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1.
Nanomaterials (Basel) ; 14(11)2024 May 24.
Article in English | MEDLINE | ID: mdl-38869545

ABSTRACT

A sequence of dye-sensitized solar cells is proposed, utilizing TiO2@Zn/Al-layered double hydroxide (LDH) as their starting materials, in which Ruthenizer N719 was used as a photon absorber. The anticipated system was turned into sheet-like TiO2@mixed metal oxide (MMO) via post-processing treatment. The crystal quality indicated a relation to power conversion efficiency (PCE); this was combined with a comparable morphology profile. In detail, the optimum DSSC device exhibited average sheet-like thickness and a dye loading amount of 43.11 nm and 4.28 ×10-3 mM/cm-2, respectively. Concurrently, a considerable PCE enhancement of the optimum DSSC device (TiO2@MMO-550°) was attained compared to pristine MMO (0.91%), which could be due to boosted electron transfer efficiency. Of the fabricated devices, DSSC fabricated at 550° exhibited the highest PCE (1.91%), with a 35.6% enhancement compared to that obtained at 450°, as a result of its increased open-circuit voltage (3.29 mA/cm2) and short-circuit current (0.81 V). The proposed work delivers an enhanced efficiency as compared to similar geometries.

2.
Front Cell Dev Biol ; 11: 1150991, 2023.
Article in English | MEDLINE | ID: mdl-38143926

ABSTRACT

Introduction: High-grade serous ovarian cancer (HGSOC) is the most prevalent and deadliest subtype of epithelial ovarian cancer (EOC), killing over 140,000 people annually. Morbidity and mortality are compounded by a lack of screening methods, and recurrence is common. Plasminogen-activator-inhibitor 1 (PAI-1, the protein product of SERPIN E1) is involved in hemostasis, extracellular matrix (ECM) remodeling, and tumor cell migration and invasion. Overexpression is associated with poor prognosis in EOC. Platelets significantly increase PAI-1 in cancer cells in vitro, and may contribute to the hematogenous metastasis of circulating tumor cells (CTCs). CTCs are viable tumor cells that intravasate and travel through the circulation-often aided by platelets - with the potential to form secondary metastases. Here, we provide evidence that PAI-1 is central to the platelet-cancer cell interactome, and plays a role in the metastatic cascade. Methods: SK-OV-3 cells where PAI-1 had been silenced, treated with healthy donor platelets, and treated with platelet-conditioned medium were used as an in vitro model of metastatic EOC. Gene expression analysis was performed using RNA-Seq data from untreated cells and cells treated with PAI-1 siRNA or negative control, each with and without platelets. Four cohorts of banked patient plasma samples (n = 239) were assayed for PAI-1 by ELISA. Treatment-naïve (TN) whole blood (WB) samples were evaluated for CTCs in conjunction with PAI-1 evaluation in matched plasma. Results and discussion: Significant phenotypic changes occurring when PAI-1 was silenced and when platelets were added to cells were reflected by RNA-seq data, with PAI-1 observed to be central to molecular mechanisms of EOC metastasis. Increased proliferation was observed in cells treated with platelets. Plasma PAI-1 significantly correlated with advanced disease in a TN cohort, and was significantly reduced in a neoadjuvant chemotherapy (NACT) cohort. PAI-1 demonstrated a trend towards significance in overall survival (OS) in the late-stage TN cohort, and correlation between PAI-1 and neutrophils in this cohort was significant. 72.7% (16/22) of TN patients with plasma PAI-1 levels higher than OS cutoff were CTC-positive. These data support a central role for PAI-1 in EOC metastasis, and highlight PAI-1's potential as a biomarker, prognostic indicator, or gauge of treatment response in HGSOC.

