Sonographic and clinical effects of manual physical therapy for plantar fasciitis: randomized prospective controlled trial.

OBJECTIVE: This study aimed to evaluate the efficacy of manual physiotherapy on clinical outcomes, morphology of plantar fascia (PF), thicknesses of calcaneal fat pad (CFP) and Kager's fat pad (KFP) with ultrasound imaging in plantar fasciitis (PFS) patients. Also, to evaluate the PF thickness, pain and foot functional outcomes among PFS phases. METHODS: A randomized controlled trial was conducted on 122 subjects divided into three groups: group A (40 patients with PFS) underwent manual physiotherapy, group B (42 patients with PFS) without any intervention and group C (40 healthy subjects) were matched by age, gender and BMI with each patient in group A and B. The following outcomes were evaluated at baseline and one-month of follow-ups: morphology of PF and thicknesses of CFP and KFP, pain, foot functional limitation. RESULTS: PF thickness was significantly thickened in group A and B compared to group C (P < 0.001). A significant decrease in incidence of PF echogenicity and CFP thickness were found in group A and B compared to group C. Moreover, significant improvement was observed in PF thickness (P < 0.001), PF echogenicity (P < 0.001) and CFP thickness (P = 0.002) in group A at one-month after the treatment. Furthermore, pain intensity and foot functional limitation was significantly improved within group A after receiving the treatment. Significant improvement was noted in PF thickness, pain intensity and foot functional limitation among patients with acute phase. CONCLUSION: The manual physiotherapy is effective in treatment of PF thickening, hypoechogenicity, pain intensity and activity limitations, particularly in patients associated with acute PFS.

An assessment of plantar fascia with ultrasound findings in patients with plantar fasciitis: a systematic review.

INTRODUCTION: Plantar fasciitis (PFS) is described by an intense pain over medial tubercle of calcaneus, increased with the first step after waking up, after rest and during weightbearing activity. It is the most common cause of plantar heel pain in adults with the prevalence estimated 10% of the general population. Ultrasound imaging is commonly being used to measure the PF thickness, evaluate the efficacy of different treatments and a guide therapeutic technique in patients with PFS. The objective of this study was to systematically review the studies that were previously published to evaluate the role of ultrasound in the assessment of PF in patients with PFS. METHODS: A systematic search was carried out over the last 5 years from 2017 to 2022 on basis the following electronic databases: Science Direct, Scopus, Web of Science, Springer and PubMed. The keywords that used in the searching were: ultrasound, sonography, ultrasonography, plantar fasciitis, imaging of plantar fascia, physiotherapy of plantar fasciitis, interventional treatment of plantar fasciitis, randomized controlled trial of plantar fasciitis and interventional ultrasound. The review focused on the assessment of PF in patients with PFS underwent different interventions using B-mode, shear wave elastography (SWE) and color Doppler ultrasound. RESULTS: During the search process, 1661 were recorded using the proper keywords from 2017 to 2022 in which 666 original articles were found after removing the review and duplicated articles. Of these, thirty articles met the inclusion criteria and included in this review. The articles have assessed the PF in patients with PFS under different conditions using different ultrasound modes. Twenty-six articles evaluated the effectiveness of different treatment on PF in patients with PFS using different ultrasound modes. In 8 of 26 articles, the ultrasound was used as both an assessment tool of PF and guide therapeutic technique in patients with PFS. In 18 articles, the ultrasound was used as only assessment tool to identify the PF thickness and its observation changes in patients with PFS. Four articles compared the PF thickness and its intrafascial changes between patients with PFS and healthy subjects. CONCLUSION: The ultrasound can be a reliable tool in assessment the effect of different interventions on PF by evaluating its thickness, echogenicity and stiffness changes in patients with PFS. There were different methods and treatments were used among the studies.

Meteorological Drought Variability and Its Impact on Wheat Yields across South Africa.

