Enriched human embryonic stem cells-derived CD133+, CD24+ renal progenitors engraft and restore function in a gentamicin-induced kidney injury in mice.

Introduction: Acute kidney injury (AKI) is a common health problem that leads to high morbidity and potential mortality. The failure of conventional treatments to improve forms of this condition highlights the need for innovative and effective treatment approaches. Regenerative therapies with Renal Progenitor Cells (RPCs) have been proposed as a promising new strategy. A growing body of evidence suggests that progenitor cells differentiated from different sources, including human embryonic stem cells (hESCs), can effectively treat AKI. Methods: Here, we describe a method for generating RPCs and directed human Embryoid Bodies (EBs) towards CD133+CD24+ renal progenitor cells and evaluate their functional activity in alleviating AKI. Results: The obtained results show that hESCs-derived CD133+CD24+ RPCs can engraft into damaged renal tubules and restore renal function and structure in mice with gentamicin-induced kidney injury, and significantly decrease blood urea nitrogen levels, suppress oxidative stress and inflammation, and attenuate histopathological disturbances, including tubular necrosis, tubular dilation, urinary casts, and interstitial fibrosis. Conclusion: The results suggest that RPCs have a promising regenerative potential in improving renal disease and can lay the foundation for future cell therapy and disease modeling.

Great potential of renal progenitor cells in kidney: From the development to clinic.

The mammalian renal organ represents a pinnacle of complexity, housing functional filtering units known as nephrons. During embryogenesis, the depletion of niches containing renal progenitor cells (RPCs) and the subsequent incapacity of adult kidneys to generate new nephrons have prompted the formulation of protocols aimed at isolating residual RPCs from mature kidneys and inducing their generation from diverse cell sources, notably pluripotent stem cells. Recent strides in the realm of regenerative medicine and the repair of tissues using stem cells have unveiled critical signaling pathways essential for the maintenance and generation of human RPCs in vitro. These findings have ushered in a new era for exploring novel strategies for renal protection. The present investigation delves into potential transcription factors and signaling cascades implicated in the realm of renal progenitor cells, focusing on their protection and differentiation. The discourse herein elucidates contemporary research endeavors dedicated to the acquisition of progenitor cells, offering crucial insights into the developmental mechanisms of these cells within the renal milieu and paving the way for the formulation of innovative treatment modalities.

Coenzyme Q10 attenuates neurodegeneration in the cerebellum induced by chronic exposure to tramadol.

BACKGROUND: Chronic use of tramadol can cause neurotoxic effects and subsequently cause neurodegeneration in the cerebellum. The main damage mechanisms identified are oxidative stress and inflammation. Currently, we investigated the effects of coenzyme Q10 (CoQ10) in attenuates of neurodegeneration in the cerebellum induced by chronic exposure to tramadol. MATERIAL AND METHODS: Seventy-two male mature albino rats were allocated into four equal groups, including; non-treated group, CoQ10 group (which received CoQ10 at 200 mg/kg/day orally for three weeks), tramadol group (which received tramadol hydrochloride at 50 mg/kg/day orally for three weeks), and tramadol+CoQ10 group (which received tramadol and CoQ10 at the same doses as the previous groups). Tissue samples were obtained for stereological, immunohistochemical, biochemical, and molecular evaluations. Also, functional tests were performed to evaluate behavioral properties. RESULTS: We found a significant increase in stereological parameters, antioxidant factors (catalase, glutathione, and superoxide dismutase), and behavioral function scores in the tramadol+CoQ10 group compared to the tramadol group (p < 0.05). In addition, malondialdehyde levels, the density of apoptotic cells, as well as the expression of pro-inflammatory (tumor necrosis factor-alpha, interleukin 1 beta, and interleukin 6) and autophagy (lysosome-associated membrane protein 2, autophagy-related 5, beclin 1, and autophagy-related 12) genes were considerably reduced in the tramadol+CoQ10 group compared to the tramadol group (p < 0.05). CONCLUSION: We conclude that the administration of CoQ10 has neuroprotective effects in the cerebellum of rats that have chronic exposure to tramadol.

