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Abstract In vitro antitumor evaluation of the synthesized 46 compounds of 3,5-diaryl-4,5-dihydropyrazoles against EAC cell lines and 3D QSAR study using pharmacophore and Comparative Molecular Field Analysis (CoMFA) methods were described. CoMFA derived QSAR model shows a good conventional squared correlation coefficient r2 and cross validated correlation coefficient r2cv 0.896 and 0.568 respectively. In this analysis steric and electrostatic field contribute to the QSAR equation by 70% and 30% respectively, suggesting that variation in biological activity of the compounds is dominated by differences in steric (van der Waals) interactions. To visualize the CoMFA steric and electrostatic field from partial least squares (PLS) analysis, contour maps are plotted as percentage contribution to the QSAR equation and are associated with the differences in biological activity. Background Pyrazole derivatives exhibit a wide range of biological properties including promising antitumor activity. Furthermore, Aldol condensation assisted organic synthesis has delivered rapid routes to N-containing heterocycles, including pyrazoles. Combining these features, the use of chalconisation-assisted processes will provide rapid access to a targeted dihydropyrazoles library bearing a hydrazino 3D QSAR study using pharmacophore and Comparative Molecular Field Analysis (CoMFA) methods were described for evaluation of antioxidant properties. Results Chalcones promoted 1 of the 2 steps in a rapid, convergent synthesis of a small library of hydrazinyl pyrazole derivatives, all of which exhibited significant antitumor activity against Ehrlich Ascites Carcinoma (EAC) human tumor cell line comparable to that of the natural anticancer doxorubicin, as a reference standard during this study. In order to understand the observed pharmacological properties, quantitative structure-activity relationship (3D QSAR) study was initiated. Conclusions Chalcones heating provides a rapid and expedient route to a series of pyrazoles to investigate their chracterization scavenging properties. Given their favorable properties, in comparison with known anticancer, these pyrazole derivatives are promising leads for further development and optimization.

Coronavirus disease 2019 (COVID-19) represented an international health risk. Variants of the interferon-induced transmembrane protein-3 ( IFITM3 ) gene can increase the risk of developing severe viral infections. This cross-sectional study investigated the association between IFITM3 rs12252A>G single nucleotide polymorphism (SNP) and COVID-19 severity and mortality in 100 Egyptian patients. All participants were subjected to serum interleukin-6 (IL-6) determination by ELISA and IFITM3 rs12252 genotyping by real-time polymerase chain reaction. Of all participants, 85.0% had the IFITM3 rs12252 homozygous AA genotype, whereas 15.0% had the heterozygous AG genotype. None of our participants had the homozygous GG genotype. The IFITM3 rs12252A allele was found in 92.5% and the G allele in only 7.5%. There was no significant association ( p  > 0.05) between the IFITM3 rs12252 SNP and COVID-19 severity, intensive care unit (ICU) admission, or IL-6 serum levels. The heterozygous AG genotype frequency showed a significant increase among participants who died (32.0%) compared with those who had been cured (9.3%). The mutant G allele was associated with patients' death. Its frequency among cured participants was 8.5%, whereas in those who died was 24.2% ( p  = 0.024) with 3.429 odds ratio [95% confidence interval: 1.1-10.4]. In conclusion, this study revealed a significant association between the G allele variant of IFITM3 rs12252 and COVID-19 mortality. However, results were unable to establish a significant link between rs12252 polymorphism, disease severity, ICU admission, or serum IL-6 levels.

The ovary's Torsion is the adnexa's total or partial rotation around its vascular axis or pedicle. Complete torsion causes venous and lymphatic blockade leading to stasis, venous congestion, hemorrhage, and necrosis. If neglected, it may result in permanent loss of the affected ovary. Ovarian torsion is one of the most critical gynecological surgical emergencies. Therefore, it requires urgent surgical intervention. It is mainly diagnosed by clinical examination and ultrasound. Ovarian torsion is primarily seen in the first trimester of pregnancy. 1,2 Infertility treatment is a significant risk factor due to ovarian stimulation. We present a case of acute abdominal pain who came to the emergency department of Al Ahli Hospital, diagnosed as right adnexal torsion with viable intrauterine pregnancy at six weeks. Laparoscopic oophorectomy was done by removing the corpus luteum cyst, which supports early pregnancy. Despite its disposal, the pregnancy continued because the hormonal therapy started in doses higher than recommended for threatened abortion. 3 Eventually, she gave birth to a healthy baby boy at 35 weeks., (© 2023 Hatata, Soliman, Hosni, Licensee HBKU Press.)