Drought is one of the natural hazards that have negatively affected the agricultural sector worldwide. The aims of this study were to track drought characteristics (duration (DD), severity (DS), and frequency (DF)) in South Africa between 2002 and 2021 and to evaluate its impact on wheat production. Climate data were collected from the South African Weather Service (SAWS) along with wheat yield data from the Department of Agriculture, Forestry and Fisheries (2002-2021). The standard precipitation index (SPI) was calculated on 3-, 6-, 9-, and 12-month time scales, and the trend was then tracked using the Mann-Kendall (MK) test. To signify the climatic effects on crop yield, the standardized yield residual series (SYRS) was computed along with the crop-drought resilience factor (CR) on a provincial scale (2002-2021). The output of the SPI analysis for 32 stations covering all of South Africa indicates a drought tendency across the country. On a regional scale, western coastal provinces (WES-C and NR-C) have been more vulnerable to meteorological droughts over the past 20 years. Positive correlation results between SYRS and wheat yield indicate that the WES-C province was highly influenced by drought during all stages of wheat growth (Apr-Nov). Historical drought spells in 2003, 2009, and 2010 with low CR = 0.64 caused the province to be highly impacted by the negative impacts of droughts on yield loss. Overall, drought events have historically impacted the western part of the country and dominated in the coastal area. Thus, mitigation plans should be commenced, and priority should be given to this region. These findings can assist policymakers in budgeting for irrigation demand in rainfed agricultural regions.

Environmental impacts of corn silage production: influence of wheat residues under contrasting tillage management types.

The intensification of specific land management operations (tillage, herbicide, etc.) is increasing land degradation and contributing to ecosystem pollution. Mulches can be a sustainable tool to counter these processes. This is particularly relevant for rural areas in low-income countries where agriculture is a vital sector. In this research, the environmental impact of different rates of wheat residues (no residues, 25, 50, 75, and 100%) in corn silage cultivation was evaluated using the life cycle assessment (LCA) method under conventional tillage (CT) and no-tillage (NT) systems in a semi-arid region in Karaj, Iran. Results showed that in both tillage systems, marine aquatic ecotoxicity (ME) and global warming potential (GWP) had the highest levels of pollution among the environmental impact indicators. In CT systems, the minimum (17,730.70 kg 1,4-dichlorobenzene (DB) eq.) and maximum (33,683.97 kg 1,4-DB eq.) amounts of ME were related to 0 and 100% wheat residue rates, respectively. Also, in the CT system, 0 and 100% wheat residue rates resulted in minimum (176.72 kg CO2 eq.) and maximum (324.95 kg CO2 eq.) amounts of GWP, respectively. However, in the NT system, the 100% wheat residue rate showed the minimum amounts of ME (11,442.39 kg 1,4-DB eq.) and GWP (120.21 kg CO2 eq.). Also, in the NT system, maximum amounts of ME (17,174 kg 1,4-DB eq.) and GWP (175.60 kg CO2 eq.) were observed with a zero wheat residue rate. On-farm emissions and nitrogen fertilizers were the two factors with the highest contribution to the degradation related to environmental parameters at all rates of wheat residues. Moreover, in the CT system, the number of environmental pollutants increased with the addition of a higher wheat residue rate, while in the NT system, increasing residue rates decreased the amount of environmental pollutants. In conclusion, this LCA demonstrates that the NT system with the full retention of wheat residues (100%) is a more environmentally sustainable practice for corn silage production. Therefore, it may be considered one of the most adequate management strategies in this region and similar semi-arid conditions. Further long-term research and considering more environmental impact categories are required to assess the real potential of crop residues and tillage management for sustainable corn silage production.

Spatial-temporal dynamic impact of changes in rainfall erosivity and vegetation coverage on soil erosion in the Eastern Mediterranean.

