Natural pyrethrins induce cytotoxicity in SH-SY5Y cells and neurotoxicity in zebrafish embryos (Danio rerio).

Natural pyrethrins are widely used in agriculture because of their good insecticidal activity. Meanwhile, natural pyrethrins play an important role in the safety evaluation of pyrethroids as precursors for structural development of pyrethroid insecticides. However, there are fewer studies evaluating the neurological safety of natural pyrethrins on non-target organisms. In this study, we used SH-SY5Y cells and zebrafish embryos to explore the neurotoxicity of natural pyrethrins. Natural pyrethrins were able to induce SH-SY5Y cells damage, as evidenced by decreased viability, cycle block, apoptosis and DNA damage. The apoptotic pathway may be related to the involvement of mitochondria and the results showed that natural pyrethrins induced a rise in Capase-3 viability, Ca2+ overload, a decrease in adenosine triphosphate (ATP) and a collapse of mitochondrial membrane potential in SH-SY5Y cells. Natural pyrethrins may mediate DNA damage in SH-SY5Y cells through oxidative stress. The results showed that natural pyrethrins induced an increase in reactive oxygen species (ROS) levels, superoxide dismutase (SOD) activity, malondialdehyde (MDA) content and catalase (CAT) activity, and induced a decrease in glutathione peroxidase (GPx) activity in SH-SY5Y cells. In vivo, natural pyrethrins induced developmental malformations in zebrafish embryos, which were mainly characterized by pericardial edema and yolk sac edema. Meanwhile, the results showed that natural pyrethrins induced damage to the Huc-GFP axis and disturbed lipid metabolism in the head of zebrafish embryos. Further results showed elevated ROS levels and apoptosis in the head of zebrafish embryos, which corroborated with the results of the cell model. Finally, the results of mRNA expression assay of neurodevelopment-related genes indicated that natural pyrethrins exposure interfered with their expression and led to neurodevelopmental damage in zebrafish embryos. Our study may raise concerns about the neurological safety of natural pyrethrins on non-target organisms.

Emerging roles of air pollution and meteorological factors in autoimmune eye diseases.

Autoimmune eye diseases (AEDs), a collection of autoimmune inflammatory ocular conditions resulting from the dysregulation of immune system at the ocular level, can target both intraocular and periorbital structures leading to severe visual deficit and blindness globally. The roles of air pollution and meteorological factors in the initiation and progression of AEDs have been increasingly attractive, among which the systemic and local mechanisms are both involved in. Exposure to excessive air pollution and extreme meteorological conditions including PM2.5/PM0.1, environmental tobacco smoke, insufficient sunshine, and high temperature, etc., can disturb Th17/Treg balance, regulate macrophage polarization, activate neutrophils, induce systemic inflammation and oxidative stress, decrease retinal blood flow, promote tissue fibrosis, activate sympathetic nervous system, adversely affect nutrients synthetization, as well as induce heat stress, therefore may together deteriorate AEDs. The crosstalk among inflammation, oxidative stress and dysregulated immune system appeared to be prominent. In the present review, we will concern and summarize the potential mechanisms underlying linkages of air pollution and meteorological factors to ocular autoimmune and inflammatory responses. Moreover, we concentrate on the specific roles of air pollutants and meteorological factors in several major AEDs including uveitis, Graves' ophthalmopathy (GO), ocular allergic disease (OAD), glaucoma, diabetic retinopathy (DR), etc.

Design, synthesis, and biological evaluation of dinuclear bismuth(III) complexes with Isoniazid-derived Schiff bases.

