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Refractory Diffuse Large B-cell Lymphoma (DLBCL) presents a major therapeutic challenge due to its resistance to standard treatments. Engineered T-cells, especially Chimeric Antigen Receptor (CAR) T-cells, have shown promise in overcoming drug resistance. This study investigates the effectiveness of WEE1-engineered T-cells in targeting and eliminating refractory DLBCL in vitro. CAR T-cells were created by transducing a 5th-generation CAR construct designed to recognize WEE1, a surface antigen commonly found on refractory DLBCL cells. The cytotoxic effect of engineered T-cells was tested against Rituximab-resistant DLBCL cells (RR-NU-DUL-1). Apoptosis and cell cycle were evaluated using flow cytometry. Quantitative Real-time PCR (RT-PCR) was used to measure the expression of WEE1, BCL2, and CDK2. The results showed a significant increase in target cell lysis, apoptosis, and necrosis, a significant reduction in the percentage of cells in the G2M phase of the cell cycle, as well as a decrease in gene expression level, indicating strong anti-tumor activity. These findings suggest that CAR T-cell therapy holds great promise for treating refractory DLBCL, offering a potential path for clinical application. This in vitro evaluation highlights the potential of WEE1-engineered T-cells as a targeted treatment strategy for refractory DLBCL, emphasizing their clinical applicability and ability to overcome resistance mechanisms in this aggressive lymphoma subtype., Competing Interests: Declarations. Financial and non-financial interests: The authors have no relevant financial or non-financial interests to disclose. Competing interests: The authors declare no competing interests., (© 2025. The Author(s).)

Background: Single nucleotide polymorphisms (SNPs) in microRNA (miRNA) genes could alter miRNA expression levels or processing and, thus, may contribute to colorectal cancer (CRC) development. Therefore, this study aimed to examine whether the MIR181A1 genomic sequence possesses SNPs that can affect the expression of hsa-miR-181a-5p and, subsequently, impact its targets and associate with CRC risk., Methods: The NCBI dbSNP database was searched for possible SNPs associated with MIR181A1. One SNP with a minor allele frequency > 5%, rs12039395 G > T was identified. In silico analyses determined the effect of the SNP on the secondary structure of the miRNA and predicted the hsa-miR-181a-5p target genes. The SNP was genotyped using allelic discrimination assay, the relative hsa-miR-181a-5p expression level was determined using quantitative real-time PCR, and immunohistochemical staining was used to detect target genes in 192 paraffin-embedded specimens collected from 160 CRC patients and 32 healthy subjects., Results: The rs6505162 SNP conferred protection against CRC, and the G-allele presence provides may provide accessibility for the transcriptional machinery. Hsa-miR-181a-5p was significantly over-expressed in the CRC group compared to controls and in samples carrying the G-allele compared to those with T-allele. PTEN, identified as the only hsa-miR-181a-5p target implicated in CRC, was significantly diminished in the CRC group compared to controls and showed an inverse relationship with hsa-miR-181a-5p expression level as well as negatively associated with the G-allele presence in CRC., Conclusion: This study highlights that rs12039395 G > T may protect against CRC by influencing the expression of hsa-mir-181a-5p and its target gene, PTEN., (© 2024. The Author(s), under exclusive licence to Springer Science+Business Media, LLC, part of Springer Nature.)

Microbial transformation is extensively utilized to generate new metabolites in bulk amounts with more specificity and improved activity. As cinnamic acid was reported to exhibit several important pharmacological properties, microbial transformation was used to obtain its new derivatives with enhanced biological activities. By manipulating the 2-stage fermentation protocol of biotransformation, five metabolites were produced from cinnamic acid. Two of them were new derivatives; N -propyl cinnamamide 2̲ and 2-methyl heptyl benzoate 3̲ produced by Alternaria alternata . The other 3 metabolites, p -hydroxy benzoic acid 4̲, cinnamyl alcohol 5̲ and methyl cinnamate 6̲, were produced by Rhodotorula rubra , Rhizopus species and Penicillium chrysogeneum , respectively. Cinnamic acid and its metabolites were evaluated for their cyclooxygenase (COX) and acetylcholinesterase (AChE) inhibitory activities. Protection against H 2 O 2 and Aβ 1-42 induced-neurotoxicity in human neuroblastoma (SH-SY5Y) cells was also monitored. Metabolite 4̲ was more potent as a COX-2 inhibitor than the parent compound with an IC 50 value of 1.85 ± 0.07 μM. Out of the tested compounds, only metabolite 2̲ showed AChE inhibitory activity with an IC 50 value of 8.27 μM. These results were further correlated with an in silico study of the binding interactions of the active metabolites with the active sites of the studied enzymes. Metabolite 3̲ was more potent as a neuroprotective agent against H 2 O 2 and Aβ 1-42 induced-neurotoxicity than catechin and epigallocatechin-3-gallate as positive controls. This study suggested the two new metabolites 2̲ and 3̲ along with metabolite 4̲ as potential leads for neurodegenerative diseases associated with cholinergic deficiency, neurotoxicity or neuroinflammation.

Background: β-Thalassemia major (BTM) is one of the most common hereditary anemias worldwide. Patients suffer from iron overload that results from repeated blood transfusion This in turn leads to multiple organ damage and endocrinopathies. This study aims to assess the prevalence of growth retardation, hypothyroidism, and diabetes mellitus in children and adolescents with BTM treated at Dubai Thalassemia Centre., Methods: A total of 105 children and adolescents were included in this retrospective observational study., Results: 39 children and 66 adolescents' data were analyzed. Females composed 51.3% (n = 20) of children and 53.0% (n = 35) of adolescents. Pretransfusion hemoglobin below 9 gm/dl was observed in 10.8% (n = 4) and 10.6% (n = 7) in children and adolescents, respectively. The mean age of menarche was 13.5 years. Among all study participants, 22.6% (n = 14) had normal height velocity whereas 37.1% (n = 23) had reduced height velocity in one year and 40.3% (n = 25) had reduced height velocity in two consecutive years. The proportion of children and adolescents showing reduced height velocity was significantly higher in females compared to the males (90.6% versus 63.3%, respectively, Chi-square = 6.597, p-value = 0.010). Although none of the study participants had diabetes mellitus, 26.1% (n = 12/46) had pre-diabetes. Elevated TSH was observed in 14.7% (n = 5) children and 8.1% (n = 5) adolescents while low FT4 was reported in one child and one adolescent., Conclusion: Of all endocrinopathies seen among children and adolescents with BTM, growth delay remains the main concern for this group of patients. Effective treatment is key to further reducing endocrinopathies. Although the sample size is limited, we postulate that the low percentage of endocrinopathies among children with BTM treated at Dubai thalassemia center and the low level of pretransfusion anemia reflect the effective transfusion and chelation at the center., (© 2024. The Author(s).)