In Syria, soil erosion (SoEr) by water is one of the major challenges for sustainability. Thus, the main goals of this research were to evaluate the spatial changes of SoEr between 2000 and 2018 in the whole coastal basin (CB) of Syria and to provide a soil water erosion risk map for the study area. For this purpose, monthly rainfall data, the SoilGrids dataset, satellite image derived NDVI layers, and Digital Elevation Model (DEM) were collected. Through the integration of these layers into the Revised Universal Soil Loss Equation (RUSLE), under a Geographic Information System (GIS), soil loss was assessed. Also, the contribution of land cover changes and R factor on SoEr were evaluated. The outcomes of this assessment illustrated that the R factor ranged from 800 to 2600 MJ mm ha-1 h-1 yr-1, while the soil erodibility factor (K factor) ranged from 0.048 to 0.035 ton ha MJ-1 mm-1. The C factor (vegetation coverage) values ranged between 0.07 and 1 with a spatial average value of 0.44 for the 2000-2009 period and 0.39 for the 2010-2018 interval. The output of RUSLE revealed that average annual SoEr was of 21.35 ton ha-1 y-1 (± 38) for 2000-2009 and 22.47 ton ha-1 y-1(± 41.8) for 2010-2018. Interestingly, the increased SoEr caused by the R factor was dominant (34.65%), followed by changes in both C factor and R factor (13.34%). However, decrease of SoEr rates is due to the increase of the C factor accounting for 36.82% of the CB. The outcome of this research can provide constructive spatial insights for rehabilitation plans for the post-war phase of Syria.

Predicting Modified Fournier Index by Using Artificial Neural Network in Central Europe.

The Modified Fournier Index (MFI) is one of the indices that can assess the erosivity of rainfall. However, the implementation of the artificial neural network (ANN) for the prediction of the MFI is still rare. In this research, climate data (monthly and yearly precipitation (pi, Ptotal) (mm), daily maximum precipitation (Pd-max) (mm), monthly mean temperature (Tavg) (°C), daily maximum mean temperature (Td-max) (°C), and daily minimum mean temperature (Td-min) (°C)) were collected from three stations in Hungary (Budapest, Debrecen, and Pécs) between 1901 and 2020. The MFI was calculated, and then, the performance of two ANNs (multilayer perceptron (MLP) and radial basis function (RBF)) in predicting the MFI was evaluated under four scenarios. The average MFI values were between 66.30 ± 15.40 (low erosivity) in Debrecen and 75.39 ± 15.39 (low erosivity) in Pecs. The prediction of the MFI by using MLP was good (NSEBudapest(SC3) = 0.71, NSEPécs(SC2) = 0.69). Additionally, the performance of RBF was accurate (NSEDebrecen(SC4) = 0.68, NSEPécs(SC3) = 0.73). However, the correlation coefficient between the observed MFI and the predicted one ranged between 0.83 (Budapest (SC2-MLP)) and 0.86 (Pécs (SC3-RBF)). Interestingly, the statistical analyses promoted SC2 (Pd-max + pi + Ptotal) and SC4 (Ptotal + Tavg + Td-max + Td-min) as the best scenarios for predicting MFI by using the ANN-MLP and ANN-RBF, respectively. However, the sensitivity analysis highlighted that Ptotal, pi, and Td-min had the highest relative importance in the prediction process. The output of this research promoted the ANN (MLP and RBF) as an effective tool for predicting rainfall erosivity in Central Europe.

Impact of Olive Oil Constituents on C-reactive Protein: In silico Evidence.