Mesenchymal stem cells (MSCs) and hepatocytes are considered valuable candidates for cell-based therapy. The use of free zoonotic media, as purified platelets derived growth factors (L-GF) and human platelet lysate (hPL), instead of using fetal bovine serum (FBS) to support the growth and proliferation of these cells could be used as a promising therapeutic tool in hepatic regeneration. This study aimed to evaluate the usage of purified platelet derived growth factors and platelet lysate in both MSCs and hepatocyte cultures and to compare them with the usage of FBS. MSCs and hepatocytes were cultured in growth media supplemented with L-GF or hPL and compared them to their culture in growth media supplemented with FBS. Cells were subjected to population doubling (PD) and generation time (GT) calculations. The best result for MSCs was that obtained by using 10% hPL or 10% FBS with the highest cell count, highest viability and shortest incubation time needed to reach confluency compared to supplementation with 10%, 20% or 30% L-GF. As for hepatocyte culture, the use of 10% FBS for supplementation of media used for hepatic cell proliferation showed better performance regarding cell count, viability, and incubation time to reach confluency compared to the use of either hPL or L-GF. In conclusion, our study showed that 10% hPL had the best results in MSCs culture which suggests that hPL could be a better alternative for the development of xenofree stem cell culture that can be used for many clinical applications. On the other hand, 10% FBS showed the best results in hepatocyte culture., (Copyright© by the Egyptian Association of Immunologists.)

Autism spectrum disorders (ASDs) comprise a heterogeneous group of pathological conditions, mainly of genetic origin, characterized by stereotyped behavior, such as marked impairment in verbal and nonverbal communication, social skills, and cognition. Excitatory/inhibitory (E/I) imbalances have been recorded as an etiological mechanism of ASD. Furthermore, GABA, the main inhibitory neurotransmitter in adult life, is known to be much lower in both patients and rodent models of ASD. We propose correcting GABA signaling as a therapeutic strategy for ASD. In this study, 40 young male western Albino rats, 3−4 weeks in age, weighing about 60−70 g, were used. The animals were randomly assigned into six experimental groups, each including eight rats. Group I served as the control group and was orally administered phosphate-buffered saline. Groups II and III served as rodent models of ASD and were orally administered a neurotoxic dose of propionic acid (PPA). The rats in the three therapeutic groups (IV, V, and IV) received the same doses of PPA, followed by 0.2 g/kg body weight of pure Bifidobacterium infantis, a probiotic mixture of ProtexinR, and pure Lactobacillus bulgaricus, respectively, for 3 weeks. Selected variables related to oxidative stress, glutamate excitotoxicity, and gut bacteria were measured in the six groups. Both pure and mixed Lactobacillus and Bifidobacterium were effective in ameliorating glutamate excitotoxicity as an autistic feature developed in the PPA-induced rodent model. Their therapeutic effects mostly involved the correction of oxidative stress, restoration of depleted GABA, and up-regulation of GABA receptor gene expression. Pure Bifidobacterium was the most effective, followed by the mixture of probiotics and finally lactobacillus. In conclusion, Bifidobacteria and lactobacilli can be used independently or in combination as psychobiotics to ameliorate oxidative stress and glutamate excitotoxicity as two confirmed etiological mechanisms through the gut−brain axis.

In relation to dietary intervention in individuals with autism spectrum disorder (ASD), certain food constituents especially gluten and casein are recognized to be challenging and should be restricted. In this study, levels of glutathione S-transferase, glutathione, lipid peroxides, serotonin (5-HT), interleukin-6 (IL-6), glutamate, and gamma aminobutyric acid (GABA) were measured in the brain homogenates of ASD rodent model. Rats were treated either with single dose clindamycin (30 mg/kg) or with propionic acid (PPA) (250 mg/kg) for 3 days and then fed a standard diet, casein-rich diet (CRD), or gluten-rich diet (GRD). The obtained data demonstrates that clindamycin and PPA induced oxidative stress, which was slightly affected by CRD. A marked increase in the proinflammatory cytokine (IL-6) concentration found in clindamycin- and PPA-treated groups was lower in CRD fed rats. Both CRDs and GRDs produced similar trends in glutamate levels. 5-HT levels were higher in the clindamycin- and PPA-treated groups and increased with a GRD but were less affected by a CRD. CRD could be less deleterious compared to GRD. Although the underlying cause of gastrointestinal symptoms in patients with ASD is not exactly known, the most widely accepted one is the opioid theory which is related to GRD and CRD., (© 2021. The Author(s), under exclusive licence to Springer Science+Business Media, LLC, part of Springer Nature.)

