Background
Pediatric-onset SLE (pSLE) is a multisystem autoimmune disease. Recently, the ficolin-2 (FCN2) gene has emerged as a potential candidate gene for susceptibility to SLE.
Objectives
The ...objective of this study was to evaluate the association of the FCN2 gene polymorphisms at positions −986 (G/A), −602 (G/A), −4 (A/G) and SNP C/T (rs3124954) located in intron 1, with susceptibility to pSLE in Egyptian children and adolescents.
Methods
This was a multicenter study of 280 patients diagnosed with pSLE, and 280 well-matched healthy controls. The FCN2 promoter polymorphisms at –986 G/A (rs3124952), −602 G/A (rs3124953), −4 A/G (rs17514136) and SNP C/T (rs3124954) located in intron 1 were genotyped by polymerase chain reaction, while serum ficolin-2 levels were assessed using enzyme-linked immunosorbent assay.
Results
The frequencies of the FCN2 GG genotype and G allele at −986 and −602 positions were significantly more represented in patients with pSLE than in controls (p < 0.001). Conversely, the FCN2 AA genotype and A allele at position −4 were more common in patients than in controls (p < 0.001). Moreover, patients carrying the FCN2 GG genotype in −986 position were more likely to develop lupus nephritis (odds ratio: 2.6 (95% confidence interval: 1.4–4.78); p = 0.006). The FCN2 AA genotype at position −4 was also identified as a possible risk factor for lupus nephritis (odds ratio: 3.12 (95% confidence interval: 1.25–7.84); p = 0.024).
Conclusion
The FCN2 promoter polymorphisms may contribute to susceptibility to pSLE in Egyptian children and adolescents. Moreover, the FCN2 GG genotype at position −986 and AA genotype at position −4 were associated with low serum ficolin-2 levels and may constitute risk factors for lupus nephritis in pSLE.
Celotno besedilo
Dostopno za:
DOBA, IZUM, KILJ, NUK, OILJ, PILJ, PNG, SAZU, UILJ, UKNU, UL, UM, UPUK
Smart pH-responsive niosomes loaded with either Oxaliplatin (Ox), Ylang ylang essential oil (Y-oil), or co-loaded with both compounds (Ox-Y) (Ox@NSs, Y@NSs, and Ox-Y@NSs, respectively) were ...formulated utilizing the thin film method. The developed nanocontainers had a spherical morphology with mean particle sizes lower than 170 nm and showed negative surface charges, high entrapment efficiencies, and a pH-dependent release over 24 h. The prepared pH-responsive niosomes' cytotoxicity was tested against the invasive triple-negative breast cancer (MDA-MB-231) cells, compared to free OX and Y-oil. All niosomal formulations loaded with Ox and/or Y-oil significantly improved cytotoxic activity relative to their free counterparts. The Ox-Y@NSs demonstrated the lowest IC50 (0.0002 µg/mL) when compared to Ox@NSs (0.006 µg/mL) and Y@NSs (18.39 µg/mL) or unloaded Ox (0.05 µg/mL) and Y-oil (29.01 µg/mL)
In addition, the percentages of the MDA-MB-231 cell population in the late apoptotic and necrotic quartiles were profoundly higher in cells treated with the smart Ox-Y@NSs (8.38% and 5.06%) than those exposed to free Ox (7.33% and 1.93%) or Y-oil (2.3% and 2.13%) treatments. Gene expression analysis and protein assays were performed to provide extra elucidation regarding the molecular mechanism by which the prepared pH-sensitive niosomes induce apoptosis. Ox-Y@NSs significantly induced the gene expression of the apoptotic markers Tp53, Bax, and Caspase-7, while downregulating the antiapoptotic Bcl2. As such, Ox-Y@NSs are shown to activate the intrinsic pathway of apoptosis. Moreover, the protein assay ascertained the apoptotic effects of Ox-Y@NSs, generating a 4-fold increase in the relative protein quantity of the late apoptotic marker Caspase-7. Our findings suggest that combining natural essential oil with synthetic platinum-based drugs in pH-responsive nanovesicles is a promising approach to breast cancer therapy.