Pain is a sensation a humans sense as a protective mechanism against physical injury. This sensation is closely related to inflammation. It ranges from mild to highly obnoxious. It is well-known that the levels of the inflammatory biomarker, C-reactive protein (CRP), increase manifold in acute inflammation and pain. Olive oil, known to have many phytochemicals, has been traditionally used to alleviate pain. Amongst major phenolic compounds in olive oil are oleuropein (OLE), hydroxytyrosol (HT), tyrosol, and oleocanthal. Whether the analgesic and anti-inflammatory properties in olive oil are due to any specific interections is not known. Therefore, this study aimed to elucidate the possible anti-inflammatory and anti-nociceptive properties in those major phenolic compounds by using molecular docking software MOE 2015, comparing the energy value and binding site of phenolic compounds to that of well-known synthetic non-steroidal anti-inflammatory drugs (NSAIDs) and phosphocholine. The docking experiment showed that all compounds could directly interact with CRP. Oleuropein had the most potent interaction with CRP (-7.7580), followed by indomethacin (-6.0775), oleocanthal (-5.5734), ibuprofen (-5.3857), phosphocholine (-4.3876), HT (-4.2782), and tyrosol (-4.2329). Interestingly, the present study found other phytochemicals in olive oil that can be exploited as potential, safe, and cost-effective lead compound(s) for analgesic and anti-inflammatory activity, as supported by its molecular docking data.

Assessing the impacts of agricultural drought (SPI/SPEI) on maize and wheat yields across Hungary.

This study examined the physical properties of agricultural drought (i.e., intensity, duration, and severity) in Hungary from 1961 to 2010 based on the Standardized Precipitation Index (SPI) and the Standardized Precipitation Evapotranspiration Index (SPEI). The study analyzed the interaction between drought and crop yield for maize and wheat using standardized yield residual series (SYRS), and the crop-drought resilient factor (CDRF). The results of both SPI and SPEI (-3, -6) showed that the western part of Hungary has significantly more prone to agricultural drought than the eastern part of the country. Drought frequency analysis reveals that the eastern, northern, and central parts of Hungary were the most affected regions. Drought analysis also showed that drought was particularly severe in Hungary during 1970-1973, 1990-1995, 2000-2003, and 2007. The yield of maize was more adversely affected than wheat especially in the western and southern regions of Hungary (1961-2010). In general, maize and wheat yields were severely non-resilient (CDRF < 0.8) in the central and western part of the country. The results suggest that drought events are a threat to the attainment of the second Sustainable Development Goals (SDG-2). Therefore, to ensure food security in Hungary and in other parts of the world, drought resistant crop varieties need to be developed to mitigate the adverse effects of climate change on agricultural production.

Lipofection of Single Guide RNA Targeting MMP8 Decreases Proliferation and Migration in Lung Adenocarcinoma Cells.

Background and Objectives: Matrix metalloproteinases (MMP) have been implicated as major determinants of tumour growth and metastasis, which are considered two of the main hallmarks of cancer. The interaction of MMP8 and other signalling molecules within and adjacent tumoral tissues, including immune cells, are rather elusive, particularly of adenocarcinoma cell type. In this study, we aimed to investigate the role of MMP8 in non-small cell lung cancer proliferation and invasiveness potential. Materials and Methods: We individually lipofected with two different single guide RNA (sgRNAs) that specifically targeted on MMP8, with CRISPR-Cas 9 protein into the cells. Results: Our results clearly indicated that the lipofection of these complexes could lead to reduced ability of A549 cells to survive and proliferate to form colonies. In addition, when compared to non-transfected cells, the experimental cell groups receiving sgRNAs demonstrated relatively decreased migration rate, hence, wider wound gaps in scratch assay. The quantitative real time-polymerase chain reaction (qRT-PCR) demonstrated significant reduction in the MAP-K, survivin and PI3-K gene expression. MMP8 might have protective roles over tumour growth and spread in our body. Conclusions: The delivery of sgRNAs targeting on the MMP8 gene could induce tumour cell death and arrest cell migratory activity.

Assessing the WEPP model performance for predicting daily runoff in three terrestrial ecosystems in western Syria.