3.
Sci Rep ; 13(1): 7462, 2023 05 08.
Article in English | MEDLINE | ID: mdl-37156818

ABSTRACT

Immunotherapies, including immune checkpoint inhibitors, have limitations in their effective treatment of malignancies. The immunosuppressive environment associated with the tumor microenvironment may prevent the achievement of optimal outcomes for immune checkpoint inhibitors alone, and nanotechnology-based platforms for delivery of immunotherapeutic agents are increasingly being investigated for their potential to improve the efficacy of immune checkpoint blockade therapy. In this manuscript, nanoparticles were designed with appropriate size and surface characteristics to enhance their retention of payload so that they can transmit their loaded drugs to the tumor. We aimed to enhance immune cell stimulation by a small molecule inhibitor of PD-1/PD-L1 (BMS202) using nanodiamonds (ND). Melanoma cells with different disease stages were exposed to bare NDs, BMS202-NDs or BMS202 alone for 6 h. Following this, melanoma cells were co-cultured with freshly isolated human peripheral blood mononuclear cells (hPBMCs). The effects of this treatment combination on melanoma cells were examined on several biological parameters including cell viability, cell membrane damage, lysosomal mass/pH changes and expression of γHA2X, and caspase 3. Exposing melanoma cells to BMS202-NDs led to a stronger than normal interaction between the hPBMCs and the melanoma cells, with significant anti-proliferative effects. We therefore conclude that melanoma therapy has the potential to be enhanced by non-classical T-cell Immune responses via immune checkpoint inhibitors delivered by nanodiamonds-based nanoparticles.


Subject(s)
Melanoma , Nanodiamonds , Humans , Immune Checkpoint Inhibitors/therapeutic use , Leukocytes, Mononuclear/pathology , Melanoma/pathology , Immunotherapy , Tumor Microenvironment , Melanoma, Cutaneous Malignant
4.
Nanomaterials (Basel) ; 13(5)2023 Feb 22.
Article in English | MEDLINE | ID: mdl-36903680

ABSTRACT

In this manuscript, a series of dye-sensitized solar cells (DSSCs) were fabricated as a function of post-processing temperature based on mesoporous CuO@Zn(Al)O-mixed metal oxides (MMO) in conjunction with dye N719 as the main light absorber; the proposed CuO@Zn(Al)O geometry was, in turn, attained using Zn/Al-layered double hydroxide (LDH) as a precursor via combination of co-precipitation and hydrothermal techniques. In particular, the dye loading amount onto the deposited mesoporous materials was anticipated via regression equation-based UV-Vis technique analysis, which evidently demonstrated a robust correlation along with the fabricated DSSCs power conversion efficiency. In detail, of the DSSCs assembled, CuO@MMO-550 exhibited short-circuit current (JSC) and open-circuit voltage (VOC) of 3.42 (mA/cm2) and 0.67 (V) which result in significant fill factor and power conversion efficiency of 0.55% and 1.24%, respectively. This could mainly be due to the relatively high surface area of 51.27 (m2/g) which in turn validates considerable dye loading amount of 0.246 (mM/cm-2).

5.
Sci Rep ; 13(1): 3704, 2023 03 06.
Article in English | MEDLINE | ID: mdl-36879003

ABSTRACT

Circulating tumour cells (CTCs) are a critical intermediate step in the process of cancer metastasis. The reliability of CTC isolation/purification has limited both the potential to report on metastatic progression and the development of CTCs as targets for therapeutic intervention. Here we report a new methodology, which optimises the culture conditions for CTCs using primary cancer cells as a model system. We exploited the known biology that CTCs thrive in hypoxic conditions, with their survival and proliferation being reliant on the activation of hypoxia-inducible factor 1 alpha (HIF-1α). We isolated epithelial-like and quasi-mesenchymal CTC phenotypes from the blood of a cancer patient and successfully cultured these cells for more than 8 weeks. The presence of CTC clusters was required to establish and maintain long-term cultures. This novel methodology for the long-term culture of CTCs will aid in the development of downstream applications, including CTC theranostics.


Subject(s)
Neoplastic Cells, Circulating , Humans , Reproducibility of Results , Hypoxia , Models, Biological , Phenotype
6.
J Biomol Struct Dyn ; 41(23): 14135-14151, 2023.
Article in English | MEDLINE | ID: mdl-36943780

