FPS-ZM1 and valsartan combination protects better against glomerular filtration barrier damage in streptozotocin-induced diabetic rats

Despite the effectiveness of renin-angiotensin blockade in retarding diabetic nephropathy progression, a considerable number of patients still develop end-stage renal disease. The present investigation aims to evaluate the protective potential of FPS-ZM1, a selective inhibitor of receptor for advanced glycation end products (RAGE), alone and in combination with valsartan, an angiotensin receptor blocker, against glomerular injury parameters in streptozotocin-induced diabetic rats. FPS-ZM1 at 1 mg/kg (i.p.), valsartan at 100 mg/kg (p.o.), and their combination were administered for 4 weeks, starting 2 months after diabetes induction in rats. Tests for kidney function, glomerular filtration barrier, and podocyte slit diaphragm integrities were performed. Combined FPS-ZM1/valsartan attenuated diabetes-induced elevations in renal levels of RAGE and phosphorylated NF-κB p65 subunit. It ameliorated glomerular injury due to diabetes by increasing glomerular nephrin and synaptopodin expressions, mitigating renal integrin-linked kinase (ILK) levels, and lowering urinary albumin, collagen type IV, and podocin excretions. FPS-ZM1 also improved renal function as demonstrated by decreasing levels of serum cystatin C. Additionally, the combination also alleviated indices of renal inflammation as revealed by decreased renal monocyte chemoattractant protein 1 (MCP-1) and chemokine (C-X-C motif) ligand 12 (CXCL12) expressions, F4/80-positive macrophages, glomerular TUNEL-positive cells, and urinary alpha-1-acid glycoprotein (AGP) levels. These findings underline the benefits of FPS-ZM1 added to valsartan in alleviating renal glomerular injury evoked by diabetes in streptozotocin rats and suggest FPS-ZM1 as a new potential adjunct to the conventional renin-angiotensin blockade.     

Structure,composition and regeneration of riparian forest along an altitudinal gradient in northern Iran

In order to protect and understand the regeneration of riparian forests, it is important to understand the environmental conditions that lead to their vegetation differentiation. We evaluated the structure, composition, density and regeneration of woody species in forests along the river Safaroud in Ramsar forest in northern Iran in relation to elevation, soil properties and distance from the river. Using 60 transects located perpendicularly to river and 300 quadrats, we examined forests 0, 50, 100, 150 and 200 m from the stream along an elevation gradient spanning from 350 to 2,400 m a.s.l. We found that total density, regeneration, diameter and basal area of trees were significantly higher in the interior of the forest whereas shrub density was higher close to the river. The uneven-aged forest structure showed no significant differences among gradient from the river to the forest interior. Hydro-geomorphic processes, flooding, the elevation gradient, distance from the river and soil properties were the most important factors that influenced plant community distribution in relation to the river.     

Characterizing of fine particulate matter (PM1) on the platforms and outdoor areas of underground and surface subway stations

A campaign was conducted to assess the PM₁ concentration and elemental composition on the platforms and adjacent outdoor areas of an underground subway station (Imam Khomeini) and a surface subway station (Sadeghiye) in Tehran from June 2014 to November 2014. The respective mean concentrations of PM₁ on the platforms and in the outdoor areas of Imam Khomeini station were 42.04 and 30.92 µg/m³ and for Sadeghiye station 31.42 and 26.02 µg/m³. Statistical analyses demonstrated that the platforms of the Imam Khomeini and Sadeghiye stations were influenced by the adjacent ambient air of these stations (p < 0.05). PM₁ was found to be highly enriched with Fe on the platforms of metro systems, which were more frequently encountered in the Imam Khomeini station than the Sadeghiye station as 41.06% and 37.73% of the total PM₁ mass respectively. Minor elements, particularly Ba, Pb, Cr, Cu, Ni, Mn, Ti, V, and Zn, were elevated for the platform of Imam Khomeini and, to a lesser degree, the platform of Sadeghiye stations, which may be due to abrasion processes between rail tracks, wheels, and brake pads.     

Study of PM10, PM2.5, and PM1 levels in during dust storms and local air pollution events in urban and rural sites in Tehran

The aim of this study is to survey the PM₁₀, PM_2.5, and PM₁ concentrations in rural and urban areas in Tehran province during cold, warm and dust storm days from December 22, 2016 to June 5, 2017 using Grimm Model aerosol spectrometer. During the study period, daily PM₁₀, PM_2.5, and PM₁ concentrations ranged from 27.2 to 244.96, 8.4 to 77.9, and 6.5 to 56.8 μg/m³ in urban sites, and 22.8 to 286.4, 6 to 41.1, and 2.1 to 20.2 μg/m³ in rural parts, respectively. Particularly, both daily WHO limits for outdoor PM₁₀ (50.0 μg/m³) and PM_2.5 (25.0 μg/m³) exceeded in 95% and 83% of the outdoor measurements in winter and 82% and 58% in total sampled days in urban site, respectively. The 24-h average PM₁₀ and PM_2.5 concentrations also exceeded by 59% and 18% in winter and by 36% and 14% of all sampling days in rural site, respectively. During the dust storm, the 24-h average PM₁₀, PM_2.5, and PM₁ concentrations were, respectively 4.7, 2, and 1.96 times higher than those in urban site and 2, 1.7, and 1.3 times more than those in rural site in all sampled days.     

Optimized potassium nutrition improves plant-water-relations of barley under PEG-induced osmotic stress

Aims

Water use efficiency (WUE) of crop plants is an important plant trait for maintaining high yield in water limited areas. By influencing osmoregulation of plants, potassium (K) plays a critical role in stress avoidance and adaptation. However, whole plant physiological mechanisms modulated by K supply in respect of plant drought tolerance and water use efficiency are not well understood. In the present study, growth, development and transpiration dynamics of two barley cultivars were evaluated with and without PEG-induced osmotic stress using an automated balance system and image based leaf area determination.

