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1.
Childs Nerv Syst ; 40(6): 1771-1776, 2024 Jun.
Article in English | MEDLINE | ID: mdl-38441628

ABSTRACT

PURPOSE: Post infective hydrocephalus (PIH) is a type of hydrocephalus which occurs after an infection of the brain or cerebrospinal fluid (CSF). Treatment of PIH requires temporary measures such as external ventricular drain (EVD) and ventriculosubgaleal shunt (VSGS) until CSF becomes clear and ready to implement VP shunt. Limited research has been done to explore the tradeoff between these approaches particularly in pediatric PIH patients. Our study compares the complications, mortality rates, and the cost of used resources of both procedures. METHODS: A prospective study was conducted for 18 months in which we compared between VSGS and EVD for management of PIH involving 42 randomized cases with 21 patients in group A operated by VSGS and 21 patients in group B operated by EVD. RESULTS: Our results show a statistically significant difference between both groups in the duration of implementation of VSGS/EVD until resolution of infection occurs. Additionally, a higher rate of pediatric intensive care unit (PICU) admission and a longer length of hospital stay (LOS) were recorded among the EVD group. No statistically significant difference between the number of complications that happened in both despite variations in their forms. Moreover, both groups showed nearly similar mortality rates. CONCLUSION: There is no significant difference in the rate of complications between VSGS and EVD for PIH. Based on that, VSGS emerges as a favorable and cost-effective option for the management of PIH which leads to less economic burden on patients and the country's health resources, especially in developing countries.


Subject(s)
Cerebrospinal Fluid Shunts , Hydrocephalus , Humans , Hydrocephalus/surgery , Hydrocephalus/etiology , Male , Female , Child, Preschool , Infant , Cerebrospinal Fluid Shunts/adverse effects , Cerebrospinal Fluid Shunts/methods , Child , Drainage/methods , Prospective Studies , Treatment Outcome
2.
Acta Trop ; 251: 107123, 2024 Mar.
Article in English | MEDLINE | ID: mdl-38242223

ABSTRACT

BACKGROUND: Childhood brain tumors are a significant global health challenge, yet the etiology of these tumors remains elusive. While research has identified potential risk factors, recent studies have explored the involvement of infectious agents, particularly Toxoplasma gondii (T. gondii), in brain tumor development. METHODS: This study aimed to explore the prevalence of T. gondii infection in children diagnosed with brain tumors and to investigate the potential association between T. gondii infection and childhood brain tumors in Egypt. A total of 64 children with brain tumors and 92 healthy controls were enrolled in this study. Demographics and risk factors data were collected using structured questionnaires. Serological assay using ELISA technique was performed to detect anti-T. gondii antibodies in both cases and control groups. RESULTS: This study revealed a significantly higher seroprevalence of T. gondii infection in brain tumor cases (62.5 %) compared to healthy controls (38 %). Furthermore, a strong association was observed between T. gondii seropositivity and childhood brain tumors (odds ratio: 2.7). Notably, the consumption of unwashed vegetables emerged as a significant risk factor for T. gondii infection in Egypt. Analysis of T. gondii seroprevalence across different subtypes of brain tumors revealed varying rates, with glioma cases displaying a striking 100 % seroprevalence. CONCLUSIONS: These findings support the hypothesis that T. gondii infection may be a risk factor for childhood brain tumors and emphasize the need for further research in this area. The study also highlights the potential implications of control of T. gondii infection for prevention and treatment of childhood brain tumors.


Subject(s)
Brain Neoplasms , Toxoplasma , Toxoplasmosis , Humans , Child , Seroepidemiologic Studies , Egypt/epidemiology , Immunoglobulin G , Toxoplasmosis/complications , Toxoplasmosis/epidemiology , Brain Neoplasms/epidemiology , Brain Neoplasms/complications , Risk Factors , Antibodies, Protozoan
3.
Naunyn Schmiedebergs Arch Pharmacol ; 397(4): 2311-2320, 2024 04.
Article in English | MEDLINE | ID: mdl-37819391