This paper presents novel concepts including stratified single-valued neutrosophic soft topogenous ( stratified svns-topogenous ), stratified single-valued neutrosophic soft filter ( stratified svns-filter ), stratified single-valued neutrosophic soft quasi uniformity ( stratified svnsq-uniformity ) and stratified single-valued neutrosophic soft quasi proximity ( stratified svnsq-proximity ). Additionally, we present the idea of single-valued neutrosophic soft topogenous structures, formed by integrating svns-topogenous with svns-filter, and discuss their properties. Furthermore, we explore the connections between these single-valued neutrosophic soft topological structures and their corresponding stratifications., Competing Interests: The authors declare the following financial interests/personal relationships which may be considered as potential competing interests: Yaser Saber reports financial support was provided by Majmaah University., (© 2024 The Author(s).)

Objective: This study aimed to assess the relative gene expression level of transforming growth factor-β1 (TGFB1) and haptoglobin (HP) in the peripheral blood of prostate cancer (PCa) patients and evaluate their diagnostic ability., Methods: A total of 125 participants were enrolled in the present study. Among them, 75 PCa patients, 25 benign prostatic hyperplasia (BPH) patients, and 25 healthy volunteers served as the control group. The relative TGFB1 and HP gene expression level was quantified using real-time polymerase chain reaction. Further, free and total PSA levels were determined using electrochemiluminescence assays., Results: TGFB1 was significantly over-expressed, whereas HP was significantly downregulated in the peripheral blood of PCa patients compared to BPH and control groups (p-value ranges from 0.034 to <0.001). Moreover, the high expression level of TGFB1 was associated with an increased risk of PCa development with OR=1.412 (95%CI: 1.081-1.869, p= 0.012). TGFB1 and HP relative expression levels had lower diagnostic performance to differentiate PCa from normal and BPH individuals compared to PSA, however, the combination of the tested parameters improved the diagnostic efficacy., Conclusions: TGFB1 and HP relative expression have moderate diagnostic efficacy in discriminating patients with PCa from BPH and healthy subjects. Furthermore, over-expression of TGFB1 may contribute to the pathogenesis of PCa.

Background: Nonalcoholic fatty liver disease (NAFLD) is the most common cause of chronic liver disease, and previous studies suggested a relationship between vitamin D deficiency and NAFLD. It is suggested that vitamin D supplementation may have significant beneficial effect on liver biochemistry and histology., Objective: This study aims to assess the degree of possible steatosis regression using controlled attenuation parameter (CAP) in NAFLD patients with vitamin D deficiency after vitamin D supplementation and evaluating its effect on lipid profile and transaminases., Patients and Methods: This study was conducted on 100 NAFLD patients with vitamin D deficiency. They received 10000 IU/week of vitamin D orally for 3 months. CAP was used to assess hepatic steatosis and fibrosis before/after intervention. Transaminases, lipid profile, and vitamin D levels were evaluated before/after treatment., Results: Serum AST, ALT, cholesterol, TG, LDL and HDL showed a significant reduction posttreatment in patients with both normal and elevated baseline levels ( P < 0.001). The posttreatment mean CAP showed a significant reduction (300.44 ± 37.56 vs. 265 ± 36.19 dB/ml) ( P  < 0.001), and there was a significant improvement in the mean fibrosis values by LSM (5.32 ± 1.53 vs. 4.86 ± 1.28 KPa) ( P  = 0.001). After supplementation, serum vitamin D level was raised significantly in the majority of patients ( P  < 0.001); however, only 13% of them reached sufficient levels (>30 ng/ml), insufficient levels (20-29 ng/ml) was reached in 83% and 5% showed vitamin D deficiency (<20 ng/ml)., Conclusion: A significant improvement was detected in hepatic steatosis (by CAP); mean values of LSM, transaminases and lipid profile after three months of oral vitamin D supplementation., (Copyright © 2023 Wolters Kluwer Health, Inc. All rights reserved.)

The major labdanes in the oleogum resin of Araucaria heterophylla (Salisb.) Franco, 13-epi-cupressic acid ( 1 ) and acetyl-13-epi-cupressic acid ( 2 ) were used to prepare seven new ( 3 - 9 ), along with one known ( 10 ) derivatives. RAW264.7 cells were used to evaluate the anti-inflammatory activity of the derivatives ( 1 - 10 ) via measuring the level of COX-2 expression and IL-6. Pre-treated RAW264.7 cells with 1 - 10 (except for derivative 7 ) at 25 µM for 24h exhibited downregulation of COX-2 expression in response to LPS stimulation. Moreover, pre-treatment with compounds 1 , 2 , or 3 significantly attenuated the LPS-stimulated IL-6 level in RAW264.7 cells ( p  < 0.05). A docking study was conducted against phospholipase A2 (PLA2), a crucial enzyme in initiating the inflammatory cascade. The significant structural features of compounds ( 1 - 10 ) as PLA2 inhibitors included the carbonyl group at C-4 (free or substituted) and the hydrophobic diterpenoid skeleton. This study suggested 13-epi-cupressic acid as a scaffold for new anti-inflammatory agents.

The effects of thermal radiation and thermophoretic particles deposition (TPD) on the hybrid nanofluid (HNF) flow across a circling sphere have momentous roles in research and engineering. Such as electrical devices, projectiles, thermal conveyance, sheet production, renewable energy, and nuclear-powered plants. Therefore, the current study presents the stagnation point flow of HNF flows about an orbiting sphere. The HNF is organized with the accumulation of aluminum alloys (AA70772 and AA7075) nanoparticles in the water. The HNF flow model equations are changed into the non-dimensional form of ODEs through the similarity variables and then numerically solved through the parametric simulation. It has been perceived that the significance of the rotation factor boosts the velocity curve, while the flow motion drops with the increasing numbers of AA7072 and AA7075 nanoparticles. Furthermore, the addition of AA7072 and AA70775 nano particulates in water lessens with the temperature profile. The energy distribution rate in case of hybrid nanoliquid enhances from 3.87 to 13.79%, whereas the mass dissemination rate enhances from 4.35 to 11.24% as the nanoparticles concentration varies from 0.01 to 0.03., (© 2023. The Author(s).)

The essential oil isolated by hydrodistillation of the oleogum resin of Araucaria heterophylla has been analyzed by GC-MS. Twenty-four components accounting to 99.89% of the total detected constituents of this essential oil were identified. The major ones were: caryophyllene oxide (14.8%), ( +)-sabinene (12.07%), D-limonene (11.22%), caryophyllene (10.36%), α-copaene (8.00%), β-pinene (6.44%), trans-verbenol (5.88%) and α-pinene oxide (5.18%). The in vitro inhibitory activities of this oil against aldose reductase, BuCHE, COX-2 and SARS-CoV-2 M pro enzymes were evaluated. This revealed promising inhibitory activity of the essential oil against both aldose reductase and BuCHE enzymes. The molecular docking study of the major components of the Araucaria heterophylla essential oil was carried out to correlate their binding modes and affinities for aldose reductase and BuCHE enzymes with the in vitro results. In conclusion, the in vitro inhibitory activity of the essential oil attributed to the synergistic effect between its components and the in silico study suggested that compounds containing epoxide and hydroxyl groups may be responsible for this activity. This study is preliminary screening for the oil to be used as antidiabetic cataract and Alzheimer's disease therapeutics and further investigations may be required., (© 2023. The Author(s).)