ABSTRACT

Traditional treatment of cancer has been plagued by a number of obstacles, such as multiple drug resistance, toxicity and financial constraints. In contrast, phytochemicals that modulate a variety of molecular mechanisms are garnering increasing interest in complementary and alternative medicine. Therefore, an approach based on network pharmacology was used in the present study to explore possible regulatory mechanisms of 6-shogaol as a potential treatment for cervical cancer (CC). A number of public databases were screened to collect information on the target genes of 6-shogaol (SuperPred, Targetnet, Swiss target prediction and PharmMapper), while targets pertaining to CC were taken from disease databases (DisGeNet and Genecards) and gene expression omnibus (GEO) provided expression datasets. With STRING and Cytoscape, protein-protein interactions (PPI) were generated and topology analysis along with CytoNCA were used to identify the Hub genes. The Gene Ontology (GO) database Enrichr was used to annotate the target proteins, while, using the Kyoto Encyclopedia of Genes and Genomes (KEGG) database, signaling pathway enrichment analysis was conducted. Molecular docking and survival analysis for the Hub genes revealed four genes (HSP90AA1, HRAS, ESR1 and EGFR) with lowest binding energy and majority of the Hub genes (EGFR, SRC, CASP-3, HSP90AA1, MTOR, MAPK-1, MDM2 and ESR1) were linked with the overall survival of CC patients. In conclusion, the present study provides the scientific evidence which strongly supports the use of 6-shogoal as an inhibitor of cellular proliferation, growth, migration as well as inducer of apoptosis via targeting the hub genes involved in the growth of CC.Communicated by Ramaswamy H. Sarma.


Subject(s)
Drugs, Chinese Herbal , Uterine Cervical Neoplasms , Humans , Female , Uterine Cervical Neoplasms/drug therapy , Uterine Cervical Neoplasms/genetics , Molecular Docking Simulation , Network Pharmacology , ErbB Receptors
7.
Biochim Biophys Acta Rev Cancer ; 1878(2): 188863, 2023 03.
Article in English | MEDLINE | ID: mdl-36796527

ABSTRACT

This review is an overview of the current knowledge regarding circulating tumour cells (CTCs), which are potentially the most lethal type of cancer cell, and may be a key component of the metastatic cascade. The clinical utility of CTCs (the "Good"), includes their diagnostic, prognostic, and therapeutic potential. Conversely, their complex biology (the "Bad"), including the existence of CD45+/EpCAM+ CTCs, adds insult to injury regarding their isolation and identification, which in turn hampers their clinical translation. CTCs are capable of forming microemboli composed of both non-discrete phenotypic populations such as mesenchymal CTCs and homotypic and heterotypic clusters which are poised to interact with other cells in the circulation, including immune cells and platelets, which may increase their malignant potential. These microemboli (the "Ugly") represent a prognostically important CTC subset, however, phenotypic EMT/MET gradients bring additional complexities to an already challenging situation.


Subject(s)
Neoplastic Cells, Circulating , Humans , Neoplastic Cells, Circulating/pathology
8.
J Biomol Struct Dyn ; 41(22): 12789-12797, 2023.
Article in English | MEDLINE | ID: mdl-36644886

ABSTRACT

Sphingosine kinase 1 (SphK1) dysfunction is well-known to be linked to various severe diseases, including breast, lung, prostate, and hematological cancers. Due to its crucial function in the onset of cancer and its progression, it is considered a notable drug target for anticancer therapy. Small molecule inhibitors with high specificity and efficacy towards SphK1 are needed for their therapeutic use. In order to find possible SphK1 inhibitors, we conducted a stepwise structure-based virtual screening of plant-based molecules available from the IMPPAT library. A multi-step virtual screening, including physicochemical and ADMET evaluation, PAINS, molecular docking, PASS analysis followed by molecular dynamics (MD) simulation and principal component analysis, identifies two compounds, Gummadiol and Isoarboreol, against SphK1. All-atom MD simulations were performed for 100 ns which examined the structural changes and stability of the docked complexes in the aqueous environment. The time evolution data of structural deviations and compactness, PCA and free energy landscapes suggested that the binding of Gummadiol and Isoarboreol with SphK1 is considerably stable throughout the trajectory. The study highlighted the use of phytochemicals in anticancer therapeutics and presented Gummadiol and Isoarboreol as promising inhibitors of SphK1.Communicated by Ramaswamy H. Sarma.