Soil erosion is one of the main threats facing the agriculture and natural resources sector all over the world, and the same is true for Syria. Several empirical and physically based tools have been proposed to assess erosion induced soil losses and runoff driving the processes, from plot to regional spatial scales. The main goal of this research is to evaluate the performance of the Water Erosion Prediction Project (WEPP) model in predicting runoff in comparison with field experiments in the Al-Sabahia region of Western Syria in three ecosystems: agricultural lands (AG), burned forest (BF) and forest (FO). To achieve this, field experimental plots (2∗1.65∗0.5 m) were prepared to obtain runoff observation data between September 2012 and December 2013. In addition, the input data (atmospheric forcing, soil, slope, land management) were prepared to run the WEPP model to estimate the runoff. The results indicate that the average observed runoffs in the AG, BF and FO were 12.54 ± 1.17, 4.81 ± 0.97 and 1.72 ± 0.16 mm/event, respectively, while the simulated runoffs in the AG, BF and FO were 15.15 ± 0.89, 9.23 ± 1.48 and 2.61 ± 0.47mm/event, respectively. The statistical evaluation of the model's performance showed an unsatisfactory performance of the WEPP model for predicting the run-offs in the study area. This may be caused by the structural flaws in the model, and/or the insufficient site-specific input parameters. So, to achieve good performance and reliable results of the WEPP model, more observation data is required from different ecosystems in Syria. These findings can provide guidance to planners and environmental engineers for proposing environmental protection and water resources management plans in the Coastal Region in Syria.

Lung development, repair and cancer: A study on the role of MMP20 gene in adenocarcinoma.

Multiple matrix metalloproteinases have significant roles in tissue organization during lung development, and repair. Imbalance of proteinases may lead to chronic inflammation, changes in tissue structure, and are also highly associated to cancer development. The role of MMP20 is not well studied in lung organogenesis, however, it was previously shown to be present at high level in lung adenocarcinoma. The current study aimed to identify the functional properties of MMP20 on cell proliferation and motility in a lung adenocarcinoma in vitro cell model, and relate the interaction of MMP20 with other molecular signalling pathways in the lung cells after gaining tumoral properties. In this study, two different single guide RNA (sgRNAs) that specifically targeted on MMP20 sites were transfected into human lung adenocarcinoma A549 cells by using CRISPR-Cas method. Following that, the changes of PI3-K, survivin, and MAP-K mRNA gene expression were determined by Real-Time Polymerase Chain Reaction (RT-PCR). The occurrence of cell death was also examined by Acridine Orange/Propidium Iodide double staining. Meanwhile, the motility of the transfected cells was evaluated by wound healing assay. All the data were compared with non-transfected cells as a control group. Our results demonstrated that the transfection of the individual sgRNAs significantly disrupted the proliferation of the A549 cell line through suppression in the gene expression of PI3-K, survivin, and MAP-K. When compared to non-transfected cells, both experimental cell groups showed reduction in the migration rate, as reflected by the wider gaps in the wound healing assay. The current study provided preliminary evidence that MMP20 could have regulatory role on stemness and proliferative genes in the lung tissues and affect the cell motility. It also supports the notion that targeting MMP20 could be a potential treatment mode for halting cancer progression.

CMIP5 climate projections and RUSLE-based soil erosion assessment in the central part of Iran.