Muslims comprise nearly a quarter of the worldwide population, with significant populations in the United States, Canada, and Europe. As clinicians, it is important to be familiar with Islamic religious and cultural perspectives on medical treatment, life-prolonging measures and comfort and palliative care, but historically, this has been a gap in the literature. Recently, there have been multiple papers discussing Islamic bioethics, particularly in regards to end of life care in adults; however, there has been a lack of literature discussing the Islamic perspective on issues related to neonatal and perinatal end of life care. This paper uses clinical scenarios to review key relevant principles of Islamic law, discussing the primary and secondary sources used in formulating fatawa, including the Quran, hadith , qiyas, and ' urf , and the importance of preservation of life and upholding of human dignity ( karamah ). Neonatal and perinatal scenarios are used to specifically explore the Islamic perspective on withholding and withdrawal of life-sustaining measures and determining what constitutes an acceptable quality of life. In some Islamic cultures the expertise of the patient's physician is given significant weight in making these judgments, and as such, families may appreciate frank assessment of the situation by the clinical team. Because of the various factors involved in issuing religious ruling, or fatwa , there is a wide spectrum of opinions on these rulings, and physicians should be aware of these differences, seek counsel and guidance from local Islamic leaders, and support families in their decision-making process., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (© 2023 Shoaib, Vawter-Lee, Venkatesan and Soliman.)

The biotransformation of vulgarin (1) , an eudesmanolides-type sesquiterpene lactone obtained from Artemisia judaica , by the microorganism, Aspergillus niger , was carried out to give three more polar metabolites; 1- epi -tetrahydrovulgarin (1α,4α-dihydroxy-5αH,6,11βH-eudesman-6,12-olide (2) , 20% yield, 1α,4α-dihydroxyeudesm-2-en-5αH,6,11βH-6,12-olide (3a) , 10% yield, and C-1 epimeric mixture (3a, b) , 4% yield, in a ratio of 4:1, 3a/3b . The structures of vulgarin and its metabolites were elucidated by 1 and 2D NMR spectroscopy in conjunction with HRESIMS. Metabolites (3a) and (3b) are epimers, and they are reported here for the first time as new metabolites obtained by biotransformation by selective reduction at C-1. Vulgarin and its metabolites were evaluated as anti-inflammatory agents using the human cyclooxygenase (COX) inhibitory assay. The obtained data showed that (1) exhibited a good preferential inhibitory activity towards COX-2 (IC50 = 07.21 ± 0.10) and had a moderate effect on COX-1 (IC50 = 11.32 ± 0.24). Meanwhile, its metabolite (3a) retained a selective inhibitory activity against COX-1 (IC50 = 15.70 ± 0.51). In conclusion, the results of this study revealed the necessity of the presence α, β unsaturated carbonyl group in (1) for better COX-2 inhibitory activity. On the other hand, the selectivity of (1) as COX-1 inhibitor may be enhanced via the reduction of C-1 carbonyl group.

The stretched surface's convective heat transfer capability can be improved by using nanoparticles. There is a significant role of the Prandtl number in determining the thermal and momentum stretching layer surfaces. It is proposed in this study that an effective Prandtl number model be used to explore the two-dimensional oblique stagnation point flow of γ A l 2 O 3 - H 2 O and γ A l 2 O 3 - C 2 H 6 O 2 nanofluids moving over a convective stretching surface. The fluid in question is subjected to a thorough investigation. It is necessary to apply non-linear ordinary differential equations in order to connect the controlling partial differential equations with the boundary conditions. To solve these equations, an efficient and reliable numerical technique is used. Shooting Method with Runge Kutta-IV in Mathematica software. Visual representations of normal and tangential velocity and temperature as well as streamlines as a function of many physical parameters are shown. The results show that as the volume fraction of nanoparticles increases, the fluid flow f ( y ) , h ( y ) and velocity f ' ( y ) , h ' ( y ) all increase, whereas the flow f ( y ) and velocity f ' ( y ) both increase against the stretching ratio parameter, while the flow h ( y ) and velocity h ' ( y ) both decrease. When the volume percentage of nanoparticles and the Biot number are both increased, the temperature rises. However, when the stretching ratio parameter is increased, the temperature falls. Physical attributes like the local skin friction coefficient and the heat flow may be characterized in many ways. A nanofluid comprised of γ A l 2 O 3 - C 2 H 6 O 2 outperformed a γ A l 2 O 3 - H 2 O nanofluid in terms of heat transfer rate. The source of zero skin friction may be observed to move to the left or right depending on the balance of obliqueness and straining motion at point x s . The computed numerical results of the current research correspond well with those accessible in the literature for the limiting scenario., Competing Interests: The authors declare no conflict of interest., (© 2023 The Authors.)

Plasma lipoproteins exist as several subpopulations with distinct particle number and size that are not fully reflected in the conventional lipid panel. In this study, we sought to quantify lipoprotein subpopulations in patients with type 2 diabetes mellitus (T2DM) to determine whether specific lipoprotein subpopulations are associated with insulin resistance and inflammation markers. The study included 57 patients with T2DM (age, 61.14 ± 9.99 years; HbA1c, 8.66 ± 1.60%; mean body mass index, 35.15 ± 6.65 kg/m 2 ). Plasma lipoprotein particles number and size were determined by nuclear magnetic resonance spectroscopy. Associations of different lipoprotein subpopulations with lipoprotein insulin resistance (LPIR) score and glycoprotein acetylation (GlycA) were assessed using multi-regression analysis. In stepwise regression analysis, VLDL and HDL large particle number and size showed the strongest associations with LPIR (R 2 = 0.960; p = 0.0001), whereas the concentrations of the small VLDL and HDL particles were associated with GlycA (R 2 = 0.190; p = 0.008 and p = 0.049, respectively). In adjusted multi-regression analysis, small and large VLDL particles and all sizes of lipoproteins independently predicted LPIR, whereas only the number of small LDL particles predicted GlycA. Conventional markers HbA1c and Hs-CRP did not exhibit any significant association with lipoprotein subpopulations. Our data suggest that monitoring insulin resistance-induced changes in lipoprotein subpopulations in T2DM might help to identify novel biomarkers that can be useful for effective clinical intervention.

India and Ethiopia employ Guizotia abyssinica (niger plant) as a source of edible vegetable oil. Previous studies have documented the niger plant's antioxidant properties and dietary benefits. Here, G. abyssinica extract was obtained and ten known bioactive components ( 1 - 10 ) were isolated. The antioxidant, antidiabetic, and prebiotic properties of whole extract and isolated components of niger and the plant's ability to cooperate symbiotically with probiotic strains were examined. Compound 10 , myricetin-3- O -L-rhamnoside, had the highest antioxidant capacity measured in the 2,2-diphenylpicrylhydrazyl (DPPH, 4629.76 ± 6.02 µmol Trolox equivalent/g compound) and ferric-reducing antioxidant power (FRAP, 2667.62 ± 7.5 mol Trolox equivalent/g compound) assays. The lowest α -amylase and glycogen phosphorylase activities and glucose diffusion were obtained with whole G. abyssinica extracts, whereas compounds 8 - 10 had moderate inhibitory effects. G. abyssinica extract also induced the highest glucose absorption by yeast cells in the presence of 5 mM of glucose. Moreover, Lactobacillus plantarum and L. rhamnosus incubated with β -sitosterol 3- O -D-glucoside (compound 7 ) showed the highest prebiotic activity score. The levels of L-(+)-lactic acid isomer in the probiotic strains were the highest in presence of the whole extract and decreased progressively in the presence of flavonoid glycosides (compounds 8 - 10 ) and β -sitosterol 3- O -D-glucoside. The enzymatic profile of the probiotic strains was unaffected by the niger extract and compounds 7 - 10 . The findings revealed that the biological activities of G. abyssinica extract are mediated by the compounds 1 - 10 , and it may be considered as a promising plant for the treatment of diabetes mellitus .

