 patients with an aneurysm of the internal carotid artery around the anterior clinoid process who underwent 3D-CTA were reviewed and compared with those of observed clinical operations. RESULTS: Among the 42 patients, there was a total of 45 aneurysms of the internal carotid artery around the anterior clinoid process. After surgery, 33 of the 45 aneurysms were confirmed as intradural aneurysms, and the other 12 were confirmed as aneurysms in the cavernous sinus. 3D-CTA imaging of the medial sagittal plane showed that 31 out of 31 (100%) intradural aneurysms of the internal carotid artery were above the virtual line between the inferior border of the anterior clinoid process and the tuberculum sellae, and 12 out of 14 (86%) cavernous sinus aneurysms were below the virtual line (P < 0.0001). CONCLUSIONS: The virtual line between the inferior border of the anterior clinoid process and the tuberculum sellae on 3D-CTA indicates the proximal dural ring of the internal carotid artery. This line helps differentiate cavernous sinus aneurysms from intradural aneurysms involving the internal carotid artery around the anterior clinoid process.

Coiling Is Not Superior to Clipping in Patients with High-Grade Aneurysmal Subarachnoid Hemorrhage: Systematic Review and Meta-Analysis.

BACKGROUND: Outcomes of coiling embolization versus clipping for patients with high-grade aneurysmal subarachnoid hemorrhage (aSAH) have not been previously compared. We reviewed current evidence regarding the safety and efficacy of clipping versus coiling for high-grade aSAH. METHODS: We conducted a meta-analysis of studies that compared clipping with coiling in patients with high-grade aSAH published from January 1999 to February 2016 in Medline, Embase, and Cochrane databases based on PRISMA inclusion and exclusion criteria. Binary outcome comparisons between clipping and coiling were described using odds ratios (ORs). RESULTS: Three randomized controlled trials (RCTs) and 16 observational studies were included. There was no statistical difference in good outcome rates between the clipping and coiling groups (OR, 1.44; 95% confidence interval [CI], 0.97-2.13). Subgroup analysis showed no significant difference between the 2 treatments in non-RCTs (OR, 1.49; 95% CI, 0.95-2.36) and RCTs (OR, 1.15; 95% CI, 0.59-2.25). Coiling was associated with higher mortality (OR, 0.55; 95% CI, 0.41-0.75). Lower mortality was associated with clipping in non-RCTs (OR, 0.54; 95% CI, 0.40-0.74), but there was no difference in the RCTs (OR, 0.79; 95% CI, 0.19-3.39). Coiling was not associated with lower rates of complications including rebleeding (OR, 0.62; 95% CI, 0.30-1.29), ischemic infarct (OR, 0.89; 95% CI, 0.53-1.49), symptomatic vasospasm (OR, 0.76; 95% CI, 0.45-1.29), or shunt-dependent hydrocephalus (OR, 1.33; 95% CI, 0.52-3.40). CONCLUSION: The outcome with coiling is not superior to clipping in patients with high-grade aSAH; moreover, coiling has a greater risk of mortality.

Protective effect of sodium nitroprusside on the rat small intestine transplanted mucosa.

The intestinal mucosal epithelium is extremely susceptible to even brief periods of ischemia. Mucosal barrier damage, which is associated with ischemia/reperfusion (I/R) injury and consequently bacterial translocation, remains a major obstacle for clinically successful small bowel transplantation (SBT). Previous studies have demonstrated a protective effect of nitric oxide (NO) on other transplanted organs and NO mediated intestinal protection has also been reported in vitro. The aim of this study was to evaluate the effect of sodium nitroprusside (SNP), NO donor, on graft mucosal histology and molecular markers of function after SBT in rats. We used SNP in different period of heterotopic SBT rats. The groups consisted of SBT, pre-SNP group, and post-SNP group. Interestingly, the pre-SNP graft samples exhibited less damage compared to the SBT and post-SNP samples. In addition, mucosal samples from the pre-SNP group showed higher Na(+)-K(+)-ATPase activity and higher levels of laminin expression compared to the SBT and post-SNP samples. The findings of the present study reveal that SNP given before graft ischemia/reperfusion injury has a protective effect on mucosal histology and molecular markers of function in the transplanted small intestine.