Subject(s)
Molecular Dynamics Simulation , Neoplasms , Humans , Molecular Docking Simulation , Phosphotransferases (Alcohol Group Acceptor)/chemistry , Phosphotransferases (Alcohol Group Acceptor)/metabolism
9.
Arab J Sci Eng ; 47(7): 7891-7909, 2022.
Article in English | MEDLINE | ID: mdl-34815927

ABSTRACT

The share of wind-based electricity generation is gradually increasing in the world energy market. Wind energy can reduce dependency on fossil fuels, as the result being attributed to a decrease in global warming. This paper discusses and reviews the basic principle parameters that affect the performance of wind turbines. An overview presents the introduction and the background of energy consumption, following the order of the elaboration of wind turbines, including mathematical models, categories of wind turbines were critically discussed. Moreover, it also focuses on materials that are commonly considered for wind turbine manufacturing, and the process used to recycle them. The scale of recycling methods for fiberglass and thermoplastic is presented in the respective section. Various parameters that reduce the function of wind turbines are explained in depth. This review also discusses various environmental impacts of wind turbines. Future research studies are suggested in the conclusion section.

10.
Polymers (Basel) ; 13(23)2021 Nov 25.
Article in English | MEDLINE | ID: mdl-34883615

ABSTRACT

In the present study, cylindrical ABS P400 polymer parts (diameter 6.5 mm) to be used as die-sinking EDM (electric discharge machining) novel electrodes were fabricated using a fused deposition modeling (FDM) process. To meet the conductivity requirement in EDM, ABS parts were metallized using an innovative method that comprised putting aluminum-charcoal (Al-C) on them followed by their copper electroplating. Real-time EDM of the mild steel workpiece was performed using novel electrodes, and machining performance of the electrodes, measured in terms of dimensional accuracy, i.e., change in diameter (ΔD) and change in depth (ΔH) of the cavity, under varying levels of three EDM factors, i.e., current (I), pulse on time (Ton), and pulse off time (Toff), was investigated. Machining results were analyzed using analysis of variance (ANOVA), perturbation graphs, and 3D surface plots. The optimal setting of the EDM parameters for minimizing ΔD and ΔH was determined using the desirability function approach. The suitability of the novel electrodes for EDM was ascertained by comparing their machining results with those of solid copper (SC) electrodes and electrodes fabricated by FDM and metallized using the electro-deposition method (FDM-EM), already reported in the literature, under similar machining conditions. From the results, it was found that ΔD and ΔH were less when EDM was performed using novel electrodes.

11.
Transl Oncol ; 14(12): 101229, 2021 Dec.
Article in English | MEDLINE | ID: mdl-34592589

ABSTRACT

Tumour metastasis accounts for over 90% of cancer related deaths. The platelet is a key blood component, which facilitates efficient metastasis. This study aimed to understand the molecular mechanisms involved in tumour-platelet cell interactions. The interaction between cancer cells and platelets was examined in 15 epithelial cell lines, representing 7 cancer types. Gene expression analysis of EMT-associated and cancer stemness genes was performed by RT-PCR. Whole transcriptome analysis (WTA) was performed using Affymetrix 2.0ST arrays on a platelet co-cultured ovarian model. Platelet adhesion and activation occurred across all tumour types. WTA identified increases in cellular movement, migration, invasion, adhesion, development, differentiation and inflammation genes and decreases in processes associated with cell death and survival following platelet interaction. Increased invasive capacity was also observed in a subset of cell lines. A cross-comparison with a platelet co-cultured mouse model identified 5 common altered genes; PAI-1, PLEK2, CD73, TNC, and SDPR. Platelet cancer cell interactions are a key factor in driving the pro-metastatic phenotype and appear to be mediated by 5 key genes which have established roles in metastasis. Targeting these metastasis mediators could improve cancer patient outcomes.