Kidney stone disease (KSD) represents an urgent medical problem because of increasing its prevalence. Several functional polymorphisms in genes involved in the renal handling of calcium were associated with KSD pathogenesis. Among those, the rs4236480 of transient receptor potential vanilloid member 5 (TRPV5) gene, the rs1801725 of calcium-sensing receptor (CASR) gene, and the rs1801197 of calcitonin receptor (CALCR) gene appear to be of great importance. Due to the scarce data on the Egyptians, this study aimed to evaluate the association of these candidate genetic variants with the risk of developing KSD in an Egyptian population. To do so, the biochemical parameters were measured along with the genotyping of the three polymorphisms using allelic discrimination assay in 134 KSD patients and 86 age and sex-matched healthy subjects. The results showed that the genotypic distributions and allelic frequencies of the studied variants were significantly different between cases and controls. The three polymorphisms increased the risk of KSD significantly under all the tested genetic models (OR ranges from 2.152 to 5.994), except for the recessive model of the CALCR rs1801197 polymorphism after Bonferroni correction. The gene-gene interaction analyzed by multifactor dimensionality reduction selected the three-locus combination as the best model associated with the susceptibility to KSD with OR 9.706. Further, synergistic interactions were identified between TRPV5 rs4236480 and CALCR rs1801197 variants and CASR rs1801725 and CALCR rs1801197 variants. In conclusion, the TRPV5 rs4236480, CASR rs1801725, and CALCR rs1801197 polymorphisms showed a significant association with the risk of KSD in the Egyptian population. Furthermore, their complex interactions might have an impact on the genetic susceptibility to develop KSD., (© 2022. The Author(s).)

Identification of host genetic factors influencing the risk of developing hepatocellular carcinoma (HCC) in patients with chronic hepatitis C virus (HCV) infection may help to refine patients' selection to benefit from specific preventative measures and/or adapted screening policies. Thus, this study aimed to investigate the association of MTHFR c.677C > T and c.1298A > C in addition to TYMS 3'-UTR 6-bp ins/del polymorphisms with the susceptibility to HCV-related HCC in an Egyptian population. Polymerase chain reaction-restriction fragment length polymorphism was performed to genotype the polymorphisms in 194 HCV-infected patients subdivided into liver cirrhotic (LC, n = 104) and HCC (n = 90) patients as well as 100 healthy subjects. In healthy controls, the MTHFR c.677C > T polymorphism under the homozygous and recessive models (p = 0.005) and the c.1298A > C polymorphism under all the tested genetic models (p-values range from < 0.001 to 0.007) were associated with an increased risk of HCC. In LC patients, the MTHFR c.677C > T polymorphism under the homozygous, dominant, and recessive models (p-values range from 0.001 to 0.007), as well as MTHFR c.1298A > C under the homozygous model only (p = 0.014), increased the susceptibility to HCC. The C/C and T/C haplotypes of MTHFR c.677C > T and MTHFR c.1298A > C polymorphisms were contributed to an increased risk of healthy subjects to develop HCC (p-values range from < 0.001 to 0.015), while only the T/C haplotype was associated with the progression of HCC in LC patients (p = 0.001). In conclusion, MTHFR c.677C > T and c.1298A > C in addition to their haplotypes may contribute to the development of HCV-related HCC in an Egyptian population. These findings may aid in the early diagnosis and management of HCC., (© 2021. The Author(s), under exclusive licence to Springer Nature Switzerland AG.)

Alpha-lipoic acid (α-LA) is characterized by its unpleasant odor, poor bioavailability and stability. Nanotechnology was applied to overcome this limitation. So we aimed in this study to formulate α-LA in two different forms of chitosan nanoparticles (CsNPs) and solid lipid nanoparticles (SLNPs) and characterize them in terms of physical properties and biological activities against aluminum chloride (AlCl 3 )-induced neurotoxicity in rats. The vivo study was processed on 50 rats divided into 5 groups as follow: control, neurotoxic, treated α-LA, treated α-lipoic acid-loaded chitosan nanoparticles (α-LA-CsNPs) and treated α-lipoic acid-loaded solid lipid nanoparticles (α-LA-SLNPs) groups. The result was depicted by transmission electron microscopy (TEM) revealed that α-LA-SLNPs had a regular spherical shape while α-LA-CsNPs showed an irregular spherical form. Dynamic light scattering (DLS) analysis showed that the average particle size for α-LA-SLNPs was about 71 nm and for α-LA-CsNPs was about 126 nm. After the experimental period, we observed that AlCl 3 administration significantly increased oxidative stress, neuroinflammation and apoptosis and decreased brain fatty acid contentsand brain-derived neurotrophic factor,while α-LA, α-LA-CsNPs and α-LA-SLNPs were able to ameliorate these negative changes in the neurotoxic rats. However, the effect of the α-LA-loaded NPs was more prominent than that of pristine α-LA but the α-LA-SLNPs group was almost close to the control group. Conclusion: α-LA can attenuate neurotoxicity induced by AlCl3, attributed to its anti-inflammatory, antioxidant and anti-apoptotic activities in addition to the effectiveness of the encapsulation technique that can increase the efficiency and stability of α-LA. Moreover, α-LA-SLNPs are more efficient than α-LA-CsNPs.

Background: Despite the favorable survival rates of childhood B-cell acute lymphoblastic leukemia (B-ALL), a significant number of patients present a dismal prognosis. Forkhead box P3 (FOXP3), a marker of regulatory T cells, functions as a transcription factor involved in immune cell regulation, and its expression correlates with prognosis in many malignancies. Therefore, this study aimed to assess the relative gene expression level of FOXP3 in childhood B-ALL and to detect its prognostic utility., Methods: The study included 139 bone marrow samples obtained from 112 patients at diagnosis and 27 healthy children. Following extraction, RNA was reverse transcribed and the relative expression level of FOXP3 was quantified by quantitative PCR. Cytogenetics, immunophenotype, and minimal residual disease were analyzed according to international guidelines., Results: A highly significant overexpression of FOXP3 was detected in childhood B-ALL patients at diagnosis, which was associated with a stronger risk for disease relapse and patients' worse survival. Moreover, multivariate regression models highlighted the independent prognostic value of FOXP3 for childhood B-ALL. Finally, the combination of FOXP3 relative expression with clinically used disease markers clearly enhanced the prediction of treatment stratification., Conclusions: High FOXP3 relative expression was associated with inferior outcome suggesting its potentiality as a molecular prognostic marker to predict childhood B-ALL patients' outcomes., (© 2021 Wiley Periodicals LLC.)

