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The intricate and multifaceted nature of Land Use Planning (LUP) necessitates a comprehensive exploration of its underlying structuring elements, notably institutions. In Iran, the complex interplay between formal and informal institutions, often fueled by their unrecognized roles, means realizing that effective LUP is fraught with formidable challenges. Our research introduces a conceptual framework for the institutional environment of LUP to gain a deeper understanding of the critical influencing factors and their interconnections in Iran. Exploring the institutional environment allows ways to mitigate the challenges in Iran's LUP to emerge. This qualitative research systematically reviews the literature and draws themes from secondary data. We then categorize Iran's land use challenges into two main areas: content-related and structural. Exploring these challenges can help us to identify the primary issues needing attention in the institutional environment of LUP, bringing us closer to understanding institutional factors in the conceptual model. The proposed framework, recognizing culture as the foundation of informal institutions, outlines formal and informal institutional components, emphasizing their interconnectedness. Subsequently, we explore the framework's significance in addressing the challenges within Iran's LUP system. Focusing on this framework and understanding Iran's institutional environment can reduce uncertainty in decision making. As a result, this research is a step towards the idealization of LUP and a basis for further studies. • The unclear role of the institutions in land use planning leads to the misallocation of resources. • Investigating land use planning's link to institutions divides them into formal and informal categories. • In complex institutional and land use contexts, a conceptual framework is critical to pursuing ideals. • The proposed framework investigates the possibilities of lowering land use planning challenges in Iran. [ABSTRACT FROM AUTHOR]

Aims Glioblastoma cancer stem-like cells (GCSCs) promote themselves proliferation by secreting the vascular endothelial growth factor A (VEGF A ) in an autocrine manner, positively regulated by phosphodiesterase IV (PDE4). In the current study, we investigated the putative cytotoxic effect of bevacizumab, a VEGF A blocker, alone and in combination with a specific inhibitor of PDE4 called rolipram on GCSCs isolated from human surgical tumor specimen with a focus on PI3K/AKT pathway. Main methods CD133 +/CD15 + GCSCs were characterized by flow cytometry and expanded in a serum-free primary culture system. The cell survival, apoptosis, and protein expression values were measured using MTT assay, TUNEL staining and western blot, successively. Intracellular cAMP and free secreted VEGF A levels were assessed by cAMP enzyme immunoassay and ELISA, respectively. Key findings Bevacizumab suppressed GCSCs survival with IC 50 ~ 6.5 μg/ml and enhanced the levels of apoptosis, p53 and cleaved-caspase3 along with a decrease in free VEGF A levels and ERKs activation. However, there was no significant modulation of AKT phosphorylation on serine 473, the intracellular PDE4A, VEGF A and cAMP levels. More cytotoxicity in co-treated cells coupled with a more substantial decline in the free VEGF A levels and a greater increase in the quantities of p53 and cleaved-caspase3 compared to those treated with bevacizumab alone. Co-treatment reduced phospho-AKT, endogenous VEGF A and PDE4A values but elevated cAMP levels. Significance This study highlighted a booster cytotoxic effect of combined rolipram and bevacizumab treatment on the GCSCs primary culture, suggesting that this approach is warranted in treatment of GBMs overexpressing VEGF A and PDE4A. [ABSTRACT FROM AUTHOR]

The unstable response to bevacizumab is a big dilemma in the antiangiogenic therapy of high-grade glioma that appears to be linked to an increase in the post-treatment intratumor levels of hypoxia-inducible factor 1 α (HIF1α) and active AKT. Particularly, a selective phosphodiesterase IV (PDE4) inhibitor, rolipram is capable of inhibiting HIF1α and AKT in cancer cells. Here, the effect of bevacizumab alone and in presence of rolipram on therapeutic efficacy, intratumor hypoxia levels, angiogenesis, apoptosis and proliferation mechanisms were evaluated. BALB/c mice bearing C6 glioma were received bevacizumab and rolipram either alone or combined for 30 days (n = 11/group). At the last day of treatments, apoptosis, proliferation and microvessel density, in xenografts (3/group) were detected by TUNEL staining, Ki67 and CD31 markers, respectively. Relative expression of target proteins was measured using western blotting. Bevacizumab initially hindered the tumor progression but its antitumor effect was weakened later despite the vascular regression and apoptosis induction. Unpredictably, bevacizumab-treated tumors exhibited the highest cell proliferation coupled with PDE4A, HIF1α and AKT upregulation and p53 downregulation and reversed by co-treatment with rolipram. Unlike a similar antivascular pattern to bevacizumab, rolipram consistently led to a more tumor growth suppression and proapoptotic effect versus bevacizumab. Co-treatment maximally hampered the tumor progression and elongated survival along with the major vascular regression, hypoxia, apoptosis induction, p53 and caspase activities. In conclusion, superior and persistent therapeutic efficacy of co-treatment provides a new insight into antiangiogenic therapy of malignant gliomas, suggesting to be a potential substitute in selected patients. [ABSTRACT FROM AUTHOR]

Introduction Hemolytic kernicterus, an indirect bilirubin-induced brain dysfunction, is associated with hyper-bilirubinemia in mammalian neonates. In this study, a new model of kernicterus has been developed using intra-peritoneal injections of phenyl hydrazine and subcutaneous injections of sulfisoxazole. These drugs can potentially induce kernicterus in neonatal through changes in hemolysis and hypo-albumin. Methods For this purpose, 7-day-old male Wistar rats ( n = 72; mean weight 11 ± 1 g) were used. The animals have been divided into six different groups which received the drugs alone and their combination, and the drugs' solvents and their combination. Biochemical parameters, brain iron and bilirubin, behavioural performance, auditory function and apoptosis were measured using auto-analyser instruments; atomic absorption spectroscopy, Sawasaki, footprint, auditory brainstem response (ABR) and TUNEL test, respectively. Result The drug-injected groups showed a significant reduction in serum haematocrit and an increase in the concentration of brain bilirubin, total and indirect bilirubin as well as TUNEL positive cells in basal ganglia. In addition, the obtained results showed that there was a significant increase in behavioural disturbance and auditory dysfunction in the group injected with the combination of two drugs. Conclusion This kernicterus-induced rat model could perfectly mimic the common conditions of the hyperbilirubinemia in human neonates. This study offers an easy technique to develop more stable models for follow-up studies. [ABSTRACT FROM AUTHOR]