79 research outputs found

    New Perspectives on Iran: The Path to Progressive Family Law Before the Islamic Revolution

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    A progressive Iranian women\u27s rights movement has slipped through the cracks of mainstream scholarship. In the 1960s, Iranian women rallied for progressive family law reforms; their efforts culminated in the Family Protection Law of 1967. This note provides an alternative view of the women\u27s rights movement in the Middle East and highlights how a social movement gave rise to comprehensive and progressive family law reform. Over the last century, Iran has been under authoritarian rule, first in the form of a monarchy and now in a theocracy. In spite of this, Iranian women have been steadfast in the fight for freedom. In 2022, Iranian women of all ages, faiths, and socioeconomic backgrounds have led an unprecedented uprising against their government. For the first time since 1979, there is hope for democracy in Iran. This note shines a light on the road to restoring women\u27s rights in Iran

    Use of p53-Silenced Endothelial Progenitor Cells to Treat Ischemia in Diabetic Peripheral Vascular Disease.

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    Background Peripheral vascular disease is a major diabetes mellitus‐related complication. In this study, we noted that expressions of proapoptotic p53 gene and its downstream cascade gene such as p21 are upregulated in hyperglycemia. Therefore, we investigated whether p53‐ and p21‐silenced endothelial progenitor cells (EPCs) were able to survive in hyperglycemic milieu, and whether transplantation of either p53 knockout (KO) or p21KO or p53‐ and p21‐silenced EPCs could improve collateral vessel formation and blood flow in diabetic vaso‐occlusive peripheral vascular disease mouse models. Methods and Results We transplanted p53 and p21KO mouse EPCs (mEPCs) into streptozotocin–induced diabetic (type 1 diabetes mellitus model) C57BL/6J and db/db (B6.BKS(D)‐Leprdb/J) (type 2 model) post–femoral artery occlusion. Similarly, Ad‐p53–silenced and Ad‐p21–silenced human EPCs (CD34+) cells were transplanted into streptozotocin‐induced diabetic NOD.CB17‐Prkdcscid/J mice. We measured blood flow at 3, 7, and 10 days and hindlimb muscles were obtained postsacrifice for mRNA estimation and CD31 staining. Enhanced blood flow was noted with delivery of p53 and p21KO mEPCs in streptozotocin‐induced diabetic C57BL/6J mice. Similar results were obtained when human Ad‐p53shEPCs(CD34+) and Ad‐p21shEPCs(CD34+) were transplanted into streptozotocin‐induced nonobese diabetic severe combined immunodeficiency mice. Gene expression analysis of p53 and p21KO EPCs transplanted hindlimb muscles showed increased expression of endothelial markers such as endothelial nitric oxide synthase, vascular endothelial growth factor A, and platelet endothelial cell adhesion molecule 1. Similarly, quantitative reverse transcriptase polymerase chain reaction of human Ad‐p53shEPCs (CD34+)– and Ad‐p21shEPCs (CD34+)–transplanted hindlimb muscles also showed increased expression of endothelial markers such as vascular endothelial growth factor A, noted primarily in the p53‐silenced EPCs group. However, such beneficial effect was not noted in the db/db type 2 diabetic mouse models. Conclusions Transient silencing of p53 using adenoviral vector in EPCs may have a therapeutic role in diabetic peripheral vascular disease

    Phytochemical screening and in vitro antimicrobial activity of Bougainvillea spectabilis flower extracts

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    Various flower extracts (Chloroform, ethyl acetate, ethanol and water) of Bougainvillea spectabilis were screened for their phytochemical constituents and also investigated for their antimicrobial activities. Phytochemical screening of flower extracts revealed the presence of alkaloids, flavonoides, phlobatannins and terpenoids. Steroids, phenol, tannins, cardinolides and volatile oils were absent in all the extracts. All flower extracts of B. spectabilis inhibited the growth of few of the bacterial and fungal strains tested with varied effectiveness. The maximum antibacterial activities were observed in ethanol and water extracts.  The maximum antifungal activities were observed in chloroform and ethanol extracts.  Thus the bioactive natural products in flower extracts of Bougainvillea spectabilis can be used in the development of new pharmaceuticals that address unmet therapeutic use

    The synergistic effects of saxagliptin and metformin on CD34+ endothelial progenitor cells in early type 2 diabetes patients: a randomized clinical trial.

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    AIMS: Type 2 diabetes is associated with endothelial dysfunction leading to cardiovascular disease. CD34+ endothelial Progenitor Cells (EPCs) are responsible for endothelial repair and neo-angiogenesis and can be used as a cardiovascular disease risk biomarker. This study investigated whether the addition of saxagliptin, a DPP-IV inhibitor, to metformin, may reduce cardiovascular disease risk in addition to improving glycemic control in Type 2 diabetes patients. METHODS: In 12 week, double-blind, randomized placebo-controlled trial, 42 subjects already taking metformin 1-2 grams/day were randomized to placebo or saxagliptin 5 mg. Subjects aged 40-70 years with diabetes for \u3c 10 years, with no known cardiovascular disease, BMI 25-39.9, HbA1C 6-9% were included. We evaluated EPCs number, function, surface markers and gene expression, in addition to arterial stiffness, blood biochemistries, resting energy expenditure, and body composition parameters. A mixed model regression to examine saxagliptin vs placebo, accounting for within-subject autocorrelation, was done with SAS (p \u3c 0.05). RESULTS: Although there was no significant increase in CD34+ cell number, CD31+ cells percentage increased. Saxagliptin increased migration (in response to SDF1α) with a trend of higher colony formation count. MNCs cytometry showed higher percentage of CXCR4 double positivity for both CD34 and CD31 positive cells, indicating a functional improvement. Gene expression analysis showed an upregulation in CD34+ cells for antioxidant SOD1 (p \u3c 0.05) and a downregulation in CD34- cells for IL-6 (p \u3c 0.01). For arterial stiffness, both augmentation index and systolic blood pressure measures went down in saxagliptin subjects (p \u3c 0.05). CONCLUSION: Saxagliptin, in combination with metformin, can help improve endothelial dysfunction in early diabetes before macrovascular complications appear. Trial registration Trial is registered under clinicaltrials.gov, NCT02024477