Soil erosion (SE) and climate change are closely related to environmental challenges that influence human wellbeing. However, the potential impacts of both processes in semi-arid areas are difficult to be predicted because of atmospheric variations and non-sustainable land use management. Thus, models can be employed to estimate the potential effects of different climatic scenarios on environmental and human interactions. In this research, we present a novel study where changes in soil erosion by water in the central part of Iran under current and future climate scenarios are analyzed using the Climate Model Intercomparison Project-5 (CMIP5) under three Representative Concentration Pathway-RCP 2.6, 4.5 and 8.5 scenarios. Results showed that the estimated annual rate of SE in the study area in 2005, 2010, 2015 and 2019 averaged approximately 12.8 t ha-1 y-1. The rangeland areas registered the highest soil erosion values, especially in RCP2.6 and RCP8.5 for 2070 with overall values of 4.25 t ha-1 y-1 and 4.1 t ha-1 y-1, respectively. They were followed by agriculture fields with 1.31 t ha-1 y-1 and 1.33 t ha-1 y-1. The lowest results were located in the residential areas with 0.61 t ha-1 y-1 and 0.63 t ha-1 y-1 in RCP2.6 and RCP8.5 for 2070, respectively. In contrast, RCP4.5 showed that the total soil erosion could experience a decrease in rangelands by - 0.24 t ha-1 y-1 (2050), and - 0.18 t ha-1 y-1 (2070) or a slight increase in the other land uses. We conclude that this study provides new insights for policymakers and stakeholders to develop appropriate strategies to achieve sustainable land resources planning in semi-arid areas that could be affected by future and unforeseen climate change scenarios.

Development of fuzzy analytic hierarchy process based water quality model of Upper Ganga river basin, India.

The ecological sustainability of rivers is in question due to severe pollution and lack of stringent regulations. Long term (1990-2016) water quality data of five stations namely Haridwar, Bareilly, Kanpur, Prayagraj and Varanasi of Upper Ganga river, India was considered for analysis using fuzzy analytical process (FAHP) based water quality index (WQI) to assess surface water quality. The value of water physical, biological and chemical parameters of temporal resolution (monthly, seasonal and yearly) indicate that value of electrical conductivity (EC), total dissolved solids (TDS), biological oxygen demand (BOD), chemical oxygen demand (COD), total alkalinity (Mg CaCO3), total hardness (Mg CaCO3), calcium (Ca), magnesium (Mg), sodium (Na), chlorine (Cl) and bicarbonate (HCO3) were observed very high compared to recommended value of Bureau of Indian Standards (BIS) and World Health Organization (WHO) at Kanpur, Prayagraj and Varanasi stations. However, low value of parameters is observed at Haridwar and Bareilly stations. Also, the high deviation was observed in water quality parameters during 1990-2010 whereas the deviation of parameters is decreased in 2011-2016. It is observed from the piper diagram that magnesium and bicarbonate at Haridwar, sodium, potassium and bicarbonate in Bareilly, Kanpur, Prayagraj and Varanasi stations are dominant during monthly and seasonal periods. The fuzzy based WQI value indicate that water quality is excellent to poor at Haridwar, while poor to unsuitable in Bareilly, Kanpur, Prayagraj and Varanasi during monthly and seasonal periods. The water quality ranges from poor to unsuitable during the 1990-2010 period and good to very poor during the 2011-2016 period at Bareilly, Kanpur, Prayagraj and Varanasi stations. Whereas very good to good during 1990-2010 and excellent to good during 2011-2016 at Haridwar. It was also determined that water quality parameters (Ca, Na+K, SO4, Hardness, Cl and Mg) and WQI values were increased with length of the stream. It indicates that drain discharge, urban growth, urban functions, ecological footprints and crop area increment were key sources of pollution.

Metabolic utilization of human osteoblast cell line hFOB 1.19 under normoxic and hypoxic conditions: A phenotypic microarray analysis.

Osteoblasts play an important role in bone regeneration and repair. The hypoxia condition in bone occurs when bone undergoes fracture, and this will trigger a series of biochemical and mechanical changes to enable bone repair. Hence, it is interesting to observe the metabolites and metabolism changes when osteoblasts are exposed to hypoxic condition. This study has looked into the response of human osteoblast hFOB 1.19 under normoxic and hypoxic conditions by observing the cell growth and utilization of metabolites via Phenotype MicroArrays™ under these two different oxygen concentrations. The cell growth of hFOB 1.19 under hypoxic condition showed better growth compared to hFOB 1.19 under normal condition. In this study, osteoblast used glycolysis as the main pathway to produce energy as hFOB 1.19 in both hypoxic and normoxic conditions showed cell growth in well containing dextrin, glycogen, maltotriose, D-maltose, D-glucose-6-phospate, D-glucose, D-mannose, D-Turanose, D-fructose-6-phosphate, D-galactose, uridine, adenosine, inosine and α-keto-glutaric acid. In hypoxia, the cells have utilized additional metabolites such as α-D-glucose-1-phosphate and D-fructose, indicating possible activation of glycogen synthesis and glycogenolysis to metabolize α-D-glucose-1-phosphate. Meanwhile, during normoxia, D-L-α-glycerol phosphate was used, and this implies that the osteoblast may use glycerol-3-phosphate shuttle and oxidative phosphorylation to metabolize glycerol-3-phosphate.