The present study investigated that maternal type 1 diabetes may contribute to autism pathogenesis in offspring, and that insulin therapy during pregnancy may prevent the onset of autism. As evidenced, selected brain biomarkers representing the accepted etiological mechanism of autism in newborn rats from diabetic mothers and diabetic mothers receiving insulin therapy compared to the propionic acid (PPA) rodent model of autism were screened. Female Wistar rats with a controlled fertility cycle were randomly divided into three groups: a control group, a group treated with a single dose of 65 mg/kg streptozotocin (STZ) to induce type 1 diabetes (T1D), and a group treated with a single dose of STZ to induce T1D along with insulin therapy. Neonatal rats from these groups were divided into four experimental groups of six animals each: the control group, oral buffered PPA-treated group administered a neurotoxic dose of 250 mg/kg PPA for 3 days to induce autism, neonatal rats from mothers with T1D, and neonatal rats from mothers with T1D receiving insulin therapy. Biochemical parameters of oxidative stress, neuroinflammation, and glutamate excitotoxicity were examined in brain homogenates from all neonatal rats. The development of pathogenic bacteria was monitored in stool samples from all rat groups. Descriptive analyses of changes in fecal microbiota and overgrowth of Clostridium species were performed in diabetic mothers, diabetic mothers treated with insulin therapy, and their offspring. Clostridium species may induce autism-relevant behaviors in offspring from mothers with T1D. Maternal T1D without insulin therapy increased lipid peroxidation levels, reduced GST activity, and lower offspring' vitamin C and GSH levels. Increased IL-6 levels and reduced GABA levels were detected in brain homogenates from neonatal rats whose mothers had T1D. Interestingly, insulin therapy reduced MDA and IL-6 levels and increased GST, GSH, and vitamin C levels in brain homogenates of neonatal rats from mothers with T1D receiving insulin therapy compared to the PPA-treated group. Based on our results, the PPA-treated group and neonatal rats from mothers with T1D exhibited similar results. These findings suggest that neonatal rats from mothers with T1D may develop autism-relevant biochemical autistic features and that insulin therapy may ameliorate oxidative stress, poor detoxification, inflammation, and excitotoxicity as ascertained mechanisms involved in the etiology of autism., (© 2021. The Author(s), under exclusive licence to Springer Science+Business Media, LLC, part of Springer Nature.)

Background: Locally advanced rectal cancer (LARC) has a high incidence of local and distant relapse even after adequate treatment. The emerging role of neoadjuvant induction chemotherapy may allow initial down staging of the primary tumor, less toxicity and early treatment of micrometastatic disease followed by chemoradiation with the hope of increased complete response rates before surgery OBJECTIVES: To identify the effect of induction chemotherapy before concurrent chemoradiation (CCRTH) in locally advanced rectal cancer in terms of response and toxicity. Primary end point is assessment of pathological complete response rate after surgery. Secondary end points are disease free survival (DFS) and overall survival (OS) after 3 years follow up., Patients and Methods: Patients with MRI based criteria for staging high-risk LARC (T4 tumors, tumors within 2 mm of mesorectal fascia, T3 tumors at or below levators and T2-4 with LN +ve tumors) were included. Thirty-five patients were recruited. Patients received 12 weeks of induction capecitabine/oxaliplatin followed by concomitant capecitabine and conventional 3D-conformal radiotherapy. Surgery was done at least 6 weeks later ., Results: Five patients (20.8%) had a pathological complete response (TRG 0) (ypT0N0). Another three patients (12.5%) had near complete pathological response (TRG 1). Regarding OS and pathological complete response corrlelation, it was statistically not significant in relation to patients with incomplete pathological response (p = 1)., Conclusion: Induction chemotherapy could be a promising option for better response rates either clinical or pathological for high risk LARC patients with acceptable toxicity., (Copyright © 2022 The Authors. Published by Elsevier Ltd.. All rights reserved.)