ABSTRACT

This current study reports, for the first time, on the potent cytotoxicity of (Z)-3-hexenyl-ß-D-glucopyranoside, as well as its cellular and molecular apoptotic mechanisms against Panc1 cancer cells. The cytotoxicity of three compounds, namely (Z)-3-hexenyl-ß-D-glucopyranoside (1), gallic acid (2), and pyrogallol (3), which were isolated from C. rotang leaf, was investigated against certain cancer and normal cells using the MTT assay. The cellular apoptotic activity and Panc1 cell cycle impact of compound (1) were examined through flow cytometry analysis and Annexin V-FITC cellular apoptotic assays. Additionally, RT-PCR was employed to evaluate the effect of compound (1) on the Panc1 apoptotic genes Casp3 and Bax, as well as the antiapoptotic gene Bcl-2. (Z)-3-hexenyl-ß-D-glucopyranoside demonstrated the highest cytotoxic activity against Panc1 cancer cells, with an IC50 value of 7.6 µM. In comparison, gallic acid exhibited an IC50 value of 21.8 µM, and pyrogallol showed an IC50 value of 198.2 µM. However, (Z)-3-hexenyl-ß-D-glucopyranoside displayed minimal or no significant cytotoxic activity against HepG2 and MCF7 cancer cells as well as WI-38 normal cells, with IC50 values of 45.8 µM, 108.7 µM, and 194. µM, respectively. (Z)-3-hexenyl-ß-D-glucopyranoside (10 µM) was demonstrated to induce cellular apoptosis and cell growth arrest at the S phase of the cell cycle in Panc1 cells. These findings were supported by RT-PCR analysis, which revealed the upregulation of apoptotic genes (Casp3 and Bax) and the downregulation of the antiapoptotic gene Bcl-2. This study emphasizes the significant cellular potency of (Z)-3-hexenyl-ß-D-glucopyranoside in specifically inducing cytotoxicity in Panc1 cells.


Subject(s)
Antineoplastic Agents , Pancreatic Neoplasms , Humans , Caspase 3 , bcl-2-Associated X Protein , Pyrogallol/pharmacology , Antineoplastic Agents/pharmacology , MCF-7 Cells , Apoptosis , Gallic Acid/pharmacology , Cell Line, Tumor
4.
RSC Adv ; 13(50): 35251-35291, 2023 Nov 30.
Article in English | MEDLINE | ID: mdl-38053691

ABSTRACT

Nanocomposite hydrogel biomaterials represent an exciting Frontier in biomedicine, offering solutions to longstanding challenges. These hydrogels are derived from various biopolymers, including fibrin, silk fibroin, collagen, keratin, gelatin, chitosan, hyaluronic acid, alginate, carrageenan, and cellulose. While these biopolymers possess inherent biocompatibility and renewability, they often suffer from poor mechanical properties and rapid degradation. Researchers have integrated biopolymers such as cellulose, starch, and chitosan into hydrogel matrices to overcome these limitations, resulting in nanocomposite hydrogels. These innovative materials exhibit enhanced mechanical strength, improved biocompatibility, and the ability to finely tune drug release profiles. The marriage of nanotechnology and hydrogel chemistry empowers precise control over these materials' physical and chemical properties, making them ideal for tissue engineering, drug delivery, wound healing, and biosensing applications. Recent advancements in the design, fabrication, and characterization of biopolymer-based nanocomposite hydrogels have showcased their potential to transform biomedicine. Researchers are employing strategic approaches for integrating biopolymer nanoparticles, exploring how nanoparticle properties impact hydrogel performance, and utilizing various characterization techniques to evaluate structure and functionality. Moreover, the diverse biomedical applications of these nanocomposite hydrogels hold promise for improving patient outcomes and addressing unmet clinical needs.

5.
J Anesth Analg Crit Care ; 3(1): 30, 2023 Aug 29.
Article in English | MEDLINE | ID: mdl-37644586

ABSTRACT

In critical care medicine, where there is a demanding career with a problematic work-life balance, mentoring is an important support tool to grow professionally, creating a network of support throughout the career. The mentoring process consists of evidence-based steps to guide critical care mentors and mentees and pair them with each other according to the correct selection and matching of participants.In order to focus on the active role of a young intensivist selected as a mentee at any level and to support their success in a mentoring relationship, the NEXT Committee of the European Society of Intensive Care Medicine (ESICM) developed 2012 a mentoring program.The critical steps of the mentoring program start from establishing a policy and program objectives, passing through the selection of participants, and matching with mentors up to the definition of the personal development plan supported by checklists, worksheets, and evaluation forms. The present manuscript provides key steps and tips for a good, essential based on our experience in the ESICM NEXT-Mentoring Program so that they guide for future mentoring programs conducted by other scientific societies. In addition, we discuss common challenges and how to avoid them.