Irrigation Regimes and Nitrogen Rates as the Contributing Factors in Quinoa Yield to Increase Water and Nitrogen Efficiencies.

Sustainable field crop management has been considered to reach the food security issue due to global warming and water scarcity. The effect of deficit irrigation and nitrogen rates on quinoa yield is a challenging issue in those areas. In this regard, the interaction effects of different N rates (0, 125, 250, and 375 kg N ha-1) and irrigation regimes [full irrigation (FI) and deficit irrigation at 0.75 FI and 0.5 FI] on quinoa yield and water and nitrogen efficiencies were evaluated with a two-year field experiment. Increasing nitrogen fertilizer application levels from 250 to 375 kg N ha-1 under FI and deficit irrigation did not cause a significant difference in seed yield and the total dry matter of quinoa. Furthermore, 20% and 34% reductions were observed for nitrogen use efficiency (NUE) and nitrogen yield efficiency with the application of 375 kg N ha-1 compared with that obtained in 250 kg N ha-1 nitrogen fertilizer, respectively. Therefore, a Nitrogen application rate of 250 kg ha-1 and applying 0.75 FI is suggested as the optimum rate to reach the highest seed water use efficiency (0.7 kg m-3) and NUE (0.28 kg m-3) to gain 4.12 Mg ha-1 quinoa seed yield. Under non-limited water resource conditions, an FI and N application rate of 375 kg ha-1 could be used for higher seed yield; however, under water-deficit regimes, an N application rate of 250 kg ha-1 could be adequate. However, questions about which environmental factors impressively restricted the quinoa growth for optimizing the potential yield need further investigation.

Anti-Inflammatory Activity of S. Marianum and N. Sativa Extracts on Macrophages.

BACKGROUND: Nigella sativa (N. sativa) and Silybum marianum (S. marianum) are used to regulate macrophage polarization in lipopolysaccharide-induced RAW 264.7 cells and thioglycollate-elicited peritoneal inflammation. METHODS: Cytotoxicity assays and acute toxicity tests were performed to investigate the safe dose and toxicity of the prepared extracts. Also, nitric oxide production was determined by Griess assay on RAW264.7 and peritoneal macrophage supernatants. After RNA extraction from macrophages, real-time PCR was performed to measure the relative gene expression of tumor necrosis factor (TNF)-α, interleukin (IL)-6, transforming growth factor (TGF)-ß, and IL-10. Finally, regulatory T cells (Treg cells) were counted by flow cytometry. RESULTS: S. marianum methanolic extract (SME), N. sativa ethanolic extract (NEE), and their mixture (SME+NEE) decreased NO levels significantly in RAW264.7 and peritoneal murine macrophages. N. sativa ethanolic extract significantly increased IL-10 gene expression and significantly decreased IL-6 and TNF-α expression in RAW264.7 cells. In mixture-treated peritoneal macrophages, IL-10 and TGF-ß expression were significantly increased, while IL-6 and TNF-α were significantly decreased. Also, the percentage of Treg cells was significantly greater in the mixture-treated cells than in controls. CONCLUSION: These results suggest that an SME and NEE mixture has anti-inflammatory and immunomodulatory activities and may be useful in the treatment of diseases of immunopathologic origin characterized by macrophage hyperactivation.

Exogenous Ghrelin Could Not Ameliorate 3,4-methylenedioxymethamphetamine-induced Acute Liver Injury in The Rat: Involved Mechanisms.