Background: Asparaginase (ASNase) is a key component in the treatment protocols of childhood acute lymphoblastic leukemia (ALL). Asparagine synthetase (ASNS) and the basic region leucine zipper activating transcription factor 5 (ATF5) mediate the anti-leukemic effect of ASNase. Only a few reports studied the association between polymorphisms in these genes and treatment-related toxicity and response. Therefore, the current study aimed to investigate the association of ASNS and ATF5 polymorphisms with the susceptibility to ASNase-related toxicity and disease outcome in a population of childhood ALL Egyptian patients., Methods: In this study, 88 children with ALL were enrolled and genotyped for ASNS T629A and ATF5 C362T polymorphisms using allelic discrimination assay., Results: The studied polymorphisms did not associate with hypersensitivity or thrombosis, while the ATF5 C362T polymorphism was associated significantly with decreased ASNase-associated pancreatitis (AAP) risk under the dominant model. Patients carrying TT/CT genotypes of ATF5 C362T polymorphism had a significantly better overall survival (OS) and longer event-free survival (EFS) compared to patients with CC genotype. Multivariate analysis confirmed the independent prognostic value of the ATF5 C362T dominant model., Conclusion: ATF5 362TT and CT genotypes were associated with decreased risk to develop AAP and better disease outcome demonstrating a low risk for events and superior survival.

Nowadays, herbal extracts are considered to be a potential source for developing new drugs that will overcome resistance to conventional chemotherapeutic agents. This study was aimed to explore the efficacy of several Egyptian plant extracts against Toxoplasma gondii infection in vitro for future development of a new, safe, and effective compound for T. gondii. Methanol extracts from Matricaria chamomilla (German chamomile), Laurus nobilis, Citrullus colocynthis, Cinnamum camphora, Boswellia scara, and Melissa officionalis plants and oil extracts (either essential or fixed oils) of some plants such as: lemon grass (Cymbopogon citratus), marjoram (Origanum majorana), watercress (Nasturtium officionale), wheat germ (Triticum aestivum), sesame (Sesamum indicum), rosemary (Salvia rosmarinus), citronella (Cymbopogon nardus), clove (Syzygum aromaticum), jojoba (Simmondsia chinesis), and basil (Ocimum basilicum) were investigated for their anti-Toxoplasma activities. The methanol extracts from C. colocynthis and L. nobilis and the oil extracts from lemon grass and marjoram were active against T. gondii with half maximal inhibitory concentrations (IC 50 ) of 22.86 µg/ml, 31.35 µg/ml, 4.6 µg/ml, and 26.24 µg/ml, respectively. Their selectivity index (SI) values were <10. Interestingly, the methanol extract from M. chamomilla and oil from citronella had the lowest IC 50 values for T. gondii (3.56 µg/ml and 2.54 µg/ml, respectively) and the highest SI values (130.33 and 15.02, respectively). In conclusion, methanol extract from M. chamomilla and oil from citronella might be potential sources of novel therapies for treating toxoplasmosis.

Background: Colorectal cancer (CRC) rates are affected by genetics, ethnicity, and environmental factors; it is considered one of the most aggressive human malignancies with high mortality and morbidity rates worldwide due, in part, to its asymptomatic nature during the early stages of disease. Objective: Owing to the impact of microRNA (miRNA) dysregulation on CRC development and progression, this study was conducted to explore the expression levels of mir-21, -23a, and -27a in the sera and tissues of Egyptian CRC patients and to evaluate their diagnostic efficacy based on circulating levels. Methods: In the test phase, the relative expression levels of the studied miRNAs were evaluated in the sera of 70 participants (35 CRC patients and 35 healthy controls) using quantitative real-time-polymerase chain reaction and to verify their diagnostic value. The exploratory phase was designed to validate the tumor-derived trait by comparing the miRNA levels in the cancerous and adjacent noncancerous tissues. Results: The relative expression levels of the studied miRNAs were significantly upregulated in both serum and tumor tissues of the patients compared to their corresponding controls. In addition, significant positive correlations were found between the relative expression levels of the studied miRNAs in serum samples and their levels in the matched CRC tissues. The serum expression levels of mir-21 and -23a were more predictive of CRC than mir-27a. Conclusion: Circulating mir-21, -23a, and -27a expression levels appear to be valuable diagnostic biomarkers for CRC, especially when combined.

Introduction: Physicians working as first-level responders in emergency departments (ED) often encounter patients, of any age group with shortness of breath (SOB). Definitive diagnosis is quite challenging once the underlying pathology is rare and unusual and/or the ED physicians recommend and rely on non-specific investigations., Presentation of Case: A 29-year-old female presented to the emergency department with sudden onset of shortness of breath and upper abdominal pain radiating to the left shoulder. Diagnosis of Bochdalek hernia was made clinically coupled with radiological findings of CXR and computed tomography (CT) by the surgeon on-call, while it was missed by an emergency care physician on her first visit., Discussion: Herniation of the abdominal contents into the thoracic cavity via the Bochdalek opening, commonly known as Bochdalek hernia is seen and diagnosed most commonly accidentally in early life. Adult cases of symptomatic Bochdalek hernia has been reported in the literature. These patients usually present with non-specific symptoms, thus pose a diagnostic challenge for an emergency care physician., Conclusion: The report of this case highlights the notion that such rare causes of acute onset dyspnea and upper abdominal pain pose a diagnostic challenge for novice emergency care physicians especially in situations where he/she does not ask for second-line help in general and recommend and rely on a non-specific investigation in specific., (Copyright © 2020 The Author(s). Published by Elsevier Ltd.. All rights reserved.)

Background: Investigating and evaluating possible alternative therapeutic strategies to control hepatocellular carcinoma (HCC) is a critical need because of its high prevalence and being one of the most lethal cancers. Curcumin and taurine showed potent anti-tumor activities in pre-clinical and clinical studies by targeting multiple pathways. Thus, this study was designed to assess the effect of a combined treatment consisted of curcumin, piperine, and taurine on circulating levels of interleukin-10 (IL-10), and microRNAs miR-141 and miR-21., Methods: Twenty eligible HCC patients administrated an oral dose of 4 g curcumin, 40 mg piperine, and 500 mg taurine daily for three successive treatment cycles, each was a 30-day. The level of IL-10 along with the expression levels of miR-141, and miR-21 were monitored in serum before starting the treatment and after each cycle. Patients were followed-up for a period of 24 months., Results: The combined treatment was able to produce a significant decrease in the levels of serum IL-10, and miR-21 while it resulted in a non-significant up-regulation of serum miR-141 expression level. At the end of the follow-up period, the median overall survival (OS) rate was found to be 17.00 months with a worse OS in patients with high baseline levels of circulating IL-10 and miR-21 compared to those with low levels. In contrast, a low baseline level of circulating miR-141 was associated with poor prognosis., Conclusions: The combined treatment may be able to increase the OS rate by altering the circulating level of IL-10 and miR-21., Competing Interests: Conflicts of Interest: The authors have no conflicts of interest to declare.