Skin is the largest mechanical barrier against invading pathogens. Following skin injury, the healing process immediately starts to regenerate the damaged tissues and to avoid complications that ...usually include colonization by pathogenic bacteria, leading to fever and sepsis, which further impairs and complicates the healing process. So, there is an urgent need to develop a novel pharmaceutical material that promotes the healing of infected wounds. The present work aimed to prepare and evaluate the efficacy of novel azithromycin-loaded zinc oxide nanoparticles (AZM-ZnONPs) in the treatment of infected wounds. The Box-Behnken design and response surface methodology were used to evaluate loading efficiency and release characteristics of the prepared NPs. The minimum inhibitory concentration (MIC) of the formulations was determined against Staphylococcus aureus and Escherichia coli. Moreover, the anti-bacterial and wound-healing activities of the AZM-loaded ZnONPs impregnated into hydroxyl propyl methylcellulose (HPMC) gel were evaluated in an excisional wound model in rats. The prepared ZnONPs were loaded with AZM by adsorption. The prepared ZnONPs were fully characterized by XRD, EDAX, SEM, TEM, and FT-IR analysis. Particle size distribution for the prepared ZnO and AZM-ZnONPs were determined and found to be 34 and 39 nm, respectively. The mechanism by which AZM adsorbed on the surface of ZnONPs was the best fit by the Freundlich model with a maximum load capacity of 160.4 mg/g. Anti-microbial studies showed that AZM-ZnONPs were more effective than other controls. Using an experimental infection model in rats, AZM-ZnONPs impregnated into HPMC gel enhanced bacterial clearance and epidermal regeneration, and stimulated tissue formation. In conclusion, AZM -loaded ZnONPs are a promising platform for effective and rapid healing of infected wounds.
Combining sonochemistry with phytochemistry is a modern trend in the biosynthesis of metallic nanoparticles (NPs), which contributes to the sustainability of chemical processes and minimizes ...hazardous effects. Herein, titanium dioxide (TiO
2
) NPs were bioengineered using a novel and facile ultrasound-assisted approach utilizing the greenly extracted essential oil of
Ocimum basilicum
. FTIR and UV-Vis spectrophotometry were used to confirm the formation of TiO
2
NPs. The X-ray diffraction (XRD) analysis showed the crystalline nature of TiO
2
NPs. TEM analysis revealed the spherical morphology of the NPs with sizes ranging from 5.55 to 13.89 nm. Energy-dispersive X-ray (EDX) confirmed the purity of the greenly synthesized NPs. TiO
2
NPs demonstrated outstanding antitumor activity against breast (MCF-7) and lung (A-549) cancer cells with estimated IC
50
values of 1.73 and 4.79 μg mL
−1
. The TiO
2
NPs were cytocompatible to normal cells (MCF-10A) with a selectivity index (SI) of 8.77 for breast and 3.17 for lung cancer. Biological assays revealed a promising potential for TiO
2
NPs to induce apoptosis and arrest cells at the sub-G1 phase of the cell cycle phase in both cancer cell lines. Molecular investigations showed the ability of TiO
2
NPs to increase apoptotic genes' expression (Bak and Bax) and their profound ability to elevate the expression of apoptotic proteins (caspases 3 and 7). Molecular docking demonstrated strong binding interactions for TiO
2
NPs with caspase 3 and EGFR-TK targets. In conclusion, the greenly synthesized TiO
2
NPs exhibited potent antitumor activity and mitochondrion-based cell death against breast and lung cancer cell lines while maintaining cytocompatibility against normal cells.
Combining sonochemistry with phytochemistry is a modern trend in the biosynthesis of metallic nanoparticles (NPs), which contributes to the sustainability of chemical processes and minimizes hazardous effects.
The abdomen is one of the most frequent sites for lymphoma in children. The role of surgery has been limited to intra-abdominal resectable tumours or as a diagnostic procedure in case of disseminated ...disease. Laparotomy without total excision of the tumour does not improve survival; moreover, it may cause complications and delays initiation of chemotherapy.
This study was undertaken to assess the role of surgery in the management of children and adolescents presenting with intra-abdominal lymphoma in order to create certain criteria to select the proper surgical modality for managing those patients.
This case-series, retrospective study was done on 33 patients of abdominal lymphoma over a period of seven years from 2000 to 2007. Patients' files were reviewed regarding the full clinical examinations, laboratory and radiological investigations as well as surgical and diagnostic procedures. Collected data were tabulated and statistically analyzed using SPSS program package.