It is proposed that gluten- and casein-rich diets (GRD and CRD) can synergistically exacerbate dysbiosis as comorbidity in autism by worsening leaky gut that affects the brain through the gut-brain axis. In this study, 35 young male rats were divided into 7 groups, Group 1 serves as control; Group 2, clindamycin (CL)-treated; and Group 3, propionic acid (PPA)-induced rodent model of autism. These three groups were fed standard diet until the end of the experiment. Groups 4-7 are rats treated similarly with CL and PPA, then fed on CRD or GRD until the end of the experiment. Serum zonulin, glutathione (GSH), lipid peroxides, and gut microbial composition were measured in the seven studied groups. Data demonstrate the significant increase in serum zonulin as marker of leaky gut in the CL-treated groups fed on CRD or GRD. Lipid peroxides were significantly higher in the serum of GRD-fed rats compared to CRD-fed or normal diet-fed rats. GSH was much lower in CL-treated groups fed on CRD or GRD compared to PPA-treated rats fed on both diets. Both diets differentially affected the diversity of the gut microbiota. This study demonstrates that CRD and GRD exacerbates leaky gut, according to serum zonulin, which was used as marker for increased gut permeability., Competing Interests: Conflict of interest: Authors state no conflict of interest., (© 2021 Hussain Al Dera et al., published by De Gruyter.)

Nanoparticles (NPs) have biological activities like antibacterial, antifungal, drug delivery, immunomodulation and antitumor activities. The aim of the current study was to investigate some of biomedical applications of silver NP synthesis using extracts from leaves of Eriobotrya japonica . Colour changes, UV-visible spectroscopy, SEM, zeta potential, dynamic light scattering, FTIR and XRD were used to confirm AgNPs formation. The UV-vis spectrum absorption band was observed at almost 430 nm. The SEM image shows quasi-spherical shape of AgNPs. The zeta potential demonstrated the negative surface charge of NPs. FTIR results showed the functional groups of AgNPs. Crystalline nature of AgNPs was confirmed by XRD pattern. MTT assay was used to study the anti-proliferative activity against MCF-7 and HeLa cells. Apoptosis was tested using a DNA-fragmentation test, and expression of P 53 . AgNPs inhibited the proliferation of MCF-7 and HeLa cells, and reduced inflammation. Treatment with AgNPs significantly decreased allergic disorder. AgNPs stimulated the phagocytosis process in BMDMs. The results suggested that AgNPs could be a promising therapy for future and preventing inflammation, reduce allergic disorders and prevent bacterial infection through the up-regulation of phagocytosis. Hence, future work such as developed and improved NPs as adjuvants, immune-modulating substances and nano-drug delivery system is needed.

Inadequate plant stand establishment due to insufficient germination is an important bottleneck in achieving the potential yields, specifically under uncertain growing conditions. Hydropriming has been publicized as a useful tool to alleviate the stress-induced consequences. Association of DNA biosynthesis in hydroprimed seeds of maize; hybrid, PEHM 5 and its parental lines (CM150 and CM151) was studied. Seeds were hydroprimed at 25 °C for 30 h and half of them were surface dried while the other half were redried back to the original moisture contents. The treated and untreated seeds were evaluated for; germination test, mean germination time, vigour index and DNA levels in embryos of fully matured seeds. Both the treatment strategies significantly enhanced the planting value of maize seeds. Vigour index I revealed significant correlation with G2/G1 ratio whereas significant negative correlation between G2/G1 ratio and mean germination time was observed. Large amounts of 2C DNA signals in flow cytometric analysis divulged that most cells might had arrested in the cell cycle at the pre synthetic G1 phase of nuclear division. Augmentation of 4C signal in the embryonic region was noticed after imbibition that could be ascribed to cells entering the synthetic phase of nuclear division. The embryonic cells showed increased 4C:2C ratios after 30 h of imbibition. Apparently, DNA synthesis preceded germination. In dry seeds, DNA histograms revealed both a 2C signal and a considerable 4C peak. A priming period of 30 h in distilled water considerably enhanced the rate and uniformity of germination in both surface dried and redried treatment strategies. Upon priming, the ratio of 4C:2C increased during the 30 h priming period, though the level in case of redried seeds did not reach the level obtained after hydration in water without drying back. However, the 4C: 2C ratio was constant after redrying the seeds to the original moisture content, indicating that the chromosomal material in the embryonic cells had stably ceased cell cycle activity at the G2 phase. The present results indicate that the beneficial effects of priming on seedling performance could be associated with the action of replicative DNA synthesis processes prior to germination., Competing Interests: The author declare that there is no conflict of interest., (© 2021 The Authors.)

