Publications by authors named "Benharouga M"

Preeclampsia (PE) is the most threatening pathology of human pregnancy. Placenta from PE patients releases harmful factors that contribute to the exacerbation of the disease. Among these factors is the prokineticin1 (PROK1) and its receptor, PROKR2 that we identified as a mediators of PE.

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  • Normal fetal growth and placental development require active blood vessel formation (angiogenesis) at the mother-baby interface during pregnancy.
  • Researchers have developed a new, noninvasive method to measure placental blood vessel growth in pregnant mice using a fluorescent molecule, Angiostamp700, that targets specific proteins found in developing blood vessels.
  • This method allows for the quantification of angiogenic activity and provides insights into pregnancy outcomes without harming the mother or fetus.
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  • Gestational trophoblastic diseases (GTD) include rare tumors related to pregnancy, with gestational choriocarcinoma (CC) being a highly aggressive type that can lead to high mortality if not treated quickly.
  • CC has a higher incidence in molar pregnancies and poses greater risks in developing countries, with rates as high as 20 cases per 1,000 pregnancies.
  • A new animal model for CC was created by injecting specific cancer cells into the placenta of pregnant mice, allowing researchers to mimic cancer development and metastasis, which highlights the role of placental blood vessels in spreading the tumor.
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  • Predicting spontaneous preterm birth is challenging for public health, especially in asymptomatic women.
  • This study aimed to assess whether circulating levels of EG-VEGF can effectively predict preterm birth in women at high risk for placenta-related issues, using data from 200 patients.
  • Results showed that women who experienced spontaneous preterm birth had significantly higher EG-VEGF levels at various points in pregnancy, suggesting that these levels could serve as a reliable biomarker for assessing this risk.
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  • - Prokineticins (PROK1 and PROK2) are small proteins that have various roles in the brain, but their specific impacts on different brain cell types and the blood-brain barrier (BBB) are not well understood.
  • - This study examined how PROK1 and PROK2 affect murine cell lines representing microvascular endothelial cells, astrocytes, and neurons, finding that PROK1 decreased neural cell proliferation while PROK2 reduced proliferation across all cell types tested.
  • - Both PROK1 and PROK2 increased cell migration in all lines, and their effects on astrocyte migration could be blocked by specific antagonists; moreover, PROKs were shown to increase BBB permeability, which could also be
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  • - The cellular prion protein (PrP) is a glycoprotein found on cell surfaces, primarily in the brain and peripheral tissues, linked to various functions including signaling, copper homeostasis, and cell adhesion.
  • - PrP is implicated in neurodegenerative diseases and has been found to be expressed in multiple types of cancers, where it aids in tumor growth, cellular invasion, and resistance to chemotherapy.
  • - The review highlights the varied expression of PrP in different cancers and suggests its potential as a therapeutic target for cancer treatment.
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  • Prokineticins (PKs) are small peptides discovered two decades ago, now recognized for their various roles as angiogenic, anorectic, proinflammatory agents, and their involvement in different diseases, making them potential biomarkers.
  • PKs interact with two receptors, PKR1 and PKR2, which have unique therapeutic potentials in treating conditions like cardiovascular, metabolic, neural diseases, pain, and cancer.
  • The article reviews the functions of the PK family, highlights knowledge gaps about their receptors and ligands, and suggests that understanding these proteins better could lead to new, safe treatment strategies.
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  • Gestational choriocarcinoma (GC) is a serious tumor connected to hydatidiform moles, with NLRP7 being a key gene linked to its development and immune response.
  • *Research shows that NLRP7 can operate through different pathways, significantly influencing cancer cell survival and aggressive traits in tumor cells compared to non-tumor cells.
  • *Finding that NLRP7 plays a crucial role in GC growth suggests it could be a valuable target for new treatment strategies for resistant patients.
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  • Preterm birth, defined as birth before 37 weeks of gestation, is linked to higher rates of perinatal death and long-term neurological issues in babies.