    The P72R Polymorphism in R248Q/W p53 Mutants Modifies the Mutant Effect on Epithelial to Mesenchymal Transition Phenotype and Cell Invasion via CXCL1 Expression

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    High-grade serous carcinoma (HGSC), the most lethal subtype of epithelial ovarian cancer (EOC), is characterized by widespread TP53 mutations (\u3e90%), most of which are missense mutations (\u3e70%). The objective of this study was to investigate differential transcriptional targets affected by a common germline P72R SNP (rs1042522) in two p53 hotspot mutants, R248Q and R248W, and identify the mechanism through which the P72R SNP affects the neomorphic properties of these mutants. Using isogenic cell line models, transcriptomic analysis, xenografts, and patient data, we found that the P72R SNP modifies the effect of p53 hotspot mutants on cellular morphology and invasion properties. Most importantly, RNA sequencing studies identified CXCL1 a critical factor that is differentially affected by P72R SNP in R248Q and R248W mutants and is responsible for differences in cellular morphology and functional properties observed in these p53 mutants. We show that the mutants with the P72 SNP promote a reversion of the EMT phenotype to epithelial characteristics, whereas its R72 counterpart promotes a mesenchymal transition via the chemokine CXCL1. These studies reveal a new role of the P72R SNP in modulating the neomorphic properties of p53 mutants via CXCL1, which has significant implications for tumor invasion and metastasis

    Anaesth Crit Care Pain Med

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    Objective To develop French guidelines on the management of patients with severe abdominal trauma. Design A consensus committee of 20 experts from the French Society of Anaesthesiology and Critical Care Medicine (SociĂ©tĂ© française d’anesthĂ©sie et de rĂ©animation, SFAR), the French Society of Emergency Medicine (SociĂ©tĂ© française de mĂ©decine d’urgence, SFMU), the French Society of Urology (SociĂ©tĂ© française d’urologie, SFU) and from the French Association of Surgery (Association française de chirurgie, AFC), the Val-de-GrĂące School (École du Val-De-GrĂące, EVG) and the Federation for Interventional Radiology (FĂ©dĂ©ration de radiologie interventionnelle, FRI-SFR) was convened. Declaration of all conflicts of interest (COI) policy by all participants was mandatory throughout the development of the guidelines. The entire guideline process was conducted independently of any industry funding. The authors were advised to follow the principles of the Grading of Recommendations Assessment, Development and Evaluation (GRADE) system for assessment of the available level of evidence with particular emphasis to avoid formulating strong recommendations in the absence of high level. Some recommendations were left ungraded. Methods The guidelines are divided in diagnostic and, therapeutic strategy and early surveillance. All questions were formulated according to Population, Intervention, Comparison, and Outcomes (PICO) format. The panel focused on three questions for diagnostic strategy: (1) What is the diagnostic performance of clinical signs to suggest abdominal injury in trauma patients? (2) Suspecting abdominal trauma, what is the diagnostic performance of prehospital FAST (Focused Abdominal Sonography for Trauma) to rule in abdominal injury and guide the prehospital triage of the patient? and (3) When suspecting abdominal trauma, does carrying out a contrast enhanced thoraco-abdominal CT scan allow identification of abdominal injuries and reduction of mortality? Four questions dealt with therapeutic strategy: (1) After severe abdominal trauma, does immediate laparotomy reduce morbidity and mortality? (2) Does a “damage control surgery” strategy decrease morbidity and mortality in patients with a severe abdominal trauma? (3) Does a laparoscopic approach in patients with abdominal trauma decrease mortality or morbidity? and (4) Does non-operative management of patients with abdominal trauma without bleeding reduce mortality and morbidity? Finally, one question was formulated regarding the early monitoring of these patients: In case of severe abdominal trauma, which kind of initial monitoring does allow to reduce the morbi-mortality? The analysis of the literature and the recommendations were conducted following the GRADEÂź methodology. Results The SFAR/SFMU Guideline panel provided 15 statements on early management of severe abdominal trauma. After three rounds of discussion and various amendments, a strong agreement was reached for 100% of recommendations. Of these recommendations, five have a high level of evidence (Grade 1±), six have a low level of evidence (Grade 2±) and four are expert judgments. Finally, no recommendation was provided for one question. Conclusions Substantial agreement exists among experts regarding many strong recommendations for the best early management of severe abdominal trauma
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