Rapid detection of Staphylococcus aureus by loop-mediated isothermal amplification.

Staphylococcus aureus, including methicillin-resistant S. aureus (MRSA), is a major bacterial pathogen associated with nosocomial and community-acquired S. aureus infections all over the world. A rapid detection assay for staphylococcal gene of nuc and mecA is needed. In this study, a rapid identification assay based on the loop-mediated isothermal amplification (LAMP) method was established. PCR and LAMP assays were used to detect Staphylococcus aureus and other related species for nuc and mecA. With optimization of the primers and reaction temperature, the LAMP successfully amplified the genes under isothermal conditions at 62 °C within 60 min, of which the results were identical with those of the conventional PCR methods. The detection limits of the LAMP for nuc and mecA were 1.47 and 14.7 pg/µl DNA per tube, respectively, by naked eye inspections, while the detection limits of the PCR for nuc and mecA were 14.7 pg/µl and 147 pg/µl DNA, respectively. Finally, The LAMP method was then applied to clinical blood plaque samples. The LAMP and PCR demonstrated identical results for the plaque samples with the culture assay. Together, the LAMP offers an alternative detection assay for nuc and mecA with a great advantage of the sensitivity and rapidity.

[Effect of GW003 on the granulocyte macrophage colony formation ability of bone marrow cells in vitro].

The aim of this study was to investigate the effect of GW003 on the ability of granulocyte colony forming in vitro of bone marrow cells. The bone marrow samples was collected from normal rhesus, the patients with leukemia in stages of remission and chemotherapy respectively, and the nucleated cells were separated and cultured for 12 days after addition of different concentrations of GW003 or rhG-CSF, or G-CSF mutant. Then the amount of colony-forming unit-granulocyte-macrophage was counted. The results indicated that GW003 could enhance the ability of bone marrow nucleated cells of rhesus to forming CFU-GM in vitro, and its effect was much better than that of rhG-CSF or G-CSF mutant at the same concentration(®). The GW003 showed dose-response relationship to CFU-GM level (r = R(2) = 0.965, P = 0.003, in a certain concentration), the GW003 also could enhance CFU-GM formation of marrow nucleated cells in leukemic patients, especially for patients receiving chemotherapy. The GW003 could relieve the marrow suppression caused by chemotherapy significantly. It is concluded that the GW003 can significantly improve the ability of bone marrow cells to form granulocyte colony in vitro as well as effectively alleviate bone marrow suppression.

Vascular endothelial growth factor in Coats' disease.

PURPOSE: To examine whether vascular endothelial growth factor (VEGF) as one of the most important intraocular cytokines for angiogenesis and increased vascular permeability is associated with Coats' disease. METHODS: The clinical interventional study included 28 patients with Coats' disease and seven control patients with congenital cataract. During intraocular surgery, we obtained aqueous humour samples in which the VEGF concentration was measured by double-antibody sandwich enzyme-linked immunosorbent assay (ELISA). Coats' disease was graded into four stages. RESULTS: The mean aqueous VEGF level was significantly higher in the Coats' study group than in the control group (158±88 versus 97±21 pg/ml; p=0.002). The VEGF concentrations increased significantly (p<0.001) from 91±32 pg/ml in Coats' disease stage 2 to 100±37 pg/ml in stage 3A1, 185±56 pg/ml in stage 3A2 to 256±93 pg/ml in patients with stage 3B. Vascular endothelial growth factor concentrations in Coats' stage 2 and 3A1 did not differ significantly from the values in the control group. Parallel to the association with the stage of the diseases, the VEGF concentrations were significantly (p<0.001) correlated with extent of exudative retinal detachment. CONCLUSIONS: Increasing severity of Coats' disease is significantly associated with intraocular VEGF concentrations. These results favour the intravitreal application of anti-VEGF drugs as medical therapy of Coats' diseases.

Study of the biological effectiveness of a nanosilver-epidermal growth factor sustained-release carrier.