  • Acute chorioamnionitis occurs in 70% of preterm labor cases and leads to significant health problems for the newborn.
  • Recent research focuses on understanding the mechanisms behind chorioamnionitis, using animal models to discover treatments, and finding early diagnostic markers to improve outcomes for both mothers and infants.
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  • Gestational choriocarcinoma (CC) is a serious type of cancer linked to abnormal pregnancies, often leading to metastasis and maternal mortality.
  • Recent research indicates a connection between recurrent hydatidiform moles and mutations in the NLRP7 gene, which is involved in immune responses.
  • NLRP7 is found to be overexpressed in CC cells, promoting immune tolerance and affecting cell behavior, which may contribute to both normal placentation and the aggressiveness of choriocarcinoma.
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  • The placenta acts as a protective barrier during pregnancy to prevent infections from reaching the fetus, but some pathogens can still breach this barrier.
  • This review focuses on the effects of specific viruses—Zika, HIV, and SARS-CoV-2—on pregnant women and their babies, examining how these infections alter immune responses and disrupt placental function.
  • By understanding how viral infections interact with the placenta, researchers aim to develop treatments to reduce the risk of harm to the fetus from such infections.
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  • * Researchers employed clinical analysis of placentas and sera, in vitro studies on tumor growth, and in vivo mouse models to study NLRP7's impact on CC.
  • * Findings revealed that NLRP7 promotes tumor cell proliferation and organization, while its absence in pregnant mice led to stronger maternal immune responses and reduced tumor growth and metastasis, highlighting its role in creating an immunosuppressive environment that aids CC progression.
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  • - Cystic fibrosis (CF) results from mutations in the CFTR gene, leading to early lung inflammation (EI) that occurs without bacterial infection, potentially linked to oxidative stress (OX-S) due to imbalances in oxidants and antioxidants.
  • - Recent research shows that copper (Cu), an essential trace element, contributes to oxidative stress in bronchial cells, but its specific role in CF-related early inflammation had not been studied before.
  • - In experiments with healthy and CF bronchial cells, it was found that CF cells exhibited inflammation independent of CFTR function, with altered mitochondrial activity, increased metal concentrations, and significant associations between elevated copper levels, oxidative stress, and inflammatory responses.
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  • - EG-VEGF, a member of the prokineticin family, plays a key role in human placental development and is linked to pregnancy issues like preeclampsia and fetal growth restriction.
  • - Research shows that targeting its receptors (PROKR1 and PROKR2) with antagonists (PC7 and PKRA) can reverse unhealthy effects, suggesting a potential therapeutic approach for pregnancy complications.
  • - A study demonstrated that using these antagonists improves trophoblast cell functions and supports better fetal growth, indicating their potential as safe treatments to enhance pregnancy outcomes.
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  • Vasculogenesis and angiogenesis are crucial for placental development during pregnancy, with vasculogenesis happening in the first trimester and angiogenesis following to form new blood vessels.
  • These processes involve remodeling at the fetomaternal interface and are influenced by various factors, including new families of proteins and homeobox genes.
  • Recent findings link changes in angiogenic and anti-angiogenic factors to serious pregnancy complications like fetal growth restriction and preeclampsia, highlighting potential clinical strategies targeting these proteins for treatment.
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  • The study investigates the role of two proteins, VEGF and EG-VEGF, along with their receptors, in head and neck cancers (HNC) to understand how they contribute to the disease’s development and progression.
  • Serum samples from 64 HNC patients and tissue samples from 14 individuals (7 with oral squamous cell carcinoma (OSCC) and 7 with epulis) were analyzed through various assays in hospitals and research institutions in Morocco and France.
  • Results showed that levels of VEGF and EG-VEGF were significantly lower in HNC patients, while receptors were upregulated in OSCC tissue, suggesting a complex relationship between these factors and the limited metastasis seen in HNC.
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  • Shadoo is part of the prion protein family, which is known for its role in diseases like Transmissible Spongiform Encephalopathies, but its biological functions are still not well understood.