MDMA (3,4-methylenedioxymethamphetamine, ecstasy) is often abused by youth as a recreational drug. MDMA abuse is a growing problem in different parts of the world. An important adverse consequence of the drug consumption is hepatotoxicity of different intensities. However, the underlying mechanism of this toxicity has not been completely understood. Ghrelin is a gut hormone with growth hormone stimulatory effect. It expresses in liver, albeit at a much lower level than in stomach, and exerts a hepatoprotective effect. In this study, we investigated hepatotoxicity effect of MDMA alone and its combination with ghrelin as a hepatoprotective agent. MDMA and MDMA+ ghrelin could transiently increase serum alanine aminotransferase (ALT) and aspartate aminotransferase (AST) followed by tissue necrosis. However, they could significantly decrease liver tumor necrosis factor-a (TNF-±) in both treatment groups. Unexpectedly, in MDMA treated rats, Bax, Bcl-xl, Bcl-2, Fas, Fas ligand (Fas-L), caspase 8, cytochrome c, caspase 3 gene expression, and DNA fragmentation were nearly unchanged. In addition, apoptosis in MDMA+ ghrelin group was significantly reduced when compared with MDMA treated animals. In all, MDMA could transiently increase serum transaminases and induce tissue necrosis and liver toxicity. Ghrelin, however, could not stop liver enzyme rise and MDMA hepatotoxicity. MDMA hepatotoxicity seems to be mediated via tissue necrosis than apoptotic and inflammatory pathways. Conceivably, ghrelin as an anti-inflammatory and anti-apoptotic agent may not protect hepatocytes against MDMA liver toxicity.

The Effect of Low-Power Laser Therapy on the TGF/ß Signaling Pathway in Chronic Kidney Disease: A Review.

Objective: The purpose of this study is to investigate the effects of low-power lasers on kidney disease by investigating several studies. Methods: A number of articles from 1998 to 2019 were chosen from the sources of PubMed, Scopus, and only the articles studying the effect of low-power lasers on kidney disease were investigated. Results: After reviewing the literature, 21 articles examining only the effects of low-power lasers on kidney disease were found. The results of these studies showed that the parameter of the lowpower laser would result in different outcomes. So, a low-power laser with various parameters can be effective in the treatment of kidney diseases such as acute kidney disease, diabetes, glomerulonephritis, nephrectomy, metabolic syndrome, and kidney fibrosis. Most studies have shown that low-power lasers can affect TGFß1 signaling which is the most important signaling in the treatment of renal fibrosis. Conclusion: Lasers can be effective in reducing or enhancing inflammatory responses, reducing fibrosis factors, and decreasing reactive oxygen species (ROS) levels in kidney disease and glomerular cell proliferation.

Simulation of Wetting and Interfacial Behavior of Quaternary Ammonium and Phosphonium Ionic Liquid Nanodroplets Over Face-Centered Cubic Metal Surfaces.

We studied the behavior of quaternary ammonium- and phosphonium-based ([N2225][NTf2] and [P2225][NTf2]) ionic liquid (IL) nanodroplets on copper (Cu) and platinum (Pt) metal surfaces using classical molecular dynamics simulations. Solid-liquid interactions were underpinned by studying the dynamic spreading, contact angle, time-dependent binding energies, mean-square displacements, number and charge density profiles, and orientational distribution of these two IL nanodroplets. In particular, the role and importance of different crystallographic facets of face-centered cubic metal surface [Cu(100), Cu(111), Pt(100), and Pt(111)] were investigated. The results indicate a vast variety of properties that are dictated highly by the structure of different crystallographic facets of the metal substrate. The nature of the facet (e.g., the atomic arrangement symmetry, the extent of closed packed, and the unit cell size) leads to an extended scale spreading of the ILs on the surface with the (111) index but not with the (100) index, while the nature of metals itself plays a role.

Gas-phase electronic properties of tri-cationic imidazolium-based ionic liquids in comparison with mono- and di-cationic ionic liquids.

The optimized geometries, electronic structures, and gas-phase properties of widely applicable non-linear trigeminal tri-cationic ILs (TT-X3) were investigated using density functional theory (DFT) calculations and compared with mono- (M-X) and di-cationic (D-X2) ionic liquids. The studied ILs are based on the imidazolium cation containing halide (X‾) anions, where X‾ = Cl‾, Br‾ and I‾. Inter-molecular hydrogen bonds were studied by atoms in molecules (AIM) and natural bond orbital (NBO) analyses. Accordingly the most significant cation-anion charge transfer is related to C1-H1 … X (X = Cl, Br, I) interaction which strongly occurs in TT-X3 ILs and especially in TT-Cl3. Among ILs under investigation, TT-Cl3 has the strongest cation-anion interaction. Also M - I IL has the largest and D-Cl2 has the smallest electrical dipole moment.