12.
Mol Cancer ; 20(1): 59, 2021 03 31.
Article in English | MEDLINE | ID: mdl-33789677

ABSTRACT

Cancer cells that transit from primary tumours into the circulatory system are known as circulating tumour cells (CTCs). These cancer cells have unique phenotypic and genotypic characteristics which allow them to survive within the circulation, subsequently extravasate and metastasise. CTCs have emerged as a useful diagnostic tool using "liquid biopsies" to report on the metastatic potential of cancers. However, CTCs by their nature interact with components of the blood circulatory system on a constant basis, influencing both their physical and morphological characteristics as well as metastatic capabilities. These properties and the associated molecular profile may provide critical diagnostic and prognostic capabilities in the clinic. Platelets interact with CTCs within minutes of their dissemination and are crucial in the formation of the initial metastatic niche. Platelets and coagulation proteins also alter the fate of a CTC by influencing EMT, promoting pro-survival signalling and aiding in evading immune cell destruction. CTCs have the capacity to directly hijack immune cells and utilise them to aid in CTC metastatic seeding processes. The disruption of CTC clusters may also offer a strategy for the treatment of advance staged cancers. Therapeutic disruption of these heterotypical interactions as well as direct CTC targeting hold great promise, especially with the advent of new immunotherapies and personalised medicines. Understanding the molecular role that platelets, immune cells and the coagulation cascade play in CTC biology will allow us to identify and characterise the most clinically relevant CTCs from patients. This will subsequently advance the clinical utility of CTCs in cancer diagnosis/prognosis.


Subject(s)
Blood Coagulation , Blood Platelets/metabolism , Immune System/immunology , Immune System/metabolism , Neoplastic Cells, Circulating/metabolism , Neoplastic Cells, Circulating/pathology , Animals , Biomarkers , Blood Coagulation Disorders/blood , Blood Coagulation Disorders/etiology , Cell Communication/genetics , Cell Communication/immunology , Disease Management , Disease Susceptibility , Epithelial-Mesenchymal Transition/genetics , Epithelial-Mesenchymal Transition/immunology , Humans , Neoplasms/blood , Neoplasms/complications , Neoplasms/etiology , Neoplasms/pathology
13.
Preprint in English | medRxiv | ID: ppmedrxiv-20248966

ABSTRACT

OBJECTIVESTo determine risk factors for death in patients with COVID-19 admitted to the main public sector hospital in Somalia and identify interventions contributing to improved clinical outcome in a low-resource and fragile setting. SETTINGMain public sector tertiary hospital in Mogadishu, Somalia. PARTICIPANTSAll 131 laboratory-confirmed COVID-19 patients admitted to the main public tertiary hospital in Somalia between 30 March and 12 June 2020. MAIN OUTCOME MEASURESWe extracted demographic and clinical data from hospital records of all 131 COVID-19 patients admitted to hospital until their death or recovery. We used Kaplan-Meier statistics to estimate survival probabilities and the log-rank test to assess significant differences in survival between groups. We used the Cox proportional hazard model to estimate likelihood of death and assess the effect of risk factors on survival. RESULTSOf the 131 patients, 52 (40%) died in the hospital and 79 (60%) survived to discharge. The factors independently associated with increased risk of in-hospital death were: age [≥] 60 years - survival probability on day 21 in patients < 60 years was 0.789 (95% confidence interval (CI): 0.658-0.874) compared with 0.339 (95% CI: 0.205-0.478) in patients [≥] 60 years; cardiovascular disease (survival probability 0.478 (95% CI: 0.332-0.610) in patients with cardiovascular disease compared with 0.719 (95% CI: 0.601-0.807) in patients without cardiovascular disease); and non-invasive ventilation on admission - patients who were not ventilated were significantly more likely to survive than those who were (P < 0.001). CONCLUSIONOur study, which includes the largest cohort of COVID-19 patients admitted to a single hospital in a sub-Saharan African country, confirms that underlying conditions and age are associated with increased risk of in-hospital death in patients with COVID-19. Our results show the advantage of medical oxygen over non-invasive ventilation in the treatment of patients with severe COVID-19 symptoms.

14.
IDCases ; 23: e01008, 2021.
Article in English | MEDLINE | ID: mdl-33294371

ABSTRACT

Mediastinal involvement of hydatidosis is rare even in endemic areas. Isolated mediastinal without lung or liver involvement is even less commonly reported. We present the case of a young gentleman who was diagnosed with primary mediastinal hydatidosis based on clinical, radiological and pathological criteria. He underwent successful resection of the lesion by VATS (Video-assisted thoracoscopic surgery) preceded by two weeks of medical treatment with albendazole and had an excellent outcome. To the best of our knowledge, this is the first reported case in the state of Qatar.