Annona muricata is one of the most important traditional medicinal plants which contains numerous chemicals that exhibit various pharmacological properties. In this study, silver nanoparticles were prepared using A. muricata peel extract as a reducing agent and the effect was enhanced through A. muricata like pharmaceutical activity. AgNPs formation was confirmed by color changes, UV-visible spectroscopy, SEM, DLS, and XRD. The anti-proliferative activity of AgNPs against THP-1, AMJ-13, and HBL cell lines was studied. Apoptotic markers were tested using AO/EtBr staining assay, cell cycle phases using flowcytometry, and the expression of P53. Autophagy takes an essential part in controlling inflammasome activation by primary bone marrow-derived macrophages (BMDMs). We report novel functions for AgNPs-affected autophagy, represented by the control of the release of IL-1β, caspase-1, adaptor protein apoptosis-associated speck-like protein containing a CARD (ASC), and NLRP3 in BMDMs following treatment with LPS+ATP. The current study revealed that the AgNPs inhibited THP-1 and AMJ-13 cell proliferation. Meanwhile, the AgNPs significantly increased autophagy and reduced IL-1b and NLRP3 levels in both in vivo and in vitro models. The secretion of IL-1β was reduced whereas the degradation of NLRP3 inflammasome was enhanced. These findings propose that AgNPs apply an anti-proliferative activity against THP-1 and AMJ-13 cells through the stimulation of apoptosis via mitochondrial damage and induction of p53 protein pathway. In addition, AgNP-induced autophagy reduced the levels of IL-1β and NLRP3 inflammasome activation. This indicated that the AgNPs augment autophagy controlled by the IL-1β pathway via two different novel mechanisms. The first one is regulating activation of the IL-1 β, caspae-1, and ASC, while the second is NLRP3 targeting for lysosomal degradation. Overall, this study suggests that AgNPs could be a potent therapy for various types of cancer and an alternative treatment for preventing inflammation via enhancing autophagy.

This paper describes the preparation, characterization, and evaluation of honey/tripolyphosphate (TPP)/chitosan (HTCs) nanofibers loaded with capsaicin derived from the natural extract of hot pepper ( Capsicum annuum L .) and loaded with gold nanoparticles (AuNPs) as biocompatible antimicrobial nanofibrous wound bandages in topical skin treatments. The capsaicin and AuNPs were packed within HTCs in HTCs-capsaicin, HTCs-AuNP, and HTCs-AuNPs/capsaicin nanofibrous mats. In vitro antibacterial testing against Pasteurella multocida, Klebsiella rhinoscleromatis, Staphylococcus pyogenes, and Vibrio vulnificus was conducted in comparison with difloxacin and chloramphenicol antibiotics. Cell viability and proliferation of the developed nanofibers were evaluated using an MTT assay. Finally, in vivo study of the wound-closure process was performed on New Zealand white rabbits. The results indicate that HTCs-capsaicin and HTCs-AuNPs are suitable in inhibiting bacterial growth compared with HTCs and HTCs-capsaicin/AuNP nanofibers and antibiotics ( P < 0.01). The MTT assay demonstrates that the nanofibrous mats increased cell proliferation compared with the untreated control ( P < 0.01). In vivo results show that the developed mats enhanced the wound-closure rate more effectively than the control samples. The novel nanofibrous wound dressings provide a relatively rapid and efficacious wound-healing ability, making the obtained nanofibers promising candidates for the development of improved bandage materials.

In the current study, the surface of superparamagnetic iron oxide (SPION) was coated with dextran (DEX), and conjugated with folic acid (FA), to enhance the targeted delivery and uptake of vinblastine (VBL) in PANC-1 pancreatic cancer cells. Numerous analyses were performed to validate the prepared FA-DEX-VBL-SPION, such as field emission scanning transmission electron microscopy, high-resolution transmission electron microscopy, dynamic light scattering (DLS), Zeta Potential, Fourier transform infrared spectroscopy, and vibrating sample magnetometry (VSM). The delivery system capacity was evaluated by loading and release experiments. Moreover, in vitro biological studies, including a cytotoxicity study, cellular uptake assessment, apoptosis analysis, and real-time PCR, were carried out. The results revealed that the obtained nanocarrier was spherical with a suitable dispersion and without visible aggregation. Its average size, polydispersity, and zeta were 74 ± 13 nm, 0.080, and -45 mV, respectively. This dual functional nanocarrier also exhibited low cytotoxicity and a high apoptosis induction potential for successful VBL co-delivery. Real-time quantitative PCR analysis demonstrated the activation of caspase-3 , NF-1 , PDL-1 , and H-ras inhibition, in PANC-1 cells treated with the FA-VBL-DEX-SPION nanostructure. Close inspection of the obtained data proved that the FA-VBL-DEX-SPION nanostructure possesses a noteworthy chemo-preventive effect on pancreatic cancer cells through the inhibition of cell proliferation and induction of apoptosis.