The aim of the present study was to elucidate the biological effectiveness and character of a nanosilver-epidermal growth factor (EGF) sustained-release carrier. This was synthesized using the self-assembly method and then characterized by transmission electron microscopy and UV spectrophotometry. The biological activity of the sustained release carrier was determined through cytological, bacteriological and wound-healing experiments. The results showed that the nanosilver-EGF sustained-release carrier was well dispersed with uniform particle size and that it had good antibacterial properties similar to those of nanosilver. The nanosilver-EGF sustained-release carrier is superior to EGFs in effectively promoting cell division and proliferation. The results of the wound-healing experiments provide evidence of its curative effects.

Triamcinolone intravitreal injection and intraocular pressure in macular edema associated with retinal vein occlusion.

PURPOSE: To study the risk factors of increased intraocular pressure (IOP) response to triamcinolone acetonide intravitreal (IVTA) injection in eyes with macular edema associated with retinal vein occlusion. METHODS: Eighty-nine eyes with macular edema associated with retinal vein occlusion first received periocular injection of 40 mg triamcinolone acetonide (TA) and were followed for one month. According to the diversity of IOP after periocular TA (PTA) injection, they were divided into the elevation IOP group (group A, 26 eyes) and the normal IOP group (group B, 63 eyes). They then received 4 mg TA intravitreal injection. IOP measurements were recorded after PTA and IVTA injections, and were followed for six months. RESULTS: Both PTA and IVTA injections caused a rise in IOP, but it was higher in the IVTA injection (40.45%) than in the PTA injection (29.21%). The mean rise in IOP was more significant in eyes with IVTA injection (28.08 ± 8.24 mmHg) than in eyes with PTA injection (20.87 ± 4.07 mmHg). Patients with an elevation IOP above 6 mmHg after PTA injection had a 73.08% chance of developing a pressure of 24 mmHg or higher, whereas only 12.70% of those with an elevation IOP below 6 mmHg after PTA injection experienced pressure elevation. CONCLUSION: IOP response to PTA injection is a good way to judge IOP response to IVTA. If the patient is highly sensitive to corticosteroid, treatments other than IVTA injection are used to avoid the increased risks associated with intravitreal corticosteroid injection.

Hyperglycemic effects of a periocular dexamethasone injection in diabetic patients after vitreoretinal surgery.

OBJECTIVE: To examine the hyperglycemic effects of periocular dexamethasone injection in type 2 diabetic patients after vitreoretinal surgery (VRS). METHODS: This was a retrospective non-randomized controlled trial. Twenty consecutive hospitalized patients with type 2 diabetes and ocular inflammatory reaction after VRS were enrolled in this study. Ten patients received 2.5 mg dexamethasone and 10 patients received 5 mg dexamethasone. Fourteen consecutive type 2 diabetic patients without ocular inflammatory reaction after VRS were used as control group. We measured fasting blood glucose (FBG) and at 2 h after each meal (post prandial glucose, PBG; 09:00, 13:00, and 19:00 h) after periocular dexamethasone injection. Differences among three groups were determined by q tests. RESULTS: The PBG levels in both dexamethasone-treated groups started to increase within 5 h after injection (i.e., PBG at 13:00 h), and were significantly increased at 19:00 h after injection (P<0.05). BG levels were almost 2-fold higher than at baseline and compared with the control group. The BG values declined gradually by 24 h to 48 h after injection. There were no differences in BG levels between the two dexamethasone-treated groups (P>0.05), except for PBG at 19:00 h on day 2 after injection (P<0.05). CONCLUSION: Periocular dexamethasone injection can cause transient hyperglycemia in diabetic patients after VRS. BG monitoring should be performed following such injection.

Retinoblastoma 94 enhances radiation treatment of esophageal squamous cell carcinoma in vitro and in vivo.