6.
Front Oncol ; 13: 1153128, 2023.
Article in English | MEDLINE | ID: mdl-37441423

ABSTRACT

Background: Pediatric classical Hodgkin lymphoma (CHL) is a curable disease; however, the optimal salvage regimen is unclear for relapsed/refractory (R/R) disease. This study aimed to compare response rates, toxicity, event-free survival (EFS), and overall survival (OS) of ifosfamide, carboplatin, and etoposide (ICE) with gemcitabine and vinorelbine (GV) regimen after first-line doxorubicin, bleomycin, vinblastine, dacarbazine (ABVD) in pediatric patients with R/R CHL. Methods: This is a retrospective cohort study of 132 pediatric patients with R/R CHL treated from July 2012 to December 2020 with ICE (n = 82) or GV (n = 50). Results: The median age at relapse was 13.9 years, and 68.2% were men. Rates of complete response, partial response, and progressive disease before consolidation were 50.6%, 3.7%, and 45.7% for ICE and 28.5%, 0%, and 71.5% for GV (P = 0.011). By multivariate analysis, regimen (P = 0.002), time to relapse (P = 0.0001), and B-symptoms (P = 0.002) were independent factors to lower response rates. Hematological toxicity, electrolyte disturbance, hemorrhagic cystitis, infectious complications, and hospital admission for fever neutropenia were statistically significant higher for the ICE regimen. Treatment-related mortalities were 2.4% for ICE and 2% for GV (P = 0.86). The 3-year EFS was 39.3% ± 11.4% for ICE and 24.9% ± 12.5% for GV (P = 0.0001), while 3-year OS was 69.3% ± 10.6% and 74% ± 12.9% (P = 0.3), respectively. By multivariate analysis, regimen (P = 0.0001), time to relapse (P = 0.011), B-symptoms (P = 0.001), and leukocytosis (P = 0.007) were significant for EFS, while anemia (P = 0.008), and progressive disease on early response evaluation (P = 0.022) were significant for OS. Conclusions: The ICE regimen had a better overall response rate and EFS, but higher toxicity, than GV; however, OS and mortality were similar.

7.
Restor Dent Endod ; 48(2): e20, 2023 May.
Article in English | MEDLINE | ID: mdl-37284341

ABSTRACT

This mini-review was conducted to present an overview of the use of exosomes in regenerating the dentin-pulp complex (DPC). The PubMed and Scopus databases were searched for relevant articles published between January 1, 2013 and January 1, 2023. The findings of basic in vitro studies indicated that exosomes enhance the proliferation and migration of mesenchymal cells, as human dental pulp stem cells, via mitogen-activated protein kinases and Wingless-Int signaling pathways. In addition, they possess proangiogenic potential and contribute to neovascularization and capillary tube formation by promoting endothelial cell proliferation and migration of human umbilical vein endothelial cells. Likewise, they regulate the migration and differentiation of Schwann cells, facilitate the conversion of M1 pro-inflammatory macrophages to M2 anti-inflammatory phenotypes, and mediate immune suppression as they promote regulatory T cell conversion. Basic in vivo studies have indicated that exosomes triggered the regeneration of dentin-pulp-like tissue, and exosomes isolated under odontogenic circumstances are particularly strong inducers of tissue regeneration and stem cell differentiation. Exosomes are a promising regenerative tool for DPC in cases of small pulp exposure or for whole-pulp tissue regeneration.