The purpose of write this paper is to study the genetic variability between and within different Halosylon salicornicum populations in different regions of Saudi arabia Kingdom, using the determination of genetic fingerprint method by Inter Simple Sequence Repeat (ISSR). Because this plant highly vulnerable to depletion by humans in all places of existence, it is an economically valuable plant where raft is an important pastoral resource in central and northern Arabia. It also has multiple medical uses. It is a plant that can withstand abiotic stresses such as drought and high temperature, making it suitable for cultivation in marginal lands in arid areas. All of the above was a catalyst for plant characterization using a number of Haloxylon salicornicum samples, collected from different regions of Saudi Arabia to find out the genetic variation of species, genetic diversity in knowing the plant community is an essential step towards the design of programs for plant breeding as well as preserved from extinction. This was done using the Inter Simple Sequence Repeat (ISSR). The results showed there were significant differences and molecular differences between plant samples. The average polymorphism between the genetic inputs of the studied Haloxylon salicornicum samples was 53.7%, and this percentage of genetic variability is significant for progress in growth and plant regeneration in the face of unfair practices against it, in addition to adverse environmental conditions in most years. As evidenced by the percentage of matrix similarity. The ISSR results indicate that the genotype between five different regions genotypes ranged from 0.365 to 0.527, indicating that Haloxylon salicornicum is a local plant capable of surviving and adapting to the environmental conditions in Saudi Arabia through the positive change in the genetic makeup of this species., Competing Interests: The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (© 2020 The Author(s).)

Background: High-mobility group box-1 (HMGB1) acts as a damage-associated molecular pattern or as an alarmin and it stimulates inflammatory and immunological activities., Aim: We sought to investigate serum HMGB1 protein expression in patients with pediatric systemic lupus erythematosus (pSLE) in relation to the disease characteristics and activity., Patients and Methods: This is a controlled cross-sectional study which comprised 50 children and adolescents with Systemic lupus erythematosus (SLE) and 50 age- and sex-matched healthy subjects who served as a control group. Study measurements included clinical assessment, laboratory workup for SLE (complete blood count, erythrocyte sedimentation rate, serum creatinine, creatinine clearance and 24-hour urinary protein, C3 and anti-double-stranded DNA, lupus anticoagulant and anticardiolipin antibodies) and measurement of serum HMGB1 by enzyme-linked immunosorbent assay in patients and controls., Results: Serum HMGB1 expression was significantly higher in the pSLE patients than the control group (P < 0.001). Patients with lupus nephritis (LN) had significantly higher serum HMGB1 as compared to those with normal kidneys (P < 0.04). Serum HMGB1 in LN patients correlated positively to the SLE Disease Activity Index (P < 0.0001), and 24 hours urinary proteins and negatively to creatinine clearance (P < 0.001). At a cut-off point of ≥40 µg/L, serum HMGB1 showed good diagnostic value for pSLE with sensitivity and specificity of 98% and 95%, respectively., Conclusion: Serum HMGB1 seems to be a reliable biomarker for diagnosis of pSLE and monitoring disease status, especially in LN. HMBG1 might prove to be a potential therapeutic target in LN., (© 2019 Asia Pacific League of Associations for Rheumatology and John Wiley & Sons Australia, Ltd.)