We performed the study to investigate whether adenovirus-mediated retinoblastoma 94 (RB94) gene transfer could enhance radiation treatment of esophageal squamous cell carcinoma (ESCC) in vitro and in vivo. ESCC cells (Kyse150 cell line) were cultivated in vitro and tumors originated from the cell line were propagated as xenografts in nude mice. Treatment with Ad-RB94 and/or ionizing radiation (IR) was carried out both in vitro and in vivo with Ad-LacZ control vector and blank control. Cell viability, cell cycle distribution, cell apoptosis, tumor growth and transfected gene expression were evaluated and tumor degeneration was analyzed. The data of quantification real-time PCR assays and immunohistochemistry staining using RB antibody indicated that RB94 was efficiently transfected into Kyse150 cells. In vitro, data of cell growth assay indicated that treatment with Ad-RB94 improved radiation treatment of Kyse150 cells. Tumor xenograft studies, pathological analysis of H.E. staining and Ki67 staining suggested transfecting RB94 enhanced tumor regression induced by radiation treatment in vivo. In addition, data of Annexin V, TUNEL and cell cycle distribution assays proposed combination treatment effectively induced cell apoptosis and cell cycle arresting in G2/M phase. In conclusion, transferring RB94 gene by the adenoviral vector enhances radiation treatment of ESCC.

Effects of HepII domain peptides V of fibronectin on corneal permeability, endothelial cells, intraocular pressure and morphology of trabecular meshwork in rats.

BACKGROUND: Trabecular meshwork (TM) cell volume may be an important determinant of aqueous humor outflow in the eye. This study aimed to evaluate the role of HepII domain peptides V on corneal permeability, corneal endothelial cells, intraocular pressure (IOP) and morphology of trabecular meshwork in rats. METHODS: The IOP of rat eyes was measured before and 3, 5, 7 and 8 hours after topical delivery of HepII domain peptides V through intracameral injections. The peptide's concentration in aqueous humor was assessed by high performance liquid chromatography (HPLC). The shape and density of endothelial cells were observed by laser confocal microscopy 8 hours, 3 and 14 days after intracameral injections of HepII domain peptides V. The morphological changes in TM of rat eyes were assessed by transmission electron microscopy (TEM). RESULTS: Intracameral injection of HepII domain peptides V significantly (P < 0.001) decreased IOP by (5.71 ± 2.10) mmHg in rats at 5 hours after injection. There were no obvious changes of the shape and the density of corneal endothelial cells. In addition, morphological changes in the TM of rats were observed including the expansion of intercellular spaces in the juxtacanalicular meshwork, removal of extracellular material, cellular relaxation, and cytoskeleton reorganization. CONCLUSIONS: HepII domain peptides V could not penetrate cornea and was safe to corneal endothelial cells. HepII domain peptides V could significantly decrease IOP in rat probably by disorganizing actin cytoskeleton and cell-junction in the TM.

Programmed cell death 1 gene polymorphisms is associated with ankylosing spondylitis in Chinese Han population.

Programmed cell death 1 (PD-1) has been reported to have a genetic association in several autoimmune diseases. The aim of this study was to investigate the association of PD-1 polymorphisms and haplotypes with ankylosing spondylitis (AS) in Chinese Han population. In a case-control association study, three single-nucleotide polymorphisms (SNP), PD-1.3 G/A, PD-1.5 C/T and PD-1.9 T/C, were genotyped in 216 AS patients and 264 healthy controls using polymerase chain reaction-restriction fragment length polymorphism assay. All genotype distributions in the patients and in the controls were in Hardy-Weinberg equilibrium. The associations of genotypes and alleles with AS were analyzed. The genotype distributions of PD-1.9 were significantly different between the patients with AS and the controls (P = 0.025). The frequencies of TC genotype and T allele of PD-1.9 were higher in the patients than those in the controls (P = 0.026 and 0.004). No association for PD-1.5 in AS was found, and PD-1.3 was non-polymorphic in Chinese Han population. Moreover, the frequency of the CT haplotype (PD-1.5 C/T, PD-1.9 T/C) was significantly higher in AS patients than the controls (21.6 vs. 13.9%, P = 0.002). The CC haplotype was more common in the controls than in the patients (57.1 vs. 44.6%, P = 0.000). The results support a genetic association between the PD-1 polymorphism and susceptibility to AS in Chinese Han population.