15.
Breast Cancer Res Treat ; 181(3): 571-580, 2020 Jun.
Article in English | MEDLINE | ID: mdl-32378053

ABSTRACT

PURPOSE: The association between pathological complete response (pCR) in patients receiving neoadjuvant chemotherapy (NAC) for breast cancer and Circulating Tumour Cells (CTCs) is not clear. The aim of this study was to assess whether CTC enumeration could be used to predict pathological response to NAC in breast cancer as measured by the Miller-Payne grading system. METHODS: Twenty-six patients were recruited, and blood samples were taken pre- and post-NAC. CTCs were isolated using the ScreenCell device and stained using a modified Giemsa stain. CTCs were enumerated by 2 pathologists and classified as single CTCs, doublets, clusters/microemboli and correlated with the pathological response as measured by the Miller-Payne grading system. χ2 or ANOVA was performed in SPSS 24.0 statistics software for associations. RESULTS: 89% of patients had invasive ductal carcinoma (IDC) and 11% invasive lobular carcinoma (ILC). At baseline 85% of patients had CTCs present, median 7 (0-161) CTCs per 3 ml of whole blood. Post-chemotherapy, 58% had an increase in CTCs. This did not correlate with the Miller-Payne grade of response. No significant association was identified between the number of CTCs and clinical characteristics; however, we did observe a correlation between pre-treatment CTC counts and body mass index, p < 0.05. CONCLUSIONS: Patients with a complete response to NAC still had CTCs present, suggesting enumeration is not sufficient to aid surgery stratification. Additional characterisation and larger studies are needed to further characterise CTCs isolated pre- and post-chemotherapy. Long-term follow-up of these patients will determine the significance of CTCs in NAC breast cancer patients.


Subject(s)
Antineoplastic Combined Chemotherapy Protocols/therapeutic use , Breast Neoplasms/pathology , Carcinoma, Ductal, Breast/pathology , Carcinoma, Lobular/pathology , Neoadjuvant Therapy/mortality , Neoplastic Cells, Circulating/pathology , Adult , Aged , Breast Neoplasms/drug therapy , Breast Neoplasms/metabolism , Carcinoma, Ductal, Breast/drug therapy , Carcinoma, Ductal, Breast/metabolism , Carcinoma, Lobular/drug therapy , Carcinoma, Lobular/metabolism , Cohort Studies , Female , Follow-Up Studies , Humans , Middle Aged , Neoplasm Grading , Neoplastic Cells, Circulating/drug effects , Receptor, ErbB-2/metabolism , Receptors, Estrogen/metabolism , Receptors, Progesterone/metabolism , Survival Rate
16.
J Orthop Trauma ; 32 Suppl 1: S66-S71, 2018 Feb.
Article in English | MEDLINE | ID: mdl-29373455

ABSTRACT

INTRODUCTION: There is no consensus regarding the postoperative radiology imaging protocol after pelvic fracture surgery. Some institutes routinely scan all patients after their surgery, others do not. The aim of this study was to assess the value of routine use of computed tomography (CT) scans after pelvic fracture surgery and to determine the sensitivity of conventional plain radiographs and intraoperative fluoroscopy in detecting metalwork malposition. PATIENTS AND METHODS: The radiographs and clinical notes of patients undergoing pelvic fracture surgery in the period between January 2010 and December 2015 were reviewed. Patients were categorized into 2 main groups: group A-patients whose fixation entailed the use of a sacroiliac (SI) screws and group B-patients whose fixation did not require an SI screw. Furthermore, the patients were classified according to the position of metalwork in their postoperative plain radiographs and perioperative fluoroscopy into 3 groups: (1) Safe: When there was no suspicion of metalwork malposition. (2) Suspicious: When there was some suspicion of malposition but radiographs were inconclusive. (3) Definite: When plain imaging showed a definite malposition. RESULTS: One hundred ninety-eight patients were included in this study (161 in group A and 37 in group B). In group A, 148 (92%) were classified as safe, 10 were suspicious (6%), and 3 (2%) showed definite malposition. Of the fractures that were believed to be safe on plain radiographs, 78% were confirmed to be safe on CT scans, whereas 22% showed malpositioned metalwork, and 7 patients (4%) required a revision surgery. Plain radiographs showed a sensitivity of 27% in detecting metalwork malposition and a specificity of 99%. Increasing the number of screws significantly increased the risk of malposition and reoperation (P = 0.006 and 0.002 respectively). The plain images of group B were all classified as safe. The CT scans detected 2 cases with long metalwork protruding into the soft tissues, none of which required a revision surgery. CONCLUSION: Perioperative fluoroscopy and plain postoperative radiographs have a low sensitivity in detecting the metalwork malposition after pelvic fracture surgery. We recommend the use of routine postoperative CT scans in patients whose fixation entails the use of SI screws. In this series, routine scanning of patients who did not have SI screws added no significant clinical value. LEVEL OF EVIDENCE: Level IV Diagnostic. See Instructions for Authors for a complete description of levels of evidence.