Protective effect of Photobiomodulation Therapy and Bone Marrow Stromal Stem Cells Conditioned Media on Pheochromocytoma Cell Line 12 Against Oxidative Stress Induced by Hydrogen Peroxide.

Introduction: Bone marrow stromal stem cells (BMSCs), a type of adult stem cells, secrete bioactive molecules such as trophic factors, growth factors, chemokine and cytokines that may be effective against oxidative stress in neurodegenerative diseases. In this study, we examined the protective effect of BMSCs conditioned media (CM) and photobiomodulation therapy (PBMT) on PC12 cells exposed to H2O2 as an oxidative injury model. Methods: BMSCs were cultured and confirmed by flow cytometry analysis and underwent osteogenic and adipogenic differentiation. Then, PC12-H2O2 cells were co-treated with BMSCs-CM and PBMT. The effect of BMSCs-CM and PBMT (He-Ne laser, 632.8nm, 3mW, 1.2J/ cm2 , 378s) on Bax/Bcl2 expression, cell viability, was assessed by real-time PCR and MTT assay. The length of the Neurite and cell body areas were assessed by Cell A software. Results: Flowcytometry analysis, as well as osteogenic and adipogenic staining, confirmed the BMSCs. The length of the Neurite was the highest in the group which received CM+PBMT and cell body areas were significant in CM+PBMT compared to other groups. Based on our results, elevating H2O2 concentration increased cell death significantly and using concentrations of 250 µM resulted in a dramatic increase in the mortality compared to the other groups. Conclusion: Our result demonstrated that the combination of CM +PBMT has a protective effect on PC12 cells against oxidative stress.

Effects of Viola tricolor Flower Hydroethanolic Extract on Lung Inflammation in a Mouse Model of Chronic Asthma.

Asthma is a chronic inflammatory disease of the lungs driven by T cell activation. Viola tricolor L. as a traditional medical herb could suppress activated T lymphocytes and has been used empirically for asthma remedy. In the present study, we investigated the anti-inflammatory effect of Viola tricolor and its underlying mechanism on asthma characteristics induced by ovalbumin (OVA) in mice. BALB/c mice were randomly divided into six groups: normal control, Ovalbumin (OVA) control, OVA mice treated with Viola tricolor (50, 100 and 200 mg/kg) and dexamethasone (3 mg/kg). All mice except normal controls were sensitized and challenged with OVA. Asthmatic mice were treated orally in the last 7 days of OVA challenge. The total and differential leukocyte counts, Interleukin (IL)-4 and interferon (IFN)-γ levels in bronchoalveolar lavage fluid (BALF) were determined. H and E staining for lung inflammation was performed. Viola tricolor treatment at 200 mg/kg significantly decreased IL-4 level but did not considerably affect the IFN-γ level. Therefore, it effectively reduced asthma characteristics including infiltration of leukocytes particularly eosinophil and peribronchial inflammation as compared to dexamethasone. However, Viola tricolor at 100 mg/kg had the most prominent inhibitory effect on the IL-4 level and also markedly increased IFN-γ level. As result, it prevented further reduction of inflammatory parameters in this group compared to the Viola tricolor-treated group at 200 mg/kg. Our study demonstrated that Viola tricolor has anti-inflammatory effects via inhibition of T-helper type 2 (Th2) cytokine production and validated its empirical usage in traditional medicine.

Sum frequency generation spectroscopy of tetraalkylphosphonium ionic liquids at the air-liquid interface.