Background: Acne vulgaris (AV) pathogenesis is multifactorial. Vitamin D (VitD) plays an important role in sebocytes' differentiation and function. Most VitD functions are mediated by the nuclear VitD receptor (VDR) following binding of its biologically active form (1,25 dihydroxyvitamin D3). Genetic variations in VDR gene may cause significant receptor dysfunction and have been found to be associated with many inflammatory skin diseases. Two adjacent single nucleotide polymorphisms of VDR, ApaI (rs7975232) and TaqI (rs731236), were commonly studied., Objective: To evaluate the association between VDR ApaI and TaqI gene polymorphism and AV., Methods: This case control study included 30 Egyptian acne patients who attended Dermatology Outpatient Clinic of Al-Zahraa University and Misr University for Science and Technology Hospitals. Thirty age- and sex-matched healthy individuals participated as controls. VDR gene ApaI and TaqI polymorphisms were examined by polymerase chain reaction restriction fragment length polymorphism. Serum 25(OH)D was measured in all participants., Results: Patients had significant decrease in ApaI A allele and AATT combined genotype (60%, 3.3%) than controls (78.3%, 20%), respectively, and significant increase in TaqI tt genotype and t allele (46.7%, 63.3%) than controls (13.3%, 41.7%), respectively. Patients showed significantly lower serum 25(OH)D3 concentration than controls., Conclusion: Polymorphisms of ApaI and TaqI may have a role in the pathogenesis of AV as A allele and AATT combined genotype could be considered protective against acne development and tt genotype and t allele may increase the risk of AV development. VitD deficiency can be considered as a risk factor for AV development., (© 2018 Wiley Periodicals, Inc.)

Cow's milk allergy (CMA) is known to be either IgE- or non-IgE mediated. Regulatory T (Treg) cell defect is involved in the pathogenesis of both types. Vitamin D has been suggested to improve the generation of allergen-specific Treg cell populations with the potential to provide safe and long-term alleviation of disease symptoms. This study aimed to assess Vitamin D status in children with physician-diagnosed CMA and to investigate the effect of in vitro cultivation with Vitamin D on the percentage of antigen-driven CD4+CD25highFoxp3+IL10+ Treg cells following in vitro stimulation of cells with cow's milk allergen in culture. This cross-sectional study included 20 children with CMA and 20 healthy age and sex-matched children as a control group. All patients were subjected to clinical evaluation, cow's milk skin prick test (SPT), cow's milk elimination and oral re-challenge test in patients with negative cow's milk SPT and in those with gastrointestinal presentation, measurement of serum Vitamin D level and assessment of the percentage of antigen-driven CD4+CD25highFoxp3+IL10+ Treg cells in response to stimulation with cow's milk allergen extract with and without Vitamin D in culture. Vitamin D deficiency was detected in 80% of children with CMA. Percentage of Foxp3+ and IL10+ co-expression on Treg cells was significantly increased after stimulation with cow's milk allergen extract in the presence of Vitamin D. A significant positive correlation was observed between serum Vitamin D level and percentage of antigen-driven CD4+CD25highFoxp3+IL10+ Treg cells as well as level of Foxp3+ and IL10+ co-expression on Treg cells at baseline (control cultures without stimulation) and after PBMCs stimulation with cow's milk allergen extract in the presence of Vitamin D. Re-stimulation with cow's milk allergen extract was performed in vitro in order to evaluate milk-induced immune stimulation and regulation. In conclusion, patients with CMA whether IgE- or non-IgE mediated had Vitamin D deficiency with a decreased number of CD4+CD25highFoxp3+IL10+ Treg cells which increased after in vitro addition of Vitamin D with increased Foxp3 and IL10 co-expression., (Copyright© by the Egyptian Association of Immunologists.)

Our objective was to elucidate the effects of different HCV peptides on TH1 cytokine synthesis (interleukin 2(IL2), gamma interferon (INFγ) and tumor necrosis factor α (TNF α)), in a proliferative response in a high risk population of HCV seronegative aviremic Egyptian healthcare workers (HCW). We studied the TH1 cytokine response to different HCV peptides among 47 HCW with and without evidence of HCV infection. Participants were classified according to the proliferation index (PI) in a CFSE proliferation assay as an indicator of previous exposure to HCV. Cytokines were analyzed using Luminex xMAP technology. Results showed that positive PI HCW produced a higher IL2 in response to all HCV peptides except NS4, a higher IFNγ response to NS3 and NS4 and no difference in TNFα response when compared to the negative PI HCWs. When compared to chronic HCV HCW, positive PI HCW showed no difference in the IL2 response, a higher IFNγ response to NS4 and NS5 HCV peptides and a higher TNFα response to all peptides. In conclusion the magnitude and type of cytokines produced in HCV infection is critical in determining the outcome of infection. NS4 & NS5 HCV peptides induce a protective TH1 response in positive PI HCW.