Eleven patients (33.3%) presented with huge pelvi-abdominal mass and eleven (33.3%) had generalized lymphadenopathy beside their abdominal affection. The remaining 11 (33.3%) patients presented with symptoms of an acute abdomen. A total of 15 laparotomies were done. 11 patients underwent emergency laparotomy for acute abdomen and 4 patients had elective abdominal exploration. Lymph node biopsies were taken in 7 patients and laparoscopy procedures were performed in 3 patients as a diagnostic tool. Out of the total 33, the remaining 8 patients underwent true cut needle biopsy for diagnosis of their disease.
Surgery still has a role in treatment of lymphoma whether non Hodgkin or Hodgkin's. However, in disseminated metastatic disease, aggressive debulking of the tumour should be avoided as chemotherapy is to be instituted primarily. Surgical resection does not cause significant change in morbidity or mortality.
Abdominal lymphoma in paediatrics, role of surgery.
In the current study, we biosynthesized copper oxide NPs (CuO NPs) utilizing the essential oils extracted from
Boswellia carterii
oleogum resin, which served as a bioreductant and capping agent with ...the help of microwave energy. Afterwards, the platinum(
ii
) based anticancer drug, carboplatin (Cr), was loaded onto the CuO NPs, exploiting the electrostatic interactions forming Cr@CuO NPs. The produced biogenic NPs were then characterized using zeta potential (ZP), high-resolution transmission electron microscopy (HRTEM), X-ray diffraction spectroscopy (XRD), and Fourier transform infrared spectroscopy (FTIR) techniques. In addition, the entrapment efficiency and release profile of the loaded Cr were evaluated. Thereafter, SRB assay was performed, where Cr@CuO NPs demonstrated the highest cytotoxic activity against human colon cancer cells (HCT-116) with an IC
50
of 5.17 μg mL
−1
, which was about 1.6 and 2.2 folds more than that of Cr and CuO NPs. Moreover, the greenly synthesized nanoparticles (Cr@CuO NPs) displayed a satisfactory selectivity index (SI = 6.82), which was far better than the free Cr treatment (SI = 2.23). Regarding the apoptosis assay, the advent of Cr@CuO NPs resulted in an immense increase in the cellular population percentage of HCT-116 cells undergoing both early (16.02%) and late apoptosis (35.66%), significantly surpassing free Cr and CuO NPs. A study of HCT-116 cell cycle kinetics revealed the powerful ability of Cr@CuO NPs to trap cells in the Sub-G1 and G2 phases and impede the G2/M transition. RT-qPCR was utilized for molecular investigations of the pro-apoptotic (Bax and p53) and antiapoptotic genes (Bcl-2). The novel Cr@CuO NPs treatment rose above single Cr or CuO NPs therapy in stimulating the p53-Bax mediated mitochondrial apoptosis. The cellular and molecular biology investigations presented substantial proof of the potentiated anticancer activity of Cr@CuO NPs and the extra benefits that could be obtained from their use.
In the current study, we biosynthesized copper oxide NPs (CuO NPs) utilizing the essential oils extracted from
Boswellia carterii
oleogum resin, which served as a bioreductant and capping agent with the help of microwave energy.
Smart pH-responsive niosomes loaded with either Oxaliplatin (Ox), Ylang ylang essential oil (Y-oil), or co-loaded with both compounds (Ox-Y) (Ox@NSs, Y@NSs, and Ox-Y@NSs, respectively) were ...formulated utilizing the thin film method. The developed nanocontainers had a spherical morphology with mean particle sizes lower than 170 nm and showed negative surface charges, high entrapment efficiencies, and a pH-dependent release over 24 h. The prepared pH-responsive niosomes’ cytotoxicity was tested against the invasive triple-negative breast cancer (MDA-MB-231) cells, compared to free OX and Y-oil. All niosomal formulations loaded with Ox and/or Y-oil significantly improved cytotoxic activity relative to their free counterparts. The Ox-Y@NSs demonstrated the lowest IC50 (0.0002 µg/mL) when compared to Ox@NSs (0.006 µg/mL) and Y@NSs (18.39 µg/mL) or unloaded Ox (0.05 µg/mL) and Y-oil (29.01 µg/mL). In addition, the percentages of the MDA-MB-231 cell population in the late apoptotic and necrotic quartiles were profoundly higher in cells treated with the smart Ox-Y@NSs (8.38% and 5.06%) than those exposed to free Ox (7.33% and 1.93%) or Y-oil (2.3% and 2.13%) treatments. Gene expression analysis and protein assays were performed to provide extra elucidation regarding the molecular mechanism by which the prepared pH-sensitive niosomes induce apoptosis. Ox-Y@NSs significantly induced the gene expression of the apoptotic markers Tp53, Bax, and Caspase-7, while downregulating the antiapoptotic Bcl2. As such, Ox-Y@NSs are shown to activate the intrinsic pathway of apoptosis. Moreover, the protein assay ascertained the apoptotic effects of Ox-Y@NSs, generating a 4-fold increase in the relative protein quantity of the late apoptotic marker Caspase-7. Our findings suggest that combining natural essential oil with synthetic platinum-based drugs in pH-responsive nanovesicles is a promising approach to breast cancer therapy.