Four dinuclear bismuth(III) Schiff-base complexes bearing Schiff-base ligands have been synthesized and structurally characterized by single-crystal X-ray diffraction, elemental analysis, and spectral techniques (FT-IR, NMR and MS). The analytical data reveal the bismuth(III) complexes possess 1:1 metal-ligand ratios. In vitro biological studies have revealed that bismuth(III) complexes displayed much higher antibacterial and antitumor activities than their parent ligands, which involves two gram-negative (S. aureus, B. subtili) and two gram-positive (E. coli, P. aeruginosa) bacteria, and human gastric cancer SNU-16 cells. The power-time curves of S. pombe exposed to tested compounds were detected by bio-microcalorimetry. Some thermokinetic parameters (k, Pmax,tG and Qtotal) were derived based on the metabolic power-time curves, and their quantitative relationships with the concentrations (c) were further discussed.

Comparative evaluation of rotational stability of toric IOLs with four-eyelet vs two-eyelet capsular tension rings in eyes with high myopia.

AIM: To compare the rotational stability of Toric intraocular lens (IOLs) implantation combined with four-eyelet or two-eyelet capsular tension rings (CTRs) in eyes with high myopia and cataract. METHODS: This prospective randomized controlled interventional study included 33 eyes which had preoperative corneal astigmatism ≥1.5 D and ocular axial length ≥25.5 mm. These eyes were randomly divided into two groups to undergo phacoemulsification and toric IOL implantation with either four-eyelet CTR implantation (group A, n=16) or two-eyelet CTR implantation (group B, n=17). Uncorrected visual acuity (UCVA), best-corrected visual acuity (BCVA), phoropter examination results, and toric IOL rotation degrees were tested 6mo after the surgery. RESULTS: In both groups, the toric IOL was in the capsular sac 6mo after surgery. The difference between the two groups in terms of visual outcome was not found to be statistically significant (P>0.05) at a follow-up of 6mo. The mean residual astigmatism values were 0.56±0.22 D and 0.92±0.24 D in A and B groups, respectively (P<0.001). The mean rotation degree of IOL was 1.00°±0.73° in group A and 3.53°±1.46° in group B (P<0.001). CONCLUSION: In cataract patients with high myopia and astigmatism, four-eyelet CTR can effectively increase the rotation stability of toric IOLs, achieving the desired goal of correcting corneal astigmatism.

Cobalt(III)-Catalyzed Oxidative Annulation of Benzaldehydes with Internal Alkynes via C-H Functionalization in Poly(ethylene glycol).

A novel Co(III)-catalyzed oxidative annulation of aromatic aldehydes with internal alkynes for accessing isocoumarins is described, which is achieved by oxidation, weak chelation-assisted C-H bond functionalization, and annulation cascades with excellent functional group compatibility, high atom economy, and step efficiency. By using environmentally benign and inexpensive poly(ethylene glycol)-400 (PEG-400), the Co/Cu/PEG-400 system could be recycled and reused.

Effects of miR-22 on viability, migration, invasion and apoptosis in retinoblastoma Y79 cells by targeting high-mobility group box 1.

AIM: To explore the effect of miR-22 on viability, migration, invasion and apoptosis in retinoblastoma (RB) Y79 cells and to further detect the potential mechanism. METHODS: Plasmids were constructed to change the expression level of miR-22 in Y79 cells. Real-time reverse transcription polymerase chain reaction (RT-PCR) was conducted to test the expression level of miR-22. After changing the expression of miR-22, the mRNA and protein levels of high-mobility group box 1 (HMGB1) were investigated using RT-PCR and Western blotting. The effect of miR-22 on viability was analyzed by using cell counting kit-8 (CCK-8) assay and the effect on apoptosis was detected by the flow cytometry. Wound healing migration assay and Transwell invasion assay were used to detect the effects of miR-22 on cell motility. RESULTS: miR-22 inhibited viability, migration and invasion, while promoting apoptosis, in RB Y79 cells. The inhibition rate of miR-22 overexpression group at 12, 24, 48h was 11.71%±2.54%, 21.36%±1.39% and 29.44%±1.15%, respectively. Cellular apoptosis was higher in miR-22 overexpression group (17.00%±0.39%) compared with negative control (4.38%±0.38%). miR-22 negatively mediated the expression of HMGB1. Furthermore, decreased HMGB1 significantly attenuated viability, migration and invasion, while promoting apoptosis. Enforced expression of HMGB1 partially rescued the effects of miR-22 overexpression on cell viability, migration, invasion and apoptosis. Moreover, the phosphorylated protein kinase B (p-AKT) was significantly downregulated in the HMGB1 shRNA group and miR-22 overexpression group and elevated in the HMGB1 overexpression group compared with the normal control. CONCLUSION: miR-22 inhibites viability, migration and invasion and increases apoptosis in Y79 cells by targeting HMGB1. These findings may provide a therapeutic strategy for RB.

