Characterizing the effects of different chemicals on stem bending of cut snapdragon flower

Background This study investigated the effects of ethylene release compounds (ethephon), ethylene-action inhibitors (silver thiosulfate: STS), and nitric oxide donor (sodium nitroprusside: SNP) on stem bending of snapdragon flowers. Moreover, the effects of plant growth supplements [6-benzyladenine (BA), gibberellic acid 3 (GA3), and calcium chloride (CaCl2)] on the stem bending were also extensively investigated. Results Ethephon completely prevented stem bending until 9 days after treatment (9 DAT). STS exhibited the highest bending rate, while SNP did not significantly affect the bending compared to the controls. The bending results were associated with the results of stem curvature, relative shoot elongation, ethylene production, and lignin content, that are involved in the stem bending mechanism. This was proven by the expression analysis of genes involved in ethylene and lignin biosynthetic pathways. The addition of plant growth supplements slightly or significantly delayed stem bending in the treatments (control, SNP, and STS) and significantly reduced petal senescence in ethephon at 9 DAT. Conclusion These results show the preventive role of ethephon in the stem bending of cut snapdragon. Moreover, the combination of ethephon with supplements also provided information that could guide the development of strategies to delay stem bending in other cut flowers that undergo serious bending during a short vase life.

CHANGES IN ACTIVITY OF INDUCIBLE NITRIC OXIDE SYNTHASE IN EXPERIMENTAL DIABETIC RETINOPATHY AND METHODS FOR ITS CORRECTION

Diabetic retinopathy according to the World Health Organization reports is known as the main cause of decreased vision and blindness in diabetes. The purpose of the study is to analysis of changes in the activity of inducible nitric oxide synthase in experimental diabetic retinopathy and in various methods of its correction. Materials and methods. The research was carried out on white Wistar rats weighting 180-220 g. The animals were divided into 7 groups: 1st group included 60 intact animals; 2nd group involved 60 animals with modelled diabetic retinopathy (DR) without further correction; 3rd group included 60 animals with modelled DR and subsequent hyperglycemia correction; 4th group included 60 animals with modelled DR, which received subsequent hyperglycemia correction with aflibercept and L-arginine solution administration; 5th group consisted of 60 animals with modelled DR and subsequent hyperglycemia correction by aflibercept and bromfenac administration; 6th group was formed by 60 animals with modelled DR and subsequent hyperglycemia correction by aflibercept, L-carnitine and bromfenac administration; and the 7th group included 60 animals with modelled DR and subsequent hyperglycemia correction by aflibercept, L-arginine solution and citicoline. Results and conclusion. The results obtained demonstrate an increase in the activity of inducible nitric oxide synthase, starting from the 30th day of the experiment and with subsequent progression to the 60 and 108 days of experimental diabetic retinopathy that points out the deterioration of the physiological pathway of nitric oxide synthesis. Correction with hypoglycemic agents in group 3 had a positive effect, but was not able to reduce the activity of inducible nitric oxide synthase, which increased in the 2nd and 3rd stages, thus, there was a need for additional agents. The use of aflibercept and nitric oxide donor in group 4 to correct the progression of diabetic retinopathy significantly reduced the activity of inducible nitric oxide synthase (most effectively on the one hundred and eighty days of the experiment), but did not reach the control values. It has been proved that the correction applied in groups 5 and 6 significantly reduced the activity of inducible nitric oxide synthase but did not reach the control values. Moreover, the marker activity in the group 5 grew up on the 108 day. The study has shown the most effective correction includes a combination of metformin, aflibercept, L-arginine and citicoline given to the rats of group 7, as evidenced by the normalization of malonic dialdehyde levels on the 60 day of the experiment; on the 108 days of experiment there has been a decrease in marker content to control values.

Visually induced changes in cytokine production in the chick choroid

Postnatal ocular growth is regulated by a vision-dependent mechanism which acts to minimize refractive error through coordinated growth of the ocular tissues. Of great interest is the identification of the chemical signals that control visually-guided ocular growth. Here we provide evidence that the pro-inflammatory cytokine, Interleukin-6 (IL-6), may play a pivotal role in the control of ocular growth using a chicken model of myopia. Microarray, real time RT-qPCR, and ELISA analyses identified IL-6 upregulation in the choroids of chick eyes under two visual conditions that introduce myopic defocus and slow the rate of ocular elongation (recovery from induced myopia and compensation for positive lenses). Intraocular administration of atropine, an agent known to slow ocular elongation, also resulted in an increase in choroidal IL-6 gene expression. Nitric oxide appears to directly or indirectly upregulate choroidal IL-6 gene expression, as administration of the non-specific nitric oxide synthase inhibitor, L-NAME, inhibited choroidal IL-6 gene expression, and application of a nitric oxide donor stimulated IL-6 gene and protein expression in isolated chick choroids. Considering the pleiotropic nature of IL-6 and involvement in many biological processes, these results suggest that IL-6 may mediate many aspects of the choroidal response in the control of ocular growth.