Soils of the Southern Syria - A big database for the future land management planning.

As non-renewable natural resources, restoring Syrian soil quality is a vital issue for sustainable future planning after conflict ends. The data provided in this research exhibit features and physiochemical properties for soils from the southern part of Syria until the Jordanian border, which can provide decision-makers with sufficient information for rehabilitation stage after conflict in a regional scale. The data were collected from 107 representative soil profiles covering diverse agroecosystems throughout the area (i.e. Dara and Alswieda governorates). The most important data findings of this research included the first detection of Palygorskite {(Mg,Al)2Si4O10(OH)•4(H2O)} in Syrian soils, which is considered a strong evidence for the direct effects of the climate change on agroecosystem. Vertisols, Inceptisols, Entisols, Mollisols, and Aridisols were the most widespread soil types in the area. Overall, the database involves the field morphological characteristics, physicochemical, and mineralogical analyses.

Dataset on the Mediterranean soils from the coastal region of the Lattakia governorate, Syria.

Soil survey is indispensable for land-use planning in any agro-ecosystem, particularly in coastal ecosystems because they often face several environmental problems such as flooding and water pollution, leading to soil degradation. The data given in this article revealing the common soil types and substantial taxonomy levels in the coastal region of Lattakia, Syria which is a key question for the land-use planning in the region. Data from 30 representative soil profiles and 60 auger points covering different agroecosystems within the Mediterranean coastal region of the Lattakia governorate, Syria were studied. The database including, the field morphological characteristics, physicochemical, mineralogical and micromorphological laboratory analyses. Entisols, Inceptisols, Mollisols, and Vertisols are the main soil types demonstrated in the area, which requiring convenient management for these divergent soils. The full profile data is available online in this data article for further reuse and for appropriate decisions to manage these soils.

Retinal degeneration rat model: A study on the structural and functional changes in the retina following injection of sodium iodate.

Retinal disorders account for a large proportion of ocular disorders that can lead to visual impairment or blindness, and yet our limited knowledge in the pathogenesis and choice of appropriate animal models for new treatment modalities may contribute to ineffective therapies. Although genetic in vivo models are favored, the variable expressivity and penetrance of these heterogeneous disorders can cause difficulties in assessing potential treatments against retinal degeneration. Hence, an attractive alternative is to develop a chemically-induced model that is both cost-friendly and standardizable. Sodium iodate is an oxidative chemical that is used to simulate late stage retinitis pigmentosa and age-related macular degeneration. In this study, retinal degeneration was induced through systemic administration of sodium iodate (NaIO3) at varying doses up to 80 mg/kg in Sprague-Dawley rats. An analysis on the visual response of the rats by electroretinography (ERG) showed a decrease in photoreceptor function with NaIO3 administration at a dose of 40 mg/kg or greater. The results correlated with the TUNEL assay, which revealed signs of DNA damage throughout the retina. Histomorphological analysis also revealed extensive structural lesions throughout the outer retina and parts of the inner retina. Our results provided a detailed view of NaIO3-induced retinal degeneration, and showed that the administration of 40 mg/kg NaIO3 was sufficient to generate disturbances in retinal function. The pathological findings in this model reveal a degenerating retina, and can be further utilized to develop effective therapies for RPE, photoreceptor, and bipolar cell regeneration.