Long-term outcomes of uveitic glaucoma treated with Ahmed valve implant in a series of Chinese patients.

AIM: To report long-term outcomes of secondary glaucoma due to uveitis treated with Ahmed glaucoma valve (AGV) implantation in a series of Chinese patients. METHODS: The retrospective study included 67 eyes from 56 patients with uveitic glaucoma who underwent AGV implantation. Success of the treatment was defined as patients achieving intraocular pressure (IOP) levels between 6 and 21 mm Hg with or without additional anti-glaucoma medications and/or a minimum of 20% reduction from baseline IOP. The main outcome measurements included IOP, the number of glaucoma medications at 1, 3, 6, 12, 24, 36, 48 and 60mo after surgery, surgical complications, final best-corrected vision acuity (BCVA), visual field (VF) and retinal nerve fiber layer (RNFL). RESULTS: The mean follow-up was 53.3±8.5 (range 48 to 60)mo. The cumulative probability of success rate was 98.5%, 95.5%, 89.6%, 83.6%, 76.1%, 70.1%, 65.7% and 61.2% at 1, 3, 6, 12, 24, 36, 48 and 60mo, respectively. IOP was reduced from a baseline of 30.8±6.8 to 9.9±4.1, 10.1±4.2, 10.9±3.7, 12.9±4.6, 13.8±3.9, 13.2±4.6, 12.3±3.5 and 13.1±3.7 mm Hg at 1, 3, 6, 12, 24, 36, 48 and 60mo, respectively (P<0.01). The number of postoperative glaucoma medications was significantly decreased compared with baseline at all time points during the study period (P<0.05). There was no significant difference between preoperative and postoperative BCVA. Remarkable surgical complications were not found after surgery. The VF and RNFL of the patients were stable after the surgery. CONCLUSION: AGV implantation is safe and effect in terms of reducing IOP, decreasing the number of glaucoma medications, and preserving vision for patients with uveitic glaucoma.

Peptidome profiling of human serum of uveal melanoma patients based on magnetic bead fractionation and mass spectrometry.

AIM: To find new biomarkers for uveal melanoma (UM) by analyzing the serum peptidome profile. METHODS: Proteomic spectra in patients with UM before and after operation were analyzed and compared with those of healthy controls. Magnetic affinity beads were used to capture serum peptides and matrix-assisted laser desorption/ionization time-of-flight (MALDI-TOF) mass spectrometer were used to compile serum peptide profiles. RESULTS: A panel of 49 peptides were differentially expressed between UM patients and controls, of which 33 peptides were of higher intensities in patient group and 16 peptides were of higher intensities in control group. Based on combined use of these potential markers, peptides with mean molecular masses of 1467 and 9289.0 Da provide high sensitivity (83.3%), specificity (100%) and accuracy rate (93.0%) together to differentiate melanoma patients from healthy controls. At the time point of 6mo postoperatively, the levels of many peptides differentially expressed before surgery showed no more statistical difference between the patients and the control group. Fibrinogen α-chain precursors were identified as potential UM markers. CONCLUSION: We have shown that a convenient and fast proteomic technique, affinity bead separation and MALDI-TOF analysis combined with bioinformatic software, facilitates the identification of novel biomarkers for UM.

Identification of phoslactomycin biosynthetic gene clusters from Streptomyces platensis SAM-0654 and characterization of PnR1 and PnR2 as positive transcriptional regulators.