8.
ACS Omega ; 8(23): 20283-20292, 2023 Jun 13.
Article in English | MEDLINE | ID: mdl-37323399

ABSTRACT

Aerogel is a high-performance thermal resistance material desired for high-temperature applications like dye-sensitized solar cells, batteries, and fuel cells. To increase the energy efficiency of batteries, an aerogel is required to reduce the energy loss arising from the exothermal reaction. This paper synthesized a different composition of inorganic-organic hybrid material by growing the silica aerogel inside a polyacrylamide (PAAm) hydrogel. The hybrid PaaS/silica aerogel was synthesized using different irradiation doses of gamma rays (10-60 kGy) and different solid contents of PAAm (6.25, 9.37, 12.5, and 30 wt %). Here, PAAm is used as an aerogel formation template and carbon precursor after the carbonization process at a temperature of (150, 350, and 1100 °C). The hybrid PAAm/silica aerogel was converted into aluminum/silicate aerogels after soaking in a solution of AlCl3. Then, the carbonization process takes place at a temperature of (150, 350, and 1100 °C) for 2 h to provide C/Al/Si aerogels with a density of around 0.18-0.040 gm/cm3 and porosity of 84-95%. The hybrid C/Al/Si aerogels presented interconnected networks of porous structures with different pore sizes depending on the carbon and PAAm contents. The sample with a solid content of 30% PAAm in the C/Al/Si aerogel was composed of interconnected fibrils whose diameter was about 50 µm. The structure after carbonization at 350 and 1100 °C was a condensed opening porous 3D network structure. This sample gives the optimum thermal resistance and a very low thermal conductivity of 0.073 (w/m·k) at low carbon content (2.71% at temperature 1100 °C) and high vpore (95%) compared with carbon content 42.38% and vpore (93%) which give 0.102 (w/m·k). This is because at 1100 °C, the carbon atoms evolve to leave an area between Al/Si aerogel particles, increasing the pore size. Furthermore, the Al/Si aerogel had excellent removal ability for various oil samples.

10.
BMC Complement Med Ther ; 23(1): 24, 2023 Jan 30.
Article in English | MEDLINE | ID: mdl-36717906

ABSTRACT

BACKGROUND: Calamus rotang L. (CR) is an Indian shrub. The leaves and other organs of the plant are traditionally used in India for treatment of various diseases. The in vitro antioxidant property of the leaves extract was previously established. Thus, the current study aimed to evaluate the antioxidant and hepatoprotective effects of CR ethyl acetate extract at a dose of 350 mg/kg on CCl4 induced hepatotoxic rats through different mechanisms. METHODS: Histopathological examination of the treated rats' group in comparison with positive and negative controls were performed. Quantitative measuring of the proinflammatory cytokines (TNF α), inflammatory regulators (Arginase, PPAR α) and the antiapoptotic protein Bcl-2 in comparison with positive and negative control groups was achieved using immunohistochemical examination. HPLC profiling of the polyphenol contents and molecular docking of the identified compounds against BH3 proapoptotic protein were correspondingly studied to evaluate the potential antiapoptotic property. RESULTS: The CR extract greatly protects the liver tissue through the suppression of TNF α, arginase and PPAR α induced by CCl4 as well as its enhancement of the antiapoptotic Bcl-2 protein. Fourteen polyphenols of different classes were identified in CR extract and tested via molecular docking for their potential antiapoptotic activities against BH3 protein. Naringin, rutin, 7-hydroxy flavone, and ellagic acid compounds exhibit the highest affinity and potential inhibition of pro-apoptotic protein BH3 via molecular docking study. CONCLUSIONS: The ethyl acetate fraction of the leaves of C. rotang is rich in polyphenols that exhibited potent hepatoprotective effect on CCl4 induced hepatotoxic rats through its antioxidant, anti-inflammatory, anti-steatosis and antiapoptotic properties.


Subject(s)
Antioxidants , Calamus , Rats , Animals , Antioxidants/chemistry , Plant Extracts/chemistry , Tumor Necrosis Factor-alpha , Molecular Docking Simulation , Arginase , PPAR alpha
11.
Eur J Hybrid Imaging ; 6(1): 37, 2022 Dec 28.
Article in English | MEDLINE | ID: mdl-36575330

ABSTRACT

BACKGROUND: Metabolic tumor volume (MTV) and total lesion glycolysis (TLG) are volumetric parameters derived from 18F-FDG PET/CT, suggested to have a prognostic value in cancer patients. Our study aimed to test whether these volumetric parameters of the primary tumor and whole-body tumor burden (WBTB) can predict overall survival (OS) in non-small cell lung cancer (NSCLC) patients. MATERIALS AND METHODS: Thirty biopsy-proven NSCLC patients who had not begun anti-tumor therapy were included in this prospective study. A baseline 18F-FDG PET/CT study was acquired. Scans were interpreted visually and semi-quantitatively by drawing a 3D volume of interest (VOI) over the primary tumor and all positive lesions to calculate metabolic, volumetric parameters, and WBTB. The PET parameters were used to stratify patients into high- and low-risk categories. The overall survival was estimated from the date of scanning until the date of death or last follow-up. RESULTS: At a median follow-up of 22.73 months, the mean OS was shorter among patients with higher tu MTV and tu TLG and high WBTB. High WB TLG was independently associated with the risk of death (p < 0.025). Other parameters, e.g., SUVmax, SUVpeak, and SUVmean, were not predictive of outcomes in these patients. CONCLUSION: In patients with NSCLC, tu MTV, tu TLG, and WBTB determined on initial staging 18F-FDG PET/CT seems to be a strong, independent imaging biomarker to predict OS, superior to the clinical assessment of the primary tumor. The WB TLG was found to be the best predictor of OS.