Currently, the main pillars in treating breast cancer involve tumorectomy pursued by hormonal, radio, or chemotherapies. Nonetheless, these approaches exhibit severe adverse effects and might suffer ...from tumor recurrence. Therefore, there is a considerable demand to fabricate an innovative controlled-release nano-delivery system to be implanted after tumor surgical removal to guard against cancer recurrence. In addition, combining platinum-based drugs with phytochemicals is a promising approach to improving the anticancer activity of the chemotherapeutics against tumor cells while minimizing their systemic effects. This study designed polycaprolactone (PCL)-based electrospun nanofiber mats encapsulating nedaplatin (N) and Peganum harmala alkaloid-rich fraction (L). In addition to physicochemical characterization, including average diameters, morphological features, degradation study, thermal stability, and release kinetics study, the formulated nanofibers were assessed in terms of cytotoxicity, where they demonstrated potentiated effects and higher selectivity towards breast cancer cells. The dual-loaded nanofiber mats (N + L@PCL) demonstrated the highest antiproliferative effects against MCF-7 cells with a recorded IC50 of 3.21 µg/mL, as well as the topmost achieved selectivity index (20.45) towards cancer cells amongst all the tested agents (N, L, N@PCL, and L@PCL). This indicates that the dual-loaded nanofiber excelled at conserving the normal breast epithelial cells (MCF-10A). The combined therapy, N + L@PCL treatment, resulted in a significantly higher percent cell population in the late apoptosis and necrosis quartiles as compared to all other treatment groups (p-value of ≤0.001). Moreover, this study of cell cycle kinetics revealed potentiated effects of the dual-loaded nanofiber (N + L@PCL) at trapping more than 90% of cells in the sub-G1 phase and reducing the number of cells undergoing DNA synthesis in the S-phase by 15-fold as compared to nontreated cells; hence, causing cessation of the cell cycle and confirming the apoptosis assay results. As such, our findings suggest the potential use of the designed nanofiber mats as perfect implants to prevent tumor recurrence after tumorectomy.
Background
Pneumonia is the foremost cause of child death worldwide. M‐ficolin is encoded by the FCN1 gene and represents a novel link between innate and adaptive immunity.
Objectives
To investigate ...the FCN1 −144 C/A (rs10117466) polymorphism as a potential marker for pneumonia severity and adverse outcome namely complications or mortality in the under‐five Egyptian children.
Methods
This was a prospective multicenter study that included 620 children hospitalized with World Health Organization‐defined severe pneumonia and 620 matched healthy control children. Polymorphism rs10117466 of the FCN1 gene promoter was analyzed by PCR‐SSP, while serum M‐ficolin levels were assessed by ELISA.
Results
The FCN1 A/A genotype and A allele at the −144 position were more frequently observed in patients compared to the control children (43.4% vs 27.6%; odds ratio OR: 1.62; 95% confidence interval {CI}: 1.18‐2.2; for the A/A genotype) and (60.8% vs 52.5%; OR: 1.4; 95% CI: 1.19‐1.65; for the A allele); P < .01. The FCN1 −144 A/A homozygous patients had significantly higher serum M‐ficolin concentrations (mean: 1844 ± 396 ng/mL) compared with those carrying the C/C or C/A genotype (mean: 857 ± 278 and 1073 ± 323 ng/mL, respectively; P = .002). FCN1 −144 A/A genotype was an independent risk factor for adverse outcomes in children with severe pneumonia (adjusted OR = 4.85, 95% CI: 2.96‐10.25; P = .01).
Conclusion
The FCN1 A/A genotype at the −144 position was associated with high M‐ficolin serum levels and possibly contributes to enhanced inflammatory response resulting in the adverse outcome of pneumonia in the under‐five Egyptian children.
PDF