Phoslactomycins (PLMs) are inhibitors of protein serine/threonine phosphatase 2A showing diverse and important antifungal, antibacterial and antitumor activity. PLMs are polyketide natural products and produced by several Streptomyces species. The PLMs biosynthetic gene clusters were identified from Streptomyces platensis SAM-0654 and localized in two separate genomic regions, consisting of 27 open reading frames that encode polyketide synthases (PKSs), enzymes for cyclohexanecarboxyl-CoA (CHC-CoA) and ethylmalonyl-CoA (Em-CoA) synthesis, enzymes for post-PKS modifications, proposed regulators, and putative resistance transporters. Bioinformatic analysis and inactivation experiment of regulatory genes suggest that PnR1 and PnR2 are two positive regulators of PLMs biosynthesis. Gene transcription analysis by reverse transcriptase PCR (RT-PCR) of the PLMs gene cluster demonstrated that PnR1 and PnR2 activate the transcription of the structural biosynthetic genes while PnR2 specially governs the transcription of pnR1 in a higher level.

[A crossover control study of prophylactic treatment of chemotherapy-induced constipation by senna extract].

OBJECTIVE: To observe the prophylactic effects of senna extract 40 mg/kg on chemotherapy-induced constipation. METHODS: Eighty-two patients suffering from constipation after chemotherapy were assigned to Group AB and Group BA. Group AB referred to patients who first took senna extract in the 1st chemotherapeutic course and the crude fiber diet in the 2nd chemotherapeutic course. But the sequence was just the opposite in Group BA. The effective rates of relieving chemotherapy-induced constipation by senna extract and by the crude fiber diet were observed. The differences of the digestive tract reaction and the hematotoxicity reaction were compared. The conditions of patients' abdominal pain and stool properties were observed after they took senna extract. RESULTS: The effective rate of constipation by taking senna extract was 92.68% and that by the crude fiber diet was 10.93%, with statistical difference shown (P < 0.01). There was no statistic difference in adverse reaction rate such as decreased neutrophils over degree II, decreased hemoglobin, decreased platelet, nausea, vomit, etc. (P > 0.05). The occurrence rate of abdominal pain over degree II after taking senna was 8.54%. In the distribution of stool properties, the rate of loose stool was 35.53%. CONCLUSION: Senna extract 40 mg/kg was effective and safe in treating chemotherapy-induced constipation.

Expression of cell proliferation and apoptosis biomarkers in pterygia and normal conjunctiva.

PURPOSE: To analyze the expression of apoptosis and cell proliferation molecules in pterygium tissues of Chinese patients. METHODS: Thirty-three pterygia were surgically removed using the bare sclera procedure, and 23 normal bulbar conjunctivas were also obtained. Formalin-fixed, paraffin-wax-embedded tissues were analyzed by immunohistochemistry with anti- proliferating cell nuclear antigen (PCNA), K(i)-67 (a proliferating cell marker), mutant p53 (mP53), Bcl-2 associated X-protein (BAX), B-cell lymphoma gene 2 (Bcl-2), and caspase-3 antibodies. Terminal deoxynucleotidyl transferase-mediated dUTP-biotin nick end labeling assay (TUNEL) analysis was used to analyze the apoptotic cells. RESULTS: Our study revealed that the positive rate of PCNA and K(i)-67 significantly increased in the pterygium samples compared to the normal conjunctiva samples. In the molecules involved in apoptosis, the results showed that the positive rate of Bcl-2 and mP53 significantly increased in the pterygium samples. However, no difference was found between the pterygium and normal conjunctiva samples in the expression of Bax and caspase-3. Through TUNEL analysis, apoptotic cells were seen in the entire width of the epithelial layer in normal conjunctivas but were found mainly confined to the outer layer of the epithelial cells in pterygia. CONCLUSIONS: The finding of high levels of cellular proliferation and low levels of cellular apoptosis in pterygia confirmed that both cell apoptosis and proliferation are known to play an important role in human pterygium pathogenesis.