Genetically-modified human mesenchymal stem cells to express erythropoietin enhances differentiation into retinal photoreceptors: An in-vitro study.

Dysfunctional or death of retinal photoreceptors is an irreversible phenomenon that is closely associated with a broad range of retinal degenerative diseases, such as retinitis pigmentosa and age-related macular degeneration (AMD), resulting in successive loss of visual function and blindness. In search for viable treatment for retinal degenerative diseases, mesenchymal stem cells (MSCs) has demonstrated promising therapeutic capabilities to repair and replace damaged photoreceptor cells in both in vitro and in vivo conditions. Nevertheless, the dearth of MSC differentiation capacity into photoreceptors has limited its use in cell replacement therapy. Erythropoietin (EPO) has vital role in early neural retinal cell differentiation and demonstrated rescue potential on dying photoreceptor cells. Hence, we aimed to evaluate the differentiation capacity of MSCs into photoreceptor cells in the presence of human EPO protein. We derived the MSC from human Wharton's jelly of umbilical cord and transduced the cells with lentivirus particles encoding EPO and green fluorescent protein (GFP) as reporter gene. The transduced cells were selectively cultured and induced to differentiate into photoreceptors by exposing to photoreceptor differentiation cocktail. Our preliminary results showed that transduced cells exposed to induction medium had an enhanced differentiation capacity when compared to non-transduced cells. Our results demonstrated a novel strategy to increase the yield of in vitro photoreceptor differentiation and may be potentially useful in improving the efficiency of stem cell transplantation for ocular disorders.

Empowering Mesenchymal Stem Cells for Ocular Degenerative Disorders.

Multipotent mesenchymal stem cells (MSCs) have been employed in numerous pre-clinical and clinical settings for various diseases. MSCs have been used in treating degenerative disorders pertaining to the eye, for example, age-related macular degeneration, glaucoma, retinitis pigmentosa, diabetic retinopathy, and optic neuritis. Despite the known therapeutic role and mechanisms of MSCs, low cell precision towards the targeted area and cell survivability at tissue needing repair often resulted in a disparity in therapeutic outcomes. In this review, we will discuss the current and feasible strategy options to enhance treatment outcomes with MSC therapy. We will review the application of various types of biomaterials and advances in nanotechnology, which have been employed on MSCs to augment cellular function and differentiation for improving treatment of visual functions. In addition, several modes of gene delivery into MSCs and the types of associated therapeutic genes that are important for modulation of ocular tissue function and repair will be highlighted.

Human Mesenchymal Stem Cells Expressing Erythropoietin Enhance Survivability of Retinal Neurons Against Oxidative Stress: An In Vitro Study.

Retinal degeneration is a prominent feature in ocular disorders. In exploring possible treatments, Mesenchymal Stem Cells (MSCs) have been recognized to yield therapeutic role for retinal degenerative diseases. Studies have also displayed that erythropoietin (EPO) administration into degenerative retina models confers significant neuroprotective actions in limiting pathological cell death. In this study, we aimed to use MSCs to deliver EPO and to evaluate the ability of EPO to rescue retinal neurons from dying upon reactive oxidative stress induction. We derived human MSCs from Wharton's jelly (hWJMSCs) of the umbilical cord and cells were transduced with lentivirus particles encoding EPO and a reporter gene of green fluorescent protein (GFP). The supernatants of both transduced and non-transduced cells were collected and used as a pre-conditioning medium for Y79 retinoblastoma cells (retinal neuron cell line) following exposure to glutamate induction. Retinal cells exposed to glutamate showed reduced mitochondrial depolarization and enhanced improvement in cell viability when incubated with pre-conditioned media of transduced cells. Our results established a proof-of-concept that MSCs could be used as a candidate for the delivery of EPO therapeutic gene in the treatment of retinal degenerations.