Resistin and visfatin have been proposed as playing a role in the pathogenesis of insulin resistance. We assessed the relationship between their serum concentrations and insulin resistance in lean, obese diabetic and obese non-diabetic. We explore their relationship with inflammatory markers and anthropometric parameters in obese patients. We measured serum resistin, visfatin levels in obese diabetic, obese nondiabetic patients and in lean subjects. The concentrations of serum resistin showed significant differences among the three groups. Higher levels of visfatin occurred in obese diabetic and non diabetic compared to lean subjects. Higher levels for HOMA-IR occurred in obese diabetic and non diabetic compared to lean subjects. Resistin correlated positively with insulin, HOMA-IR and with hs-CRP in obese diabetic subjects. Visfatin correlated positively with insulin and HOMA-IR in obese diabetic and non-diabetic subjects. Resistin might be involved in the pathogenesis of diabetes. Additionally, IL-18 might be a predictor of insulin resistance.

CD4+CD25+high Foxp3 regulatory T (Treg) cells are known to play a key role in balancing immune response to maintain peripheral tolerance against harmless antigens or allergens. Defective immunological suppression by CD4+CD25+high Foxp3 Treg cells can be a cause of the inflammation that leads to an allergic condition such as asthma. The aims of the study are to (1) determine CD4+CD25+high Foxp3 Treg cells frequency in the peripheral blood of children with and without asthma; and (2) investigate the association between CD4+CD25+high Foxp3 Treg cells frequency with disease severity and corticosteroid therapy. Sixty asthmatic children with varying disease severity (20 mild, 20 moderate and 20 severe) were enrolled in the study. Severe asthmatic children were further subdivided into two groups, one on corticosteroid therapy and the other was not on corticosteroid. Twenty age and sex matched healthy children were enrolled as controls. Number of circulating CD4+CD25+high Foxp3 Tregs were measured using flow cytometry. Our finding demonstrates that children with asthma had a significant decrease of CD4+CD25high Foxp3 Treg cells and Tregs/T effectors ratio in peripheral blood compared to children without asthma. Patients with moderate asthma demonstrated lower frequency of CD4+CD25+high Foxp3 Treg cells compared to mild and severe asthmatic patients. Those on corticosteroid therapy revealed significant increase in CD4+CD25+high Foxp3 Treg cells and decrease in T effectors. It is concluded that asthmatic children have decreased number of CD4+CD25+high Foxp3 Treg cells leading to increase in effectors cells which mediate inflammation in the airways. Corticosteroid therapy plays a role in elevating number of CD4+CD25+high Foxp3 Treg cells and maintaining its suppressor function.

The pathogenesis of scleroderma encompasses vascular, immunological, and fibrotic processes, which contribute to clinical manifestations. We investigated the prevalence of anti-annexin V IgG and IgM antibodies in sera of scleroderma patients and their relation to the presence of other antibodies and development of disease morbidity. Sera of 40 scleroderma patients and 15 healthy controls were examined for IgG and IgM anti-annexin V antibodies by ELISA and anticentromere antibodies by indirect immunofluorescence. Serum level of anti-annexin V IgG antibodies in scleroderma patients was significantly higher than that of the control (P < 0.001) and correlated significantly with the presence of digital ischemia (P = 0.023) and pulmonary fibrosis (P = 0.02). IgM isotype was comparable between patients and controls (P = 0.317). Anticentromere antibodies are more prevalent in the limited cutaneous subtype (P = 0.017). In conclusion, measurement of serum anti-annexin V IgG antibodies in scleroderma patients may be important for early diagnosis of vascular and pulmonary complications.

This study examined relationships between blood microfilaria (MF) counts and parasite uptake and maturation in Culex pipiens fed on Egyptian volunteers with bancroftian filariasis. Uptake of MF and production of infective larvae (L3) were more closely correlated with MF counts in finger prick blood than in venous blood. Only a minority of ingested MF developed into L3. Few MF were ingested, and very few L3 were produced by mosquitoes that fed on infected subjects who were amicrofilaremic by 50 microL thick blood smear; the contribution of such carriers to filariasis transmission in Egypt is probably negligible. These results suggest that filariasis elimination programs should aim to achieve MF smear rates of zero. Single-dose diethylcarbamazine therapy reduced MF counts by 87.9% 6-7 months after treatment; similar reductions were observed for MF uptake, MF/mosquito, infectivity, and L3/mosquito. Thus, single-dose diethylcarbamazine had a major impact on MF ingestion and L3 production by mosquitoes.