Subject(s)
Fracture Fixation, Internal/methods , Fractures, Bone/diagnostic imaging , Fractures, Bone/surgery , Pelvic Bones/injuries , Postoperative Care/methods , Tomography, X-Ray Computed/methods , Adolescent , Adult , Aged , Cohort Studies , Female , Follow-Up Studies , Fracture Fixation, Internal/adverse effects , Fracture Healing/physiology , Humans , Male , Middle Aged , Retrospective Studies , Unnecessary Procedures/statistics & numerical data , Young Adult
17.
Sci Rep ; 8(1): 679, 2018 01 12.
Article in English | MEDLINE | ID: mdl-29330439

ABSTRACT

Citrullination, or the post-translational deimination of polypeptide-bound arginine, is involved in several pathological processes in the body, including autoimmunity and tumorigenesis. Recent studies have shown that nanomaterials can trigger protein citrullination, which might constitute a common pathogenic link to disease development. Here we demonstrated auto-antibody production in serum of nanomaterials-treated mice. Citrullination-associated phenomena and PAD levels were found to be elevated in nanomaterials -treated cell lines as well as in the spleen, kidneys and lymph nodes of mice, suggesting a systemic response to nanomaterials injection, and validated in human pleural and pericardial malignant mesothelioma (MM) samples. The observed systemic responses in mice exposed to nanomaterials support the evidence linking exposure to environmental factors with the development of autoimmunity responses and reinforces the need for comprehensive safety screening of nanomaterials. Furthermore, these nanomaterials induce pathological processes that mimic those observed in Pleural MM, and therefore require further investigations into their carcinogenicity.


Subject(s)
Autoantibodies/blood , Hydrolases/metabolism , Nanowires/administration & dosage , Nickel/chemistry , Proteins/metabolism , A549 Cells , Animals , Antibody Formation , Cell Line, Tumor , Citrullination , Female , Humans , Hydrolases/immunology , Kidney/metabolism , Kidney/pathology , Lymph Nodes/metabolism , Lymph Nodes/pathology , Mesothelioma/metabolism , Mesothelioma/pathology , Mice , Mice, Inbred C57BL , Nanowires/chemistry , Spleen/metabolism , Spleen/pathology
18.
Toxicol Sci ; 150(1): 40-53, 2016 Mar.
Article in English | MEDLINE | ID: mdl-26612840

ABSTRACT

Amorphous silica nanoparticles (ASNP) can be synthetized via several processes, 2 of which are the thermal route (to yield pyrogenic silica) and the wet route from a solution containing silicate salts (to obtain precipitated, colloidal, mesoporous silica, or silica gel). Both methods of synthesis lead to ASNP that are applied as food additive (E551). Current food regulation does not require that production methods of additives are indicated on the product label, and, thus, the ASNP are listed without mentioning the production method. Recent results indicate, however, that pyrogenic ASNP are more cytotoxic than ASNP synthesized through the wet route. The present study was aimed at clarifying if 2 representative preparations of ASNP, NM-203 (pyrogenic) and NM-200 (precipitated), of comparable size, specific surface area, surface charge, and hydrodynamic radius in complete growth medium, had different effects on 2 murine macrophage cell lines (MH-S and RAW264.7 cells). Our results show that, when incubated in protein-rich fluids, NM-203 adsorbed on their surface more proteins than NM-200 and, once incubated with macrophages, elicited a greater oxidative stress, assessed from Hmox1 induction and ROS production. Flow cytometry and helium ion microscopy indicated that pyrogenic NM-203 interacted with macrophages more strongly than the precipitated NM-200 and triggered a more evident inflammatory response, evaluated with Nos2 induction, NO production and the secretion of TNF-α, IL-6 and IL-1ß. Moreover, both ASNP synergized macrophage activation by bacterial lipopolysaccharide (LPS), with a higher effect observed for NM-203. In conclusion, the results presented here demonstrate that, compared to precipitated, pyrogenic ASNP exhibit enhanced interaction with serum proteins and cell membrane, and cause a larger oxidative stress and stronger proinflammatory effects in macrophages. Therefore, these 2 nanomaterials should not be considered biologically equivalent.