Sum frequency generation (SFG) spectroscopy is a nonlinear vibrational spectroscopic technique used in the study of interfaces, due to its unique ability to distinguish surface molecules that have preferential ordering compared to the isotropic bulk. Here, a series of alkyltrioctylphosphonium chloride ionic liquids, systematically varied by cation structure, were characterized at the air-liquid interface by SFG. The effect on surface structure resulting from molecular variation (i.e., addition of cyano- and methoxy-functional groups) of the cation alkyl chain was investigated. SFG spectra in the C-H stretching region (2750-3100 cm-1) for [P8 8 8 n ][Cl], where n = 4, 5, 8, 10, 12, or 14, showed characteristic changes as the alkyl chain length was increased. Spectral profiles for n = 4, 5, 8, or 10 appeared similar; however, when the fourth alkyl chain was sufficiently long (as in the case of n = 12 or n = 14), abrupt changes occurred in the spectra. Molecular dynamics (MD) simulation of a slab of each ionic liquid (with n = 8, 10, or 12) confirmed gauche defects, with enhancement for the long alkyl chain and an abrupt increase of gauche occurrence from n = 8 to n = 10. A comparison of the tilt angle distribution from the simulation and the SFG analysis show a broad distribution of angles. Using experimental SFG spectra in conjunction with MD simulations, a comprehensive molecular picture at the surface of this unique class of liquids is presented.

Cartilage Tissue Engineering Via Icariin and Adipose-derived Stem Cells in Fibrin Scaffold.

BACKGROUND: Nowadays, cartilage tissue engineering is the best candidate for regeneration of cartilage defects. This study evaluates the function of herbal extracts icariin (ICA), the major pharmacological constituent of herba Epimedium, compared with transforming growth factor ß3 (TGFß3) to prove its potential effect for cartilage tissue engineering. MATERIALS AND METHODS: ICA, TGFß3, and TGFß3 + ICA were added fibrin-cell constructions derived from adipose tissue stem cells. After 14 days, cell viability analyzed by 3-(4,5-dimethyl-2-thiazolyl)-2,5-diphenyl-2H- tetrazolium bromide assay and the expression of cartilage genes was evaluated with real-time polymerase chain reaction (RT-PCR). RESULTS: The results showed ICA, TGFß3, and TGFß3 + ICA increased the rate of proliferation and viability of cells; but there were no significant differences between them (P > 0.05). Furthermore, quantitative RT-PCR analysis demonstrated that cooperation of ICA with TGFß3 showed a better effect in expression of cartilaginous specific genes and increased Sox9, type II collagen, and aggrecan expression significantly. Furthermore, the results of the expression of type I and X collagens revealed that TGFß3 increased the expression of them (P < 0.01); However, treatment with ICA + TGFß3 down regulated the expression of these genes significantly. CONCLUSION: The results indicated ICA could be a potential factor for chondrogenesis and in cooperation with TGFß3 could reduce its hypertrophic effects and it is a promising factor for cartilage tissue engineering.

An economic analysis of implementing the SIGN third molar guideline: implications for the design and analysis of implementation studies.

OBJECTIVES: To compare the cost-effectiveness of four third molar guideline implementation strategies. METHODS: Fifty-one dental practices in Scotland were randomized to one of four implementation strategies. The effectiveness of the strategies was measured by general dental practitioners' compliance with the guideline. RESULTS: The effectiveness of the guideline depended crucially upon the type of patient treated. In particular, for a minority of patients (14%) with no clinical signals of their 'type', the implementation strategies generate potentially large gains in evidence-based practice. However, the cost per patient of achieving these gains is large given that the costs are incurred for all patients, but benefits accrue only to a minority. DISCUSSION: The results show that the type of patient presenting for treatment can influence the effectiveness, cost-effectiveness and therefore policy conclusions. Consequently, the design and analysis of studies need to be sufficiently sensitive to detect subtle interaction effects. This may explain the dearth of guideline implementation trials with significant findings. The results also suggest that a more cost-effective implementation method in primary care dentistry may be to subsidize treatment conditional upon patient type.