12.
Nanoscale Adv ; 4(24): 5330-5342, 2022 Dec 06.
Article in English | MEDLINE | ID: mdl-36540120

ABSTRACT

The photocatalytic degradation of uranium complexes is considered among the most efficient techniques for the efficient removal of uranium ions/complexes from radioactive wastewater. Described here is a nanostructured photocatalyst based on a cobalt-doped TiO2 composite with induced oxygen vacancies (Co@TiO2-C) for the photocatalytic removal of uranium complexes from contaminated water. The synergy between oxygen vacancies and Co-doping produced a material with a 1.7 eV bandgap, while the carbon network facilitates electron movement and hinders the e-h recombination. As a result, the new photocatalyst enables the decomposition of uranium-arsenazo iii complexes (U-ARZ3), followed by photocatalytic reduction of hexavalent uranium to insoluble tetravalent uranium. Combined with the nanosheet structure's high surface area, the photocatalytic decomposition, reduction efficiency, and kinetics were significantly enhanced, achieving almost complete U(vi) removal in less than 20 minutes from solution with a concentration as high as 1000 mL g-1. Moreover, the designed photocatalyst exhibits excellent stability and reusability without decreasing the photocatalytic performance after 5 cycles.

13.
Front Psychol ; 13: 868530, 2022.
Article in English | MEDLINE | ID: mdl-36483706

ABSTRACT

Introduction: Visual attention span is a measure of multielement parallel processing. Individuals with higher visual attention span are expected to allocate more attention to letters within strings, which boosts letter identification and translates into more efficient reading. Given the high visual complexity of the Arabic writing system, we expected visual attention span to be an important predictor of reading in the Arabic language. Methods: Native Arabic readers from Grade 4 and Grade 5 were recruited in Iraqi schools. We assessed the contribution of visual attention span to their reading fluency performance in tasks of fully vowelized word and pseudo-word reading, non-vowelized text reading, and written text comprehension. Their phonological awareness, IQ, and single letter processing speed were further evaluated. Results: Results showed that visual attention span was a significant unique predictor of all the reading measures. Visual attention span and phonological awareness accounted for a similar amount of variance in word and pseudo-word reading fluency. Visual attention span was a far higher predictor than phonological awareness for text reading fluency and the sole predictor of text comprehension. Discussion: The role of visual attention span to reading is discussed by reference to current word recognition models. Higher involvement of visual attention is expected in vowelized script to compensate for increased crowding in the presence of diacritics. Visual attention would thus contribute to sub-lexical orthographic parsing and favor orthography-to-phonology mapping, in particular for the pseudo-words that do not benefit from efficient lexical feedback. In non-vowelized script, higher visual attention would enhance the accurate and fast identification of root letters within words, thus resulting in faster word recognition.

14.
Childs Nerv Syst ; 38(11): 2155-2162, 2022 11.
Article in English | MEDLINE | ID: mdl-36214898

ABSTRACT

BACKGROUND: The management of post-infectious hydrocephalus (PIH) remains challenging for neurosurgeons. It requires a temporary diversion procedure till the normalization of CSF parameters prior to the permanent one. Ventriculosubgaleal shunt (VSGS) was widely used in pediatric cases with post-hemorrhagic hydrocephalus (PHH). However, its role in PIH is still lacking. This study was done to elucidate the safety and efficacy of VSGS as a temporary CSF diversion procedure before the permanent one in patients with PIH. PATIENTS AND METHODS: This retrospective investigation analyzed the data of 50 consecutive cases who underwent VSGS for PIH. RESULTS: The age of the included patients ranged between 1 and 10 months. Twenty-six cases had meningitis and or ventriculitis (52%), while the remaining had shunt infection. At follow-up, arresting of hydrocephalus was noted in ten patients (20%), while another 36 cases required the permanent diversion procedure within 35 days. Regarding the shunt complications, scalp infection, tissue breakdown, and shunt exposure were encountered in ten cases (20%), while CSF leakage was noted in 12 cases (24%). Shunt migration was noted in only two patients (4%). Shunt revision was needed in 16 cases (32%). Mortality was encountered in four cases (8%) because of sepsis. Risk factors for morbimortality included younger age, lower weight, male gender, and meningitis and or ventriculitis. CONCLUSION: VSGS is a safe and effective procedure in infants awaiting definitive VPS for postinfectious hydrocephalus. It was proven that VSGS has shortened the hospital stay and the economic burden on the country.