Methods

Experiments were conducted to study the effects of varied K supply under different osmotic stress treatments on a wide range of morphological, biochemical and physiological characteristics of barley plants such as leaf area development, daily whole plant transpiration rate (DTR), stomatal conductance (g_s), assimilation rate (A_N), biomass and leaf water use efficiency (WUE) as well as foliar abscisic acid (ABA) concentrations. Two barley cultivars (cv. Sahin-91 and cv. Milford) were treated with two K supply levels (0.04 and 0.8 mM K) and osmotic stress induced by polyethylene glycol 6000 (PEG) for a period of 9 days (in total 48 days experiment) in the hydroponic plant culture (non-PEG and + 20% PEG ).

Results

Without PEG, low-K supply depressed dry matter (DM) by almost 60% averaged across both cultivars. Under osmotic stress (+PEG), total leaf area was reduced by almost 70% in low-K compared to adequate-K plants. Low K concentration under PEG stress was correlated with higher ABA concentration and was correlated with lower leaf- and whole plant transpiration rate. Biomass-WUE under low K supply decreased significantly in both barley cultivars, to a greater extent in cv. Milford under osmotic stress. However, leaf-WUE was not affected by K supply in the absence of osmotic stress.

Conclusions

It was suggested that reduced biomass-WUE in low-K treated barley plants was not related to inefficient stomatal control under K deficiency, but instead due to reduced assimilation rate. It was further hypothesized that under low K supply, a number of energy consuming activities reduce biomass-WUE, which are not distinguished by measuring leaf-WUE. This study showed that low K supply under osmotic stress increases foliar ABA concentration thereby decreasing plant transpiration.

     

An annotated list and molecular data on larvae of gryporhynchid tapeworms (Cestoda: Cyclophyllidea) from freshwater fishes in Africa

An annotated list of larvae (metacestodes) of gryporhynchid tapeworms (Cestoda: Cyclophyllidea) from freshwater fishes in Africa is provided with numerous new host and geographical records. Newly collected materials from Burundi, Democratic Republic of the Congo, Kenya, Madagascar, Namibia, Senegal, South Africa, Sudan and Zimbabwe practically double the total number of species reported from African fish so far. We confirm the occurrence of 16 species (five unidentified to the species level and most likely representing new taxa) belonging to the genera Amirthalingamia Bray, 1974 (1 species), Cyclustera Fuhrmann, 1901 (2 species), Dendrouterina Fuhrmann, 1912 (1 species), Neogryporhynchus Baer & Bona, 1960 (1 species), Paradilepis Hsü, 1935 (4 species), Parvitaenia Burt, 1940 (5 species), and Valipora Linton, 1927 (2 species). Additionally, metacestodes of four unidentified species of Paradilepis and Parvitaenia are reported from fish for the first time. Rostellar hooks of all species are illustrated and their measurements are provided together with a host-parasite list. The molecular phylogenetic analysis based on partial LSU rDNA sequences offers the first insight into the internal phylogenetic relationships within the family. Together with the morphological observations, the present study provides a taxonomic baseline for future studies on this largely neglected, but widely distributed and relatively frequent, group of parasites of African fishes, including economically important cichlids like tilapias and cyprinids.     

Autophagic,apoptotic, and necrotic cancer cell fates triggered by acidic pH microenvironment

Cancer as a multifactorial and smart disease is now considered a challenging problem. Despite many investigations on drug discovery, it remains incurable, in part, due to insufficient understanding of its special mechanisms. For the first time, we collaterally investigated the effect of acidosis on the contribution of apoptosis, necrosis, and autophagy in MDA-MB 231 cells. Our data showed that necrosis, apoptosis, and intracellular reactive oxygen species production drastically decreased from 48 to 72 hr while cell viability and autophagy increased along with a gap between the percentages. Eventually, the decrease of necrosis and apoptosis was related to upregulation of nicotinamide adenine dinucleotide phosphate (NADPH) oxidase and fatty acid synthetase, respectively. It seems that at the early stage of cancer progression, apoptosis is the main mechanism of cell mortality and afterward autophagy would be the main mechanism of cell survival. Therefore, at the acute phase of cancer, apoptotic inducer medications would be effective while at the chronic phase of cancer progression, autophagy inhibitor medication would be added as well. This eventually means that autophagy acts as both cell death and survival mechanisms at the onset of cancer progression with the approach towards cell survival. Besides other unknown cell survival mechanisms are involved in cell viability, except for apoptosis and necrosis inhibition and autophagy improvement. This study reiterates the inefficaciousness of autophagy inhibitor's medication at the onset of disease. It also emphasizes discovering other cell death mechanisms for cancer cell adaptation at the onset of disease with the aim of their targeting in cancer invasion therapy.     

Autophagy,anoikis, ferroptosis,necroptosis, and endoplasmic reticulum stress: Potential applications in melanoma therapy

Melanoma as the most major skin malignancy has attracted much attention, so far. Although a successful therapeutic strategy requires an accurate understanding of the precise mechanisms for the initiation and progression of the melanoma. Several types of cell death mechanisms have recently been identified along with conventional cell death mechanisms such as apoptosis and necrosis. Among those mechanisms, necroptosis, anoikis, ferroptosis, and autophagy may be considered to have remarkable modulatory impacts on melanoma. In the present review, we explain the mechanisms of cell death signaling pathways related to autophagy, ferroptosis, anoikis, necroptosis, and reticulum endoplasmic stress in cells and describe how those mechanisms transduce signals in melanoma cells. Meanwhile, we describe how we can modulate those mechanisms to eliminate melanoma.