This paper presents a framework to address three dimensional (3-D) dynamic walking for a bipedal exoskeleton with underactuated legs. To achieve this goal, the framework is constructed via a trajectory generator and an optimized inverse kinematics algorithm that can cope with underactuation. In order to feasibly attain task velocities with underactuated legs, the inverse kinematics algorithm makes use of a task prioritization method via the exploitation of null space. In doing so, the tasks with lower priority, e.g., swing foot orientation, are attained as much as possible without disrupting the higher priority tasks, such as CoM trajectory. Meanwhile, the trajectory generator utilizes the ZMP concept analytically and ensures the acceleration continuity throughout the whole walking period, regardless of the contact and phase changes. The proposed method is verified via a lumped human-bipedal exoskeleton model that is developed and simulated in MSC.ADAMS simulation environment. As a result, we obtained feasible and dynamically balanced 3-D walking motion, in which no oblique foot landing or exaggerated torso orientation variations were observed, despite the underactuated nature of the robot legs.

In this paper, we present our research study concerning the design and development of an exoskeleton that aims to provide 3D walking support with minimum number of actuators. Following a prior simulation study, the joint configuration was primarily determined. In order for the exoskeleton to possess advanced characteristics, the following design criteria were investigated: i) all the actuators (hip/knee/ankle) were deployed around the waist area to decrease leg weight and improve wearability, ii) custom-built series elastic actuators were used to power system for high fidelity torque-controllability, iii) 3D walking support is potentially enabled with reduced power requirements. As a result, we built the first actual prototype to experimentally verify the aforementioned design specifications. Furthermore, the preliminary torque control experiments indicated the viability of torque control.

Aims: As a source of growth factors and with its cytoprotective properties, platelet-rich plasma (PRP) received considerable attention in regenerative medicine. Thus, this study was designed to evaluate the protective efficacy of PRP against γ-radiation-induced nephrotoxicity., Main Methods: Forty male rats were distributed in four groups: 1) control, 2) PRP, 3) Radiation, and 4) PRP + radiation. Nephrotoxicity was examined in rats after a whole body γ-irradiation at a single dose of 8 Gy. Activated PRP (0.5 ml/kg BW) was injected subcutaneously twice weekly for three successive weeks prior to γ-irradiation. At the end of the experiment, creatinine, urea, albumin, and neutrophil gelatinase-associated lipocalin (NGAL) serum levels, as well as renal relative gene expression level of kidney injury molecule-1 (KIM-1) were estimated. Further, malondialdehyde level, nitric oxide content and reduced glutathione content in addition to superoxide dismutase and catalase activities were measured. Moreover, the expression levels of B-cell lymphoma 2 (Bcl-2), Bcl-2-associated X (Bax), and caspase-3 proteins were assayed., Key Findings: PRP pre-treatment significantly reduced the radiation-induced abnormalities in kidney histology and attenuated the induced cell injury. Furthermore, PRP notably ameliorated the state of oxidative stress and appeared to inhibit the induced apoptosis., Significance: This study lends a probable protective role of PRP against γ-radiation-induced nephrotoxicity which can highlight the possibilities of its application as a complementary procedure during radiotherapy., (Copyright © 2019 Elsevier Inc. All rights reserved.)

Background and aim: Imaging guided microwave ablation (MWA) for hepatocellular carcinoma (HCC) has become a widely used method over recent years. Tumors close to the diaphragm, gastrointestinal tract, gallbladder, pancreas, hepatic hilum and major bile duct or vessels are generally considered relative contraindications for microwave ablation. This study was conducted to assess the effectiveness and safety of ultrasonography-guided MWA in treating patients with HCC in difficult anatomical sites in comparison to those in conventional sites. Patients and methods: Eighty-eight patients were included and divided into two groups: the study group of 44 with 46 lesions lying <5mm from the diaphragm, hepatic capsule, gall bladder (GB) or large vessel; and the control group of 44 patients with 50 lesions in non-risky sites. Each lesion was ablated using an ultrasound guided microwave probe using a detailed protocol. Results: Most of the patients were males, with a mean age of 57.8 years. In the study group, two patients had lesions adjacent to the GB, twelve were perivascular and 32 were subcapsular. The overall successful ablation rates were 84.8% and 92% in the study and control groups, respectively. Within the study group, ablation rates were 100%, 75% and 87.5% for lesions close to the GB, perivascular lesions and subcapsular lesions, respectively. One patient developed a subcutaneous abscess, with good outcome after proper treatment. Fever, pain and asymptomatic pleural effusion were reported after ablation without statistically significant difference between the groups or among subgroups. In conclusion: MWA for HCC in difficult anatomical sites is as effective and safe as for ordinary sites., (Creative Commons Attribution License)

Because of the potential regenerative and cytoprotective effects of its content of numerous bioactive growth factors and cytokines, platelet-rich plasma (PRP) became an attractive biomaterial for therapeutic purposes. Therefore, the current study was designed to investigate the potential therapeutic effect of PRP against lead nitrate- and/or γ-radiation-induced hepatotoxicity. To do so, hepatotoxicity was induced in rats by intraperitoneal administration of lead nitrate (7.5 mg/kg) thrice weekly for two consecutive weeks and/or a whole-body γ-irradiation at a single dose of 6 Gy. Activated PRP (0.5 ml/kg) was injected subcutaneously 24 h after the last dose of lead nitrate and/or γ-irradiation and continued twice weekly for three successive weeks. Lead nitrate intoxication and/or γ-irradiation resulted in a significant elevation of serum alanine transaminase and aspartate transaminase activities accompanied with a significant decrease in serum levels of total protein and albumin. Further, a significant increase in malondialdehyde level and nitric oxide content accompanied with a significant decrease in the reduced glutathione content and the enzyme activities of glutathione-S-transferase, superoxide dismutase, and catalase were observed. Additionally, hepatic extracellular signal-regulated kinase (ERK) and Akt signaling pathways were stimulated. PRP treatment notably ameliorated the induced cell injury, reduced the intracellular oxidative and interestingly increased the upregulation of phosphorylated ERK1/2 and Akt. Moreover, PRP treatment relieved lead nitrate and/or γ-radiation-induced hepatic histological damages. In conclusion, this study sheds the light on a probable therapeutic role of PRP against lead nitrate- and/or γ-radiation-induced hepatotoxicity which might attribute to its ability to activate ERK and Akt signaling pathways.

The original publication of this paper contains adjustment errors.