Subject(s)
Cerebral Ventriculitis , Hydrocephalus , Meningitis , Infant , Humans , Male , Child , Retrospective Studies , Cerebral Ventriculitis/complications , Cerebrospinal Fluid Shunts/methods , Hydrocephalus/etiology , Hydrocephalus/surgery , Meningitis/etiology , Ventriculoperitoneal Shunt/adverse effects
15.
Bioorg Chem ; 127: 105972, 2022 10.
Article in English | MEDLINE | ID: mdl-35728290

ABSTRACT

The popularity of nanogel as nano drug carrier lies in its adjustable physical properties, and the ability to encapsulate drug particles with improved properties is being developed to meet the diverse pH-sensitive nanogel for anticancer agent. Monitoring pH has been identified as an important diagnostic element during the treatment process. A pH-sensitive nanogel consisting of (PEG/PMAc) in the ratio of (50:50%) hasbeen cross-linkedby γ-irradiation techniques at an irradiation dose of 5 kGy. Compound 4 and its nanogel 5 were synthesized and assessed for their anticancer effects against HepG2, A549, MCF-7 and HCT-116 as dual VEGFR-2 and EGFR tyrosine kinases inhibitors. The molecular design was performed to investigate the binding mode of compound 4 with VEGFR-2 and EGFR receptors. Our compound 5 in nanogel showed enhanced anticancer activities against the four tested cancer cell lines and also showed higher inhibition activities against VEGFR-2 and EGFRT790M kinases than the derivative 4. Finally, our derivative 4 showed good in silico calculated ADMET profile. It was expected to show good GIT absorption in human, lower CNS side effects, no hepatotoxic actions and higher acute and oral chronic toxic doses in comparing to sorafenib and erlotinib. The obtained results showed that, our compound could be useful as a template for future design, optimization, adaptation and investigation to produce more potent and selective dual VEGFR-2/EGFRT790M inhibitors with higher anticancer activity.


Subject(s)
Antineoplastic Agents , Lung Neoplasms , Acrylates , Antineoplastic Agents/chemistry , Cell Proliferation , Drug Delivery Systems , Drug Design , Drug Screening Assays, Antitumor , ErbB Receptors , Ethylene Glycol/pharmacology , Humans , Hydrogen-Ion Concentration , Molecular Docking Simulation , Mutation , Nanogels , Protein Kinase Inhibitors/chemistry , Structure-Activity Relationship , Vascular Endothelial Growth Factor Receptor-2
18.
Nat Prod Res ; 36(1): 136-141, 2022 Jan.
Article in English | MEDLINE | ID: mdl-32448002

ABSTRACT

The ethyl acetate fraction of the dried aerial parts of Senecio glaucus L. exhibited significant antimicrobial activity against some of selected bacteria and fungi. Also, it showed potent cytotoxicity against PANC-1 cancer cell lines under glucose deficient medium. The ethyl acetate fraction was subjected to different chromatographic techniques for isolation of the bioactive compounds. A new benzofuran glucoside; 2,3-dihydro-3ß-hydroxyeuparin 3-O-glucopyranoside (1) was isolated. Additionally, two known flavonoid compounds isorhamentin 3-O-ß-D-glucoside (2), and isorhamentin 3-O-ß-D-rutinoside (3) were first identified in S. glaucus. Compound 1 exhibited potent antimicrobial activities against two Gram-positive bacteria, one Gram-negative bacteria, and two fungi. Also, it displayed potent cytotoxic activity against PANC-1 cancer cell lines under glucose deficient medium (IC50 7.5 µM). However, the isolated flavonoid glycosides (2 & 3) showed moderate antimicrobial activities against two Gram-positive bacteria, two Gram-negative bacteria, four fungi, and did not show any cytotoxic activity against PANC-1.