  • Previous experiments on the Sprn gene showed mixed results, but an in-depth analysis using a specific genetic background revealed that knocking out the Sprn gene led to increased embryonic lethality, stunted growth in pups, and lactation issues in mothers.
  • The study also found that Shadoo plays significant roles in early mouse embryogenesis and tissue development, suggesting a complex relationship between Shadoo and other prion proteins like PrP.
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  • Preeclampsia (PE) is a serious pregnancy condition that occurs due to improper trophoblast cell invasion affecting blood circulation between the mother and fetus.
  • CK2, an enzyme involved in cellular processes, was found to be more active during early pregnancy and its inhibition negatively impacted trophoblast cell functions essential for healthy development.
  • The study observed that CK2 activity increases in placentas from PE patients and in PE mouse models, suggesting its role in supporting feto-maternal circulation, potentially indicating a compensatory response to the challenges in PE.
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  • Preeclampsia affects 2-8% of pregnancies globally and is a significant cause of maternal and fetal health issues, prompting a study focused on its incidence and risk factors in Casablanca.
  • The research analyzed 401 cases from a local maternity hospital over 2010-2011, revealing a 7.1% incidence rate, with many affected being first-time mothers around the age of 30 and lacking adequate prenatal care.
  • Key risk factors identified included obesity and chronic hypertension, while low gestational age and absence of prenatal care were linked to poorer health outcomes for mothers and babies; improved prenatal care could help lower preeclampsia rates.
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Fetal growth restriction (FGR) the leading cause of perinatal mortality and morbidity is highly related to abnormal placental development, and placentas from FGR pregnancies are often characterized by increased inflammation. However, the mechanisms of FGR-associated inflammation are far from being understood. NLRP7, a member of a family of receptors involved in the innate immune responses, has been shown to be associated with gestational trophoblastic diseases.

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  • - Bronchial epithelium serves as a crucial barrier against inhaled pollutants and pathogens, but this barrier can fail due to inflammatory airway diseases caused by oxidative stress, leading to increased permeability and shedding of the epithelium.
  • - The cellular prion protein (PrP) plays an important role in maintaining this barrier by localizing to junctional complexes, interacting with proteins such as E-cadherin and desmoglein, and regulating the response to oxidative stress.
  • - Activation of PrP expression helps protect against oxidative damage and supports the stability of junctional proteins, suggesting a potential link between PrP deregulation and respiratory diseases related to impaired barrier function.
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  • - The study investigates the role of endogenous vascular endothelial growth factor (EG-VEGF) in colorectal cancer (CRC) and its link to metastatic peritoneal carcinomatosis (PC), highlighting that high levels of circulating EG-VEGF are associated with advanced cancer stages.
  • - Increased circulating levels of EG-VEGF were found in metastatic PC patients compared to those with CRC and healthy controls, and local EG-VEGF expression was linked to higher tumor and nodal stages in CRC.
  • - The research suggests that the EG-VEGF and its receptors could play a key role in CRC's progression to PC and propose that circulating EG-VEGF might serve as a useful prognostic marker for CRC patients. *
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  • Researchers created new animal models to study pregnancy-induced hypertension (PIH), which includes conditions like gestational hypertension and preeclampsia.
  • They found evidence that a factor called EG-VEGF may play a role in the development of PIH.
  • A specific protocol showed that keeping EG-VEGF levels high in pregnant mice for over 11 days led to symptoms resembling preeclampsia.
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  • Choriocarcinoma (CC) is a serious form of gestational trophoblastic disease that often arises from complete hydatidiform moles, but the mechanisms behind its development and progression remain unclear.* -
  • Recent research has identified endocrine gland-derived vascular endothelial growth factor (EG-VEGF) as a crucial factor in trophoblast growth, which can be targeted for CC treatment through various experimental approaches, including clinical investigations and a new mouse model.* -
  • Findings indicate that elevated levels of EG-VEGF are associated with CC, and using antagonists to block its receptors can significantly reduce tumor progression and support pregnancy, offering a potential alternative to traditional chemotherapy.*
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