Toxoplasmosis is a worldwide parasitic disease responsible for serious health problems to human. The currently available drugs used for toxoplasmosis treatment showed a limited efficacy and cause serious host toxicity. The in vitro screening for toxoplasmicidal activity of Araucaria heterophylla resin (AHR) extract and its major component 13-epi-cupressic acid (CUP) showed that both AHR (EC 50  = 3.90) and CUP (EC 50  = 3.69) have high toxoplasmicidal activity in comparison with standard cotrimoxazole (EC 50  = 4.28). The antiprotozoal effects of AHR and CUP were investigated against acute and chronic toxoplasmosis using mice models. Two groups of Swiss albino mice were infected by RH Toxoplasma strain intraperitoneally and by Me49 strain orally. Both groups were treated with AHR and CUP in different doses. Their effects were evaluated by survival rate, peritoneal, spleen and liver parasite burdens, brain cyst burden, NO serum level and histopathological lesions. The ultrastructural changes of tachyzoites of acutely infected mice were studied using scanning electron microscopy (SEM). There is an evidence of toxoplasmicidal activity of AHR and CUP in acute and chronic experimental toxoplasmosis. In the acute model, mice treated with AHR and CUP showed prolonged survival rates, a significant decrease in the parasite density in peritoneal lavage and pathological insult in both liver and spleen compared with that of untreated ones. SEM results denote evident morphological alterations of treated tachyzoites. In chronic experimental toxoplasmosis, AHR and CUP treated groups could significantly reduce brain cyst burden by 96.05% and 98.02% respectively. This study indicates that AHR and CUP showed potent toxoplasmicidal activities experimentally and could be used as a potential natural nontoxic agent for treatment of toxoplasmosis., (Copyright © 2018 Elsevier Inc. All rights reserved.)

Background: Cartonectin is a potent anti-inflammatory adipokine that might be implicated in metabolism and energy storage. Our objective was to evaluate the influence of weight reduction following laparoscopic sleeve gastrectomy (LSG) on serum cartonectin and vaspin levels., Subjects and Methods: Thirty-two individuals (29 female and 3 male) with morbid obesity underwent LSG. Anthropometric indices, lipid profile, fasting serum concentrations of glucose, insulin, vaspin, and cartonectin were measured prior and 3 months after LSG. Insulin sensitivity was determined using the homeostasis model assessment of insulin resistance (HOMA-IR)., Results: Following LSG, circulating cartonectin level increased significantly while serum vaspin was significantly decreased. The percentage change of serum cartonectin level correlated negatively with the percentage changes in body mass index, waist circumference, and waist-hip ratio and positively with percentage changes in LDL-C, triglycerides, and HOMA-IR after adjustment for age and sex. Moreover, the changes in vaspin concentration positively correlated with the changes in insulin level and HOMA-IR after adjustment for age and sex. In a multiple stepwise linear regression model, the changes in waist circumference explained 13% variability of changes in cartonectin level while the changes in HOMA-IR and LDL-C were responsible for 31% of the variability in changes of vaspin level., Conclusion: LSG-induced weight loss rapidly increases serum cartonectin level and decreases the serum vaspin level in morbidly obese subjects. The changes in cartonictin level seem to be influenced by the changes of waist circumference while the changes of HOMA-IR and LDL-C might be determinant factors of the changes in vaspin level.

Despite their clinical benefits in cancer treatment, the deleterious effects on heart following chemo/radiotherapy are of increasing importance. Zingerone, a natural polyphenol, possesses multiple biological activities, such as antioxidant and anti-inflammatory. Thus, the current study was designed to assess the potential cardioprotective effects of zingerone against cisplatin or γ-radiation. Zingerone was given by intragastric intubation (25 mg/kg) daily for three successive weeks prior to the induction of cardiotoxicity using a single dose of cisplatin (20 mg/kg, i.p.) or a whole body γ-irradiation at a single dose of 6 Gy. Zingerone pre-treatment significantly reduced the abnormalities in heart histology and the increase in the cardiotoxicity indices, serum lactate dehydrogenase, and creatine kinase-MB activities, as well as plasma cardiac troponin T and B-natriuretic peptide, induced by cisplatin or γ-radiation. Further, zingerone, except for superoxide dismutase, notably ameliorated the state of oxidative stress as evidenced by a significant decrease in malondialdehyde level accompanied with a significant increase in the reduced glutathione content and catalase activity. Additionally, zingerone mitigated the increase in the inflammatory markers including serum level of tumor necrosis factor-alpha, cardiac myeloperoxidase activity, and cyclooxygenase-2 protein expression. Moreover, zingerone alleviated the elevation of caspase-3 gene expression and the prominent nuclear DNA fragmentation and attenuated the decrease in mitochondrial complexes' activities. This study sheds the light on a probable protective role of zingerone as an antioxidant, anti-inflammatory, and antiapoptotic agent against cisplatin- or γ-radiation-induced cardiotoxicity and holds a potential in regard to therapeutic intervention for chemo/radiotherapy mediated cardiac damage.

This study was designed to assess the relationship between serum levels of anti-Müllerian hormone and 25-hydroxy vitamin D in chronic kidney disease male patients. For that, serum 25-hydroxy vitamin D and anti-Müllerian hormone along with follicle-stimulating hormone, luteinising hormone, prolactin, total testosterone and estradiol were assayed in 59 patients with different stages of chronic kidney disease and 21 healthy participants. Compared to controls, serum levels of anti-Müllerian hormone and 25-hydroxy vitamin D were significantly decreased in patients with chronic kidney disease. The decreased anti-Müllerian hormone level correlated positively with estimated glomerular filtration rate and serum levels of testosterone and 25-hydroxy vitamin D. Meanwhile, it was negatively correlated with age and serum levels of urea, creatinine, follicle-stimulating hormone, luteinising hormone and prolactin. 25-Hydroxy vitamin D and luteinising hormone explained the 65.9% variability of anti-Müllerian hormone in a multiple linear regression model. However, anti-Müllerian hormone in crude correlation was more strongly associated with serum 25-hydroxy vitamin D than luteinising hormone. In conclusion, serum level of 25-hydroxy vitamin D might be a determinant factor of anti-Müllerian hormone level, and their relationship might explain in part the dysfunction of Sertoli cells and the impaired testicular functions in chronic kidney disease male patients., (© 2018 Blackwell Verlag GmbH.)

Autoimmune diseases are considered the 3rd leading cause of morbidity and mortality in the industrialized countries. Autoimmune thyroid diseases (ATDs) are associated with high prevalence of nonorgan-specific autoantibodies, such as antinuclear antibodies (ANA), antidouble-stranded deoxyribonucleic acid (anti-dsDNA), antiextractable-nuclear antigens (anti-ENAs), rheumatoid factor (RF), and anticyclic-citrullinated peptides (anti-CCP) whose clinical significance is unknown.We aimed to assess the prevalence of various nonorgan-specific autoantibodies in patients with ATD, and to investigate the possible association between these autoantibodies and occurrence of rheumatic diseases and, if these autoantibodies could be considered as predictor markers for autoimmune rheumatic diseases in the future.This study had 2 phases: phase 1; in which 61 ATD patients free from rheumatic manifestations were assessed for the presence of these nonorgan-specific autoantibodies against healthy 61 control group, followed by 2nd phase longitudinal clinical follow-up in which cases are monitored systematically to establish occurrence and progression of any rheumatic disease in association to these autoantibodies with its influences and prognosis.Regarding ATD patients, ANA, anti-dsDNA, Anti-ENA, and RF were present in a percentage of (50.8%), (18%), (21.3%), and (34.4%), respectively, with statistically significance difference (P < 0.5) rather than controls. Nearly one third of the studied group (32.8%) developed the rheumatic diseases, over 2 years follow-up. It was obvious that those with positive anti-dsDNA had higher risk (2.45 times) to develop rheumatic diseases than those without. There was a statistically significant positive linear relationship between occurrence of disease in months and (age, anti-dsDNA, anti-CCP, RF, and duration of thyroiditis). Anti-dsDNA and RF are the most significant predictors (P < 0.0001).ATD is more associated with rheumatic diseases than previously thought. Anti-dsDNA, RF, and anti-CCP antibodies may be used as predictive screening markers of systemic lupus erythematosus and RA, with early referral to rheumatologists for close follow-up and early diagnoses for appropriate disease management of the disease, as early disease control will allow better quality of life., Competing Interests: The authors have no funding and conflicts of interest to disclose.