Subject(s)
Anti-Infective Agents , Benzofurans , Glucosides , Senecio , Anti-Infective Agents/pharmacology , Benzofurans/pharmacology , Glucosides/pharmacology , Microbial Sensitivity Tests , Plant Extracts/pharmacology , Senecio/chemistry
19.
Int J Mol Sci ; 22(10)2021 May 14.
Article in English | MEDLINE | ID: mdl-34069142

ABSTRACT

Bone healing is a complex, well-organized process. Multiple factors regulate this process, including growth factors, hormones, cytokines, mechanical stimulation, and aging. One of the most important signaling pathways that affect bone healing is the Notch signaling pathway. It has a significant role in controlling the differentiation of bone mesenchymal stem cells and forming new bone. Interventions to enhance the healing of critical-sized bone defects are of great importance, and stem cell transplantations are eminent candidates for treating such defects. Understanding how Notch signaling impacts pluripotent stem cell differentiation can significantly enhance osteogenesis and improve the overall healing process upon transplantation. In Rancourt's lab, mouse embryonic stem cells (ESC) have been successfully differentiated to the osteogenic cell lineage. This study investigates the role of Notch signaling inhibition in the osteogenic differentiation of mouse embryonic and induced pluripotent stem cells (iPS). Our data showed that Notch inhibition greatly enhanced the differentiation of both mouse embryonic and induced pluripotent stem cells.


Subject(s)
Amyloid Precursor Protein Secretases/antagonists & inhibitors , Cell Differentiation/drug effects , Osteogenesis/genetics , Pluripotent Stem Cells/cytology , Pluripotent Stem Cells/drug effects , Animals , Bone and Bones/metabolism , Cell Cycle Proteins/genetics , Cell Differentiation/physiology , Core Binding Factor Alpha 1 Subunit/genetics , Core Binding Factor Alpha 1 Subunit/metabolism , Dexamethasone/pharmacology , Diamines/pharmacology , Gene Expression Regulation/drug effects , Induced Pluripotent Stem Cells/cytology , Induced Pluripotent Stem Cells/drug effects , Induced Pluripotent Stem Cells/physiology , Mesoderm/cytology , Mice , Mouse Embryonic Stem Cells/cytology , Mouse Embryonic Stem Cells/drug effects , Osteoblasts/cytology , Osteoblasts/drug effects , Osteoblasts/physiology , Osteogenesis/drug effects , Pluripotent Stem Cells/metabolism , Receptors, Notch/metabolism , Thiazoles/pharmacology , Transcription Factor HES-1/genetics , Vitamin D/pharmacology
20.
Virus Evol ; 7(1): veab045, 2021 Jan.
Article in English | MEDLINE | ID: mdl-34040797

ABSTRACT

Viral laboratory evolution has been used for different applications, such as modeling viral emergence, drug-resistance prediction, and therapeutic virus optimization. However, these studies have been mainly performed in cell monolayers, a highly simplified environment, raising concerns about their applicability and relevance. To address this, we compared the evolution of a model virus in monolayers, spheroids, and tissue explants. We performed this analysis in the context of cancer virotherapy by performing serial transfers of an oncolytic vesicular stomatitis virus (VSV-Δ51) in 4T1 mouse mammary tumor cells. We found that VSV-Δ51 gained fitness in each of these three culture systems, and that adaptation to the more complex environments (spheroids or explants) correlated with increased fitness in monolayers. Most evolved lines improved their ability to suppress ß-interferon secretion compared to the VSV-Δ51 founder, suggesting that the selective pressure exerted by antiviral innate immunity was important in the three systems. However, system-specific patterns were also found. First, viruses evolved in monolayers remained more oncoselective that those evolved in spheroids, since the latter showed concomitant adaptation to non-tumoral mouse cells. Second, deep sequencing indicated that viral populations evolved in monolayers or explants tended to be more genetically diverse than those evolved in spheroids. Finally, we found highly variable outcomes among independent evolutionary lines propagated in explants. We conclude that experimental evolution in monolayers tends to be more reproducible than in spheroids or explants, and better preserves oncoselectivity. Our results also suggest that monolayers capture at least some relevant selective pressures present in more complex systems.

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