Therapeutic Drugs and Devices for Tackling Ocular Hypertension and Glaucoma, and Need for Neuroprotection and Cytoprotective Therapies

Damage to the optic nerve and the death of associated retinal ganglion cells (RGCs) by elevated intraocular pressure (IOP), also known as glaucoma, is responsible for visual impairment and blindness in millions of people worldwide. The ocular hypertension (OHT) and the deleterious mechanical forces it exerts at the back of the eye, at the level of the optic nerve head/optic disc and lamina cribosa, is the only modifiable risk factor associated with glaucoma that can be treated. The elevated IOP occurs due to the inability of accumulated aqueous humor (AQH) to egress from the anterior chamber of the eye due to occlusion of the major outflow pathway, the trabecular meshwork (TM) and Schlemm’s canal (SC). Several different classes of pharmaceutical agents, surgical techniques and implantable devices have been developed to lower and control IOP. First-line drugs to promote AQH outflow via the uveoscleral outflow pathway include FP-receptor prostaglandin (PG) agonists (e.g., latanoprost, travoprost and tafluprost) and a novel non-PG EP2-receptor agonist (omidenepag isopropyl, Eybelis®). TM/SC outflow enhancing drugs are also effective ocular hypotensive agents (e.g., rho kinase inhibitors like ripasudil and netarsudil; and latanoprostene bunod, a conjugate of a nitric oxide donor and latanoprost). One of the most effective anterior chamber AQH microshunt devices is the Preserflo® microshunt which can lower IOP down to 10–13 mmHg. Other IOP-lowering drugs and devices on the horizon will be also discussed. Additionally, since elevated IOP is only one of many risk factors for development of glaucomatous optic neuropathy, a treatise of the role of inflammatory neurodegeneration of the optic nerve and retinal ganglion cells and appropriate neuroprotective strategies to mitigate this disease will also be reviewed and discussed.

Effects of Naringin on Cardiomyocytes From a Rodent Model of Type 2 Diabetes

Diabetic cardiomyopathy (DCM) is a primary disease in diabetic patients characterized by diastolic dysfunction leading to heart failure and death. Unfortunately, even tight glycemic control has not been effective in its prevention. We have found aberrant diastolic Ca2+ concentrations ([Ca2+]d), decreased glucose transport, elevated production of reactive oxygen species (ROS), and increased calpain activity in cardiomyocytes from a murine model (db/db) of type 2 diabetes (T2D). Cardiomyocytes from these mice demonstrate significant cell injury, increased levels of tumor necrosis factor-alpha and interleukin-6 and expression of the transcription nuclear factor-κB (NF-κB). Furthermore, decreased cell viability, and reduced expression of Kir6.2, SUR1, and SUR2 subunits of the ATP-sensitive potassium (KATP) channels. Treatment of T2D mice with the citrus fruit flavonoid naringin for 4 weeks protected cardiomyocytes by reducing diastolic Ca2+ overload, improving glucose transport, lowering reactive oxygen species production, and suppressed myocardial inflammation. In addition, naringin reduced calpain activity, decreased cardiac injury, increased cell viability, and restored the protein expression of Kir6.2, SUR1, and SUR2 subunits of the KATP channels. Administration of the KATP channel inhibitor glibenclamide caused a further increase in [Ca2+]d in T2D cardiomyocytes and abolished the naringin effect on [Ca2+]d. Nicorandil, a KATP channel opener, and nitric oxide donor drug mimic the naringin effect on [Ca2+]d in T2D cardiomyocyte; however, it aggravated the hyperglycemia in T2D mice. These data add new insights into the mechanisms underlying the beneficial effects of naringin in T2D cardiomyopathy, thus suggesting a novel approach to treating this cardiovascular complication.

The Nitric Oxide Donor, S-Nitrosoglutathione, Rescues Peroxisome Number and Activity Defects in PEX1G843D Mild Zellweger Syndrome Fibroblasts

Peroxisome biogenesis disorders (PBDs) are a group of metabolic developmental diseases caused by mutations in one or more genes encoding peroxisomal proteins. Zellweger syndrome spectrum (PBD-ZSS) results from metabolic dysfunction caused by damaged or non-functional peroxisomes and manifests as a multi-organ syndrome with significant morbidity and mortality for which there is no current drug therapy. Mild PBD-ZSS patients can exhibit a more progressive disease course and could benefit from the identification of drugs to improve the quality of life and extend the lifespan of affected individuals. Our study used a high-throughput screen of FDA-approved compounds to identify compounds that improve peroxisome function and biogenesis in human fibroblast cells carrying the mild PBD-ZSS variant, PEX1G843D. Our screen identified the nitrogen oxide donor, S-nitrosoglutathione (GSNO), as a potential therapeutic for this mild form of PBD-ZSS. Further biochemical characterization showed that GSNO enhances both peroxisome number and function in PEX1G843D mutant fibroblasts and leads to increased survival and longer lifespan in an in vivo humanized Drosophila model carrying the PEX1G843D mutation. GSNO is therefore a strong candidate to be translated to clinical trials as a potential therapeutic for mild PBD-ZSS.