Anti-C1q autoantibodies have been proposed as a useful marker in SLE. This study aimed at measuring serum levels of anti-C1q antibodies in patients with SLE and investigates correlations of this level with the histopathological classes of renal biopsies and disease activity. The anti-C1q antibody level was measured in 30 females SLE patients and 20 controls. The activity of SLE disease was calculated according to the SLE disease activity index. A renal biopsy from patients with clinical manifestations of renal disease was obtained. There was a significant increase in the level of anti-C1q antibodies in SLE patients than controls and in patients with active LN than inactive LN (P<0.05). There were significant positive correlations between anti-C1q antibody level and SLEDAI & rSLEDAI scores and activity index score of renal biopsies. Anti-C1q antibodies showed higher diagnostic sensitivity and specificity than anti-dsDNA antibodies. In conclusion, anti-C1q antibodies are useful and sensitive non-invasive biomarker with high specificity in combination with anti-dsDNA antibodies for the diagnosis of renal disease activity., (Copyright© by the Egyptian Association of Immunologists.)

Background/aims: Cholesterol biosynthesis suppresses the replication of HCV-1b replicons, thus influencing hepatitis C virus (HCV) natural history. This study aimed at comparing the efficacy and safety of fluvastatin (FLV) as an adjuvant therapy to the standard of care (SOC) therapy, i.e., pegylated interferon (PEG-IFN) and ribavirin, for the treatment of HCV patients., Materials and Methods: Sixty HCV patients were enrolled and allocated to either group I, who received the triple therapy (fluvastatin + SOC), or group II, who received SOC; the duration for both treatments was 48 weeks. All patients were subjected to pretreatment liver biopsy and monthly biochemical tests (liver profile, CBC), and quantitative HCV-RNA test was performed at weeks 0, 4, 12, 48, and 72., Results: All virological responses were higher in group I than in group II, with no statistical difference. Group I showed no manifestations of hepatotoxicity., Conclusion: Fluvastatin yielded a borderline, significantly higher complete early virological response than SOC; therefore, it is a safe adjuvant to the SOC therapy.

Background: Hepatocellular carcinoma (HCC) is the second most common malignancy in Egypt. Data mining is a method of predictive analysis which can explore tremendous volumes of information to discover hidden patterns and relationships. Our aim here was to develop a non-invasive algorithm for prediction of HCC. Such an algorithm should be economical, reliable, easy to apply and acceptable by domain experts., Methods: This cross-sectional study enrolled 315 patients with hepatitis C virus (HCV) related chronic liver disease (CLD); 135 HCC, 116 cirrhotic patients without HCC and 64 patients with chronic hepatitis C. Using data mining analysis, we constructed a decision tree learning algorithm to predict HCC., Results: The decision tree algorithm was able to predict HCC with recall (sensitivity) of 83.5% and precession (specificity) of 83.3% using only routine data. The correctly classified instances were 259 (82.2%), and the incorrectly classified instances were 56 (17.8%). Out of 29 attributes, serum alpha fetoprotein (AFP), with an optimal cutoff value of ≥50.3 ng/ml was selected as the best predictor of HCC. To a lesser extent, male sex, presence of cirrhosis, AST>64U/L, and ascites were variables associated with HCC., Conclusion: Data mining analysis allows discovery of hidden patterns and enables the development of models to predict HCC, utilizing routine data as an alternative to CT and liver biopsy. This study has highlighted a new cutoff for AFP (≥50.3 ng/ml). Presence of a score of >2 risk variables (out of 5) can successfully predict HCC with a sensitivity of 96% and specificity of 82%.

SLE is a heterogeneous disease, characterized by variation in clinical and serological manifestations. This study intended to verify the role of anti-nucleosome (anti-NCS) antibodies in diagnosis of SLE and lupus nephritis and to establish the correlation between antibody reactivity and disease activity. Study subjects included 35 patients diagnosed as SLE and two control groups. While the first is a group with other collagen diseases (n = 80), the second included 50 matched apparently healthy subjects. Serum IgG anti-NCS antibodies in all subjects were detected by ELISA. Serum anti-NCS were higher in SLE than in the two control groups (P < 0.001). Serum anti-NCS antibody levels were higher in SLE patients with renal affection (P < 0.001), malar rash and with hematological disorders (P < 0.05). Anti-NCS antibodies showed a higher diagnostic sensitivity (74.7%) and specificity (96%) than anti-dsDNA. Combining data of anti-NCS and anti-dsDNA antibodies increased the diagnostic specificity to 97.3%. In conclusion, serum anti-NCS antibodies have diagnostic value and play role in the assessment of disease activity especially active renal disease and may predict disease outcome.

Owing to the suggested role of osteopontin (OPN) in inflammation, autoimmunity and fibrosis, we investigated their serum concentrations in chronic hepatitis C virus (HCV) infected patients with and without autoimmune manifestations and correlated those levels to clinical manifestations and the histological severity of hepatic fibrosis. A total of 70 chronic HCV-infected patients (35 with and 35 without autoimmune rheumatic manifestations‏) were compared with 35 healthy volunteers matched for age and gender. Epidemiological, clinical, immunochemical and virological data were prospectively collected. OPN serum levels were assessed by an Enzyme Linked Immunosorbant Assay. The mean serum OPN levels were higher in HCV patients with autoimmune rheumatologic manifestations and in patients without; than that for the normal controls (p = 0.000). The mean OPN values progressively increased by increasing severity of liver fibrosis (p = 0.009). Multivariate analysis revealed that the presence of rheumatologic manifestations had the highest predictive value (b = 7.141, Beta = 0.414, p = 0.000) followed by liver fibrosis (b = 4.522, Beta = 0.444, p = 0.000) on the variation of OPN levels in our HCV patients. Among the group of patients with HCV and rheumatologic involvement, OPN serum levels were higher in patients with positive cryoglobulin and rheumatoid factor than in those without, and with systemic vasculitis than in those without. Correlation analysis didn't reveal any statistical significance of OPN with age, serum albumin, aminotransferases and viral load. Our data suggests OPN as a promising marker for HCV associated autoimmune rheumatologic involvement, particularly with regard to development of vasculitis and cryoglobinemia. In addition, it could serve as a biomarker to evaluate the severity of liver damages in HCV infected subjects.