Subject(s)
Immunity, Innate/drug effects , Macrophages, Alveolar/drug effects , Nanoparticles/toxicity , Silicon Dioxide/toxicity , Animals , Cell Culture Techniques , Cell Line , Chemical Precipitation , Cytokines/genetics , Cytokines/metabolism , Dose-Response Relationship, Drug , Flow Cytometry , Macrophages, Alveolar/immunology , Mice , Microscopy, Electron, Transmission , Nanoparticles/chemistry , Nanoparticles/metabolism , Nanotechnology/methods , Nitric Oxide/biosynthesis , Reactive Oxygen Species/metabolism , Silicon Dioxide/chemistry , Silicon Dioxide/metabolism , Surface Properties
19.
Methods Mol Biol ; 1326: 67-77, 2015.
Article in English | MEDLINE | ID: mdl-26498614

ABSTRACT

The IN Cell Analyzer 1000 possesses several distinguishing features that make it a valuable tool in research today. This fully automated high content screening (HCS) system introduced quantitative fluorescent microscopy with computerized image analysis for use in cell-based analysis. Previous studies have focused on live cell assays, where it has proven to be a powerful and robust method capable of providing reproducible, quantitative data. Using HCS as a tool to investigate antigen expression in duodenal biopsies, we developed a novel approach to tissue positioning and mapping. We adapted IN Cell Analyzer 1000's image acquisition and analysis software for the investigation of tissue transglutaminase (tTG) and smooth muscle alpha-actin (SM α-actin) staining in paraffin-embedded duodenal tissue sections from celiac patients and healthy controls. These innovations allowed a quantitative analysis of cellular structure and protein expression. The results from routine biopsy material indicated the intensity of protein expression was altered in celiac disease compared to normal biopsy material.


Subject(s)
Celiac Disease/pathology , Biopsy , Humans , Microscopy, Fluorescence
20.
Nanomedicine ; 11(4): 815-24, 2015 May.
Article in English | MEDLINE | ID: mdl-25652898

ABSTRACT

Bismuth Ferrite (BFO) nanoparticles (BFO-NP) display interesting optical (nonlinear response) and magnetic properties which make them amenable for bio-oriented diagnostic applications as intra- and extra membrane contrast agents. Due to the relatively recent availability of this material in well dispersed nanometric form, its biocompatibility was not known to date. In this study, we present a thorough assessment of the effects of in vitro exposure of human adenocarcinoma (A549), lung squamous carcinoma (NCI-H520), and acute monocytic leukemia (THP-1) cell lines to uncoated and poly(ethylene glycol)-coated BFO-NP in the form of cytotoxicity, haemolytic response and biocompatibility. Our results support the attractiveness of the functional-BFO towards biomedical applications focused on advanced diagnostic imaging. FROM THE CLINICAL EDITOR: Bismuth Ferrite nanoparticles (BFO-NP) have been recently successfully introduced as photodynamic tools and imaging probes. However, how these nanoparticles interact with various cells at the cellular level remains poorly understood. In this study, the authors performed in vitro experiments to assess the effects of uncoated and PEG-coated BFO-NP in the form of cytotoxicity, haemolytic response and biocompatibility.


Subject(s)
Bismuth/chemistry , Coated Materials, Biocompatible/chemistry , Contrast Media/chemistry , Ferric Compounds/chemistry , Materials Testing , Nanoparticles/chemistry , Cell Line, Tumor , Humans
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